Study investigates optimal antibiotics for non-ventilator-associated hospital-acquired pneumonia

Non-ventilator-associated hospital-acquired pneumonia (HAP) is a pervasive threat within healthcare settings. The urgency to provide treatment lies not only in its prevalence as the most common healthcare-associated infection but also in the critical challenge of selecting effective antibiotics. This is why researchers from McMaster University’s Department of Health Research Methods, Evidence, and Impact (HEI) have published findings that investigate the optimal antibiotics for HAP. Maryam Ghadimi, a Health Research Methodology PhD candidate, led this work under the supervision of HEI faculty members Gordon Guyatt, Reed Siemieniuk, Mark Loeb, Behnam Sadeghirad, and Romina Brignardello-Petersen.

Understanding hospital-acquired pneumonia

HAP is defined as occurring at least 48 hours after hospital admission. Microbiological results do not become available until 24 to 72 hours after diagnosis. Even then, these lab test results are often inconclusive and initial treatment of HAP through antibiotic therapy is based on educated guesses about the most common infecting organisms. This is called empiric antibiotic therapy: treatment given based on clinical experience and practice guidelines rather than test results. Inadequate empiric antibiotic therapy for HAP is associated with increased mortality and use of healthcare resources such as longer hospitalization due to ineffective initial treatment.

Addressing current limitations

Current guideline recommendations for HAP antibiotic therapy vary and don’t prioritize one treatment option over others. This is due to limited direct comparisons between different empiric antibiotics for HAP. To address current limitations, the research team conducted the first network meta-analysis to present the comparative effectiveness and safety of all alternative regimens in empiric therapy of HAP.

A network meta-analysis is a technique for comparing multiple treatment options simultaneously in a single analysis to see which treatments work best. This combines both direct and indirect evidence across a network of studies, allowing estimation of relative effects of interventions even if they haven’t been directly compared head-to-head in trials.

The research team used data from 39 randomized controlled trials (RCTs) with 5,392 participants. Pairs of reviewers independently extracted information from each eligible RCT, including trial and patient characteristics, and outcomes of interest. Discrepancies were resolved through discussion or adjudication by a third reviewer.

“We used standardized criteria to assess the risk of bias and assessed the certainty of the evidence and interpreted results using the GRADE methodology including a modification that allowed worthwhile inferences despite limitations in the evidence,” said Guyatt, HEI professor and principal investigator of the study.

The best defense

The research team concluded from eligible trials that piperacillin-tazobactam, a combination antibiotic that includes piperacillin (effective against a wide range of bacteria) and tazobactam (which helps piperacillin work better against resistant bacteria), appears to be one of the most effective antibiotics for preventing treatment failure in adults with HAP. This conclusion was drawn particularly in comparison to certain cephalosporins (another type of antibiotic that interferes with bacterial cell wall formation) and fluoroquinolones (antibiotics that target bacterial DNA to stop their growth). The study also found that adding an antibiotic active against methicillin-resistant Staphylococcus aureus (a type of bacteria referred to as MRSA) to the empirical regimen for all patients does not suggest additional benefit in reducing mortality.

Data on hospital stay length and adverse events were limited, and no specific analysis was conducted for these outcomes. Additionally, the study did not find sufficient evidence to explore how the severity of pneumonia, or the presence of specific bacteria influenced treatment outcomes.

“Whether a broader empiric antibiotic coverage improves outcomes among HAP patients with risk factors for resistant infection remains uncertain” said Ghadimi, corresponding author of the study.

The available RCTs on empiric therapy of HAP are relatively old with serious concerns in methodological quality and fail to evaluate all patient-important outcomes and lack data on factors that may modify the effects of antibiotic treatment.

“Our findings highlight the need for robust RCTs on empiric antibiotics for HAP,” emphasized Siemieniuk, HEI assistant professor.

This is essential for advancing our understanding and improving treatment strategies, as well as limiting the unnecessary use of broad-spectrum antibiotics, which is associated with the emergence of resistant bacteria.

Access the study to learn more.

Ghadimi, M., Siemieniuk, R. A. C., Guyatt, G., Loeb, M., Hazzan, A. A., Aminaei, D., Gomaa, H., Wang, Y., Yao, L., Agarwal, A., Basmaji, J., Grant, A., Kim, W. S. H., Alvarado-Gamarra, G., Likhvantsev, V., Lima, J. P., Motaghi, S., Couban, R., Sadeghirad, B., & Brignardello-Petersen, R. (2024). Empiric antibiotic regimens in adults with non-ventilator-associated hospital-acquired pneumonia: a systematic review and network meta-analysis of randomized controlled trials. Clinical Microbiology and Infection. https://doi.org/10.1016/j.cmi.2024.05.017