International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Oct 2016
Observational StudyVariability of piperacillin concentrations in relation to tazobactam concentrations in critically ill patients.
Therapeutic drug monitoring for critically ill patients receiving piperacillin/tazobactam is described as a useful tool. However, the minimum inhibitory concentration of piperacillin depends on a sufficiently high concentration of tazobactam in case of β-lactamase-producing strains. Therefore, the relationship between piperacillin and tazobactam concentrations was assessed in a heterogeneous group of critically ill patients. ⋯ A 70 mg/L threshold for total piperacillin trough levels would be necessary to ensure that tazobactam concentrations are >5.7 mg/L. Because of the observed variability of piperacillin/tazobactam quotients, defining the total piperacillin target range ≥70 mg/L might be useful to ensure that tazobactam concentrations do not fall below 5.7 mg/L. Further studies are necessary to confirm that the used therapeutic ranges are associated with optimal outcomes in critically ill patients.
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Int. J. Antimicrob. Agents · Aug 2016
Pharmacokinetics and pharmacodynamics of meropenem in children with severe infection.
This study aimed to describe the pharmacokinetic (PK) characteristics of meropenem in children with severe infections and to assess the pharmacokinetic/pharmacodynamic (PK/PD) profiles of various meropenem dosage regimens in these patients. Fourteen children with severe infections received intravenous (i.v.) bolus doses of meropenem (20 mg/kg/dose) every 8 h (q8h). Serum samples were obtained before and serially after the second dose of meropenem, and a population PK analysis was performed. ⋯ Using a 3-h infusion of a 20 mg/kg/dose, the PTA was 0.999 and 0.765 for organisms with MICs of 4 mg/L and 8 mg/L, respectively. Meropenem given as i.v. bolus doses of 20 mg/kg/dose q8h appeared to be inadequate for PK/PD target attainment for organisms with an MIC of 1 mg/L. The simulations showed that meropenem administration via a 3-h infusion using the same dose improved the PTA.
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Int. J. Antimicrob. Agents · Jun 2016
Should β-lactam antibiotics be administered by continuous infusion in critically ill patients? A survey of Australia and New Zealand intensive care unit doctors and pharmacists.
Although there is a biological precedent for administration of β-lactam antibiotics by continuous or extended infusion, there is no definitive evidence of a survival benefit compared with intermittent administration. The aim of this study was to explore clinician uncertainty with regard to the administration of β-lactam antibiotics by continuous infusion. Doctors and pharmacists in Australian and New Zealand intensive care units (ICUs) were surveyed to investigate current β-lactam antibiotic administration practices as well as the degree of uncertainty regarding the benefit of continuous infusion of two commonly used broad-spectrum β-lactams, namely meropenem and piperacillin/tazobactam (TZP). ⋯ Both groups reported uncertainty as to whether administration by continuous infusion resulted in better patient outcomes (65.9% and 74.6%, respectively; P = 0.85). Overall, 91.0% of respondents were prepared to enrol eligible patients into a definitive randomised controlled trial on β-lactam antibiotic administration. In conclusion, there is equipoise among clinicians working in Australian and New Zealand ICUs as to whether administration by continuous infusion offers a survival benefit in critically ill patients.
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Int. J. Antimicrob. Agents · Apr 2016
ReviewEffect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: A structured review.
The increased prevalence of obesity presents challenges for clinicians aiming to provide optimised antimicrobial dosing in the intensive care unit. Obesity is likely to exacerbate the alterations to antimicrobial pharmacokinetics when the chronic diseases associated with obesity exist with the acute pathophysiological changes associated with critical illness. The purpose of this paper is to review the potential pharmacokinetic (PK) changes of antimicrobials in obese critically ill patients and the implications for appropriate dosing. ⋯ For antifungals, little data exist in obese critically ill patients; during fluconazole therapy, an obese patient had a lower V(d) and higher CL than non-obese comparators. Overall, most studies suggested that standard dosage regimens of most commonly used antimicrobials are sufficient to achieve PD targets. However, it is likely that larger doses would be required for pathogens with higher minimum inhibitory concentrations.
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Int. J. Antimicrob. Agents · Apr 2016
Observational StudyEmpirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia: Impact of revised CLSI breakpoints.
Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. ⋯ Of note, isolates with a CTX MIC≤8mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ=1.00; P=0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC≤1mg/L.