Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Apr 2022
New Insights in the Pathophysiology of Hospital- and Ventilator-Acquired Pneumonia: A Complex Interplay between Dysbiosis and Critical-Illness-Related Immunosuppression.
Both hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) have long been considered as diseases resulting from the invasion by pathogens of a previously sterile lung environment. Based on this historical understanding of their pathophysiology, our approaches for the prevention and treatment have significantly improved the outcomes of patients, but treatment failures remain frequent. Recent studies have suggested that the all-antimicrobial therapy-based treatment of pneumonia has reached a glass ceiling. ⋯ We proposed that HAP and VAP should be considered as a state of dysbiosis, defined as the emergence of a dominant pathogen thriving at the same time from the catastrophic collapse of the fragile ecosystem of the lower respiratory tract and from the development of critical-illness-related immunosuppression. This multidimensional approach to the pathophysiology of HAP and VAP holds the potential to achieve future successes in research and critical care. Microbiome and mucosal immunity can indeed be manipulated and used as adjunctive therapies or targets to prevent or treat pneumonia.
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Semin Respir Crit Care Med · Apr 2022
Risk Factors and Algorithms for the Empirical Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia.
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) continue to be major concerns for morbidity and mortality, especially in patients treated in the intensive care unit. With the rise in multidrug-resistant organisms, HAP and VAP treatment is challenged by the need for early appropriate treatment, with broad-spectrum agents, while still being aware of the principles of antibiotic stewardship. The two major society guidelines proposed a series of risk factors in their most recent guidelines to help identify patients who can most benefit from narrow- or broad-spectrum initial empiric antibiotic therapy. The guidelines reveal differences in the proposed risk factors and treatment approaches, as well as major similarities.
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Semin Respir Crit Care Med · Apr 2022
Pharmacokinetic/Pharmacodynamic Optimization of Hospital-Acquired and Ventilator-Associated Pneumonia: Challenges and Strategies.
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated with high mortality rates worldwide. Thus, the administration of antibiotic therapy with appropriate dosing regimen is critical. An efficient antibiotic is needed to maintain an adequate concentration at the infection site, for a sufficient period of time, to achieve the best therapeutic outcome. ⋯ Another major hurdle faced in optimizing treatment for HAP/VAP is the reduction of the in vitro potency. Therapeutic drug monitoring (TDM), if available, may allow health care providers to personalize treatment to maximize efficacy of the drug exposures while minimizing toxicity. TDM can be of significant importance in populations whom PK are less defined and for resistant infections to achieve the best therapeutic outcome.
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Nosocomial pneumonia is associated with worsened prognosis when diagnosed in intensive care unit (ICU), ranging from 12 to 48% mortality. The incidence rate of ventilation-acquired pneumonia tends to decrease below 15/1,000 intubation-day. Still, international guidelines are heterogeneous about diagnostic criteria because of inaccuracy of available methods. ⋯ The development of molecular diagnostic tools may improve the adequacy of antimicrobial therapies of ventilated patients with pneumonia, but we need to further assess its impact in non-ventilated pneumonia. In this review we introduce distinction between hospital-acquired pneumonia according to the localization in the hospital and the oxygenation/ventilation mode. A clarification of definition is the first step to develop more accurate diagnostic strategies and to improve the patients' prognosis.
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Semin Respir Crit Care Med · Apr 2022
ReviewNew Antibiotics for Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia.
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) represent one of the most common hospital-acquired infections, carrying a significant morbidity and risk of mortality. Increasing antibiotic resistance among the common bacterial pathogens associated with HAP and VAP, especially Enterobacterales and nonfermenting gram-negative bacteria, has made the choice of empiric treatment of these infections increasingly challenging. ⋯ The approved antibiotics include ceftobiprole, ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and cefiderocol. Their major advantages include their high activity against multidrug-resistant gram-negative pathogens.