Gary A. Noskin

Randomized, Double-Blind Clinical Trial of Amphotericin B Colloidal Dispersion vs. Amphotericin B in the Empirical Treatment of Fever and Neutropenia

We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/[kg.d]) or amphotericin B (0.8 mg/[kg.d]) for < or = 14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment.

Recovery of Vancomycin-Resistant Enterococci on Fingertips and Environmental Surfaces

OBJECTIVE To determine the recovery of vancomycin-resistant enterococci (VRE) on fingertips, gloved fingertips, and environmental surfaces commonly encountered in the healthcare setting, and to examine the importance of handwashing on the removal of these organisms. DESIGN Two clinical isolates of VRE (Enterococcus faecalis and Enterococcus faecium) were inoculated onto the hands of healthy human volunteers and the following environmental surfaces: countertops, bedrails, telephones, and stethoscopes. Following inoculation, samples were obtained at various time intervals to determine rates of recovery of organisms. To evaluate the effects of handwashing on enterococcal recovery, two different soap preparations were tested. Hands were washed with water alone or with one of the soaps and water. The soap and water studies were performed with a 5-second and a 30-second wash. RESULTS Both enterococcal strains survived for at least 60 minutes on gloved and ungloved fingertips. The E faecalis was recoverable from countertops for 5 days; the E faecium persisted for 7 days. For bedrails, both enterococcal species survived for 24 hours without significant reduction in colony counts. The bacteria persisted for 60 minutes on the telephone handpiece and for 30 minutes on the diaphragmatic surface of the stethoscope. A 5-second wash with water alone resulted in virtually no change in recovery of enterococci; a 30-second wash with water plus either soap was necessary to eradicate the bacteria from hands completely. CONCLUSION VRE are capable of prolonged survival on hands, gloves, and environmental surfaces. Hands should be washed thoroughly and gloves removed following contact with patients infected or colonized with these multidrug-resistant bacteria. Finally, environmental surfaces may serve as potential reservoirs for nosocomial transmission of VRE and need to be considered when formulating institutional infection control policies.

Resistance to Linezolid: Characterization of Mutations in rRNA and Comparison of Their Occurrences in Vancomycin-Resistant Enterococci

ABSTRACT To assess the potential for emergence of resistance during the use of linezolid, we tested 10 clinical isolates of vancomycin-resistant enterococci (VRE) (four Enterococcus faecalis, fiveEnterococcus faecium, and one Enterococcus gallinarum) as well as a vancomycin-susceptible control (ATCC 29212) strain of E. faecalis. The enterococci were exposed to doubling dilutions of linezolid for 12 passes. After the final passage, the linezolid plate growing VRE contained a higher drug concentration with E. faecalis than with E. faecium. DNA sequencing of the 23S rRNA genes revealed that linezolid resistance in three E. faecalis isolates was associated with a guanine to uracil transversion at bp 2576, while the one E. faecium isolate for which the MIC was 16 μg/ml contained a guanine to adenine transition at bp 2505.

Results of the Medications At Transitions and Clinical Handoffs (MATCH) Study: An Analysis of Medication Reconciliation Errors and Risk Factors at Hospital Admission

BackgroundThis study was designed to determine risk factors and potential harm associated with medication errors at hospital admission.MethodsStudy pharmacist and hospital-physician medication histories were compared with medication orders to identify unexplained history and order discrepancies in 651 adult medicine service inpatients with 5,701 prescription medications. Discrepancies resulting in order changes were considered errors. Logistic regression was used to analyze the association of patient demographic and clinical characteristics including patients’ number of pre-admission prescription medications, pharmacies, prescribing physicians and medication changes; and presentation of medication bottles or lists. These factors were tested after controlling for patient demographics, admitting service and severity of illness.ResultsOver one-third of study patients (35.9%) experienced 309 order errors; 85% of patients had errors originate in medication histories, and almost half were omissions. Cardiovascular agents were commonly in error (29.1%). If undetected, 52.4% of order errors were rated as potentially requiring increased monitoring or intervention to preclude harm; 11.7% were rated as potentially harmful. In logistic regression analysis, patient’s age ≥65 [odds ratio (OR), 2.17; 95% confidence interval (CI), 1.09–4.30] and number of prescription medications (OR, 1.21; 95% CI, 1.14–1.29) were significantly associated with errors potentially requiring monitoring or causing harm. Presenting a medication list (OR, 0.35; 95% CI, 0.19–0.63) or bottles (OR, 0.55; 95% CI, 0.27–1.10) at admission was beneficial.ConclusionOver one-third of the patients in our study had a medication error at admission, and of these patients, 85% had errors originate in their medication histories. Attempts to improve the accuracy of medication histories should focus on older patients with a large number of medications. Primary care physicians and other clinicians should help patients utilize and maintain complete, accurate and understandable medication lists.

Influence of Role Models and Hospital Design on Hand Hygiene of Health Care Workers

We assessed the effect of medical staff role models and the number of health-care worker sinks on hand-hygiene compliance before and after construction of a new hospital designed for increased access to handwashing sinks. We observed health-care worker hand hygiene in four nursing units that provided similar patient care in both the old and new hospitals: medical and surgical intensive care, hematology/oncology, and solid organ transplant units. Of 721 hand-hygiene opportunities, 304 (42%) were observed in the old hospital and 417 (58%) in the new hospital. Hand-hygiene compliance was significantly better in the old hospital (161/304; 53%) compared to the new hospital (97/417; 23.3%) (p<0.001). Health-care workers in a room with a senior (e.g., higher ranking) medical staff person or peer who did not wash hands were significantly less likely to wash their own hands (odds ratio 0.2; confidence interval 0.1 to 0.5); p<0.001). Our results suggest that health-care worker hand-hygiene compliance is influenced significantly by the behavior of other health-care workers. An increased number of hand-washing sinks, as a sole measure, did not increase hand-hygiene compliance.

Tigecycline: A New Glycylcycline for Treatment of Serious Infections

Tigecycline is a new semisynthetic glycylcycline for the treatment of serious infections. Of the glycylcyclines, tigecycline is the most studied and appears to hold promise as a new antimicrobial agent that can be administered as monotherapy to patients with many types of serious bacterial infections. For patients with serious infections, the initial choice for empirical therapy with broad-spectrum antibiotics is crucial, and, if the choice is inappropriate, it may have adverse consequences for the patient. Tigecycline has been designed to overcome many existing mechanisms of resistance among bacteria and confers broad antibiotic coverage against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and many species of multidrug-resistant gram-negative bacteria. Tigecycline has been efficacious and well tolerated in human clinical phase 2 studies, which warranted further evaluation of tigecycline in larger studies for treatment of many indications, including complicated skin and skin-structure infections, complicated intra-abdominal infections, and infections of the lower respiratory tract.

Insights from the sharp end of intravenous medication errors: implications for infusion pump technology

Background: Intravenous (IV) medication errors are a common type of error identified in hospitals and can lead to considerable harm. Over the past 20 years there have been several hundred FDA reported incidents involving IV pumps, many of which have led to patient deaths. Objective: To determine the actual types, frequency, and severity of medication errors associated with IV pumps. To evaluate the likelihood that smart pump technology without an interface to other systems could have prevented errors. Methods: Using a point prevalence approach, investigators prospectively compared the medication, dose, and infusion rate on the IV pump with the prescribed medication, doses, and rate in the medical record. Preventability with smart pump technology was retrospectively determined based on a rigorous definition of currently available technology. Results: A total of 426 medications were observed infusing through an IV pump. Of these, 285 (66.9%) had one or more errors associated with their administration. There were 389 documented errors overall; 37 were “rate deviation” errors and three of these were judged to be due to a programming mistake. Most of the documented events would not have caused patient harm (NCC MERP category C). Only one error would have been prevented by smart pump technology without additional interface and software capabilities. Conclusion: Medication errors associated with IV pumps occur frequently, have the potential to cause harm, and are epidemiologically diverse. Smart pumps are a necessary component of a comprehensive safe medication system. However, currently available smart pumps will fail to generate meaningful improvements in patient safety until they can be interfaced with other systems such as the electronic medical record, computerized prescriber order entry, bar coded medication administration systems, and pharmacy information systems. Future research should focus on the effectiveness of new technology in preventing latent and active errors, and on new types of error that any technology can introduce.

National Trends in Staphylococcus aureus Infection Rates: Impact on Economic Burden and Mortality over a 6-Year Period (1998–2003)

BACKGROUND We evaluated historical trends in the Staphylococcus aureus infection rate, economic burden, and mortality in US hospitals from 1998 through 2003. METHODS The Nationwide Inpatient Sample was used to assess trends over time of S. aureus infection during 1998-2003. Historical trends were determined for 5 strata of hospital stays, including all inpatient stays, surgical procedure stays, invasive cardiovascular surgical stays, invasive orthopedic surgical stays, and invasive neurosurgical stays. RESULTS During the 6-year study period from 1998 through 2003, the rate of S. aureus infection increased significantly for all inpatient stays (from 0.74% to 1.0%; annual percentage change (APC), 7.1%; P=.004), surgical stays (from 0.90% to 1.3%; APC, 7.9%; P=.001), and invasive orthopedic surgical stays (from 1.2% to 1.8%; APC, 9.3%; P<.001). For invasive neurosurgical stays, the rate of S. aureus infection did not change from 1998 to 2000 but increased at an annual rate of 11.0% from 2000 to 2003 (from 1.4% to 1.8%; P=.034). The total economic burden of S. aureus infection for hospitals also increased significantly for all stay types, with the annual percentage increase ranging from 9.2% to 17.9% (P<.05 for all). In 2003, the total economic burden of S. aureus infection was estimated to be

Screening for Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae among High-Risk Patients and Rates of Subsequent Bacteremia

14.5 billion for all inpatient stays and

A multicenter intervention to prevent catheter-associated bloodstream infections.

12.3 billion for surgical patient stays. However, there were significant decreases in the risk of S. aureus-related in-hospital mortality from 1998 to 2003 for all inpatient stays (from 7.1% to 5.6%; APC, -4.6%; P=.001) and for surgical stays (from 7.1% to 5.5%; APC, -4.6%; P=.002). CONCLUSIONS The inpatient S. aureus infection rate and economic burden of S. aureus infections for US hospitals increased substantially from 1998 to 2003, whereas the in-hospital mortality rate decreased.