Antibiotic treatment of severe bacterial pneumonia: a scoping review to characterise the evidence for current treatment options

<ns3:p> Background The FAIR project is evaluating flagellin aerosol therapy (FLAMOD) as an adjunct to enhance the effectiveness of antibiotic therapy in antimicrobial-resistant (AMR) pneumonia. Our scoping review characterises the existing evidence for the antibiotic treatment of patients with severe bacterial pneumonia (SBP) to inform future health economic modelling of FLAMOD versus standard-of-care. Methods A systematic search identified relevant publications (January 2001 to July 2021) in MEDLINE, Embase, Cochrane Library, and other sources. Clinical trials and cohort studies of antibiotic treatments in hospitalised patients with SBP reporting clinical efficacy, mortality, or length of hospital stay were eligible. Two reviewers independently applied the review methods. The study data were extracted into a bespoke Microsoft Access database. Results Over half of the 327 included studies were retrospective cohort studies and the remainder were RCTs (20%) or prospective cohort studies (23%). Community-acquired pneumonia (CAP) was the most common type of pneumonia (39%). Among 144 studies that treated specific bacteria, gram-negative pathogens (22.2%), <ns3:italic>Acinetobacter baumannii</ns3:italic> (20.1%), and <ns3:italic>Pseudomonas aeruginosa</ns3:italic> (19.4%) were the most common. In 236 studies reporting treatment with specific antibiotics, 44% used an antibiotic from the WHO reserve list of antibiotics and a third mapped to a single drug class (commonly polymyxins, 20 studies). Mortality was the most frequently reported outcome (27.9% of studies on severe CAP). Conclusion We characterised evidence for antibiotic treatment in patients with SBP. Our database provides us with the flexibility to identify evidence for a future economic model to assess whether FLAMOD can be a cost-effective adjunct to conventional antibiotic treatment of AMR. Evidence for the effectiveness of antibiotics in SBP is plentiful, but heterogeneous. We highlight challenges for evidence synthesis, including difficulties in identifying studies specifically on severe pneumonia, lack of clear reporting about whether treatment is empirical or definitive, and inconsistent reporting of the line of therapy and levels of antibiotic resistance. </ns3:p>