A pharmacodynamic simulation to evaluate tigecycline in treatment of nosocomial pneumonia caused by multidrug-resistant Acinetobacter baumannii.

The shortage of effective antibiotics against multidrug-resistant Acinetobacter baumannii (MDR-Ab) has posed great threat to the public health. But the advent of tigecycline gives us new hope. The goal of our research was to assess the clinical efficacy of tigecycline at different doses by using a pharmacokinetic/pharmacodynamic (PK/PD) model which can incorporate pharmacokinetic data of tigecycline from patients with pneumonia and MICs of MDR-Ab from a tertiary hospital. A 10000-patient Monte-Carlo Simulation based on the PK/PD model was conducted to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of tigecycline. 97% isolates displayed susceptibility and 3% were tigecycline-intermediate strains and the values of MIC ranged from 0.125 to 4 µ g/ml. A CFR of 61.62% was predicted for tigecycline at current dosage (50 mg q12h). When the dosage was increased, the predicted CFRs for 75 mg q12h, 100 mg q12h, 125 mg q12h, 150 mg q12h were 81.00%, 89.86%, and 94.57%, 96.77%, respectively. Despite presented higher susceptibility, the CFR obtained was not optimal at current dosage. A higher CFR indicating a better clinical efficacy can be gained by the increased dosage.

[Antimicrobial resistance and genotyping of Acinetobacter baumannii in ICU].

OBJECTIVE: To investigate the outbreak of acinetobacter baumannii in the ICU, and to explore the antimicrobial resistance characteristics of pathogens, and therefore to determine the optimal prevention strategies. METHODS: From May to June 2007, most of the cases of infection by acinetobacter baumannii in our ICU were collected. PFGE (pulsed field gel electrophoresis) and standard disk diffusion susceptibility tests were performed on the strains isolated from the patients' body fluids including sputum, blood, urine, secretion and from the ICU environment involving the patients' bed sheet, skin surface and medical staff's hands, humidification water of ventilator tubes. RESULTS: Twelve strains were resistant to imipenem and meropenem. Colistin sulphate and tigecycline showed a high rate of antimicrobial activity against the strains, the rate of susceptibility being 100% and 91.7% respectively. These strains belonged to 3 clones (clone A, B, C) and there were 2 sub-clones (A1, A2) belonging to clone A. The sub-clone A1 was isolated from the surface of unwashed medical staff's hands and patients' body fluids. From intermediate to resistance, the antimicrobial characteristics of clone A and clone B to minocycline changed over a month, and there was one strain that was resistant to tigecycline. CONCLUSION: The outbreak of acinetobacter baumannii in the ICU was caused by carbapenem resistant acinetobacter baumannii (CRAb). The delicate changes of disk diffusion susceptibility in clones A and B occurred in one month. Unwashed hands of medical staff were probably responsible for the outbreak.

Healthcare-associated Pneumonia: Clinical Features and Retrospective Analysis Over 10 Years.

BACKGROUND: Healthcare-associated pneumonia (HCAP) is associated with drug-resistant pathogens and high mortality, and there is no clear evidence that this is due to inappropriate antibiotic therapy. This study was to elucidate the clinical features, pathogens, therapy, and outcomes of HCAP, and to clarify the risk factors for drug-resistant pathogens and prognosis. METHODS: Retrospective observational study among hospitalized patients with HCAP over 10 years. The primary outcome was 30-day all-cause hospital mortality after admission. Demographics (age, gender, clinical features, and comorbidities), dates of admission, discharge and/or death, hospitalization costs, microbiological results, chest imaging studies, and CURB-65 were analyzed. Antibiotics, admission to Intensive Care Unit (ICU), mechanical ventilation, and pneumonia prognosis were recorded. Patients were dichotomized based on CURB-65 (low- vs. high-risk). RESULTS: Among 612 patients (mean age of 70.7 years), 88.4% had at least one comorbidity. Commonly detected pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and coagulase-negative staphylococci. Initial monotherapy with ß-lactam antibiotics was the most common initial therapy (50%). Mean age, length of stay, hospitalization expenses, ICU admission, mechanical ventilation use, malignancies, and detection rate for P. aeruginosa, and Staphylococcus aureus were higher in the high-risk group compared with the low-risk group. CURB-65 ≥3, malignancies, and mechanical ventilation were associated with an increased mortality. Logistic regression analysis showed that cerebrovascular diseases and being bedridden were independent risk factors for HCAP. CONCLUSION: Initial treatment of HCAP with broad-spectrum antibiotics could be an appropriate approach. CURB-65 ≥3, malignancies, and mechanical ventilation may result in an increased mortality.

[Mutant prevention concentrations of fluoroquinolones for Staphylococcus aureus].

OBJECTIVE: To establish a method to measure mutant prevention concentration (MPC) in vitro, and to measure MPC of fluoroquinolones for staphylococcus aureus. METHODS: The staphylococcus aureus strain ATCC25923 and 20 ciprofloxacin-susceptible clinical isolates were enriched in broth, and the bacterial concentrations were adjusted to 10(10) colony forming units per milliliter. The minimal inhibitory concentration (MIC), MIC for 99% of input cells (MIC99), provisional MPC (MPCpr) and MPC of moxifloxacin, gatifloxacin, pasufloxacin and ciprofloxacin for staphylococcus aureus were determined by agar plates dilution method. RESULTS: The MPC of moxifloxacin, gatifloxacin, pasufloxacin and ciprofloxacin for staphylococcus aureus strain ATCC25923 were 0.18, 0.3, 0.75 and 1.8 microg/ml, and the MPC/MIC99 were 9.0, 7.5, 8.0 and 10.6 respectively. The MPC for 90% of the isolates (MPCpr90) of moxifloxacin, gatifloxacin, pasufloxacin and ciprofloxacin for 20 staphylococcus aureus clinical isolates were 1, 1, 4 and 8 microg/ml, and the MPCpr90/MIC90 were 8, 8, 16 and 16 respectively. CONCLUSION: The capacity of moxifloxacin and gatifloxacin for restricting the selection of staphylococcus aureus resistant mutants were stronger than that of pasufloxacin and ciprofloxacin. Combined with pharmacokinetic parameters, moxifloxacin and gatifloxacin may restrict the selective enrichment of resistant mutants among ciprofloxacin-susceptible staphylococcus aureus clinical isolates, and ciprofloxacin is expected to selectively enrich mutants easily.

Treatment of community-acquired pneumonia with moxifloxacin: a meta-analysis of randomized controlled trials.

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality throughout the world. To investigate whether moxifloxacin monotherapy is associated with better clinical outcomes than other antibiotics recommended for CAP among adults with mild-to-moderate or severe CAP, we performed a meta-analysis. MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched for randomized control trials (RCTs). The efficacy and safety of moxifloxacin were compared with other antimicrobial agents used to treat CAP. Fourteen RCTs, consisting of 6923 total patients, were included in the meta-analysis. No difference was found regarding the incidence of adverse events and mortality between moxifloxacin and the compared regimens. We found that moxifloxacin is as effective and well-tolerated as other recommended antibiotics for the treatment of CAP and possesses a better pathogen eradication rate than beta-lactam-based therapy.