Cefepime-Enmetazobactam: A Drug Review of a Novel Beta-Lactam/Beta-Lactamase Inhibitor.

OBJECTIVE: To describe and analyze the pharmacodynamic and pharmacokinetic properties and clinical evidence supporting the efficacy and use of cefepime-enmetazobactam (FEP-EMT). DATA SOURCES: A literature search was conducted using MEDLINE and EMBASE databases (January 2015 to May 2024). Search terms included: "cefepime-enmetazobactam" or "cefepime" or "enmetazobactam" or "cefepime" or "novel beta-lactamase inhibitor" and "complicated urinary tract infection" or "cUTI." Conference abstracts, bibliographies, clinical trials, and drug monographs were included for review. STUDY SELECTION AND DATA EXTRACTION: Relevant studies in English and clinical trials conducted in humans were reviewed. DATA SYNTHESIS: In February 2024, the Food and Drug Administration (FDA) approved the combination beta-lactam/beta-lactamase inhibitor (BL/BLI) FEP-EMT for the treatment of complicated urinary tract infections (cUTIs) and acute pyelonephritis following the completion of the Phase III ALLIUM trial comparing it to piperacillin-tazobactam (TZP). The trial resulted in 79.1% of the FEP-EMT group versus 58.9% of the TZP group meeting the primary outcome of clinical cure and microbiological eradication (95% CI 21.2 [14.3 to 27.9]). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING AGENTS: This review describes the use of FEP-EMT for the treatment of cUTI and compares its use to other novel BL/BLI combinations including utility in drug-resistant infections. CONCLUSIONS: FEP-EMT provides an antimicrobial option to reduce overuse of carbapenems for extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. However, unlike other novel BL/BLI combinations, its limited spectrum of antibacterial effect for more difficult-to-treat pathogens and cost may also impact its overall utilization.

Oteseconazole for the Treatment of Recurrent Vulvovaginal Candidiasis: A Drug Review.

OBJECTIVE: The objective of the study is to describe and analyze the pharmacodynamics and pharmacokinetics of oteseconazole as well as the clinical evidence supporting the efficacy of oteseconazole in treating recurrent vulvovaginal candidiasis (RVVC). DATA SOURCES: A literature search was conducted using MEDLINE and EMBASE databases (2015-June 2023). Search terms included "oteseconazole" OR "VT-1161" or "VIVJOA" AND "RVVC" or "recurrent vulvovaginal candidiasis" or "vulvovaginal candidiasis." Conference abstracts, bibliographies, clinical trials, and drug monographs were included for review. STUDY SELECTION AND DATA EXTRACTION: Relevant studies in English and clinical trials conducted in humans were reviewed. DATA SYNTHESIS: Oteseconazole is approved for the treatment of RVVC. In 2 identical phase III studies, oteseconazole was superior to placebo through 48 weeks for preventing recurrence of RVVC (6.7% vs 42.8%, P < 0.001 and 3.9% vs 39.4%, P < 0.001). In the only phase III trial comparing oteseconazole against active drug, oteseconazole was well tolerated and exhibited noninferiority to fluconazole in acute treatment and superiority to placebo for prevention maintenance through 50 weeks (5.1% vs 42.2%, P < 0.001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING AGENTS: This review describes the use of oteseconazole for the treatment of RVVC as compared with fluconazole. Oteseconazole is an effective treatment option for common pathogens causing vulvovaginal candidiasis, including Candida and fluconazole-resistant Candida. CONCLUSIONS: Oteseconazole is an effective and safe treatment option for the management of RVVC though current research lacks comparison with established maintenance regimens. Additional research is needed to ascertain the placement of oteseconazole in the treatment of RVVC.

False negative diagnostic errors with polymerase chain reaction for the detection of cryptococcal meningoencephalitis.

The accuracy of the BioFire FilmArray Meningitis/Encephalitis (ME) panel for the identification of Cryptococcus has recently been called into question. The primary objective of this study was to assess the agreement between the BioFire ME polymerase chain reaction (PCR) and other markers of cryptococcal infection. This retrospective review identified five patients with cryptococcal meningoencephalitis, 4 of whom had a negative ME panel for Cryptococcus. All five cases had positive serum cryptococcal antigens, and three of five had a positive cerebrospinal fluid (CSF) culture for Cryptococcus. The BioFire ME panel does not appear to be reliable for ruling out Cryptococcus meningoencephalitis; multiple testing methods are recommended.

Novel Drug-Drug Interaction of Potential Rifabutin-Induced Edoxaban Failure: A Case Report.

Purpose: To report an incident of a breakthrough deep vein thrombosis (DVT) and potential example of a drug-drug interaction in a patient treated with edoxaban and rifabutin who was being treated for respiratory tuberculosis. Case: A 76-year-old male presented with anemia requiring transfusion and subsequent shortness of breath that was later diagnosed to be respiratory tuberculosis. He experienced a prolonged hospital stay due to persistently positive Mycobacterium tuberculosis respiratory samples and a complicated social situation that required continuous hospitalization for approximately five months. During his treatment the patient was transitioned from apixaban to edoxaban due to a drug-drug interaction with rifabutin. He subsequently had a DVT while on edoxaban after two months of therapy that would require him to transition to warfarin. Conclusion: This case represents an example of a potentially significant drug-drug interaction between edoxaban and rifabutin. Other direct oral anticoagulants (DOACs) exhibit a potential drug-drug interaction that limit their effectiveness when used with rifamycins. This report describes the first known case of a patient experiencing a DVT after prolonged edoxaban use in combination with rifabutin. Treatment with DOACs for patients taking concomitant cytochrome P450 (CYP) inducers such as rifabutin may be more complicated than previously believed.

Describing the decision process of post-operative opioid and pain prescribing patterns in orthopedic and general surgeons.

OBJECTIVE: To describe the post-operative opioid prescribing behaviors of orthopedic and general surgeons through the use of the Integrated Behavioral Model (IBM), and subsequently the steps and logic used by providers in determining post-operative pain prescriptions. DESIGN: This study was a prospective, cross-sectional, cohort study utilizing qualitative methods consisting of semistructured interviews. Data were analyzed using thematic analysis to categorize and identify themes to describe prescriber behavior. SETTING: All participants were from a regional health system in central Appalachia. PATIENTS AND PARTICIPANTS: Mixed population of orthopedic and general surgeons who completed residency training and performed nontraumatic procedures. MAIN OUTCOME MEASURE: Categorization and identification of themes within the constructs of the IBM that described surgeon opioid prescribing. RESULTS: Fifteen surgeons participated in this study. Themes were identified within the context of the IBM. Attitudes by surgeons consisted of blame toward the government, a lack of personal screening of patients, and a theme of the abusing population of patients only being a small group. Norms were identified that included prescribing based on a standard prescribing set, realization of patient fear, and the idea of past mentality. Surgeons believed in their ability to prescribe responsibly and conservatively. CONCLUSIONS: The prescribing patterns of surgeons and their keenness to assess patients for opioid abuse vary. Most surgeons did not actively participate in screening activities but rely on ancillary staff. Surgeons utilize federal and state laws to back prescribing patterns and thwart patient attempts for additional medications. Prescribers maintain a sense of self-confidence with their own knowledge and ability to taper and keep patients from becoming reliant on opioid prescribing.

An Unusual Case of COVID-19 Presenting as Acute Psychosis.

PURPOSE: To report a case of COVID-19 presenting with acute psychosis, without the hallmark respiratory symptoms of fever, cough, and shortness of breath associated with the novel virus. CASE SUMMARY: A 58 year-old male presented with acute psychosis and no symptoms associated with COVID-19. He denied fever, chills, chest pain, shortness of breath, or gastrointestinal symptoms. The patient had a medical history of coronary artery disease, chronic hepatitis C, polysubstance abuse (including cocaine and alcohol), liver disease, anxiety, and panic disorder. Patient was confused, disruptive, unable to communicate, and admitted to hallucinations. Prior to transfer to a psychiatric facility, the patient developed a cough, triggering COVID-19 testing and a positive result. He was initially treated with hydroxychloroquine before this was discontinued. The patient was treated with haloperidol and lorazepam before returning to baseline. He was discharged home with continued isolation. CONCLUSION: Acute psychosis, with or without other symptoms, appears to be a potential presentation of COVID-19 and should be considered by clinicians as a possible presenting manifestation. Other coronaviruses appear to have also been linked to neurological manifestations, including psychosis. Neurological manifestations of the virus vary widely, but have been reported multiple times. Treatment, as shown in this case report, appears to be supportive and symptom based for the associated psychotic symptoms. Optimal antiviral treatment is still yet to be clearly defined, as research continues on how to best treat the virus itself.

Clinical Pharmacy Practice Patterns Among North Carolina Rural Hospitals.

INTRODUCTION: Rural hospitals are isolated without adequate funding needed to provide for clinical services offered at larger health systems. The purpose of this study is to determine the clinical pharmacy services available and desired by rural hospitals in North Carolina. METHODS: This prospective, cross-sectional, survey was distributed to a cohort of rural pharmacy directors and managers at rural hospitals across North Carolina. Data collected pertained to characteristics of the hospital and pharmacy, pharmacy director, clinical services, and responder impressions on their ability to maintain or enhance clinical services. Responses were summarized utilizing descriptive statistics and free-responses were coded for similar themes. RESULTS: Seventeen respondents (32.6%) completed the survey. Clinical activities varied, as did characteristics of the hospitals and staff. Improved patient care is the primary reason why hospital pharmacies expand their clinical participation (46.7%). Pharmacy directors believed growth of clinical activities was a long-term goal while reporting regulations, staff, and finances as barriers to growth. CONCLUSION: Clinical pharmacy services vary in NC rural hospitals. Directors exhibit a willingness to expand clinical responsibilities. Rural hospital pharmacy directors desire pharmacists to be active clinically in patient care, but face barriers in reaching that goal.

Using the extended self-regulatory model to characterise diabetes medication adherence: a cross-sectional study.

OBJECTIVES: To cluster the adherence behaviours of patients with type 2 diabetes based on their beliefs in medicines and illness perceptions and examine the psychosocial, clinical and sociodemographic characteristics of patient clusters. DESIGN: Cross-sectional study. SETTING: A face-to-face survey was administered to patients at two family medicine clinics in the Midwest, USA. PARTICIPANTS: One hundred and seventy-four ≥20-year-old, English-speaking adult patients with type 2 diabetes who were prescribed at least one oral diabetes medicine daily were recruited using convenience sampling. PRIMARY AND SECONDARY OUTCOME MEASURES: Beliefs in medicines and illness perceptions were assessed using the Beliefs about Medicines Questionnaire and the Brief Illness Perception Questionnaire, respectively. Self-reported medication adherence was assessed using the Morisky Medication Adherence Scale. Psychosocial correlates of adherence, health literacy and self-efficacy were measured using the Newest Vital Sign and the Self-efficacy for Appropriate Medication Use, respectively. Two-step cluster analysis was used to classify patients. RESULTS: Participants' mean age was 58.74 (SD=12.84). The majority were women (57.5%). Four clusters were formed (non-adherent clusters: ambivalent and sceptical; adherent clusters: indifferent and accepting). The ambivalent cluster (n=30, 17.2%) included low-adherent patients with high necessity beliefs, high concern beliefs and high illness perceptions. The sceptical cluster (n=53, 30.5%) included low adherent patients with low necessity beliefs but high concern beliefs and high illness perceptions. Both the accepting (n=40, 23.0%) and indifferent (n=51, 29.3%) clusters were composed of patients with high adherence. Significant differences between the ambivalent, sceptical, accepting and indifferent adherent clusters were based on self-efficacy, illness perception domains (treatment control and coherence) and haemoglobin A1c (p<0.01). CONCLUSIONS: Patients with diabetes in specific non-adherent and adherent clusters still have distinct beliefs as well as psychosocial characteristics that may help providers target tailored medication adherence interventions.

The association of health literacy with illness perceptions, medication beliefs, and medication adherence among individuals with type 2 diabetes.

BACKGROUND: Beliefs in medications and illness perceptions is associated with medication adherence among individuals with diabetes and several adherence interventions focus on patients' beliefs in medicines and illnesses. Though health literacy is important in medication adherence, the relationship between health literacy and medication adherence remains inconclusive; thus raising the question as to whether health literacy has an amplifying or reducing effect on the relationship between beliefs and adherence. OBJECTIVE: The study examined (1) the association between health literacy, beliefs in medicines, illness perceptions, and medication adherence in individuals with type 2 diabetes and (2) the moderating effects of health literacy (including numeracy and document literacy) on the relationship between illness perceptions, beliefs in medicines, and medication adherence. METHODS: Adults ≥20 years taking oral diabetes medicines at two family medicine clinics, completed a cross-sectional survey. Participants were assessed on beliefs in medicines, illness perceptions, health literacy, self-efficacy, and medication adherence. Multiple linear regressions examined the effect of health literacy, beliefs and self-efficacy, and the moderator effect of health literacy in the relationship between beliefs and adherence. RESULTS: Of the 174 participants, more than half were women (57.5%) and white (67.8%). There was a significant positive association between self-efficacy and adherence (ß = 0.486, p < .001), and a negative association between threatening illness perceptions and adherence (ß = -0.292, p < .001). Health literacy had a significant moderator effect on the relationship between adherence and concerns beliefs (ß = -0.156, p = .014) and threatening illness perceptions (ß = 0.196, p = .002). The concern beliefs - adherence association was only significant at marginal and adequate literacy levels. When health literacy was separated into numeracy and document literacy, only numeracy moderated the illness perceptions - adherence relationship (ß = 0.149, p = .038). CONCLUSIONS: Health literacy, especially numeracy, needs to be initially addressed before diabetes adherence interventions that address individual concerns about medicines and threatening illness perceptions can work.