2171. Minocycline Susceptibility in Carbapenem-Resistant Acinetobacter baumannii Blood Isolates in South Korea: Role of tetB Gene in Resistance

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) represents a growing global threat with minimal therapeutic options. Minocycline (MIN), a semisynthetic tetracycline derivative, has been suggested as an attractive therapeutic option for CRAB infection. However, the optimal dosing and breakpoint for MIN in treating CRAB infection remain unclear. Furthermore, nonsusceptibility to MIN may occur through the efflux pump, in particular, TetB. As the prevalence of tetB in A. baumannii has increased, so have the MIN minimum inhibitory concentrations (MICs) for A. baumannii strains carrying tetB. Here, we evaluated the MIN susceptibility rate in CRAB clinical strains and the association between tetB carriage and MIN susceptibility. Methods Representative CRAB blood isolates were collected from a tertiary care center in South Korea. The Clinical and Laboratory Standards Institute (CLSI) MIN susceptibility breakpoint for A. baumannii was defined as MIC ≤4 mg/L, whereas a new MIN breakpoint of 1 mg/L was suggested based on pharmacokinetic (PK)/pharmacodynamic (PD) studies. For comparison of the impact of the tetB resistance, tigecycline was used. Tigecycline susceptibility breakpoint for Enterobacterales defined by EUCAST was applied (≤0.5 mg/L). TetB carriage was detected by polymerase chain reaction. Results Of 160 CRAB isolates, 134 (84%) were susceptible to MIN according to the CLSI criteria, among which 40% (53/134) were PK-PD non-susceptible. The MIN MIC 50/90 was 1/8 mg/L. Seventy-nine (49%) isolates carried tetB. One-third (26/79) of tetB-positive and none of the tetB-negative isolates were CLSI non-susceptible, while 66% of tetB-positive and 33% of tetB-negative isolates were PK-PD non-susceptible. TetB carriage was correlated with a higher MIN MIC than non-tetB carriage (MIC 50/90 2/8 mg/L vs. 1/2 mg/L) (Figure 1). However, no clear correlation was observed between tetB-positivity and tigecycline MIC (Figure 2). Overall, tetB positivity demonstrated 100% sensitivity for MIN CLSI non-susceptibility and 66% sensitivity for PK-PD non-susceptibility. tetB positivity and MICs of minocycline for carbapenem-resistant A. baumannii. The CLSI susceptibility breakpoint for minocycline is ≤4 mg/L, whereas a new MIN PK-PD breakpoint of 1 mg/L was suggested. Figure2. tetB positivity and MICs of tigecycline for carbapenem-resistant A. baumannii. The tigecycline susceptibility breakpoint for Enterobacterales defined by EUCAST was applied (≤0.5 mg/L). Conclusion In our study, 49% CRAB isolates carried tetB gene. Our findings suggest that the lack of tetB is not a reliable marker of MIN PK-PD susceptibility. Therefore, further clinical data on MIN usage is necessary. Disclosures All Authors: No reported disclosures