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.

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 difficile infection, especially to investigate which agent was superior for treating either mild or severe C. difficile infection. 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. difficile infection 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. difficile infection, 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. difficile infection 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. difficile infection (RR=0.95, 95% CI=0.56-1.60, p=0.85) and severe C. difficile infection (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. difficile infection compared with metronidazole, especially in patients with severe C. difficile infection. In view of these data, vancomycin may be considered first line therapy for severe C. difficile infection.

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.

In vitro activity of fosfomycin in combination with colistin against clinical isolates of carbapenem-resistant Pseudomas aeruginosa.

The shortage of effective antibiotics against carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a public health threat. Combination treatment may represent a good choice for treating infections caused by CRPA. The aim of this study was to evaluate the in vitro efficacy of fosfomycin in combination with colistin against clinical CRPA isolates. Eighty-seven isolates were collected from three hospitals in China. The checkerboard method and time-kill assay were used to assess the interactions between fosfomycin and colistin. The fosfomycin/colistin combination displayed synergistic and partial synergistic activity against 21.84% and 27.59% of the isolates, respectively. Antagonism was not observed. In combination, the colistin MIC values were ⩽0.5 µg ml(-1) for 91.95% of the isolates. This result differed significantly from those obtained using a single agent treatment (The colistin MIC values were ⩽0.5 µg ml(-1) for only 25.29% of the isolates). In addition, the time-kill assay demonstrated that the fosfomycin/colistin combination treatment exerted bactericidal effects against five isolates and that the regrowth observed after colistin monotherapy was prevented. In summary, the combination of fosfomycin and colistin demonstrated synergistic activity against the CRPA isolates tested in this study. Furthermore, fosfomycin may potentially widen the therapeutic window of colistin, suggesting that this combination could be applied clinically to control infections caused by CRPA.

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 I(2) 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 microbiological 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.

In vitro activity of tigecycline in combination with cefoperazone-sulbactam against multidrug-resistant Acinetobacter baumannii.

Over the last decade, multidrug-resistant Acinetobacter baumannii (MDRAB) has emerged as one of the most problematic nosocomial pathogens. Empirical combination therapy has become a common practice to treat patients infected with MDRAB. In vitro interactions of tigecycline with cefoperazone-sulbactam were assessed in 72 MDRAB isolates. Minimum inhibitory concentrations (MICs) were determined by broth microdilution method. Antibiotic interactions were determined by chequerboard and time-kill assays. Chequerboard analysis showed 29·2% synergy and no antagonistic interactions. Time-kill assays confirmed the synergistic interaction between two agents for three of four selected extensively drug-resistant A. baumannii (XDRAB) isolates. No antagonism was revealed by time-kill assays. Moreover, tigecycline in combination with cefoperazone-sulbactam appeared to be more effective than tigecycline in combination with sulbactam against XDRAB. In conclusion, in vitro synergistic activities of tigecycline in combination with cefoperazone-sulbactam against MDRAB were demonstrated, suggesting a superior treatment option against MDRAB.

In vitro synergy of polymyxins with other antibiotics for Acinetobacter baumannii: a systematic review and meta-analysis.

In order to provide preliminary guidance for rational antibiotic combination therapy in the clinic, a systematic review and meta-analysis was performed to evaluate the in vitro synergistic activity of polymyxins combined with other antibiotics against Acinetobacter baumannii. An extensive literature search was undertaken without restriction according to region, publication type or language. All available in vitro synergy tests on antibiotic combinations consisting of polymyxins were included. The primary outcome assessed was the in vitro activity of combination therapy on bacterial kill or inhibition. In total, 70 published studies and 31 conference proceedings reporting testing of polymyxins in combination with 11 classes consisting of 28 antibiotic types against 1484 A. baumannii strains were included in the analysis. In time-kill studies, high in vitro synergy and bactericidal activity were found for polymyxins combined with several antibiotic classes such as carbapenems and glycopeptides. Carbapenems or rifampicin combination could efficiently suppress the development of colistin resistance and displayed a >50% synergy rate against colistin-resistant strains. Synergy rates of chequerboard microdilution and Etest methods in most antibiotic combinations were generally lower than those of time-kill assays. The benefits of these antibiotic combinations should be further demonstrated by well-designed clinical studies.

[Bibliometric analysis of bacterial quantitative proteomics in English literatures].

OBJECTIVE: To analyze the worldwide advances on bacterial quantitative proteomics over the past fifteen years with bibliometric approach. METHODS: Literature retrieval was conducted throughout the databases of Pubmed, Embase and Science citation index (SCI), using "bacterium" and "quantitative proteomics" as the key words. The deadline is July 2013. We sorted and analyzed these articles with Endnote X6 from the aspects of published year, the first author, name of journal, published institution, cited frequency and publication type. RESULTS: 932 English articles were included in our research after deleting the duplicates. The first article on bacterial quantitative proteomics was reported in 1999. The maximal publications were 163 related articles in 2012. Up till July 2013, authors from more than 23 countries and regions have published articles in this field. China ranks the fourth. The main publication type is original articles. The most frequently cited article is entitled with "Absolute quantification of proteins by LCMSE: a virtue of parallel MS acquisition" by Silva JC, Gorenstein MV, Li GZ, et al in Mol Cell Proteomics 2006. The most productive author is Smith RD from Biological Sciences Division, Pac. Northwest National Laboratory. The top journal publishing bacterial quantitative proteomics is Proteomics. CONCLUSION: More and more researchers pay attention to quantitative proteomics which will be widely used in bacteriology.

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.

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. .

Different microbiological and clinical aspects of lower respiratory tract infections between China and European/American countries.

BACKGROUND: National treatment/diagnosis guidelines for lower respiratory tract infections (LRTIs) are generally based on local epidemiological data. Etiology and drug-resistance patterns could differ between China and European/American countries, and simply following their respective guidelines might cause problems in clinical practice. Therefore, we need to summarize the microbiology and clinical manifestations of LRTIs in China and develop our own guidelines. METHODS: Three major national multicenter epidemiology surveillance studies on LRTI were completed recently. The data were compared in detail with those from European/American studies. RESULTS: Clinical and microbiological differences were observed in community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and pulmonary mycosis between our country and European/American countries. CONCLUSIONS: The microbiological and clinical characteristics of the major LRTIs in China differ in many respects from those in European/American countries. Patients should have personal treatment plans instead of simply following the guidelines from foreign countries.