Are Fluoroquinolones or Macrolides Better for Treating <i>Legionella</i> Pneumonia? A Systematic Review and Meta-analysis

Jasper, Annie S; Musuuza, Jackson; Tischendorf, Jessica S; Stevens, Vanessa; Gamage, Shantini D.; Osman, Fauzia; Safdar, Nasia

doi:10.1093/cid/ciaa441

Cited by 33 publications

(23 citation statements)

References 38 publications

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“…Third, it is unclear how many of the sampled individuals had previously received or had not received a large-spectrum antibiotic therapy able to specifically target Legionella [ 83 ]. As macrolides have been extensively delivered to SARS-CoV-2 patients during the early stages of the pandemic [ 22 , 48 , 84 , 85 , 86 ], we cannot rule out that a significant share of actual co-infections with signs and symptoms of atypical pneumonia may have benefited from early antimicrobial courses [ 22 , 85 , 87 ], with their eventual impact on Legionella infections.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2–Legionella Co-Infections: A Systematic Review and Meta-Analysis (2020–2021)

et al. 2022

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Legionnaires’ Disease (LD) is a severe, sometimes fatal interstitial pneumonia due to Legionella pneumophila. Since the inception of the SARS-CoV-2 pandemic, some contradictory reports about the effects of lockdown measures on its epidemiology have been published, but no summary evidence has been collected to date. Therefore, we searched two different databases (PubMed and EMBASE) focusing on studies that reported the occurrence of LD among SARS-CoV-2 cases. Data were extracted using a standardized assessment form, and the results of such analyses were systematically reported, summarized, and compared. We identified a total of 38 articles, including 27 observational studies (either prospective or retrospective ones), 10 case reports, and 1 case series. Overall, data on 10,936 SARS-CoV-2 cases were included in the analyses. Of them, 5035 (46.0%) were tested for Legionella either through urinary antigen test or PCR, with 18 positive cases (0.4%). A pooled prevalence of 0.288% (95% Confidence Interval (95% CI) 0.129–0.641), was eventually calculated. Moreover, detailed data on 19 co-infections LD + SARS-CoV-2 were obtained (males: 84.2%; mean age: 61.9 years, range 35 to 83; 78.9% with 1 or more underlying comorbidities), including 16 (84.2%) admissions to the ICU, with a Case Fatality Ratio of 26.3%. In summary, our analyses suggest that the occurrence of SARS-CoV-2–Legionella infections may represent a relatively rare but not irrelevant event, and incident cases are characterized by a dismal prognosis.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2–Legionella Co-Infections: A Systematic Review and Meta-Analysis (2020–2021)

et al. 2022

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“…These findings lead to some important considerations: first, it is mandatory to perform urinary antigen test for Legionella at the time of hospital admission in all cases of severe CAP; this is a recommendation already contained in the current guidelines for CAP [ 12 ]. Second, if the test is not available at the time of CAP diagnosis, initial antimicrobial therapy should include a drug with in vitro activity against Legionella (azithromycin, clarithromycin, or levofloxacin); to this end, a recent systematic review found no difference in the effectiveness of fluoroquinolones vs. macrolides in reducing mortality among patients with LP [ 13 ], although very few data compared the two classes of antibiotics in some settings such as immunosuppressed patients, severe patients needing ICU admission and patients with nosocomial legionellosis [ 14 ]. Finally, a positive or negative urinary antigen test prompts withdrawal or continuation of antibiotic treatment directed at Legionella pathogen.…”

Section: Discussionmentioning

confidence: 99%

Predictors of intensive care unit admission in patients with Legionella pneumonia: role of the time to appropriate antibiotic therapy

et al. 2020

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Purpose Legionella spp. pneumonia (LP) is a cause of community-acquired pneumonia (CAP) that requires early intervention. The median mortality rate varies from 4 to 11%, but it is higher in patients admitted to intensive care unit (ICU). The objective of this study is to identify predictors of ICU admission in patients with LP. Methods A single-center, retrospective, observational study conducted in an academic tertiary-care hospital in Pisa, Italy. Adult patients with LP consecutively admitted to study center from October 2012 to October 2019. Results During the study period, 116 cases of LP were observed. The rate of ICU admission was 20.7% and the overall 30-day mortality rate was 12.1%. Mortality was 4.3% in patients hospitalized in medical wards versus 41.7% in patients transferred to ICU (p < 0.001). The majority of patients (74.1%) received levofloxacin as definitive therapy, followed by macrolides (16.4%), and combination of levofloxacin plus a macrolide (9.5%). In the multivariate analysis, diabetes (OR 8.28, CI 95% 2.11–35.52, p = 0.002), bilateral pneumonia (OR 10.1, CI 95% 2.74–37.27, p = 0.001), and cardiovascular events (OR 10.91, CI 95% 2.83–42.01, p = 0.001), were independently associated with ICU admission, while the receipt of macrolides/levofloxacin therapy within 24 h from admission was protective (OR 0.20, CI 95% 0.05–0.73, p = 0.01). Patients who received a late anti-Legionella antibiotic (> 24 h from admission) underwent urinary antigen test later compared to those who received early active antibiotic therapy (2 [2–4] vs. 1 [1–2] days, p < 0.001). Conclusions Admission to ICU carries significantly increased mortality in patients with diagnosis of LP. Initial therapy with an antibiotic active against Legionella (levofloxacin or macrolides) reduces the probability to be transferred to ICU and should be provided in all cases until Legionella etiology is excluded.

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“…In this regard, a recent systematic review and meta-analysis compared the effectiveness of fluoroquinolone versus macrolide monotherapy in Legionella pneumonia [ 81 ]. A total of 3525 patients from 21 publications were included in this meta-analysis.…”

Section: Antimicrobial Treatmentmentioning

confidence: 99%

“…The results of these systematic reviews and meta-analyses support the present guidelines regarding the use of a fluoroquinolone or a macrolide for the treatment of Legionella pneumonia. However, certain limitations of the current data should be recognized [ 81 – 83 ]. First, the usefulness of these antibiotics has not been extensively evaluated in some subgroups of patients, such as immunocompromised patients or those requiring admission to the ICU.…”

Section: Antimicrobial Treatmentmentioning

confidence: 99%

Legionnaires’ Disease: Update on Diagnosis and Treatment

et al. 2022

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Legionellosis is the infection caused by bacteria of the genus Legionella , including a non-pneumonic influenza-like syndrome, and Legionnaires’ disease is a more serious illness characterized by pneumonia. Legionellosis is becoming increasingly important as a public health problem throughout the world; although it is an underreported disease, studies have consistently documented a high incidence. In addition, health costs associated with the disease are high. Diagnosis of Legionnaires’ disease is based mainly on the detection of Legionella pneumophila serogroup 1 antigen in urine. However, there have been advances in detection tests for patients with legionellosis. New methodologies show greater sensitivity and specificity, detect more species and serogroups of Legionella spp., and have the potential for use in epidemiological studies. Testing for Legionella spp. is recommended at hospital admission for severe community-acquired pneumonia, and antibiotics directed against Legionella spp. should be included early as empirical therapy. Inadequate or delayed antibiotic treatment in Legionella pneumonia has been associated with a worse prognosis. Either a fluoroquinolone (levofloxacin or moxifloxacin) or a macrolide (azithromycin preferred) is the recommended first-line therapy for Legionnaires’ disease; however, little information is available regarding adverse events or complications, or about the duration of antibiotic therapy and its association with clinical outcomes. Most published studies evaluating antibiotic treatment for Legionnaires’ disease are observational and consequently susceptible to bias and confounding. Well-designed studies are needed to assess the usefulness of diagnostic tests regarding clinical outcomes, as well as randomized trials comparing fluoroquinolones and macrolides or combination therapy that evaluate outcomes and adverse events.

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Are Fluoroquinolones or Macrolides Better for Treating Legionella Pneumonia? A Systematic Review and Meta-analysis

Cited by 33 publications

References 38 publications

SARS-CoV-2–Legionella Co-Infections: A Systematic Review and Meta-Analysis (2020–2021)

SARS-CoV-2–Legionella Co-Infections: A Systematic Review and Meta-Analysis (2020–2021)

Predictors of intensive care unit admission in patients with Legionella pneumonia: role of the time to appropriate antibiotic therapy

Legionnaires’ Disease: Update on Diagnosis and Treatment

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