International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Dec 2016
Review Meta AnalysisColonisation with extended-spectrum β-lactamase-producing Enterobacteriaceae and risk for infection among patients with solid or haematological malignancy: a systematic review and meta-analysis.
Cancer patients are vulnerable to infections, including those with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), and most of these infections are associated with colonisation of the gastrointestinal tract. The aim of this study was to estimate the prevalence of gastrointestinal colonisation with ESBL-PE cancer populations and to determine the risk for subsequent bloodstream infection (BSI) with these pathogens. PubMed and EMBASE databases were searched from 1 January 1991 to 1 March 2016 to identify studies regarding ESBL-PE colonisation among patients with malignancies. ⋯ We found that, overall, one in five patients with cancer is colonised with ESBL-PE and the incidence can be as high as one in three in Asia. This is important because colonisation was associated with an almost 13 times higher risk for developing BSI with ESBL-PE. Screening measures should be evaluated to identify their clinical benefit in patients with malignancy.
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Int. J. Antimicrob. Agents · Dec 2016
Comparative StudyPropensity score-matched analysis comparing the therapeutic efficacies of cefazolin and extended-spectrum cephalosporins as appropriate empirical therapy in adults with community-onset Escherichia coli, Klebsiella spp. and Proteus mirabilis bacteraemia.
In this study, the therapeutic efficacy of cefazolin was compared with that of extended-spectrum cephalosporins (ESCs) (cefotaxime, ceftriaxone and ceftazidime) as appropriate empirical therapy in adults with community-onset monomicrobial bacteraemia caused by Escherichia coli, Klebsiella spp. or Proteus mirabilis (EKP). Compared with cefazolin-treated patients (n = 135), significantly higher proportions of patients in the ESC treatment group (n = 456) had critical illness at bacteraemia onset (Pitt bacteraemia score ≥4) and fatal co-morbidities (McCabe classification). ⋯ Similarly, no significant differences were observed in the mean of time to defervescence (4.1 days vs. 4.9 days; P = 0.15), late clinical failure rate (18.2% vs. 10.7%; P = 0.10) and 28-day crude mortality rate (0.8% vs. 3.3%; P = 0.37) between the two groups. These data suggest that the efficacy of cefazolin is similar to that of ESCs when used as appropriate empirical antimicrobial treatment for community-onset EKP bacteraemia.
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Int. J. Antimicrob. Agents · Dec 2016
Observational StudyTotal and unbound ceftriaxone pharmacokinetics in critically ill Australian Indigenous patients with severe sepsis.
In the absence of specific data to guide optimal dosing, this study aimed to describe the pharmacokinetics of ceftriaxone in severely septic Australian Indigenous patients and to assess achievement of the pharmacodynamic target of the regimens prescribed. A pharmacokinetic study was conducted in a remote hospital intensive care unit in patients receiving ceftriaxone dosing of 1 g every 12 h (q12h). Serial blood and urine samples were collected over one dosing interval on two consecutive days. ⋯ The unbound fraction of ceftriaxone ranged between 14% and 43%, with a higher unbound fraction present at higher total concentrations. The unbound concentrations at 720 min from the initiation of infusion for the first and second dosing intervals were 7.2 (4.8-10.7) mg/L and 7.8 (4.7-12.1) mg/L respectively, which exceeds the minimum inhibitory concentration of all typical target pathogens. In conclusion, the regimen of ceftriaxone 1 g q12h is adequate for critically ill Australian Indigenous patients with severe sepsis caused by non-resistant pathogens.
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Int. J. Antimicrob. Agents · Nov 2016
Observational StudyOptimising meropenem dosing in critically ill Australian Indigenous patients with severe sepsis.
Currently there are no pharmacokinetic (PK) data to guide antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis. This study aimed to determine whether the population pharmacokinetics of meropenem were different between critically ill Australian Indigenous and critically ill Caucasian patients. Serial plasma and urine samples as well as clinical and demographic data were collected over two dosing intervals from critically ill Australian Indigenous patients. ⋯ Significant differences were observed for meropenem clearance between the Indigenous and Caucasian groups [median 11.0 (range 3.0-14.1) L/h vs. 17.4 (4.3-30.3) L/h, respectively; P <0.01]. Standard dosing regimens (1 g intravenous every 8 h as a 30-min infusion) consistently achieved target exposures at the minimum inhibitory concentration breakpoint in the absence of augmented renal clearance. No significant interethnic differences in meropenem pharmacokinetics between the Indigenous and Caucasian groups were detected and CLCr was found to be the strongest determinant of appropriate dosing regimens.
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Int. J. Antimicrob. Agents · Nov 2016
Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections.
There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for <14 days at Palmetto Health Hospitals in Columbia, SC, from 1 January 2010 through 31 December 2013 and discharged on oral antibiotics were included in this study. ⋯ Risk of treatment failure in the multivariate Cox model was higher in patients receiving antibiotics with moderate [adjusted hazard ratio (aHR) = 5.9, 95% CI 1.6-38.5; P = 0.005] and low bioavailability (aHR = 7.7, 95% CI 1.9-51.5; P = 0.003) compared with those receiving oral antimicrobial agents with high bioavailability. These data demonstrate the effectiveness of oral antibiotics with high bioavailability for definitive therapy of Gram-negative BSI. Risk of treatment failure increases as bioavailability of the oral regimen declines.