Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Sep 2014
Epidemiology and predictors of multidrug-resistant community-acquired and health care-associated pneumonia.
There are limited U. S. data describing the risk factors for multidrug-resistant organism (MDRO) isolation in community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP). However, concern for the presence of these pathogens drives the prescribing of empiric broad-spectrum antibiotics for CAP and HCAP. ⋯ MDROs were uncommon in HCAP and CAP. HCAP did not predict MDRO isolation. Local etiology of community onset pneumonia and specific MDRO risk factors should be integrated into therapeutic decisions to prevent empirical overprescribing of antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa.
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Antimicrob. Agents Chemother. · Sep 2014
First detection of TR46/Y121F/T289A and TR34/L98H alterations in Aspergillus fumigatus isolates from azole-naive patients in Denmark despite negative findings in the environment.
Azole-resistant Aspergillus fumigatus harboring the TR34/L98H or TR46/Y121F/T289A alterations is increasingly found in Europe and Asia. Here, we present the first clinical cases of TR46/Y121/T289A and three cases of TR34/L98H outside the cystic fibrosis (CF) population in Denmark and the results of environmental surveys. Four patients (2012 to 2014) with 11 A. fumigatus and 4 Rhizomucor pusillus isolates and 239 soil samples (spring 2010 and autumn 2013, respectively) with a total of 113 A. fumigatus isolates were examined. ⋯ TR34/L98H and TR46/Y121F/T289A alterations appear to be emerging in the clinical setting in Denmark and now involve azole-naive patients. Two recent soil-sampling surveys in Denmark were unable to indicate any increased prevalence of azole-resistant A. fumigatus in the environment. These findings further support the demand for real-time susceptibility testing of all clinically relevant isolates and for studies investigating the seasonal variation and ecological niches for azole-resistant environmental A. fumigatus.
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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 Multicenter Study Comparative StudyMulticenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections.
Ceftolozane-tazobactam (TOL-TAZ) is a novel antibacterial with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, that are associated with complicated intra-abdominal infections (cIAIs). This prospective, double-blind, randomized, multicenter, phase II trial assessed patient clinical and microbiological responses to and the safety of TOL-TAZ plus metronidazole compared with those of meropenem. Hospitalized adults with cIAIs that required surgical intervention were randomized (2:1) to receive intravenous (i.v.) TOL-TAZ (1.5 g [containing 1,000 mg TOL and 500 mg TAZ] every 8 h [q8h]) with or without i.v. metronidazole (500 mg q8h) or i.v. meropenem (1 g q8h) for 4 to 7 days. ⋯ The adverse event rates were similar in the groups (50.0% with TOL-TAZ and 48.8% with meropenem). TOL-TAZ in combination with metronidazole was well tolerated and resulted in clinical and microbiological success rates supportive of further clinical development in patients with cIAIs. (This study has been registered at ClinicalTrials.gov under registration no. NCT01147640.).
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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.).