Serum bactericidal titres for monitoring antimicrobial therapy: current status and potential role in the management of multidrug-resistant gram-negative infections

Abstract Background Serum bactericidal titres (SBTs) were widely used in the 1970s and 1980s to monitor antimicrobial therapy but are now seldom recommended. It is the only laboratory test that integrates drug pharmacodynamics, host pharmacokinetics, and synergistic or antagonistic interactions of antimicrobial combinations into a single index of antimicrobial activity. We hypothesized that SBTs could play a renewed role in monitoring antibiotic treatment of MDR gram-negative infections. However, the last critical appraisal of the test was published over 30 years ago. Objectives This narrative review provides an updated assessment of the SBT test and its methodological limitations. We performed a diagnostic meta-analysis to estimate the value of SBTs for predicting clinical failure or death during antibiotic treatment. Sources A comprehensive literature search of PubMed including all English publications was performed in December 2019 using the Medical Subject Headings (MeSH search terms “serum”, “bactericidal”, “inhibitory”, “titre”, “monitoring”, “anti-infective agents” “antimicrobial therapy” and “therapeutic drug monitoring.”) Content Although standardised methods for performing SBTs were approved in 1999, the test remains labour-intensive, and results may not be available until 72 hours. However, the use of non-culture-based endpoints (i.e. spectrophotometric or fluorescent) may shorten test time to 24 hours. Despite considerable heterogeneity in published studies, a meta-analysis of 11 evaluable studies published from 1974-2007 indicated a critical SBT result (peak SBT ≤ 1:8 or trough ≤1:2) is associated with a diagnostic odds ratio (DOR) for clinical failure during antibiotic treatment of 12.27 (95% CI 5.28-28.54) and a 5.32 (95% 1.32-21.42) odds of death. Implications SBTs have prognostic value for identifying patients at high risk for antibiotic treatment failure, but the slow turnaround time of the current test limits its clinical utility. Standardisation of a more rapid SBT testing method is needed.