Seminars in respiratory and critical care medicine
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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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Semin Respir Crit Care Med · Apr 2022
Invasive Pulmonary Aspergillosis in Hospital and Ventilator-Associated Pneumonias.
Pneumonia is the commonest nosocomial infection complicating hospital stay, with both non-ventilated hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) occurring frequently amongst patients in intensive care. Aspergillus is an increasingly recognized pathogen amongst patients with HAP and VAP, and is associated with significantly increased mortality if left untreated. Invasive pulmonary aspergillosis (IPA) was originally identified in patients who had been profoundly immunosuppressed, however, this disease can also occur in patients with relative immunosuppression such as critically ill patients in intensive care unit (ICU). ⋯ Amphotericin has excellent antimold coverage, but a less advantageous side effect profile. Echinocandins are less effective against IPA, but may play a role in rescue therapy, or as an adjuvant to triazole therapy. A high index of suspicion for IPA should be maintained when investigating patients with HAP or VAP, especially when they have specific risk factors or are not responding to appropriate empiric antibacterial therapy.
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Nosocomial pneumonia, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), are the most common nosocomial infections occurring in critically ill patients requiring intensive care. However, challenges exist in making a timely and accurate diagnosis of HAP and VAP. Under diagnosis of HAP and VAP can result in greater mortality risk, especially if accompanied by delays in the administration of appropriate antimicrobial treatment. ⋯ Optimal diagnosis and management of HAP and VAP require a systematic approach that combines clinical and radiographic assessments along with proper microbiologic techniques. The use of more invasive sampling methods (bronchoalveolar lavage and protected specimen brush) may enhance specimen collection resulting in more specific diagnoses to limit unnecessary antibiotic exposure. Molecular techniques, currently in use and investigational technique, may improve the diagnosis of HAP and VAP by allowing more rapid identification of offending pathogens, if present, thus increasing both appropriate antibiotic treatment and avoiding unnecessary drug exposure.
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Semin Respir Crit Care Med · Apr 2022
Defining Clinical and Microbiological Nonresponse in Ventilator-Associated Pneumonia.
Ventilator-associated pneumonia (VAP) is a severe complication of mechanical ventilation, with mortality reduced most effectively by adequate early antibiotic treatment. The clinical and microbiologic response can be assessed easily from 72 hours after starting antibiotic treatment. Evidence of nonresponse is based on several factors: (1) lack of clinical improvement, (2) radiographic progression, (3) an impaired Sequential Organ Failure Assessment (SOFA) score, (4) no improvement by days 3 to 5 on the Clinical Pulmonary Infection Score (CPIS), (5) no decreased in biomarkers on day 3, and (6) isolation of a new pathogen on day 3. ⋯ Physicians must evaluate whether treatments are adequate in terms of sensitivity, dose, and route. Pharmacokinetically and pharmacodynamically optimized doses are recommended in these patients. Clinical stabilization of comorbidities or underlying conditions may be of benefit.