Evaluation of early clinical failure criteria in Enterococcus species bloodstream infection.

PURPOSE: Early clinical failure criteria (ECFC) were recently introduced to predict unfavorable outcomes in patients with Gram-negative bloodstream infections (BSI). ECFC include hypotension, tachycardia, tachypnea or mechanical ventilation, altered mental status, and leukocytosis evaluated at 72-96 h after BSI. The aim of this retrospective cohort study was to assess performance of ECFC in predicting 28-day mortality in Enterococcus species BSI. METHODS: Hospitalized adults with Enterococcus species BSI at Prisma Health hospitals from 1 January 2015 to 31 July 2018 were identified. Multivariate logistic regression was used to determine the association between ECFC and 28-day mortality. Area under the receiver operating characteristic (AUROC) curve was used to measure model discrimination. RESULTS: Among 157 patients, 28 (18%) died within 28 days of BSI. After adjustments in multivariate model, the risk of 28-day mortality increased in the presence of each additional ECFC (OR 1.6, 95% CI 1.2-2.3, p = 0.005). Infective endocarditis (OR 3.9, 95% CI 1.4-10.7, p = 0.01) was independently associated with 28-day mortality. AUROC curve of ECFC model in predicting 28-day mortality was 0.74 with ECFC of 2 identified as the best breakpoint. Mortality was 8% in patients with ECFC < 2 compared to 33% in those with ECFC ≥ 2 (p < 0.001). CONCLUSION: ECFC had good discrimination in predicting 28-day mortality in patients with Enterococcus species BSI. These criteria may have utility in future clinical investigations.

Dose-Dependent Hyperkalemia Among Hospitalized, HIV-Infected Patients Receiving Sulfamethoxazole/Trimethoprim.

Background: Sulfamethoxazole-trimethoprim (SXT) therapy is commonly used in HIV-infected patients and is associated with hyperkalemia and elevated serum creatinine (SCr). Objective: The purpose of this study was to examine the frequency of hyperkalemia and elevated SCr in hospitalized, HIV-infected patients receiving SXT. Methods: This was a retrospective, single-center cohort study. HIV-infected hospitalized patients receiving a minimum of 3 consecutive days of SXT were included. Patients were grouped according to high dose (≥10 mg/kg/d) and low dose (<10 mg/kg/d) trimethoprim. The primary end point was the frequency of hyperkalemia, severe hyperkalemia, and elevated SCr. Secondary end points included an evaluation of concomitant potassium-altering medications and concomitant nephrotoxic drugs. Results: A total of 100 consecutive patients were selected from all possible patients who met inclusion criteria. Overall, 47 patients experienced at least 1 adverse drug event (ADE) of either hyperkalemia or increased SCr, with 20 patients experiencing these ADEs in the low-dose group and 27 patients experiencing these ADEs in the high-dose group (P = 0.229). The ADEs of hyperkalemia or increased SCr occurred after a shorter period (5.5 vs 8.7 days) in the high-dose group (P = 0.049). Overall frequency of elevated SCr was 24% and of elevated serum K was 36%. Hyperkalemia requiring a therapeutic intervention occurred in 12 patients in the high-dose group compared with 2 in the low-dose group (P = 0.009). Conclusion and Relevance: Rates of elevated SCr and hyperkalemia in hospitalized HIV-infected patients receiving SXT are significant. Hyperkalemia requiring intervention is more common in patients receiving high-dose SXT.

Evaluation of Antimicrobial Utilization and Concordance with National Guidelines at a Tertiary Hospital in the Southern Highlands Zone of Tanzania.

Antimicrobial resistance is a growing concern in sub-Saharan Africa, and antimicrobial stewardship (AMS) programs have not been widely implemented in this region. We evaluated antibiotic prescribing patterns and concordance with national guidelines at Mbeya Zonal Referral Hospital (MZRH) in Tanzania. Adult inpatient medical records were chronologically reviewed from January 1, 2018 until 100 records documenting antibiotic therapy were evaluated. The primary endpoint was concordance with national guidelines for indication-based antibiotic selection and duration. Data were summarized using descriptive statistics. Overall, 155 records with sufficient data were reviewed. The 100 records which involved antibiotic therapy represented 171 unique antibiotic courses. The most common indication for antibiotics was bacterial pneumonia. Ceftriaxone and metronidazole, the most commonly used antibiotics, were administered in 40% and 24% of courses, respectively. Indication-based antibiotic selection was concordant with national guidelines in 63% of courses, but this fell to 15% when course duration was taken into account. Antibiotic courses were completed as prescribed 28% of the time among evaluable courses. A microbiologic culture of any kind was obtained in 17% of patients. In conclusion, antibiotic therapy was often incomplete, was generally guideline discordant, exhibited limited diversity of selection, and frequently lacked diagnostic confirmation. These data, combined with local susceptibility patterns, may be used to foster AMS efforts for improved compliance with guidelines at MZRH in the future.

Safety and Tolerability of Stribild in the Southeast United States.

PURPOSE: The purpose of this study is to assess postmarketing safety and tolerability of Stribild (elvitegravir [EVG]/cobicistat [COBI]/tenofovir disoproxil fumarate [TDF]/emtricitabine [FTC]). METHODS: A retrospective, pharmacoepidemiologic study in 2 outpatient HIV clinics in the Southeast United States was conducted among adults receiving EVG/COBI/TDF/FTC. We evaluated incidence and treatment-related adverse events, including change in serum creatinine (SCr). RESULTS: Patients were primarily treatment experienced (n = 173, 60%), African American (n = 210, 73%), and males (n = 187, 65%). One hundred ninety-five (68%) patients had any increase in SCr, and 65 (23%) had an increase of ≥0.3 mg/dL. Mean SCr change from baseline to peak was 0.2 mg/dL. Being treatment experienced (odds ratio [OR] = 2.21, 95% confidence interval [CI]: 1.12-4.38) was associated with SCr ≥0.3 mg/dL, while body mass index ≥30 kg/m(2) (OR = 0.41, 95% CI: 0.18-0.93) was protective. Twenty (7%) patients discontinued therapy, 3 due to acute kidney injury. CONCLUSION: Our results demonstrate limited adverse events and low discontinuation rates associated with EVG/COBI/TDF/FTC.

Impact of Drug Shortages on Health System Pharmacies in the Southeastern United States.

BACKGROUND: Drug shortages have become all too common and affect all aspects of the health care delivery system. The increased number of drug shortages has had a negative impact on patient care as well as costly financial implications. OBJECTIVES: This article identifies the current problems and negative outcomes drug shortages have caused and provides a framework for how to best prepare for and combat future shortages. It highlights specific problems faced by health care system pharmacies in the Southeastern United States and the managerial responses to address these shortage situations. METHODS: A 34-question, multiple-choice survey was distributed to pharmacy directors in North Carolina, South Carolina, Georgia, and Florida. RESULTS: Of 549 surveys distributed, 219 (40%) responses were received. Respondents reported that drug shortages cause 1% to 5% error rates in hospitals and that 60% of the time drug shortages create unsafe conditions for patients and staff. Many of the respondents reported a 300% to 500% markup on medications on the shortage list. Seventy-six percent of institutions have autosubstitutions for drug shortages that have been preapproved by Pharmacy & Therapeutics Committees. CONCLUSIONS: The causes of drug shortages are multifaceted, and the safety and financial implications can be costly. In the short term, health care institutions can utilize pharmacists to assist in circumventing the drug shortage problem. The combined efforts of all health care professionals, the US government, manufacturers, and the lay public are necessary to bring awareness and plausible solutions to the drug shortage problems in the long term.

Adherence among rural HIV-infected patients in the deep south: a comparison between single-tablet and multi-tablet once-daily regimens.

BACKGROUND: Once-daily (QD), combination antiretroviral therapy (ART) can impact the willingness and ability of patients to take medications as directed. The impact of antiretroviral (ARV) drug adherence influenced by single-tablet (STR) versus multi-tablet regimens (MTR) among patients enrolled in the AIDS Drug Assistance Program (ADAP) in a rural environment has not yet been assessed. MATERIAL AND METHODS: A retrospective chart review evaluated adherence and outcomes in adult HIV-infected patients enrolled in the ADAP at 2 ambulatory clinics in the Southeast, taking either a QD STR (efavirenz [EFV]/emtricitabine/tenofovir [TDF]) or a QD protease inhibitor (PI)-based, MTR (atazanavir [ATV], ritonavir [RTV], and emtricitabine/TDF) by evaluating pharmacy refill records, patient self-reported adherence, and virologic response. RESULTS: A total of 389 patient records were analyzed (STR, n = 165 versus MTR, n = 224). There were more males, a higher percentage of treatment-naive patients, and more patients with a baseline CD4 count of >200 cells/mm(3) in the MTR group. Based on refill records, more patients on MTR were >90% adherent (61.6% versus 51.5%, P = .047). In a multivariable analysis, being treatment experienced was a negative predictor (odds ratio [OR] = 0.48, 0.29-0.78) for adherence. Regimen choice was not associated with adherence. More patients taking MTR were virologically suppressed at the end of the observation period. Regardless of the regimen, being >90% adherent was a significant predictor of virologic suppression (OR = 3.51, 1.98-6.23). CONCLUSION: Treatment-experienced patients enrolled in ADAP are less likely to be adherent. A QD PI-based MTR may result in comparable adherence to an STR in a rural HIV-infected population.

Infusion-related reaction following daptomycin two-minute rapid intravenous administration.

BACKGROUND: Erythroderma, or red man's syndrome, is a common infusion-related reaction following vancomycin administration. Erythroderma following daptomycin rapid infusion has not been documented. OBJECTIVE: To report a case of erythroderma following daptomycin 2-minute intravenous (IV) injection. CASE REPORT: A review of published literature suggests that this is the first published case of a flushing (nonallergic) reaction resulting from a 2-minute IV injection of daptomycin that is not present with standard IV infusion. A 69-year-old woman following right knee reconstructive surgery presented with right knee joint swelling, purulent discharge, and fever. Subsequently, she was diagnosed with a presumed postsurgical infection and was initiated on vancomycin therapy. Following removal of the infected hardware, the patient was discharged and continued outpatient vancomycin therapy. The patient's renal function began to decline and therapy was discontinued. Daptomycin 6 mg/kg every 48 hours was initiated via 2-minute IV push. On the initial dose, approximately 2 hours post IV infusion, the patient began to notice redness and a warm sensation on her face, neck, and upper part of the chest. Diphenhydramine 25 mg provided limited immediate relief, but all symptoms subsided within 3 to 4 hours. The patient received her next dose 48 hours later over a 40-minute IV infusion with no adverse effects. Subsequent infusions continued at the same dose over 30 minutes for 4 weeks with no further adverse effects. CONCLUSION: A 2-minute intravenous injection of daptomycin in this patient yielded a reaction that was not present on rechallenge with standard, extended infusion.

Safety and effectiveness of daptomycin across a hospitalized obese population: results of a multicenter investigation in the southeastern United States.

STUDY OBJECTIVE: Data are limited for antimicrobial outcomes in obese patients. This study investigated the safety and clinical outcomes of daptomycin therapy in a hospitalized obese population in the southeastern United States. DESIGN: Multicenter retrospective cohort study. SETTING: Thirteen hospitals in the southeastern United States. PATIENTS: A total of 126 hospitalized adult obese patients (body mass index [BMI] more than 30 kg/m(2) ) admitted from January 2005 through May 2010 who received daptomycin dosed on actual body weight for any indication for a minimum of 7 days. MEASUREMENTS AND MAIN RESULTS: Primary safety outcomes included incidence of creatine phosphokinase (CPK) elevations more than 1000 units/L, more than 500 units/L, myalgias, and discontinuation of therapy due to adverse drug events (ADEs). Patients were stratified by BMI class (I, II, or III) for analyses. The average weight was 121 kg, and 39% of patients were considered morbidly obese. Factors associated with an increased risk of primary safety outcomes were assessed through regression analysis. Clinical effectiveness was evaluated as a secondary outcome. CPK elevations more than 1000 units/L occurred in 8.4% of evaluable patients and specifically in 1 (3.6%), 3 (10.3%), and 4 (10.5%) patients in BMI class I, II, and III, respectively (p=0.554). CPK elevations more than 500 units/L occurred in 13.7% of patients with no statistically significant difference noted across BMI classes. Discontinuation due to ADEs occurred in 8 patients (6.3%). One patient developed rhabdomyolysis on day 9 of therapy. Clinical effectiveness was documented in 71% of patients and was consistent across BMI classes. CONCLUSION: Although elevations in CPK increased in high-risk obese patients on daptomycin, discontinuation rates due to ADEs remained low. Further evaluation in a prospective trial is warranted.