The Role of AdeABC, AdeFGH and AdeIJK Efflux Pumps in Reduced Susceptibility to Tigecycline: Emergence of an Outbreak Associated With an International Clone Variant of Acinetobacter Baumannii Isolated From Burn Patients in Iran
Tigecycline is a new therapeutic agent for treating multiple drug-resistant (MDR) Acinetobacter baumannii infections. However, recent reports have suggested the efficacy of tigecycline in fighting A. baumannii infections has been reduced. In this study we investigated the role of resistance-nodulation cell division (RND) efflux pumps in reducing the efficacy of tigecycline against clinical isolates of A. baumannii collected from hospitalized burn patients in Iran. The susceptibility of 100
... tes to 19 antimicrobial agents was determined using the disc diffusion method, with the exception of colistin and tigecycline, which were assessed using the Etest method. PCR was used to detect the prevalence of genes. Real-time PCR was used to analyze the expression levels of genes encoding RND efflux pumps. Additionally, a three loci dual assay and multiple loci variable number tandem repeat analysis (MLVA) were used to define PCR-based groups (G) and epidemiological studies of isolates, respectively. Colistin (99%), followed by tigecycline (71%) could be effective therapeutic options against A. baumannii. Forty-three percent of all isolates belonged to G variants. The high antibiotic resistance rate and over expression of RND efflux pumps were observed in G variants. MLVA identified 44 distinct types with 11 clusters and 29 singleton genotypes. The mean expression levels of AdeB in 29 tigecycline non-susceptible A. baumannii (TNAB) counterpart 71 tigecycline susceptible A. baumannii (TSAB) increased approximately 7- fold. All TNAB and TSAB isolates were shown to express adeG at higher level than adeB and adeJ, exceptionally TNAB isolates expressed adeB at a greater level than others. Four fold or greater decrease in tigecycline MIC was observed in 20% and 79% of TSAB and TNAB isolates, respectively. We observed an increasing trend in the rate of TNAB isolates and G variants in burn patients. The mechanism of their resistance was mediated by an increase in the expression of AdeABC efflux pump; AdeFGH and AdeIJK were not observed to have a direct role in tigecycline resistance. Also, this is the first study to report on the tendency of increase to spread of TNAB G variants, as the sub-clone of G1, in Iranian burn center.