Nathaniel J Rhodes1,2, Caroline E Cruce3,4, J Nicholas O'Donnell5, Richard G Wunderink6, Alan R Hauser7,8. 1. Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, 555 31st St., Downers Grove, IL, 60515, USA. nrhode@midwestern.edu. 2. Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA. nrhode@midwestern.edu. 3. Department of Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, 555 31st St., Downers Grove, IL, 60515, USA. 4. Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA. 5. Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY, USA. 6. Department of Internal Medicine, Division of Pulmonary Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 7. Department of Internal Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 8. Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Abstract
PURPOSE OF REVIEW: Hospital-acquired and ventilator-associated pneumonia (VAP) are frequent causes of infection among critically ill patients. VAP is the most common hospital-acquired bacterial infection among mechanically ventilated patients. Unfortunately, many of the nosocomial Gram-negative bacteria that cause VAP are increasingly difficult to treat. Additionally, the evolution and dissemination of multi- and pan-drug resistant strains leave clinicians with few treatment options. VAP patients represent a dynamic population at risk for antibiotic failure and under-dosing due to altered antibiotic pharmacokinetic parameters. Since few antibiotic agents have been approved within the last 15 years, and no new agents specifically targeting VAP have been approved to date, it is anticipated that this problem will worsen. Given the public health crisis posed by resistant Gram-negative bacteria, it is essential to establish a firm understanding of the current epidemiology of VAP, the changing trends in Gram-negative resistance in VAP, and the current issues in drug development for Gram-negative bacteria that cause VAP. RECENT FINDINGS: Rapid identification technologies and phenotypic methods, new therapeutic strategies, and novel treatment paradigms have evolved in an attempt to improve treatment outcomes for VAP; however, clinical data supporting alternative treatment strategies and adjunctive therapies remain sparse. Importantly, new classes of antimicrobials, novel virulence factor inhibitors, and beta-lactam/beta-lactamase inhibitor combinations are currently in development. Conscientious stewardship of new and emerging therapeutic agents will be needed to ensure they remain effective well into the future.
PURPOSE OF REVIEW: Hospital-acquired and ventilator-associated pneumonia (VAP) are frequent causes of infection among critically ill patients. VAP is the most common hospital-acquired bacterial infection among mechanically ventilated patients. Unfortunately, many of the nosocomial Gram-negative bacteria that cause VAP are increasingly difficult to treat. Additionally, the evolution and dissemination of multi- and pan-drug resistant strains leave clinicians with few treatment options. VAP patients represent a dynamic population at risk for antibiotic failure and under-dosing due to altered antibiotic pharmacokinetic parameters. Since few antibiotic agents have been approved within the last 15 years, and no new agents specifically targeting VAP have been approved to date, it is anticipated that this problem will worsen. Given the public health crisis posed by resistant Gram-negative bacteria, it is essential to establish a firm understanding of the current epidemiology of VAP, the changing trends in Gram-negative resistance in VAP, and the current issues in drug development for Gram-negative bacteria that cause VAP. RECENT FINDINGS: Rapid identification technologies and phenotypic methods, new therapeutic strategies, and novel treatment paradigms have evolved in an attempt to improve treatment outcomes for VAP; however, clinical data supporting alternative treatment strategies and adjunctive therapies remain sparse. Importantly, new classes of antimicrobials, novel virulence factor inhibitors, and beta-lactam/beta-lactamase inhibitor combinations are currently in development. Conscientious stewardship of new and emerging therapeutic agents will be needed to ensure they remain effective well into the future.
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