Seminars in respiratory and critical care medicine
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Carbapenemase-producing Enterobacteriaceae (CPE) were almost nonexistent up to the 1990s, but are today encountered routinely in hospitals and other healthcare facilities in many countries including the United States. KPC-producing Klebsiella pneumoniae was the first to emerge and spread globally and is endemic in the United States, Israel, Greece, and Italy. Recently, NDM-producing Enterobacteriaceae and OXA-48-producing K. pneumoniae appear to be disseminating from South Asia and Northern Africa, respectively. ⋯ To obtain the maximal benefit from the limited options available, dosing of antimicrobial agents should be optimized based on pharmacokinetic data, especially for colistin and carbapenems. In addition, multiple observational studies have associated combination antimicrobial therapy with lower mortality compared with monotherapy for these infections. The outcomes appear to be especially favorable when patients are treated with a carbapenem and a second agent such as colistin, tigecycline, and gentamicin, but the best approach is yet to be defined.
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Semin Respir Crit Care Med · Feb 2015
ReviewStenotrophomonas, achromobacter, and nonmelioid burkholderia species: antimicrobial resistance and therapeutic strategies.
Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nonmelioid Burkholderia species, namely, Burkholderia cepacia complex, collectively are a group of troublesome nonfermenters. Although not inherently virulent organisms, these environmental Gram negatives can complicate treatment in those who are immunocompromised, critically ill in the intensive care unit and those patients with suppurative lung disease, such as cystic fibrosis. ⋯ Despite trimethoprim-sulfamethoxazole often being the mainstay of treatment, resistance is widely encountered, and alternative regimens, including combination therapy, are often used. This review will highlight the important aspects and unique challenges that these three nonfermenters pose, and, in the absence of clinical outcome data, our therapeutic recommendations will be based on reported antimicrobial susceptibility and pharmacokinetic/pharmacodynamic profiles.
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Semin Respir Crit Care Med · Feb 2015
ReviewTreatment of Methicillin-Resistant Staphylococcus aureus: Vancomycin and Beyond.
There has been a welcome increase in the number of agents available for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin remains an acceptable treatment option, with moves toward individualized dosing to a pharmacokinetic/pharmacodynamic (PK/PD) target. Numerous practicalities, however, would need to be resolved before implementation. ⋯ Whether these strengths and features are agent or class specific are unclear but will likely be answered with the marketing of tedizolid. There are insufficient data to recommend either quinupristin/dalfopristin or tigecycline, as first line in the treatment of severe MRSA infections. These agents however remain options in patients with no other alternatives.
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Semin Respir Crit Care Med · Feb 2015
ReviewColistin: How should It Be Dosed for the Critically Ill?
Colistin, an "old" polymyxin antibiotic, is increasingly being used as last-line treatment against infections caused by multidrug-resistant gram-negative bacteria. It is administered in patients, parenterally or by inhalation, as its inactive prodrug colistin methanesulfonate (CMS). Scientifically based recommendations on how to optimally dose colistin in critically ill patients have become available over the last decade and are extremely important as colistin has a narrow therapeutic window. ⋯ Inhalation of CMS achieves considerably higher colistin concentrations in lung fluids than is possible with intravenous administration, with negligible plasma exposure. Similarly, for central nervous system infections, dosing CMS directly into the cerebrospinal fluid generates significantly higher colistin concentrations at the infection site compared with what can be achieved with systemic administration. While questions remain to be addressed via ongoing research, this article reviews the significant advances that have been made toward optimizing the clinical use of colistin.
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Semin Respir Crit Care Med · Feb 2015
ReviewAcinetobacter baumannii: Evolution of Antimicrobial Resistance-Treatment Options.
The first decade of the 20th century witnessed a surge in the incidence of infections due to several highly antimicrobial-resistant bacteria in hospitals worldwide. Acinetobacter baumannii is one such organism that turned from an occasional respiratory pathogen into a major nosocomial pathogen. An increasing number of A. baumannii genome sequences have broadened our understanding of the genetic makeup of these bacteria and highlighted the extent of horizontal transfer of DNA. ⋯ Treatment of carbapenem-resistant A. baumannii infection therefore involves the use of combinations of last resort agents such as colistin and tigecycline, but the efficacy and safety of these approaches are yet to be defined. Antimicrobial-resistant A. baumannii has high potential to spread among ill patients in intensive care units. Early recognition and timely implementation of appropriate infection control measures is crucial in preventing outbreaks.