Use of Severity Scoring and Stratification Factors in Clinical Trials of Hospital‐Acquired and Ventilator‐Associated Pneumonia

Abstract

Clinical studies of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) enroll patients with a very wide spectrum of disease, in part, related to the patient and/or host, the causative pathogen, and the severity of the pulmonary disease, severity of illness, and other comorbidities. Studies have identified the presence of some baseline variables (eg, Acute Physiologic Assessment and Chronic Health Evaluation II score <or= 20 or absence of comorbidities) as independent predictors of survival. Incorporation of severity scoring and risk adjustment in clinical trials of HAP and VAP may be a significant advancement because it has been noted that all-cause mortality varies widely on the basis of a number of these factors. In this article, we review the use of severity scoring and risk stratification factors, including time of onset, severity of disease, scoring systems, underlying disease and comorbidities, and effects of prior antibiotic therapy (including impact on treatment effect) in clinical trials of HAP and/or VAP.

TGF-β Blood Levels Distinguish Between Influenza A (H1N1)pdm09 Virus Sepsis and Sepsis due to Other Forms of Community-Acquired Pneumonia

“…This study compared their usefulness in evaluating patients presenting to the authors' hospital with clinical manifestations suggestive of influenza infection during the influenza A (H1N1)pdm09 pandemic. Three of the most common clinical scores-CURB-65, APACHE II, and SOFA-were evaluated, all of which have been used to evaluate the severity of viral and bacterial CAP (15,19,31). Recently, studies demonstrated that CURB-65 is not a good predictor of the severity of pneumonia caused by influenza A (H1N1)pdm09 (29,36).…”

Tracheostomy: Epidemiology, Indications, Timing, Technique, and OutcomesDiscussion

“…The diagnostic accuracy of CPIS is limited in surgical, trauma, and burn patients, as CPIS was unable to differentiate VAP from systemic inflammatory response syndrome. 54 Furthermore, the utility of the modified CPIS to diagnose VAP was assessed in 740 subjects enrolled in a multi-center randomized trial, and no CPIS threshold was clinically useful (receiver operating characteristic area under the curve 0.47, 95% CI 0.42-0.53). 55 The authors concluded that early tracheostomy (performed after 6 -8 d of endotracheal intubation) did not result in significant reduction in the incidence of VAP compared with late tracheostomy (performed after 13-15 d of endotracheal intubation) and was associated with an adverse event related to the tracheostomy procedure in more than one third of subjects.…”

Considerations Unique to Pediatrics for Clinical Trial Design in Hospital‐Acquired Pneumonia and Ventilator‐Associated Pneumonia

“…For adults, the Clinical Pulmonary Infection Score and similar scoring systems have been used to describe severity of infection and prognosis [21]. Such scoring systems have been used to describe the natural history of disease and have the potential to assess the benefit of investigational therapy.…”