Computer-Assisted Antimicrobial Recommendations for Optimal Therapy: Analysis of Prescribing Errors in an Antimicrobial Stewardship Trial.

Clinician education and prospective audit and feedback interventions, deployed separately and concurrently, did not reduce antimicrobial use errors or rates compared to a control group of general medicine inpatients at our public hospital. Additional research is needed to define the optimal scope and intensity of hospital antimicrobial stewardship interventions. Infect Control Hosp Epidemiol 2017;38:857-859.

Pharmacokinetic drug evaluation of ceftobiprole for the treatment of MRSA.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA), while decreasing in overall incidence, is still a prominent concern world-wide. New agents coming to market in the last 10 years allow practitioners to optimize treatment for MRSA infections. Ceftobiprole is a cephalosporin agent with MRSA activity, currently approved in selected countries for the treatment of community-acquired pneumonia and hospital-acquired pneumonia. Areas covered: Relevant literature regarding spectrum of activity, pharmacokinetics, pharmacodynamics, and clinical trials will be discussed. Expert opinion: Ceftobiprole is an addition to a growing number of antimicrobials with activity against MRSA. Concern for appropriate dosing in critically ill patients remains due to its ineffectiveness for the treatment of ventilator-associated pneumonia (VAP). While ceftobiprole has activity against gram-negative organisms, the allowance for use of an additional agent for gram-negative infections in clinical trials limits recommendations for monotherapy for empirical treatment of HAP. Ceftobiprole's place in therapy will lie in its activity against gram positive organisms, such as Streptococcus spp. and Staphylococcus spp.

Nephrotoxicity Associated with Concomitant Use of Ledipasvir-Sofosbuvir and Tenofovir in a Patient with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection.

Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection, with superior efficacy and safety compared to interferon-based therapies. Despite these improvements, drug interactions with DAAs exist and may be clinically relevant in human immunodeficiency virus (HIV)-coinfected patients. We present a case of nephrotoxicity associated with concomitant use of tenofovir disoproxil fumarate (TDF) and ledipasvir-sofosbuvir (LDV-SOF). A 56-year-old woman with HIV infection who had been taking efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) for 6 years developed acute kidney injury 8 weeks after initiating LDV-SOF for the treatment of HCV infection. Her serum creatinine concentration peaked at 10 mg/dL, compared with her baseline concentration of 0.9-1 mg/dL. Kidney biopsy revealed acute tubular necrosis and acute interstitial nephritis. Both LDV-SOF and TDF were discontinued, and the patient's serum creatinine concentration decreased to 1.3 mg/dL over the following 6 weeks. We postulate that this adverse drug reaction may have been secondary to the known interaction between ledipasvir and TDF, which results in increased TDF exposure. Despite knowledge of this interaction, LDV-SOF is commonly prescribed in patients with HIV-HCV coinfection, as patients who received LDV-SOF- and TDF-containing regimens in trials have not demonstrated adverse clinical consequences related to this interaction. This case highlights the rare but potentially serious nephrotoxicity that can result from TDF toxicity and serves as a reminder to clinicians to implement close renal function monitoring in patients receiving both LDV-SOF and TDF. Clinicians prescribing LDV-SOF to HCV-HIV-coinfected patients receiving TDF should be cautious about use with concomitant nephrotoxic medications and monitor markers of tubular dysfunction, including urinary phosphorus excretion, and renal injury at baseline and week 4 of therapy. Tenofovir alafenamide and alternative DAAs may also have a role in the management of patients at high risk for renal adverse effects from TDF.

Pharmacokinetic and pharmacodynamic evaluation of ceftaroline fosamil.

INTRODUCTION: Ceftaroline fosamil is a 5th generation cephalosporin with an in vitro spectrum of activity including Streptococcus agalactiae, penicillin- and cephalosporin-resistant S. pneumoniae, S. pyogenes, methicillin-susceptible S. aureus and methicillin-resistant S. aureus, Haemophilus influenzae, Klebsiella oxytoca, K. pneumoniae and Moraxella catarrhalis. It is currently approved by the FDA for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) in adults. AREAS COVERED: This review covers the mechanism of action; bacterial resistance; pharmacokinetic characteristics in various patient populations; pharmacodynamic data in animal and in vitro models as well as human studies; efficacy observed in clinical trials for ABSSSI and CABP; and adverse effects. EXPERT OPINION: Ceftaroline provides in vitro bactericidal activity against methicillin-, vancomycin-, daptomycin-, and linezolid-resistant Gram-positive organisms and select Gram-negative pathogens. The pharmacodynamics of ceftaroline is similar to other ß-lactam agents. Ceftaroline exhibits a favorable adverse effect profile and is generally well tolerated. There is little data on clinical success of ceftaroline in patients with bacteremia or endocarditis other than what has been published in a small series of case reports. Randomized-control studies are needed to establish clinical outcomes and safety in these patient populations.

How low can you go? Use of low- and standard-dose liposomal amphotericin B for treatment of invasive fungal infections.

OBJECTIVES: Recommended doses of liposomal amphotericin B (L-AMB) range from 3 to 6 mg/kg/day, but 1mg/kg/day may be equally effective and a lower cost alternative for many indications. The objective of this analysis was to assess indications and clinical outcomes of patients who received low-dose (1mg/kg/day rounded up in 50-mg increments) and standard-dose (≥2 mg/kg/day) L-AMB. METHODS: This was a retrospective analysis of adult L-AMB recipients with suspected invasive fungal infections (IFI) at a single center from 2006 to 2011. The primary outcome was clinical response at the end of treatment. Secondary outcomes included survival and toxicity. Results were analyzed using Chi-square and descriptive statistics. RESULTS: Of 89 adult L-AMB recipients included, 36 had proven or probable IFIs. Nineteen (53%) received low doses and 17 (47%) received standard doses. Median doses were 1.5 and 3.0mg/kg/day. Cryptococcus was the most common fungal pathogen in the low-dose group (37%), and Candida spp. in the standard-dose group (47%). Forty-seven percent of subjects in both groups improved clinically. Sixty-eight percent of low-dose recipients and 76% of standard-dose recipients survived to discharge. Rates of nephrotoxicity and hypokalemia were comparable. CONCLUSIONS: Comparable rates of clinical improvement, survival to discharge, and toxicity were identified among low- and standard-dose L-AMB recipients.

Implementation of an extended-infusion piperacillin-tazobactam program at an urban teaching hospital.

PURPOSE: The development and implementation of an extended-infusion piperacillin-tazobactam program at an urban teaching hospital are described. SUMMARY: A multidisciplinary team was formed to address the feasibility of converting from the standard 30-minute infusion to an extended infusion of piperacillin- tazobactam. Before hospitalwide implementation, feasibility studies were performed in a subset of patients to identify potential barriers to program implementation. On the day of hospitalwide conversion, the orderables for piperacillin-tazobactam were reprogrammed in the computerized prescriber-order-entry system to allow separate options for the 30-minute infusion (for pediatric patients) and the extended-infusion regimen. After selecting the orderable for the extended-infusion regimen, an electronic message appeared to remind prescribers of the rationale for this change and recommended indications for piperacillin-tazobactam. Program success was prospectively evaluated on 11 weekdays after hospitalwide conversion for all 96 adult inpatients receiving piperacillin-tazobactam. Of the 194 piperacillin-tazobactam doses observed, 90% were appropriate, with compliance increasing to 100% by the end of the observation period. There was near-complete cessation of the every-6-hour dosage interval and a marked increase in the every-8-hour and every-12-hour dosage intervals. The number of piperacillin-tazobactam doses per 1000 patient-days significantly decreased during the postimplementation period. During the postimplementation period, pharmacy expenditures related to piperacillin-tazobactam decreased by 18% and the total number of grams of piperacillin-tazobactam purchased decreased by 24%. CONCLUSION: A hospitalwide program for the administration of extended-infusion piperacillin-tazobactam was safely and successfully implemented using a multi-disciplinary approach in an urban teaching hospital.

Antimicrobial consumption data from pharmacy and nursing records: how good are they?

OBJECTIVE: To determine whether randomly selected intravenous (IV) antimicrobial doses dispensed from an inpatient pharmacy were administered. DESIGN: This was a prospective, cross-sectional study in which dose administration was confirmed by direct observation and by assessment of the medication administration record (MAR). A retrospective analysis of the return rate of unused IV antimicrobial doses was performed subsequently. SETTING: Medical and surgical intensive care units (ICUs) and non-ICUs of a 550-bed urban public teaching hospital. PARTICIPANTS: Hospitalized patients with an order in the pharmacy database for an IV antimicrobial during 9 non-consecutive weekdays in June 1999. RESULTS: Of 397 doses, 221 (55.7%) assessed by bedside observation and 238 (59.9%) assessed by MAR review were classified as administered; 139 doses (35.0%) were dispensed but changes in the drug order or the patient's status prevented their administration. In the subsequent assessment, of 745 IV antimicrobial doses dispensed during 24 hours, 322 (43.2%) were returned to the pharmacy unused; 423 (56.8%) of the doses-consistent with our prior observations-were presumably administered. CONCLUSIONS: Because computerized pharmacy data may overestimate actual antimicrobial consumption, such data should be validated when used in studies of hospital antimicrobial use. Dispense-return analysis offers a simple validation method.

Antibiotic combinations with redundant antimicrobial spectra: clinical epidemiology and pilot intervention of computer-assisted surveillance.

Redundant antibiotic combinations are a potentially remediable source of antibiotic overuse. At a public teaching hospital, we determined the incidence, cost, and indications for such combinations and measured the effects of a pharmacist-based intervention. Of 1189 inpatients receiving >or=2 antibiotics, computer-assisted screening identified 192 patients (16.1%) receiving potentially redundant combinations. Chart reviews showed that 137 episodes (71%) were inappropriate. Physician overprescribing errors were found in 77 episodes (56%); most involved redundant coverage for gram-positive or anaerobic organisms. In 76 episodes (55%), lapses in the medication ordering and distribution system led to the persistence in the pharmacy records of regimens no longer active according to the patient charts. The incidence of redundant antibiotic combinations was significantly higher in the intensive care unit and surgery services, compared with medical services. Interventions to discontinue redundant agents were successful in 134 (98%) of the 137 episodes. Potential drug cost savings and reduction in redundant antibiotic combination days were 10,800 dollars and 584 days, respectively; pharmacist time for patient review and intervention cost 2880 dollars. Use of redundant antibiotic combinations was common, and a pharmacist-based intervention was feasible, with a potential annualized cost savings of 48,000 dollars.