Empiric antibiotic regimens in adults with non-ventilator-associated hospital-acquired pneumonia: a systematic review and network meta-analysis of randomized controlled trials.

Liang Yao, Shahrzad Motaghi, William S H Kim, Alexandre Grant, Danial Aminaei, Afeez Abiola Hazzan, Ying Wang, Behnam Sadeghirad, Maryam Ghadimi, Gordon Guyatt, João Pedro Lima, Reed A C Siemieniuk, John Basmaji, Rachel Couban, Arnav Agarwal, Valery Likhvantsev, Mark Loeb, Romina Brignardello-Petersen, Huda Gomaa, Giancarlo Alvarado-Gamarra

Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2024;30(11):1351-1363

PMID: 38823453

Free Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

The optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain.

OBJECTIVES

To compare the effectiveness and safety of alternative empiric antibiotic regimens in HAP using a network meta-analysis.

DATA SOURCES

Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from database inception to July 06, 2023.

STUDY ELIGIBILITY CRITERIA

RCTs.

PARTICIPANTS

Adults with clinical suspicion of HAP.

INTERVENTIONS

Any empiric antibiotic regimen vs. another, placebo, or no treatment.

ASSESSMENT OF RISK OF BIAS

Paired reviewers independently assessed risk of bias using a modified Cochrane tool for assessing risk of bias in randomized trials.

METHODS OF DATA SYNTHESIS

Paired reviewers independently extracted data on trial and patient characteristics, antibiotic regimens, and outcomes of interest. We conducted frequentist random-effects network meta-analyses for treatment failure and all-cause mortality and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.

RESULTS

Thirty-nine RCTs proved eligible. Thirty RCTs involving 4807 participants found low certainty evidence that piperacillin-tazobactam (RR compared to all cephalosporins: 0.65; 95% CI: 0.42, 1.01) and carbapenems (RR compared to all cephalosporins: 0.77; 95% CI: 0.53, 1.11) might be among the most effective in reducing treatment failure. The findings were robust to the secondary analysis comparing piperacillin-tazobactam vs. antipseudomonal cephalosporins or antipseudomonal carbapenems vs. antipseudomonal cephalosporins. Eleven RCTs involving 2531 participants found low certainty evidence that ceftazidime and linezolid combination may not be convincingly different from cephalosporin alone in reducing all-cause mortality. Evidence on other antibiotic regimens is very uncertain. Data on other patient-important outcomes including adverse events was sparse, and we did not perform network or pairwise meta-analysis.

CONCLUSIONS

For empiric antibiotic therapy of adults with HAP, piperacillin-tazobactam might be among the most effective in reducing treatment failure. Empiric methicillin-resistant Staphylococcus aureus coverage may not exert additional benefit in reducing mortality.

REGISTRATION

PROSPERO (CRD 42022297224).

Address: Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada. Electronic address: [email protected].; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada; MAGIC Evidence Ecosystem Foundation, Oslo, Norway.; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.; Department of Healthcare Studies, State University of New York, Brockport, NY, USA.; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.; Department of Biostatistics, High Institute of Public Health, Alexandria University, Egypt.; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada.; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Division of Critical Care, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.; Faculty of Medicine and Dentistry, University of Alberta, Alberta, Canada.; Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Pediatrics, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru; Instituto de Investigación Nutricional, Lima, Peru.; Deputy Director, V. Negovsky Reanimatology Research Institute FNCC RR, Moscow, Russia; Anesthesiology and Intensive Care Department, First Moscow State Medical University (Sechenov University), Moscow, Russia.; Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada.

DOI: 10.1016/j.cmi.2024.05.017

Link outs

Free resources

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S1198...

Medical:

https://medlineplus.gov/antibiotics.html

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-BRIP1-5

MeSH Terms: Adult, Humans, Anti-Bacterial Agents, Healthcare-Associated Pneumonia, Piperacillin, Tazobactam Drug Combination, Randomized Controlled Trials as Topic, Treatment Outcome