Nasia Safdar

Background: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in critically ill patients. The clinical and economic consequences of VAP are unclear, with a broad range of values reported in the literature Objective: To perform a systematic review to determine the incidence of VAP and its attributable mortality rate, length of stay, and costs. Data Source: Computerized PUBMED and MEDLINE search supplemented by manual searches for relevant articles, limited to articles published after 1990. Study Selection: English-language observational studies and randomized trials that provided data on the incidence of VAP were included. Matched cohort studies were included for calculation of attributable mortality rate and length of stay. Data Extraction: Data were extracted on patient population, diagnostic criteria for VAP, incidence, outcome, type of intensive care unit, and study design. Data Synthesis: The cumulative incidence of VAP was calculated by combining the results of several studies using standard formulas for combining proportions, in which the weighted average and variance are calculated. Results from studies comparing intensive care unit and hospital mortality due to VAP, additional length of stay, and additional days of mechanical ventilation were pooled using a random effects model, with assessment of heterogeneity. Results: Our findings indicate a) between 10% and 20% of patients receiving >48 hrs of mechanical ventilation will develop VAP; b) critically ill patients who develop VAP appear to be twice as likely to die compared with similar patients without VAP (pooled odds ratio, 2.03; 95% confidence interval, 1.16–3.56); c) patients with VAP have significantly longer intensive care unit lengths of stay (mean = 6.10 days; 95% confidence interval, 5.32–6.87 days); and d) patients who develop VAP incur ≥$10,019 in additional hospital costs. Conclusions: Ventilator-associated pneumonia occurs in a considerable proportion of patients undergoing mechanical ventilation and is associated with substantial morbidity, a two-fold mortality rate, and excess cost. Given these findings, strategies that effectively prevent VAP are urgently needed. LEARNING OBJECTIVES On completion of this article, the reader should be able to: Define the incidence of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Explain the economic consequences of VAP. Use this information in a clinical setting. All authors have disclosed that they have no financial relationships or interests in any commercial companies pertaining to this educational activity. Wolters Kluwer Health has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit.

BACKGROUND: A double-sandwich enzyme-linked immunosorbent galactomannan assay has been approved for surveillance for invasive aspergillosis in immunocompromised patients. We undertook a meta-analysis to assess the accuracy of a galactomannan assay for diagnosing invasive aspergillosis. METHODS: Studies of the galactomannan assay that used the European Organization for Research and Treatment of Cancer or similar criteria as a reference standard and provided data to calculate sensitivity and specificity were included. Pooled sensitivity and specificity and summary measures of accuracy, Q* (the upper left-most point on the summary receiver-operating characteristic curve), mean D (a log odds ratio), and Youden index were calculated. Subgroup analyses were performed to explore heterogeneity. RESULTS: Twenty-seven studies from 1966 to 28 February 2005 were included. Overall, the galactomannan assay had a sensitivity of 0.71 (95% confidence interval [CI], 0.68-0.74) and specificity of 0.89 (95% CI, 0.88-0.90) for proven cases of invasive aspergillosis. The Youden index, mean D, and Q* were 0.54 (95% CI, 0.41-0.65), 2.74 (95% CI, 21.12-3.36), and 0.80 (95% CI, 0.74-0.86), respectively, indicating moderate accuracy. Subgroup analyses showed that the performance of the test differed by patient population and type of reference standard used. Significant heterogeneity was present. CONCLUSIONS: The galactomannan assay has moderate accuracy for diagnosis of invasive aspergillosis in immunocompromised patients. The test is more useful in patients who have hematological malignancy or who have undergone hematopoietic cell transplantation than in solid-organ transplant recipients. Further studies with attention to the impact of antifungal therapy, rigorous assessment of false-positive test results, and assessment of the utility of the test under nonsurveillance conditions are needed.

BACKGROUND: Invasive candidiasis (IC) is an important healthcare-related infection, with increasing incidence and a crude mortality exceeding 50%. Numerous treatment options are available yet comparative studies have not identified optimal therapy. METHODS: We conducted an individual patient-level quantitative review of randomized trials for treatment of IC and to assess the impact of host-, organism-, and treatment-related factors on mortality and clinical cure. Studies were identified by searching computerized databases and queries of experts in the field for randomized trials comparing the effect of ≥2 antifungals for treatment of IC. Univariate and multivariable analyses were performed to determine factors associated with patient outcomes. RESULTS: Data from 1915 patients were obtained from 7 trials. Overall mortality among patients in the entire data set was 31.4%, and the rate of treatment success was 67.4%. Logistic regression analysis for the aggregate data set identified increasing age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02; P = .02), the Acute Physiology and Chronic Health Evaluation II score (OR, 1.11; 95% CI, 1.08-1.14; P = .0001), use of immunosuppressive therapy (OR, 1.69; 95% CI, 1.18-2.44; P = .001), and infection with Candida tropicalis (OR, 1.64; 95% CI, 1.11-2.39; P = .01) as predictors of mortality. Conversely, removal of a central venous catheter (CVC) (OR, 0.50; 95% CI, .35-.72; P = .0001) and treatment with an echinocandin antifungal (OR, 0.65; 95% CI, .45-.94; P = .02) were associated with decreased mortality. Similar findings were observed for the clinical success end point. CONCLUSIONS: Two treatment-related factors were associated with improved survival and greater clinical success: use of an echinocandin and removal of the CVC.

Use of peripherally inserted central catheters (PICCs) has grown substantially in recent years. Increasing use has led to the realization that PICCs are associated with important complications, including thrombosis and infection. Moreover, some PICCs may not be placed for clinically valid reasons. Defining appropriate indications for insertion, maintenance, and care of PICCs is thus important for patient safety. An international panel was convened that applied the RAND/UCLA Appropriateness Method to develop criteria for use of PICCs. After systematic reviews of the literature, scenarios related to PICC use, care, and maintenance were developed according to patient population (for example, general hospitalized, critically ill, cancer, kidney disease), indication for insertion (infusion of peripherally compatible infusates vs. vesicants), and duration of use (≤5 days, 6 to 14 days, 15 to 30 days, or ≥31 days). Within each scenario, appropriateness of PICC use was compared with that of other venous access devices. After review of 665 scenarios, 253 (38%) were rated as appropriate, 124 (19%) as neutral/uncertain, and 288 (43%) as inappropriate. For peripherally compatible infusions, PICC use was rated as inappropriate when the proposed duration of use was 5 or fewer days. Midline catheters and ultrasonography-guided peripheral intravenous catheters were preferred to PICCs for use between 6 and 14 days. In critically ill patients, nontunneled central venous catheters were preferred over PICCs when 14 or fewer days of use were likely. In patients with cancer, PICCs were rated as appropriate for irritant or vesicant infusion, regardless of duration. The panel of experts used a validated method to develop appropriate indications for PICC use across patient populations. These criteria can be used to improve care, inform quality improvement efforts, and advance the safety of medical patients.

Recent years have witnessed a rapidly growing crisis in antimicrobial resistance, especially among microorganisms that cause nosocomial infection. To better understand common risk factors among multiresistant organisms, this review explores risk factors for nosocomial infection with methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococcus, Clostridium difficile, extended-spectrum beta-lactamase-producing gram-negative bacilli, and Candida. This review comprises data from 74 published studies; 53 (71%) were retrospective studies and addressed few risk factors or did not quantify risk. The analysis shows impressive commonality of risk factors across these diverse multiresistant organisms: advanced age; underlying diseases and severity of illness; inter-institutional transfer of the patient, especially from a nursing home; prolonged hospitalization; gastrointestinal surgery or transplantation; exposure to invasive devices of all types, especially central venous catheters; and exposure to antimicrobial drugs, especially cephalosporins. More restricted use of antibiotics, especially cephalosporins, and strategies to prevent medical device-related infection and cross-infection in the hospital would yield benefit with all types of resistant organisms. Preemptive isolation of all patients with risk factors for infection by resistant organisms would very likely reduce secondary spread within the hospital. Conversely, programs that focus on only one organism or one antimicrobial drug are unlikely to succeed. Prospective studies of sufficient size that address all potential risk factors, especially individual anti-infective agents, and that use matched controls who are shown by surveillance cultures to be free of colonization by resistant organisms would enhance understanding of the epidemiology of antimicrobial resistance in institutions and guide efforts to develop more effective strategies for prevention.