The safety of short-course compared to long-course antibiotic therapy for ventilator-associated pneumonia

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Mar 7 2023

In a recent study published in The Lancet’s eClinical Medicine, researchers performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the safety of short-course antibiotic treatment (≤8.0 days) versus long-course antibiotic treatment (≥10.0 to 15.0 days) for ventilator-associated pneumonia (VAP), particularly late-onset VAP caused due to non-fermenting-type of gram-negative bacterial organisms (NF-GNB).

Background

VAP, frequently observed among intensive care unit (ICU)-admitted patients, is related to poor outcomes, including hospitalizations and death. Despite VAP treatment guidelines, the optimum treatment duration is unclear, particularly for NF-GNB-caused VAP. Among non-NF-GNB VAP patients, previous studies have reported that short antibiotic courses did not elevate mortality or recurrence risks while reducing resistant bacteria emergence. 

However, the findings were of a subgroup analysis that included all hospital-acquired pneumonia subtypes, only two RCTs on NF-GNB-caused VAP patients, and only the abstract was available for one RCT. On the contrary, other studies have reported increased chances of recurrence following short-course antibiotic treatment for NF-GNB-caused VAP.

About the study

In the present study, researchers evaluated VAP recurrence and relapse rates among patients receiving short-course and long-course antibiotic therapy.

Data were searched without any language restrictions for RCTs in Embase, Cochrane Database of Systematic Reviews (CDSR), United States (US) national library of medicine, National Institute of Health MEDLINE/PubMed, web of science, Google Scholar, and Cochrane central register of controlled trials (CENTRAL) databases, published between 2000 and 1 September 2022.

In addition, reference lists of included studies were checked for identifying additional RCTs, and several registries of clinical trials, including the Australian New Zealand clinical trial registry, currently controlled trial registry, and Prospero registration and university hospital medical data network clinical trials registry, were searched for ongoing RCTs.

The prime study endpoint was VAP recurrence and relapse, and secondary study endpoints included 28.0-day deaths, duration of mechanical ventilator support, extra-pulmonary infections, and the duration of intensive care unit stay. Random effects modeling was performed, and the odds ratios (ORs) were calculated. The team included randomized controlled trials that compared short-course vs. long-course of antibiotic treatment for VAP among adults from records of peer-reviewed scientific journals. Data from non-comparative analyses, reviews, abstracts, editorial letters, case series of <10 cases, and comments were not analyzed.

The included records were assessed using the consolidated standards of reporting trials (CONSORT) guidelines, and RCTs with scores below 14 were eliminated. Bias risks in the included studies were assessed using the Cochrane risk of a bias assessment tool. Two researchers performed data screening independently, and another researcher resolved disagreements. The quality of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) tool.

Data extracted included first author names, age, publication country, publication year, sequential organ failure assessment (SOFA) scores, simplified acute physiology scores (SAPS II), VAP definitions, study population, duration and type of antibiotic treatment, VAP onset, and CONSORT scores. Subgroup analyses were limited to late-onset VAP patients and NF-GNB-caused VAP patients.

Results

A total of 307 records were identified, from which duplicate records were eliminated. Following title and abstract screening, five records were considered for the final analysis, comprising 1,069 patients, among which 530 and 539 were treated with short-course and long-course antibiotic therapy, respectively.

No significant differences were observed between short-course and long-course antibiotic treatment for ventilator-associated pneumonia recurrence and relapse, with OR values of 1.48 and 1.45, respectively, including NF-GNB-caused cases (OR values of 1.9 and 1.8, respectively). The 28.0-day mortality rates (OR 1.2), duration of mechanical ventilator support, extra-pulmonary infection counts, and the duration of intensive care unit admission did not significantly differ between the two groups.

However, short-course treatment was associated with a significantly higher number of no-antibiotic days. The most commonly prescribed antibiotics were broad-spectrum β-lactam antibiotics in combination with fluoroquinolones or aminoglycosides. The subgroup analyses of NF-GNB-caused and late-onset VAP showed no statistically significant differences between the two antibiotic treatment groups, with OR values of 1.3 and 1.3, respectively.

Further, two RCTs evaluating the acquisition of multi-drug resistant (MDR) pathogenic organisms following antibiotic treatment for VAP found comparable proportions of MDR pathogenic organism acquisition during the duration of ICU admission (OR 0.7).

Conclusion

Overall, the study findings showed that short-course antibiotic treatment for VAP did not significantly impact VAP recurrence, relapse, or associated mortality, compared to long-course antibiotic treatment. For NF-GNB-caused VAP, even though greater recurrence risks were documented, the findings did not translate clinically to ICU stay duration and death. Additionally, short-course treatment had several beneficial consequences, including lesser antibiotic exposure, lower antibiotic resistance, and lesser overall cost of treatment.