Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Sep 2014
Efficacy of fosfomycin compared to vancomycin in treatment of implant-associated chronic methicillin-resistant Staphylococcus aureus osteomyelitis in rats.
Fosfomycin monotherapy was compared to therapy with vancomycin for the treatment of implant-associated methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis in an experimental rat model. The proximal tibiae were inoculated with 15 μl of a suspension containing 1×10(8) to 5×10(8) CFU/ml of a clinical isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later, treatment was started for 28 days with either 50 mg/kg of body weight vancomycin intraperitoneally twice daily (n=11) or 75 mg/kg fosfomycin intraperitoneally once daily (n=10). ⋯ Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P=0.324), and fosfomycin was superior to the no-drug control and vancomycin (P<0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.
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Antimicrob. Agents Chemother. · Sep 2014
Randomized Controlled Trial Comparative StudyPreliminary study of colistin versus colistin plus fosfomycin for treatment of carbapenem-resistant Acinetobacter baumannii infections.
Ninety-four patients infected with carbapenem-resistant Acinetobacter baumannii were randomized to receive colistin alone or colistin plus fosfomycin for 7 to 14 days. The patients who received combination therapy had a significantly more favorable microbiological response and a trend toward more favorable clinical outcomes and lower mortality than those who received colistin alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01297894.).
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Antimicrob. Agents Chemother. · Sep 2014
Randomized Controlled TrialRandomized comparison of the efficacies and tolerabilities of three artemisinin-based combination treatments for children with acute Plasmodium falciparum malaria in the Democratic Republic of the Congo.
An open-label, randomized controlled trial was carried out in 2011-2012 in the Democratic Republic of the Congo to test the efficacy, safety, and tolerability of the artemisinin-based combination treatments dihydroartemisinin-piperaquine, amodiaquine-artesunate, and artemether-lumefantrine. Six hundred eighty-four children aged 3 to 59 months with uncomplicated Plasmodium falciparum malaria were randomly allocated to each study arm. Children were hospitalized for 3 days, given supervised treatment, and followed up weekly for 42 days. ⋯ The day 7 plasma concentration of piperaquine was below 30 ng/ml in 47% of the children treated with dihydroartemisinin-piperaquine, and the day 7 lumefantrine concentration was below 280 ng/ml in 37.0% of children who received artemether-lumefantrine. Thus, although cure rates were all satisfactory, they could be improved by increasing the dose. (This study has been registered with the International Standard Randomized Controlled Trial Number Register [www.isrctn.org] under registration no. ISRCTN20984426.).
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Antimicrob. Agents Chemother. · Sep 2014
Frequency of outpatient antibiotic prescription on discharge to hospice care.
The use of antibiotics is common in hospice care despite limited evidence that it improves symptoms or quality of life. Patients receiving antibiotics upon discharge from a hospital may be more likely to continue use following transition to hospice care despite a shift in the goals of care. We quantified the frequency and characteristics for receiving a prescription for antibiotics on discharge from acute care to hospice care. ⋯ Among documented infections, 40.3% were bloodstream infections, septicemia, or endocarditis, and 38.9% were pneumonia. Independent risk factors for receiving an antibiotic prescription were documented infection during the index admission (adjusted odds ratio [AOR]=7.00; 95% confidence interval [95% CI]=4.68 to 10.46), discharge to home hospice care (AOR=2.86; 95% CI=1.92 to 4.28), and having a cancer diagnosis (AOR=2.19; 95% CI=1.48 to 3.23). These data suggest that a high proportion of patients discharged from acute care to hospice care receive an antibiotic prescription upon discharge.
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Antimicrob. Agents Chemother. · Sep 2014
Evaluation of the pharmacokinetics and pharmacodynamics of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infections using data from two phase 2 clinical studies.
The pharmacokinetic-pharmacodynamic (PK-PD) relationships between serum exposure measures of liposomal amikacin for inhalation (LAI) and the change in pulmonary function test (PFT) measures and number of CFU from baseline were evaluated in cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. A dose of 70, 140, 280, or 560 mg of LAI or placebo was administered to CF patients once daily for 28 days. PFTs and sputum samples for microbiology were assessed on days 7, 14, 21, 28, 35 (for log10 CFU), and 56 (for PFTs). ⋯ The increases in the relative change in FEV1 and FEV1% predicted of 11% and 9.9%, respectively, and a 1.23-log10 CFU reduction per 560 mg of LAI estimated on day 7 were comparable to the observed increases of 10.7% and 10.3%, respectively, and a 1.24-log10 CFU reduction on the same day. The model-estimated PFT effects were predicted to be sustained to day 28. An additional 0.451-log10 CFU reduction (P=0.022) was estimated on day 14 relative to day 7, with a persistence of effect predicted to day 35.