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改訂のポイント:
  1. 『成人肺炎診療ガイドライン2024』の発行に伴い、関連した記載を改訂した。
  1. 「成人肺炎診療ガイドライン2024」では、わが国から報告されたレジオネラ診断予測スコアの使用が推奨されている(Miyashita N, et al. J Infect Chemother. 2019 Jun;25(6):407-412.)。このスコアは6つのパラメーターからなり、各項目を1点として合計3点以上でレジオネラ肺炎を疑う。
  1. わが国におけるレジオネラ症の性別・年齢群別報告数のデータを更新した。

概要・推奨   

  1. レジオネラ肺炎とは、細胞内寄生細菌であるLegionella が原因でおこる疾患で、日本では、感染症法4類疾患で「ただちに届出が必要」な疾患である。
  1. Legionella は、水中の原生動物(自由生活性アメーバ)のなかで寄生・増殖している。季節性があり夏から秋に多いが、年間を通じて発生する。感染源によっては、大規模な集団感染につながり、院内発生もある。ヒト-ヒト感染はない。
  1. 症状は多彩で、咳、呼吸困難、胸痛などの肺炎症状から、消化器症状(下痢、腹痛)、神経症状(頭痛、意識障害)などの肺外症状がみられる。肺炎球菌などの定型肺炎と比較して、肺外症状を呈しやすい。
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  1. レジオネラ肺炎の原因は、わが国では半数前後がL. pneumophila serogroup 1である。尿中抗原検査(イムノクロマト法)で検出できるのは、従来はL. pneumophila 血清型1のみであった。2019年に15種類の血清型(1~15)を検出できる尿中抗原検査が日本で販売された。したがって、各施設で用いている検査キットの特徴を確認する必要がある(推奨度1)
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病態・疫学・診察 

疾患情報(疫学・病態)  
  1. レジオネラ肺炎とは、細胞内寄生細菌であるLegionella が原因でおこる疾患で、肺炎と肺外症状(肝、腎、消化器、中枢神経系)を来す。
  1. なお、Legionella は、肺炎のほかにインフルエンザ様熱性疾患であるポンティアック熱を来すこともあるが、本項はレジオネラ肺炎について示す。
  1. Legionella は、水中のバイオフィルム内に生息する原生動物(自由生活性アメーバ)のなかで寄生・増殖している。季節性があり夏から秋に多いが、年間を通じて発生する。感染源によっては、大規模な集団感染につながり、院内発生もある。ヒト-ヒト感染はない。
  1. Legionella に曝露しても発病率(attack rate)は2~7%と高くないが、臓器移植や免疫抑制患者では高い[1][2]。潜伏期間は2~10日である[1]
  1. レジオネラ肺炎は、成人市中肺炎の2~3%、院内肺炎の1%未満、小児肺炎の1%未満で原因になる。
  1. 日本では、感染症法4類疾患で「ただちに届出が必要」な疾患である。これによると、2010年は751件であったが、それ以降毎年報告数が増加している。
 
感染症法に基づく日本でのレジオネラ症の届出数

1999年(平成11年)の感染症法の施行以降の届け出数を示す。2008年以降800件前後が報告されていたが、2010年以降は増加し、2013年には1,111例が報告された。2020年には2,000例を超えている。

出典

「レジオネラ症」(厚生労働省)(https://www.mhlw.go.jp/stf/newpage_00393.html#Q9)(2024年11月閲覧)
 
  1. レジオネラ肺炎は、市中肺炎において鑑別するよう推奨される。また、医療介護関連肺炎・院内肺炎においても、頻度は高くないが重症化しやすい患者群であり、ハイリスク者では鑑別として考慮する(推奨度1)
  1. 日本呼吸器学会成人肺炎診療ガイドライン2017によると、レジオネラ肺炎は、市中肺炎の1.0%を占める[3]
  1. また、院内肺炎においてもレジオネラは原因菌になり得ることを示したコホート研究がある。2010年Jespersenらの報告で、1995~2005年のデンマークのpopulation-basedなサーベイランスシステムを利用したレジオネラ肺炎の入院例を調査した結果、272例(81.9%)の市中例と60例(18.1%)の院内例(院内の定義=10日以内の退院歴または入院後2日以降の発症)があった[4]
  1. 発症から診断までの時間は、市中:5.5日vs 院内例:12日で、院内例で長かった(p<0.001)。30日死亡率は、市中例12.9%、院内例33.3%であった[4]
  1. デンマークにおけるレジオネラ肺炎の入院サーベイランス(1995~2005年):図<図表>
  1. 日本における医療関連レジオネラ肺炎の報告は、新生児病棟の給水系・加湿器・ミルク加温器に関連した院内例(慶応大学、1996年)[5]、院内展望風呂(24時間風呂)に関連した院内例(名古屋大学、2000年)[6][7]などがある。
  1. 家庭用加湿器が感染源となる事例は1990年代から報告されていたが、高齢者介護施設での集団発生を受けて、2018年に厚労省は「レジオネラ症を予防するために必要な措置に関する技術上の指針」[8]を改訂し、加湿器対策を明記した。この事例は、2017年12月大分県の老人ホームで80代男性2名が発病、2018年1月にショートステイ利用の90代男性1名が発病し、1名死亡したものである。
  1. この指針では、「高齢者、新生児及び免疫機能の低下を来す疾患にかかっている者が多い医療施設、社会福祉施設等においては、入浴設備、空気調和設備の冷却塔、給湯設備、加湿器等における衛生上の措置を徹底して講ずることが必要である。」と記載されている。
  1. 現実には、医療施設などにおける水質衛生の認知と対策は不十分であり、近年の医療施設における環境調査報告ではレジオネラ菌の高い陽性率が指摘されている[9][10][11][12]
  1. これらのことから、レジオネラ肺炎は、市中肺炎において鑑別するよう推奨される。また、院内肺炎においても、まれではあるが報告はあるため、移植や免疫抑制患者などのハイリスク者では鑑別として重要となる。
 
デンマークにおけるレジオネラ肺炎の入院サーベイランス(1995~2005年)

市中例<緑>272例(81.9%)、院内例<青>60例(18.1%)(院内の定義=10日以内の退院歴または入院後2日以降の発症)の生存曲線

出典

Jespersen S, Søgaard OS, Schønheyder HC, Fine MJ, Ostergaard L.
Clinical features and predictors of mortality in admitted patients with community- and hospital-acquired legionellosis: a Danish historical cohort study.
BMC Infect Dis. 2010 May 21;10:124. doi: 10.1186/1471-2334-10-124. Epub 2010 May 21.
Abstract/Text BACKGROUND: Legionella is a common cause of bacterial pneumonia. Community-acquired [CAL] and hospital-acquired legionellosis [HAL] may have different presentations and outcome. We aimed to compare clinical characteristics and examine predictors of mortality for CAL and HAL.
METHODS: We identified hospitalized cases of legionellosis in 4 Danish counties from January 1995 to December 2005 using the Danish national surveillance system and databases at departments of clinical microbiology. Clinical and laboratory data were retrieved from medical records; vital status was obtained from the Danish Civil Registration System. We calculated 30- and 90-day case fatality rates and identified independent predictors of mortality using logistic regression analyses.
RESULTS: We included 272 cases of CAL and 60 cases of HAL. Signs and symptoms of HAL were less pronounced than for CAL and time from in-hospital symptoms to legionellosis diagnosis was shorter for CAL than for HAL (5.5 days vs. 12 days p < 0.001). Thirty-day case fatality was 12.9% for CAL and 33.3% for HAL; similarly 90-day case fatalities in the two groups were 15.8% and 55.0%, respectively. In a logistic regression analysis (excluding symptoms and laboratory tests) age >65 years (OR = 2.6, 95% CI: 1.1-5.9) and Charlson comorbidty index > or =2 (OR = 2.7, 95% CI: 1.1-6.5) were associated with an increased risk of death in CAL. We identified no statistically significant predictors of 30-day mortality in HAL.
CONCLUSIONS: Signs and symptoms were less pronounced in HAL compared to CAL. Conversely, 30-day case fatality was almost 3 times higher. Clinical awareness is important for the timely diagnosis and treatment especially of HAL. There is a need for further studies of prognostic factors in order to improve the therapeutic approach to legionellosis and potentially reduce mortality.

PMID 20492639
問診・診察のポイント  
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文献 

Doebbeling BN, Wenzel RP.
The epidemiology of Legionella pneumophila infections.
Semin Respir Infect. 1987 Dec;2(4):206-21.
Abstract/Text The study of outbreaks of Legionella pneumophila has been essential in understanding the organism, the disease, and its pathogenesis. Early epidemics defined the clinical spectrum: Pontiac fever is an acute, self-limited, febrile illness with an attack rate of 95% to 100% and an incubation period of 36 hours. In contrast, legionnaires' disease is a life-threatening bronchopneumonia with an attack rate of 2% to 7% and an incubation period of two to ten days. Three times as many males as females are affected with legionnaires' disease, and age, cigarette smoking, and chronic medical disease (particularly immunosuppression) appear to be separate risk factors. Furthermore, L pneumophila is responsible for approximately 1% to 3% of community-acquired pneumonias, 13% of those acquired in the hospital and as many as 26% of atypical pneumonias. Diverse environmental reservoirs have been identified, including cooling systems, potable or domestic water systems, respiratory therapy devices, industrial coolants, and whirlpool spas. Hot water temperature, stagnant water, sediment, and the presence of other microorganisms are important factors in the amplification of the Legionellaceae. Although airborne transmission has been widely suggested, aspiration may be an important mode in certain patients. Regional and national surveillance may identify common sources and allow the introduction of early control measures. The latter have included primarily pulse and continuous hyperchlorination and super-heating hot water systems to 50 to 60 degrees C. Experimental data suggest that ozone and UV light may be useful in the future. Additionally, cooling towers and evaporative condensers have been decontaminated and maintained with a variety of biocides. The prevention of outbreaks requires thoughtful planning, redesign, and good engineering practices.

PMID 3328890
Silk BJ, Foltz JL, Ngamsnga K, Brown E, Muñoz MG, Hampton LM, Jacobs-Slifka K, Kozak NA, Underwood JM, Krick J, Travis T, Farrow O, Fields BS, Blythe D, Hicks LA.
Legionnaires' disease case-finding algorithm, attack rates, and risk factors during a residential outbreak among older adults: an environmental and cohort study.
BMC Infect Dis. 2013 Jun 27;13:291. doi: 10.1186/1471-2334-13-291. Epub 2013 Jun 27.
Abstract/Text BACKGROUND: During a Legionnaires' disease (LD) outbreak, combined epidemiological and environmental investigations were conducted to identify prevention recommendations for facilities where elderly residents live independently but have an increased risk of legionellosis.
METHODS: Survey responses (n = 143) were used to calculate attack rates and describe transmission routes by estimating relative risk (RR) and 95% confidence intervals (95% CI). Potable water collected from five apartments of LD patients and three randomly-selected apartments of residents without LD (n = 103 samples) was cultured for Legionella.
RESULTS: Eight confirmed LD cases occurred among 171 residents (attack rate = 4.7%); two visitors also developed LD. One case was fatal. The average age of patients was 70 years (range: 62-77). LD risk was lower among residents who reported tub bathing instead of showering (RR = 0.13, 95% CI: 0.02-1.09, P = 0.03). Two respiratory cultures were characterized as L. pneumophila serogroup 1, monoclonal antibody type Knoxville (1,2,3), sequence type 222. An indistinguishable strain was detected in 31 (74%) of 42 potable water samples.
CONCLUSIONS: Managers of elderly-housing facilities and local public health officials should consider developing a Legionella prevention plan. When Legionella colonization of potable water is detected in these facilities, remediation is indicated to protect residents at higher risk. If LD occurs among residents, exposure reduction, heightened awareness, and clinical surveillance activities should be coordinated among stakeholders. For prompt diagnosis and effective treatment, clinicians should recognize the increased risk and atypical presentation of LD in older adults.

PMID 23806063
日本呼吸器学会:成人肺炎診療ガイドライン2017.
Jespersen S, Søgaard OS, Schønheyder HC, Fine MJ, Ostergaard L.
Clinical features and predictors of mortality in admitted patients with community- and hospital-acquired legionellosis: a Danish historical cohort study.
BMC Infect Dis. 2010 May 21;10:124. doi: 10.1186/1471-2334-10-124. Epub 2010 May 21.
Abstract/Text BACKGROUND: Legionella is a common cause of bacterial pneumonia. Community-acquired [CAL] and hospital-acquired legionellosis [HAL] may have different presentations and outcome. We aimed to compare clinical characteristics and examine predictors of mortality for CAL and HAL.
METHODS: We identified hospitalized cases of legionellosis in 4 Danish counties from January 1995 to December 2005 using the Danish national surveillance system and databases at departments of clinical microbiology. Clinical and laboratory data were retrieved from medical records; vital status was obtained from the Danish Civil Registration System. We calculated 30- and 90-day case fatality rates and identified independent predictors of mortality using logistic regression analyses.
RESULTS: We included 272 cases of CAL and 60 cases of HAL. Signs and symptoms of HAL were less pronounced than for CAL and time from in-hospital symptoms to legionellosis diagnosis was shorter for CAL than for HAL (5.5 days vs. 12 days p < 0.001). Thirty-day case fatality was 12.9% for CAL and 33.3% for HAL; similarly 90-day case fatalities in the two groups were 15.8% and 55.0%, respectively. In a logistic regression analysis (excluding symptoms and laboratory tests) age >65 years (OR = 2.6, 95% CI: 1.1-5.9) and Charlson comorbidty index > or =2 (OR = 2.7, 95% CI: 1.1-6.5) were associated with an increased risk of death in CAL. We identified no statistically significant predictors of 30-day mortality in HAL.
CONCLUSIONS: Signs and symptoms were less pronounced in HAL compared to CAL. Conversely, 30-day case fatality was almost 3 times higher. Clinical awareness is important for the timely diagnosis and treatment especially of HAL. There is a need for further studies of prognostic factors in order to improve the therapeutic approach to legionellosis and potentially reduce mortality.

PMID 20492639
乳児院におけるレジオネラ症の集団発生例. 感染症誌78:404~410,2004.
レジオネラによる院内感染と感染防止対策. 環境感染誌24:1,2009.
厚生労働省:レジオネラ症を予防するために必要な措置に関する技術上の指針 平成15年7月25日厚生労働省告示第264号(平成30年8月3日厚生労働省告示第297号により一部改正).
大屋日登美,鈴木美雪,政岡智佳,中嶋直樹,古川一郎,前川純子,倉文明,泉山信司,黒木俊郎:医療機関の給水設備におけるレジオネラ属菌の汚染実態.日本感染症学雑誌 2018;92(5):678-685.
磯目賢一,中島佳代,池町真実,山崎貴之,中浴伸二,宮川一也,永澤浩志:院内感染で判明したレジオネラ菌による給湯系汚染とその後の対応.日本感染症学雑誌 2020;35(2):81-86.
中村造:病院におけるWater Hygiene管理.日本環境感染学会誌 2019;34(6):271-276.
Nakamura I, Miura Y, Umeda A, Imura R, Watanabe Y, Watanabe H.
The Legionella contamination of tap water in a brand-new hospital in Japan before patients move in.
Infect Control Hosp Epidemiol. 2020 Aug;41(8):998-999. doi: 10.1017/ice.2020.79. Epub 2020 Jun 2.
Abstract/Text
PMID 32484124
Sopena N, Pedro-Botet ML, Sabrià M, García-Parés D, Reynaga E, García-Nuñez M.
Comparative study of community-acquired pneumonia caused by Streptococcus pneumoniae, Legionella pneumophila or Chlamydia pneumoniae.
Scand J Infect Dis. 2004;36(5):330-4. doi: 10.1080/00365540410020091.
Abstract/Text The objective of this study was to compare epidemiological data and clinical presentation of community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae, Legionella pneumophila or Chlamydia pneumoniae. From May 1994 to February 1996, 157 patients with S. pneumoniae (n = 68), L. pneumophila (n = 48) and C. pneumoniae (n = 41) pneumonia with definitive diagnosis, were prospectively studied. The following comparisons showed differences at a level of at least p < 0.05. Patients with S. pneumoniae pneumonia had more frequently underlying diseases (HIV infection and neoplasm) and those with C. pneumoniae pneumonia were older and had a higher frequency of chronic obstructive pulmonary disease (COPD), while L. pneumophila pneumonia prevailed in patients without comorbidity, but with alcohol intake. Presentation with cough and expectoration were significantly more frequent in patients with S. pneumoniae or C. pneumoniae pneumonia, while headache, diarrhoea and no response to betalactam antibiotics prevailed in L. pneumophila pneumonia. However, duration of symptoms > or = 7 d was more frequent in C. pneumoniae pneumonia. Patients with CAP caused by L. pneumophila presented hyponatraemia and an increase in CK more frequently, while AST elevation prevailed in L. pneumophila and C. pneumoniae pneumonia. In conclusion, some risk factors and clinical characteristics of patients with CAP may help to broaden empirical therapy against atypical pathogens until rapid diagnostic tests are available.

PMID 15287376
Mandell: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th ed. 232 Legionella.
Miyashita N, Horita N, Higa F, Aoki Y, Kikuchi T, Seki M, Tateda K, Maki N, Uchino K, Ogasawara K, Kiyota H, Watanabe A.
Validation of a diagnostic score model for the prediction of Legionella pneumophila pneumonia.
J Infect Chemother. 2019 Jun;25(6):407-412. doi: 10.1016/j.jiac.2019.03.009. Epub 2019 Mar 29.
Abstract/Text BACKGROUND: Community-acquired pneumonia (CAP) due to Legionella has a high mortality rate in patients who do not receive adequate antibiotic therapy. In a previous study, we developed a simple Legionella Score to distinguish patients with Legionella and non-Legionella pneumonia based on clinical information at diagnosis. In the present study, we validated this Legionella Score for the presumptive diagnosis of Legionella CAP.
METHODS: This validation cohort included 109 patients with Legionella CAP and 683 patients with non-Legionella CAP. The Legionella Score includes six parameters by assigning one point for each of the following items: being male, absence of cough, dyspnea, C-reactive protein (CRP) ≥ 18 mg/dL, lactate dehydrogenase (LDH) ≥ 260 U/L, and sodium < 134 mmol/L.
RESULTS: When the Legionella CAP and non-Legionella CAP were compared by univariate analysis, most of the evaluated symptoms and laboratory test results differed substantially. The six parameters that were used for the Legionella Score also indicated clear differences between the Legionella and non-Legionella CAP. All Legionella patients had a score of 2 points or higher. The median Legionella Scores were 4 in the Legionella CAP cases and 2 in the non-Legionella CAP cases. A receiver operating characteristics curve showed that the area under the curve was 0.93. The proposed best cutoff, total score ≥3, had sensitivity of 93% and specificity of 75%.
CONCLUSION: Our Legionella Score was shown to have good diagnostic ability with a positive likelihood of 3.7 and a negative likelihood of 0.10.

Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PMID 30935766
日本呼吸器学会:成人肺炎診療ガイドライン2024.
Cunha BA.
The atypical pneumonias: clinical diagnosis and importance.
Clin Microbiol Infect. 2006 May;12 Suppl 3:12-24. doi: 10.1111/j.1469-0691.2006.01393.x.
Abstract/Text The most common atypical pneumonias are caused by three zoonotic pathogens, Chlamydia psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii (Q fever), and three nonzoonotic pathogens, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella. These atypical agents, unlike the typical pathogens, often cause extrapulmonary manifestations. Atypical CAPs are systemic infectious diseases with a pulmonary component and may be differentiated clinically from typical CAPs by the pattern of extrapulmonary organ involvement which is characteristic for each atypical CAP. Zoonotic pneumonias may be eliminated from diagnostic consideration with a negative contact history. The commonest clinical problem is to differentiate legionnaire's disease from typical CAP as well as from C. pneumoniae or M. pneumonia infection. Legionella is the most important atypical pathogen in terms of severity. It may be clinically differentiated from typical CAP and other atypical pathogens by the use of a weighted point system of syndromic diagnosis based on the characteristic pattern of extrapulmonary features. Because legionnaire's disease often presents as severe CAP, a presumptive diagnosis of Legionella should prompt specific testing and empirical anti-Legionella therapy such as the Winthrop-University Hospital Infectious Disease Division's weighted point score system. Most atypical pathogens are difficult or dangerous to isolate and a definitive laboratory diagnosis is usually based on indirect, i.e., direct flourescent antibody (DFA), indirect flourescent antibody (IFA). Atypical CAP is virtually always monomicrobial; increased IFA IgG tests indicate past exposure and not concurrent infection. Anti-Legionella antibiotics include macrolides, doxycycline, rifampin, quinolones, and telithromycin. The drugs with the highest level of anti-Legionella activity are quinolones and telithromycin. Therapy is usually continued for 2 weeks if potent anti-Legionella drugs are used. In adults, M. pneumoniae and C. pneumoniae may exacerbate or cause asthma. The importance of the atypical pneumonias is not related to their frequency (approximately 15% of CAPs), but to difficulties in their diagnosis, and their nonresponsiveness to beta-lactam therapy. Because of the potential role of C. pneumoniae in coronary artery disease and multiple sclerosis (MS), and the role of M. pneumoniae and C. pneumoniae in causing or exacerbating asthma, atypical CAPs also have public health importance.

PMID 16669925
Gupta SK, Imperiale TF, Sarosi GA.
Evaluation of the Winthrop-University Hospital criteria to identify Legionella pneumonia.
Chest. 2001 Oct;120(4):1064-71. doi: 10.1378/chest.120.4.1064.
Abstract/Text STUDY OBJECTIVE: To measure the ability of a set of clinical parameters, the Winthrop-University Hospital (WUH) criteria, to identify Legionella pneumonia while discriminating against bacteremic pneumococcal pneumonia at the time of hospitalization for community-acquired pneumonia (CAP).
DESIGN: Retrospective case-control study.
SETTING: An urban county hospital and a tertiary-care Veterans Affairs hospital.
PATIENTS: Thirty-seven patients with Legionella pneumonia (diagnosed by a positive result of a urinary Legionella antigen test) and 31 patients with bacteremic pneumococcal pneumonia. A subgroup of patients with all required laboratory criteria were studied further.
RESULTS: The WUH criteria correctly identified 29 of 37 patients with Legionella pneumonia (sensitivity, 78%; 95% confidence interval [CI], 61 to 90%), while successfully excluding legionellosis in 20 of 31 patients with bacteremic pneumococcal pneumonia (specificity, 65%; 95% CI, 45 to 80%). The positive and negative predictive values, adjusted for a relative prevalence of 1:3 between Legionella and Streptococcus pneumoniae bacteremia, were 42% (95% CI, 25 to 61%) and 90% (95% CI, 74 to 97%), respectively. In the subgroup analysis, the WUH criteria were successful in identifying 20 of 23 patients with Legionella pneumonia (sensitivity, 87%; 95% CI, 65 to 97%), while excluding legionellosis in 9 of 18 patients with bacteremic pneumococcal pneumonia (specificity, 50%; 95% CI, 27 to 73%). The adjusted positive and negative predictive values for a 1:3 relative prevalence were 37% (95% CI, 20 to 59%) and 92% (95% CI, 62 to 98%), respectively. The predictive values were changed in the directions expected for an increased relative prevalence of 1:1. The areas under the receiver operating characteristic curves were 0.72 +/- 0.06 for the entire study group and 0.68 +/- 0.09 for the subgroup.
CONCLUSIONS: Although the WUH criteria discriminated fairly well between cases (mean +/- SE) and control subjects, the sensitivity is not high enough to exclude legionellosis confidently. These results suggest that empiric therapy for Legionella pneumonia should be included in the initial antibiotic regimen for hospitalized patients with CAP.

PMID 11591540
Priest PC, Slow S, Chambers ST, Cameron CM, Balm MN, Beale MW, Blackmore TK, Burns AD, Drinković D, Elvy JA, Everts RJ, Hammer DA, Huggan PJ, Mansell CJ, Raeder VM, Roberts SA, Robinson MC, Sathyendran V, Taylor SL, Thompson AW, Ussher JE, van der Linden AJ, Williams MJ, Podmore RG, Anderson TP, Barratt K, Mitchell JL, Harte DJ, Hope VT, Murdoch DR.
The burden of Legionnaires' disease in New Zealand (LegiNZ): a national surveillance study.
Lancet Infect Dis. 2019 Jul;19(7):770-777. doi: 10.1016/S1473-3099(19)30113-6. Epub 2019 Jun 10.
Abstract/Text BACKGROUND: Legionnaires' disease is under-diagnosed because of inconsistent use of diagnostic tests and uncertainty about whom to test. We assessed the increase in case detection following large-scale introduction of routine PCR testing of respiratory specimens in New Zealand.
METHODS: LegiNZ was a national surveillance study done over 1-year in which active case-finding was used to maximise the identification of cases of Legionnaires' disease in hospitals. Respiratory specimens from patients of any age with pneumonia, who could provide an eligible lower respiratory specimen, admitted to one of 20 participating hospitals, covering a catchment area of 96% of New Zealand's population, were routinely tested for legionella by PCR. Additional cases of Legionnaires' disease in hospital were identified through mandatory notification.
FINDINGS: Between May 21, 2015, and May 20, 2016, 5622 eligible specimens from 4862 patients were tested by PCR. From these, 197 cases of Legionnaires' disease were detected. An additional 41 cases were identified from notification data, giving 238 cases requiring hospitalisation. The overall incidence of Legionnaires' disease cases in hospital in the study area was 5·4 per 100 000 people per year, and Legionella longbeachae was the predominant cause, found in 150 (63%) of 238 cases.
INTERPRETATION: The rate of notified disease during the study period was three-times the average over the preceding 3 years. Active case-finding through systematic PCR testing better clarified the regional epidemiology of Legionnaires' disease and uncovered an otherwise hidden burden of disease. These data inform local Legionnaires' disease testing strategies, allow targeted antibiotic therapy, and help identify outbreaks and effective prevention strategies. The same approach might have similar benefits if applied elsewhere in the world.
FUNDING: Health Research Council of New Zealand.

Copyright © 2019 Elsevier Ltd. All rights reserved.
PMID 31196812
Fraser DW, Tsai TR, Orenstein W, Parkin WE, Beecham HJ, Sharrar RG, Harris J, Mallison GF, Martin SM, McDade JE, Shepard CC, Brachman PS.
Legionnaires' disease: description of an epidemic of pneumonia.
N Engl J Med. 1977 Dec 1;297(22):1189-97. doi: 10.1056/NEJM197712012972201.
Abstract/Text An explosive, common-source outbreak of pneumonia caused by a previously unrecognized bacterium affected primarily persons attending an American Legion convention in Philadelphia in July, 1976. Twenty-nine of 182 cases were fatal. Spread of the bacterium appeared to be air borne. The source of the bacterium was not found, but epidemiologic analysis suggested that exposure may have occurred in the lobby of the headquarters hotel or in the area immediately surrounding the hotel. Person-to-person spread seemed not to have occurred. Many hotel employees appeared to be immune, suggesting that the agent may have been present in the vicinity, perhaps intermittently, for two or more years.

PMID 335244
Higa F, Shinzato T, Toyama M, Haranaga S, Furugen M, Tateyama M, Kawakami K, Saito A.
Efficacy of pazufloxacin mesilate in Legionnaires' disease: a case report and in vitro study of the isolate.
J Infect Chemother. 2005 Jun;11(3):164-8. doi: 10.1007/s10156-005-0381-3.
Abstract/Text We report here a case of culture-proven Legionnaires' disease successfully treated with intravenous injection of pazufloxacin mesilate (PZFX), a fluoroquinolone newly approved in Japan. The patient was a 51-year-old man hospitalized after a diagnosis of community-acquired pneumonia. Legionella pneumophila SG1 was isolated from the patient's bronchoalveolar lavage (BAL) fluid, and the soluble antigen of the bacterium was detected in the fluid as well. Subsequently, intravenous PZFX was administered for a week and proved markedly effective. An in vitro study confirmed that PZFX had excellent extracellular and intracellular activity against the isolate from the patient. This case suggests that PZFX is an option for treating Legionnaires' disease.

PMID 15990982
Blázquez Garrido RM, Espinosa Parra FJ, Alemany Francés L, Ramos Guevara RM, Sánchez-Nieto JM, Segovia Hernández M, Serrano Martínez JA, Huerta FH.
Antimicrobial chemotherapy for Legionnaires disease: levofloxacin versus macrolides.
Clin Infect Dis. 2005 Mar 15;40(6):800-6. doi: 10.1086/428049. Epub 2005 Feb 17.
Abstract/Text BACKGROUND: The community outbreak of legionnaires disease that occurred in Murcia, Spain, in July 2001--to our knowledge, the largest such outbreak ever reported--afforded an unusual opportunity to compare the clinical response of patients with Legionella pneumonia treated with levofloxacin with that of patients treated with macrolides and to determine the role of rifampicin combined with levofloxacin in treating severe legionellosis.
METHODS: An observational, prospective, nonrandomized study was conducted involving 292 patients seen at our hospital (Hospital "J. M. Morales Meseguer"; Murcia, Spain) who received a diagnosis of Legionella pneumonia during the Murcia outbreak. To compare both antibiotic regimens (macrolides vs. levofloxacin), patients were stratified by the severity of pneumonia. Duration of fever, clinical outcome, complications, side effects, and length of hospital stay were recorded. To assess the potential effects of adjuvant therapy with rifampicin, 45 case patients treated with levofloxacin plus rifampicin were evaluated and compared with 45 control pairs who were treated with levofloxacin alone.
RESULTS: With the exception of 2 patients who died, all patients were cured. There were no significant differences between treatment groups in clinical outcome for patients with mild-to-moderate pneumonia. Nevertheless, in patients with severe pneumonia, levofloxacin exerted superior activity; it was associated with fewer complications (3.4% of patients receiving levofloxacin experienced complications, compared with 27.2% of patients receiving macrolides; P=.02) and shorter mean hospital stays (5.5 vs. 11.3 days; P=.04). Addition of rifampicin to the treatment regimen for patients receiveing levofloxacin for severe pneumonia provides no additional benefit.
CONCLUSIONS: Our findings strongly suggest that monotherapy with levofloxacin is a safe and effective treatment for legionnaires disease, including in patients with severe disease. In these patients, levofloxacin appears to be more effective than clarithromycin.

PMID 15736011
Mykietiuk A, Carratalà J, Fernández-Sabé N, Dorca J, Verdaguer R, Manresa F, Gudiol F.
Clinical outcomes for hospitalized patients with Legionella pneumonia in the antigenuria era: the influence of levofloxacin therapy.
Clin Infect Dis. 2005 Mar 15;40(6):794-9. doi: 10.1086/428059. Epub 2005 Feb 17.
Abstract/Text BACKGROUND: Although the reduction in case-fatality rate recently observed among patients with Legionella pneumonia has been largely attributed to the progressive utilization of urine antigen testing, other factors, such as changes in empirical antibiotic therapy, may also have contributed. We have analyzed more-recent outcomes of Legionella pneumonia in an institution where urine antigen testing was reflexly performed in cases of community-acquired pneumonia without an etiological diagnosis.
METHODS: From a prospective series of 1934 consecutive cases of community-acquired pneumonia in nonimmunocompromised adults, 139 cases of Legionella pneumophila pneumonia were selected for observational review. Legionella cases were analyzed for outcome with respect to antibiotic treatment, mortality, complications, length of stay, time to defervescence, and stability.
RESULTS: The early case-fatality rate was 2.9% (4 of 139 patients), and the overall case-fatality rate was 5% (7 of 139 patients). One hundred twenty patients (86.3%) received an appropriate initial therapy, which included macrolides (i.e., erythromycin or clarithromycin) in 80 patients and levofloxacin in 40. Levofloxacin progressively replaced macrolides as the initial therapy during the study period. Compared with patients who received macrolides, patients who received levofloxacin had a faster time to defervescence (2.0 vs. 4.5 days; P<.001) and to clinical stability (3 vs. 5 days; P=.002). No differences were found regarding the development of complications (25% vs. 25%; P=.906) and case-fatality rate (2.5% vs. 5%; P=.518). The median length of hospital stay was 8 days in patients treated with levofloxacin and 10 days in those who received macrolides (P=.014).
CONCLUSIONS: Legionella pneumonia is still associated with significant complications in hospitalized patients, but recent mortality is substantially lower than that found in earlier series. Levofloxacin may produce a faster clinical response than older macrolides, allowing for shorter hospital stay.

PMID 15736010
Sabrià M, Pedro-Botet ML, Gómez J, Roig J, Vilaseca B, Sopena N, Baños V; Legionnaires Disease Therapy Group.
Fluoroquinolones vs macrolides in the treatment of Legionnaires disease.
Chest. 2005 Sep;128(3):1401-5. doi: 10.1378/chest.128.3.1401.
Abstract/Text BACKGROUND: Erythromycin has been the treatment of choice for Legionnaires disease (LD). However, treatment failure and experimental evidence of its bacteriostatic effect have led to evaluation of new drugs such as fluoroquinolones. This study compared the evolution of patients with LD treated with macrolides and fluoroquinolones.
METHODS: A prospective observational study was performed, and 130 patients from three centers were included. Diagnoses were made using Legionella urinary antigen assay in all patients. Patients receiving any antibiotic > 36 h before starting the study therapy were excluded. Group 1 included 76 patients who received macrolides (33 patients with erythromycin and 43 patients with clarithromycin), and group 2 included 54 patients treated with fluoroquinolones (50 patients with levofloxacin and 4 patients with ofloxacin).
RESULTS: No significant differences were seen between the two groups regarding age, sex, smoking, alcohol intake, underlying diseases, or community/hospital acquisition. The time from onset of LD symptoms until the initiation of antibiotic treatment was 78.5 h and 92.7 h in groups 1 and 2, respectively (p = 0.1). Time to apyrexia was significantly longer in the macrolide group (77.1 h vs 48 h for groups 1 and 2, respectively; p = 0.000). There were no differences according to radiology, clinical complications, or mortality. Nevertheless, a trend to a longer hospital stay was observed in the macrolide group (9.9 days vs 7.6 days in groups 1 and 2, respectively; p = 0.09).
CONCLUSIONS: Fluoroquinolones were as effective as erythromycin in the treatment of LD. It is of note that time to apyrexia was significantly shorter and hospital stay tended to be shorter in patients receiving fluoroquinolones.

PMID 16162735
Haranaga S, Tateyama M, Higa F, Miyagi K, Akamine M, Azuma M, Yara S, Koide M, Fujita J.
Intravenous ciprofloxacin versus erythromycin in the treatment of Legionella pneumonia.
Intern Med. 2007;46(7):353-7. doi: 10.2169/internalmedicine.46.6006. Epub 2007 Apr 2.
Abstract/Text BACKGROUND: Erythromycin (EM) and rifampicin (RFP) have mainly been used to treat patients with Legionella pneumonia. Since intravenous ciprofloxacin (CPFX) became available in Japan from 2000, many reports have been published detailing successful treatment of Legionella pneumonia with CPFX. In this study, we compared the evolution of patients with Legionella pneumonia treated with CPFX to those treated with EM.
METHODS: The study included nine patients treated with CPFX and eighteen patients treated with EM. Diagnosis of these patients was made by culture, PCR, urinary antigen assay or a serological method. A comparison was made of the patients' characteristics, severity of pneumonia, efficacy of each agent and the clinical course.
RESULTS: No significant differences were observed between the two groups, in regard to age, gender, underlying disease or severity of pneumonia. In addition, the period of time from onset of the disease until appropriate therapy did not differ significantly between the two groups. In the CPFX group, all of the patients were cured and in the EM group 16 out of the 18 patients were cured. Although there were no significant differences, the time to apyrexia, normalization of leukocytosis and a 50% decrease in C-reactive protein (CRP) occurred within a relatively shorter time frame in the CPFX group than in the EM group (3.5 versus 4 days, 4 versus 5.2 days, and 2.9 versus 10.3 days, respectively). And, the duration of antibiotic treatment in the CPFX group was significantly shorter than in the EM group.
CONCLUSION: CPFX was as effective as erythromycin in the treatment of Legionella pneumonia. The effects of treatment may appear relatively earlier and the duration of treatment was significantly shorter in patients treated with CPFX therapy than with EM therapy.

PMID 17409596
Griffin AT, Peyrani P, Wiemken T, Arnold F.
Macrolides versus quinolones in Legionella pneumonia: results from the Community-Acquired Pneumonia Organization international study.
Int J Tuberc Lung Dis. 2010 Apr;14(4):495-9.
Abstract/Text BACKGROUND: Data supporting a quinolone or a macrolide as preferred therapy for community-acquired pneumonia (CAP) due to Legionella pneumophila are not firmly established. Some literature suggests a benefit of quinolones over macrolides.
OBJECTIVE: To compare time to clinical stability (TCS) and length of hospital stay (LOS) in patients with Legionella pneumonia who were treated with levofloxacin (LVX) compared to those treated with newer macrolides.
DESIGN: An analysis of patients with Legionnaires' disease from the Community-Acquired Pneumonia Organization database was performed. Patients were diagnosed with CAP using radiographic and clinical criteria, while Legionella was detected by urinary antigen or sputum culture. All patients received a macrolide (azithromycin or clarithromycin) or LVX. TCS was defined as the time from hospital admission to candidacy for switch to oral therapy.
RESULTS: A total of 39 patients were included for analysis. The mean TCS for the macrolide group was 5.1 days vs. 4.3 days for the LVX group (P = 0.43). The mean LOS for the macrolide group was 12.7 days vs. 8.9 days for the quinolone group (P = 0.10).
CONCLUSION: LOS and TCS were not statistically different between the macrolide and the LVX groups in treating CAP due to Legionella, despite trends in both outcomes favoring LVX.

PMID 20202309
Jasper AS, Musuuza JS, Tischendorf JS, Stevens VW, Gamage SD, Osman F, Safdar N.
Are Fluoroquinolones or Macrolides Better for Treating Legionella Pneumonia? A Systematic Review and Meta-analysis.
Clin Infect Dis. 2021 Jun 1;72(11):1979-1989. doi: 10.1093/cid/ciaa441.
Abstract/Text BACKGROUND: The Infectious Diseases Society of America recommends either a fluoroquinolone or a macrolide as a first-line antibiotic treatment for Legionella pneumonia, but it is unclear which antibiotic leads to optimal clinical outcomes. We compared the effectiveness of fluoroquinolone versus macrolide monotherapy in Legionella pneumonia using a systematic review and meta-analysis.
METHODS: We conducted a systematic search of literature in PubMed, Cochrane, Scopus, and Web of Science from inception to 1 June 2019. Randomized controlled trials and observational studies comparing macrolide with fluoroquinolone monotherapy using clinical outcomes in patients with Legionella pneumonia were included. Twenty-one publications out of an initial 2073 unique records met the selection criteria. Following PRISMA guidelines, 2 reviewers participated in data extraction. The primary outcome was mortality. Secondary outcomes included clinical cure, time to apyrexia, length of hospital stay (LOS), and the occurrence of complications. The review and meta-analysis was registered with PROSPERO (CRD42019132901).
RESULTS: Twenty-one publications with 3525 patients met inclusion criteria. The mean age of the population was 60.9 years and 67.2% were men. The mortality rate for patients treated with fluoroquinolones was 6.9% (104/1512) compared with 7.4% (133/1790) among those treated with macrolides. The pooled odds ratio assessing risk of mortality for patients treated with fluoroquinolones versus macrolides was 0.94 (95% confidence interval, .71-1.25, I2 = 0%, P = .661). Clinical cure, time to apyrexia, LOS, and the occurrence of complications did not differ for patients treated with fluoroquinolones versus macrolides.
CONCLUSIONS: We found no difference in the effectiveness of fluoroquinolones versus macrolides in reducing mortality among patients with Legionella pneumonia.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
PMID 32296816
Cunha BA, Burillo A, Bouza E.
Legionnaires' disease.
Lancet. 2016 Jan 23;387(10016):376-385. doi: 10.1016/S0140-6736(15)60078-2. Epub 2015 Jul 28.
Abstract/Text Since first identified in early 1977, bacteria of the genus Legionella are recognised as a common cause of community-acquired pneumonia and a rare cause of hospital-acquired pneumonia. Legionella bacteria multisystem manifestations mainly affect susceptible patients as a result of age, underlying debilitating conditions, or immunosuppression. Water is the major natural reservoir for Legionella, and the pathogen is found in many different natural and artificial aquatic environments such as cooling towers or water systems in buildings, including hospitals. The term given to the severe pneumonia and systemic infection caused by Legionella bacteria is Legionnaires' disease. Over time, the prevalence of legionellosis or Legionnaires' disease has risen, which might indicate a greater awareness and reporting of the disease. Advances in microbiology have led to a better understanding of the ecological niches and pathogenesis of the condition. Legionnaires' disease is not always suspected because of its non-specific symptoms, and the diagnostic tests routinely available do not offer the desired sensitivity. However, effective antibiotics are available. Disease notification systems provide the basis for initiating investigations and limiting the scale and recurrence of outbreaks. This report reviews our current understanding of this disease.

Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID 26231463
Plouffe JF, Breiman RF, Fields BS, Herbert M, Inverso J, Knirsch C, Kolokathis A, Marrie TJ, Nicolle L, Schwartz DB.
Azithromycin in the treatment of Legionella pneumonia requiring hospitalization.
Clin Infect Dis. 2003 Dec 1;37(11):1475-80. doi: 10.1086/379329. Epub 2003 Oct 29.
Abstract/Text Azithromycin is highly active against Legionella pneumophila and has been shown to be efficacious in animal models and in clinical studies of patients with legionnaires disease. This open, prospective, multicenter trial evaluated azithromycin for the treatment of legionnaires disease. Twenty-five hospitalized patients with community-acquired pneumonia and a positive result of a L. pneumophila serogroup 1 urinary antigen assay received monotherapy with intravenous azithromycin (500 mg/day) for 2-7 days, followed by oral azithromycin (1500 mg administered over the course of 3 or 5 days). The mean total duration of intravenous plus oral therapy was 7.92 days. The overall cure rate among clinically evaluable patients was 95% (20 of 21 patients) at 10-14 days after therapy and 96% (22 of 23 patients) at 4-6 weeks after therapy. The results of this study support previously reported data demonstrating that azithromycin is both safe and efficacious for the treatment of hospitalized patients with legionnaires disease.

PMID 14614670
Kuzman I, Soldo I, Schönwald S, Culig J.
Azithromycin for treatment of community acquired pneumonia caused by Legionella pneumophila: a retrospective study.
Scand J Infect Dis. 1995;27(5):503-5. doi: 10.3109/00365549509047054.
Abstract/Text A clinical, retrospective and non-comparative study was undertaken to assess the clinical efficacy and tolerability of azithromycin in the treatment of community-acquired pneumonia caused by Legionella pneumophila. A total of 16 patients with a serologically confirmed diagnosis of Legionnaires' diseases were included. Azithromycin was administered orally at a total dose of 1.5 g for either 3 or 5 days. All patients were no side-effects requiring discontinuation of the treatment. Further increase of abnormal baseline liver function was recorded in 2 patients and in 1 patient mild, transient eosinophilia. Equal clinical efficacy and tolerability were observed with the 3- and 5-day dosage regimen. These results indicate that azithromycin given at a standard dose of 1.5 g is effective and well tolerated in the treatment of Legionnaires' disease.

PMID 8588143
Sánchez F, Mensa J, Martínez JA, Badia R, Albarracín M, Losa JE, Ruiz M, Marcos MA, Torres A, Soriano E.
[Treatment of pneumonia caused by Legionella with azithromycin].
Rev Esp Quimioter. 1998 Jun;11(2):147-51.
Abstract/Text Nineteen patients with pneumonia caused by Legionella, who did not need to be admitted to ICU were treated with 500 mg/day of azithromycin. The etiological diagnosis was made retrospectively by detecting Legionella pneumophila in the urine of nine patients and/or by serology (seroconversion or single titer 1/256) in 19 cases. None of them met the criteria for ICU admittance nor had received prior treatment with antibiotics which were potentially active against L. pneumophila. Serology tests and radiography of the thorax were carried out on all the patients in the study during their convalescence period. The average age (+/- SD) of the group was 58.5 +/- 16.2 years. The average respiratory frequency (+/- SD) 26 +/- 6 breaths per minute; the radiologic extension was of one lobule in 18 cases and two lobules in one case. No patients showed bilateral disease. Arterial gasometry (FiO2 0.21) showed a pO2 average of (+/- SD) 53 +/- 14 mmHg and the hemogram an average of 6.700 leukocytes/mm3 (range: 4,200-41-800). All the patients progressed favorably. The average duration of fever was 1.8 days; the average stay (+/- SD) was 6.1 +/- 2 days. The treatment was well tolerated. One month after discharge radiographies were clear for all patients. There were no relapses. In conclusion, 3-day administration of azithromycin was found to be a useful guide in the treatment of community acquired pneumonia caused by Legionella in patients whose clinical situation does not require ICU administration and allows for oral administration.

PMID 9795300
医薬品インタビューフォーム. ジスロマック錠250mg. ファイザー株式会社. 2016年9月改訂(第20版).
29 Macrolides, Clindamycin, and Ketolides. In: John E. Bennett, Raphael Dolin, Martin J. Blaser: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases 8th ed. Saunders, 2014.
Grau S, Antonio JM, Ribes E, Salvadó M, Garcés JM, Garau J.
Impact of rifampicin addition to clarithromycin in Legionella pneumophila pneumonia.
Int J Antimicrob Agents. 2006 Sep;28(3):249-52. doi: 10.1016/j.ijantimicag.2006.03.029. Epub 2006 Jul 25.
Abstract/Text We evaluated the effectiveness and safety of rifampicin addition to clarithromycin in the treatment of Legionnaires' disease. An observational cohort study was conducted on patients assigned to a Legionnaires' disease outbreak. Of 32 patients with confirmed Legionella pneumonia, 11 received clarithromycin monotherapy and 21 received combination therapy of clarithromycin with rifampicin. Both groups had similar baseline characteristics and all patients were cured. Patients who received rifampicin had a 50% longer length of stay (P=0.035) and a trend towards higher bilirubin levels (P=0.053). Length of stay was directly correlated with the duration of rifampicin treatment (P=0.001). Combination therapy of clarithromycin and rifampicin had no additional benefit compared with clarithromycin monotherapy and could prolong the length of stay owing to possible negative drug interactions that could also affect other antibiotics.

PMID 16870401
Varner TR, Bookstaver PB, Rudisill CN, Albrecht H.
Role of rifampin-based combination therapy for severe community-acquired Legionella pneumophila pneumonia.
Ann Pharmacother. 2011 Jul;45(7-8):967-76. doi: 10.1345/aph.1Q074. Epub 2011 Jul 20.
Abstract/Text OBJECTIVE: To review the literature concerning the role of rifampin in the combination treatment of Legionella pneumophila pneumonia.
DATA SOURCES: A search of MEDLINE and Ovid databases was conducted (January 1970-May 2011) using the search terms Legionella pneumophila, pneumonia, Legionnaires' disease, rifampin or rifampicin, macrolide, fluoroquinolone, erythromycin, clarithromycin, levofloxacin, ciprofloxacin, and moxifloxacin
STUDY SELECTION AND DATA EXTRACTION: In vivo studies published in English that compared antimicrobial therapies including rifampin for the treatment of Legionella pneumonia, as well as in vitro studies including an assessment of rifampin bioactivity, were included.
DATA SYNTHESIS: Macrolides and fluoroquinolones have been effective as monotherapy in the treatment of L. pneumophila pneumonia. This review includes evidence summaries from 4 bioactivity evaluations, 6 clinical studies, and 6 reported cases of combination rifampin use. Combined with supporting evidence, the role of combination rifampin therapy is further delineated.
CONCLUSIONS: Interpretation of the data is limited by the potential for selection bias and lack of consistent comparators. Rifampin therapy should be considered only for patients with severe disease or significant comorbid conditions (eg, uncontrolled diabetes, smoking, or obstructive lung disease) including immunocompromised hosts and those refractory to conventional monotherapy regimens. Caution for significant adverse drug events and drug-drug interactions should be taken with the addition of rifampin.

PMID 21775694
Siegel JD, Rhinehart E, Jackson M, Chiarello L; Health Care Infection Control Practices Advisory Committee.
2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings.
Am J Infect Control. 2007 Dec;35(10 Suppl 2):S65-164. doi: 10.1016/j.ajic.2007.10.007.
Abstract/Text
PMID 18068815
Sehulster L, Chinn RY; CDC; HICPAC.
Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC).
MMWR Recomm Rep. 2003 Jun 6;52(RR-10):1-42.
Abstract/Text The health-care facility environment is rarely implicated in disease transmission, except among patients who are immunocompromised. Nonetheless, inadvertent exposures to environmental pathogens (e.g., Aspergillus spp. and Legionella spp.) or airborne pathogens (e.g., Mycobacterium tuberculosis and varicella-zoster virus) can result in adverse patient outcomes and cause illness among health-care workers. Environmental infection-control strategies and engineering controls can effectively prevent these infections. The incidence of health-care--associated infections and pseudo-outbreaks can be minimized by 1) appropriate use of cleaners and disinfectants; 2) appropriate maintenance of medical equipment (e.g., automated endoscope reprocessors or hydrotherapy equipment); 3) adherence to water-quality standards for hemodialysis, and to ventilation standards for specialized care environments (e.g., airborne infection isolation rooms, protective environments, or operating rooms); and 4) prompt management of water intrusion into the facility. Routine environmental sampling is not usually advised, except for water quality determinations in hemodialysis settings and other situations where sampling is directed by epidemiologic principles, and results can be applied directly to infection-control decisions. This report reviews previous guidelines and strategies for preventing environment-associated infections in health-care facilities and offers recommendations. These include 1) evidence-based recommendations supported by studies; 2) requirements of federal agencies (e.g., Food and Drug Administration, U.S. Environmental Protection Agency, U.S. Department of Labor, Occupational Safety and Health Administration, and U.S. Department of Justice); 3) guidelines and standards from building and equipment professional organizations (e.g., American Institute of Architects, Association for the Advancement of Medical Instrumentation, and American Society of Heating, Refrigeration, and Air-Conditioning Engineers); 4) recommendations derived from scientific theory or rationale; and 5) experienced opinions based upon infection-control and engineering practices. The report also suggests a series of performance measurements as a means to evaluate infection-control efforts.

PMID 12836624
Skogberg K, Nuorti JP, Saxen H, Kusnetsov J, Mentula S, Fellman V, Mäki-Petäys N, Jousimies-Somer H.
A newborn with domestically acquired legionnaires disease confirmed by molecular typing.
Clin Infect Dis. 2002 Oct 15;35(8):e82-5. doi: 10.1086/342886. Epub 2002 Sep 19.
Abstract/Text Legionella pneumophila serogroup 6 was recovered from a bronchoalveolar lavage specimen from a 1-week-old, full-term newborn with pneumonia, as well as from water samples from the maternity hospital and the newborn's home (an apartment). Amplified fragment-length polymorphism typing revealed that the strains isolated from the newborn and her home were indistinguishable from each other but were clearly different from the hospital and control strains. To our knowledge, this is the first report of domestic acquisition of legionnaires disease in a newborn to have been confirmed by molecular typing.

PMID 12355396
Venezia RA, Agresta MD, Hanley EM, Urquhart K, Schoonmaker D.
Nosocomial legionellosis associated with aspiration of nasogastric feedings diluted in tap water.
Infect Control Hosp Epidemiol. 1994 Aug;15(8):529-33. doi: 10.1086/646971.
Abstract/Text PROBLEM: Two cases of nosocomial legionellosis due to Legionella pneumophila serogroup 6 (Lp6) were identified in the intensive care unit. Both patients had a history of aspiration of nasogastric tube feedings, developed pulmonary infiltrates, had positive cultures for Lp6, had serological titer rises to Legionella, were treated, and recovered.
METHOD: Isolates of Lp6 from the potable water system and patients were characterized by DNA restriction enzyme analyses using pulsed-field gel electrophoresis (PFGE).
RESULTS: Water samples grew > 10(4) CFU/L of Lp6, and the same PFGE pattern was observed with the patient and water isolates. Potable water was used only for delivering medications and diluting feeding solutions given through the nasogastric tubes of the patients. Heat shock of the hot water system (140 degrees to 160 degrees F or 60 degrees to 70 degrees C, 4 hours) was performed and the temperature was maintained between 131 degrees to 140 degrees F (55 degrees to 60 degrees C). Surveillance over 18 months revealed a reduction in Legionella to < 10(2) CFU/L.
CONCLUSION: We speculate that nosocomial Legionella pneumonia occurred due to aspiration of nasogastric tube solutions diluted with tap water. A nursing practice change to use only sterile water to dilute feedings and flush medications for nasogastric administration was instituted. The hot water temperature at the faucet was increased to > or = 131 degrees F (> or = 60 degrees C) to control Legionella. No further nosocomial cases have occurred.

PMID 7983346
Johnson JT, Yu VL, Best MG, Vickers RM, Goetz A, Wagner R, Wicker H, Woo A.
Nosocomial legionellosis in surgical patients with head-and-neck cancer: implications for epidemiological reservoir and mode of transmission.
Lancet. 1985 Aug 10;2(8450):298-300. doi: 10.1016/s0140-6736(85)90349-6.
Abstract/Text A prospective pneumonia study was conducted simultaneously on head-and-neck surgery wards at two hospitals over 2 years; one hospital had a water supply contaminated with Legionella pneumophila but no record of having had a case of legionella pneumonia, and the other had just decontaminated its water supply because of known endemic nosocomial legionellosis. Special laboratory tests for legionella were done on all cases of nosocomial pneumonia irrespective of clinical impression. Over the first 18 months, the rate of nosocomial legionellosis was 30% at the first hospital and 0% at the second. Patients who underwent laryngectomy did not acquire the disease. Hyperchlorination at the first hospital was followed by a fall (p less than 0.01) in legionella pneumonias. Thus legionella pneumonias can be overlooked if special laboratory tests are not applied routinely, and surgical patients with head-and-neck cancer may be at high risk of nosocomial legionellosis because of the potential for pulmonary aspiration of contaminated water or orophyaryngeal microflora and/or frequent manipulation of the respiratory tract. This study demonstrates the benefits of examining the environment for legionella despite the absence of documented disease.

PMID 2862467
Garrison LE, Kunz JM, Cooley LA, Moore MR, Lucas C, Schrag S, Sarisky J, Whitney CG.
Vital Signs: Deficiencies in Environmental Control Identified in Outbreaks of Legionnaires' Disease - North America, 2000-2014.
MMWR Morb Mortal Wkly Rep. 2016 Jun 10;65(22):576-84. doi: 10.15585/mmwr.mm6522e1. Epub 2016 Jun 10.
Abstract/Text BACKGROUND: The number of reported cases of Legionnaires' disease, a severe pneumonia caused by the bacterium Legionella, is increasing in the United States. During 2000-2014, the rate of reported legionellosis cases increased from 0.42 to 1.62 per 100,000 persons; 4% of reported cases were outbreak-associated. Legionella is transmitted through aerosolization of contaminated water. A new industry standard for prevention of Legionella growth and transmission in water systems in buildings was published in 2015. CDC investigated outbreaks of Legionnaires' disease to identify gaps in building water system maintenance and guide prevention efforts.
METHODS: Information from summaries of CDC Legionnaires' disease outbreak investigations during 2000-2014 was systematically abstracted, and water system maintenance deficiencies from land-based investigations were categorized as process failures, human errors, equipment failures, or unmanaged external changes.
RESULTS: During 2000-2014, CDC participated in 38 field investigations of Legionnaires' disease. Among 27 land-based outbreaks, the median number of cases was 10 (range = 3-82) and median outbreak case fatality rate was 7% (range = 0%-80%). Sufficient information to evaluate maintenance deficiencies was available for 23 (85%) investigations. Of these, all had at least one deficiency; 11 (48%) had deficiencies in ≥2 categories. Fifteen cases (65%) were linked to process failures, 12 (52%) to human errors, eight (35%) to equipment failures, and eight (35%) to unmanaged external changes.
CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Multiple common preventable maintenance deficiencies were identified in association with disease outbreaks, highlighting the importance of comprehensive water management programs for water systems in buildings. Properly implemented programs, as described in the new industry standard, could reduce Legionella growth and transmission, preventing Legionnaires' disease outbreaks and reducing disease.

PMID 27281485
Nguyen TM, Ilef D, Jarraud S, Rouil L, Campese C, Che D, Haeghebaert S, Ganiayre F, Marcel F, Etienne J, Desenclos JC.
A community-wide outbreak of legionnaires disease linked to industrial cooling towers--how far can contaminated aerosols spread?
J Infect Dis. 2006 Jan 1;193(1):102-11. doi: 10.1086/498575. Epub 2005 Nov 28.
Abstract/Text A community-wide outbreak of legionnaires disease occurred in Pas-de-Calais, France, in November 2003-January 2004. Eighteen (21%) of 86 laboratory-confirmed cases were fatal. A case-control study identified smoking, silicosis, and spending >100 min outdoors daily as risk factors for acquiring the disease. Legionella pneumophila strain Lens was isolated from cooling towers, wastewater, and air samples from plant A. This unique strain matched all 23 clinical isolates, as assessed by pulsed-field gel electrophoresis subtyping. Modeling of atmospheric dispersion of aerosols emitted from plant A cooling towers showed good coverage of the communes where patients lived and showed that the dispersion extended over a distance of at least 6 km from plant A. No other aerosol-producing installation was identified as a plausible source, and no common source of indoor exposure was found. These findings implicate plant A as the most likely outbreak source and suggest that the distance of airborne transmission of L. pneumophila may be greater than previously reported.

PMID 16323138
Correia AM, Ferreira JS, Borges V, Nunes A, Gomes B, Capucho R, Gonçalves J, Antunes DM, Almeida S, Mendes A, Guerreiro M, Sampaio DA, Vieira L, Machado J, Simões MJ, Gonçalves P, Gomes JP.
Probable Person-to-Person Transmission of Legionnaires' Disease.
N Engl J Med. 2016 Feb 4;374(5):497-8. doi: 10.1056/NEJMc1505356.
Abstract/Text
PMID 26840151
厚生労働省:感染症法に基づく医師の届出のお願い(2014年2月6日閲覧).
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[2024年]
監修:上原由紀 : 研究費・助成金など(花王(株))[2024年]

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