Omadacycline for a Carbapenem-Resistant Enterobacter cloacae-Associated Wound Infection.

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) are problematic pathogens because infections caused by these organisms are associated with significant morbidity and mortality. These organisms often harbor multiple resistance mechanisms, which makes it difficult to treat their associated infections. Treatment typically consists of intravenous antibiotics that are selected based on the specific susceptibility pattern for the pathogen. Data on the use of oral antibiotics for the treatment of infections caused by CRE are sparse. Case Presentation: In this case, a 62-year-old female presented with a chronic left leg wound infection. She previously underwent surgical debridement and skin grafting, which were unsuccessful. She was initially prescribed minocycline for the infection, but the wound got re-infected. At this time, the wound had significant surrounding erythema, drainage, and slough. A wound culture was obtained and demonstrated growth of carbapenem-resistant Enterobacter cloacae and methicillin-resistant Staphylococcus aureus. The patient was initiated on oral omadacycline, and she responded with resolution of the cellulitis and wound drainage. Conclusion: This case demonstrates that omadacycline may be beneficial as an oral medication for the treatment of complicated acute bacterial skin and skin structure infections caused by carbapenem-resistant Enterobacter cloacae.

Cost comparison of AUC:MIC- versus trough-based vancomycin monitoring for MRSA bacteremia.

OBJECTIVES: It is anticipated that the updated vancomycin monitoring guidelines will reconsider area under the concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC)-based monitoring instead of trough-based monitoring for methicillin-resistant Staphylococcus aureus (MRSA) infections. The AUC:MIC can be estimated using 2 steady-state serum concentrations and first-order pharmacokinetic equations or Bayesian modeling. The cost of AUC:MIC-based monitoring compared with trough-based monitoring is unknown and has been cited as a potential barrier to implementing this monitoring method. The objective of this study was to compare the total vancomycin drug and monitoring cost for patients with MRSA bacteremia who received AUC:MIC- or trough-based monitoring. DESIGN: This was a single-center, retrospective cohort study. SETTING AND PARTICIPANTS: This study included patients who were treated for MRSA bacteremia between May 1, 2013 and December 31, 2018, with an 8-month washout period between trough and AUC:MIC-based monitoring at our institution. OUTCOME MEASURES: The primary outcome was the aggregate cost of vancomycin therapy, which included the cost associated with sample collection (i.e., supply cost and nursing time), sample analysis (i.e., assay cost and laboratory technician time), result interpretation (i.e., pharmacist time), and drug cost (i.e., cost of total administered vancomycin dose) during the hospital stay. RESULTS: A total of 52 patients met inclusion criteria with 26 patients in each group. The median (interquartile range) total vancomycin drug and monitoring cost was $338.14 ($235.07-$601.05) for the AUC:MIC-based group compared with $316.79 ($253.36-$520.96) for the trough-based group (P = 0.687). CONCLUSION: Vancomycin monitoring using 2 steady-state serum concentrations and first-order pharmacokinetic equations to calculate AUC:MIC was no more costly than a trough-based approach in patients with MRSA bacteremia at our institution.

Ibalizumab, a Novel Monoclonal Antibody for the Management of Multidrug-Resistant HIV-1 Infection.

Limited antiretrovirals are currently available for the management of multidrug-resistant (MDR) HIV-1 infection. Ibalizumab, a recombinant humanized monoclonal antibody, represents the first novel agent for HIV-1 management in over a decade and is the first monoclonal antibody for the treatment of MDR HIV-1 infection in combination with other forms of antiretroviral therapy in heavily treatment-experienced adults who are failing their current antiretroviral regimen. Ibalizumab demonstrates a novel mechanism of action as a CD4-directed postattachment inhibitor and has a favorable pharmacokinetic profile that allows for a dosing interval of every 14 days after an initial loading dose. Clinical studies have demonstrated reasonably substantial antiretroviral activity with ibalizumab among a complex patient population with advanced HIV-1 infection who are receiving an optimized background regimen, where limited therapeutic options exist. Ibalizumab was well tolerated in clinical trials, and the most common adverse effects included diarrhea, nausea, dizziness, fatigue, pyrexia, and rash. Resistance to ibalizumab has also been observed via reduced expression or loss of the potential N-linked glycosylation sites in the V5 loop of the envelope glycoprotein 120. The mechanism of action, pharmacokinetic parameters, efficacy, and safety of ibalizumab present an advance in the management of MDR HIV-1 infection. Future studies and postmarketing experience will further determine longer-term clinical efficacy, safety, and resistance data for ibalizumab.

Readiness to implement vancomycin monitoring based on area under the concentration-time curve: A cross-sectional survey of a national health consortium.

PURPOSE: The purpose of this study was to (1) determine whether academic medical centers implemented area under the concentration-time curve (AUC)-based monitoring for vancomycin and (2) characterize perceived barriers to implementation and challenges experienced during the implementation process. METHODS: A multicenter, cross-sectional electronic survey was distributed to pharmacy representatives from 124 academic medical centers within the Vizient University Health System Consortium Pharmacy Network. RESULTS: Seventy-eight institutions completed the survey, representing a 62.9% response rate. Most institutions were approximately 500-1,000 beds (68/78, 87.2%), and pharmacists were primarily responsible for vancomycin therapeutic drug monitoring (66/78, 84.6%) using pharmacist-driven protocols (57/78, 73.1%). Less than one fourth (18/78, 23.1%) of responding academic medical centers performed AUC-based vancomycin monitoring, and the majority (12/18, 66.7%) used 2-point pharmacokinetics, with a smaller fraction using either Bayesian software or population-based pharmacokinetics. Of the responding institutions that only perform trough-based therapeutic drug monitoring (60/78, 76.9%), most (53/60, 88.3%) did not plan to or were unsure about transitioning to AUC-based monitoring within the next year. Both the most common challenge encountered (13/18, 72.2%) for institutions performing AUC-based monitoring and the most common barrier (44/60, 73.3%) to implementation of this monitoring strategy were pharmacist and/or provider unfamiliarity. CONCLUSION: The majority of surveyed academic medical centers have not yet implemented AUC-based vancomycin monitoring, and most institutions did not plan to adopt or were unsure about adopting this monitoring strategy within the next year.

Clinical utility of patiromer, sodium zirconium cyclosilicate, and sodium polystyrene sulfonate for the treatment of hyperkalemia: an evidence-based review.

INTRODUCTION: Hyperkalemia is a serious medical condition that often manifests in patients with chronic kidney disease and heart failure. Renin-angiotensin-aldosterone system inhibitors are known to improve outcomes in these disease states but can also cause drug-induced hyperkalemia. New therapeutic options exist for managing hyperkalemia in these patients which warrant evidence-based evaluation. AIM: The objective of this article was to review the efficacy and safety evidence for patiromer, sodium zirconium cyclosilicate (ZS9), and sodium polystyrene sulfonate (SPS) for the treatment of hyperkalemia. EVIDENCE REVIEW: Current treatment options to enhance potassium excretion are SPS and loop diuretics, which are complicated by ambiguous efficacy and known toxicities. Patiromer and ZS9 are new agents designed to address this treatment gap. Both unabsorbable compounds bind potassium in the gastrointestinal (GI) tract to facilitate fecal excretion. The capacity to bind other medications in the GI tract infers high drug-drug interaction potential, which has been demonstrated with patiromer but not yet investigated with ZS9 or SPS. Phase II and III clinical trials of patiromer and ZS9 demonstrated clear evidence of a dose-dependent potassium-lowering effect and the ability to initiate, maintain, or titrate renin-angiotensin-aldosterone system inhibitors. There is limited evidence base for SPS: two small clinical trials indicated potassium reduction in chronic hyperkalemia. All agents may cause adverse GI effects, although they are less frequent with ZS9. Concerns remain for SPS to cause rare GI damage. Electrolyte abnormalities occurred with patiromer and SPS, whereas urinary tract infections, edema, and corrected QT-interval prolongations were reported with ZS9. CONCLUSION: Patiromer and ZS9 have improved upon the age-old standard SPS for the treatment of hyperkalemia. Additional research should focus on drug-drug interactions in patients on multiple medications, incidence of rare adverse events, and use in high-risk populations.

Systematic Review and Meta-Analysis of Patiromer and Sodium Zirconium Cyclosilicate: A New Armamentarium for the Treatment of Hyperkalemia.

OBJECTIVE: To compare and contrast the efficacy and safety of patiromer and sodium zirconium cyclosilicate (ZS-9) in the treatment of hyperkalemia. DESIGN: A systematic review and meta-analysis of phase II and III clinical trial data was completed. PATIENTS OR PARTICIPANTS: Eight studies (two phase II and four phase III trials with two subgroup analyses) were included in the qualitative analysis, and six studies (two phase II and four phase III trials) were included in the meta-analysis. MEASUREMENTS AND RESULTS: Significant heterogeneity was found in the meta-analysis with an I2 value ranging from 80.6-99.6%. A random-effects meta-analysis was applied for all end points. Each clinical trial stratified results by hyperkalemia severity and dosing; therefore, these were considered separate treatment groups in the meta-analysis. For patiromer, a significant -0.70 mEq/L (95% confidence interval [CI] -0.48 to -0.91 mEq/L) change was noted in potassium at 4 weeks. At day 3 of patiromer treatment, potassium change was -0.36 mEq/L (range of standard deviation 0.07-0.30). The primary end point for ZS-9-change in potassium at 48 hours-was -0.67 mEq/L (95% CI -0.45 to -0.89 mEq/L). By 1 hour after ZS-9 administration, change in potassium was -0.17 mEq/L (95% CI -0.05 to -0.30). Analysis of pooled adverse effects from these trials indicates that patiromer was associated with more gastrointestinal upset (7.6% constipation, 4.5% diarrhea) and electrolyte depletion (7.1% hypomagnesemia), whereas ZS-9 was associated with the adverse effects of urinary tract infections (1.1%) and edema (0.9%). CONCLUSION: Patiromer and ZS-9 represent significant pharmacologic advancements in the treatment of hyperkalemia. Both agents exhibited statistically and clinically significant reductions in potassium for the primary end point of this meta-analysis. Given the adverse effect profile and the observed time-dependent effects, ZS-9 may play more of a role in treating acute hyperkalemia.