Expert review of anti-infective therapy
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Expert Rev Anti Infect Ther · Sep 2017
ReviewTreatment of Pneumocystis jirovecii pneumonia in HIV-infected patients: a review.
Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART. ⋯ Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent for Pneumocystis pneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles for Pneumocystis pneumonia is warranted.
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Expert Rev Anti Infect Ther · Sep 2017
ReviewCandida auris: a worrisome, globally emerging pathogen.
Candida auris is a recently discovered, rapidly emerging fungal pathogen. Infections due to C. auris are hospital-acquired, multidrug resistant and associated with high mortality. Areas covered: This review highlights epidemiology, pathogenesis, microbiological characteristics, clinical presentation, diagnostic challenges and treatment options of C. auris infections. ⋯ Early diagnosis of C. auris is essential for better outcomes and the implementation of infection prevention measures. Lack of widespread awareness, absence of general availability of diagnostic testing methods, and limited options for treatment of C. auris infections make it a difficult-to-treat pathogen. Further studies are needed for better understanding of this emerging pathogen.
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Expert Rev Anti Infect Ther · Jul 2017
ReviewExtended infusion of beta-lactam antibiotics: optimizing therapy in critically-ill patients in the era of antimicrobial resistance.
Beta-lactams are at the cornerstone of therapy in critical care settings, but their clinical efficacy is challenged by the rise in bacterial resistance. Infections with multi-drug resistant organisms are frequent in intensive care units, posing significant therapeutic challenges. The problem is compounded by a dearth in the development of new antibiotics. ⋯ Several reports show promising results. Expert commentary: Reviewing the currently available evidence, we conclude that EI/CI is probably beneficial in the treatment of critically-ill patients in whom an organism has been identified, particularly those with respiratory infections. Further studies are needed to evaluate the efficacy of EI/CI in the management of infections with resistant organisms.
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Expert Rev Anti Infect Ther · Jul 2017
Optimizing β-lactams treatment in critically-ill patients using pharmacokinetics/pharmacodynamics targets: are first conventional doses effective?
The pharmacokinetic/pharmacodynamic index determining β-lactam activity is the percentage of the dosing interval (%T) during which their free serum concentration remains above a critical threshold over the minimum inhibitory concentration (MIC). Regrettably, neither the value of %T nor that of the threshold are clearly defined for critically-ill patients. Areas covered: We review and assess the targets proposed for β-lactams in critical illness by screening the literature since 1997. ⋯ Simulation studies, however, show that this target will not be reached at first dose for the majority of critically-ill patients if using the most commonly recommended doses. Expert commentary: Considering that critically-ill patients are highly vulnerable and likely to experience antibiotic underexposure, and because effective initial treatment is a key determinant of clinical outcome, we support the use of a target of 100%T > 4xMIC, which could not only maximize efficacy but also minimize emergence of resistance. Clinical and microbiological studies are needed to test for the feasibility and effectiveness of reaching such a demanding target.