今日の臨床サポート 今日の臨床サポート

著者: 久保健児 日本赤十字社和歌山医療センター 感染症内科部・救急科部

監修: 山本舜悟 大阪大学大学院医学系研究科 変革的感染制御システム開発学

著者校正済:2025/06/10
現在監修レビュー中
参考ガイドライン:
  1. 米国感染症学会:Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America.
患者向け説明資料

改訂のポイント:
  1. 血液培養の陽性化までの時間差(DTP、DTTP)について、メタアナリシスおよび観察研究によるエビデンスを追加した。
  1. 2023年発表のDhaliwalらのメタアナリシス(23の研究、2,526件対象)では、DTP2時間差は、感度81.3%、特異度91.8%、LR+(陽性尤度比) 9.89、LR-(陰性尤度比) 0.20であった。ただし、黄色ブドウ球菌(感度は低いが、特異度は高い)、カンジダ(感度は高いが、特異度は低い)という結果であった(Dhaliwal M, et al. Clin Infect Dis. 2023 Aug 14;77(3):428-437.)。菌種別による研究数が十分ではないため、さらなる検討を要する。
  1. また、2020年発表のOrihuela-Martínらの単施設研究では、15年間の512件の血流感染症のエピソード(うちCRBSI 302件)において、DTPの識別力は、AmpC産生腸内細菌科は高く(AUC 0.944)、緑膿菌は中等度(AUC 0.841)、それ以外の菌種では低かった。DTP ≥2 時間で感度が低い菌種もあった(コアグラーゼ陰性ブドウ球菌 60%、AmpC を産生しない腸内細菌科 42%、腸球菌 40%、黄色ブドウ球菌 34%)。DTP ≥1 時間のカットオフとすると、AmpC 産生腸内細菌の感度が向上した(90%)(Orihuela-Martín J, et al. Clin Microbiol Infect. 2020 Mar;26(3):383.e1-383.e7.)。
  1. CRBSIを疑っておらず、事前確率が低い状況では、むやみにカテーテル採血によるDTPを適用しないほうがよいとされる。これは、採取時の汚染菌やカテーテル内の定着菌が検出される確率が高まり、CRBSIの過剰診断から不必要な処置につながるためである(Mermel LA, et al. Open Forum Infect Dis. 2024 May 2;11(5):ofae248.)。
  1. 2024年に日本でもミッドラインカテーテルが発売されたことから、関連したエビデンスを追加した。
  1. ミッドラインカテーテルはPICCよりも遅れて開発され、日本では2024年に発売された。末梢静脈路の確保が困難な場合や、末梢静脈路の問題点(皮下漏れ、血管痛、頻回穿刺など)を低減したい場合に有用で、7日以上の比較的長期間の抗菌薬静注治療に考慮される。
  1. 2022年Swaminathanらの前向きコホート研究では、静脈路確保が困難または30日以内の抗菌薬治療を受けた入院患者を対象に、5,105人のミッドラインカテーテル留置患者と5,758人のPICC留置患者を比較し、留置期間は比較的短期間だった(ミッドラインカテーテル:6(3-12)日間、PICC:14(7-27)日間)。ロジットモデルで留置期間等を調整した結果、PICCの方が主要な合併症が多く(1.99; 95% CI, 1.61-2.47)、CRBSIおよび血栓症の発生はミッドラインカテーテルの方が少なかった(CRBSI:0.4%vs 1.6%; P <.001、血栓症:2.1%vs 7.0%; P <.001)。ただし、深部静脈血栓症の発生はPICCの方が少なかった(ハザード比0.53; 95%CI 0.38-0.74 )(Swaminathan L, et al. JAMA Intern Med. 2022 Jan 1;182(1):50-58.)。
  1. 2025年のPajeらによるミシガン州69病院での後ろ向きコホート研究では、外来静注抗菌薬治療の適応がある入院患者において、ミッドラインカテーテルとPICCとを比較した。対象はミッドラインカテーテル留置患者1,999人とPICC留置患者825人で、留置期間はミッドラインカテーテル:12 (8-17) 日間、PICC:19 (12-27)日間であった。主要な合併症は、ミッドラインカテーテルは16人(0.8%)、PICCは28人(3.4%)であった(P < .001 )(Paje D, et al. JAMA Intern Med. 2025 Jan 1;185(1):83-91.)。

概要・推奨   

診断
  1. カテーテル関連血流感染(catheter-related blood stream infection:CRBSI)を疑っていない状況でのルーチンの血管内カテーテル先端培養は、行わないよう推奨される(推奨度3、O)
  1. 中心静脈カテーテル留置患者において、刺入部の所見が陰性であることを根拠に、CRBSIを否定しないよう推奨される(推奨度4、O)
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病態・疫学・診察 

疾患情報  
  1. カテーテル関連血流感染(catheter-related blood stream infection:CRBSI)とは、血管内カテーテルに関連して発生した血流感染を指す。血流感染とは、菌血症または真菌血症のことである。
  1. 代表的な原因微生物は、コアグラーゼ陰性ブドウ球菌(coagulase negative Staphylococcus:CNS)、黄色ブドウ球菌(S. aureus:MRSA)、カンジダ(Candida)、腸球菌(Enterococcus)、グラム陰性桿菌(大腸菌[E.coli]、エンテロバクター[Enterobacter]、クレブシエラ[Klebsiella] などの腸内細菌目、および緑膿菌[P. aeruginosa]など )である。
 
血流感染症とその合併症:
  1. CRBSIは、血管内カテーテルに関連して発生した血流感染(菌血症または真菌血症)であり、以下に示すような合併症を呈し得る。
 
CRBSIに関連した合併症(種類と特徴)

参考文献:
  1. Pearson ML. Guideline for prevention of intravascular device-related infections. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1996; 17:438-73.
  1. Mermel LA, Allon M, Bouza E, et al. 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; 49:1.

出典

著者提供
 
診断基準  
  1. 血管内カテーテルに関連した感染症は、血流感染以外にも種類があり、2009年のIDSAガイドラインの診断基準が参考になる。その中でCRBSIは、「①末梢血からの血液培養結果が1セット以上陽性で、②感染の臨床症状(発熱、悪寒、低血圧など)があり、③血管内にカテーテル等のデバイスが留置中で、④その血管内デバイス以外に原因となる感染巣が明らかではない、菌血症または真菌血症。」と定義されている。
 
 

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文献 

Brun-Buisson C, Abrouk F, Legrand P, Huet Y, Larabi S, Rapin M.
Diagnosis of central venous catheter-related sepsis. Critical level of quantitative tip cultures.
Arch Intern Med. 1987 May;147(5):873-7.
Abstract/Text The results of a simplified quantitative broth dilution quantitative tip culture (QTC) of 331 central venous catheters were compared with clinical data prospectively recorded in critically III patients to diagnose bacteremic or nonbacteremic catheter-related sepsis (CRS) (36 catheters), as opposed to contamination (42 catheters) or simple colonization from a distant septic focus (seven catheters). Thirty-five of 36 catheters associated with CRS yielded 10(3) colony-forming units per milliliter (CFU/mL) or more, and 3.8 X 10(2) Candida organisms grew from one. In contrast, 5 X 10(2) CFU/mL or less grew from 37 of 42 contaminated catheters. A QTC of 10(3) CFU/mL or more was 97.5% sensitive and 88% specific for the diagnosis of CRS. The QTC appeared especially useful for the diagnosis of CRS secondary to blood-borne seeding of catheters, or associated with coagulase-negative staphylococci.

PMID 3555377
Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK.
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 These updated guidelines replace the previous management guidelines published in 2001. The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them.

PMID 19489710
Safdar N, Maki DG.
Inflammation at the insertion site is not predictive of catheter-related bloodstream infection with short-term, noncuffed central venous catheters.
Crit Care Med. 2002 Dec;30(12):2632-5. doi: 10.1097/00003246-200212000-00003.
Abstract/Text BACKGROUND: Noncuffed, percutaneously inserted central venous catheters (CVCs) are widely used and cause at least 250,000 bloodstream infections (BSIs) in U.S. hospitals each year. We report a prospective study to determine whether inflammation at the insertion site is predictive of CVC-related BSI.
METHODS: Percutaneously inserted, noncuffed CVCs inserted into the subclavian, internal jugular, or femoral vein in two randomized trials during 1998-2000 were prospectively studied; most patients were in an intensive care unit. The condition of the insertion site was evaluated daily by research nurses, quantifying pain (0, 1), erythema (0-2), swelling (0, 1), and purulence (0, 1); the lowest possible overall inflammation score was 0 and the highest was 5. CVC-related BSI was confirmed in each case by demonstrating concordance between isolates from the catheter segment and from blood cultures by restriction-fragment DNA subtyping.
RESULTS: Among 1,263 CVCs prospectively studied, 333 (26.3%) were colonized at removal; of these, 35 catheters (2.7%) caused BSIs (5.9 per 1000 CVC days). BSIs were caused by coagulase-negative staphylococci (n = 27), enterococci (n = 4), enteric Gram-negative bacilli (n = 3), or (n = 1). Most insertion sites showed little or no inflammation at the time of removal. There were no significant differences among mean scores for each inflammatory variable examined or overall score among colonized CVCs (0.1 +/- 0.1), catheters causing CVC-related BSI (0.2 +/- 0.4), and noncolonized CVCs (0.1 +/- 0.1). The sensitivity of local inflammation for diagnosis of CVC-related BSI was dismal (0-3%).
CONCLUSION: Local inflammation is uncommon with infected CVCs, probably because most catheter-associated infections are currently caused by coagulase-negative staphylococci, a pathogen that incites little local or systemic inflammation. Whereas overt inflammation of the insertion site should raise suspicion of CVC-related BSI caused by or Gram-negative bacilli, especially if the patient has fever or other signs of sepsis, in general, site appearance cannot be relied on to identify catheter colonization or CVC-related BSI.

PMID 12483050
Cotton DJ, Gill VJ, Marshall DJ, Gress J, Thaler M, Pizzo PA.
Clinical features and therapeutic interventions in 17 cases of Bacillus bacteremia in an immunosuppressed patient population.
J Clin Microbiol. 1987 Apr;25(4):672-4. doi: 10.1128/jcm.25.4.672-674.1987.
Abstract/Text We retrospectively examined episodes of Bacillus bacteremia at a hospital with a large proportion of immunosuppressed patients. Seventeen episodes in 9.5 years met our case definition: two of two bottles of one blood culture or one of two bottles of two or more separately obtained blood cultures drawn on the same date. During the same period, there were 59 additional episodes in which a single blood culture had only one of two bottles positive for Bacillus species. Only 2 of 59 such episodes resulted in recurrent bacteremia (3%), as compared with 5 of 17 episodes meeting our case definition (29%) (P = 0.004). In four of five episodes complicated by recurrent bacteremia and in which appropriate antibiotics were used, a Hickman-Broviac catheter was in place and was not removed. We suggest that our case definition permits the differentiation of infection from contamination based on outcome and that patients with Bacillus bacteremia have chronic venous catheters removed as well as receive antibiotic treatment.

PMID 3571476
Finkelstein R, Fusman R, Oren I, Kassis I, Hashman N.
Clinical and epidemiologic significance of coagulase-negative staphylococci bacteremia in a tertiary care university Israeli hospital.
Am J Infect Control. 2002 Feb;30(1):21-5. doi: 10.1067/mic.2002.118406.
Abstract/Text OBJECTIVES: To characterize the clinical significance of coagulase-negative staphylococci (CNS) bacteremia.
DESIGN: Prospective cohort study.
SETTING: A 900-bed hospital in Haifa, Israel, from November 1996 to March 1997.
RESULTS: Of 137 episodes of positive blood cultures for CNS, 41 (30%) were considered as true infection. Twenty-seven of 119 episodes associated with only 1 blood culture positive for CNS (23%) met the definition of infection as compared with 14 of 18 episodes (78%) associated with 2 or more blood cultures positive for CNS (P <.001). Methicillin resistance was significantly more frequent among Staphylococcus epidermidis isolates of episodes of true bacteremia than of episodes of contamination (15 of 22 [68%] vs. 11 of 33 [33%], respectively; P =.02). S hominis was isolated only in episodes considered as contamination (P =.01). It was estimated that CNS represents 24% of all nosocomial bloodstream pathogens. When CNS were isolated in the first 48 hours of hospitalization, an intravascular device was more frequently associated with episodes of true bacteremia than in those considered as contamination (7 of 7 [100%] vs. 10 of 57 [18%], respectively; P <.001). The mortality rate among patients with true CNS bacteremia was 16%.
CONCLUSION: Some laboratory parameters may help identify episodes of true CNS bacteremia, which appears to be more common than previously considered.

PMID 11852412
Ruhe J, Menon A, Mushatt D, Dejace P, Hasbun R.
Non- epidermidis coagulase-negative staphylococcal bacteremia: clinical predictors of true bacteremia.
Eur J Clin Microbiol Infect Dis. 2004 Jun;23(6):495-8. doi: 10.1007/s10096-004-1134-4. Epub 2004 May 13.
Abstract/Text In order to explore the clinical significance and risk factors for true bacteremia caused by coagulase-negative staphylococci (CNS) other than Staphylococcus epidermidis, a retrospective cohort study of 160 patients with at least one blood culture positive for non- epidermidis CNS was performed. True bacteremia was diagnosed in 32 (20%) of the patients. On multivariate analysis the following factors were associated with true bacteremia: (i) more than one positive blood culture, (ii) presence of a central venous catheter, and (iii) methicillin resistance. The results of this study indicate that non- epidermidis CNS can cause significant bloodstream infections.

PMID 15141334
Raad I, Hanna HA, Alakech B, Chatzinikolaou I, Johnson MM, Tarrand J.
Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections.
Ann Intern Med. 2004 Jan 6;140(1):18-25. doi: 10.7326/0003-4819-140-1-200401060-00007.
Abstract/Text BACKGROUND: Catheter-related bloodstream infections are associated with recognized morbidity and mortality, especially in critically ill patients. Accurate diagnosis of such infections results in proper management of patients and in reducing unnecessary removal of catheters.
OBJECTIVE: To evaluate differential time to positivity as a method for diagnosing catheter-related bacteremias caused by both short-term and long-term use of central venous catheters.
DESIGN: Prospective study design.
SETTING: M.D. Anderson Cancer Center, Houston, Texas, a tertiary care cancer center.
PATIENTS: All patients, between September 1999 and November 2000, who had the same organism isolated from blood cultures drawn simultaneously through the central venous catheter and the peripheral vein.
MEASUREMENTS: Time necessary for the blood cultures from the central venous catheter and the peripheral vein to become positive, as well as other relevant patient information.
RESULTS: 191 bloodstream infections with positive simultaneous central venous catheter and peripheral vein blood cultures were included. One hundred eight patients had catheter-related bacteremias, and 83 had non-catheter-related bacteremias. Catheter-related bacteremias were more frequently caused by staphylococci and less likely to be associated with underlying hematologic malignant conditions, neutropenia, and longer duration of hospitalization. As a diagnostic tool for catheter-related bacteremia (using a composite definition reference standard according to the Infectious Diseases Society of America guidelines), differential time to positivity of 120 minutes or more was associated with 81% sensitivity and 92% specificity for short-term catheters and 93% sensitivity and 75% specificity for long-term catheters.
CONCLUSION: Differential time to positivity of 120 minutes or more is highly sensitive and specific for catheter-related bacteremia in patients who have short- and long-term catheters.

PMID 14706968
Rijnders BJ, Verwaest C, Peetermans WE, Wilmer A, Vandecasteele S, Van Eldere J, Van Wijngaerden E.
Difference in time to positivity of hub-blood versus nonhub-blood cultures is not useful for the diagnosis of catheter-related bloodstream infection in critically ill patients.
Crit Care Med. 2001 Jul;29(7):1399-403. doi: 10.1097/00003246-200107000-00016.
Abstract/Text OBJECTIVE: The differential time to positivity (DTTP), defined as the difference in time necessary for the blood cultures taken by a peripheral puncture and through the catheter to become positive has been suggested to be useful in differentiating between catheter-related bloodstream infection (CR-BSI) and other sources of bacteremia. A DTTP of >120 mins was found predominantly in CR-BSI. The objective of our study was to investigate whether DTTP is useful for the diagnosis of CR-BSI in a medical-surgical intensive care unit.
DESIGN: Prospective clinical study.
SETTING: A 60-bed medical-surgical intensive care unit of a university hospital.
PATIENTS: One hundred consecutive adult patients from whom catheter(s) were to be removed for suspected CR-BSI were studied.
INTERVENTION: A blood culture (using aerobic and anaerobic culture bottles) was first taken from a new puncture site. Next, a blood culture was taken through every intravascular catheter in place.
MEASUREMENTS AND RESULTS: DTTP was calculated using the automated BacT/Alert blood culture system. Three patients had CR-BSI and nine patients had noncatheter-related bacteremia. Five patients had catheter-related sepsis without proven bacteremia. There was no significant difference in median DTTP between patients with CR-BSI and noncatheter-related bacteremia (2.1 hrs and 3.3 hrs, respectively; p =.6). Moreover, catheter-related sepsis in patients without bacteremia could not be detected using DTTP.
CONCLUSION: DTTP seems not to be useful for the diagnosis of CR-BSI in a medical-surgical intensive care unit.

PMID 11445695
Safdar N, Fine JP, Maki DG.
Meta-analysis: methods for diagnosing intravascular device-related bloodstream infection.
Ann Intern Med. 2005 Mar 15;142(6):451-66. doi: 10.7326/0003-4819-142-6-200503150-00011.
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.

PMID 15767623
Dhaliwal M, Daneman N.
Utility of Differential Time to Positivity in Diagnosing Central Line-Associated Bloodstream Infections: A Systematic Review and Meta-Analysis.
Clin Infect Dis. 2023 Aug 14;77(3):428-437. doi: 10.1093/cid/ciad225.
Abstract/Text BACKGROUND: Differential time to positivity (DTP), defined as pathogen growth at least 2 hours earlier from catheter versus paired peripheral blood cultures, is sometimes used to diagnose central line-associated bloodstream infections (CLABSIs). Previous studies assessing DTP, however, have been small, provided conflicting results, and did not assess heterogeneity across important subgroups.
METHODS: We systematically reviewed the diagnostic characteristics of DTP for CLABSI using MEDLINE, Embase, WoS, CINAHL, LILACS, AMED, and the Cochrane database. Studies were included if they reported sensitivities, specificities, predictive values, likelihood ratios, or 2 × 2 tables of DTP for diagnosing CLABSI. Extracted data were analyzed by using forest plots, bivariate model meta-analysis, and QUADAS-2 quality assessment.
RESULTS: We identified 274 records, of which 23 met the criteria for meta-analysis. Among 2526 suspected CLABSIs, DTP demonstrated a summary sensitivity of 81.3% (95% confidence interval [CI]: 72.8%-87.7%), specificity of 91.8% (95% CI: 84.5%-95.8%), positive likelihood ratio of 9.89 (95% CI: 5.14-19.00), and negative likelihood ratio of 0.20 (95% CI: .14-.30). Covariate analysis based on catheter duration, study design, and patient immune status demonstrated no significant differences. However, DTP performed worse for Staphylococcus aureus (low sensitivity but high specificity) and Candida (high sensitivity but low specificity) compared to other organisms.
CONCLUSIONS: DTP performs well in ruling CLABSIs in or out. Obtaining paired catheter and peripheral blood cultures for DTP when the infectious source is unclear may prevent unnecessary line removal and diagnostic tests. However, this must be balanced against higher contamination rates from catheter cultures.

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PMID 37062596
Orihuela-Martín J, Rodríguez-Núñez O, Morata L, Cardozo C, Puerta-Alcalde P, Hernández-Meneses M, Ambrosioni J, Linares L, Bodro M, de Los Angeles Guerrero-León M, Del Río A, Garcia-Vidal C, Almela M, Pitart C, Marco F, Soriano A, Martínez JA.
Performance of differential time to positivity as a routine diagnostic test for catheter-related bloodstream infections: a single-centre experience.
Clin Microbiol Infect. 2020 Mar;26(3):383.e1-383.e7. doi: 10.1016/j.cmi.2019.07.001. Epub 2019 Jul 6.
Abstract/Text OBJECTIVE: To assess the performance of differential time to positivity (DTP) for the diagnosis of catheter-related bloodstream infections (CRBSI).
METHODS: From all episodes of bloodstream infections (BSI) diagnosed during a 15-year period (2003-17) those in which a paired set of blood cultures drawn from a catheter and a peripheral vein were positive for the same microorganism and had a clinically and/or microbiologically defined source were selected. To assess diagnostic discrimination ability and accuracy of DTP for CRBSI, area under the receiver operating characteristic curves (AUC) and performance characteristics of a DTP ≥2 h were computed.
RESULTS: A total of 512 BSI were included, of which 302 (59%) were CRBSI. Discrimination ability of DTP was low for Staphylococcus aureus (AUC 0.656 ± 0.06), coagulase-negative staphylococci (AUC 0.618 ± 0.081), enterococci (AUC 0.554 ± 0.117) and non-AmpC-producing Enterobacteriaceae (AUC 0.653 ± 0.053); moderate for Pseudomonas aeruginosa (AUC 0.841 ± 0.073), and high for AmpC-producing Enterobacteriaceae (AUC 0.944 ± 0.039). For the entire sample, DTP had a low-to-moderate discrimination ability (AUC 0.698 ± 0.024). A DTP ≥2 h has a low sensitivity for coagulase-negative staphylococci (60%) and very low for S. aureus (34%), enterococci (40%) and non-AmpC-producing Enterobacteriaceae (42%). A DTP cut-off of 1 h improved sensitivity (90%) for AmpC-producing Enterobacteriaceae.
CONCLUSIONS: Differential time to positivity performs well for diagnosing CRBSI only when AmpC-producing Enterobacteriaceae and P. aeruginosa are involved. Performance is low for common Gram-positive organisms and non-AmpC-producing enteric bacilli; a negative test should not be used to rule out CRBSI due to these microorganisms. A DTP ≥1 h may improve accuracy for AmpC-producing Enterobacteriaceae, particularly Enterobacter spp.

Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 31288101
Mermel LA, Rupp ME.
Should Blood Cultures Be Drawn Through an Indwelling Catheter?
Open Forum Infect Dis. 2024 May;11(5):ofae248. doi: 10.1093/ofid/ofae248. Epub 2024 May 2.
Abstract/Text There is no practical way to definitively diagnose a catheter-related bloodstream infection in situ if blood cultures are only obtained percutaneously unless there is the rare occurrence of purulent drainage from a central venous catheter insertion site. That is why the Infectious Diseases Society of America guidelines for diagnosis and management of catheter-related bloodstream infections and Infectious Diseases Society of America guidelines for evaluation of fever in critically ill patients both recommend drawing blood cultures from a central venous catheter and percutaneously if the catheter is a suspected source of infection. However, central venous catheter-drawn blood cultures may be more likely to be positive reflecting catheter hub, connector, or intraluminal colonization, and many hospitals in the United States discourage blood culture collection from catheters in an effort to reduce reporting of central-line associated bloodstream infections to the Centers for Disease Control and Prevention. As such, clinical decisions are made regarding catheter removal or other therapeutic interventions based on incomplete and potentially inaccurate data. We urge clinicians to obtain catheter-drawn blood cultures when the catheter may be the source of suspected infection.

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PMID 38770214
Freeman JT, Elinder-Camburn A, McClymont C, Anderson DJ, Bilkey M, Williamson DA, Berkahn L, Roberts SA.
Central line-associated bloodstream infections in adult hematology patients with febrile neutropenia: an evaluation of surveillance definitions using differential time to blood culture positivity.
Infect Control Hosp Epidemiol. 2013 Jan;34(1):89-92. doi: 10.1086/668431. Epub 2012 Nov 20.
Abstract/Text We used differential time to positivity between central and peripheral blood cultures to evaluate the positive predictive value (PPV) of the National Healthcare Safety Network central line-associated bloodstream infection (CLABSI) surveillance definition among hematology patients with febrile neutropenia. The PPV was 27.7%, which suggests that, when the definition is applied to this population, CLABSI rates will be substantially overestimated.

PMID 23221198
Sihler KC, Chenoweth C, Zalewski C, Wahl W, Hyzy R, Napolitano LM.
Catheter-related vs. catheter-associated blood stream infections in the intensive care unit: incidence, microbiology, and implications.
Surg Infect (Larchmt). 2010 Dec;11(6):529-34. doi: 10.1089/sur.2009.084.
Abstract/Text BACKGROUND: Catheter-associated blood stream infections (CA-BSI) and catheter-related blood stream infections (CR-BSIs) differ in the degree of proof required to show that the catheter is the cause of the infection. The U.S. Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infections Surveillance [NNIS] group) collects data regarding CA-BSI nationally. We hypothesized that there would be a significant difference in the rates reported according to the definition.
METHODS: Prospective surveillance of CA-BSI (defined as bacteremia with no extravascular source identified) is performed in all intensive care units (ICUs) at our institution and reported as the rate per 1,000 catheter-days. In January 2006, we initiated cultures of all catheter tips to evaluate for CR-BSI (defined as a catheter tip culture with >15 colony-forming units of the same microorganism(s) found in the blood culture) in the surgical, trauma-burn, and medical ICUs.
RESULTS: The CA-BSI rate across all ICUs for the 24-mo study period was 1.4/1,000 catheter-days. The CR-BSI rate was 0.4/1,000 catheter days, for a rate difference of 1.0 infections/1,000 catheter-days (p < 0.001 vs. CA-BSI). The pathogens identified in CA-BSI included many organisms that are not associated with catheter-related BSIs.
CONCLUSIONS: The CR-BSI rate is significantly lower than the CA-BSI rate. The organisms identified in CA-BSI surveillance often are not common in catheter-related infections. Reporting CR-BSI thus is a more accurate measure of complications of central venous catheter use, and this rate may be more sensitive to catheter-specific interventions designed to reduce rates of BSI in the ICU.

PMID 20969471
Ekkelenkamp MB, van der Bruggen T, van de Vijver DA, Wolfs TF, Bonten MJ.
Bacteremic complications of intravascular catheters colonized with Staphylococcus aureus.
Clin Infect Dis. 2008 Jan 1;46(1):114-8. doi: 10.1086/524077.
Abstract/Text Patients with Staphylococcus aureus colonization of an intravascular catheter but without demonstrated bacteremia within 24 h after intravascular catheter removal had a 24% (12 of 49 patients) chance of subsequent S. aureus bacteremia if they did not receive immediate antistaphylococcal antibiotics. Treatment within 24 h after intravascular catheter removal led to a 83% reduction in the incidence of subsequent bacteremia.

PMID 18171225
Park KH, Kim SH, Song EH, Jang EY, Lee EJ, Chong YP, Choi SH, Lee SO, Woo JH, Kim YS.
Development of bacteraemia or fungaemia after removal of colonized central venous catheters in patients with negative concomitant blood cultures.
Clin Microbiol Infect. 2010 Jun;16(6):742-6. doi: 10.1111/j.1469-0691.2009.02926.x. Epub 2009 Sep 11.
Abstract/Text There are limited data on the clinical significance of positive central venous catheter (CVC) tip cultures associated with concomitant negative blood cultures performed at the time of CVC removal. A retrospective cohort study of all patients who yielded isolated positive CVC tip cultures was conducted in a tertiary-care hospital with 2200 beds during a 10-year period. All patients with isolated positive CVC tip cultures were observed for the development of subsequent bacteraemia or fungaemia between 2 and 28 days after CVC removal. An isolated positive CVC tip culture was defined as a case in which (i) a CVC tip culture yielded > or = 15 colonies using a semiquantitative culture method and (ii) at least two sets of blood samples revealed no organism at, or close to, the time of CVC removal (48 h before to 48 h after CVC removal). During the study period, 312 patients with isolated positive CVC cultures were enrolled. Eight (2.6%; 95% CI 1.2-5.1) of the 312 patients yielding isolated bacterial or fungal CVC tip cultures developed subsequent bloodstream infection (BSI) caused by the same species as that isolated from the tip culture (Staphylococcus aureus, 1: Enterococcus spp.; 2: Pseudomonas aeruginosa; and 3: Candida spp.). Among 125 patients from whose CVC tips the above four organisms were grown, seven (12.3%) of 57 patients who did not receive appropriate antibiotic therapy within 48 h after CVC removal subsequently developed BSI, but only one (1.5%) of 68 patients who did receive appropriate therapy developed BSI (OR 0.11, p 0.02).

PMID 19747217
Rijnders BJ, Peetermans WE, Verwaest C, Wilmer A, Van Wijngaerden E.
Watchful waiting versus immediate catheter removal in ICU patients with suspected catheter-related infection: a randomized trial.
Intensive Care Med. 2004 Jun;30(6):1073-80. doi: 10.1007/s00134-004-2212-x. Epub 2004 Mar 4.
Abstract/Text OBJECTIVE: To find a subset of patients with suspected central venous catheter (CVC)-related infection (CRI) in whom CVC removal is not needed.
DESIGN: Randomized controlled trial.
SETTING: Thirty-three-bed ICU.
PATIENTS AND PARTICIPANTS: One hundred and forty four patients with suspected CRI in which a change of CVCs was planned were evaluated for inclusion.
INTERVENTIONS: Hemodynamically stable patients without proven bacteremia, no insertion site infection, and no intravascular foreign body were randomized to a standard-of-care group (SOC, all CVCs were changed as planned) or a watchful waiting group (WW, CVCs changed when bacteremia was subsequently confirmed or hemodynamic instability occurred).
MEASUREMENT AND RESULTS: Study groups were compared for incidence of CVC-related bloodstream infection (CR-BSI), resolution of fever, C-reactive protein, SOFA score, duration of ICU stay, and mortality. Of 144 patients with suspected CRI, 80 patients met exclusion criteria. Sixty-four were randomized. Forty-seven of 80 excluded patients were shown to be bacteremic, 20 (25%) of whom had a CR-BSI. Five of 64 (8%) included patients had a CR-BSI during their subsequent ICU stay (two in SOC and three in WW group). All 38 CVCs were changed in the SOC group versus 16 of 42 in the WW group (62% reduction, P<0.01). Resolution of fever, C-reactive protein, SOFA score, duration of ICU stay, and ICU mortality did not differ between SOC and WW group ( P>0.1 for all).
CONCLUSIONS: The use of a simple clinical algorithm permits a substantial decrease in the number of unnecessarily removed CVCs without increased morbidity.

PMID 14999442
Fowler VG Jr, Justice A, Moore C, Benjamin DK Jr, Woods CW, Campbell S, Reller LB, Corey GR, Day NP, Peacock SJ.
Risk factors for hematogenous complications of intravascular catheter-associated Staphylococcus aureus bacteremia.
Clin Infect Dis. 2005 Mar 1;40(5):695-703. doi: 10.1086/427806. Epub 2005 Feb 4.
Abstract/Text BACKGROUND: The role of both host and pathogen characteristics in hematogenous seeding following Staphylococcus aureus bacteremia is incompletely understood.
METHODS: Consecutive patients with intravascular catheter-associated Staphylococcus aureus bacteremia were prospectively recruited over a 91-month period. The corresponding bloodstream isolates were examined for the presence of 35 putative virulence determinants. Patient and bacterial characteristics associated with the development of hematogenous complications (HCs) (i.e., septic arthritis, vertebral osteomyelitis, or endocarditis) were defined.
RESULTS: HC occurred in 42 (13%) of 324 patients. Patient characteristics at diagnosis that were associated with HC included community onset (relative risk [RR], 2.25; 95% confidence interval [CI], 1.24-4.07; P=.007), increased symptom duration (odds ratio for each day, 1.14; 95% CI, 1.06-1.2; P<.001), presence of a long-term intravascular catheter or noncatheter prosthesis (RR, 4.02; 95% CI, 1.74-9.27; P<.001), hemodialysis dependence (RR, 3.84; 95% CI, 2.08-7.10; P<.001), and higher APACHE II score (P=.02). Bacterial characteristics included sea (RR, 2.03; 95% CI, 1.16-3.55; P=.011) and methicillin-resistant S. aureus (MRSA) (RR, 2.09; 95% CI, 1.19-3.67; P=.015). Subsequent failure to remove a catheter was also associated with HC (RR, 2.28; 95% CI, 1.22-4.27; P=.011). On multivariable analysis, symptom duration, hemodialysis dependence, presence of a long-term intravascular catheter or a noncatheter device, and infection with MRSA remained significantly associated with HC.
CONCLUSIONS: This investigation identifies 4 host- and pathogen-related risk factors for hematogenous bacterial seeding and reaffirms the importance of prompt catheter removal.

PMID 15714415
Nucci M, Colombo AL, Silveira F, Richtmann R, Salomão R, Branchini ML, Spector N.
Risk factors for death in patients with candidemia.
Infect Control Hosp Epidemiol. 1998 Nov;19(11):846-50. doi: 10.1086/647743.
Abstract/Text OBJECTIVE: To analyze possible risk factors for death among patients with nosocomial candidemia. To identify risk factors for death in patients with candidemia, we analyzed demographic, clinical, and microbiological data.
SETTING: Six tertiary hospitals in Brazil.
PATIENTS: A cohort of 145 patients with candidemia.
DESIGN: 26 possible risk factors for death, including age, underlying disease, signs of deep-seated infection, neutropenia, number of positive blood cultures, removal of a central venous catheter, etiologic agent of the candidemia, susceptibility pattern of the isolate to amphotericin B, and antifungal treatment were evaluated by univariate stepwise logistic regression analysis.
RESULTS: Non-albicans species accounted for 63.4% of the candidemias. Risk factors for death in univariate analysis were older age, catheter retention, poor performance status, candidemia due to species other than Candida parapsilosis, hypotension, candidemia due to species other than Candida parapsilosis, and no antifungal treatment. In multivariate analysis, older age and nonremoval of a central venous catheter were the only factors associated with an increased risk for death.
CONCLUSIONS: These data suggest that patients with candidemia and a central venous catheter should have the catheter removed.

PMID 9831941
Atkinson JB, Chamberlin K, Boody BA.
A prospective randomized trial of urokinase as an adjuvant in the treatment of proven Hickman catheter sepsis.
J Pediatr Surg. 1998 May;33(5):714-6. doi: 10.1016/s0022-3468(98)90194-4.
Abstract/Text BACKGROUND/PURPOSE: Chronic vascular access catheters have become an important adjunct to the treatment of children with complex medical diseases, particularly malignancy. One of the major complications of chronic venous access devices is bacterial infection of the catheter site and bloodstream. Infusion of systemic antibiotics directly into the catheter has been the standard initial therapy with failure leading to catheter removal and replacement. It has been suggested by a number of investigators that the addition of urokinase as a thrombolytic agent to lyse any accumulated thrombus or fibrin would increase the successful catheter clearance by antibiotics. This study was designed as a prospective, randomized trial to compare treatment of children with positive catheter blood cultures with either antibiotics alone or in combination with urokinase 5,000 U boluses 12 and 24 hours after study entry.
METHODS: A total of 63 patients were entered in the study. Thirty-three received antibiotics and urokinase, and 30 received antibiotics alone.
RESULTS: A total of 45 catheters (71%) were cleared of infection and salvaged. Treatment failures leading to catheter removal occurred in 9 of 33 in the experimental group and 9 of 30 in the control population (no significant difference).
CONCLUSIONS: Urokinase could not be shown to act as an adjuvant in the clearance of infection from chronic central venous access catheters that had no evidence of clot or thrombus. This study required the performance of a dye study and excluded any patient with a known thrombus. This conclusion must therefore be limited to patients with no evidence of a clot or fibrin sheath.

PMID 9607475
La Quaglia MP, Caldwell C, Lucas A, Corbally M, Heller G, Steinherz L, Brown AE, Groeger J, Exelby PR.
A prospective randomized double-blind trial of bolus urokinase in the treatment of established Hickman catheter sepsis in children.
J Pediatr Surg. 1994 Jun;29(6):742-5. doi: 10.1016/0022-3468(94)90359-x.
Abstract/Text BACKGROUND: The incidence of Hickman catheter sepsis is 10% to 40%, with resultant catheter loss in one third of infections. Urokinase causes dissolution of colonized intracatheter fibrin thrombi and may improve salvage.
STUDY AIMS: To evaluate the efficacy of 12-hour-interval slow-push urokinase infusion in addition to standard antibiotic therapy in the treatment of catheter sepsis in a pediatric oncology population.
METHODS: A two-arm randomized double-blind trial was undertaken, with catheter salvage rate as the end point. Patients with Hickman catheter sepsis were randomized after culture data confirmed the diagnosis. The study drug was administered by a slow intravenous push and given at 12-hour intervals for a total of four doses. The catheters were aspirated after 1 hour.
RESULTS AND CONCLUSIONS: The trial was stopped after 41 patients were entered into the study; 18 patients received a placebo, and 23 received the urokinase. In the placebo group, six catheters were lost; in the urokinase group, eight were lost. The rate of bacterial clearance was equivalent for both. After administration of the study drug, each group had three episodes of fever and chills; two of these resulted in hypotension (one in each group). The authors conclude that slow-push urokinase infusion during established Hickman catheter sepsis does not result in improved catheter salvage or bacterial clearance. Slow intravenous push infusions in this setting may provoke hemodynamic instability even after initiation of antibiotics.

PMID 8078010
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB.
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.

PMID 15306996
Lorente L, Jiménez A, Santana M, Iribarren JL, Jiménez JJ, Martín MM, Mora ML.
Microorganisms responsible for intravascular catheter-related bloodstream infection according to the catheter site.
Crit Care Med. 2007 Oct;35(10):2424-7. doi: 10.1097/01.CCM.0000284589.63641.B8.
Abstract/Text OBJECTIVE: Current guidelines for the management of intravascular catheter-related bloodstream infection (IVC-RBSI) recommend that empirical antimicrobial therapy must have activity against Gram-positive bacteria, but additional empirical coverage for Gram-negative bacteria may be needed for severely ill or immunocompromised patients, and antifungal therapy may be needed in some situations. We hypothesized that the spectrum of etiological microorganisms responsible for IVC-RBSI and, in relation to that, the choice of empirical antimicrobial therapy depends on the catheter insertion site. We therefore compared the proportion of IVC-RBSI due to Gram-negative bacteria and yeasts according to catheter site.
DESIGN: Prospective cohort study from May 1, 2000, to April 30, 2004.
SETTING: A 24-bed medical-surgical intensive care unit in a 650-bed tertiary hospital.
PATIENTS: Patients requiring a central venous or arterial catheter.
MEASUREMENTS AND MAIN RESULTS: We diagnosed 88 IVC-RBSIs, comprising 36 femoral catheter sites (26 femoral venous and ten femoral arterial sites) and 52 other catheter sites (36 jugular venous, 11 subclavian venous, and five radial arterial sites). No differences were found between IVC-RBSI of femoral vs. other catheter sites for age, sex, Acute Physiology and Chronic Health Evaluation II, diagnosis at admission, use of antimicrobials, the time the catheter responsible for IVC-RBSI had been in place, or the duration of intensive care unit stay before IVC-RBSI. The proportion of IVC-RBSIs due to Gram-negative bacteria was higher in femoral, 14 of 36 (38.89%), than in the other catheter sites, 4 of 52 (7.69%) (odds ratio, 7.48; 95% confidence interval, 2.19-25.54; p = .001). Also, the proportion of IVC-RBSIs due to yeasts was higher in femoral, 6 of 36 (16.67%), than in the other catheter sites, 1 of 52 (1.92%) (odds ratio, 10.20; 95% confidence interval, 1.17-88.85; p = .035).
CONCLUSIONS: Empirical antifungal therapy would seem to be indicated in patients with suspected femoral catheter-related bloodstream infection.

PMID 17717493
Raad I, Kassar R, Ghannam D, Chaftari AM, Hachem R, Jiang Y.
Management of the catheter in documented catheter-related coagulase-negative staphylococcal bacteremia: remove or retain?
Clin Infect Dis. 2009 Oct 15;49(8):1187-94. doi: 10.1086/605694.
Abstract/Text BACKGROUND: Studies and guidelines recommending the retention of the central venous catheter (CVC) in patients with coagulase-negative staphylococcal bacteremia were based on loose definitions of bacteremia and/or did not evaluate the risk of recurrence. In this study, we used strict definitions of coagulase-negative staphylococcal bacteremia to determine the impact of CVC retention on response to and recurrence of infection.
METHODS: During the period from July 2005 through December 2007, we retrospectively evaluated 188 patients with coagulase-negative staphylococcal bacteremia. Bacteremia was defined using the strict Centers for Disease Control and Prevention criteria of 2 positive blood culture results. Catheter-related bacteremia was confirmed by differential quantitative blood cultures (>or=3:1) or time to positivity (>2 h).
RESULTS: Resolution of infection within 48 h after commencement of antimicrobial therapy was not influenced by CVC removal or exchange versus retention and occurred in 175 patients (93%). Multiple logistic regression analysis showed that infection was 7.0 times (95% confidence interval [CI], 1.5-32.6 times) more likely to fail to resolve in patients with an intensive care unit stay prior to infection ( P = .013 ) and 3.8 times (95% CI, 1.1-13.3 times) more likely to fail to resolve in patients who had other concurrent sites of infection (P = .041 ). Duration of therapy did not affect recurrence. Multiple logistic regression analysis revealed that patients with catheter retention were 6.6 times (95% CI, 1.8-23.9 times) more likely to have a recurrence than were those whose catheter was removed or exchanged (P = .004).
CONCLUSIONS: CVC retention does not have an impact on the resolution of coagulase-negative staphylococcal bacteremia but is a significant risk factor of recurrence.

PMID 19780661
Rijnders BJ, Van Wijngaerden E, Vandecasteele SJ, Stas M, Peetermans WE.
Treatment of long-term intravascular catheter-related bacteraemia with antibiotic lock: randomized, placebo-controlled trial.
J Antimicrob Chemother. 2005 Jan;55(1):90-4. doi: 10.1093/jac/dkh488. Epub 2004 Dec 1.
Abstract/Text OBJECTIVES: The use of an antibiotic lock (AB-lock) for the treatment of catheter-related bloodstream infection (CRBSI) has been suggested, but randomized trials have never been performed.
METHODS: A randomized, blinded, multicentre trial was set up to compare an AB-lock-containing vancomycin for Gram-positive or ceftazidime for Gram-negative bacteria-with placebo, in addition to parenteral AB therapy. We included only CRBSI from a long-term intravascular device (LTID) whether tunnelled or totally implanted.
RESULTS: During 30 months, 174 patients with an LTID and bacteraemia were evaluated, of whom 85 had a CRBSI. Forty-six patients were included. Frequent reasons for exclusion were: catheter not vacant for >8-12 h/day for the AB-lock (n =10); yeast infection or mixed Gram-positive/negative infections (n =13); catheter removal preferred by the treating physician (n =7); and CRBSI <14 days after insertion or pocket/tunnel infection (n =10). Forty-four patients met the criteria for modified intention-to-treat analysis. The primary endpoint was failure to cure the CRBSI or relapse with the same strain. On study day 180 by Kaplan-Meier analysis, this occurred in 33% (seven of 21) in the AB-lock arm and in 57% (13 of 23) in the placebo arm (hazard ratio 0.55, P =0.10). A relapse with the same strain occurred in 9/23 with the placebo and 3/21 with the AB-lock (P =0.06).
CONCLUSION: Future studies should take into account the barriers to the use of AB-lock observed in this study. Most importantly, shorter lock dwell times and broader spectrum locks (e.g. antiseptic) should be investigated to target a larger patient population.

PMID 15574481
Abraham J, Mansour C, Veledar E, Khan B, Lerakis S.
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.

PMID 14999206
Fowler VG Jr, Li J, Corey GR, Boley J, Marr KA, Gopal AK, Kong LK, Gottlieb G, Donovan CL, Sexton DJ, Ryan T.
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. doi: 10.1016/s0735-1097(97)00250-7.
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.

PMID 9316542
Sochowski RA, Chan KL.
Implication of negative results on a monoplane transesophageal echocardiographic study in patients with suspected infective endocarditis.
J Am Coll Cardiol. 1993 Jan;21(1):216-21. doi: 10.1016/0735-1097(93)90739-n.
Abstract/Text OBJECTIVES: This study was conducted to determine the implications of negative findings on a transesophageal echocardiographic study in which neither a vegetation nor an abscess is identified in patients with clinically suspected infective endocarditis.
BACKGROUND: Echocardiography is the procedure of choice for evaluating suspected infective endocarditis in patients. Transesophageal echocardiography has been shown to be superior to transthoracic imaging. Although the importance of positive results or a diagnostic study is known, the significance of negative findings on a transesophageal study is not clear.
METHODS: All transesophageal echocardiographic studies performed over a 2-year period for suspected infective endocarditis were reviewed and the clinical course of patients with an initially negative study result was assessed to determine their final diagnosis.
RESULTS: Of the 105 patients identified, 65 had a negative transesophageal study result. In the majority of this group (56 of 65), an alternate diagnosis was made or there was no infective endocarditis on follow-up examination, or both. Of the remaining nine patients, four were treated for endocarditis without a definite diagnosis and five had infective endocarditis proved by either repeat transesophageal study (n = 3), pathologic findings (n = 1) or a diagnostic clinical course (n = 1). Gram-positive bacteremia and the presence of a prosthetic valve in the aortic position tended to be more common in the latter group.
CONCLUSIONS: A negative transesophageal study result reduces the likelihood that endocarditis is present. Repeat examination, however, should be considered in high risk patients, such as those with prosthetic valves or unexplained bacteremia, to avoid a missed diagnosis.

PMID 8417064
Raad II, Sabbagh MF.
Optimal duration of therapy for catheter-related Staphylococcus aureus bacteremia: a study of 55 cases and review.
Clin Infect Dis. 1992 Jan;14(1):75-82. doi: 10.1093/clinids/14.1.75.
Abstract/Text Over the last two decades, the optimal duration of therapy for catheter-related Staphylococcus aureus bacteremia has become the subject of controversy. A review of the literature revealed an occasional association between relapse of the infection and a short course of therapy (less than 10 days of iv antibiotic therapy). From records kept between 1983 and 1989 at the University of Florida's affiliated hospitals, we identified 55 patients with catheter-related S. aureus bacteremia. Nine patients (16%) developed acute early complications (e.g., endocarditis or osteomyelitis) while receiving antibiotics. The results of multivariate analysis showed that an early complicated course was characterized by fever and/or bacteremia that persisted for greater than 3 days after catheter removal (P = .02). The remaining 46 patients were followed up for at least 3 months. During follow-up, three of the 18 patients treated for less than 10 days with iv antibiotics developed relapsing septicemia, whereas none of the 28 patients treated for a longer period developed this condition (P = .05). Fever and/or bacteremia that persists for greater than 3 days after catheter removal and initiation of antibiotic therapy suggests an acutely complicated course requiring prolonged treatment. The duration of iv antibiotic therapy in uncomplicated cases should not be less than 10 days but need not be greater than 2 weeks.

PMID 1571466
Daneman N, Downing M, Zagorski BM.
How long should peripherally inserted central catheterization be delayed in the context of recently documented bloodstream infection?
J Vasc Interv Radiol. 2012 Jan;23(1):123-5. doi: 10.1016/j.jvir.2011.09.024.
Abstract/Text The risk of relapsing bacteremia was assessed retrospectively among a cohort of 348 patients who underwent peripherally inserted central catheter (PICC) insertion within 6 weeks of a documented bacteremia. The overall risk of relapsing bacteremia was low (three of 348; 0.9%) when PICC insertion was performed in the context of a recent bloodstream infection. The relapse risk was higher when PICCs were inserted within 2 days (two of 31; 6.5%) versus at least 3 days (one of 317; 0.3%) after documentation of bacteremia (P = .02).

Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.
PMID 22221476
Takakura S, Fujihara N, Saito T, Kimoto T, Ito Y, Iinuma Y, Ichiyama S.
Improved clinical outcome of patients with Candida bloodstream infections through direct consultation by infectious diseases physicians in a Japanese university hospital.
Infect Control Hosp Epidemiol. 2006 Sep;27(9):964-8. doi: 10.1086/504934. Epub 2006 Aug 14.
Abstract/Text OBJECTIVE: To examine whether intervention by infectious diseases physicians (IDPs) in the treatment decisions that emphasize adequate antifungal treatment and early removal of central venous catheter for patients with Candida bloodstream infection (BSI) improves prognosis.
DESIGN: Retrospective cohort study of patients with Candida BSI, comparing the prognosis of patients before and after the start of the intervention.
SETTING: A 1,240-bed, tertiary care university hospital.
PATIENTS: Forty patients with Candida BSI during a 2-year period, from January 2001 to December 2002, were included in the study. Twenty-three patients in the first year after the start of intervention by IDPs (intervention group) were compared with 17 patients in the first year before the start of the IDP intervention (baseline group).
INTERVENTIONS: In January 2002, a total of 5 IDPs at Kyoto University Hospital gave unsolicited recommendations on antifungal treatment and advised all physicians treating inpatients who had Candida BSI to remove the central venous catheter.
RESULTS: No significant difference was seen between the 2 groups in patients' clinical background, species, and fluconazole susceptibility of the causative organisms. The 30-day survival rate was significantly better in the intervention group (18 [78%] of 23 patients) than in the baseline group (7 [44%] of 16 patients; P=.04 by Fisher's exact test). More patients in the intervention group than in the baseline group received appropriate antifungal therapy (81% vs 50%) and had their central venous catheter removed at an appropriate time (95% vs 81%).
CONCLUSION: The introduction of an active system of IDP consultation for every case of Candida BSI in our hospital substantially improved patient outcomes.

PMID 16941324
Fowler VG Jr, Sanders LL, Sexton DJ, Kong L, Marr KA, Gopal AK, Gottlieb G, McClelland RS, Corey GR.
Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients.
Clin Infect Dis. 1998 Sep;27(3):478-86. doi: 10.1086/514686.
Abstract/Text To determine whether recommendations of infectious diseases specialists affect outcome for patients, we evaluated 244 hospitalized patients with Staphylococcus aureus bacteremia. We offered our management recommendations to each patient's physicians and then assessed the clinical outcome for both patients for whom our consultative advice was followed and those for whom our advice was not heeded. All patients were followed up for 12 weeks after their first positive blood culture. Our management advice was followed for 112 patients (45.9%) and partially or completely ignored for 132 patients (54.1%). Patients for whom our recommendations were followed were more likely to be cured of their S. aureus infection and less likely to relapse (P < .01), despite having significantly more metastatic infections (P < .01) at the outset of therapy, than were those for whom our recommendations were not followed. Failure to follow recommendations to remove an infected intravascular device was the most important risk for treatment failure. After controlling for other factors, logistic regression analysis revealed that patients whose intravascular device was not removed were 6.5 times more likely to relapse or die of their infection than were those whose device was removed. Our findings suggest that patient-specific management advice by infectious diseases consultants can improve the clinical outcome for patients with S. aureus bacteremia.

PMID 9770144
Swaminathan L, Flanders S, Horowitz J, Zhang Q, O'Malley M, Chopra V.
Safety and Outcomes of Midline Catheters vs Peripherally Inserted Central Catheters for Patients With Short-term Indications: A Multicenter Study.
JAMA Intern Med. 2022 Jan 1;182(1):50-58. doi: 10.1001/jamainternmed.2021.6844.
Abstract/Text IMPORTANCE: Peripherally inserted central catheters (PICCs) and midlines are frequently used for short-term venous access; whether one is safer than the other in this setting has not been adequately reported.
OBJECTIVE: To compare outcomes between patients who had a PICC vs midline placed for the indication of difficult vascular access or antibiotic therapy for 30 or fewer days.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from a multihospital registry including patients admitted to a participating site from December 2017 through January 2020 who had a PICC or midline placement for the indications of difficult venous access or intravenous antibiotic therapy prescribed for 30 or fewer days. Data were analyzed from October 2020 to March 2021.
EXPOSURES: PICC and midline placement.
MAIN OUTCOMES AND MEASURES: Major complications, including a composite of symptomatic catheter-associated deep vein thrombosis (DVT), catheter-related bloodstream infection, and catheter occlusion. Logistic regression and Cox proportional hazards regression models (taking into account catheter dwell) were used to estimate risk for major complications, adjusting for patient and device characteristics and the clustered nature of the data. Sensitivity analyses limiting analyses to 10 days of device dwell were performed.
RESULTS: Data on 10 863 patients, 5758 with PICCs and 5105 with midlines (median [IQR] age of device recipients, 64.8 [53.4-75.4] years; 5741 [52.8%] were female), were included. After adjusting for patient characteristics, comorbidities, catheter lumens, and dwell time in logit models, patients who received PICCs had a greater risk of developing a major complication compared with those who received midlines (odds ratio, 1.99; 95% CI, 1.61-2.47). Reduction in complications stemmed from lower rates of occlusion (2.1% vs 7.0%; P < .001) and bloodstream infection (0.4% vs 1.6%; P < .001) in midlines vs PICCs; no significant difference in the risk of DVT between PICCs and midlines was observed. In time-to-event models, similar outcomes for bloodstream infection and catheter occlusion were noted; however, the risk of DVT events was lower in patients who received PICCs vs midlines (hazard ratio, 0.53; 95% CI, 0.38-0.74). Results were robust to sensitivity analyses.
CONCLUSIONS AND RELEVANCE: In this cohort study among patients with placement of midline catheters vs PICCs for short-term indications, midlines were associated with a lower risk of bloodstream infection and occlusion compared with PICCs. Whether DVT risk is similar or greater with midlines compared with PICCs for short-term use is unclear. Randomized clinical trials comparing these devices for this indication are needed.

PMID 34842905
Paje D, Walzl E, Heath M, McLaughlin E, Horowitz JK, Tatarcuk C, Swaminathan L, Kaatz S, Malani AN, Vaughn VM, Bernstein SJ, Flanders SA, Chopra V.
Midline vs Peripherally Inserted Central Catheter for Outpatient Parenteral Antimicrobial Therapy.
JAMA Intern Med. 2025 Jan 1;185(1):83-91. doi: 10.1001/jamainternmed.2024.5984.
Abstract/Text IMPORTANCE: Little is known about the safety of midline catheters vs peripherally inserted central catheters (PICCs) for outpatient parenteral antimicrobial therapy (OPAT).
OBJECTIVE: To compare outcomes from midline catheters vs PICCs for OPAT.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients who received antimicrobial therapy through a midline catheter or PICC between January 2017 and November 2023 across 69 Michigan hospitals. Because peripherally compatible OPAT was the indication of interest, vancomycin therapy was excluded. Data were analyzed from April to June 2024.
EXPOSURES: Insertion of a midline catheter or PICC for OPAT following hospitalization.
MAIN OUTCOMES AND MEASURES: The primary outcome was major device complications (ie, catheter-related bloodstream infection or catheter-related venous thromboembolism). Secondary outcomes included minor device complications (eg, catheter dislodgement, occlusion, tip migration, infiltration, superficial thrombophlebitis, or exit site concerns) and device failure, defined as catheter removal following device complication. Cox proportional hazards regression models were fit to device type and outcomes, adjusting for patient and device confounders and device dwell.
RESULTS: Of 2824 included patients, 1487 (53.5%) were male, and the median (IQR) age was 66.8 (55.9-77.1) years. Of 2824 devices placed for OPAT, 1999 (70.8%) were midline catheters and 825 (29.2%) were PICCs. The median (IQR) dwell time was 12 (8-17) days for midline catheters and 19 (12-27) days for PICCs (P < .001). A major device complication occurred in 44 patients (1.6%) overall, including 16 (0.8%) with midline catheters and 28 (3.4%) with PICCs (P < .001). OPAT delivered via midline catheters was associated with a lower risk of major complications vs PICCs (adjusted hazard ratio [aHR], 0.46; 95% CI, 0.23-0.91). Risks of minor complications and device failure were similar across device types (minor complications: 206 of 1999 [10.3%] vs 114 of 825 [13.8%]; aHR, 1.07; 95% CI, 0.83-1.38; device failure: 191 of 1999 [9.6%] vs 100 of 825 [12.1%]; aHR, 1.26; 95% CI, 0.96-1.65). For device dwell of 14 or fewer days, midline catheters were associated with a lower risk of major complications (12 of 1324 [0.9%] vs 16 of 304 [5.3%]; aHR, 0.29; 95% CI, 0.12-0.68) and similar risk of failure (151 of 1324 [11.4%] vs 52 of 304 [17.1%]; aHR, 0.79; 95% CI, 0.56-1.12) vs PICCs. For dwell longer than 14 days, no significant difference in rates of major complications (4 of 675 [0.6%] vs 12 of 521 [2.3%]; aHR, 0.42; 95% CI, 0.13-1.40) or device failure (40 of 675 [5.9%] vs 48 of 521 [9.2%]; aHR, 1.02; 95% CI, 0.64-1.61) were observed.
CONCLUSIONS AND RELEVANCE: In this study, midline catheters appeared to be safe alternatives to PICCs for OPAT, particularly if infusions were planned for 14 or fewer days.

PMID 39527077
Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H, Cosgrove S, Sexton B, Hyzy R, Welsh R, Roth G, Bander J, Kepros J, Goeschel C.
An intervention to decrease catheter-related bloodstream infections in the ICU.
N Engl J Med. 2006 Dec 28;355(26):2725-32. doi: 10.1056/NEJMoa061115.
Abstract/Text BACKGROUND: Catheter-related bloodstream infections occurring in the intensive care unit (ICU) are common, costly, and potentially lethal.
METHODS: We conducted a collaborative cohort study predominantly in ICUs in Michigan. An evidence-based intervention was used to reduce the incidence of catheter-related bloodstream infections. Multilevel Poisson regression modeling was used to compare infection rates before, during, and up to 18 months after implementation of the study intervention. Rates of infection per 1000 catheter-days were measured at 3-month intervals, according to the guidelines of the National Nosocomial Infections Surveillance System.
RESULTS: A total of 108 ICUs agreed to participate in the study, and 103 reported data. The analysis included 1981 ICU-months of data and 375,757 catheter-days. The median rate of catheter-related bloodstream infection per 1000 catheter-days decreased from 2.7 infections at baseline to 0 at 3 months after implementation of the study intervention (P< or =0.002), and the mean rate per 1000 catheter-days decreased from 7.7 at baseline to 1.4 at 16 to 18 months of follow-up (P<0.002). The regression model showed a significant decrease in infection rates from baseline, with incidence-rate ratios continuously decreasing from 0.62 (95% confidence interval [CI], 0.47 to 0.81) at 0 to 3 months after implementation of the intervention to 0.34 (95% CI, 0.23 to 0.50) at 16 to 18 months.
CONCLUSIONS: An evidence-based intervention resulted in a large and sustained reduction (up to 66%) in rates of catheter-related bloodstream infection that was maintained throughout the 18-month study period.

Copyright 2006 Massachusetts Medical Society.
PMID 17192537
Berenholtz SM, Lubomski LH, Weeks K, Goeschel CA, Marsteller JA, Pham JC, Sawyer MD, Thompson DA, Winters BD, Cosgrove SE, Yang T, Louis TA, Meyer Lucas B, George CT, Watson SR, Albert-Lesher MI, St Andre JR, Combes JR, Bohr D, Hines SC, Battles JB, Pronovost PJ; On the CUSP: Stop BSI program.
Eliminating central line-associated bloodstream infections: a national patient safety imperative.
Infect Control Hosp Epidemiol. 2014 Jan;35(1):56-62. doi: 10.1086/674384. Epub 2013 Nov 26.
Abstract/Text BACKGROUND: Several studies demonstrating that central line-associated bloodstream infections (CLABSIs) are preventable prompted a national initiative to reduce the incidence of these infections.
METHODS: We conducted a collaborative cohort study to evaluate the impact of the national "On the CUSP: Stop BSI" program on CLABSI rates among participating adult intensive care units (ICUs). The program goal was to achieve a unit-level mean CLABSI rate of less than 1 case per 1,000 catheter-days using standardized definitions from the National Healthcare Safety Network. Multilevel Poisson regression modeling compared infection rates before, during, and up to 18 months after the intervention was implemented.
RESULTS: A total of 1,071 ICUs from 44 states, the District of Columbia, and Puerto Rico, reporting 27,153 ICU-months and 4,454,324 catheter-days of data, were included in the analysis. The overall mean CLABSI rate significantly decreased from 1.96 cases per 1,000 catheter-days at baseline to 1.15 at 16-18 months after implementation. CLABSI rates decreased during all observation periods compared with baseline, with adjusted incidence rate ratios steadily decreasing to 0.57 (95% confidence intervals, 0.50-0.65) at 16-18 months after implementation.
CONCLUSION: Coincident with the implementation of the national "On the CUSP: Stop BSI" program was a significant and sustained decrease in CLABSIs among a large and diverse cohort of ICUs, demonstrating an overall 43% decrease and suggesting the majority of ICUs in the United States can achieve additional reductions in CLABSI rates.

PMID 24334799
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
久保健児 : 特に申告事項無し[2025年]
監修:山本舜悟 : 特に申告事項無し[2025年]

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