Our purpose was to compare conventional meta-analysis and network meta-analysis to evaluate the efficacy of different prophylactic systemic antibiotic classes in patients undergoing chemotherapy or haematopoietic stem cell transplant (HSCT). We included randomised trials if patients had cancer or were HSCT recipients and the intervention was systemic antibacterial prophylaxis. Three types of control groups were used: (1) placebo, no antibiotic and non-absorbable antibiotic separately; (2) placebo and no antibiotic combined; and (3) all three combined. These gave different network geometries. Strategies synthesised were fluoroquinolone, trimethoprim-sulfamethoxazole, cephalosporin and parenteral glycopeptide versus control groups. In total 113 trials met the eligibility criteria. Where treatment effects could be estimated with both conventional and network meta-analysis, values were generally similar. However, where events were sparse, network meta-analysis could be more precise. For example, trimethoprim-sulfamethoxazole versus placebo for infection-related mortality showed a relative risk ratio (RR) of 0.55, 95% CI (0.21 to 1.44) with conventional, and RR 0.43, 95% credible region (0.20 to 0.82) with network meta-analysis. Cephalosporin versus fluoroquinolone was comparable only indirectly using the network approach and yielded RR 0.59, 95% credible region (0.28 to 1.20) to reduce bacteraemia. Incoherence (difference between direct and indirect estimates raising concerns about network meta-analysis validity) was observed with network geometry where control groups were separated, but not where control groups were combined. In this situation, conventional and network meta-analysis yielded similar results in general. Network meta-analysis results could be more precise when events were rare. Some analysis could only be performed with the network approach. These results identify scenarios in which network meta-analysis may be advantageous.
- infectious diseases
- statistics & research methods
- infection control
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JPDM and PDR are joint first authors.
GT and LS are joint senior authors.
Contributors JPDM, PDR, GT and LS conceptualised the study, designed the study, analysed the network meta-analysis and wrote the manuscript. GE and PDR collected the data and conducted the conventional meta-analysis. All authors critically revised the manuscript for important content. All authors approve the final version of the manuscript.
Funding This meta-analysis was funded by the Pediatric Oncology Group of Ontario (POGO). It was editorially independent from the funder. LS is supported by a Canada Research Chair in Pediatric Oncology Supportive Care.
Competing interests BF’s institution receives research funding from Pfizer and Merck, and he serves on a Data Safety Monitoring Board for Astellas. TL has received research grants from Gilead Sciences, is a consultant to Astellas, Basilea, Gilead Sciences and Merck/MSD, and served at the speaker's bureau of Astellas, Gilead Sciences, Merck/MSD and Pfizer.
Provenance and peer review Not commissioned; externally peer reviewed.