Journal of Pharmacy Practice

Purpose: To provide a summarization of the most significant infectious diseases (ID) pharmacotherapy articles published in peer-reviewed literature in 2024. Summary: Members of the Houston Infectious Diseases Network (HIDN) nominated notable articles providing significant contributions to ID pharmacotherapy in 2024. Article nominations included those pertaining to general ID and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pharmacotherapy in 2024. To aid selection of the most significant articles in 2024, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP). Out of the 21 total articles nominated by HIDN/SIDP members, 19 pertained to general ID pharmacotherapy, and 2 had pertained to HIV/AIDS pharmacotherapy. Of the SIDP members who participated in the survey, 185 voted for the top 10 general ID pharmacotherapy articles and 46 votes were recorded for the top HIV/AIDS article. The most notable publications are summarized. Conclusion: This review provides a summary of the most recently published ID literature with aims to update clinicians on the current potential practice changing ID pharmacotherapy publications from 2024.

Background: Buprenorphine is an opioid that has recently gained interest for acute pain management in post-operative patients. It has theoretical advantages due to its unique mechanism and favorable adverse effect profile. Currently, no studies have evaluated intravenous buprenorphine for acute pain management in a critically ill medical patient population. Objective: The objective of this study was to compare the use of intravenous buprenorphine with or without a full agonist IV opioid vs a full agonist IV opioid alone for acute pain in non-ventilated, non-surgical critically ill patients. Methods: A retrospective cohort study was completed of patients who received IV buprenorphine or full-agonist opioids while admitted to the medical intensive care unit at an academic medical center and community hospital. Results: The median DVPRS difference in the buprenorphine group compared to the control group was 5 vs 6. The non-inferiority t-test showed buprenorphine was not significantly non-inferior with mean DVPRS score at day 3 for the buprenorphine group was 5.02 and the control group was 5.07 (P = 0.85). Respiratory depression within 7 days occurred less in the buprenorphine group (20.6% vs 42.9%, P = 0.004). Oversedation occurred less in the buprenorphine group (27% vs 46.8%, P = 0.01. The ICU LOS was longer in the buprenorphine group (8 vs 5 days, P = 0.01). The median daily OME on day 1 was less in the buprenorphine group (29 vs 42.5, P = 0.03). Conclusion: Intravenous buprenorphine may be a comparable alternative to full agonist intravenous opioids for pain control in the medical intensive care unit.

Purpose: In observational trials, midodrine decreased vasopressor duration, length of stay (LOS), and mortality but not in randomized controlled trials. The goal of this study is to assess the efficacy and safety of using midodrine to wean intravenous (IV) vasopressors in patients with septic shock. Materials and Methods: This single-center, retrospective study was conducted at a 505-bed community teaching hospital between September 2021 and December 2022. Patients were ≥18 years of age with septic shock, admitted to the intensive care unit (ICU), required IV vasopressors for hemodynamic support, and demonstrated clinical stability. Outcomes were compared across patients receiving IV vasopressors with midodrine vs. IV vasopressors alone. Results: Among 139 patients, midodrine was associated with increased time to IV vasopressor discontinuation, 5.5 ± 6.5 days vs. 2.4 ± 1.6 days (mean difference 3.1, 95% confidence interval 1.5 to 4.7, P = 0.0003). In patients started on midodrine within 48 hours of stability, time to IV vasopressor discontinuation was similar to the vasopressor alone cohort. Secondary outcomes including ICU and hospital LOS after vasopressor initiation, ICU and in-hospital mortality, and ICU readmission were similar between groups. Twenty patients were discharged from the hospital on midodrine. Incident bradycardia was increased in the midodrine group, but hypertension was similar between groups. Conclusions: Patients in the midodrine group exhibited a longer time to vasopressor discontinuation; however, this difference was only apparent in those with midodrine initiation more than 48 hours after hemodynamic stability in a post-hoc subgroup analysis. These outcomes may be attributed to midodrine being used as salvage therapy.

Purpose: There is extensive evidence linking Potentially Inappropriate Medication (PIM) use and adverse health outcomes. The VIONE core team and VA multidisciplinary partners created, implemented and disseminated the VIONE methodology across VA sites nationwide to facilitate and track deprescribing, through coaching, medical informatics and integration with the electronic health record. The purpose of this article is to report 3 sites in the federal health system (2 VA and 1 Indian Health Services) unique experiences of implementing and adapting VIONE locally while maintaining fidelity to fundamental VIONE intervention strategies. Methods: Three VA sites reported experiences of implementing VIONE, including an overview of the clinical workflow, clinicians involved, facilitators and barriers of implementation, and results. Results: The VIONE intervention was adapted for site-specific implementation. Personnel included trainees, clinical pharmacists, and home based primary care programs. Local and national dashboards were used to identify Veterans at high risk for polypharmacy and to track deprescribing. Implementation remained consistent with the VIONE core characteristics and facilitated education and conversations about medications with patients and caregivers. Adaptations were made at each site to meet that site’s needs. Implementation resulted in safe deprescribing practices and staff empowerment with significant cost savings. Conclusion: The VIONE methodology and tools are adaptable across clinical settings with inherent flexibility to local workflows and practice preferences by end users. VIONE presents a standardized, easy-to-use method for promoting medication review for older adults. Further evaluation may help identify best practices to promote positive outcomes related to deprescribing and reducing polypharmacy in older adults.

Background: Cephalosporins are increasingly used to treat severe urinary tract infections (sUTI) due to rising resistance with standard antibioics. When switching from intravenous to oral cephalosporins there is limited clinical outcome data to guide selection. Objective: To compare the failure rate between cephalexin and cefdinir when used as oral step-down therapy in sUTI. Methods: In this retrospective study, we assessed patients admitted to 3 hospitals for sUTI over a 1-year period. Cases were identified using ICD-10 codes N10, N39.0, and A41.9. Patients who received intravenous antibiotics for >24 hours and completed treatment with cephalexin or cefdinir were included. The primary composite outcome was death, rehospitalization for UTI in 30 days, unplanned clinic or emergency visit for UTI in 30 days, hospitalization for any reason in 90 days, or Clostridoides difficile infection. Secondary outcomes included each individual composite outcome element. Results: Overall, 75 cefdinir and 135 cephalexin cases were included. Patients were similar in baseline characteristics. Pyelonephritis occurred among the cephalexin group (30.2% vs 46.7%, P = 0.024). Composite failure occurred in 8% of patients receiving cefdinir and 14.1% receiving cephalexin (P = 0.193). Secondary outcomes did not differ except clinic or emergency visit for UTI was lower among patients receiving cefdinir than cephalexin (0% vs 7.2%; P = 0.028). Logistic regression revealed no significant variable associations with treatment failure, except for cephalexin use, which was associated with clinic or emergency visit for UTI (r² = 0.075). Conclusions: Treatment failure rates did not differ between cefdinir and cephalexin; however, patients receiving cephalexin had more unplanned clinic and emergency visits.

Introduction: Intravenous (IV) regular insulin treats acute hyperkalemia. No guideline recommendations exist on the appropriate dose to be administered to maximize safety and efficacy. Objectives: The objective of this study was to evaluate the safety and efficacy of IV regular insulin in patients who received 5 units of IV regular insulin to any dose greater than 5 units for acute hyperkalemia treatment. Methods: This was a single-center, retrospective, observational, cohort study. Patients were included if they were at least 18 years old, received greater than or equal to 5 units IV regular insulin, had pre-insulin potassium greater than or equal to 5.1 mEq/L and blood glucose measured within three hours before and 12 hours after insulin administration. The primary outcome was the incidence of hypoglycemia within 12 hours of insulin administration. Results: Eight-hundred and ninety-six charts were reviewed and 290 patients were included; 126 patients received 5 units and 164 patients received more than 5 units of IV regular insulin. Six patients (4.7%) who received 5 units experienced hypoglycemia compared to 23 patients (14%) who received greater than 5 units (P = 0.0014). Twenty-six of 29 (90%) who experienced hypoglycemia had renal impairment. Groups had a similar baseline mean potassium of 5.9 mEq/L (P = 0.32) and follow-up mean potassium of 5.3 mEq/L (P = 0.87). Conclusion: Patients who received 5 units of IV regular insulin had a lower incidence of hypoglycemia with a similar reduction in serum potassium when compared to patients who received doses greater than 5 units.

Emergency department (ED) practitioners frequently prescribe antibiotics for sepsis and other infections, with quality and performance metrics often influencing broad-spectrum antibiotic selection. This study objective was to evaluate improvements in antibiotic selection in the ED following implementation and revision of sepsis order sets designed to adhere to Centers for Medicare and Medicaid Services sepsis performance measure bundle across time periods. This single-center, retrospective analysis assessed antibiotic orders in the ED across three periods of order set availability: no sepsis order set (period 1), general broad-spectrum order set (period 2), and infectious-source specific order set (period 3). Order rates of narrow-spectrum β-lactams, extended-spectrum cephalosporins, antipseudomonal β-lactams, fluoroquinolones, clindamycin, and other agents were assessed. Individual patient encounters with antibiotic orders for period 1 (n = 4228), period 2 (n = 4407), and period 3 (n = 5129) were assessed. Order set use for antibiotic ordering increased across time periods (4% vs 20.6% vs 53.3%; P < 0.001). Period 3 was associated with an increase in narrow spectrum β-lactam use (3% vs 3% vs 15.2%; P < 0.001), a decrease in antipseudomonal β-lactam use (30.1% vs 36.1% vs 27.7%; P < 0.001), and a decrease in targeted antibiotics associated with high risk for adverse effects (28% vs 16% vs 6.9%; P < 0.001). The creation and utilization of an infectious source-specific sepsis antibiotic order set was associated with improved antibiotic ordering trends in the emergency department. This intervention should be considered by hospital antimicrobial stewardship programs.

Ibuprofen and ketorolac are nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used to treat acute back pain in the Emergency Department (ED). Data comparing pain relief between oral and intramuscular administration at their proposed ceiling doses is lacking. The aim of this study was to compare oral (PO) ibuprofen 400 mg to intramuscular (IM) ketorolac 10 mg for the treatment of acute, atraumatic, musculoskeletal back pain. This single-center, double-blind, double-placebo, randomized study compared PO ibuprofen 400 mg to IM ketorolac 10 mg for acute, atraumatic musculoskeletal back pain in adult patients presenting to an urban ED. Subjects were randomized to receive PO ibuprofen 400 mg suspension plus IM placebo injection or IM ketorolac 10 mg plus PO placebo suspension. The primary outcome was absolute reduction in pain score 1 hour after medication administration, as measured by visual analog scale (VAS). Secondary outcomes included rescue analgesia administration at 60 minutes and adverse drug reactions. The author’s enrolled 93 patients; 47 in the ibuprofen group and 46 in the ketorolac group. VAS score reduction from baseline to 1 hour with ibuprofen or ketorolac was 35 vs 32, respectively (95% Confidence Interval: −8.03 to 15.03). Rescue analgesia administration at 60 minutes was similar between both groups; adverse reactions were reported in the ketorolac group only as pain at injection site in two patients. In this prospective analysis, PO ibuprofen 400 mg and IM ketorolac 10 mg provide comparable pain relief for the treatment of acute, atraumatic, musculoskeletal back pain.

Background: Optimizing early antimicrobial therapy and incorporating clinical pharmacists into sepsis treatment strategies are essential for improving patient outcomes. Objective: To examine the appropriateness of empiric antimicrobial selection for patients presenting with community onset sepsis with confirmed bacteremia, to characterize de-escalation practices, and to evaluate pharmacy involvement throughout the sepsis care process. Methods: We conducted a retrospective review of adult patients with community-onset sepsis and confirmed bacteremia who presented to the Emergency Department (ED) between 9/2022 and 5/2023 at our hospital. The primary outcome was the percent of patients with ineffective empiric antimicrobials. Secondary outcomes included time to de-escalation, sepsis outcomes, sepsis guidelines adherence, and pharmacy interventions. Results: 109 patients were included. Median Charlson Comorbidity Index (CCI) was 6 (IQR 3-8) and Pitt bacteremia score 0 (IQR 0-1). Median time to first antibiotic administration was 29 minutes (IQR 15-50). Ineffective empiric antimicrobials occurred in 13.7% of cases, with median time to effective antibiotics at 24 h. De-escalation occurred in 84% of cases. The median time for discontinuation was 2 days for antimicrobial coverage against MRSA and atypical organisms and 4 days for coverage against P. aeruginosa. Initial therapy adhered to guidelines in 70.6% of cases, with deviation primarily due to vancomycin administration in the absence of MRSA risk factors. Antibiotic-related pharmacy recommendations were made in 40% (n = 44/109) of ED patients and 96% (n = 105/109) of hospitalized patients. In-hospital mortality, ICU admission, 30-day infection related re-admission and C. difficile infection within 6 months were 8.3% (n = 9), 42.2% (n = 46), 8.3% (n = 9), and 1.8% (n = 2), respectively. Conclusion: Pharmacist involvement led to appropriate antimicrobial selection in the ED, effective de-escalation, and favorable sepsis outcomes.

Background: Methocarbamol is a central nervous system depressant with antispasmodic properties used as a skeletal muscle relaxant as part of a multimodal analgesia regimen in critically ill patients. Intravenous (IV) methocarbamol contains polyethylene glycol (PEG) 300 and propylene glycol (PG) which have been associated with acute kidney injury (AKI). To mitigate AKI risk, IV methocarbamol is limited to 72 consecutive hours, followed by a 48-hour drug-free interval (DFI). Objective: To characterize the incidence of AKI in intensive care unit (ICU) patients receiving IV methocarbamol. Methods: This is a single-center, retrospective evaluation of adult trauma or surgical ICU patients who received at least 3 consecutive doses of IV methocarbamol. The primary outcome was the difference in SCr from day 1 through day 7 after IV methocarbamol initiation. Results: A total of 68 patients met inclusion criteria. Four patients were classified in the non-DFI group. There was no difference in the median (IQR) SCr (mg/dL) measured at any time point from day 1 through day 7 after IV methocarbamol initiation in the entire cohort [0.83 (0.71, 1.08) vs 0.74 (0.62, 1.33), P = 0.55]. There was no difference between the median (IQR) SCr (mg/dL) from day 1 through day 7 in patients that had no DFI [1.04 (0.89, 2.56) vs 1.20 (0.79, 2.92), P = 0.84]. Conclusion: No statistically significant change in SCr was observed over time in critically ill patients receiving IV methocarbamol regardless of DFI use.

To describe a case of Fournier’s gangrene associated with ertugliflozin. A 51-year-old male was admitted due to scrotal pain, urinary urgency, and subjective infectious symptoms. He was diagnosed with Fournier’s gangrene, likely related to patient’s home medication of ertugliflozin. Management and hospital course included antimicrobial and antifungal courses and was complicated by numerous surgical debridements by the urology team. After over 2 weeks, patient was discharged to rehabilitation facility. This report reiterates the importance of awareness of Fournier’s gangrene as a potential adverse event of sodium-glucose cotransporter-2 inhibitors, including ertugliflozin.

Sirolimus is an immunosuppressive agent for solid organ transplant recipients and is commercially available as an oral tablet and liquid solution. Current package labeling does not support crushing tablets for administration via feeding tubes. A 72 year old white male presented to the trauma intensive care unit after a motor vehicle crash with a reported history of an orthotopic cardiac transplantation on maintenance sirolimus and prednisone, both of which were resumed on hospital day 1. During admission, the patient required intubation with placement of a nasogastric tube (NG) due to worsening respiratory status. Sirolimus was subsequently given by crushing the tablet and administering via the NG tube. Prior to sirolimus resumption on hospital day 1, a baseline sirolimus level resulted as 2.4 ng/mL and repeat trough levels of 1.7 ng/mL and 2.1 ng/mL were obtained on hospital days 17 and 24, respectively. The patient was discharged to a long term care facility after placement of a tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube with orders to continue maintenance sirolimus and prednisone administered crushed via PEG tube. This report describes a novel administration method of sirolimus in a critically ill adult with detectable sirolimus levels throughout admission. This administration technique appears to be safe and warrants further investigation as a potentially efficacious alternative to standard oral administration.

Olmesartan, an angiotensin II receptor blocker (ARB) approved in 2002, is used to treat hypertension, either alone or with other antihypertensive drugs. It has been frequently associated with sprue-like enteropathy, while few cases of colitis have been reported. Differentiating between sprue-like enteropathy and colitis is of clinical concern, since just the first condition is a well-documented adverse event of olmesartan. Diagnosis of these occurrences is difficult, as symptoms are unspecific namely diarrhoea, weight loss, fatigue, nausea, and abdominal discomfort, with laboratory findings showing anaemia, electrolyte imbalances, and vitamin deficiencies. Here, we report two cases of patients in treatment for hypertension with olmesartan in association with hydrochlorothiazide and amlodipine, who developed sprue-like enteropathy and colitis, respectively. We then conducted a disproportionality analysis of cases retrieved from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to assess the association level between these conditions and olmesartan. We found a strong association between olmesartan and sprue-like enteropathy (ROR 8499.53 (95% CI: 8402.05 – 16383.99)). Olmesartan resulted to be associated also with colitis (ROR 2.56 (95% CI: 2.28 – 2.88)). In light of the diagnostic challenges posed by nonspecific symptoms, these findings underscore the importance of distinguishing between the two conditions in patients exposed to olmesartan, to improve the spectrum of knowledge.

Medications account for nearly two-thirds of all cases of syndrome of inappropriate antidiuretic hormone secretion (SIADH). Numerous psychotropics including antipsychotics have been associated with SIADH but it is difficult to show a causal relationship. We report a unique case where a patient developed hyponatremia and upon rechallenge with aripiprazole resulted in a second incidence. There is limited literature recognizing aripiprazole induced SIADH and especially any focused on medication rechallenge.

Many patients living with human immunodeficiency virus (HIV) may develop long-term metabolic complications due to various reasons, such as chronic inflammation and adverse effects from antiretrovirals (ARVs). A particularly significant metabolic complication is type 2 diabetes (T2DM); however, limited evidence is available regarding the management of this disease state among people living with HIV (PLWH). We review the available resources and evidence on the management of T2DM among PLWH. Diagnosis and monitoring of T2DM are slightly different from the general population as hemoglobin A1c may underestimate the level of glycemia PLWH experience. Although PLWH are typically not reported within landmark clinical trials for antidiabetic medications, treatment is likely similar to those without the virus. There are several drug-drug interactions to note between ARVs and antidiabetic medications with one of the most notable being between dolutegravir and metformin. This interaction requires the maximum daily dose of metformin to be reduced. Additionally, modifications may be considered to a patient’s ARV regimen in order to reduce metabolic disturbances as these medications may affect fat redistribution, lipids, weight, and insulin resistance. This review article is intended to aide clinicians in clinical decision making when treating PLWH diagnosed with T2DM.