Evaluation of early antimicrobial therapy adaptation guided by the BetaLACTA® test: a case-control study

Abstract

Background: Rapid diagnostic tests detecting microbial resistance are needed for limiting the duration of inappropriateness of empirical antimicrobial therapy (EAT) in intensive care unit patients, besides reducing the use of broad-spectrum antibiotics. We hypothesized that the betaLACTA® test (BLT) could lead to early increase in the adequacy of antimicrobial therapy.

Methods: This was a case-control study. Sixty-one patients with BLT-guided adaptation of EAT were prospectively included, and then matched with 61 "controls" having similar infection characteristics (community or hospital-acquired, and source of infection), in whom EAT was conventionally adapted to antibiogram results. Endpoints were to compare the proportion of appropriate (primary endpoint) and optimal (secondary endpoint) antimicrobial therapies with each of the two strategies, once microbiological sample culture results were available.

Results: Characteristics of patients, infections and EAT at inclusion were similar between groups. Nine early escalations of EAT occurred in the BLT-guided adaptation group, reaching 98% appropriateness vs. 77% in the conventional adaptation group (p < 0.01). The BLT reduced the time until escalation of an inappropriate EAT from 50.5 (48-73) to 27 (24-28) hours (p < 0.01). Seventeen early de-escalations occurred in the BLT-guided adaptation group, compared to one in the conventional adaptation group, reducing patients' exposure to broad-spectrum beta-lactam such as carbapenems. In multivariate analysis, use of the BLT was strongly associated with early appropriate (OR = 18 (3.4-333.8), p = 0.006) and optimal (OR = 35.5 (9.6-231.9), p < 0.001) antimicrobial therapies. Safety parameters were similar between groups.

Conclusions: Our study suggests that a BLT-guided adaptation strategy may allow early beta-lactam adaptation from the first 24 hours following the beginning of sepsis management.

Keywords: Antimicrobial agent administration; Beta-lactam resistance; Extended-spectrum beta-lactamase; Intensive care unit; Microbial susceptibility tests.

Fig. 1

Empirical antimicrobial therapy adaptation in the case of a negative (upper panel) or positive (lower panel) betaLACTA® test (BLT). Whatever the beta-lactam empirically administered to patients, cefotaxime was chosen to pursue antimicrobial therapy once the BLT results were negative. Conversely, carbapenems were chosen if the BLT was positive. The definitive antimicrobial therapy was prescribed after the results of antibiotic susceptibility tests, confirming the BLT-adapted beta-lactam antibiotic or using another molecule if necessary. Amox. amoxicillin, Clav. clavulanate, Pip. piperacillin, Taz. tazobactam

Fig. 2

Flow chart of the study. During the betaLACTA test (BLT)-guided adaptation period, 622 patients receiving empirical antimicrobial therapy (EAT) were screened, among whom 61 cases were finally included. The comparative conventional adaptation group included 61 controls matched both on the site and the community-acquired or healthcare-associated status of the infection among the 671 patients having received EAT during the last 24 months before the introduction of the BLT in our institution

Fig. 3

Empirical antimicrobial therapy adaptations in the conventional and BetaLACTA® test (BLT)-guided groups. In the conventional adaptation group, only one early de-escalation occurred once the results of the culture of the microbiological sample were available. The other 32 modifications occurred after the results of the antibiotic susceptibility tests, in particular 14 escalations for which patients received an inappropriate beta-lactam antibiotic. Conversely, in the BLT-guided adaptation group, 9 early escalations and 17 early de-escalations occurred once the results of the culture of the microbiological samples were available, among which no false positives and one false negative occurred. Amox. amoxicillin, Clav. clavulanate, Pip. piperacillin, Taz. Tazobactam, ESBL Extended-spectrum beta-lactamases, ^3rd GC and ^4th GC, 3^rd and 4^th generation cephalosporins