Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Jun 2017
ReviewHow Should We Treat HAP/VAP Caused by Carbapenemase-Producing Enterobacteriaceae?
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) represent a common problem in hospital setting worldwide. Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are an emergent problem due to the lack of therapeutic options available, leading to significant increases in morbidity and mortality. ⋯ This review focuses on the current epidemiology of CRE, with a specific focus on HAP/VAP. Moreover, we will suggest a possible strategy for the empiric and targeted treatment of HAP and VAP in which the involvement of CRE is suspected or is confirmed.
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Semin Respir Crit Care Med · Jun 2017
ReviewNew Strategies Targeting Virulence Factors of Staphylococcus aureus and Pseudomonas aeruginosa.
Morbidity, mortality, and economic burden of nosocomial pneumonia caused by Staphylococcus aureus and Pseudomonas aeruginosa remain high in mechanically ventilated and hospitalized patients despite the use of empirical antibiotic therapy or antibiotics against specific classes of pathogens and procedures to reduce nosocomial infections in hospital settings. Newer agents that neutralize or inhibit specific S. aureus or P. aeruginosa virulence factors may eliminate or reduce the risk for developing pneumonia before or during mechanical ventilation and may improve patient outcomes through mechanisms that differ from those of antibiotics. In this article, we review the types, mechanisms of action, potential advantages, and stage of development of antivirulence agents (AVAs) that hold promise as alternative preventive or interventional therapies against S. aureus– and P. aeruginosa–associated nosocomial pneumonias. We also present and discuss challenges to the effective utilization of AVAs separately from or in addition to antibiotics and the design of clinical trials and meaningful study end points.
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Semin Respir Crit Care Med · Jun 2017
ReviewEmergence of Antimicrobial Resistance among Pseudomonas aeruginosa: Implications for Therapy.
Pseudomonas aeruginosa (PA), a nonlactose fermenting gram-negative bacillus, is a common cause of nosocomial infections in critically ill or debilitated patients, particularly ventilator-associated pneumonia (VAP), and infections of bloodstream, urinary tract, intra-abdominal, wounds/skin/soft tissue. PA rarely affects healthy individuals, but may cause serious infections in patients with chronic structural lung disease, comorbidities, advanced age, impaired immune defenses, or with medical devices (e.g., urinary or intravascular catheters, foreign bodies). ⋯ Over the past three decades, antimicrobial resistance among PA has escalated globally, via dissemination of several international multidrug-resistant “epidemic” clones. We review the emergence of antimicrobial resistance to this pathogen, and discuss approaches to therapy (both empirical and definitive).
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Semin Respir Crit Care Med · Jun 2017
ReviewHow Should We Treat Hospital-Acquired and Ventilator-Associated Pneumonia Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae?
Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) due to extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) represent a growing problem. Indeed, ESBL-PE is endemic in many countries, and 5 to 25% of intensive care unit (ICU) patients are ESBL-PE carrier on ICU admission. ESBL-PE HAP/VAP is associated with a higher mortality than HAP/VAP due to susceptible Enterobacteriaceae because the resistance profile decreases the adequacy rate of empiric therapy. ⋯ The alternative β-lactams such as β-lactams/β-lactamases inhibitor combinations could be proposed as a step-down therapy according to the antibiotic susceptibility result. Optimization of pharmacokinetics requires high dosage and continuous or prolonged infusions for β-lactams. When the patient is stabilized, a therapy of duration 7 to 8 days is recommended.
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Semin Respir Crit Care Med · Jun 2017
ReviewShould We Immediately Start Antibiotics in Every Patient with a Clinical Suspicion of HAP/VAP?
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) remain two of the most commonly diagnosed nosocomial infections. Both are responsible for significant morbidity and mortality in hospitalized patients. The development of HAP and VAP is related to bacterial colonization of the oropharynx (and endotracheal tube in VAP) with subsequent microaspiration and development of clinical infection. ⋯ However, when possible, therapy should be directed at a confirmed infection following a positive culture result. Decisions regarding specific empiric regimens should be based on the local prevalence of infectious microorganisms along with their associated antimicrobial susceptibilities. Patients deemed at risk of infection with multidrug-resistant pathogens merit broader spectrum therapy, and immunosuppressed patients should have consideration of antifungal coverage.