Elizabeth D. Hermsen

Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: A systematic review and meta-analysis

Introduction:Compared with glycopeptides, linezolid achieves higher lung epithelial lining fluid concentrations, which may correlate with improved efficacy in the treatment of nosocomial pneumonia. However, clinical superiority has not been demonstrated. Objective:To test the hypothesis that linezolid may be superior to glycopeptides. Methods:Prospective randomized trials that tested linezolid vs. vancomycin or teicoplanin for treatment of nosocomial pneumonia were included. Heterogeneity was analyzed by I2 and Q statistics. Meta-analysis relative risks were based on fixed and random-effects models. Outcomes evaluated consisted of clinical cure, microbiological eradication, and side effects. Results:Nine linezolid trials (vancomycin [7]; teicoplanin [2]) were included (n = 2329). The linezolid vs. glycopeptide analysis shows clinical cure relative risk of 1.01 (95% confidence interval, 0.93-1.10; p = .83; I2 = 0%) and microbiological eradication relative risk of 1.10 (95% confidence interval, 0.98 -1.22; p = .10; I2 = 0%). Methicillin-resistant Staphylococcus aureus subgroup analysis yielded a microbiological eradication relative risk of 1.10 (95% confidence interval, 0.87-1.38; p = .44; I2 = 16%). If linezolid is compared with vancomycin only, then clinical cure relative risk is 1.00 (95% confidence interval, 0.90-1.12), microbiological eradication and methicillin-resistant Staphylococcus aureus relative risks are 1.07 (95% confidence interval, 0.90-1.26; p = .45) and 1.05 (95% confidence interval, 0.82-1.33; p = .71). The risks of thrombocytopenia (relative risk, 1.93; 95% confidence interval, 1.30-2.87; p = .001) and gastrointestinal events (relative risk, 2.02; 95% confidence interval, 1.10-3.70; p = .02) are higher with linezolid, but no differences are seen for renal dysfunction (relative risk, 0.89; 95% confidence interval, 0.56-1.43; p = .64) or all-cause mortality (relative risk, 0.95; 95% confidence interval, 0.76-1.18; p = .63). Conclusions:Our study does not demonstrate clinical superiority of linezolid vs. glycopeptides for the treatment of nosocomial pneumonia despite a statistical power of 95%. Linezolid shows a significant two-fold increase in the risk of thrombocytopenia and gastrointestinal events. Vancomycin and teicoplanin are not associated with more renal dysfunction than linezolid.

Insights from the Society of Infectious Diseases Pharmacists on Antimicrobial Stewardship Guidelines from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America

In 2007, the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America published a document that addressed the major considerations for the justification, description, and conduct of antimicrobial stewardship programs. Our document is intended to continue the dialogue of these formalized programmatic strategies. We briefly review the guidelines, including the two primary strategies (prospective auditing with feedback, and preauthorization), and the supplemental strategies (education, information technology, transitional therapy, deescalation or streamlining, and dose optimization). Discussions are introduced or furthered in the areas of program goals, barriers and solutions, and outcome measures. Definition and training of infectious diseases pharmacists are presented in detail. We offer keys to future success, which include continued collaboration and expanded use of information technology.

Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections

Objective: Higher vancomycin concentrations are thought necessary for treatment of deep-seated methicillin-resistant Staphylococcus aureus (MRSA) infection, yet this may result in greater risk of nephrotoxicity. We evaluated the relationship of serum vancomycin trough concentration with clinical outcomes and nephrotoxicity for patients with deep-seated MRSA infection. Methods: A retrospective cohort study evaluated adults with MRSA pneumonia, endocarditis or osteomyelitis who received vancomycin for ≥ 5 days from June 2005 to June 2007. Patients were stratified by mean vancomycin trough level [low (< 15 mg/l), high (≥ 15 mg/l)]. Outcomes were clinical response, mortality, length of stay (LOS) and nephrotoxicity. Three definitions of nephrotoxicity were used: i) rise in serum creatinine (SCr) ≥ 0.5 mg/dl; ii) 50% increase in SCr; and iii) 25% decrease in estimated creatinine clearance. Results: Fifty-five patients experiencing MRSA pneumonia (n = 28), endocarditis (n = 9), osteomyelitis (n = 20) and multiple infections (n = 2) were stratified into low (n = 39) and high (n = 16) groups. High group patients were more likely to be septic (p = 0.01) and have a higher APACHE II score (p = 0.01). After adjustment for APACHE II score, clinical response rates among survivors did not differ significantly. Risk of death was not significantly different between the high (19%) and low (5%) group patients (p = 0.1). LOS did not differ significantly between groups (p = 0.7). Nephrotoxicity occurred in the low and high groups, respectively, for 10 and 31% (p = 0.04) with definition 1, 10 and 31% (p = 0.04) with definition 2, and 13 and 25% (p = 0.1) with definition 3. After adjustment for APACHE II score, odds of nephrotoxicity based on definitions 1 or 2 were increased among the high versus low groups (OR = 3.27, 95% CI: 0.7 – 15.25, p = 0.1), although not statistically significant. Conclusions: Clinical outcomes did not differ significantly between high and low trough groups for deep-seated MRSA infections. Nephrotoxicity was consistently higher in the high trough group, regardless of the definition used.

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.

Is there a role for oral human immunoglobulin in the treatment for norovirus enteritis in immunocompromised patients

Florescu DF, Hermsen ED, Kwon JY, Gumeel D, Grant WJ, Mercer DF, Kalil AC. Is there a role for oral human immunoglobulin in the treatment for norovirus enteritis in immunocompromised patients? Pediatr Transplantation 2011: 15: 718–721.

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

IntroductionDue 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.MethodsWe 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. Paphitous rule included diabetes, total parenteral nutrition (TPN) and dialysis with or without antibiotics. Ostrosky-Zeichners 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).ResultsA 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.ConclusionsBased 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.

Recommendations for Training and Certification for Pharmacists Practicing, Mentoring, and Educating in Infectious Diseases Pharmacotherapy : Joint Opinion of the Society of Infectious Diseases Pharmacists and the Infectious Diseases Practice and Research Network of the American College of Clinical Pharmacy

Recently created guidelines for the development of institutional antimicrobial stewardship programs recommend that a pharmacist with infectious diseases training be included as a core member of the antimicrobial stewardship team. However, training and certification requirements for infectious diseases‐trained clinical pharmacists have not been established. Although pharmacists have nurtured their interest in infectious diseases by self‐directed learning or on‐the‐job experiences, this mode of training is not considered feasible or sufficient for reliable training of future clinical specialists in infectious diseases. This document, therefore, is forward looking and provides overarching recommendations for future training and certification of pharmacists practicing, mentoring, and educating in infectious diseases pharmacotherapy, with the recognition that full implementation may take several years. We recommend that future pharmacists wishing to obtain a clinical position as an infectious diseases‐trained pharmacist should complete a postgraduate year (PGY) 1 residency and a PGY2 residency in infectious diseases, that practitioners become board‐certified pharmacotherapy specialists, that a certification examination in infectious diseases be developed, that practitioners maintain a portfolio of educational experiences to maintain qualifications, that current nonaccredited training programs seek accreditation, and that employers and academicians recognize the desirability of these qualifications in hiring decisions.

Inappropriate use of urinary catheters: a prospective observational study.

BACKGROUND Despite the well-recognized role of urinary catheters in nosocomial urinary tract infections, data on risk factors associated with inappropriate urinary catheter use are scarce. METHODS A prospective review of electronic medical records of 436 patients admitted to an adult medical-surgical unit between October and December 2007 was performed to examine the appropriateness of urinary catheter use. RESULTS The use of 157 urinary catheters in 144 patients was observed. A total of 557 urinary catheter-days were recorded in these patients, of which 175 (31.4%) were found to be inappropriate based on the study criteria. The total number of catheters used and the total duration of catheterization were risk factors for inappropriate urinary catheter use (P < .05). Inappropriate catheter use was not associated with such adverse events as mortality, readmission, intensive care unit admission, catheter complications, or urine culture rates, but was associated with a trend toward longer duration of hospitalization. CONCLUSIONS Significant rates of inappropriate urinary catheter use and a trend toward longer duration of hospitalization with inappropriate catheter use were observed. These findings underscore the importance of establishing guidelines and effective policy implementation for the appropriate use of urinary catheters in hospitalized patients.

Vancomycin Susceptibility Trends and Prevalence of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus in Clinical Methicillin-Resistant S. aureus Isolates

ABSTRACT Due to the rise in methicillin-resistant Staphylococcus aureus (MRSA) infections and widespread use of vancomycin, MRSA isolates with reduced susceptibility to vancomycin are emerging (i.e., MIC creep). However, the prevalence of heterogeneous vancomycin-intermediate S. aureus (hVISA) is unknown due to the difficulty in detecting this phenotype. Recently, Etest glycopeptide resistance detection (GRD) strips have been developed to detect hVISA. This study assessed vancomycin susceptibility in MRSA isolates and determined the prevalence of hVISA by Etest GRD and population analysis profile-area under the curve ratio (PAP-AUC). The genetic backgrounds of 167 MRSA isolates collected from 2000 to 2008 were identified by pulsed-field gel electrophoresis. Vancomycin MICs were determined using Etest and two broth microdilution assays, MicroScan and Sensititre. Etest GRD was performed on all isolates, and those exhibiting a hVISA phenotype were further tested by PAP-AUC. The vancomycin MIC modes remained consistent at 1 μg/ml, as assessed by Sensititre and MicroScan. Etest reported a significant increase (mode MIC = 1.5 μg/ml) in the MIC between 2000 and 2008 (P < 0.01); however, this increase did not reflect a ≥2-fold change. In addition, the slight MIC increase did not increase linearly from 2000 to 2008, suggesting biological fluctuation, and is inconsistent with the concept of MIC creep. Etest GRD identified six hVISA isolates, two of which were confirmed to be hVISA by PAP-AUC. In conclusion, reduced vancomycin susceptibility was not detected in our hospital over a 9-year period using three different MIC methodologies, and the hVISA incidence was 1.2%, as determined by Etest GRD and PAP-AUC.