Drug-resistant Acinetobacter baumannii (A. baumannii) infections are a critical global problem, with limited treatment choices. This study aims to determine the in vitro activities of colistin–sitafloxacin combinations against multidrug-, carbapenem- and colistin-resistant A. baumannii (MDR-AB, CRAB, CoR-AB, respectively) clinical isolates from tertiary care hospitals. We used the broth microdilution checkerboard and time-kill methods in this study. Synergy was found using both methods. The colistin–sitafloxacin combination showed synergy in MDR-AB, CRAB, and CoR-AB isolates (3.4%, 3.1%, and 20.9%, respectively). No antagonism was found in any type of drug-resistant isolate. The majority of CoR-AB isolates became susceptible to colistin (95.4%). The time-kill method also showed that this combination could suppress regrowth back to the initial inocula of all representative isolates. Our results demonstrated that the colistin–sitafloxacin combination might be an interesting option for the treatment of drug-resistant A. baumannii. However, further in vivo and clinical studies are required.

No abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen in human diseases. Thirtyseven clinical clones from different patients were tested for a molecular study of the mecA gene and multilocus sequence types (ST). Total genomic extraction, followed by a polymerase chain reaction (PCR) for DNA amplification with specific primers for mecA, and specific primers for various ST were used. Molecular typing for the study of genetic relationships among clones was performed by enterobacterial repetitive intergenic consensus (ERIC)-PCR. Antimicrobial susceptibility testing for all clones to 9 drugs was performed by the disk diffusion and vancomycin Etest. The presence of mecA was detected in all clones. The most common ST was MRSA-ST30, accounting for 81.1% of all MRSA tested, followed by MRSA-ST8/ST97/ST779 (8.1%), MRSA-ST239 (2.7%) and MRSA-nontypeable clones (8.1%). Molecular typing by ERIC-PCR demonstrated DNA fingerprints with corresponding results with sequence types. All clones were susceptible (70-100%) to fosfomycin, fusidic acid, gentamicin, tetracycline, trimethoprimsulfamethoxazole and vancomycin [minimal inhibitory concentration (MIC) range, MIC 50 and MIC 90 were 0.25-1.0, 0.5 and 0.75 µg/ml, respectively by using E-test] but resistant to ciprofloxacin, clindamycin and erythromycin. Inducible macrolide, lincosamide-type B streptogramin resistance (iMLSB) phenotype was 5.4% while constitutive MLSB phenotype was 91.9%. For MRSA-ST30 clones, 96.7% were multi-drug resistant (MDR) with the most common pattern being resistant to ciprofloxacin, clindamycin and erythromycin. These results suggest the importance of MRSA in the field of epidemiology at a hospital in Thailand.

BackgroundMultidrug-resistant Acinetobacter baumannii (MDR-AB) is a major cause of nosocomial infections, and associated with high mortality rate. The objective of this study was to test synergistic effect of sitafloxacin and colistin against MDR-AB clinical isolates in Thailand.MethodsThe synergistic effect of sitafloxacin in combination with colistin against the 264 MDR-AB clinical isolates from 13 tertiary care hospitals in Thailand were tested. The fractional inhibitory concentration index (FICI) of combination was determined using the checkerboard method according to CLSI 2016. Time–kill assays were performed for 2 strains (H25 and K21) using sitafloxacin alone and in combination with colistin.ResultsThe MICs of sitafloxacin and colistin range from 0.0156 to 8 µg/mL, and 0.5–16 µg/mL, respectively. The results of synergy testing for the 264 MDR-AB isolates are shown in Table 1. Sitafloxacin reduced the MIC of colistin 2-fold to 8-fold from the original concentrations (Figure 1). From 43 colistin-resistant isolates in combination tested, 39 isolates (90.7%) become susceptible to colistin. In the time-kill assay, synergistic effects were found for two isolates in all concentrations tested, and bactericidal activity was observed within 4 hours and maintained over 24 hours (Figures 2 and 3).Table 1:Synergistic Effect of Sitafloxacin and Colistin Against MDR-AB Isolates (n = 264) Using the Checkerboard AssayAntimicrobial AgentsNo. of Isolates (%)Synergy (FICI ≤0.5)Partial Synergy (FICI >0.5–<1)Additive (FICI = 1)Indifference (FICI >1–<4)Antagonism (FICI ≥4)Sitafloxacin and colistin9(3.4)99(37.5)75(28.4)81(30.7)0(0)Figure 1:MIC reduction of colistin in combination with sitafloxacin against MDR-AB (n = 264).Figure 2:Time–kill curves for sitafloxacin and colistin alone against two isolates of MDR-AB.Figure 3:Time–kill curves with various concentrations of colistin (C) and sitafloxacin (S) in combination against two isolates of MDR-AB.ConclusionThe synergistic effect of sitafloxacin and colistin combination was found. Most of isolates had at least a 2-fold decrease in MIC of colistin, which could be implied to reduce dose of colistin 50% from regular dose. Sitafloxacin combined with colistin may be benefit for alternative treatment of MDR-AB infections.Disclosures T. Paiboonvong, Daiichi Sankyo (Thailand) Ltd.: Grant support, Research support. P. Montakantikul, Daiichi Sankyo (Thailand) Ltd.: Grant support, Research grant.