International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Oct 2013
ReviewWhat is the relevance of fosfomycin pharmacokinetics in the treatment of serious infections in critically ill patients? A systematic review.
As treatment options for critically ill patients with multidrug-resistant bacteria diminish, older antibiotics such as fosfomycin are being investigated for use as last-resort drugs. Fosfomycin is a broad-spectrum antibiotic with activity both against Gram-positive and Gram-negative bacteria. The aim of this review was to examine the effectiveness of current fosfomycin dosing strategies in critically ill patients. ⋯ If altered as seen in acute kidney injury, toxic blood concentrations may develop. Fosfomycin has a volume of distribution comparable with β-lactams and aminoglycosides and may therefore increase in critically ill patients. Altered dosing strategies may be required to optimise dosing given these PK changes, although the current paucity of data on fosfomycin in critically ill patients prevents accurate dosing guidance being recommended at this time.
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Int. J. Antimicrob. Agents · Oct 2013
ReviewCandidaemia in the non-neutropenic patient: a critique of the guidelines.
Several guidelines have been published on the management of candidaemia. These guidelines vary in their recommendations, and the lack of consistency between the guidelines has implications for the management of candidaemia. ⋯ We found that too much emphasis has been placed on themes such as predicting the infecting species (and therefore fluconazole susceptibility) or the need for investigations such as echocardiography. We also stress that guidelines fail to provide adequate information (due to lack of evidence) on the most relevant issues that clinicians face when managing candidaemia, such as the place for fluconazole in the treatment of C. glabrata, the clinical relevance of dose-dependent susceptibility to fluconazole, and the timing of step-down therapy.
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Int. J. Antimicrob. Agents · Jun 2013
ReviewTreatment of bacteraemia: meticillin-resistant Staphylococcus aureus (MRSA) to vancomycin-resistant S. aureus (VRSA).
Around the world, Staphylococcus aureus remains a dominant cause of bacteraemia. Whilst meticillin resistance remains the major phenotype of concern, various levels of reduced glycopeptide susceptibility are emerging with increasing frequency. The most common MRSA phenotypes now have raised vancomycin MICs within the susceptible range (MICs of 1-2mg/L). ⋯ If a patient is risk-assessed or screen-positive for MRSA, and infection is not serious, then vancomycin or teicoplanin is appropriate empirical therapy, providing loading doses are given to achieve therapeutic concentrations immediately (trough 15 mg/L). For life-threatening infections, the glycopeptides are inadequate unless the isolate is likely to be fully susceptible (Etest<1.5mg/L). If not, daptomycin (8-10mg/L) can be used as monotherapy but the MIC should be measured as soon as possible.
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Int. J. Antimicrob. Agents · Jun 2013
ReviewIntraventricular and intrathecal colistin as the last therapeutic resort for the treatment of multidrug-resistant and extensively drug-resistant Acinetobacter baumannii ventriculitis and meningitis: a literature review.
Acinetobacter baumannii ventriculitis/meningitis due to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has become a clinical entity of considerable importance in recent years. A review of the available literature regarding intraventricular (IVT) or intrathecal (ITH) administration of colistin in MDR and XDR A. baumannii ventriculitis/meningitis was conducted and a total of 83 episodes in 81 patients were identified (71 cases in adults and 10 in children and neonates). Colistin was administered via the IVT and ITH route in 52 and 22 cases, respectively, whilst in 7 cases the exact route was not identified. ⋯ The median duration of treatment of IVT/ITH polymyxin E was 18.5 days, whilst the median time to achieve sterilisation of cerebrospinal fluid was 4 days. The rate of successful outcome was 89%, and toxicity related to treatment mainly manifested as reversible chemical ventriculitis/meningitis was reported in nine cases (11%). Nowadays, IVT and ITH colistin represents the last resort treatment of MDR and XDR A. baumannii ventriculitis/meningitis, offering a unique, rather safe and successful mode of therapy.
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The failure of the PROWESS-SHOCK study of recombinant human activated protein C (drotrecogin alfa) has generated much scepticism about the future of immunomodulatory interventions in sepsis. This review presents a summary of the few remaining promising strategies for immunointervention. ⋯ This approach comprises: septic shock and multiple organ dysfunction syndrome arising in the field of ventilator-associated pneumonia as an indication for intravenous clarithromycin; abdominal severe sepsis/shock for PMX-B haemoperfusion; sepsis and acute coagulopathy for rTM; and early septic shock for IgMA. However, specific diagnostic tools should be developed to make this personalised approach more robust.