Effect of clarithromycin in patients with suspected Gram-negative sepsis: results of a randomized controlled trial

Giamarellos‐Bourboulis, Evangelos J.; Mylona, Vassiliki; Antonopoulou, Anastasia; Tsangaris, Iraklis; Koutelidakis, Ioannis; Marioli, Androniki; Rosario, Maria; Kopterides, Petros; Lymberopoulou, Korina; Mouktaroudi, Maria; Papageorgiou, Christos; Papaziogas, B.; Georgopoulou, Antonia-Panagiota; Τσαγανός, Θωμάς; Papadomichelakis, Evangelos; Gogos, Charalambos; Ladas, Malvina; Savva, Athina; Πελεκάνου, Αιμιλία; Baziaka, Fotini; Koutoukas, Pantelis; Kanni, Theodora; Spyridaki, Aikaterini; Maniatis, Nikolaos A.; Pelekanos, Nikolaos; Kotsaki, Antigone; Vaki, Ilia; Douzinas, Emmanuel E.; Koratzanis, George; Armaganidis, Apostolos

doi:10.1093/jac/dkt475

Cited by 46 publications

(50 citation statements)

References 19 publications

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“…Similar result was obtained for two RCTs with follow-up periods of 4 days [38] and 30 days [20] respectively (RR 1.06; 95% CI 0.22-5.02). We found a moderate quality of evidence for two cohort studies and two RCTs and low quality of evidence for one case-crossover study using GRADE.…”

Section: Strokesupporting

confidence: 83%

Managing Cardiovascular Risk of Macrolides: Systematic Review and Meta-Analysis

et al. 2017

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(150-250 words, 250 words)Introduction It was postulated that antibiotics including macrolides could be used for secondary prevention of coronary heart disease but recent studies showed that macrolides increase the cardiovascular risk. We aimed to review the evidence of cardiovascular risk associated with macrolides regarding duration of effect and risk factors; and explore the potential effect of statins for the prevention of cardiovascular events due to macrolide use.Methods Several electronic databases(PubMed, EMBASE, Cochrane library) were searched to identify eligible studies. Observational studies and randomized controlled trials(RCTs) that investigated the association between macrolides and cardiovascular events in adults aged≥18 years were included. Meta-analysis was conducted to investigate the short and long-term risks of cardiovascular mortality, myocardial infarction, arrhythmia and stroke. Methodological quality was assessed by the Newcastle-Ottawa scale and the Cochrane Collaboration's tool. The body of evidence was evaluated by the Grading of Recommendations Assessment, Development, and Evaluation guidelines.Results Observational studies were found to have short-term risk of cardiovascular outcomes including cardiovascular mortality, myocardial infarction and arrhythmia associated with macrolides but no risk was found in RCTs. However no association for long-term risk (>3 years) was observed in observational studies or RCTs. LimitationsThe included studies reported different units of denominators for absolute risk and used different outcome definitions, which might increase the heterogeneity. ConclusionsMore studies are required to investigate the short-term cardiovascular outcomes associated with different types of macrolides. Future studies are warranted to evaluate the effect of statins for preventing excess acute cardiovascular events associated with clarithromycin or other macrolides. Keypoints The short-term risk of cardiovascular outcomes associated with macrolides was found in observational studies but not in randomised controlled trials. No long-term cardiovascular risk (>3 years) associated with macrolides was observed.2  There was limited evidence for the use of statins to prevent excess acute cardiovascular events associated with clarithromycin or other macrolides.

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Section: Strokesupporting

confidence: 83%

Managing Cardiovascular Risk of Macrolides: Systematic Review and Meta-Analysis

et al. 2017

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“…E. J. Giamarellos-Bourboulis has received two unrestricted educational grants (paid to the University of Athens) by Abbott SA for the conduct of studies with intravenous clarithromycin in sepsis (5,6). He has also received honoraria for providing scientific advice to the following: AbbVie, Chicago IL; Astellas, Athens, Greece; Biotest AG, Dreieich, Germany; and Thermo Fisher Scientific GmbH, Henningdorf, Germany.…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…However, it was puzzling that despite the earlier resolution of VAP, the overall all-cause mortality rates between the two groups were similar. In order to confirm the findings, another RCT was conducted by our group in a population of 600 patients with sepsis developing after clinically suspected or microbiologically proven infections of Gram-negative origin; 298 patients were allocated to placebo treatment and 302 patients to clarithromycin treatment (6). In that study, the period of treatment was extended to 4 days.…”

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confidence: 98%

Clarithromycin Leads to Long-Term Survival and Cost Benefit in Ventilator-Associated Pneumonia and Sepsis

Τσαγανός

Rosario

Pratikaki

et al. 2016

Antimicrob Agents Chemother

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cIncreasing numbers of admissions for sepsis impose a heavy burden on health care systems worldwide, while novel therapies have proven both expensive and ineffective. We explored the long-term mortality and hospitalization costs after adjunctive therapy with intravenous clarithromycin in ventilator-associated pneumonia (VAP). Two hundred patients with sepsis and VAP were enrolled in a published randomized clinical trial; 100 were allocated to blind treatment with a placebo and another 100 to clarithromycin at 1 g daily for three consecutive days. Long-term mortality was recorded. The hospitalization cost was calculated by direct quantitation of imaging tests, medical interventions, laboratory tests, nonantibiotic drugs and antibiotics, intravenous fluids, and parenteral and enteral nutrition. Quantities were priced by the respective prices defined by the Greek government in 2002. The primary endpoint was 90-day mortality; cumulative hospitalization cost was the secondary endpoint. All-cause mortality rates on day 90 were 60% in the placebo arm and 43% in the clarithromycin arm (P ‫؍‬ 0.023); 141 patients were alive on day 28, and mortality rates between days 29 and 90 were 44.4% and 17.4%, respectively (P ‫؍‬ 0.001). The mean cumulative costs on day 25 in the placebo group and in the clarithromycin group were €14,701.10 and €13,100.50 per patient staying alive, respectively (P ‫؍‬ 0.048). Respective values on day 45 were €26,249.50 and €19,303.10 per patient staying alive (P ‫؍‬ 0.011); this was associated with the savings from drugs other than antimicrobials. It is concluded that intravenous clarithromycin for three consecutive days as an adjunctive treatment in VAP and sepsis offers long-term survival benefit along with a considerable reduction in the hospitalization cost. (This study has been registered at ClinicalTrials.gov under registration no. NCT00297674.)

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“…Despite this, beneficial effects have been observed in clinical practice with their use, including earlier resolution of VAP, earlier extubation, and a reduced risk of death from sepsis and multiple organ dysfunction [29,30]. An RCT of macrolide therapy conducted in gram-negative sepsis due to extrapulmonary infection failed to meet its primary endpoint of reduced mortality [31]. However, an analysis of secondary endpoints showed a shorter duration to resolution of infection and decreased hospitalization costs without any increase in adverse events with macrolide treatment.…”

Section: 2mentioning

confidence: 99%

Update on the combination effect of macrolide antibiotics in community-acquired pneumonia

O’Brien

Restrepo

Martín‐Loeches

2015

Respiratory Investigation

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Effect of clarithromycin in patients with suspected Gram-negative sepsis: results of a randomized controlled trial

Abstract: Intravenous clarithromycin did not affect overall mortality; however, administration shortened the time to resolution of infection and decreased the hospitalization costs.

Cited by 46 publications

References 19 publications

Managing Cardiovascular Risk of Macrolides: Systematic Review and Meta-Analysis

Managing Cardiovascular Risk of Macrolides: Systematic Review and Meta-Analysis

Clarithromycin Leads to Long-Term Survival and Cost Benefit in Ventilator-Associated Pneumonia and Sepsis

Update on the combination effect of macrolide antibiotics in community-acquired pneumonia

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