Validation and comparison of clinical prediction rules for invasive candidiasis in intensive care unit patients: a matched case-control study.

INTRODUCTION: Due to the increasing prevalence and severity of invasive candidiasis, investigators have developed clinical prediction rules to identify patients who may benefit from antifungal prophylaxis or early empiric therapy. The aims of this study were to validate and compare the Paphitou and Ostrosky-Zeichner clinical prediction rules in ICU patients in a 689-bed academic medical center. METHODS: We conducted a retrospective matched case-control study from May 2003 to June 2008 to evaluate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each rule. Cases included adults with ICU stays of at least four days and invasive candidiasis matched to three controls by age, gender and ICU admission date. The clinical prediction rules were applied to cases and controls via retrospective chart review to evaluate the success of the rules in predicting invasive candidiasis. Paphitou's rule included diabetes, total parenteral nutrition (TPN) and dialysis with or without antibiotics. Ostrosky-Zeichner's rule included antibiotics or central venous catheter plus at least two of the following: surgery, immunosuppression, TPN, dialysis, corticosteroids and pancreatitis. Conditional logistic regression was performed to evaluate the rules. Discriminative power was evaluated by area under the receiver operating characteristic curve (AUC ROC). RESULTS: A total of 352 patients were included (88 cases and 264 controls). The incidence of invasive candidiasis among adults with an ICU stay of at least four days was 2.3%. The prediction rules performed similarly, exhibiting low PPVs (0.041 to 0.054), high NPVs (0.983 to 0.990) and AUC ROCs (0.649 to 0.705). A new prediction rule (Nebraska Medical Center rule) was developed with PPVs, NPVs and AUC ROCs of 0.047, 0.994 and 0.770, respectively. CONCLUSIONS: Based on low PPVs and high NPVs, the rules are most useful for identifying patients who are not likely to develop invasive candidiasis, potentially preventing unnecessary antifungal use, optimizing patient ICU care and facilitating the design of forthcoming antifungal clinical trials.

Ethanol lock technique: review of the literature.

Central venous catheters (CVCs) are commonly used among adult and pediatric patients for administration of fluids, medications, and nutrition. Central line-associated (CLA) bloodstream infection (BSI) is a serious complication following CVC insertion. The aim of this review is to summarize available data regarding the ethanol lock technique, which is a proposed method for sterilizing the lumen of the catheter by instilling an ethanol solution and allowing it to dwell in the catheter for a certain amount of time. Studies on ethanol lock technique differ in ethanol concentrations, luminal dwell times, catheter types, inclusion of anticoagulants, use of systemic antibiotics, and use of the technique for prevention or for treatment of CLA BSI. In vitro studies demonstrate the efficacy of ethanol in the eradication of various pathogens. Definitive catheter integrity data are limited. Clinical trials report tolerable adverse events with ethanol locks, as well as encouraging results for prevention and treatment of CLA BSI.

Comparison of the Modification of Diet in Renal Disease and Cockcroft-Gault equations for dosing antimicrobials.

STUDY OBJECTIVES: To determine the concordance between the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault equations for glomerular filtration rate (GFR) estimation, the impact of using each equation on antimicrobial dosing, the difference in estimated GFR in patients with acute kidney disease (AKD) versus chronic kidney disease (CKD), and the correlation between the MDRD, Cockcroft-Gault equation, and expert medical opinion for estimating GFR in patients with AKD. DESIGN: Retrospective cohort study. SETTING: A 689-bed academic medical center. PATIENTS: A total of 372 adults hospitalized with either AKD or CKD between January 1, 2007, and May 31, 2007, and who received at least one antimicrobial drug; patients with stage 1 or 2 CKD or those receiving dialysis were excluded. MEASUREMENTS AND MAIN RESULTS: Data were collected from electronic medical records on patient characteristics, laboratory values, antimicrobial drugs requiring dosage adjustment due to renal dysfunction, and estimated GFRs provided by the laboratory (MDRD estimation). In addition, estimated GFRs were calculated using the Cockcroft-Gault equation. For patients with AKD, a third GFR was estimated by a nephrologist. For all patients, the MDRD GFR was significantly higher than the Cockcroft-Gault GFR (p<0.001). Level of concordance for the need for dosage adjustment based on the two equations was moderate (kappa coefficient 0.57, 95% confidence interval 0.5-0.63); 99.1% of patients with discordant dose recommendations would receive a higher dose if the MDRD GFR was used. In the AKD versus CKD groups, mean MDRD GFR was significantly higher than the Cockcroft-Gault GFR in both groups (p<0.0001), but the difference was significantly greater in the CKD group (p<0.0001). In patients with AKD, the GFR estimated by expert opinion was greater than that estimated by the Cockcroft-Gault equation (p=0.04), but was similar to the MDRD equation (p=0.07). CONCLUSION: The estimated GFR obtained with the MDRD equation was consistently higher than that from the Cockcroft-Gault equation in patients with AKD or CKD. In patients with AKD, the MDRD GFR more closely correlated with expert opinion than the Cockcroft-Gault, suggesting that the MDRD method may be applicable to this patient population. Moderate concordance between the two equations for the need for antimicrobial dosage adjustment due to renal dysfunction was found, but the specific dosage change was different for approximately 40% of patients, with 99% receiving higher doses when the MDRD GFR is used. These dosing differences may be significant, depending on drug safety profile, type of infection, and causative pathogen.