In vitro and in vivo Evaluation of Antibiotic Combination against Imipenem Resistant Acinetobacter baumannii Strains Isolated from Bangladeshi Patients

Abstract

Acinetobacter baumannii is becoming a common etiological agent of nosocomial infections resulting in septicemia, meningitis, endocarditis, pneumonia, wound, and urinary tract infections within the healthcare setting. There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of imipenem, ceftazidime, amikacin and their combinations against imipenem resistant A. baumannii in experimental rat models. We also detected MBL encoding genes such as blaNDM-1, blaVIM and blaIMP and ESBL encoding genes such as blaCTX-M-15 and blaOXA-1 genes by Polymerase chain reaction (PCR). MBL encoding genes such as blaNDM-1 (83.33%), blaVIM (66.67%) and blaIMP (41.67%) and ESBL encoding genes such as blaCTX-M-15 (16.67%) and blaOXA-1 (12.50%) were detected among imipenem resistant Acinetobacter baumannii by PCR. In vitro activities of imipenem, ceftazidime, amikacin, ciprofloxacin, tigecycline and their combinations were tested using agar dilution method. The proportions of synergy observed in imipenem-ceftazidime, imipenem-amikacin, imipenem-ciprofloxacin and amikacin-tigecycline combinations were 25%, 54.17%, 12.50% and 41.67% respectively in vitro. Rat septicaemic models were evaluated using the imipenem resistant A. baumannii strain. Rats were treated with three antimicrobials and their combinations. For the rat model, the efficacies of imipenem, amikacin and imipenem plus ceftazidime and imipenem plus amikacin were assayed. In the septicaemic rat model, compared to the control group, (i) imipenem alone, (ii) ceftazidime alone (iii) imipenem plus ceftazidime (iv) imipenem plus amikacin showed increased sterile blood culture (50%, 16.67%, 66.67% and 83.33%). Imipenem plus amikacin or amikacin plus tigecycline may be appropriate for the treatment against imipenem resistant Acinetobacter baumannii infections.