Inhaled antibiotics for the treatment of pneumonia.

PURPOSE OF REVIEW: To describe recent developments in trials exploring inhaled antibiotics for treating severe pneumonia. RECENT FINDINGS: Three recent randomized studies investigated the potential role for aerosolized antibiotics for gram-negative pneumonia in ventilated patients. One single center, nonblinded investigation suggested a benefit with inhaled amikacin for resistant gram-negative infections. However, two multicenter, blinded trials found no benefit to adjunctive nebulized amikacin for severe gram-negative pneumonia. SUMMARY: Well done clinical trials do not support the routine use of inhaled amikacin for pneumonia in ventilated patients. There may be a potential role for aerosolized antibiotics when other options are limited.

Corticosteroids and transition to delirium in patients with acute lung injury.

OBJECTIVE: Delirium is common in mechanically ventilated patients in the ICU and associated with short- and long-term morbidity and mortality. The use of systemic corticosteroids is also common in the ICU. Outside the ICU setting, corticosteroids are a recognized risk factor for delirium, but their relationship with delirium in critically ill patients has not been fully evaluated. We hypothesized that systemic corticosteroid administration would be associated with a transition to delirium in mechanically ventilated patients with acute lung injury. DESIGN: Prospective cohort study. SETTING: Thirteen ICUs in four hospitals in Baltimore, MD. PATIENTS: Five hundred twenty mechanically ventilated adult patients with acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Delirium evaluation was performed by trained research staff using the validated Confusion Assessment Method for the ICU screening tool. A total of 330 of the 520 patients (64%) had at least two consecutive ICU days of observation in which delirium was assessable (e.g., patient was noncomatose), with a total of 2,286 days of observation and a median (interquartile range) of 15 (9, 28) observation days per patient. These 330 patients had 99 transitions into delirium from a prior nondelirious, noncomatose state. The probability of transitioning into delirium on any given day was 14%. Using multivariable Markov models with robust variance estimates, the following factors (adjusted odds ratio; 95% CI) were independently associated with transition to delirium: older age (compared to < 40 years old, 40-60 yr [1.81; 1.26-2.62], and ≥ 60 yr [2.52; 1.65-3.87]) and administration of any systemic corticosteroid in the prior 24 hours (1.52; 1.05-2.21). CONCLUSIONS: After adjusting for other risk factors, systemic corticosteroid administration is significantly associated with transitioning to delirium from a nondelirious state. The risk of delirium should be considered when deciding about the use of systemic corticosteroids in critically ill patients with acute lung injury.

Challenges and opportunities in the treatment of ventilator-associated pneumonia.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a distinct clinical entity characterized by an onset after 48 hours of the application of mechanical ventilation (MV). Protocols exist to aid in the prevention of VAP, but this infection carries a devastating impact on patient morbidity and potentially mortality. Areas covered: In this review we present key concepts from existing guidelines to aid clinicians. Challenges remain in defining this disease and, most importantly appropriate empiric antimicrobial treatment is the main determinant of outcome. We highlight that the selection of initial antibiotics is critical, as VAP can by caused by a broad array of drug resistant organisms (DROs), the appropriate duration of treatment for VAP is an evolving concept, but may, in part, be guided by biomarkers, and provide focus on diagnostic challenges, initial therapies and treatment strategies for VAP. Both traditional and novel antimicrobials are presented, including developments in the modes of delivery. Expert commentary: The clinical approach to VAP continues to evolve. Recent evidence regarding the changes in microbiology, diagnostics approaches, and treatment strategies for VAP are important for clinicians to remain informed of to provide optimal patient care.

Bacteremia in Staphylococcus aureus pneumonia: outcomes and epidemiology.

PURPOSE: Staphylococcus aureus represents a major cause of pneumonia in critically ill patients. Although bacteremia may complicate S aureus pneumonia, the epidemiology of and outcomes associated with bacteremia in this syndrome are poorly described. MATERIALS AND METHODS: We retrospectively identified (January 2005-December 2007) all patients admitted to the hospital with S aureus pneumonia necessitating mechanical ventilation. All subjects underwent lower airway and concurrent blood cultures. The prevalence of bacteremia served as a primary end point. We assessed the impact of bacteremia on mortality and length of stay via either logistic regression or a Cox proportional hazard model, respectively. In both models, we controlled for multiple covariates (eg, demographics, severity of illness, comorbidities, and appropriateness of initial antibiotics). We subsequently developed a prediction rule to identify subjects likely to have concurrent bacteremia based on variables assessed at the time of presentation. RESULTS: The cohort included 59 patients (mean ± SD age, 58.0 ± 17.4 years; 55.9% male, 59.3% methicillin resistant, 39.0% crude mortality). Bacteremia complicated nearly 20% of cases. The mortality rate in those with bacteremia was 39.1% vs 8.3% in persons without bacteremia (P = .007). Three variables were independently associated with mortality in S aureus pneumonia: age, need for vasopressors, and concurrent bacteremia. Bacteremia independently conferred a 6-fold increase in the risk for death (adjusted odds ratio, 5.96; 95% confidence interval [CI], 1.08-33.10). Bacteremia also correlated with a longer length of stay. The adjusted hazard ratio for remaining hospitalized if bacteremic was 2.65 (95% CI, 1.14-6.18). For the clinical prediction rule for concurrent bacteremia, we assigned points as follows: 2 points if the patient had received prior antibiotic therapy and 1 point each for acute lung injury and for the need for vasopressors. As the total score increased, the prevalence of bacteremia increased (P < .001). As a screening test for bacteremia in S aureus pneumonia, the scoring system had good predictive value. The area under the receiver operating curve measured 0.83 (95% CI, 0.72-0.94). CONCLUSIONS: Bacteremia often arises in S aureus pneumonia and is associated with both increased morbidity and mortality. Several simple clinical factors to determine clinical features identify patients with S aureus pneumonia likely to have simultaneous bacteremia.

Resistant pathogens in nonnosocomial pneumonia and respiratory failure: is it time to refine the definition of health-care-associated pneumonia?

BACKGROUND: The concept of health-care-associated pneumonia (HCAP) exists to identify patients infected with highly resistant pathogens. It is unclear how precise this concept is and how well it performs as a screening tool for resistance. METHODS: We retrospectively identified patients presenting to the hospital with pneumonia complicated by respiratory failure. We examined the microbiology of these infections based on pneumonia type and determined the sensitivity and specificity of HCAP as a screen for resistance. Through logistic regression and modeling, we created a scoring tool for determining who may be infected with resistant pathogens. RESULTS: The cohort included 190 subjects (37% with ARDS) and we noted resistant pathogens in 33%. Resistance was more common in HCAP (78% vs 44%, P = .001). HCAP alone performed poorly as a screening test (sensitivity and specificity 78.3% and 56.2%, respectively). Variables independently associated with a resistant organism included immunosuppression (adjusted odds ratio [AOR] 4.85, P < .001), long-term care admission (AOR 2.36, P = .029), and prior antibiotics (AOR 2.12, P = .099). A decision rule based only on these factors performed moderately well at identifying resistant infections. The presence of HCAP itself, based on meeting defined criteria, was not independently associated with resistance using logistic regression to control for covariates. CONCLUSIONS: HCAP is common in patients presenting to the hospital with pneumonia leading to respiratory failure. The HCAP concept does not correlate well with the presence of infection due to a resistant pathogen. A simpler clinical decision rule based on select HCAP criteria performs as well as the HCAP concept for potentially guiding antibiotic decision making.