Implementation of targeted interventions to decrease antiretroviral-related errors in hospitalized patients.

PURPOSE: The implementation and effectiveness of targeted interventions aimed at decreasing the frequency of antiretroviral-related errors in hospitalized patients with human immunodeficiency virus (HIV) are described. SUMMARY: A prospective investigation conducted at the University of North Carolina Hospitals revealed a high rate of antiretroviral-related errors occurring on admission to the hospital and throughout a patient's hospital stay. The high frequency of errors emphasized the need for targeted interventions aimed at preventing these errors and quickly identifying and resolving errors that do occur. Several interventions aimed at decreasing this error rate were instituted, including the addition of computer alerts for incorrect doses and drug interactions to the pharmacy order-entry system, distribution of an educational pocket-sized card among the staff, addition of commercially available combination antiretroviral products to the hospital formulary, updates of the computerized prescriber-order-entry (CPOE) system to include common dosage defaults, involvement of the infectious diseases consultation service to evaluate prescribed regimens of newly admitted patients with HIV, and daily review of newly initiated anti-retroviral regimens by a clinical pharmacist trained in HIV care. A follow-up analysis was conducted after these interventions were implemented to evaluate their effectiveness. Of the 78 patients identified during the postintervention analysis, 12 (15%) had at least one error in their initial drug regimen versus 49 patients (72%) in the preintervention study (p < 0.001). CONCLUSION: Antiretroviral medication error rates decreased after the implementation of targeted interventions that included distributing an educational pocket-sized card, adding alerts to the pharmacy order- entry system, incorporating default dosages into the CPOE system, and adding combination antiretrovirals to the formulary.

Severe sepsis caused by Arcanobacterium haemolyticum: a case report and review of the literature.

OBJECTIVE: To describe a case of severe sepsis, cavitary pneumonia, and pyomyositis caused by Arcanobacterium haemolyticum. CASE SUMMARY: An 18-year-old male with a medical history significant for mild asthma presented to the emergency department complaining of a 7-day history of fever, diffuse myalgias, nausea, vomiting, diarrhea, and pain in his right upper quadrant, right shoulder, and left thigh. Cultures of blood, bronchoalveolar fluid, and surface and surgical swabs from the patient's left lower extremity grew A. haemolyticum. The patient was successfully treated with intravenous penicillin G 4 million units every 4 hours and azithromycin 500 mg once daily for 14 days. Within 36 hours after initiation of focused therapy, he became afebrile, pain decreased, and pulmonary symptoms abated. Oral azithromycin 500 mg/day for an additional 3 weeks was prescribed on discharge, and the patient showed no relapse at 2-month follow-up. DISCUSSION: A. haemolyticum is a weakly acid-fast, branching gram-positive bacillus most commonly implicated in pharyngitis in healthy adolescents and skin and soft-tissue infections in older, immunocompromised patients. Systemic infections are rarely reported in the literature. This organism remains susceptible to most classes of antimicrobials, including penicillins, cephalosporins, carbapenems, macrolides, tetracyclines, clindamycin, and vancomycin. Routine resistance has been reported only with trimethoprim/sulfamethoxazole. CONCLUSIONS: To our knowledge, there are no published case reports of severe sepsis caused by A. haemolyticum. While treatment options are numerous, we recommend the use of intravenous penicillin or a cephalosporin as first-line pharmacologic management of deep-seated infections caused by this rare organism.

Frequency of HIV-related medication errors and associated risk factors in hospitalized patients.

BACKGROUND: Retrospective studies of hospitalized HIV-infected patients have noted a high occurrence of drug-related errors, ranging from 5% to 30%. OBJECTIVE: To prospectively evaluate errors in antiretroviral (ARV) prescribing in the inpatient setting of a hospital tertiary care center and the association of risk factors with the occurrence of errors. METHODS: HIV-infected patients who received care and continued their ARVs for HIV infection on admission to a large academic teaching hospital between January and April 2006 were included in this study. The care and assessment of these patients was conducted on a daily basis by an infectious diseases/HIV specialized clinical pharmacist. All errors were documented and classified based on a severity scale. RESULTS: Among the 68 patients who met the study's eligibility criteria, at least one error in the initial HIV regimen occurred in 72% of patients, and in 56% of patients, the error had the potential to cause moderate-to-severe discomfort or clinical deterioration. Patients on atazanavir-based therapy had a statistically significant increased occurrence of errors throughout their hospitalization (RR = 1.69; 95% CI 1.03 to 2.78; p = 0.02). Receiving nonformulary (combination) HIV medications increased patients' risk of having more than one error occur in their ARV regimen on admission and during hospitalization (RR = 1.95; 95% CI 1.25 to 3.04; p = 0.02). The clinical pharmacist recommendations had 100% acceptance. CONCLUSIONS: The alarmingly high frequency of potentially harmful errors uncovered in this study necessitates further investigation using larger sample sizes. Interventions to reduce and prevent these errors must be sought to eliminate the unintended harm associated with hospitalization.

Effect of omeprazole on the plasma concentrations of indinavir when administered alone and in combination with ritonavir.

PURPOSE: The effects of omeprazole on indinavir when administered alone or in combination with ritonavir were evaluated. METHODS: Fourteen men and women age 18-55 years not infected with human immunodeficiency virus who met study qualifications were randomized to receive placebo, 20 mg of omeprazole, or 40 mg of omeprazole daily. After seven days, the single-dose pharmacokinetic profile of an 800-mg dose of indinavir alone or in combination with 200 mg of ritonavir was evaluated. Study participants received each of four study regimens in one of four randomly assigned orders. Blood samples were collected, and plasma indinavir and ritonavir concentrations were analyzed using high-performance liquid chromatography. RESULTS: The coadministration of 20 or 40 mg of omeprazole with indinavir significantly reduced the mean indinavir area under the concentration-versus-time curve (AUC) from 30.0 mg x hr/L (95% confidence interval [CI], 21.9-41.1 mg x hr/L) to 19.7 mg x hr/L (95% CI, 14.6-26.8 mg x hr/L) or 16.0 mg x hr/L (95% CI, 11.8-21.7 mg x hr/L), respectively (p < 0.002). The addition of 200 mg of ritonavir to 800 mg of indinavir in combination with 40 mg of omeprazole significantly increased the mean indinavir AUC from 30.0 mg x hr/L (95% CI, 21.9-41.1 mg x hr/L) to 46.6 mg x hr/L (95% CI, 34.0-63.8 mg x hr/L), but it did not significantly affect mean omeprazole concentrations (p < or = 0.02). CONCLUSION: The AUC of indinavir was substantially decreased in healthy volunteers who received omeprazole 20 or 40 mg daily for seven days before the administration of a single 800-mg dose of indinavir. Concomitant administration of ritonavir 200 mg with indinavir in participants receiving omeprazole led to a significant increase in the AUC of indinavir.

Anidulafungin: review of a new echinocandin antifungal agent.

Anidulafungin (Vicuron Pharmaceuticals) is a new echinocandin antifungal with potent activity against Aspergillus and Candida spp. Anidulafungin is a noncompetitive inhibitor of (1,3)-beta-D-glucan synthase within fungal cells. The drug is rapidly distributed and steady-state concentrations are achieved after the first dose, when a loading dose of twice the daily maintenance dose is given on day 1. Drug biotransformation occurs via chemical degradation, with no hepatic metabolism or renal elimination. A favorable pharmacokinetic profile and lack of significant drug interactions suggest that patients can receive anidulafungin without dosage adjustments. These characteristics, in addition to comparable efficacy to fluconazole (Diflucan, Pfizer Ltd) in the treatment of esophageal candidiasis, support further investigation of its use in the treatment of systemic fungal infections caused by Candida and Aspergillus spp.

Single versus combined antibiotic therapy for gram-negative infections.

OBJECTIVE: To evaluate the available clinical data regarding single versus combination antimicrobial therapy for treatment of gram-negative infections, focusing on the more recent data in predominantly nonneutropenic hosts. In vitro and in vivo data regarding various antimicrobial combinations are also discussed. DATA SOURCES: Clinical trials, review articles, and meta-analyses were identified from a MEDLINE search (1960-July 2003). Special attention was given to clinical outcome trials performed since 1989. Search terms included gram-negative infections, drug synergism, Pseudomonas aeruginosa, monotherapy, combination therapy, carbapenems, beta-lactams, cefepime, aminoglycosides, and fluoroquinolones. DATA SYNTHESIS: Although most of the studies were not randomized, double-blind, or controlled, the most recent literature indicates that monotherapy with agents that are active against isolated organisms, including P. aeruginosa, may be appropriate for most patients. Efficacy outcomes, including mortality, did not significantly differ in most studies comparing single and combination therapies. Some trials suggest that combination therapy may be preferred in neutropenic patients and those with pseudomonal infections. CONCLUSIONS: Hospitalized patients with gram-negative infections are often treated with combination antimicrobial agents; however, some of the recently available data, although limited, suggest that administration of monotherapy is a feasible alternative in certain patient populations.

Treatment of tick-borne diseases.

OBJECTIVE: To review the data regarding the pharmacotherapy of Lyme disease, Rocky Mountain spotted fever (RMSF), and the human ehrlichioses. DATA SOURCES: English-language literature was identified via MEDLINE (1966-January 2002) using the keywords Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis. Textbooks and other pertinent resources were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles identified through the data sources above were evaluated and reviewed if pertinent to the objective. DATA SYNTHESIS: Tick-borne diseases are the most common vector-transmitted diseases in North America. Each disease causes significant morbidity and, in the case of RMSF, mortality if patients go untreated. If the disease syndromes are recognized early and treatment is initiated, complications are greatly reduced. Doxycycline is active against each of the causative organisms, simplifying empiric treatment. CONCLUSIONS: Effective pharmacotherapy exists to treat each of these diseases, assuming diagnosis is made quickly. The beta-lactam and tetracycline antibiotics appear to be the most effective therapy for Lyme disease. The tetracyclines, but not the beta-lactams, are effective for RMSF and the human ehrlichioses. Since Borrelia burgdorferi and the human granulocytic ehrlichiosis agent are becoming more common coinfecting pathogens, tetracycline or doxycycline should be considered the drugs of choice for patients from endemic areas where exposure to both pathogens may have occurred. Doxycycline is the preferred agent because of decreased frequency of administration and adverse effects.

In vitro assessment of urinary isolates of ampicillin-resistant enterococci.

OBJECTIVE: Susceptibility and minimum inhibitory concentration (MIC) studies of ampicillin-resistant enterococci (ARE) were performed with vancomycin, ciprofloxacin, and trovafloxacin. Ampicillin MICs were determined to make comparisons with achievable urinary concentrations of ampicillin. DESIGN: From July 1998 to April 1999, all enterococci isolated from urinary specimens were tested for susceptibility to ampicillin by disk diffusion. For all ARE, vancomycin, ciprofloxacin, and trovafloxacin susceptibilities were determined by use of either disk diffusion or the E-test. Ampicillin MICs were determined for these isolates by liquid agar microdilution testing. ARE were identified to the species level on the basis of biochemical reactions. SETTING: The study was performed at a university-affiliated tertiary care hospital. OUTCOME MEASURES: In vitro susceptibility studies and MIC determinations were performed in accordance with the National Committee for Clinical Laboratory Standards. RESULTS: A total of 310 urine samples were culture positive for enterococcus. Thirty (9.7%) unduplicated isolates were resistant to ampicillin. Of these, nine ARE isolates (30%) were also vancomycin resistant, whereas only 2 ampicillin-susceptible isolates were vancomycin resistant (p < 0.05). All ARE were resistant to ciprofloxacin, and 29 (96.7%) were resistant to trovafloxacin. Nine (30%), 18 (60%), and 3 (10%) isolates had an ampicillin MIC of 128, 256, and 512 micrograms/mL, respectively. Ampicillin MICs did not differ significantly between vancomycin-susceptible and -resistant isolates (p = 0.963). Twenty-seven isolates (90%) were identified as Enterococcus faecium; the other 3 were either Enterococcus avium or Enterococcus raffinosus. CONCLUSIONS: Ampicillin resistance is associated with resistance to vancomycin. Most ARE are resistant to fluoroquinolone antibiotics such as ciprofloxacin and trovafloxacin. Ampicillin MICs for ARE found in these urinary specimens were all within 1 dilution of 256 micrograms/mL, a concentration achievable in the urine with higher doses of oral amoxicillin or intravenous ampicillin. Additional studies are needed to assess the clinical implications of these data.