COLISTIN-CARBAPENEM COMBINATION THERAPY AGAINST CARBAPENEM RESISTANT GRAM NEGATIVE BACILLI INFECTIONS: CLINICAL AND AN IN VITRO SYNERGY STUDY

Objective: Combination therapy is recommended for carbapenem resistant Gram negative bacilli (CR GNB) infections. However, limited data exists on the clinical effectiveness of antibiotic combinations. The purpose of this study was to evaluate the efficacy of colistin-carbapenem combination against CR GNB infection in a clinical study and an in vitro synergy study using Etest. Methods: A study was conducted in a tertiary care hospital to evaluate the clinical outcome of patients with CR GNB infections who were treated with colistin-carbapenemcombination between January to April, 2013. It was comprised of 33 patients with CR GNB infection. Detection of in vitro synergy was performed by Etest for colistin-meropenem combination on five isolates. These isolates were also screened for the resistant genes blaOXA-23, blaVIMand blaNDM using single target PCR. Results: 33 CR GNB included Acinetobacterspp. (19), Pseudomonas aeruginosa (7) and Enterobacteriaceae spp. (7). Overall clinical success of 60.6% was observed in patients receiving colistin-carbapenem combination therapy. In respiratory infection, the clinical success rate was only 25%, whereas in soft tissue infection it was 57.1%. In bloodstream infection 100%  clinical success was observed. All five isolates screened using PCR was carrying bla NDM gene, whereas isolate of Acinetobacter baumannii also carried blaOXA-23 and blaVIM gene. Indifferent interactions were observed between colistin and meropenem against all five isolates. Conclusion: We observed low clinical success rate for colistin-carbapenem combination therapy, probably due to indifferent interactions between colistin and meropenem against NDM producing strain. In addition, probable pharmacokinetic concern of colistin may have a role to play

CHARACTERIZATION OF CARBAPENEM RESISTANT ACINETOBACTER BAUMANNII ISOLATED IN A TERTIARY CARE HOSPITAL: EPIDEMIOLOGY AND TREATMENT OUTCOME

Objective: Carbapenem resistant Acinetobacter baumannii (CR-Ab) has emerged as a major nosocomial pathogen, but optimal treatment regimens are unknown. Our objectives were to determine the epidemiology and outcome of CR-Ab infections at a tertiary care hospital.Methods: CR-Ab isolates were collected from January to April 2013. MICs were determined and isolates were subjected to screening for carbapenemase production by Modified Hodge test (MHT), metallo-β-lactamase (MBLs) by EDTA disk synergy test and AmpC β-lactamase by AmpC disk test. 15 isolates were subjected to PCR for detection of resistant genes, blaOXA-23, blaVIM and blaNDM. Treatment outcomes of infections were evaluated.Results: 51 CR-Ab isolates from tracheal aspirate (21), blood (15); tissue/wound/drainage (13) and urine samples (2) were collected. Colistin appeared to be the most effective agent with 98% in vitro activity. MHT showed 98% positivity, MBLs production was detected in 94.1% isolates and 64.7% were positive for AmpC β-lactamase production. All 15 isolates carried blaOXA-23 and blaVIM, of these 3 also carried blaNDM gene. Colistin containing combinations were more commonly used (68.3%). Colistin-noncarbapenem combination showed improved clinical response compared to colistin-carbapenem combination against Acinetobacter isolates carrying blaOXA-23 and blaVIM.Conclusion: A stringent infection control practice along with antimicrobial stewardship is needed to prevent emergence of Acinetobacter carrying multiple carbapenemase genes along with blaNDM. Various colistin combinations are preferentially used to treat CR-Ab infections. Identification of antimicrobial combinations with proven in vitro activity that encompass local susceptibility patterns as well as molecular mechanisms of resistance is needed to provide better outcome.Keywords: Acinetobacter baumannii, Carbapenem resistance, Carbapenemases, Colistin combination, metallo-β-lactamase, NDMÂ