Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Feb 2015
ReviewOptimizing antimicrobial therapy of sepsis and septic shock: focus on antibiotic combination therapy.
There has been little improvement in septic shock mortality in the past 70 years, despite ever more broad-spectrum and potent antimicrobials. In the past, resuscitative elements have been the primary area of clinical septic shock management and research. The question of the optimal use of antimicrobial therapy was relatively ignored in recent decades. ⋯ Several meta-analyses have failed to demonstrate improvement of outcome with combination therapy in immunocompetent patients with sepsis and/or gram-negative bacteremia. These meta-analyses did not undertake subgroup analyses of the septic shock population. This article reviews the existing evidence supporting combination therapy for severe infections, sepsis, and septic shock.
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Semin Respir Crit Care Med · Feb 2015
ReviewApplying pharmacokinetic/pharmacodynamic principles in critically ill patients: optimizing efficacy and reducing resistance development.
The recent surge in multidrug-resistant pathogens combined with the diminishing antibiotic pipeline has created a growing need to optimize the use of our existing antibiotic armamentarium, particularly in the management of intensive care unit (ICU) patients. Optimal and timely pharmacokinetic/pharmacodynamic (PK/PD) target attainment has been associated with an increased likelihood of clinical and microbiological success in critically ill patients. ⋯ This article summarizes the relevance of PK/PD characteristics of different antibiotic classes on the development of antibiotic resistance. On the basis of the available data, we propose dosing recommendations that can be adopted in the clinical setting, to maximize therapeutic success and limit the emergence of resistance in the ICU.
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Semin Respir Crit Care Med · Feb 2015
ReviewCombination Antibiotic Treatment of Serious Methicillin-Resistant Staphylococcus aureus Infections.
Outcomes from methicillin-resistant Staphylococcus aureus (MRSA) infections are relatively poor, at least in part due to the limitations of vancomycin (the current standard treatment for MRSA). Combination antibiotic treatment for MRSA infections is an attractive alternative as it could address most of vancomycin's shortcomings, including poor tissue penetration, slow bacterial killing, and emerging resistance in some strains of MRSA. However, the theoretical promise of combination therapy for MRSA infections has not been borne out in most in vitro and animal studies. ⋯ Although MRSA is by definition inherently resistant to nearly all β-lactam antibiotics, this class of drugs has consistently shown evidence of synergy with either daptomycin or vancomycin in over 25 separate in vitro studies, and a limited number of animal and human observational studies. However, there are currently insufficient data to recommend β-lactam combination therapy in routine clinical use. Results of current and planned randomized controlled trials of this strategy are awaited.
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Semin Respir Crit Care Med · Feb 2015
ReviewPseudomonas aeruginosa: Evolution of Antimicrobial Resistance and Implications for Therapy.
Pseudomonas aeruginosa is a formidable pathogen in the infection arena. It is able to easily adapt to the environment which it inhabits and can also colonize and invade the human host to cause serious infections. In 2011, it was responsible for 7.1% of all health care-associated infection in the United States. ⋯ With this has come reduced antibiotic treatment options. Consideration of antibiotic infusions, combination therapy, and inhalational therapy has occurred in an attempt to gain the upper ground. Gram-negative resistance has appropriately been described as a global emergency.