Comparison of the Drug-Drug Interaction Potential of Daptomycin in Combination with Rifampin in Healthy Adult Volunteers.

We evaluated the effects of rifampin coadministration and MDR1 single nucleotide polymorphisms on the disposition of daptomycin in twelve healthy adults. There were no significant changes from baseline in the clearance (0.53 versus 0.55 liters/h, P = 1.00), volume of distribution (7.0 versus 7.2 liter, P = 0.62), or half-life (9.7 versus 9.6 h, P = 0.89) of daptomycin after exposure to rifampin. The tested MDR1 polymorphisms were not associated with significant differences in daptomycin disposition.

Diagnostic and therapeutic evaluation of community-acquired methicillin-resistant Staphylococcus Aureus (MRSA) skin and soft tissue infections in the emergency department.

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections commonly present as skin and soft-tissue infections (SSTIs). Treatment often includes incision and drainage with or without adjunctive antibiotics. Emergency department (ED) pharmacists wished to provide specific data to emergency physicians to better inform antibiotic choices for patients with SSTIs. STUDY OBJECTIVES: The objectives of this study were to describe local susceptibility trends of CA-MRSA isolates obtained from patients with SSTIs and describe diagnostic and empiric therapeutic management of CA-MRSA SSTIs among ED health care providers at University of Utah Hospitals and Clinics. METHODS: Susceptibility of all unique CA-MRSA SSTI isolates for 2008 were identified and compiled into an antibiogram. ED providers evaluated their diagnostic and treatment habits using a self-assessment questionnaire, which was verified against charted information documented in the electronic medical records for patients presenting to the ED with a CA-MRSA SSTI. RESULTS: The ED antibiogram indicated that 57/58 (98%) CA-MRSA SSTI isolates were susceptible to sulfamethoxazole/trimethoprim (SMX/TMP); 50/58 (86%) isolates were susceptible to tetracycline, and 47/58 (81%) isolates were susceptible to clindamycin. Incision and drainage were performed in 23/25 (92%) patient cases, which was consistent with providers' perceived habits (100%). SMX/TMP monotherapy was preferred among 23/35 (66%) providers, however, SMX/TMP combined with cephalexin was the antibiotic regimen prescribed in 9/22 (41%) patient cases. CONCLUSIONS: Cephalexin was often added to cover for potential cellulitis due to Streptococcus spp., however, the surrounding erythema may simply be an extension of the CA-MRSA infection. Department-specific antibiograms are useful in guiding empiric antibiotic selection and may help providers judiciously prescribe antibiotics only when necessary.

Angiotensin-converting enzyme inhibitors reduce community-acquired pneumonia hospitalization and mortality.

BACKGROUND: Pneumonia is a global disorder and a common reason for prolonged hospitalization. Angiotensin-converting enzyme inhibitors (ACEi) have pleiotropic effects that support a role in modulating pneumonia, but results have been controversial. OBJECTIVES: The present study was conducted to elucidate an ACEi-induced pneumonia benefit in at-risk neurologically impaired population and to determine whether a mortality benefit exists. METHODS: A cohort study using a large health-system of 29,011 unique ACEi users and 1635 case patients 65 years of age or older without neurological disorders affecting swallowing who were admitted with community-acquired pneumonia hospitalization and followed up from January 1, 2015 to December 31, 2019 (5 years). The association between ACEi use and pneumonia hospitalization and mortality were determined after propensity score matching using Cox and logistic regression. RESULTS: The experimental cohort was 74.9 ± 7.3 years and 51% were male. ACEi users had lower odds of acquiring pneumonia versus ACEi non-users (odds ratio) 0.72 [95% Confidence Interval (CI) 0.51 to 0.99]; p = 0.048. The risk of short-term mortality (<30 days) (HR) 0.42, p < 0.001 and long-term mortality (≥30 day) (HR) 0.83, p < 0.002 was significantly lower for ACEi users compared with the ACEi non-users. CONCLUSIONS: ACEi use in patients at risk of pneumonia without neurological swallowing disorders is associated with reduction in hospitalization and lowering of short- and long-term mortality. Given the high incidence of morbidity and mortality associated with pneumonia, and the susceptibility in older populations with underlying cardiovascular or renal disease or social dependencies, our data support the prescribing of ACEi in these populations to reduce pneumonia hospitalization risk as well as short- and long-term mortality.

Impact of a Multiplex PCR Assay for Bloodstream Infections With and Without Antimicrobial Stewardship Intervention at a Cancer Hospital.

Implementation of Biofire FilmArray Blood Culture Identification Multiplex PCR panel (BCID) at a cancer hospital was associated with reduced time to appropriate antimicrobial therapy. Additional reductions were not observed when BCID was coupled with antimicrobial stewardship intervention.

Patient Variables Associated with Nafcillin Plasma Concentrations and Toxicity.

PRIMARY OBJECTIVE: To retrospectively review nafcillin plasma concentrations (CNAF ) and determine nafcillin clearance (CLNAF ) in a diverse sample of patients treated with nafcillin administered as a continuous infusion. SECONDARY OBJECTIVE: To identify clinical variables associated with CLNAF and nafcillin-related adverse drug reactions (ADRs). METHODS: Retrospective chart review of patients receiving nafcillin via continuous infusion at University of Utah Health Care from 2006 to 2013 who had at least one steady-state CNAF measured. CLNAF was determined by dividing the nafcillin rate of infusion by CNAF . Adverse drug reactions (ADRs) were defined using the National Institutes of Health, Division of Microbiology and Infectious Diseases criteria and scored for probability of association with nafcillin by using Naranjo criteria. Multivariate models were constructed to identify independent variables associated with CLNAF and ADRs. MAIN RESULTS: Seventy-six CNAF from 54 patients were included. Median CLNAF was 13.9 L/hour (range ≤ 4.2 to 36.9 L/hr). Congestive heart failure (p=0.007), hyperbilirubinemia (p<0.0001), and serum creatinine (p<0.0001) were associated with reduced CLNAF , and Hispanic race (p=0.002) was associated with increased CLNAF by multivariate analysis. Twenty patients (37.0%) experienced an ADR. CNAF were significantly higher between patients that experienced an ADR and those that did not (66.0 vs 25.5 mg/L, p<0.001). Individual ADRs associated with CNAF included hepatotoxicity (62.8 vs 27.0 mg/L, p=0.001), nausea/vomiting (80.0 vs 28.5 mg/L, p=0.01), and diarrhea (66.5 vs 26.5 mg/L, p<0.001). Multivariate analysis identified CNAF as being independently associated with ADRs. A putative toxicity relationship between CNAF and predicted probability of ADR was established. CONCLUSIONS: Several patient variables were associated with impaired CLNAF , and elevated CNAF were associated with ADRs. Additional studies assessing the utility of nafcillin therapeutic drug monitoring to minimize toxicity are warranted.

Performance of a vancomycin dosage regimen developed for obese patients.

PURPOSE: An original and a revised vancomycin dosing protocol for obese patients were compared with respect to attainment of target serum trough vancomycin concentrations and the occurrence of nephrotoxicity. METHODS: The attainment of target vancomycin trough values (10-20 µg/mL) and nephrotoxicity were compared retrospectively between an original protocol (vancomycin 15 mg/kg i.v. every 8-12 hours), which had been associated with high troughs, and a revised protocol (10 mg/kg i.v. every 12 hours or 15 mg/kg every 24 hours). Patients were included if they were obese (weight ≥ 100 kg and total body weight ≥ 140% of ideal body weight), had normal renal function (creatinine clearance ≥ 60 mL/min), had received i.v. vancomycin for at least 48 hours, and had one evaluable vancomycin trough value. Nephrotoxicity was defined as an increase in serum creatinine concentration of 0.5 mg/dL or of 50% over baseline, whichever was greater. RESULTS: Seventy-four and 64 patients were stratified into groups that had been treated with the revised and original protocols, respectively. The mean ± S.D. maintenance dose was 19 ± 2 mg/kg/day with the revised protocol and 34 ± 7 mg/kg/day with the original protocol (p < 0.001). Compared with the original protocol, the revised protocol resulted in a higher frequency of target troughs (59% versus 36%, p = 0.006) and below-target troughs (23% versus 9%, p = 0.033) and a lower frequency of above-target troughs (18% versus 55%, p < 0.001). Nephrotoxicity occurred in two patients in each group. CONCLUSION: Compared with the original vancomycin protocol for obese patients, a revised vancomycin protocol using lower total daily doses improved the attainment of target trough concentrations, with minimal nephrotoxicity.