Acinetobacter baumannii'de kolistin direncine neden olan konak ve bakteriyel faktorler

Health-care associated infections (HAIs) have become a significant life-threatening problem over the time because of global increase in antibiotic resistant bacterial population. Acinetobacter baumannii (A.baumannii) is capable of survive in hospital environment for long time periods and cause severe infections with high mortality rates especially in intensive care units because of its multi-drug resistant (MDR) phenotype. Colistin is one of the last therapeutic options for treatment of MDR gram negative infections. Today, emergence of colistin resistance is a global concern because of the limitation of antimicrobial therapy. There are two mechanisms of colistin resistance in A.baumannii. Point mutations in pmrCAB operon induce PEtn addition on LPS which inhibits the colistin binding. Second mechanism is the prevention of colistin binding to cell wall by complete loss of LPS as a result of mutations or insertions in lpxA, lpxC, and lpxD genes. In this study, we aimed to reveal the association between the host demographic factors, clinical progression of the disease, and molecular variations of A.baumannii which may promote colistin resistance. A total of 29 colistin resistant A.baumannii isolates from 4 different hospitals located in different parts of Turkey were collected between April 2015 and June 2016. Patient's demographic data, clinical progress of the disease, and outcome were recorded. To find the genetic basis of resistance, pmrCAB complete operon, lpxA, lpxC, and lpxD genes were sequenced. The expression levels of pmrC, pmrA, and pmrB were studied to find a connection between mutations and altered expression levels. The patient's data and the results of molecular tests were analyzed by using R Studio program. In PmrA, PmrB, PmrC, and LpxD several amino acid changes were detected. The most common amino acid changes were T138A in PmrB, V42I& F150L in PmrC, and E117K in LpxD regions, and these mutations were found to be associated with the high colistin MIC values (p: 0.0022, 0.00086, 0.00086, 0.00086 respectively). According to the qRT-PCR results, 35.3-fold increase in pmrC, 12.3-fold in pmrA, and 8.2-fold in pmrB were detected. The duration of colistin therapy was found to be significantly associated with the overexpression of pmrB (p: 0.046). Having operation within one month before the isolation of colistin resistant A.baumannii is found to be significantly associated with overexpression of pmrB (p: 0.039). In conclusion, the overexpression of pmrC, pmrA, and pmrB along with the point mutations in corresponding genes and lpxD gene may trigger colistin resistance. The duration of colistin therapy and operation within last month before the isolation of colistin resistant A.baumannii are substantial factors on emergence of colistin resistance. Therefore, physicians should consider the therapeutic options during colistin therapy by controlling the duration of usage and combining colistin with other antibiotics. Surveillance cultures before the surgery should be encouraged and protective precautions should be taken to prevent the dissemination of resistance.