A meta-analysis of metronidazole and vancomycin for the treatment of Clostridium difficile infection, stratified by disease severity

The aim of this meta-analysis was to compare the efficacy of metronidazole and vancomycin for the treatment of Clostridium difficileinfection, especially to investigate which agent was superior for treating either mild or severe C. difficileinfection. A meta-analysis of randomized controlled trials and cohort studies identified in Pubmed, Embase, and the Cochrane Library was conducted. Four randomized controlled trials and two cohort studies involving 1218 patients were included in this meta-analysis. Metronidazole was inferior to vancomycin for treating C. difficileinfection in terms of both initial clinical cure rates (risk ratio, RR = 0.91, 95% confidence interval, CI = 0.84-0.98, p= 0.02) and sustained cure rates (RR = 0.88, 95% CI = 0.82-0.96, p= 0.003). For mild C. difficileinfection, the efficacy of metronidazole and vancomycin resulted in similar clinical cure rates (RR = 0.94, 95% CI = 0.84-1.04, p= 0.21) and sustained cure rates (RR = 0.93, 95% CI = 0.83-1.05, p= 0.26). For severe C. difficileinfection the efficacy of vancomycin was superior to metronidazole in terms of clinical cure rates (RR = 0.81, 95% CI = 0.69-0.95, p= 0.009), whereas sustained cure rates were similar (RR = 0.86, 95% CI = 0.72-1.02, p= 0.08). Regarding microbiological cure metronidazole therapy was as effective as vancomycin therapy (RR = 0.88, 95% CI = 0.64-1.21, p= 0.43). Recurrence rates with metronidazole and vancomycin for both mild C. difficileinfection (RR = 0.95, 95% CI = 0.56-1.60, p= 0.85) and severe C. difficileinfection (RR = 1.27, 95% CI = 0.85-1.91, p= 0.25) were not different. Likewise, no difference in all-cause mortality was found as well (RR = 0.87, 95% CI = 0.56-1.35, p= 0.53). In conclusion, vancomycin provides improved initial clinical and sustained cure rates in patients with C. difficileinfection compared with metronidazole, especially in patients with severe C. difficileinfection. In view of these data, vancomycin may be considered first line therapy for severe C. difficileinfection.

Efficacy of polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis

In recent years, carbapenem-resistant Enterobacteriaceae has become endemic in many countries. Because of limited treatment options, the abandoned "old antibiotics", polymyxins, have been reintroduced to the clinic. To evaluate the clinical efficacy of polymyxins in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae, we systemically searched the PubMed, Embase, and Cochrane Library databases and analyzed the available evidence. The Preferred Reporting Items for Systematic reviews and Meta-Analysis statement were followed, and the I2 method was used for heterogeneity. Nineteen controlled and six single-arm cohort studies comprising 1086 patients met the inclusion criteria. For controlled studies, no significant difference was noted for overall mortality (OR, 0.79; 95% CI, 0.58-1.08; p = 0.15), clinical response rate (OR, 1.24; 95% CI, 0.61-2.54; p = 0.55), or microbiolog- ical response rate (OR, 0.59; 95% CI, 0.26-1.36; p = 0.22) between polymyxin-treated groups and the control groups. Subgroup analyses showed that 28-day or 30-day mortality was lower in patients who received polymyxin combination therapy than in those who received monotherapy (OR, 0.36; 95% CI, 0.19-0.68; p < 0.01) and the control groups (OR, 0.49; 95% CI, 0.31-0.75; p < 0.01). The results of the six single-arm studies were in accordance with the findings of controlled studies. One controlled and two single-arm studies that evaluated the occurrence of nephrotoxicity reported a pooled incidence rate of 19.2%. Our results suggest that polymyxins may be as efficacious as other antimicrobial therapies for the treatment of carbapenem-resistant Enterobacteriaceae infection. Compared to polymyxin monotherapy, combination regimens may achieve lower 28-day or 30-day mortality. Future large-volume, well-designed randomized control trials are required to determine the role of polymyxins in treating carbapenem-resistant Enterobacteriaceae infections.

Colistin and anti-Gram-positive bacterial agents against Acinetobacter baumannii

Introduction Acinetobacter baumannii has attained an alarming level of resistance to antibacterial drugs. Clinicians are now considering the use of older agents or unorthodox combinations of licensed drugs against multidrug-resistant strains to bridge the current treatment gap. We investigated the in vitro activities of combination treatments that included colistin with vancomycin, norvancomycin or linezolid against multidrug-resistant Acinetobacter baumannii. Methods The fractional inhibitory concentration index and time-kill assays were used to explore the combined effects of colistin with vancomycin, norvancomycin or linezolid against 40 clinical isolates of multidrug-resistant Acinetobacter baumannii. Transmission electron microscopy was performed to evaluate the interactions in response to the combination of colistin and vancomycin. Results The minimum inhibitory concentrations (MICs) of vancomycin and norvancomycin for half of the isolates decreased below the susceptibility break point, and the MIC of linezolid for one isolate was decreased to the blood and epithelial lining fluid concentration using the current dosing regimen. When vancomycin or norvancomycin was combined with subinhibitory doses of colistin, the multidrug-resistant Acinetobacter baumannii test samples were eradicated. Transmission electron microscopy revealed that subinhibitory doses of colistin were able to disrupt the outer membrane, facilitating a disruption of the cell wall and leading to cell lysis. Conclusions Subinhibitory doses of colistin significantly enhanced the antibacterial activity of vancomycin, norvancomycin, and linezolid against multidrug-resistant Acinetobacter baumannii. .