Minocycline Susceptibility of Carbapenem-Resistant Acinetobacter baumannii Blood Isolates from a Single Center in Korea: Role of tetB in Resistance

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) represents a devastating and growing global threat, calling for new antibiotic treatments. In Korea, the challenge of treating CRAB is compounded by high nosocomial acquisition rates and limited availability of novel antibiotics. Minocycline, a semisynthetic tetracycline derivative, has been proposed as a therapeutic option for CRAB infections. Nonsusceptibility to minocycline may occur through the efflux pump, TetB. The prevalence of tet8 in A. baumannii has increased, along with higher minocycline minimum inhibitory concentrations (MICs). We aimed to evaluate minocycline susceptibility rates in clinical strains of CRAB, and the association between tet8 carriage and minocycline susceptibility across different genotypes. Materials and Methods: Representative CRAB blood isolates were collected from Asan Medical Center, Seoul. Minocycline susceptibility was assessed using the Clinical and Laboratory Standards Institute (CLSI) breakpoint (<= 4 mg/L) and the proposed pharmacokinetics (PK)/pharmacodynamics (PD) breakpoint (<= 1 mg/L). Tigecycline was used as a comparator, and its susceptibility breakpoint for Enterobacterales defined by EUCAST was applied (<= 0.5 mg/L). The presence of tet8 was detected by PCR, and multilocus sequence typing (MLST) was performed using seven housekeeping genes. Results: Of the 160 CRAB blood isolates, 83.8% were susceptible to minocycline by the CLSI criteria, and 50.6% were PK-PD susceptible by the PK-PD criteria. The minocycline minimum inhibitory concentration (MIC)50/MIC90 was 1/8 mg/L. tet8 was present in 49% of isolates and was associated with a higher minocycline MIC (MIC50/90 2/8 mg/L vs. 1/2 mg/L). No clear correlation was observed between tet8 positivity and tigecycline MIC. Nine MLSTs were identified, with significant differences in tet8 carriage rates between the major sequence types. Notably, ST191, associated with non-tet8 carriage and greater susceptibility to minocycline, declined over the study period (P=0.004), while ST451, associated with tet8 carriage, increased. Conclusion: tet8 was present in 49% of CRAB isolates and was associated with higher MICs and non-susceptibility by both CLSI and PK-PD criteria. However, absence of tet8 was not a reliable predictor of minocycline PK-PD susceptibility. Additionally, shifts over time towards genotypes with reduced minocycline susceptibility were observed. Further research is needed to correlate these findings with clinical outcomes and identify additional resistance mechanisms.