Rapid versus standard antimicrobial susceptibility testing to guide treatment of bloodstream infection

Background Rapid antimicrobial susceptibility tests are expected to reduce the time to clinically important results of a blood culture. This might enable clinicians to better target therapy to a person's needs, and thereby, improve health outcomes (mortality, length of hospital stay), and reduce unnecessary prescribing of broad-spectrum antibiotics; thereby reducing antimicrobial resistance rates. Objectives To assess the eIects of rapid susceptibility testing versus standard susceptibility testing for bloodstream infections (BSIs). Search methods To identify studies with selected outcomes, we searched the Cochrane Infectious Diseases Group Specialised Register, CENTRAL, MEDLINE, LILACS, and two trials registries, between 1987 and October 2020. We used 'bloodstream infection' and 'antimicrobial susceptibility tests' as search terms. We had no language or publication status limitations. Selection criteria Randomized controlled trials (RCTs) comparing rapid antimicrobial susceptibility testing (with a time-to-result of L 8 hours) versus conventional antimicrobial susceptibility testing in people with a BSI caused by any bacteria, as identified by a positive blood culture. Data collection and analysis Two review authors independently screened references, full-text reports of potentially relevant studies, extracted data from the studies, and assessed risk of bias. Any disagreement was discussed and resolved with a third review author. For mortality, a dichotomous outcome, we extracted the number of events in each arm, and presented a risk ratio (RR) with 95% confidence interval (CI) to compare rapid susceptibility testing to conventional methods. We used Review Manager 5.4 to meta-analyse the data. For other outcomes, which are time-to-event outcomes (time-to-discharge from hospital, time-to-first appropriate antibiotic change), we conducted qualitative narrative synthesis, due to heterogeneity of outcome measures. Main results We included six trials, with 1638 participants. For rapid antimicrobial susceptibility testing compared to conventional methods, there was little or no diIerence in mortality between groups (RR 1.10, 95% CI 0.82 to 1.46; 6 RCTs, 1638 participants; low-certainty evidence). In subgroup analysis, for rapid genotypic or molecular antimicrobial susceptibility testing compared to conventional methods, there was little or no diIerence in mortality between groups (RR 1.02, 95% CI 0.69 to 1.49; 4 RCTs, 1074 participants; low-certainty evidence). For phenotypic rapid susceptibility testing compared to conventional methods, there was little or no diIerence in mortality between groups (RR 1.37, 95% CI 0.80 to 2.35; 2 RCTs, 564 participants; low-certainty evidence). In qualitative analysis, rapid susceptibility testing may make little or no diIerence in time-to-discharge (4 RCTs, 1165 participants; lowcertainty evidence). In qualitative analysis, rapid genotypic susceptibility testing compared to conventional testing may make little or no diIerence in time-to-appropriate antibiotic (3 RCTs, 929 participants; low-certainty evidence). In subgroup analysis, rapid phenotypic susceptibility testing compared to conventional testing may improve time-to-appropriate antibiotic (RR -17.29, CI -45.05 to 10.47; 2 RCTs, 564 participants; low-certainty evidence). Authors' conclusions The theoretical benefits of rapid susceptibility testing have not been demonstrated to directly improve mortality, time-to-discharge, or time-to-appropriate antibiotic in these randomized studies. Future large prospective studies should be designed to focus on the most clinically meaningful outcomes, and aim to optimize blood culture pathways.