In vitro Synergism of Six Antituberculosis Agents Against Drug-Resistant Mycobacterium tuberculosis Isolated from Retreatment Tuberculosis Patients.

BACKGROUND: Retreatment tuberculosis (TB) has become a major source of drug-resistant TB. In contrast to the combination of isoniazid (INH) and rifampicin (RIF), that of pasiniazid (Pa) and rifabutin (RFB) or rifapentine (RFP) appears to have better activity in vitro against drug-resistant Mycobacterium tuberculosis (MTB), especially when combined with moxifloxacin (MXF). However, there has been limited study of potential synergism among Pa, RFB, RFP, and MXF, or simultaneous comparison with the standard INH and RIF combination. METHODS: In vitro synergism of four two-drug combinations (INH and RIF, Pa and RFB, Pa and RFP, MXF and Pa) and two three-drug combinations (MXF and Pa combined with RFB or RFP) was evaluated against 90 drug-resistant MTB strains isolated from retreatment TB patients by the checkerboard method. The fractional inhibitory concentration index (FICI) was calculated for each combination. RESULTS: The synergistic activity of the combination of Pa with RFB or RFP was higher than that of INH and RIF or MXF and Pa, and the synergistic activity of Pa in combination with RFP was even higher than that of RFB, although RFP yielded an MIC90 of 64 mg/liter, higher than that of RFB of 8 mg/liter against 90 drug-resistant MTB strains. Meanwhile, for three-drug combinations, the synergistic effects of MXF and Pa combined with RFB or RFP were similar. Further stratification analysis showed that, for XDR-MTB strains, the synergistic effect of the Pa and RFP combination was also better than those of other two-drug combinations. CONCLUSION: The combination of Pa with RFP shows better in vitro synergism than Pa with RFB and standard INH with RIF combinations, which can provide a reference for new regimens for retreatment TB patients.

A retrospective analysis of carbapenem-resistant Acinetobacter baumannii-mediated nosocomial pneumonia and the in vitro therapeutic benefit of cefoperazone/sulbactam.

BACKGROUND: Acinetobacter baumannii has been reported increasingly as a significant causative organism of various nosocomial infections, including hospital-acquired pneumonia (HAP). The aim of this study was to investigate the clinical characteristics of HAP induced by carbapenem-resistant A. baumannii (CRAB) in elderly patients and the in vitro antimicrobial effects of cefoperazone/sulbactam combination therapy. METHODS: Seventy-one elderly patients in the geriatric ward of the General Hospital of the People's Liberation Army (PLAGH) with CRAB-induced HAP were analyzed retrospectively. The checkerboard method was used to determine the in vitro drug sensitivity of 60 CRAB strains to antimicrobial combinations (cefoperazone/sulbactam with meropenem, minocycline, or levofloxacin). The occurrence of carbapenemase genes was detected by PCR. RESULTS: CRAB-induced HAP occurred mostly in patients with underlying diseases. Prior to onset, most patients had received antimicrobial therapies including broad-spectrum ß-lactams, invasive mechanical ventilation, and catheterization. The 30-day survival rate was 95.1% in patients using cefoperazone/sulbactam, with or without combination with antimicrobial drugs, and 73.3% in patients not using cefoperazone/sulbactam (p<0.05). When cefoperazone/sulbactam was used in combination with minocycline, levofloxacin, and meropenem, minimum inhibitory concentrations MIC50 and MIC90 were reduced for each drug. The genes OXA-23 and OXA-51 were amplified in 96.7% of the strains, but the genes OXA-24, OXA-58, SIM, VIM, and IMP were not amplified. CONCLUSIONS: CRAB-induced HAP occurred mostly in patients with anemia or decreased levels of serum albumin, but with elevated levels of C-reactive protein and creatinine. Cefoperazone/sulbactam in combination with minocycline, meropenem, and levofloxacin had a synergistic and additive in vitro bacteriostatic action on CRAB.

Combined Activity of Polymyxin B with Meropenem Against 110 Strains of Multidrug-resistant Acinetobacter baumannii / 中华医院感染学杂志

OBJECTIVE To evaluate the antibiotic effects of polymyxin B combined with meropenem against 110 strains of multidrug-resistant Acinetobacter baumannii.METHODS The protocol was designed by checkerboard method and the MICs of polymyxin B combined with meropenem against the 110 strains of A.baumannii were determined by broth dilution method,the FIC index was calculated according to MIC results.RESULTS The percentage of the FIC indexes less than 0.5,from 0.5 to 1,from 1 to 2 and more than 2 were 98%,2%,0% and 0%,respectively.CONCLUSIONS When polymyxin B combined with meropenem against 110 strains of A.baumannii the synergism and additivity are the main,there are no autonomy and antagonism.