Youning Liu

Systematic Review and Meta-Analysis of the Effectiveness and Safety of Tigecycline for Treatment of Infectious Disease

ABSTRACT The aim of this study was to compare the efficacy and safety of tigecycline, a newly developed glycylcycline antibiotic, with those of empirical antibiotic regimens which have been reported to possess good efficacy for complicated skin and skin structure infections (cSSSIs), complicated intra-abdominal infections (cIAIs), community-acquired pneumonia (CAP), and other infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE). A meta-analysis of randomized controlled trials (RCTs) identified in PubMed, the Cochrane Library, and Embase was performed. Eight RCTs involving 4,651 patients were included in the meta-analysis. Compared with therapy with empirical antibiotic regimens, tigecycline monotherapy was associated with similar clinical treatment success rates (for the clinically evaluable [CE] population, odds ratio [OR] = 0.92, 95% confidence interval [CI] = 0.76 to 1.12, P = 0.42; for the clinical modified intent-to-treat [c-mITT] population, OR = 0.86, 95% CI = 0.74 to 1.01, P = 0.06) and similar microbiological treatment success rates (for the microbiologically evaluable [ME] population, OR = 0.86, 95% CI = 0.69 to 1.07, P = 0.19). The incidence of adverse events in the tigecycline group was significantly higher than that in the other therapy groups with a statistical margin (for the modified intent-to-treat [mITT] population, OR = 1.33, 95% CI = 1.17 to 1.52, P < 0.0001), especially in the digestive system (mITT population, OR = 2.41, 95% CI = 1.67 to 3.46, P < 0.00001). No difference regarding all-cause mortality and drug-related mortality between tigecycline and the other regimens was found, although numerically higher mortality was found in the tigecycline group. This meta-analysis provides evidence that tigecycline monotherapy may be used as effectively as the comparison therapy for cSSSI, cIAIs, CAP, and infections caused by MRSA/VRE. However, because of the high risk of mortality, AEs, and emergence of resistant isolates, prudence with the clinical use of tigecycline monotherapy in infections is required.

Effectiveness and safety of macrolides in cystic fibrosis patients: a meta-analysis and systematic review

OBJECTIVES To evaluate the efficacy and safety of macrolides in cystic fibrosis (CF). METHODS Randomized controlled trials (RCTs) of macrolides for the treatment of CF published in PubMed, the Cochrane Library and Embase were searched. Application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality were independently performed in duplicate. The primary efficacy outcome was the impact on the deterioration of lung function (changes in FEV(1) and FVC). Safety outcomes included adverse events and mortality. RESULTS Eight RCTs (seven with azithromycin and one with clarithromycin) were found in the systematic review and six RCTs with azithromycin (654 patients) were included in the meta-analysis. Azithromycin treatment showed a significant increase in FEV(1)% (3.22%, 95% CI = 1.38-5.06, P = 0.0006, I(2) = 0%) and FVC% (3.23%, 95% CI = 1.62-4.85, P < 0.0001, I(2) = 0%) compared with placebo. In individuals with baseline Pseudomonas aeruginosa colonization, both FEV(1)% (4.80%, 95% CI = 1.66-7.94, P = 0.003, I(2) = 42%) and FVC% (4.74%, 95% CI = 1.92-7.57, P = 0.001, I(2) = 0%) increased significantly. The incidence rates of the main side effects (cough, headache, abdominal pain, vomiting, nausea and diarrhoea) were not significantly different between the azithromycin-treated group and the placebo group. The RCT of clarithromycin, involving 18 patients, showed its effects on clinical improvement; however, the small sample size made comparisons with azithromycin difficult. CONCLUSIONS Long-term use of azithromycin can improve lung function, especially for P. aeruginosa-colonized CF patients. There was no evidence of increased adverse events with azithromycin. More data are needed to verify the best azithromycin regimen and to evaluate other macrolides in CF patients.

Causative agent distribution and antibiotic therapy assessment among adult patients with community acquired pneumonia in Chinese urban population

BackgroundKnowledge of predominant microbial patterns in community-acquired pneumonia (CAP) constitutes the basis for initial decisions about empirical antimicrobial treatment, so a prospective study was performed during 2003–2004 among CAP of adult Chinese urban populations.MethodsQualified patients were enrolled and screened for bacterial, atypical, and viral pathogens by sputum and/or blood culturing, and by antibody seroconversion test. Antibiotic treatment and patient outcome were also assessed.ResultsNon-viral pathogens were found in 324/610 (53.1%) patients among whom M. pneumoniae was the most prevalent (126/610, 20.7%). Atypical pathogens were identified in 62/195 (31.8%) patients carrying bacterial pathogens. Respiratory viruses were identified in 35 (19%) of 184 randomly selected patients with adenovirus being the most common (16/184, 8.7%). The nonsusceptibility of S. pneumoniae to penicillin and azithromycin was 22.2% (Resistance (R): 3.2%, Intermediate (I): 19.0%) and 79.4% (R: 79.4%, I: 0%), respectively. Of patients (312) from whom causative pathogens were identified and antibiotic treatments were recorded, clinical cure rate with β-lactam antibiotics alone and with combination of a β-lactam plus a macrolide or with fluoroquinolones was 63.7% (79/124) and 67%(126/188), respectively. For patients having mixed M. pneumoniae and/or C. pneumoniae infections, a better cure rate was observed with regimens that are active against atypical pathogens (e.g. a β-lactam plus a macrolide, or a fluoroquinolone) than with β-lactam alone (75.8% vs. 42.9%, p = 0.045).ConclusionIn Chinese adult CAP patients, M. pneumoniae was the most prevalent with mixed infections containing atypical pathogens being frequently observed. With S. pneumoniae, the prevalence of macrolide resistance was high and penicillin resistance low compared with data reported in other regions.

Systematic review and meta-analysis of the efficacy and safety of therapy with linezolid containing regimens in the treatment of multidrug-resistant and extensively drug-resistant tuberculosis

BACKGROUND Linezolid containing regimens have been proposed as potentially valuable alternatives for the treatment of patients with multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant TB (XDR-TB). METHODS A systematic review and meta-analysis was conducted to assess the efficacy, safety and tolerability of linezolid for drug-resistant TB (DR-TB) treatment. We searched the Cochrane Controlled Trial Registry, PubMed, Embase, Science Citation Index Expanded (SCI) and China National Knowledge Infrastructure (CNKI), database up to May 2014 to identify studies providing data of the use of linezolid for the treatment of DR-TB. RESULTS The search yielded 15 studies (367 patients) including one randomized controlled trial (RCT), covering 239 patients who could be evaluated for effectiveness; 83% [95% confidence interval (CI), 75-90%; I(2)=62.8%] had a favorable outcome, defined as either cure or treatment completion. The pooled rate of culture conversion was 89% (95% CI, 83-95%; I(2)=49.6%). Between the group receiving daily linezolid doses of ≤600 or >600 mg, the mortality was considerably lower in patients treated with less than 600 mg/day (P value <0.001). Of 367 patients for whom data on safety was available, peripheral neuropathy (31%, 95% CI, 19-42%; I(2)=81.7%) and anemia (25%, 95% CI, 15-34%; I(2)=76.6%) were the main adverse effects. Patients receiving less than 600 mg/day were more likely to experience nervous system adverse events (P value <0.01). CONCLUSIONS The available evidence suggests that linezolid could be considered as a promising option as treatment of MDR/XDR TB. Randomized trials are warranted to define the dose and frequency of administration.

In vitro antimicrobial activity and mutant prevention concentration of colistin against Acinetobacter baumannii.

ABSTRACT The antimicrobial activities of colistin and other antibiotics against clinical Acinetobacter baumannii and the mutant prevention concentration (MPC) of colistin against multidrug-resistant A. baumannii were studied. All 70 stains tested were sensitive to colistin. The MPC range of colistin against 30 multidrug-resistant A. baumannii stains was approximately 32 to >128 μg/ml, and the MPC at which 90% of the isolates tested were prevented (MPC90) exceeded 128 μg/ml, which was much higher than the plasma concentration of colistin at the current recommended dosage. So, combination therapy for colistin treatment of A. baumannii would be prudent to slow the emergence of resistance.

Effects of Efflux Pump Inhibitors on Colistin Resistance in Multidrug-Resistant Gram-Negative Bacteria

ABSTRACT We tested the effects of various putative efflux pump inhibitors on colistin resistance in multidrug-resistant Gram-negative bacteria. Addition of 10 mg/liter cyanide 3-chlorophenylhydrazone (CCCP) to the test medium could significantly decrease the MICs of colistin-resistant strains. Time-kill assays showed CCCP could reverse colistin resistance and inhibit the regrowth of the resistant subpopulation, especially in Acinetobacter baumannii and Stenotrophomonas maltophilia. These results suggest colistin resistance in Gram-negative bacteria can be suppressed and reversed by CCCP.

Mutant prevention concentration of tigecycline for carbapenem-susceptible and -resistant Acinetobacter baumannii

Mutant prevention concentration of tigecycline for carbapenem-susceptible and -resistant Acinetobacter baumannii

Laboratory diagnosis, clinical management and infection control of the infections caused by extensively drug-resistant Gram-negative bacilli: a Chinese consensus statement

Extensively drug-resistant (XDR) Gram-negative bacilli (GNB) are defined as bacterial isolates susceptible to two or fewer antimicrobial categories. XDR-GNB mainly occur in Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. The prevalence of XDR-GNB is on the rise in China and in other countries, and it poses a major public health threat as a result of the lack of adequate therapeutic options. A group of Chinese clinical experts, microbiologists and pharmacologists came together to discuss and draft a consensus on the laboratory diagnosis, clinical management and infection control of XDR-GNB infections. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created according to documents from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). Multiple risk factors of XDR-GNB infections are analyzed, with long-term exposure to extended-spectrum antimicrobials being the most important one. Combination therapeutic regimens are summarized for treatment of XDR-GNB infections caused by different bacteria based on limited clinical studies and/or laboratory data. Most frequently used antimicrobials used for the combination therapies include aminoglycosides, carbapenems, colistin, fosfomycin and tigecycline. Strict infection control measures including hand hygiene, contact isolation, active screening, environmental surface disinfections, decolonization and restrictive antibiotic stewardship are recommended to curb the XDR-GNB spread.

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.

Chinese Guidelines for Diagnosis and Treatment of Influenza (2011)

Influenza, an acute respiratory infection caused by influenza virus, is one of public concerns to human health. Epidemiologically, influenza is characterized by a sudden outbreak and rapid transmission with varying epidemics, seasonality, and a high morbidity yet low case fatality (usually 0.003% to 0.03% except for human avian flu). The past 300 years has witnessed at least six global pandemics, including four in the 20th century -- three of them originated in China.