International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Sep 2015
ReviewCeftolozane/tazobactam and ceftazidime/avibactam: two novel β-lactam/β-lactamase inhibitor combination agents for the treatment of resistant Gram-negative bacterial infections.
The rise in resistant Gram-negative bacteria is a major concern and has led to difficulty in treating multidrug-resistant (MDR) infections. Two recently approved combination antibiotics, ceftolozane/tazobactam and ceftazidime/avibactam, may be effective in treating these resistant infections. Ceftolozane is a novel cephalosporin that has been developed in combination with tazobactam, a recognised β-lactamase inhibitor (BLI). ⋯ Both agents have been approved for the indications of complicated intra-abdominal infection (with metronidazole) and complicated urinary tract infection, and have ongoing phase 3 trials for the treatment of ventilator-associated and nosocomial pneumonia. This manuscript will review current data available regarding the spectrum of activity and clinical trials that led to the US Food and Drug Administration (FDA) approval of these agents. Both agents appear to be well tolerated and show promise in the treatment of MDR Gram-negative infections.
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Int. J. Antimicrob. Agents · Sep 2015
Review Historical ArticleThe history and evolution of outpatient parenteral antibiotic therapy (OPAT).
Outpatient parenteral antibiotic therapy (OPAT) is now a widely accepted and safe therapeutic option for carefully selected patients. Benefits include cost savings and improved patient satisfaction; risks include failure to adhere to care, unexpected changes in the underlying infection, and adverse drug and intravenous access events. We report on our 40-year experience with OPAT in a single healthcare system in the USA and highlight OPAT developments in several countries. ⋯ OPAT was safe, with rehospitalisation rates of 6% and 1% in Periods 1 and 2, respectively. We recommend increased access to structured OPAT teams and the development of standard definitions and criteria for important outcome measures (e.g. clinical 'cure' and unplanned hospital re-admissions). These steps are critical for patient safety and financial stewardship of resources.
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Int. J. Antimicrob. Agents · Aug 2015
Multicenter StudyMolecular identification of aminoglycoside-modifying enzymes in clinical isolates of Escherichia coli resistant to amoxicillin/clavulanic acid isolated in Spain.
The activity of eight aminoglycosides (amikacin, apramycin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin and tobramycin) against a collection of 257 amoxicillin/clavulanic acid (AMC)-resistant Escherichia coli isolates was determined by microdilution. Aminoglycoside resistance rates, the prevalence of aminoglycoside-modifying enzyme (AME) genes, the relationship between AME gene detection and resistance phenotype to aminoglycosides, and the association of AME genes with mechanisms of AMC resistance in E. coli isolates in Spain were investigated. Aminoglycoside-resistant isolates were screened for the presence of genes encoding common AMEs [aac(3)-Ia, aac(3)-IIa, aac(3)-IVa, aac(6')-Ib, ant(2″)-Ia, ant(4')-IIa and aph(3')-Ia] or 16S rRNA methylases (armA, rmtB, rmtC and npmA). ⋯ The ant(2″)-Ia gene was usually associated with OXA-1 [21/30; 70%], whilst 23/25 (92%) strains producing CTX-M-15 had the aac(6')-Ib gene. The most prevalent AME gene was aac(6')-Ib (18/41; 44%) in nosocomial isolates, whilst ant(2″)-Ia and aph(3')-Ia genes (20/64; 31%) were more frequent in strains of community origin. In 64.6% isolates the phenotypic profile correlated with the presence of commonly encountered AMEs.
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Int. J. Antimicrob. Agents · Jul 2015
Randomized Controlled Trial Comparative StudyPharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: A randomised controlled trial of continuous infusion versus intermittent bolus administration.
Here we describe the pharmacokinetics of piperacillin administered by continuous infusion (CI) versus intermittent bolus (IB) dosing in critically ill patients receiving continuous venovenous haemofiltration (CVVH) and compare the frequency of pharmacodynamic/pharmacokinetic (PK/PD) target attainment with each dosing strategy. This was a prospective pharmacokinetic trial in 16 critically ill patients with severe sepsis or septic shock undergoing CVVH and randomised to receive either CI or IB administration of a standard daily dose of piperacillin/tazobactam (11.25g/day on Day 1 followed by 9g/day). Serial blood samples were measured on two occasions. ⋯ Total clearance and clearance not mediated by CVVH were significantly higher with CI administration [median (interquartile range), 1.0 (0.7-1.1) and 0.8 (0.6-1.0)mL/kg/min; P=0.001 and 0.001, respectively]. The estimated unbound piperacillin concentrations were four times above the target susceptibility breakpoint (16mg/L) for the entire dosing interval (100%fT>4xMIC) in 87.5% of patients receiving CI administration (sampling occasion 1), compared with 62.5% of IB patients achieving the desired target (50%fT>4xMIC). Compared with IB dosing, and despite similar CVVH settings, CI administration of piperacillin results in a pharmacokinetic profile that may optimise outcomes for less susceptible pathogens.
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Int. J. Antimicrob. Agents · Jun 2015
Comparative StudyAg5IO6: novel antibiofilm activity of a silver compound with application to medical devices.
This work explores the unique antibiofilm activity of pentasilver hexaoxoiodate (Ag(5)IO(6)). To test this activity, wound dressings were impregnated with Ag(5)IO(6) and compared with various commercially available silver-containing dressings, as well as dressings containing chlorhexidine, iodine and polyhexamethylene biguanide (PHMB). The materials were tested against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans for their ability to prevent micro-organism adherence, eliminate planktonic micro-organisms and disrupt/eliminate mature biofilms generated using the MBEC™ assay within 24 h of microbial exposure. ⋯ The Ag(5)IO(6) dressings demonstrated complete kill (>4 log reduction) in a standard 30-min planktonic log reduction assay against all species. These results demonstrate that Ag(5)IO(6) has superior activity to a number of antimicrobials, with broad-spectrum efficacy that includes long-term prevention of microbial adherence, rapid kill of planktonic micro-organisms, and the ability to disrupt and eliminate mature biofilms. Thus, Ag(5)IO(6) may be a valuable antimicrobial agent for use in a number of medical device applications, including wound dressings, various catheters or implants.