Association of Repeated Blood Cultures With Mortality in Adult Patients With Gram-Negative Bacilli Bacteremia: A Systematic Review and Meta-analysis

Abstract

Background Performing repeated blood cultures after initial positive culture (i.e., follow-up blood cultures [FUBCs]) in patients with gram-negative bacilli (GNB) bacteremia is controversial. We aimed to comprehensively review the association of FUBCs with improvement in patient-relevant clinical outcomes in GNB bacteremia. Methods We performed systematic review and random-effects meta-analysis to calculate summary effect estimates. We used hazard ratios as the effect measure. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were lengths of treatment and hospital stay. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (Central) without language restrictions from inception to April 29, 2022. Original clinical studies evaluating the association between FUBCs and mortality in adult patients with GNB bacteremia were included. FUBC details were reviewed. Two independent reviewers used the Risk of Bias in Non-randomised Studies of Interventions tool. Results We identified nine eligible retrospective studies. In total, 7,778 hospitalized patients with GNB bacteremia were included. The studies were clinically heterogeneous and had a critical risk of bias. The utilization of FUBCs varied across studies (18%–89%). Random-effects meta-analysis of covariate-adjusted estimates found that FUBC use was associated with reduced mortality. Although not a result of the meta-analysis, lengths of treatment and hospital stay were longer for patients with FUBCs than for those without. Adverse events were not reported. Conclusions FUBC acquisitions was associated with lower mortality and longer hospital stay and treatment duration in GNB bacteremia. The risk of bias was critical, and no firm data were available to support mechanisms.

The effect of follow-up blood cultures on mortality and antibiotic use in gram-negative bloodstream infections

“…In two recently published meta-analyses, FUBC was associated with a lower risk of mortality. Low mortality risk may be associated with early detection of complications, early source control, and early initiation of appropriate antibiotic therapy in FUBC groups [ 16 , 17 ]. However, in studies with low mortality risk in FUBC groups, the rates of FUBC (17–68%) were lower than in studies that did not affect mortality (67–89%) [ 3 – 13 ].…”

“…In previous studies, antibiotic treatment duration is 2–5 days longer in FUBC groups because of waiting for FUBC results or starting new antibiotics according to the result [ 16 ]. However, the comparison of treatment durations in studies is based on the first effective antibiotic, and the effect of sequential treatments is often ignored [ 4 – 6 , 13 , 15 ].…”

“…Early detection of persistent and breakthrough infections with routine FUBC in GN-BSIs can reduce mortality through appropriate antimicrobial therapy and early source control. However, this hypothesis has still not been confirmed due to the high risk of bias in published publications [ 16 , 17 ]. Early mortality before FUBC leads to the misleading association of FUBC with low mortality in these articles.…”

“…Articles report controversial results for the relationship between mortality and FUBC. However, the common result of many studies is that FUBC prolongs antibiotic exposure [ 16 ]. This comparison includes only primary effective antibiotic treatments.…”