International journal of antimicrobial agents
-
Int. J. Antimicrob. Agents · Apr 2018
Sustained multimodal antimicrobial stewardship in an Australian tertiary intensive care unit from 2008-2015: an interrupted time-series analysis.
The long-term outcomes and sustainability of antimicrobial stewardship (AMS) in the intensive care unit (ICU) require evaluation. This study analysed the effect of a multimodal ICU AMS introduced in a 15-bed medical-surgical tertiary Australian adult ICU in November 2008, using interrupted time-series analysis of antibiotic usage, Gram-negative resistance and cost from November 2005 to October 2015, including national ICU average usage as a control. Overall ICU mortality, 30-day blood stream infection (BSI) mortality and length of stay (LOS) were compared over the same period. ⋯ Over the study period, severity-adjusted ICU mortality declined from 12.9% to 10.4%; risk ratio (RR) 0.92 (95%CI 0.82, 1.03) and BSI 30-day mortality from 37.9% to 26.3%; RR, 0.76 (95%CI 0.56, 1.03). Median ICU LOS for ICU survivors increased from 2.3 to 2.6 days. Multimodal AMS sustainably embedded in ICU was associated with reductions in broad-spectrum Gram-negative antibiotic use, overall antibiotic costs and Gram-negative resistance, without adverse clinical impact.
-
Int. J. Antimicrob. Agents · Apr 2018
Observational StudyOutcomes of adjunctive therapy with intrathecal or intraventricular administration of colistin for post-neurosurgical meningitis and ventriculitis due to carbapenem-resistant acinetobacter baumannii.
The efficacy and safety of intrathecal (ITH) or intraventricular (IVT) colistin in addition to intravenous (IV) colistin for meningitis and ventriculitis due to carbapenem-resistant Acinetobacter baumannii (CRAB) is unclear. In this retrospective observational study of 40 patients with post-neurosurgical meningitis and ventriculitis due to CRAB, 33 patients without concomitant infection received appropriate dosage regimens of IV colistin. Of the 33 patients, 17 received additional ITH/IVT colistin and 16 received only IV colistin. ⋯ The initial Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow Coma Scale (GCS) scores were associated with 30-day mortality with odds ratios (95% confidence intervals) of 1.21 (1.08-1.46) and 0.77 (0.44-0.85), respectively. Chemical meningitis from ITH/IVT colistin was mild and resolved spontaneously. Treatment of post-neurosurgical CRAB meningitis and ventriculitis with ITH/IVT colistin as an adjunct to IV colistin was associated with shorter lengths of hospital and ICU stay and a trend to lower mortality, especially among severely ill patients.
-
Int. J. Antimicrob. Agents · Apr 2018
Observational StudyPopulation pharmacokinetics of continuous infusion of piperacillin in critically ill patients.
Dosing recommendations for continuous infusion of piperacillin, a broad-spectrum beta-lactam antibiotic, are mainly guided by outputs from population pharmacokinetic models constructed with intermittent infusion data. However, the probability of target attainment in patients receiving piperacillin by continuous infusion may be overestimated when drug clearance estimates from population pharmacokinetic models based on intermittent infusion data are used, especially when higher doses (e.g. 16 g/24 h or more) are simulated. Therefore, the purpose of this study was to describe the population pharmacokinetics of piperacillin when infused continuously in critically ill patients. ⋯ In critically ill patients with renal clearance higher than 90 mL/min/1.73 m2, a high-dose continuous infusion of 24 g/24 h is insufficient to achieve adequate exposure (pharmacokinetic/pharmacodynamic target of 100% fT>4 x MIC) against susceptible Pseudomonas aerginosa isolates (MIC ≤16 mg/L). These findings suggest that merely increasing the dose of piperacillin, even with continuous infusion, may not always result in adequate piperacillin exposure. This should be confirmed by evaluating piperacillin target attainment rates in critically ill patients exhibiting high renal clearance.
-
Int. J. Antimicrob. Agents · Apr 2018
Clinical experience with ceftazidime/avibactam for treatment of antibiotic-resistant organisms other than Klebsiella pneumoniae.
Ceftazidime/avibactam is a newly approved β-lactam/β-lactamase inhibitor combination with activity against antibiotic-resistant Gram-negative organisms, including many carbapenem-resistant strains. Although this agent may offer a promising treatment option for serious infections with limited alternatives available, clinical experience with ceftazidime/avibactam in treatment of infections caused by multidrug-resistant Gram-negative organisms other than Klebsiella pneumoniae is limited. ⋯ For infections caused by antibiotic-resistant Gram-negative organisms other than K. pneumoniae, clinical and microbiological success rates for patients treated with ceftazidime/avibactam were similar to those that have been reported for K. pneumoniae. Ceftazidime/avibactam appears to be a promising treatment option for infections caused by a variety of resistant Gram-negative organisms when limited alternatives exist.
-
Int. J. Antimicrob. Agents · Apr 2018
Case ReportsGenotypic variations between wild-type and small colony variant of Staphylococcus aureus in prosthetic valve infectious endocarditis: a comparative genomic and transcriptomic analysis.
Staphylococcus aureus small colony variants (SCVs) can cause persistent infections. However, the genomes and transcriptomes of S. aureus SCVs remain poorly understood. A pair of isogenic wild-type and SCV methicillin-resistant S. aureus (MRSA) strains (IE1 and IE2, respectively) were isolated from a patient with prosthetic valve infectious endocarditis. ⋯ Most of the differentially expressed genes were involved in metabolism. Expression levels of several genes involved in the pathways to which plsY, deoC, eap and sstD belonged were changed, associated with the metabolism and virulence of S. aureus. In conclusion, the reduced growth rate and decreased virulence of MRSA SCV strains may be related to mutations in and downregulation of genes associated with metabolism and virulence, especially plsY, deoC, eap and sstD.