Laura Evans, Andrew Rhodes, Waleed Alhazzani, Massimo Antonelli, Craig M Coopersmith, Craig French, Flávia R Machado, Lauralyn Mcintyre, Marlies Ostermann, Hallie C Prescott, Christa Schorr, Steven Simpson, W Joost Wiersinga, Fayez Alshamsi, Derek C Angus, Yaseen Arabi, Luciano Azevedo, Richard Beale, Gregory Beilman, Emilie Belley-Cote, Lisa Burry, Maurizio Cecconi, John Centofanti, Angel Coz Yataco, Jan De Waele, R Phillip Dellinger, Kent Doi, Bin Du, Elisa Estenssoro, Ricard Ferrer, Charles Gomersall, Carol Hodgson, Morten Hylander Møller, Theodore Iwashyna, Shevin Jacob, Ruth Kleinpell, Michael Klompas, Younsuck Koh, Anand Kumar, Arthur Kwizera, Suzana Lobo, Henry Masur, Steven McGloughlin, Sangeeta Mehta, Yatin Mehta, Mervyn Mer, Mark Nunnally, Simon Oczkowski, Tiffany Osborn, Elizabeth Papathanassoglou, Anders Perner, Michael Puskarich, Jason Roberts, William Schweickert, Maureen Seckel, Jonathan Sevransky, Charles L Sprung, Tobias Welte, Janice Zimmerman, Mitchell Levy
Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.
Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337.
Abstract/Text
D T Durack, A S Lukes, D K Bright
New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service.
Am J Med. 1994 Mar;96(3):200-9.
Abstract/Text
PURPOSE: This study was designed to develop improved criteria for the diagnosis of infective endocarditis and to compare these criteria with currently accepted criteria in a large series of cases.
PATIENTS AND METHODS: A total of 405 consecutive cases of suspected infective endocarditis in 353 patients evaluated in a tertiary care hospital from 1985 to 1992 were analyzed using new diagnostic criteria for endocarditis. We defined two "major criteria" (typical blood culture and positive echocardiogram) and six "minor criteria" (predisposition, fever, vascular phenomena, immunologic phenomena, suggestive echocardiogram, and suggestive microbiologic findings). We also defined three diagnostic categories: (1) "definite" by pathologic or clinical criteria, (2) "possible," and (3) "rejected." Each suspected case of endocarditis was classified using both old and new criteria. Sixty-nine pathologically proven cases were reclassified after exclusion of the surgical or autopsy findings, enabling comparison of clinical diagnostic criteria in proven cases.
RESULTS: Fifty-five (80%) of the 69 pathologically confirmed cases were classified as clinically definite endocarditis. The older criteria classified only 35 (51%) of the 69 pathologically confirmed cases into the analogous probable category (p < 0.0001). Twelve (17%) pathologically confirmed cases were rejected by older clinical criteria, but none were rejected by the new criteria. Seventy-one (21%) of the remaining 336 cases that were not proven pathologically were probable by older criteria, whereas the new criteria almost doubled the number of definite cases, to 135 (40%, p < 0.01). Of the 150 cases rejected by older criteria, 11 were definite, 87 were possible, and 52 were rejected by the new criteria.
CONCLUSION: Application of the proposed new criteria increases the number of definite diagnoses. This should be useful for more accurate diagnosis and classification of patients with suspected endocarditis and provide better entry criteria for epidemiologic studies and clinical trials.
J S Li, D J Sexton, N Mick, R Nettles, V G Fowler, T Ryan, T Bashore, G R Corey
Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis.
Clin Infect Dis. 2000 Apr;30(4):633-8. doi: 10.1086/313753. Epub 2000 Apr 3.
Abstract/Text
Although the sensitivity and specificity of the Duke criteria for the diagnosis of infective endocarditis (IE) have been validated by investigators from Europe and the United States, several shortcomings of this schema remain. The Duke IE database contains records collected prospectively on >800 cases of definite and possible IE since 1984. Databases on echocardiograms and on patients with Staphylococcus aureus bacteremia at Duke University Medical Center are also maintained. Analyses of these databases, our experience with the Duke criteria in clinical practice, and analysis of the work of others have led us to propose the following modifications of the Duke schema. The category "possible IE" should be defined as having at least 1 major criterion and 1 minor criterion or 3 minor criteria. The minor criterion "echocardiogram consistent with IE but not meeting major criterion" should be eliminated, given the widespread use of transesophageal echocardiography (TEE). Bacteremia due to S. aureus should be considered a major criterion, regardless of whether the infection is nosocomially acquired or whether a removable source of infection is present. Positive Q-fever serology should be changed to a major criterion.
Mervyn Singer, Clifford S Deutschman, Christopher Warren Seymour, Manu Shankar-Hari, Djillali Annane, Michael Bauer, Rinaldo Bellomo, Gordon R Bernard, Jean-Daniel Chiche, Craig M Coopersmith, Richard S Hotchkiss, Mitchell M Levy, John C Marshall, Greg S Martin, Steven M Opal, Gordon D Rubenfeld, Tom van der Poll, Jean-Louis Vincent, Derek C Angus
The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
Abstract/Text
IMPORTANCE: Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
OBJECTIVE: To evaluate and, as needed, update definitions for sepsis and septic shock.
PROCESS: A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment).
KEY FINDINGS FROM EVIDENCE SYNTHESIS: Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant.
RECOMMENDATIONS: Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.
CONCLUSIONS AND RELEVANCE: These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.
Manu Shankar-Hari, Gary S Phillips, Mitchell L Levy, Christopher W Seymour, Vincent X Liu, Clifford S Deutschman, Derek C Angus, Gordon D Rubenfeld, Mervyn Singer, Sepsis Definitions Task Force
Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
JAMA. 2016 Feb 23;315(8):775-87. doi: 10.1001/jama.2016.0289.
Abstract/Text
IMPORTANCE: Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition.
OBJECTIVE: To develop a new definition and clinical criteria for identifying septic shock in adults.
DESIGN, SETTING, AND PARTICIPANTS: The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005-2010; n = 28,150), University of Pittsburgh Medical Center (UPMC) (2010-2012; n = 1,309,025), and Kaiser Permanente Northern California (KPNC) (2009-2013; n = 1,847,165) electronic health record (EHR) data sets.
MAIN OUTCOMES AND MEASURES: Evidence for and agreement on septic shock definitions and criteria.
RESULTS: The systematic review identified 44 studies reporting septic shock outcomes (total of 166,479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock-associated crude mortality was 46.5% (95% CI, 42.7%-50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to test using cohort studies. Based on these 3 variables alone or in combination, 6 patient groups were generated. Examination of the SSC database demonstrated that the patient group requiring vasopressors to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L (18 mg/dL) after fluid resuscitation had a significantly higher mortality (42.3% [95% CI, 41.2%-43.3%]) in risk-adjusted comparisons with the other 5 groups derived using either serum lactate level greater than 2 mmol/L alone or combinations of hypotension, vasopressors, and serum lactate level 2 mmol/L or lower. These findings were validated in the UPMC and KPNC data sets.
CONCLUSIONS AND RELEVANCE: Based on a consensus process using results from a systematic review, surveys, and cohort studies, septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.
L A Mermel, D G Maki
Detection of bacteremia in adults: consequences of culturing an inadequate volume of blood.
Ann Intern Med. 1993 Aug 15;119(4):270-2.
Abstract/Text
The yield of blood cultures depends on the volume of blood cultured. We recently discovered that 15% of blood-culture specimens from adults in our hospital were being collected in 3.5-mL pediatric tubes and that another 5%, drawn in 10-mL adult tubes, contained less than 5 mL of blood. A comparison of 829 matched pairs of standard-volume (mean, 8.7 mL) and low-volume (mean, 2.7 mL) blood cultures showed that standard-volume cultures had a substantially higher detection rate for bloodstream infection than did low-volume cultures (92% compared with 69%; difference, 23% [95% CI, 9% to 37%]; P < 0.001). Our data, together with an analysis of previous studies, show that the yield of blood cultures in adults increases approximately 3% per millilitre of blood cultured. A survey of 158 U.S. clinical microbiology laboratory directors in the American Society of Clinical Pathologists showed that only 20% of 71 responding laboratories record the volume of blood submitted for culture and that the practice of culturing suboptimal volumes of blood from adults is widespread. Clinical laboratories should routinely monitor the volume of blood cultured as a quality-assurance measure. Blood-culture specimens from adults should not be drawn using small pediatric tubes.
Michael L Towns, L Barth Reller
Diagnostic methods. Current best practices and guidelines for isolation of bacteria and fungi in infective endocarditis.
Cardiol Clin. 2003 May;21(2):197-205.
Abstract/Text
As the etiological character of IE changes, the microbiological tools used to confirm the diagnosis have also evolved. Here the authors have reviewed the current methods for optimal laboratory diagnosis of bacterial and fungal endocarditis using traditional growth-based technologies and offered good practice guidelines and recommendations. Newer techniques will be required to improve sensitivity of detection for known organisms and to identify emerging or as-yet unknown pathogens (see article by Lepidi et al in this issue).
Nathan I Shapiro, Richard E Wolfe, Sharon B Wright, Richard Moore, David W Bates
Who needs a blood culture? A prospectively derived and validated prediction rule.
J Emerg Med. 2008 Oct;35(3):255-64. doi: 10.1016/j.jemermed.2008.04.001. Epub 2008 May 16.
Abstract/Text
The study objective was to derive and validate a clinical decision rule for obtaining blood cultures in Emergency Department (ED) patients with suspected infection. This was a prospective, observational cohort study of consecutive adult ED patients with blood cultures obtained. The study ran from February 1, 2000 through February 1, 2001. Patients were randomly assigned to derivation (2/3) or validation (1/3) sets. The outcome was "true bacteremia." Features of the history, co-morbid illness, physical examination, and laboratory testing were used to create a clinical decision rule. Among 3901 patients, 3730 (96%) were enrolled with 305 (8.2%) episodes of true bacteremia. A decision rule was created with "major criteria" defined as: temperature > 39.5 degrees C (103.0 degrees F), indwelling vascular catheter, or clinical suspicion of endocarditis. "Minor criteria" were: temperature 38.3-39.4 degrees C (101-102.9 degrees F), age > 65 years, chills, vomiting, hypotension (systolic blood pressure < 90 mm Hg), neutrophil% > 80, white blood cell count > 18 k, bands > 5%, platelets < 150 k, and creatinine > 2.0. A blood culture is indicated by the rule if at least one major criterion or two minor criteria are present. Otherwise, patients are classified as "low risk" and cultures may be omitted. Only 4 (0.6%) low-risk patients in the derivation set and 3 (0.9%) low-risk patients in the validation set had positive cultures. The sensitivity was 98% (95% confidence interval [CI] 96-100%) (derivation) and 97% (95% CI 94-100%) (validation). We developed and validated a promising clinical decision rule for predicting bacteremia in patients with suspected infection.
Leonard A Mermel, Michael Allon, Emilio Bouza, Donald E Craven, Patricia Flynn, Naomi P O'Grady, Issam I Raad, Bart J A Rijnders, Robert J Sherertz, David K Warren
Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America.
Clin Infect Dis. 2009 Jul 1;49(1):1-45. doi: 10.1086/599376.
Abstract/Text
Nasia Safdar, Jason P Fine, Dennis G Maki
Meta-analysis: methods for diagnosing intravascular device-related bloodstream infection.
Ann Intern Med. 2005 Mar 15;142(6):451-66.
Abstract/Text
BACKGROUND: No consensus exists on the best methods for diagnosis of intravascular device (IVD)-related bloodstream infection.
PURPOSE: To identify the most accurate methods for diagnosis of IVD-related bloodstream infection.
DATA SOURCES: 51 English-language studies published from 1966 to 31 July 2004.
STUDY SELECTION: Studies of diagnostic tests for IVD-related bloodstream infection that described a reference standard and provided sufficient data to calculate sensitivity and specificity.
DATA EXTRACTION: Study quality, diagnostic tests examined, patient characteristics, prevalence, sensitivity, and specificity.
DATA SYNTHESIS: Pooled sensitivity and specificity were calculated for 8 diagnostic methods. Summary measures of accuracy were Q* (the upper leftmost point on the summary receiver-operating characteristic curve) and mean D (a log odds ratio). Subgroup analyses were used to assess heterogeneity. Overall, the most accurate test was paired quantitative blood culture (Q* = 0.94 [95% CI, 0.88 to 1.0]), followed by IVD-drawn quantitative [corrected] blood culture (Q* = 0.89 [CI, 0.79 to 0.99]) and the acridine orange leukocyte cytospin test (Q* = 0.89 [CI, 0.79 to 0.91]). The most accurate catheter segment culture test was quantitative culture (Q* = 0.87 [CI, 0.81 to 0.93]), followed by semi-quantitative culture (Q* = 0.84 [CI, 0.80 to 0.88]). Significant heterogeneity in pooled sensitivity and specificity was observed across all test categories.
LIMITATIONS: The limited number of studies of some of the diagnostic methods precludes precise estimates of accuracy.
CONCLUSIONS: Paired quantitative blood culture is the most accurate test for diagnosis of IVD-related bloodstream infection. However, most other methods studied showed acceptable sensitivity and specificity (both >0.75) and negative predictive value (>99%). The positive predictive value of all tests increased greatly with high pretest clinical probability. Catheters should not be cultured routinely but rather only if IVD-related bloodstream infection is suspected clinically.
Sara E Cosgrove, Vance G Fowler
Management of methicillin-resistant Staphylococcus aureus bacteremia.
Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S386-93. doi: 10.1086/533595.
Abstract/Text
Staphylococcus aureus bacteremia and endocarditis are serious infections that demand prompt clinical attention to ensure good outcomes. Of foremost importance is identifying and managing the source of infection and any associated complications. Evaluation for the presence of cardiac involvement is essential because inadequately managed S. aureus endocarditis is life threatening. Thus, physicians must aggressively negotiate treatment paths, considering whether the S. aureus bacteremia is complicated, whether foreign sources of infection should be removed or replaced, and whether surgical intervention is necessary. Selection of an antibiotic treatment is also an essential factor for optimal management. The increasing prevalence of methicillin-resistant S. aureus (MRSA) infections has created a tremendous demand for effective and safe antimicrobial agents other than the historic anti-MRSA agent vancomycin.
Vance G Fowler, Maren K Olsen, G Ralph Corey, Christopher W Woods, Christopher H Cabell, L Barth Reller, Allen C Cheng, Tara Dudley, Eugene Z Oddone
Clinical identifiers of complicated Staphylococcus aureus bacteremia.
Arch Intern Med. 2003 Sep 22;163(17):2066-72. doi: 10.1001/archinte.163.17.2066.
Abstract/Text
BACKGROUND: Complications of Staphylococcus aureus bacteremia (SAB) are often difficult to identify. The ability to accurately predict the likelihood of these complications would impact patient management. This investigation sought to define readily available clinical characteristics that could help identify patients at risk for complicated SAB.
METHODS: A prospective, observational cohort study was conducted from September 1994 through December 1999. Patients were followed up for 12 weeks after the initial positive blood culture result. The primary end point was complicated SAB (attributable mortality, complicated infection, embolic stroke, or recurrent S aureus infection during the 12-week follow-up period). The predictive model was validated using bootstrap resampling.
RESULTS: Complicated SAB was present in 43% of 724 consecutive adult hospitalized patients identified during the study period. The full predictive model had a high discriminative ability (bootstrap-corrected c index, 0.78). The strongest predictor of complicated SAB was a positive follow-up blood culture result at 48 to 96 hours. A scoring system based on the presence or absence of 4 risk factors (community acquisition, skin examination findings suggesting acute systemic infection, persistent fever at 72 hours, and positive follow-up blood culture results at 48-96 hours) accurately identified complicated SAB (bootstrap-corrected c index, 0.76).
CONCLUSION: Readily available clinical variables can help identify patients at risk for complicated SAB.
Liu Catherine C, Bayer Arnold A, Cosgrove Sara E SE, Daum Robert S RS, Fridkin Scott K SK, Gorwitz Rachel J RJ, Kaplan Sheldon L SL, Karchmer Adolf W AW, Levine Donald P DP, Murray Barbara E BE, J Rybak Michael M, Talan David A DA, Chambers Henry F HF, Infectious Diseases Society of America
Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.
Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4.
Abstract/Text
Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.
Peter G Pappas, Carol A Kauffman, David R Andes, Cornelius J Clancy, Kieren A Marr, Luis Ostrosky-Zeichner, Annette C Reboli, Mindy G Schuster, Jose A Vazquez, Thomas J Walsh, Theoklis E Zaoutis, Jack D Sobel
Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.
Clin Infect Dis. 2016 Feb 15;62(4):e1-50. doi: 10.1093/cid/civ933. Epub 2015 Dec 16.
Abstract/Text
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
M P Weinstein, M L Towns, S M Quartey, S Mirrett, L G Reimer, G Parmigiani, L B Reller
The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults.
Clin Infect Dis. 1997 Apr;24(4):584-602.
Abstract/Text
To assess changes since the mid-1970s, we reviewed 843 episodes of positive blood cultures in 707 patients with septicemia. The five most common pathogens were Staphylococcus aureus, Escherichia coli, coagulase-negative staphylococci (CNS), Klebsiella pneumoniae, and Enterococcus species. Although CNS were isolated most often, only 12.4% were clinically significant. Half of all episodes were nosocomial, and a quarter had no recognized source. Leading identifiable sources included intravenous catheters, the respiratory and genitourinary tracts, and intraabdominal foci. Septicemia-associated mortality was 17.5%. Patients who received appropriate antimicrobial therapy throughout the course of infection had the lowest mortality (13.3%). Multivariate analysis showed that age (relative risk [RR], 1.80), microorganism (RR, 2.27), source of infection (RR, 2.86), predisposing factors (RR, 1.98), blood pressure (RR, 2.29), body temperature (RR, 2.04), and therapy (RR, 2.72) independently influenced outcome. Bloodstream infections in the 1990s are notable for the increased importance of CNS as both contaminants and pathogens, the proportionate increase in fungi and decrease in anaerobes as pathogens, the emergence of Mycobacterium avium complex as an important cause of bacteremia in patients with advanced human immunodeficiency virus infection, and the reduction in mortality associated with infection.
A K Gopal, V G Fowler, M Shah, D Gesty-Palmer, K A Marr, R S McClelland, L K Kong, G S Gottlieb, K Lanclos, J Li, D J Sexton, G R Corey
Prospective analysis of Staphylococcus aureus bacteremia in nonneutropenic adults with malignancy.
J Clin Oncol. 2000 Mar;18(5):1110-5.
Abstract/Text
PURPOSE: To determine the primary sources and secondary complications of Staphylococcus aureus bacteremia (SAB) in cancer patients, as well as predictors of outcome in cancer patients with SAB.
PATIENTS AND METHODS: Fifty-two patients at Duke University Medical Center met entry criteria between September 1994 and December 1996 for this prospective cohort study involving hospitalized nonneutropenic adult cancer patients with SAB. All subjects were observed throughout initial hospitalization and were evaluated again at 6 and 12 weeks or until death.
RESULTS: SAB was intravascular device-related in 42%, tissue infection-related (TIR) in 44%, and unidentifiable focus-related (UFR) in 13%. Seventeen patients (33%) were found to have metastatic infections or conditions, with eight (15%) developing infectious endocarditis (IE). Patients with TIR bacteremia were less likely than other patients to develop IE (4% v 24%, P =.06). The overall mortality rate was 38%, the SAB-related mortality rate was 15%, and the rate of SAB relapse was 12%. Methicillin resistance was not associated with adverse outcome. Inability to identify a point of entry (UFR bacteremia), however, was associated with a higher overall mortality rate (100% v 24%, P =.0006). Furthermore, a 72-hour surveillance blood culture positive for organisms was associated with an increased incidence of IE (P =.0006), metastatic infections or conditions (P =.0002), SAB relapse (P =.038), and SAB-related death (P =.038).
CONCLUSION: SAB in cancer patients is associated with significant morbidity from frequent metastatic infections or conditions including IE, as well as considerable mortality. Unknown initial infection site and 72-hour surveillance cultures positive for organisms were predictive of a complicated course and poor final outcome.
Feng-Yee Chang, Brent B MacDonald, James E Peacock, Daniel M Musher, Patricia Triplett, Joseph M Mylotte, Alice O'Donnell, Marilyn M Wagener, Victor L Yu
A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance.
Medicine (Baltimore). 2003 Sep;82(5):322-32. doi: 10.1097/01.md.0000091185.93122.40.
Abstract/Text
Our objectives were to determine the incidence of endocarditis in patients whose Staphylococcus aureus bacteremia was community-acquired, related to hemodialysis, or hospital-acquired; to assess clinical factors that would reliably distinguished between S. aureus bacteremia and S. aureus endocarditis; to assess the emergence of methicillin-resistant S. aureus (MRSA) as a cause of endocarditis; and to examine risk factors for mortality in patients with S. aureus endocarditis. We conducted a prospective observational study in 6 university teaching hospitals; we evaluated 505 consecutive patients with Staphylococcus aureus bacteremia. Thirteen percent of patients with S. aureus bacteremia were found to have endocarditis, including 21% with community-acquired S. aureus bacteremia, 5% with hospital-acquired bacteremia, and 12% on hemodialysis. Infection was due to MRSA in 31%. Factors predictive of endocarditis included underlying valvular heart disease, history of prior endocarditis, intravenous drug use, community acquisition of bacteremia, and an unrecognized source. Twelve patients with bacteremia had a prosthetic valve; 17% developed endocarditis. Unexpectedly, nonwhite race proved to be an independent risk factor for endocarditis by both univariate and multivariate analyses. Persistent bacteremia (positive blood cultures at day 3 of appropriate therapy) was identified as an independent risk factor for both endocarditis and mortality, a unique observation not reported in other prospective studies of S. aureus bacteremia. Patients with endocarditis due to MRSA were significantly more likely to have complicating renal insufficiency and to experience persistent bacteremia than those with endocarditis due to MSSA. The 30-day mortality was 31% among patients with endocarditis compared to 21% in patients who had bacteremia without endocarditis (p = 0.055). Risk factors for death due to endocarditis included severity of illness at onset of bacteremia (as measured by Apache III and Pitt bacteremia score), MRSA infection, and presence of atrioventricular block on electrocardiogram. Patients with S. aureus bacteremia who have community acquisition of infection, underlying valvular heart disease, intravenous drug use, unknown portal of entry, history of prior endocarditis, and possibly, nonwhite race should undergo echocardiography to screen for the presence of endocarditis. We recommend that blood cultures be repeated 3 days following initiation of antistaphylococcal antibiotic therapy in all patients with S. aureus bacteremia. Positive blood cultures at 3 days may prove to be a useful marker in promoting more aggressive management, including more potent antibiotic therapy and surgical resection of the valve in endocarditis cases. MRSA as the infecting organism should be added to the list of risk factors for consideration of valvular resection in cases of endocarditis.
Anne Marie Valente, Rajiv Jain, Mark Scheurer, Vance G Fowler, G Ralph Corey, A Resai Bengur, Stephen Sanders, Jennifer S Li
Frequency of infective endocarditis among infants and children with Staphylococcus aureus bacteremia.
Pediatrics. 2005 Jan;115(1):e15-9. doi: 10.1542/peds.2004-1152. Epub 2004 Dec 15.
Abstract/Text
PURPOSE: The prevalence of infective endocarditis (IE) among children with Staphylococcus aureus bacteremia (SAB) is unknown. The objective of this study was to determine prospectively the prevalence of IE among pediatric patients with SAB in a large tertiary care center.
METHODS: Between July 1998 and June 2001, all children who developed SAB whose parent/guardian signed informed consent underwent echocardiography. Clinical and follow-up results were collected prospectively. Endocarditis was classified according to the modified Duke criteria.
RESULTS: Fifty-one children developed SAB during the study interval. Definite (6 patients [11.8%]) or possible (4 patients [7.8%]) IE was present in 10 of 51 (20%) children with SAB. Most children (73%) developed bacteremia as a consequence of an infected intravascular device. Children with underlying congenital heart disease had a significantly higher prevalence of definite or possible IE, compared with those with structurally normal hearts (53% vs 3%). All patients with definite IE had multiple positive blood cultures. Mortality was high among patients with and without IE (40% vs 12%).
CONCLUSIONS: In this study, the prevalence of definite IE among children with SAB was approximately 12% and was frequently associated with congenital heart disease and multiple positive blood cultures. The mortality for children with SAB and definite or possible S aureus IE is high.
Vance G Fowler, Jose M Miro, Bruno Hoen, Christopher H Cabell, Elias Abrutyn, Ethan Rubinstein, G Ralph Corey, Denis Spelman, Suzanne F Bradley, Bruno Barsic, Paul A Pappas, Kevin J Anstrom, Dannah Wray, Claudio Q Fortes, Ignasi Anguera, Eugene Athan, Philip Jones, Jan T M van der Meer, Tom S J Elliott, Donald P Levine, Arnold S Bayer, ICE Investigators
Staphylococcus aureus endocarditis: a consequence of medical progress.
JAMA. 2005 Jun 22;293(24):3012-21. doi: 10.1001/jama.293.24.3012.
Abstract/Text
CONTEXT: The global significance of infective endocarditis (IE) caused by Staphylococcus aureus is unknown.
OBJECTIVES: To document the international emergence of health care-associated S aureus IE and methicillin-resistant S aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE.
DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study set in 39 medical centers in 16 countries. Participants were a population of 1779 patients with definite IE as defined by Duke criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003.
MAIN OUTCOME MEASURE: In-hospital mortality.
RESULTS: S aureus was the most common pathogen among the 1779 cases of definite IE in the International Collaboration on Endocarditis Prospective-Cohort Study (558 patients, 31.4%). Health care-associated infection was the most common form of S aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to 54.2% (Brazil) of cases. Most patients with health care-associated S aureus IE (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was independently associated with MRSA IE (odds ratio, 6.2; 95% confidence interval, 2.9-13.2). Patients in the United States were most likely to be hemodialysis dependent, to have diabetes, to have a presumed intravascular device source, to receive vancomycin, to be infected with MRSA, and to have persistent bacteremia (P<.001 for all comparisons).
CONCLUSIONS: S aureus is the leading cause of IE in many regions of the world. Characteristics of patients with S aureus IE vary significantly by region. Further studies are required to determine the causes of regional variation.
José M Miro, Ignasi Anguera, Christopher H Cabell, Anita Y Chen, Judith A Stafford, G Ralph Corey, Lars Olaison, Susannah Eykyn, Bruno Hoen, Elias Abrutyn, Didier Raoult, Arnold Bayer, Vance G Fowler, International Collaboration on Endocarditis Merged Database Study Group
Staphylococcus aureus native valve infective endocarditis: report of 566 episodes from the International Collaboration on Endocarditis Merged Database.
Clin Infect Dis. 2005 Aug 15;41(4):507-14. doi: 10.1086/431979. Epub 2005 Jul 6.
Abstract/Text
BACKGROUND: Staphylococcus aureus native valve infective endocarditis (SA-NVIE) is not completely understood. The objective of this investigation was to describe the characteristics of a large, international cohort of patients with SA-NVIE.
METHODS: The International Collaboration on Endocarditis Merged Database (ICE-MD) is a combination of 7 existing electronic databases from 5 countries that contains data on 2212 cases of definite infective endocarditis (IE).
RESULTS: Of patients with native valve IE, 566 patients [corrected] had IE due to S. aureus, and 1074 patients had IE due to pathogens other than S. aureus (non-SA-NVIE). Patients with S. aureus IE were more likely to die (20% vs. 12%; P < .001), to experience an embolic event (61% [corrected] vs. 31%; P < .001), or to have a central nervous system event (21% [corrected] vs. 13%; P < .001) and were less likely to undergo surgery (26% vs. 39%; P < .001) than were patients with non-SA-NVIE. Multivariate analysis of prognostic factors of mortality identified age (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.7), periannular abscess (OR, 2.4; 95% CI, 1.0 [corrected] -5.6), heart failure (OR, 3.9; 95% CI, 2.3-6.7), and absence of surgical therapy (OR, 2.3; 95% CI, 1.3-4.2) as variables that were independently associated with mortality in patients with SA-NVIE. After adjusting for patient-, pathogen-, and treatment-specific characteristics by multivariate analysis, geographical region was also found to be associated with mortality in patients with SA-NVIE (P < .001).
CONCLUSIONS: S. aureus is an important and common cause of IE. The outcome of SA-NVIE is worse than that of non-SA-NVIE. Several clinical parameters are independently associated with mortality for patients with SA-NVIE. The clinical characteristics and outcome of SA-NVIE vary significantly by geographic region, although the reasons for such regional variations in outcomes of SA-NVIE are unknown and are probably multifactorial. A large, prospective, multinational cohort study of patients with IE is now under way to further investigate these observations.
V G Fowler, J Li, G R Corey, J Boley, K A Marr, A K Gopal, L K Kong, G Gottlieb, C L Donovan, D J Sexton, T Ryan
Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients.
J Am Coll Cardiol. 1997 Oct;30(4):1072-8.
Abstract/Text
OBJECTIVES: The purpose of this prospective study was to examine the role of echocardiography in patients with Staphylococcus aureus bacteremia (SAB).
BACKGROUND: The reported incidence of infective endocarditis (IE) among patients with SAB varies widely. Distinguishing patients with uncomplicated bacteremia from those with IE is therapeutically and prognostically important, but often difficult.
METHODS: One hundred-three consecutive patients undergoing both transthoracic (TTE) echocardiography and transesophageal (TEE) echocardiography were prospectively evaluated. All patients presented with fever and > or = 1 positive blood culture and were followed up for 12 weeks.
RESULTS: Although predisposing heart disease was present in 42 patients (41%), clinical evidence of infective endocarditis (IE) was rare (7%). TTE revealed anatomic abnormalities in 33 patients, but vegetations in only 7 (7%), and was considered indeterminate in 19 (18%). TEE identified vegetations in 22 patients (aortic valve in 5, mitral valve in 9, tricuspid valve in 4, catheter in 2 and pacemaker in 2, abscesses in 2, valve perforation in 1 and new severe regurgitation in 1; 26 total [25%]). Using Duke criteria for the diagnosis of IE, definite IE was present in 26 patients (25%). Clinical findings and predisposing heart disease did not distinguish between patients with and without IE. The sensitivity of TTE for detecting IE was 32%, and the specificity was 100%. The addition of TEE increased the sensitivity to 100%, but resulted in one false positive result (specificity 99%). TEE detected evidence of IE in 19% of patients with a negative TTE and 21% of patients with an indeterminate TTE. At follow-up, cure of staphylococcal infection occurred in a similar percentage of patients with and without IE (77% and 75%, respectively). However, death due to sepsis was significantly more likely among patients with IE (4 of 26 [15%]) than among those without IE (2 of 77 [3%]) (p = 0.03).
CONCLUSIONS: Our results suggest that IE is common among patients admitted to the hospital with SAB and is associated with an increased risk of death due to sepsis. TEE is essential to establish the diagnosis and to detect associated complications. Therefore, the test should be considered part of the early evaluation of patients with SAB.
P R Marantz, M Linzer, C J Feiner, S A Feinstein, A M Kozin, G H Friedland
Inability to predict diagnosis in febrile intravenous drug abusers.
Ann Intern Med. 1987 Jun;106(6):823-8.
Abstract/Text
Although hospitalization is recommended for all febrile intravenous drug abusers, this practice has not been tested and validated. To determine the distribution of disease and the predictive value of clinical information available in the emergency room for diagnosis in these patients, we prospectively evaluated the clinical and laboratory data for 87 consecutive admissions involving 75 intravenous drug abusers with temperature of 38.1 degrees C or more, emergency room physicians' diagnostic predictions, and final diagnosis. Final diagnoses were pneumonia in 38% of the patients, trivial illness (viral syndrome, pharyngitis, or pyrogen reaction) in 26%, infective endocarditis in 13%, and other conditions in 23%. Neither emergency room physicians' diagnostic predictions nor clinical data correlated with a final diagnosis of endocarditis. Although physicians' prediction of trivial illness was associated with a final diagnosis of trivial illness (p less than 0.05), 29% of these patients had a more serious final diagnosis. These data confirm the need to hospitalize all intravenous drug abusers presenting with fever at an emergency room.
A Lance Sullenberger, Lena S Avedissian, Steven M Kent
Importance of transesophageal echocardiography in the evaluation of Staphylococcus aureus bacteremia.
J Heart Valve Dis. 2005 Jan;14(1):23-8.
Abstract/Text
BACKGROUND AND AIM OF THE STUDY: Staphylococcus aureus is a leading cause of bacteremia and is often associated with endocarditis. The diagnosis of endocarditis may be missed when relying on clinical risk prediction, and this has led others to recommend transesophageal echocardiography (TEE) for diagnosis in most cases of S. aureus bacteremia (SAB). The study aim was to determine the likelihood of finding vegetations on TEE in patients with SAB in a suburban teaching hospital setting, and to identify risk factors predictive of vegetation on TEE.
METHODS: All cases of SAB at Walter Reed Army Medical Center between January 2000 and May 2003 were evaluated. The prevalence of vegetations was determined in those cases selected for TEE. Potential risk factors for endocarditis were analyzed by review of medical records.
RESULTS: A total of 176 patients had documented SAB during the time frame of the study, and 64 of these had TEE performed. Among the latter patients, 14% had a previously unidentified vegetation discovered by TEE. Patients with vegetation on TEE were as likely as those without vegetation to have nosocomial bacteremia, an alternate source of infection, and lack of valvular disease by prior surface echocardiography. Patients with a vegetation were significantly older (mean age 68.4+/-10.9 versus 54.6+/-19.6 years; p = 0.04).
CONCLUSION: TEE identified a significant number of vegetations resulting from SAB. The clinical risk profile and transthoracic echocardiography did not reliably exclude vegetation. These findings support the liberal use of TEE for the diagnosis of SAB.
James Abraham, Craig Mansour, Emir Veledar, Bobby Khan, Stamatios Lerakis
Staphylococcus aureus bacteremia and endocarditis: the Grady Memorial Hospital experience with methicillin-sensitive S aureus and methicillin-resistant S aureus bacteremia.
Am Heart J. 2004 Mar;147(3):536-9. doi: 10.1016/j.ahj.2003.09.018.
Abstract/Text
BACKGROUND: Staphylococcus aureus has become the leading cause of endocarditis in most published series, and nosocomial acquisition is becoming more frequent. Previous studies involved community acquired methicillin-sensitive S aureus (MSSA), but recently, methicillin-resistant S aureus(MRSA) infection has increased. This may reflect the growing presence of this microorganism in clinical practice. Few data exist comparing the relative rates of endocarditis with MSSA and MRSA bacteremia. The purpose of this study was to compare these rates in a bacteremic population referred for diagnostic echocardiography.
METHODS: Since July 1999, the demographic and clinical information of 104 consecutive patients with at least 2 blood cultures with positive results for S aureus who were referred for echocardiography to be evaluated for endocarditis at Grady Memorial Hospital (Atlanta, Ga) have been entered into a database. This database has further been restricted to patients who have undergone either a transesophageal echocardiogram or a transthoracic echocardiogram.
RESULTS: Of the 104 patients with S aureus bacteremia, 53 had an infection of MSSA and 51 had an infection of MRSA. There were 33 patients (31.7%) with echocardiographically confirmed endocarditis, 23 patients (43.4%) in the MSSA group versus 10 patients (19.6%) in the MRSA group (P <.009). Community-acquired MSSA bacteremia was the cause of most of the community-acquired S aureus endocarditis (20 patients [87%] vs 3 patients [30%], P =.004), and the nosocomial-acquired MRSA bacteremia was the cause of most of the nosocomial-acquired S aureus endocarditis (3 patients [13%] vs 7 patients [70%], P =.0001).
CONCLUSION: Our study confirms that S aureus bacteremia is associated with high rates of endocarditis. MSSA bacteremia is associated with higher rates of endocarditis than MRSA. Community MSSA is the cause of most of the community endocarditis, whereas nosocomial MRSA is the cause of most of the MRSA endocarditis. Patients with S aureus bacteremia should be aggressively evaluated for endocarditis.
Howard S An, J Alex Seldomridge
Spinal infections: diagnostic tests and imaging studies.
Clin Orthop Relat Res. 2006 Mar;444:27-33. doi: 10.1097/01.blo.0000203452.36522.97.
Abstract/Text
Clinical signs and symptoms caused by spinal infections often are subtle and insidious; therefore, clinical suspicion in patients with nonmechanical pain is important in making the correct diagnosis in the early stage of disease. Serologic tests such as erythrocyte sedimentation rate and C-reactive protein are quite sensitive, but specificity is relatively low. Imaging tests include plain radiographs, radionuclide studies, computed tomography scan, and magnetic resonance imaging. Changes on plain radiographs appear at least 3 to 4 weeks after the onset of disease. Bone scan is a sensitive but not a specific test. Computed tomography provides structural details in the bone and intervertebral disc but magnetic resonance imaging is a superior imaging test for diagnosing infections earlier and more accurately. In many patients, percutaneous or open biopsy is required to make the definitive diagnosis of discitis or osteomyelitis and the organism responsible for the infection. Early and accurate diagnosis of spinal infections will lead to less invasive treatment for the patient. Level of Evidence: Level V (Expert Opinion). Please see the Guidelines for Authors for a complete description of levels of evidence.
Modic M T MT, Feiglin D H DH, Piraino D W DW, Boumphrey F F, Weinstein M A MA, Duchesneau P M PM, Rehm S S
Vertebral osteomyelitis: assessment using MR.
Radiology. 1985 Oct;157(1):157-66.
Abstract/Text
Thirty-seven patients who were clinically suspected of having vertebral osteomyelitis were prospectively evaluated with magnetic resonance (MR), radiography, and radionuclide studies. These findings were correlated with the final clinical, microbiologic, or histologic diagnoses. Based on the results of these latter studies, 23 patients were believed to have osteomyelitis. MR examinations consisted of at least a sagittal image (TE = 30 msec, TR = 0.5 sec) and an image obtained at TE = 120 msec, TR = 2-3 sec. All patients underwent radiographic and MR examinations, 36 underwent technetium 99m-HDP bone scanning, and 20 patients underwent gallium 67 scanning. Nineteen patients underwent both bone and gallium scanning. The imaging studies were reviewed independently by investigators blinded to the final diagnoses. MR had a sensitivity of 96%, specificity of 92%, and accuracy of 94%. Combined gallium and bone scan studies (19 cases) had a sensitivity of 90%, specificity of 100%, and accuracy of 94%. Bone scans alone had a sensitivity of 90%, specificity of 78%, and accuracy of 86%. Plain radiographs had a sensitivity of 82%, specificity of 57%, and accuracy of 73%. The MR appearance of vertebral osteomyelitis in this study was characteristic, and MR was as accurate and sensitive as radionuclide scanning in the detection of osteomyelitis.
L S Fishman, J R Griffin, F L Sapico, R Hecht
Hematogenous Candida endophthalmitis--a complication of candidemia.
N Engl J Med. 1972 Mar 30;286(13):675-81. doi: 10.1056/NEJM197203302861301.
Abstract/Text
U G Hodgin, J P Sanford
Gram-negative rod bacteremia. An analysis of 100 patients.
Am J Med. 1965 Dec;39(6):952-60.
Abstract/Text
Joseph M Mylotte, Ammar Tayara, Susan Goodnough
Epidemiology of bloodstream infection in nursing home residents: evaluation in a large cohort from multiple homes.
Clin Infect Dis. 2002 Dec 15;35(12):1484-90. doi: 10.1086/344649. Epub 2002 Dec 2.
Abstract/Text
This study sought to reevaluate the epidemiology of bloodstream infection in nursing home residents. The records of 166 nursing home residents admitted to an urban, public, university-affiliated hospital with 169 episodes of bloodstream infection between January 1997 and April 2000 were retrospectively reviewed. The most common organisms isolated were Escherichia coli (27% of isolates), Staphylococcus aureus (18%; 29% were methicillin-resistant strains), and Proteus mirabilis (13%). There was minimal resistance to quinolones and third-generation cephalosporins among aerobic gram-negative bacilli. The most common sources were the urinary tract (51% of episodes) and the lungs (11%); a source was not identified in 22% of episodes. Hospital mortality was 18%. Independent predictors of hospital mortality were a pulmonary source of infection, systolic blood pressure <90 mm Hg, and leukocytosis >20,000 cells/mm3. Compared with other studies published in the past 2 decades, mortality was lower. The most common resistant organism was methicillin-resistant S. aureus.
George G Zhanel, Tamiko L Hisanaga, Nancy M Laing, Melanie R DeCorby, Kim A Nichol, Lorraine P Palatnik, Jack Johnson, Ayman Noreddin, Godfrey K M Harding, Lindsay E Nicolle, Daryl J Hoban, NAUTICA Group
Antibiotic resistance in outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA).
Int J Antimicrob Agents. 2005 Nov;26(5):380-8. doi: 10.1016/j.ijantimicag.2005.08.003.
Abstract/Text
The goal of the North American Urinary Tract Infection Collaborative Alliance (NAUTICA) study was to determine antibiotic susceptibility to commonly used agents for urinary tract infections against outpatient urinary isolates obtained in various geographic regions in the USA and Canada. Forty-one medical centres (30 from the USA and 11 from Canada) participated, with each centre submitting up to 50 consecutive outpatient midstream urine isolates. Isolates were identified to species level by the standard protocol of each laboratory. Susceptibility testing was determined using the National Committee for Clinical Laboratory Standards (NCCLS) microdilution method. Resistance breakpoints used were those published by the NCCLS, including: ampicillin (resistant > or = 32 microg/mL), sulphamethoxazole/trimethoprim (SMX/TMP) (resistant > or = 4 microg/mL), nitrofurantoin (resistant > or = 128 microg/mL), ciprofloxacin (resistant > or = 4 microg/mL) and levofloxacin (resistant > or = 8 microg/mL). Of the 1990 isolates collected, 75.1% (1494) were collected from the USA and 24.9% (496) were collected from Canada. The mean age of the patients was 48.3 years (range 1 month to 99 years), and 79.5% and 20.5% of isolates were obtained from women and men, respectively. The most common organisms were Escherichia coli (57.5%), Klebsiella pneumoniae (12.4%), Enterococcus spp. (6.6%), Proteus mirabilis (5.4%), Pseudomonas aeruginosa (2.9%), Citrobacter spp. (2.7%), Staphylococcus aureus (2.2%), Enterobacter cloacae (1.9%), coagulase-negative staphylococci (1.3%), Staphylococcus saprophyticus (1.2%), Klebsiella spp. (1.2%), Enterobacter aerogenes (1.1%) and Streptococcus agalactiae (1.0%). Among all 1990 isolates, 45.9% were resistant to ampicillin, 20.4% to SMX/TMP, 14.3% to nitrofurantoin, 9.7% to ciprofloxacin and 8.1% to levofloxacin. Fluoroquinolone resistance was highest in patients > or = 65 years of age. For the 1142 E. coli isolates, resistance rates were: ampicillin 37.7%, SMX/TMP 21.3%, ciprofloxacin 5.5%, levofloxacin 5.1% and nitrofurantoin 1.1%. For all 1990 isolates and for the 1142 E. coli only, resistance rates were significantly higher in US compared with Canadian medical centres. This study reports higher rates of antibiotic resistance in US versus Canadian outpatient urinary isolates and demonstrates the continuing evolution of resistance to antimicrobial agents.
Joseph S Solomkin, John E Mazuski, John S Bradley, Keith A Rodvold, Ellie J C Goldstein, Ellen J Baron, Patrick J O'Neill, Anthony W Chow, E Patchen Dellinger, Soumitra R Eachempati, Sherwood Gorbach, Mary Hilfiker, Addison K May, Avery B Nathens, Robert G Sawyer, John G Bartlett
Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America.
Clin Infect Dis. 2010 Jan 15;50(2):133-64. doi: 10.1086/649554.
Abstract/Text
Evidence-based guidelines for managing patients with intra-abdominal infection were prepared by an Expert Panel of the Surgical Infection Society and the Infectious Diseases Society of America. These updated guidelines replace those previously published in 2002 and 2003. The guidelines are intended for treating patients who either have these infections or may be at risk for them. New information, based on publications from the period 2003-2008, is incorporated into this guideline document. The panel has also added recommendations for managing intra-abdominal infection in children, particularly where such management differs from that of adults; for appendicitis in patients of all ages; and for necrotizing enterocolitis in neonates.
Qiwen Yang, Hui Wang, Minjun Chen, Yuxing Ni, Yunsong Yu, Bijie Hu, Ziyong Sun, Wenxiang Huang, Yunjian Hu, Huifen Ye, Robert E Badal, Yingchun Xu
Surveillance of antimicrobial susceptibility of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in China: the 2002-2009 Study for Monitoring Antimicrobial Resistance Trends (SMART).
Int J Antimicrob Agents. 2010 Dec;36(6):507-12. doi: 10.1016/j.ijantimicag.2010.09.001. Epub 2010 Oct 30.
Abstract/Text
The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli (GNB) isolated from patients with intra-abdominal infections (IAIs) in China. From 2002 to 2009, minimum inhibitory concentrations of 14 antibiotics for 3420 aerobic and facultative GNB from up to eight hospitals in six cities were determined by the broth microdilution method. Enterobacteriaceae comprised 82.9% (2834/3420) of the total isolates, with Escherichia coli (49.2%) being the most commonly isolated species followed by Klebsiella pneumoniae (17.0%), Enterobacter cloacae (5.8%) and Citrobacter freundii (2.3%). Amongst the antimicrobial agents tested, the three carbapenems (ertapenem, imipenem and meropenem) were the most active agents against Enterobacteriaceae, with susceptibility rates of 96.1-99.6% (2002-2009), 98.2-100% (2002-2009) and 99.6-100% (2002-2004), respectively, followed by amikacin (86.8-95.1%) and piperacillin/tazobactam (84.5-94.3%). Susceptibility rates of all tested third- and fourth-generation cephalosporins against Enterobacteriaceae declined by nearly 30%, with susceptibility rates of 40.2%, 39.1%, 56.3% and 51.8% in 2009 for ceftriaxone, cefotaxime, ceftazidime and cefepime, respectively. The occurrence of extended-spectrum β-lactamases increased rapidly, especially for E. coli (from 20.8% in 2002 to 64.9% in 2009). Susceptibility of E. coli to ciprofloxacin decreased from 57.6% in 2002 to 24.2% in 2009. The least active agent against Enterobacteriaceae was ampicillin/sulbactam (SAM) (25.3-44.3%). In conclusion, Enterobacteriaceae were the major pathogens causing IAIs, and carbapenems retained the highest susceptibility rates over the 8-year study period. Third- and fourth-generation cephalosporins, fluoroquinolones and SAM may not be ideal choices for empirical therapy of IAIs in China.
Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
David R Snydman, Nilda V Jacobus, Laura A McDermott, Yoav Golan, David W Hecht, Ellie J C Goldstein, Lizzie Harrell, Stephen Jenkins, Duane Newton, Carl Pierson, John D Rihs, Victor L Yu, Richard Venezia, Sydney M Finegold, Jon E Rosenblatt, Sherwood L Gorbach
Lessons learned from the anaerobe survey: historical perspective and review of the most recent data (2005-2007).
Clin Infect Dis. 2010 Jan 1;50 Suppl 1:S26-33. doi: 10.1086/647940.
Abstract/Text
BACKGROUND: The rationale and lessons learned through the evolution of the National Survey for the Susceptibility of Bacteroides fragilis Group from its initiation in 1981 through 2007 are reviewed here. The survey was conceived in 1980 to track emerging antimicrobial resistance in Bacteroides species.
METHODS: Data from the last 11 years of the survey (1997-2007), including 6574 isolates from 13 medical centers, were analyzed for in vitro antimicrobial resistance to both frequently used and newly developed anti-anaerobic agents. The minimum inhibitory concentrations of the antibiotics were determined using agar dilution in accordance with Clinical and Laboratory Standards Institute recommendations.
RESULTS: The analyses revealed that the carbapenems (imipenem, meropenem, ertapenem, and doripenem) and piperacillin-tazobactam were the most active agents against these pathogens, with resistance rates of 0.9%-2.3%. In the most recent 3 years of the survey (2005-2007), resistance to some agents was shown to depend on the species, such as ampicillin-sulbactam against Bacteroides distasonis (20.6%) and tigecycline against Bacteroides uniformis and Bacteroides eggerthii ( approximately 7%). Very high resistance rates (>50%) were noted for moxifloxacin and trovafloxacin, particularly against Bacteroides vulgatus. During that period of study, non-B. fragilis Bacteroides species had >40% resistance to clindamycin. Metronidazole-resistant Bacteroides strains were also first reported during that period.
CONCLUSIONS: In summary, resistance to antibiotics was greater among non-B. fragilis Bacteroides species than among B. fragilis and was especially greater among species with a low frequency of isolation, such as Bacteroides caccae and B. uniformis. The emergence of resistance among the non-B. fragilis Bacteroides species underscores the need for speciation of B. fragilis group isolates and for clinicians to be aware of associations between species and drug resistance.
Harald Seifert, Axel Dalhoff, PRISMA Study Group
German multicentre survey of the antibiotic susceptibility of Bacteroides fragilis group and Prevotella species isolated from intra-abdominal infections: results from the PRISMA study.
J Antimicrob Chemother. 2010 Nov;65(11):2405-10. doi: 10.1093/jac/dkq321. Epub 2010 Sep 16.
Abstract/Text
OBJECTIVES: To determine the susceptibility of Gram-negative anaerobic bacteria of the family Bacteroidaceae from hospitalized patients with intra-abdominal infections (IAIs) to moxifloxacin and other antimicrobial agents with known activity against anaerobes.
METHODS: Four hundred and thirty anaerobic bacterial isolates of the family Bacteroidaceae obtained from patients with IAIs were collected from 32 centres in Germany in 2007. MICs were determined using microbroth dilution for the following antimicrobials: ampicillin/sulbactam; ertapenem; meropenem; levofloxacin; moxifloxacin; clindamycin; and metronidazole. EUCAST and CLSI guidelines (for moxifloxacin) were used for interpretation.
RESULTS: Overall, metronidazole exhibited the lowest resistance rates against the study isolates (four isolates, 0.9%), while the resistance rate was 4.9% for ampicillin/sulbactam, 5.3% for ertapenem and 4.9% for meropenem. Moxifloxacin showed good activity against most Bacteroides species. Resistance rates ranged between 10% and 22% for the various species except Bacteroides vulgatus, with 59% of isolates being resistant. Clindamycin had only poor activity, with 9%-56% of Bacteroides isolates being resistant.
CONCLUSIONS: Resistance among Bacteroides spp. involved in IAIs to antimicrobials with known activity against anaerobes does occur and the resistance rate observed for the carbapenems is a cause of concern. These data emphasize the need not only for periodic monitoring of the susceptibility of anaerobic pathogens to guide empirical treatment but also for species identification and susceptibility testing in selected patients with severe infections involving anaerobic bacteria.
Hilmar Wisplinghoff, Tammy Bischoff, Sandra M Tallent, Harald Seifert, Richard P Wenzel, Michael B Edmond
Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study.
Clin Infect Dis. 2004 Aug 1;39(3):309-17. doi: 10.1086/421946. Epub 2004 Jul 15.
Abstract/Text
BACKGROUND: Nosocomial bloodstream infections (BSIs) are important causes of morbidity and mortality in the United States.
METHODS: Data from a nationwide, concurrent surveillance study (Surveillance and Control of Pathogens of Epidemiological Importance [SCOPE]) were used to examine the secular trends in the epidemiology and microbiology of nosocomial BSIs.
RESULTS: Our study detected 24,179 cases of nosocomial BSI in 49 US hospitals over a 7-year period from March 1995 through September 2002 (60 cases per 10,000 hospital admissions). Eighty-seven percent of BSIs were monomicrobial. Gram-positive organisms caused 65% of these BSIs, gram-negative organisms caused 25%, and fungi caused 9.5%. The crude mortality rate was 27%. The most-common organisms causing BSIs were coagulase-negative staphylococci (CoNS) (31% of isolates), Staphylococcus aureus (20%), enterococci (9%), and Candida species (9%). The mean interval between admission and infection was 13 days for infection with Escherichia coli, 16 days for S. aureus, 22 days for Candida species and Klebsiella species, 23 days for enterococci, and 26 days for Acinetobacter species. CoNS, Pseudomonas species, Enterobacter species, Serratia species, and Acinetobacter species were more likely to cause infections in patients in intensive care units (P<.001). In neutropenic patients, infections with Candida species, enterococci, and viridans group streptococci were significantly more common. The proportion of S. aureus isolates with methicillin resistance increased from 22% in 1995 to 57% in 2001 (P<.001, trend analysis). Vancomycin resistance was seen in 2% of Enterococcus faecalis isolates and in 60% of Enterococcus faecium isolates.
CONCLUSION: In this study, one of the largest multicenter studies performed to date, we found that the proportion of nosocomial BSIs due to antibiotic-resistant organisms is increasing in US hospitals.
Vered Schechner, Vandack Nobre, Keith S Kaye, Moshe Leshno, Michael Giladi, Peter Rohner, Stephan Harbarth, Deverick J Anderson, Adolf W Karchmer, Mitchell J Schwaber, Yehuda Carmeli
Gram-negative bacteremia upon hospital admission: when should Pseudomonas aeruginosa be suspected?
Clin Infect Dis. 2009 Mar 1;48(5):580-6. doi: 10.1086/596709.
Abstract/Text
BACKGROUND: Pseudomonas aeruginosa is an uncommon cause of community-acquired bacteremia among patients without severe immunodeficiency. Because tension exists between the need to limit unnecessary use of anti-pseudomonal agents and the need to avoid a delay in appropriate therapy, clinicians require better guidance regarding when to cover empirically for P. aeruginosa. We sought to determine the occurrence of and construct a model to predict P. aeruginosa bacteremia upon hospital admission.
METHODS: A retrospective study was conducted in 4 tertiary care hospitals. Microbiology databases were searched to find all episodes of bacteremia caused by gram-negative rods (GNRs) RESULTS: P. aeruginosa caused 6.8% of 4114 unique patient episodes of GNR bacteremia upon hospital admission (incidence ratio, 5 cases per 10,000 hospital admissions). Independent predictors of P. aeruginosa bacteremia were severe immunodeficiency, age >90 years, receipt of antimicrobial therapy within past 30 days, and presence of a central venous catheter or a urinary device. Among 250 patients without severe immunodeficiency, if no predictor variables existed, the likelihood of having P. aeruginosa bacteremia was 1:42. If >or= 2 predictors existed, the risk increased to nearly 1:3.
CONCLUSIONS: P. aeruginosa bacteremia upon hospital admission in patients without severe immunodeficiency is rare. Among immunocompetent patients with suspected GNR bacteremia who have >or= 2 predictors, empirical anti-pseudomonal treatment is warranted.
M Paul, I Silbiger, S Grozinsky, K Soares-Weiser, L Leibovici
Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis.
Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003344. doi: 10.1002/14651858.CD003344.pub2. Epub 2006 Jan 25.
Abstract/Text
BACKGROUND: Optimal antibiotic treatment for sepsis is imperative. Combining a beta-lactam antibiotic with an aminoglycoside antibiotic may have certain advantages over beta-lactam monotherapy.
OBJECTIVES: We compared clinical outcomes for beta lactam-aminoglycoside combination therapy versus beta lactam monotherapy for sepsis.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 3, 2004); MEDLINE (1966 to July 2004); EMBASE (1980 to March 2003); LILACS (1982 to July 2004); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2003). We scanned citations of all identified studies and contacted all corresponding authors.
SELECTION CRITERIA: We included randomized and quasi-randomized trials comparing any beta-lactam monotherapy to any combination of one beta-lactam and one aminoglycoside for sepsis.
DATA COLLECTION AND ANALYSIS: The primary outcome was all-cause fatality. Secondary outcomes included treatment failure, superinfections, colonization, and adverse events. Two authors independently collected data. We pooled relative risks (RR) with their 95% confidence intervals (CI) using the fixed effect model. We extracted outcomes by intention-to-treat analysis whenever possible.
MAIN RESULTS: We included 64 trials, randomizing 7586 patients. Twenty trials compared the same beta-lactam in both study arms, while the remaining compared different beta-lactams using a broader spectrum beta-lactam in the monotherapy arm. In studies comparing the same beta-lactam, we observed no difference between study groups with regard to all-cause fatality, RR 1.01 (95% CI 0.75-1.35) and clinical failure, RR 1.11 (95% CI 0.95-1.29). In studies comparing different beta-lactams, we observed an advantage to monotherapy: all cause fatality RR 0.85 (95% CI 0.71-1.01), clinical failure RR 0.77 (95% CI 0.69-0.86). No significant disparities emerged from subgroup and sensitivity analyses, including the assessment of patients with Gram-negative and Pseudomonas aeruginosa infections. We detected no differences in the rate of resistance development. Adverse events rates did not differ significantly between the study groups overall, although nephrotoxicity was significantly more frequent with combination therapy, RR 0.30 (95% CI 0.23-0.39). We found no heterogeneity for all comparisons. We included a small subset of studies addressing patients with Gram-positive infections, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies.
AUTHORS' CONCLUSIONS: The addition of an aminoglycoside to beta-lactams for sepsis should be discouraged. All-cause fatality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.
Nasia Safdar, Jo Handelsman, Dennis G Maki
Does combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis.
Lancet Infect Dis. 2004 Aug;4(8):519-27. doi: 10.1016/S1473-3099(04)01108-9.
Abstract/Text
The use of combination antimicrobial therapy for bacteraemia caused by Gram-negative bacilli is controversial. We did a meta-analysis of published studies to determine whether a combination of two or more antimicrobials reduces mortality in patients with Gram-negative bacteraemia. Criteria for inclusion were: analytic studies of patients with documented Gram-negative bacteraemia that included patients receiving a single antibiotic (monotherapy) and patients receiving two or more antibiotics (combination therapy). Data on mortality (outcome) had to be provided. A pooled odds ratio was calculated with the random effects model of DerSimonian and Laird. Assessment of heterogeneity was done with the Breslow-Day test and reasons for heterogeneity were explored. 17 studies met the inclusion criteria, five prospective cohort studies, two prospective randomised trials, and ten retrospective cohort studies. Most studies used beta-lactams or aminoglycosides alone and in combination. The summary odds ratio was 0.96 (95% CI 0.70-1.32), indicating no mortality benefit with combination therapy. Subgroup analyses adjusting for year of publication, study design, and severity of illness did not change the results. Considerable heterogeneity was present in the main analyses. Analysis of only Pseudomonas aeruginosa bacteraemias showed a significant mortality benefit (OR 0.50, 95% CI 0.30-0.79). Our analysis does not support the routine use of combination antimicrobial therapy for Gram-negative bacteraemia, beyond settings where infection by P aeruginosa is strongly suspected or more than one drug would be desirable to assure in-vitro efficacy.
M L Panceri, F E Vegni, A Goglio, A Manisco, R Tambini, A Lizioli, A D Porretta, G Privitera, Gruppo SEPSI
Aetiology and prognosis of bacteraemia in Italy.
Epidemiol Infect. 2004 Aug;132(4):647-54.
Abstract/Text
A prospective multi-centre study was conducted to assess the microbiological pattern and prognostic factors of bacteraemia and their impact on clinical outcome. All patients admitted to 41 Italian hospitals over 2 months, from whom one or more clinically significant organisms were isolated from blood culture, were studied according to a standardized protocol and case definition. A total of 156 episodes of bacteraemia were identified in 20,601 patients. There were 3.9 episodes of nosocomially acquired bacteraemia and 3.7 episodes of community-acquired bacteraemia per 1000 admissions. The most frequent pathogens isolated were Gram-negative bacteria (44.9%) but Gram-positive species accounted for 40.4 % of episodes. Fungal infections due to Candida spp. were found in 3.8 % of episodes, and multiple pathogens were recovered from 9.6% of episodes. The clinical response to bacteraemia was classified as sepsis in 90 episodes (577%), severe sepsis in 21 (13.5%) and septic shock in 26 (167%); 19 episodes (12.2%) showed no clinical response. The total in-hospital mortality was 25.0%. By multivariate logistic regression, the variables which independently predicted mortality were increasing age, the presence of septic shock, infection with Gram-positive bacteria or fungi and nosocomial acquisition.
Michael Rybak, Ben Lomaestro, John C Rotschafer, Robert Moellering, William Craig, Marianne Billeter, Joseph R Dalovisio, Donald P Levine
Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists.
Am J Health Syst Pharm. 2009 Jan 1;66(1):82-98. doi: 10.2146/ajhp080434.
Abstract/Text
José Garnacho-Montero, Ana Díaz-Martín, Emilio García-Cabrera, Maite Ruiz Pérez de Pipaón, Clara Hernández-Caballero, Javier Aznar-Martín, José M Cisneros, Carlos Ortiz-Leyba
Risk factors for fluconazole-resistant candidemia.
Antimicrob Agents Chemother. 2010 Aug;54(8):3149-54. doi: 10.1128/AAC.00479-10. Epub 2010 May 24.
Abstract/Text
Previous studies have sought to determine the risk factors associated with candidemia caused by non-albicans Candida spp. or with potentially fluconazole-resistant Candida spp. (C. glabrata and C. krusei). Non-albicans Candida strains are a heterogeneous group that includes species with different levels of virulence, and only a limited number of C. glabrata isolates are resistant to fluconazole. We set out to identify the risk factors associated with microbiologically proven fluconazole-resistant candidemia. A prospective study including adult patients with candidemia was performed. Data were collected on patient demographics; underlying diseases; exposure to corticosteroids, antibiotics, or fluconazole; and invasive procedures. Risk factors associated either with non-albicans Candida spp. or potentially fluconazole-resistant Candida spp. (C. glabrata or C. krusei) or with Candida spp. with microbiologically confirmed fluconazole resistance were assessed using logistic regressions. We included 226 candidemia episodes. Non-albicans Candida isolates accounted for 53.1% of the fungal isolates, but only 18.2% of the cases were caused by potentially fluconazole-resistant organisms. Thirty isolates exhibited microbiologically confirmed fluconazole resistance. The multivariate analysis revealed that independent predictors associated with fluconazole-resistant Candida spp. were neutropenia (odds ratio [OR]=4.94; 95% confidence interval [CI]=1.50 to 16.20; P=0.008), chronic renal disease (OR=4.82; 95% CI=1.47 to 15.88; P=0.01), and previous fluconazole exposure (OR=5.09; 95% CI=1.66 to 15.6; P=0.004). Independently significant variables associated with non-albicans Candida bloodstream infection or with potentially fluconazole-resistant Candida spp. did not include previous fluconazole exposure. We concluded that prior fluconazole treatment is an independent risk factor only for candidemia caused by microbiologically confirmed fluconazole resistant species. Our findings may be of value for selecting empirical antifungal therapy.
E Geoffrey Playford, Deborah Marriott, Quoc Nguyen, Sharon Chen, David Ellis, Monica Slavin, Tania C Sorrell
Candidemia in nonneutropenic critically ill patients: risk factors for non-albicans Candida spp.
Crit Care Med. 2008 Jul;36(7):2034-9. doi: 10.1097/CCM.0b013e3181760f42.
Abstract/Text
OBJECTIVE: The objective of this study was to determine the clinical features associated with candidemia caused by non-albicans Candida spp. and with potentially fluconazole-resistant Candida spp. (C. glabrata and C. krusei) among candidemic intensive care unit patients.
DESIGN: The authors conducted a nationwide prospective cohort study.
SETTING: The study was conducted in Australian intensive care units.
PATIENTS: All patients with intensive care unit-acquired candidemia over a 3-yr period were included in the study.
MEASUREMENTS: Clinical risk factors occurring up to 30 days before candidemia, Candida spp. associated with candidemia, and outcomes were determined. Risk factors associated with either non-albicans Candida spp. or with potentially fluconazole-resistant Candida spp. (C. glabrata or C. krusei) were assessed using multivariate logistic regression.
MAIN RESULTS: Among 179 episodes of intensive care unit-acquired candidemia, C. albicans accounted for 62%, C. glabrata 18%, C. krusei 4%, and other Candida spp. 16%. Independently significant variables associated with non-albicans Candida bloodstream infection included recent prior gastrointestinal surgery (adjusted odds ratio, 2.87; 95% confidence interval, 1.68-4.91) and recent prior systemic antifungal exposure (4.6; 1.36-15.53). Those associated with potentially fluconazole-resistant candidemia included recent prior gastrointestinal surgery (3.31; 1.79-6.11) and recent prior fluconazole exposure (5.47; 1.23-24.32). No significant differences in outcomes were demonstrated for non-albicans or potentially fluconazole-resistant candidemia.
CONCLUSIONS: Among candidemic intensive care unit patients, prior gastrointestinal surgery and systemic antifungal exposure were significantly associated with both a non-albicans Candida spp. and a potentially fluconazole-resistant Candida spp.
Ingi Lee, Neil O Fishman, Theoklis E Zaoutis, Knashawn H Morales, Mark G Weiner, Marie Synnestvedt, Irving Nachamkin, Ebbing Lautenbach
Risk factors for fluconazole-resistant Candida glabrata bloodstream infections.
Arch Intern Med. 2009 Feb 23;169(4):379-83. doi: 10.1001/archinte.169.4.379.
Abstract/Text
BACKGROUND: Bloodstream infections (BSIs) caused by Candida glabrata have increased substantially. Candida glabrata is often associated with resistance to fluconazole therapy. However, to our knowledge, risk factors for fluconazole-resistant C glabrata BSIs have not been studied.
METHODS: A case-case-control study was conducted at 3 hospitals from January 1, 2003, to May 31, 2007. The 2 case groups included patients with fluconazole-resistant C glabrata BSIs (minimum inhibitory concentration > or =16 microg/mL) and patients with fluconazole-susceptible C glabrata BSIs (minimum inhibitory concentration < or =8 microg/mL). Hospitalized patients without C glabrata BSIs were randomly selected for inclusion in the control group and were frequency matched to cases on the basis of time at risk. Two case-control studies were performed using this shared control group. The primary risk factor of interest, previous fluconazole use, was evaluated at multivariate analyses, adjusting for demographic data, comorbid conditions, and antimicrobial exposures.
RESULTS: We included 76 patients with fluconazole-resistant C glabrata BSIs, 68 patients with fluconazole-susceptible C glabrata BSIs, and 512 control patients. Previous fluconazole use (adjusted odds ratio [95% confidence interval], 2.3 [1.3-4.2]) and linezolid use (4.6 [2.2-9.3]) were independent risk factors for fluconazole-resistant C glabrata BSIs; previous cefepime use (2.2 [1.2-3.9]) and metronidazole use (2.0 [1.1-3.5]) were independent risk factors for fluconazole-susceptible C glabrata BSIs.
CONCLUSIONS: Previous fluconazole use is a significant risk factor for health care-associated fluconazole-resistant C glabrata BSIs. Future studies will be needed to evaluate the effect of decreasing fluconazole use on rates of fluconazole-resistant C glabrata BSIs.
Alison G Freifeld, Eric J Bow, Kent A Sepkowitz, Michael J Boeckh, James I Ito, Craig A Mullen, Issam I Raad, Kenneth V Rolston, Jo-Anne H Young, John R Wingard, Infectious Diseases Society of Americaa
Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America.
Clin Infect Dis. 2011 Feb 15;52(4):427-31. doi: 10.1093/cid/ciq147. Epub 2011 Jan 4.
Abstract/Text
This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.
P M Small, H F Chambers
Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users.
Antimicrob Agents Chemother. 1990 Jun;34(6):1227-31.
Abstract/Text
The clinical courses of 13 consecutive intravenous drug users with Staphylococcus aureus endocarditis treated principally with vancomycin were reviewed. Two patients, one with only right-sided endocarditis and the other with tricuspid and mitral valve endocarditis, had recurrences of positive blood cultures 2 days after completing a 4-week course of vancomycin. Two patients, both of whom eventually were cured, had modifications of therapy because of bacteremia persisting 7 and 16 days into therapy. One patient required an operation for recurrent fevers, and the resected vegetation showed evidence of active infection. Time-kill studies performed with nafcillin and vancomycin for 10 isolates of S. aureus showed that vancomycin was less rapidly bactericidal than nafcillin. Although vancomycin is used as an alternative to penicillinase-resistant penicillins for treatment of staphylococcal endocarditis, these findings raise the question of whether it is equivalent to these drugs in efficacy.
C A Gentry, K A Rodvold, R M Novak, R C Hershow, O J Naderer
Retrospective evaluation of therapies for Staphylococcus aureus endocarditis.
Pharmacotherapy. 1997 Sep-Oct;17(5):990-7.
Abstract/Text
We retrospectively evaluated antiinfective therapy for methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) endocarditis in 54 patients who had 57 treatment courses for the disease. Three treatments were assessed: 27 nafcillin-treated courses of MSSA endocarditis, 18 vancomycin-treated courses of MSSA endocarditis, and 11 vancomycin-treated courses of MRSA endocarditis. At baseline, patients with MSSA treated with vancomycin had more chronic conditions (p<0.01), a lower frequency of intravenous drug use (p<0.01), a lower hematocrit concentration (p<0.05), and a higher serum creatinine concentration (p<0.05) than the nafcillin group. Vancomycin-treated patients had a higher complication rate during therapy (p<0.05) and a longer duration in an intensive care unit (p<0.01) than the nafcillin group. The trend was for a higher complete response rate in the nafcillin group (74% vs 50%, p=0.12), but no difference in mortality (22% vs 28%, p=0.73). Patients with MRSA infection treated with vancomycin had higher mortality than those with MSSA who received that drug (55% vs 28%, p=0.24). Patients with vancomycin-treated MSSA endocarditis may have a poorer outcome than those who receive nafcillin, but this may be influenced by different or more severe clinical features.
Feng-Yee Chang, James E Peacock, Daniel M Musher, Patricia Triplett, Brent B MacDonald, Joseph M Mylotte, Alice O'Donnell, Marilyn M Wagener, Victor L Yu
Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study.
Medicine (Baltimore). 2003 Sep;82(5):333-9. doi: 10.1097/01.md.0000091184.93122.09.
Abstract/Text
Staphylococcus aureus bacteremia is associated with substantial morbidity. Recurrence is common, but incidence and risk factors for recurrence are uncertain. The emergence of methicillin resistance and the ease of administering vancomycin, especially in patients who have renal insufficiency, have led to reliance on this drug with the assumption that it is as effective as beta-lactam antibiotics, an assumption that remains open to debate. We initiated a multicenter, prospective observational study in 6 university hospitals and enrolled 505 consecutive patients with S. aureus bacteremia. All patients were monitored for 6 months and patients with endocarditis were followed for 3 years. Recurrence was defined as return of S. aureus bacteremia after documentation of negative blood cultures and/or clinical improvement after completing a course of antistaphylococcal antibiotic therapy. All blood isolates taken from patients with recurrent bacteremia underwent pulsed-field gel electrophoresis testing. Recurrence was subclassified as reinfection (different pulsed-field gel electrophoresis patterns) or relapse (same pulsed-field gel electrophoresis pattern).Forty-two patients experienced 56 episodes of recurrence (79% were relapses and 21% were reinfection). Relapse occurred earlier than reinfection (median, 36 versus 99 d, p < 0.06). Risk factors for relapse of S. aureus bacteremia included valvular heart disease, cirrhosis of the liver, and deep-seated infection (including endocarditis). Nafcillin was superior to vancomycin in preventing bacteriologic failure (persistent bacteremia or relapse) for methicillin-susceptible S. aureus (MSSA) bacteremia. Failure to remove infected intravascular devices/catheters and vancomycin therapy were common factors in patients experiencing multiple (greater than 2) relapses. However, by multivariate analysis, only endocarditis and therapy with vancomycin (versus nafcillin) were significantly associated with relapse. Recurrences occurred in 9.4% of S. aureus bacteremias following antistaphylococcal therapy, and most were relapses. Duration of antistaphylococcal therapy was not associated with relapse, but type of antibiotic therapy was. Nafcillin was superior to vancomycin in efficacy in patients with MSSA bacteremia.
Stryjewski Martin E ME, Szczech Lynda A LA, Benjamin Daniel K DK Jr, Inrig Jula K JK, Kanafani Zeina A ZA, Engemann John J JJ, Chu Vivian H VH, Joyce Maria J MJ, Reller L Barth LB, Corey G Ralph GR, Fowler Vance G VG Jr
Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia.
Clin Infect Dis. 2007 Jan 15;44(2):190-6. doi: 10.1086/510386. Epub 2006 Dec 8.
Abstract/Text
BACKGROUND: Because of its ease of dosing, vancomycin is commonly used to treat methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in patients undergoing long-term hemodialysis. Clinical outcomes resulting from such a therapeutic strategy have not been well defined.
METHODS: We prospectively identified patients undergoing long-term hemodialysis who received a diagnosis of MSSA bacteremia. Clinical outcomes were grouped according to the predominant antibiotic received during their therapy (vancomycin or a first-generation cephalosporin [cefazolin]). Treatment failure (defined as death or recurrent infection) was determined at 12 weeks after the initial positive blood culture results. A multivariable analysis was used to adjust for confounders.
RESULTS: During an 84-month period, 123 hemodialysis-dependent patients with MSSA bacteremia were identified. Patients receiving vancomycin (n=77) tended to be younger (51 vs. 57 years; P=.06) and had a lower rates of metastatic complications at presentation (11.7% vs. 36.7%; P=.001) than did those receiving cefazolin (n=46). The 2 groups were similar with regard to Acute Physiology and Chronic Health Evaluation II scores, comorbidities, source of infection, type of hemodialysis access, and access removal rates. Treatment failure was more common among patients receiving vancomycin (31.2% vs. 13%; P=.02). In the multivariable analysis, factors independently associated with treatment failure included vancomycin use (odds ratio, 3.53; 95% confidence interval, 1.15-13.45) and retention of the hemodialysis access (odds ratio, 4.99; 95% confidence interval, 1.89-13.76).
CONCLUSIONS: Hemodialysis-dependent patients with MSSA bacteremia treated with vancomycin are at a higher risk of experiencing treatment failure than are those receiving cefazolin. In the absence of patient specific circumstances (e.g., allergy to beta-lactams), vancomycin should not be continued beyond empirical therapy for hemodialysis-dependent patients with MSSA bacteremia.
Robert C Moellering
Linezolid: the first oxazolidinone antimicrobial.
Ann Intern Med. 2003 Jan 21;138(2):135-42.
Abstract/Text
Linezolid is the first of a new class of antimicrobial agents, the oxazolidinones, to be approved for clinical use in the United States and elsewhere. The drug is a totally synthetic compound, which lessens the likelihood of naturally occurring resistance mechanisms. It has excellent activity against virtually all important gram-positive pathogens, including methicillin-resistant staphylococci, penicillin-resistant pneumococci, macrolide-resistant streptococci, and vancomycin-resistant enterococci. Development of resistance to the compound has been infrequent thus far. Linezolid is 100% bioavailable, so it can be given in equal doses orally or parenterally. Its elimination half-life allows dosing twice per day, and alteration of drug dosage is not required in patients with impaired renal or hepatic function. Linezolid has approved indications for skin and soft tissue infections; lower respiratory tract infections; and vancomycin-resistant Enterococcus faecium infections, including cases with concurrent bacteremia. The drug has an acceptable profile of adverse events, but reversible myelosuppression has occurred in patients receiving high doses for more than 2 weeks.
Mark H Wilcox, Kenneth J Tack, Emilio Bouza, Daniel L Herr, Bernhard R Ruf, M Marian Ijzerman, Rodney V Croos-Dabrera, Mark J Kunkel, Charles Knirsch
Complicated skin and skin-structure infections and catheter-related bloodstream infections: noninferiority of linezolid in a phase 3 study.
Clin Infect Dis. 2009 Jan 15;48(2):203-12. doi: 10.1086/595686.
Abstract/Text
BACKGROUND: Catheter-related bloodstream infection (CRBSI) causes substantial morbidity and mortality, but few randomized, controlled studies have been conducted to guide therapeutic interventions.
METHODS: To determine whether linezolid would be noninferior to vancomycin in patients with CRBSI, we conducted an open-label, multicenter, comparative study. Patients with suspected CRBSI were randomized to receive linezolid or vancomycin (control group). The primary end point was microbiologic outcome at test of cure 1-2 weeks after treatment, as assessed by step-down procedure. The first analysis population was complicated skin and skin structure infection (cSSSI) in patients with suspected CRBSI; patients with CRBSI were analyzed if noninferiority criteria (lower bound of the 95% confidence interval [CI] not outside -15%) were met.
RESULTS: Noninferiority criteria were met for cSSSI (microbiologic success rate for linezolid recipients, 89.6% [146 for 163 patients]; for the control group, 89.9% [134 of 149]; 95% CI, -7.1 to 6.4) and CRBSI (for linezolid recipients, 86.3% [82 of 95]; for the control group, 90.5% [67 of 74]; 95% CI, -13.8 to 5.4). The frequency and severity of adverse events were similar between groups. Mortality rates were 10.4% for linezolid recipients (28 of 269 patients) and 10.1% for control subjects (26 of 257) in the modified intent-to-treat population (i.e., all patients with gram-positive baseline culture) through test of cure, and they were 21.5% for linezolid recipients (78 of 363) and 16.0% for the control group (58 of 363; 95% CI, -0.2 to 11.2) for all treated patients through poststudy treatment day 84.
CONCLUSIONS: Linezolid demonstrated microbiologic success rates noninferior to those for vancomycin in patients with cSSSIs and CRBSIs caused by gram-positive organisms. Patients with catheter-related infections must be carefully investigated for the heterogeneous underlying causes of high morbidity and mortality, particularly for infections with gram-negative organisms.
Helen Boucher, Loren G Miller, Raymund R Razonable
Serious infections caused by methicillin-resistant Staphylococcus aureus.
Clin Infect Dis. 2010 Sep 15;51 Suppl 2:S183-97. doi: 10.1086/653519.
Abstract/Text
Although first identified just >4 decades ago, methicillin-resistant Staphylococcus aureus (MRSA) has undergone rapid evolutionary changes and epidemiologic expansion to become a major cause of nosocomial and community-acquired infections worldwide. Increasing resistance to vancomycin among MRSA strains in conjunction with availability of new antibiotics, including daptomycin and linezolid, have increased treatment choices but made clinical treatment decisions more challenging. This article describes the clinical features and management issues of 2 challenging-to-treat manifestations of MRSA infection, bacteremia and/or endocarditis and osteomyelitis. It also presents a brief review of community-associated MRSA infections and preventive strategies directed against MRSA.
M Sonne, E Jawetz
Comparison of the action of ampicillin and benzylpenicillin on enterococci in vitro.
Appl Microbiol. 1968 Apr;16(4):645-8.
Abstract/Text
The bactericidal activity of benzylpenicillin and ampicillin on 21 strains of enterococci was evaluated and compared to the activity of these drugs in combination with streptomycin (20 mug/ml). On a weight basis, ampicillin was about twice as effective as benzylpenicillin. Neither of the drugs was rapidly and completely bactericidal for any of the 21 strains of enterococci when used alone. The addition of streptomycin greatly enhanced the early bactericidal rate achieved with any given amount of either penicillin and permitted the elimination of viable organisms in vitro. These results suggest that, for the time being, combined antibiotic therapy might be desirable in enterococcus endocarditis and that ampicillin, although more effective than benzylpenicillin, should not be relied upon as a single drug in that disease.
Larry M Baddour, Walter R Wilson, Arnold S Bayer, Vance G Fowler, Imad M Tleyjeh, Michael J Rybak, Bruno Barsic, Peter B Lockhart, Michael H Gewitz, Matthew E Levison, Ann F Bolger, James M Steckelberg, Robert S Baltimore, Anne M Fink, Patrick O'Gara, Kathryn A Taubert, American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council
Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association.
Circulation. 2015 Oct 13;132(15):1435-86. doi: 10.1161/CIR.0000000000000296. Epub 2015 Sep 15.
Abstract/Text
BACKGROUND: Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today's myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances.
METHODS AND RESULTS: This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations.
CONCLUSIONS: Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.
© 2015 American Heart Association, Inc.
W Graninger, R Ragette
Nosocomial bacteremia due to Enterococcus faecalis without endocarditis.
Clin Infect Dis. 1992 Jul;15(1):49-57.
Abstract/Text
During a 2-year observation period at a 2,200-bed university hospital, bacteremia due to Enterococcus faecalis was observed in 111 patients. Fifty-five patients with nosocomial bacteremia due to E. faecalis could be evaluated. The most common entry sites were the urinary tract (25%), the intraabdominal cavity (13%), and burn and decubital wounds (11%). Bacteremia was preceded by administration of cephalosporins, imipenem, and aztreonam (n = 39); ciprofloxacin (n = 11); and other antibiotics (n = 4). Age, sex, underlying disease, portal of entry, previous antibiotic therapy, and bacteremia due to other organisms had no influence on mortality. Treatment of bacteremia with penicillins (n = 45) and glycopeptides (n = 4) resulted in a mortality rate of 37%. The addition of a high-dose aminoglycoside to a penicillin did not result in a better survival rate.
J Gray, P J Marsh, D Stewart, S J Pedler
Enterococcal bacteraemia: a prospective study of 125 episodes.
J Hosp Infect. 1994 Jul;27(3):179-86.
Abstract/Text
One hundred and twenty-five episodes of enterococcal bacteraemia occurring over a 50-month period were studied prospectively. Enterococcus faecium was the commonest species, accounting for 76 (59.8%) of the 127 isolates. Overall, 33.1% of isolates were resistant to ampicillin and one isolate (0.8%) to vancomycin; high-level gentamicin resistance was detected in 4.3% of 93 isolates tested. The percentage of nosocomial episodes was 70.4, and 95.2% of the patients had significant underlying illness. Central venous catheters (CVCs) were the commonest source of infection. Eighty-four per cent of episodes were ultimately treated with appropriate antibiotics. The overall mortality rate was 17.6%, and that directly attributable to infection was 8.0%. An increased mortality rate was observed in intensive care and neonatal unit patients, and in patients who had received antimicrobial therapy in the 2 weeks prior to enterococcemia. CVC-related infections were associated with a reduced mortality. No other clinical or microbiological factors were found to influence outcome.
J Zimbelman, A Palmer, J Todd
Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection.
Pediatr Infect Dis J. 1999 Dec;18(12):1096-100.
Abstract/Text
CONTEXT: Animal model studies have demonstrated the failure of penicillin to cure Streptococcus pyogenes myositis and have suggested that clindamycin is a more effective treatment.
OBJECTIVE: To determine the most effective antibiotic treatment for invasive S. pyogenes infection in humans.
DESIGN AND SETTING: We conducted a retrospective review of the outcomes of all inpatients from 1983 to 1997 treated for invasive S. pyogenes infection at Children's Hospital.
PATIENTS: Fifty-six children were included, 37 with initially superficial disease and 19 with deep or multiple tissue infections.
MAIN OUTCOME MEASURE: Lack of progression of disease (or improvement) after at least 24 h of treatment.
RESULTS: The median number of antibiotic exposures was 3 per patient (range 1 to 6) with clindamycin predominating in 39 of 45 courses of protein synthesis-inhibiting antibiotics and beta-lactams predominating amongst the cell wall-inhibiting antibiotics in 123 of 126 of the remainder. Clindamycin was often used in combination with a beta-lactam antibiotic. Overall there was a 68% failure rate of cell wall-inhibiting antibiotics when used alone. Patients with deep infection were more likely to have a favorable outcome if initial treatment included a protein synthesis-inhibiting antibiotic as compared with exclusive treatment with cell wall-inhibiting antibiotics (83% vs. 14%, P = 0.006) with a similar trend in those with superficial disease (83% vs. 48%, P = 0.07). For those children initially treated with cell wall-inhibiting antibiotics alone, surgical drainage or debridement increased the probability of favorable outcome in patients with superficial disease (100% vs. 41%, P = 0.04) with a similar trend in a smaller number of deep infections (100% vs. 0%, P = 0.14).
CONCLUSIONS: This retrospective study suggests that clindamycin in combination with a beta-lactam antibiotic (with surgery if indicated) might be the most effective treatment for invasive S. pyogenes infection.
D L Stevens
Streptococcal toxic shock syndrome associated with necrotizing fasciitis.
Annu Rev Med. 2000;51:271-88. doi: 10.1146/annurev.med.51.1.271.
Abstract/Text
Streptococcal toxic shock syndrome (strep TSS) with associated necrotizing fasciitis is a rapidly progressive process that kills 30-60% of patients in 72-96 h. Violaceous bullae, hypotension, fever, and evidence of organ failure are late clinical manifestations. Thus, the challenge to clinicians is to make an early diagnosis and to intervene with aggressive fluid replacement, emergent surgical debridement, and general supportive measures. Superantigens such as pyrogenic exotoxin A interact with monocytes and T lymphocytes in unique ways, resulting in T-cell proliferation and watershed production of monokines (e.g. tumor necrosis factor alpha, interleukin 1, interleukin 6), and lymphokines (e.g. tumor necrosis factor beta, interleukin 2, and gamma-interferon). Penicillin, though efficacious in mild Streptococcus pyogenes infection, is less effective in severe infections because of its short postantibiotic effect, inoculum effect, and reduced activity against stationary-phase organisms. Emerging treatments for strep TSS include clindamycin and intravenous gamma-globulin.
D M Livermore
Clinical significance of beta-lactamase induction and stable derepression in gram-negative rods.
Eur J Clin Microbiol. 1987 Aug;6(4):439-45.
Abstract/Text
Most strains of enterobacteria and Pseudomonas aeruginosa produce chromosomally-determined Class I beta-lactamases. When synthesized copiously these enzymes cause resistance to almost all beta-lactams, except imipenem and, sometimes, carbenicillin and tenocillin. Elevated beta-lactamase production arises transiently, via induction, in Pseudomonas aeruginosa and Enterobacter, Citrobacter, Morganella, indole-positive Proteus and Serratia spp. when these organisms are exposed to beta-lactams. Permanent high-level enzyme production arises via mutation, in the stably-derepressed mutants of these species. These mutants arise spontaneously at high frequency (10(-5) -10(-8). Most early penicillins and first-generation cephalosporins are strong inducers of Class I enzymes at sub-inhibitory concentrations, as are cefoxitin and imipenem. Consequently their MICs reflect what lability these antibiotics have to inducibly-expressed beta-lactamase. Except with imipenem this lability usually is so great that the inducible enzyme causes clinical resistance. Although most other newer cephalosporins and ureidopenicillins are labile to the Class I enzymes they induce poorly below the MIC, and their lability is not reflected in resistance unless secondary inducers (e.g. cefoxitin or imipenem) are present. Although the weak inducer activity of these agents helps to maintain their activity against the inducible cells it renders the drugs highly selective for the pre-existing stably-derepressed mutants. Many cases have been reported where stably-derepressed mutants have overrun inducible populations of bacteria in patients undergoing therapy with beta-lactamase-labile weak inducers such as ureidopenicillin and third-generation cephalosporins.
R N Jones
Important and emerging beta-lactamase-mediated resistances in hospital-based pathogens: the Amp C enzymes.
Diagn Microbiol Infect Dis. 1998 Jul;31(3):461-6.
Abstract/Text
Resistance to third-generation cephalosporins mediated by beta-lactamases is an increasing problem for clinical therapeutics. A wide range of Enterobacteriaceae produce these AmpC enzymes (Bush-Jacoby-Medeiros group 1), including Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp., and Serratia marcescens. Resistance via this mechanism has been shown to be statistically correlated with the use of some third-generation cephalosporins, and the infections caused by these stably derepressed enzyme-producing species seem to occur most frequently in the seriously ill. More recently the genes encoding this enzyme have been documented on plasmids capable of transfer into other species such as Klebsiella pneumoniae. Fourth-generation cephalosporins, with stability and low affinity for the Amp C beta-lactamases and the ability to penetrate rapidly into the periplasmic space of Gram-negative organisms, offer a viable alternative in the treatment of these infections or as empiric regimens. Furthermore, these compounds (example: cefpirome) possess greater potency against the frequently occurring Gram-positive cocci such as oxacillin-susceptible staphylococci and the streptococci (including some penicillin-resistant strains) as compared to previously used anti-pseudomonal cephalosporias, ceftazidime.
J W Chow, M J Fine, D M Shlaes, J P Quinn, D C Hooper, M P Johnson, R Ramphal, M M Wagener, D K Miyashiro, V L Yu
Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy.
Ann Intern Med. 1991 Oct 15;115(8):585-90.
Abstract/Text
OBJECTIVES: To study the effect of previously administered antibiotics on the antibiotic susceptibility profile of Enterobacter, the factors affecting mortality, and the emergence of antibiotic resistance during therapy for Enterobacter bacteremia.
DESIGN: Prospective, observational study of consecutive patients with Enterobacter bacteremia.
SETTING: Three university tertiary care centers, one major university-affiliated hospital, and two university-affiliated Veterans Affairs medical centers.
PATIENTS: A total of 129 adult patients were studied.
MEASUREMENTS: The two main end points were emergence of resistance during antibiotic therapy and death.
MAIN RESULTS: Previous administration of third-generation cephalosporins was more likely to be associated with multiresistant Enterobacter isolates in an initial, positive blood culture (22 of 32, 69%) than was administration of antibiotics that did not include a third-generation cephalosporin (14 of 71, 20%; P less than 0.001). Isolation of multiresistant Enterobacter sp. in the initial blood culture was associated with a higher mortality rate (12 of 37, 32%) than was isolation of a more sensitive Enterobacter sp. (14 of 92, 15%; P = 0.03). Emergence of resistance to third-generation cephalosporin therapy (6 of 31, 19%) occurred more often than did emergence of resistance to aminoglycoside (1 of 89, 0.01%; P = 0.001) or other beta-lactam (0 of 50; P = 0.002) therapy.
CONCLUSIONS: More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp., which in turn may result in a lower mortality for Enterobacter bacteremia. When Enterobacter organisms are isolated from blood, it may be prudent to avoid third-generation cephalosporin therapy regardless of in-vitro susceptibility.
Dafna Yahav, Erica Franceschini, Fidi Koppel, Adi Turjeman, Tanya Babich, Roni Bitterman, Ami Neuberger, Nesrin Ghanem-Zoubi, Antonella Santoro, Noa Eliakim-Raz, Barak Pertzov, Tali Steinmetz, Anat Stern, Yaakov Dickstein, Elias Maroun, Hiba Zayyad, Jihad Bishara, Danny Alon, Yonatan Edel, Elad Goldberg, Claudia Venturelli, Cristina Mussini, Leonard Leibovici, Mical Paul, Bacteremia Duration Study Group
Seven versus fourteen Days of Antibiotic Therapy for uncomplicated Gram-negative Bacteremia: a Non-inferiority Randomized Controlled Trial.
Clin Infect Dis. 2018 Dec 11;. doi: 10.1093/cid/ciy1054. Epub 2018 Dec 11.
Abstract/Text
Background: Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited.
Methods: Randomized, multicenter, open-label, non-inferiority trial. Inpatients with Gram-negative bacteremia, afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative or distant complications; and re-admission or extended hospitalization (>14 days). The non-inferiority margin was set at 10%.
Results: We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in three centers in Israel and Italy. The source of the infection was urinary in 411/604 (68%); causative pathogens were mainly Enterobacteriaceae (543/604, 90%). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140/306 (45.8%) patients in the 7 days group versus 144/298 (48.3%) in the 14 days group (risk difference [RD] -2.6%, 95% confidence interval [CI] -10.5% to 5.3%). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short therapy arm.
Conclusions: In patients hospitalized with Gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was non-inferior to 14 days. Reducing antibiotic treatment for uncomplicated Gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. (ClinicalTrials.gov number, NCT01737320).
José Molina, Enrique Montero-Mateos, Julia Praena-Segovia, Eva León-Jiménez, Clara Natera, Luis E López-Cortés, Lucía Valiente, Clara M Rosso-Fernández, Marta Herrero, Ana I Aller-García, Ángela Cano, Belén Gutiérrez-Gutiérrez, Ignacio Márquez-Gómez, Rocío Álvarez-Marín, Carmen Infante, Cristina Roca, Adoración Valiente-Méndez, Jerónimo Pachón, José María Reguera, Juan Enrique Corzo-Delgado, Julián Torre-Cisneros, Jesús Rodríguez-Baño, José Miguel Cisneros, SHORTEN trial team
Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized, controlled trial.
Clin Microbiol Infect. 2022 Apr;28(4):550-557. doi: 10.1016/j.cmi.2021.09.001. Epub 2021 Sep 9.
Abstract/Text
OBJECTIVE: To prove that 7-day courses of antibiotics for bloodstream infections caused by members of the Enterobacterales (eBSIs) allow a reduction in patients' exposure to antibiotics while achieving clinical outcomes similar to those of 14-day schemes.
METHODS: A randomized trial was performed. Adult patients developing eBSI with appropriate source control were assigned to 7 or 14 days of treatment, and followed 28 days after treatment cessation; treatments could be resumed whenever necessary. The primary endpoint was days of treatment at the end of follow-up. Clinical outcomes included clinical cure, relapse of eBSI and relapse of fever. A superiority margin of 3 days was set for the primary endpoint, and a non-inferiority margin of 10% was set for clinical outcomes. Efficacy and safety were assessed together with a DOOR/RADAR (desirability of outcome ranking and response adjusted for duration of antibiotic risk) analysis.
RESULTS: 248 patients were assigned to 7 (n = 119) or 14 (n = 129) days of treatment. In the intention-to-treat analysis, median days of treatment at the end of follow-up were 7 and 14 days (difference 7, 95%CI 7-7). The non-inferiority margin was also met for clinical outcomes, except for relapse of fever (-0.2%, 95%CI -10.4 to 10.1). The DOOR/RADAR showed that 7-day schemes had a 77.7% probability of achieving better results than 14-day treatments.
CONCLUSIONS: 7-day schemes allowed a reduction in antibiotic exposure of patients with eBSI while achieving outcomes similar to those of 14-day schemes. The possibility of relapsing fever in a limited number of patients, without relevance to final outcomes, may not be excluded, but was overcome by the benefits of shortening treatments.
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