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.

Therapeutic Options for Adult Patients With Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Narrative Review.

OBJECTIVE: To compare the efficacy of antimicrobial therapies used in the management of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. DATA SOURCES: A literature search using the PubMed database (inception to December 2022) was conducted using the search terms "Staphylococcus aureus bacteremia," "methicillin-susceptible Staphylococcus aureus bacteremia," "persistent methicillin-susceptible Staphylococcus aureus bacteremia," and "refractory methicillin-susceptible Staphylococcus aureus bacteremia ." In addition, therapeutic agents which could be used as treatment for MSSA including "nafcillin," "oxacillin," "cefazolin," "ceftaroline," "gentamicin," "rifampin," and "daptomycin" were also combined with the aforementioned search terms to capture data using these agents. STUDY SELECTION/DATA EXTRACTION: Clinical data were limited to those published in the English language. Articles and abstracts were considered for inclusion in addition to ongoing trials identified through ClinicalTrials.gov. DATA SYNTHESIS: A total of 78 articles were reviewed including 17 in vitro or animal model studies and 39 studies including patient data. The remaining 22 articles included guidelines, review articles, and editorials. Recent data evaluating use of dual ß-lactam regimens for persistent MSSA bacteremia were limited to 8 case reports or case series. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: At present, there is little guidance on how to best manage patients with persistent MSSA bacteremia. This narrative review collates the available data to assist clinicians in selecting the best possible antimicrobial regimen when facing this clinical conundrum. CONCLUSIONS: Modification of antimicrobial therapy, in conjunction with source control and infectious diseases consultation, may all be necessary to sterilize blood cultures in patients with persistent MSSA bacteremia.

Comparison of pharmacists' scoring of fall risk to other fall risk assessments.

OBJECTIVES: Given their professional education and participation within the health care system, pharmacists are ideal candidates to assess drug-associated fall risk for patients. The purpose of this investigation was to determine whether pharmacists can quantitatively differentiate individuals who reported falling within the previous year (fallers) from those who do not (nonfallers), and to compare the pharmacists' evaluation with 2 recently published fall risk assessments. DESIGN: Cross-sectional design of pharmacists' assessments of fall risk. SETTING AND PARTICIPANTS: This is a cross-sectional study where 6 licensed pharmacists evaluated patient records from Wave 1 of the National Social Life, Health and Aging Project dataset using generic drug list (drug counts), age, and body mass index to generate a Pharmacist Risk Score (PRS) based on these variables. Pharmacists were allowed to use drug information resources and were provided with a simple 5-point scale to assist them in scoring patients. OUTCOME MEASURES: The main outcome measure of this study was a comparison of the following fall risk assessments (PRS, drug counts, Medication-Based Index of Physical Function, Quantitative Drug Index, and Timed Up and Go [TUG]) capacity to differentiate fallers from nonfallers. RESULTS: Each fall risk assessment was highly correlated (P < 0.001) with the number of reported falls. Drug-associated fall risk assessments were highly correlated (P < 0.001) with each other, but not with TUG. Each fall risk assessment differentiated fallers from nonfallers based on logistic regression (P ≤ 0.001). Receiver operating characteristic (ROC) curve analysis was significant (P ≤ 0.002) for each assessment. The comparison of ROC area under the curve for the fall risk assessments found no significant difference between the PRS and other assessments. CONCLUSION: Fall risk assessment by pharmacists was comparable with other fall risk assessments in distinguishing fallers from nonfallers.

Utility of the respiratory viral panel as an antimicrobial stewardship tool.

WHAT IS KNOWN AND OBJECTIVE: The development of rapid diagnostics has revolutionized antimicrobial stewardship with efforts targeting earlier de-escalation or discontinuation of antibiotics. The respiratory viral panel (RVP) is one tool quickly able to detect common viral and bacterial pathogens using polymerase chain reaction technology. Utility may be further enhanced in conjunction with procalcitonin (PCT). However, the optimal use of the RVP to the clinical pharmacist in the treatment of community-acquired respiratory infections remains unclear. METHODS: The purpose of this guide is to review the available literature regarding the impact of the RVP with and without procalcitonin on antimicrobial stewardship efforts and to provide guidance on how to use each of these tools. RESULTS AND DISCUSSION: In total, 13 studies were included, 5 of which utilized PCT in conjunction with RVP and 8 of which did not use PCT. The majority of studies were retrospective in nature, and the most common outcomes evaluated were antibiotic days of therapy (DOT) and time to antibiotic discontinuation. WHAT IS NEW AND CONCLUSION: After review, RVP alone has limited value to antimicrobial stewardship; however, when used in conjunction with procalcitonin, RVP has the potential to reduce antibiotic use and duration.

Vancomycin plus piperacillin/tazobactam and acute kidney injury risk: A review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Acute kidney injury is a devastating consequence observed with antibiotic therapy. The objective of this review was to summarize available data regarding the rates of acute kidney injury with vancomycin plus piperacillin/tazobactam compared to other beta-lactam combinations. METHODS: A PubMed search from 2011 to May 2020 was conducted using the following search terms: vancomycin AND piperacillin/tazobactam AND acute kidney injury. Additional references were identified from a review of citations. Articles evaluating exclusively paediatric patients and articles evaluating vancomycin monotherapy as the comparator group were excluded. Case reports and case series were also excluded. RESULTS AND DISCUSSION: There were 18 studies included. Ten studies adjusted for potential confounders of acute kidney injury. Fourteen retrospective studies, one prospective study and three meta-analyses found the combination of vancomycin/piperacillin/tazobactam to be associated with a higher rate of acute kidney injury than the comparator group(s). WHAT IS NEW AND CONCLUSION: Although there are data to support that the combination of vancomycin plus piperacillin-tazobactam increases the risk of acute kidney, much of the data come from small retrospective studies with variable adjustment for confounders. Furthermore, study heterogeneity on inclusion criteria and evaluation of long-term outcomes should be cautiously interpreted. Finally, additional data suggest that the risk of acute kidney injury seems to be minimized with shorter courses of therapy. Without prospective studies available, antimicrobial stewardship efforts should continue to target reducing broad-spectrum regimens, often limiting the need for long-term vancomycin/piperacillin/tazobactam combination.

Assessment of risk factors for increased resource utilization in kidney transplantation.

BACKGROUND: There are only a limited number of studies that have sought to identify patients at high risk for medication errors and subsequent adverse clinical outcomes. This study sought to identify risk factors for increased health care resource utilization in kidney transplant recipients based on drug-related problems and self-administered surveys. METHODS: In this prospective observational study, adult kidney transplant recipients seen in the transplant clinic between September and November 2015 were surveyed for self-reported demographics, medication adherence, and health status/outlook. Subsequently, patients were assessed for associations between survey results, pharmacist-derived drug-related problems, and health resource utilization over a minimum 6-mo follow-up period. Based on univariate associations, two risk cohorts were identified and compared for health care utilization using multivariable Poisson regression. RESULTS: A total of 237 patients were included, with a mean follow-up of 8 mo. From the patient survey data, Medicaid insured or self-rated poor health status were identified as a significant risk cohort. From pharmacist assessments, those who received incorrect medication or lacked appropriate follow-up medication monitoring were identified as a significant risk cohort (pharmacy errors). The Medicaid insured or self-rated poor health status cohort experienced 43% more total health care encounters (incident rate ratios [IRR] 1.43, 1.01-2.02) and 35% more transplant clinic visits (IRR 1.35, 1.03-1.77). The pharmacy errors cohort experienced 4.2 times the rate of total health care encounters (IRR 4.17, 1.55-11.2), 4.1 times the rate of hospital readmissions (IRR 4.09, 1.58-10.6), and 2.3 times the rate of transplant clinic visits (IRR 2.31, 1.04-5.11). CONCLUSIONS: Medicaid insurance, self-rated poor health status, and errors in the medication regimen or monitoring were significant risk factors for increased health care utilization in kidney transplant recipients. Further research is warranted to validate these potential risk factors, determine the long-term impact on graft/patient survival, and assess the mutability of these risks through prospective identification and intervention.

Enoxaparin Dosing at Extremes of Weight: Literature Review and Dosing Recommendations.

OBJECTIVE: To review the literature on both thromboprophylaxis and treatment of venous thromboembolism (VTE) with enoxaparin in low- and high-body-weight patients and to make dosing and monitoring recommendations in these patient populations. DATA SOURCES: A search using PubMed was conducted (1995 to January 2018) using the following key words: enoxaparin, body weight, AND thromboprophylaxis, or AND treatment. Additional references were identified from a review of citations. STUDY SELECTION AND DATA EXTRACTION: Studies included examined the effect of body weight and/or body mass index (BMI) on VTE, bleeding, enoxaparin dosing, and/or anti-Xa concentrations for thromboprophylaxis and treatment-dose enoxaparin. Studies in pediatric and pregnant patients were excluded. DATA SYNTHESIS: Optimal enoxaparin dosing strategies for VTE prophylaxis and treatment for patients at extremes of weight have not yet been elucidated by clinical trials; however, data suggest that standard dosing regimens may not be appropriate in these patients. Relevance to Patient Care and Clinical Practice: This review provides a thorough discussion on both thromboprophylaxis and treatment of VTE with enoxaparin in low- and high-body-weight patients. It includes dosing recommendations to guide clinicians caring for these patient populations. CONCLUSIONS: Patients at extremes of weight require special consideration to determine appropriate enoxaparin doses. Specifically, low-body-weight patients may benefit from 30 mg subcutaneously daily for VTE prophylaxis, and standard weight-based dosing for VTE treatment. Conversely, in patients with BMIs ≥40 kg/m2, 40 mg subcutaneously twice daily is recommended, with consideration for higher doses in patients with BMIs ≥50 kg/m2.

Treatment strategies for persistent methicillin-resistant Staphylococcus aureus bacteraemia.

WHAT IS KNOWN AND OBJECTIVE: Treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a long-standing challenge to health care, often complicated by metastatic infections, treatment failure and mortality. When MRSA bacteraemia persists despite adequate initial treatment, current Infectious Diseases Society of America guidelines recommend evaluation and removal of possible sources of infection. In addition, a change in therapy may be considered. The objective of this review was to explore the therapeutic options for the treatment of persistent MRSA bacteraemia. METHODS: A literature search of PubMed, MEDLINE and Google Scholar was performed using the following search terms: [methicillin-resistant Staphylococcus aureus OR MRSA] AND [bacteraemia OR bloodstream infection] AND [persistent OR persistence OR refractory OR treatment failure OR salvage] AND treatment. We evaluated relevant, adult, English-language, peer-reviewed studies published between 1985 and May 2018. In vitro and animal studies were considered as supportive of in vivo data. RESULTS AND DISCUSSION: Randomized, controlled trials are lacking. However, case series and case reports support multiple treatment options including high-dose daptomycin in combination with an antistaphylococcal ß-lactam, ceftaroline, trimethoprim-sulfamethoxazole (TMP-SMX) or fosfomycin; ceftaroline alone or in combination with vancomycin or TMP-SMX; linezolid alone or in combination with a carbapenem, or telavancin. WHAT IS NEW AND CONCLUSION: Given the heterogeneity of the data, a preferred regimen has not emerged. Prescribers must take into consideration recent exposure, source control, and available synergy and clinical data. Further comparative trials are needed to establish a preferred regimen and the creation of a universal treatment algorithm.

Predicting and preventing readmissions in kidney transplant recipients.

A lack of research exploring post-transplant process optimization to reduce readmissions and increasing readmission rates at our center from 2009 to 2013 led to this study, aimed at assessing the effect of patient and process factors on 30-d readmission rates after kidney transplantation. This was a retrospective case-control study in adult kidney transplant recipients. Univariate and multivariate analyses were utilized to assess patient and process determinants of 30-d readmissions. 384 patients were included; 30-d readmissions were significantly associated with graft loss and death (p = 0.001). Diabetes (p = 0.049), pharmacist identification of poor understanding or adherence, and prolonged time on hemodialysis prior to transplant were associated with an increased risk of 30-d readmissions. After controlling for risk factors, readmission rates were only independently predicted by pharmacist identification of patient lack of understanding or adherence regarding post-transplant medications and dialysis exposure for more than three yr (OR 2.3, 95% CI 1.10-4.71, p = 0.026 and OR 2.1, 95% CI 1.22, 3.70, respectively), both of which were significantly modified by history of diabetes. Thirty-d readmissions are attributable to both patient and process-level factors. These data suggest that a lack of post-transplant medication knowledge in high-risk patients drives early hospital readmission.

A primer on Post-COVID-19 conditions and implications for clinical pharmacists.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is largely viewed as an acute illness involving multiple organ systems. In the wake of the acute illness, many survivors fully recover and return to baseline, while others suffer from a wide range of lingering symptoms collectively known as "post-COVID conditions". The recognition of these conditions as a clinical entity represents the first step in developing a targeted plan for recovery and symptom mitigation. While interventions to directly minimize or reduce new, recurrent, or persistent symptoms are currently unknown, pharmacists can play a key role in optimizing management of these patients.

Direct-acting oral anticoagulant use at extremes of body weight: Literature review and recommendations.

PURPOSE: To review the literature on treatment of venous thromboembolism (VTE) and prevention of cardioembolic stroke with direct-acting oral anticoagulants (DOACs) in low- and high-body-weight patients and to make recommendations regarding agent selection and dosing in these patient populations. SUMMARY: The selection and optimal dosing of DOACs in low- and high-body-weight patients has not yet been fully elucidated by clinical trials; however, evidence suggests that issues of both safety and efficacy in patients at the extremes of body weight may warrant careful consideration when selecting a DOAC for such patients. This review provides a thorough discussion of the use of DOACs in the treatment of VTE and prevention of cardioembolic stroke in patients at the extremes of body weight and provides guidance regarding agent selection. CONCLUSION: While the published evidence on use of DOACs in patients at extremes of body weight is sparse, apixaban and rivaroxaban appear to have the most favorable safety and efficacy profiles. Edoxaban and dabigatran should be avoided.

Direct oral anticoagulants in patients with cancer.

PURPOSE: This review summarizes the available evidence concerning direct oral anticoagulant (DOAC) use to treat venous thromboembolism (VTE) in patients with cancer as well as pertinent safety data on the use of DOACs in patients with both cancer and atrial fibrillation. SUMMARY: The introduction of DOACs into clinical practice changed the way thrombotic complications are managed and prevented in diverse patient populations, including VTE and atrial fibrillation. Low-molecular-weight heparins have been the standard of care for treating VTE in cancer patients due to superiority over vitamin K antagonists in preventing recurrent VTE. Therefore, widespread DOAC use for VTE in patients with active cancer has not been adopted. CONCLUSION: Recent randomized clinical trials (SELECT-D, Hokusai VTE Cancer) have provided evidence that DOACs may have a role in treating VTE in cancer patients.

Development of a Predictive Model for Drug-Related Problems in Kidney Transplant Recipients.

STUDY OBJECTIVE: Drug-related problems (DRPs) are associated with increased rates of infection, rejection, and graft loss in kidney transplant recipients. This study aimed to develop a model to predict which patients are at highest risk of DRPs to streamline pharmacists' workflow in a chronic kidney transplant clinic. DESIGN: Prospective observational study. SETTING: Chronic kidney transplant clinic at a large, tertiary care, academic hospital. PATIENTS: Two hundred thirty-seven adults seen in the kidney transplant clinic between September 16, 2015, and November 30, 2015, who were at least 90 days posttransplantation at the time of their clinic visit. MEASUREMENTS AND MAIN RESULTS: Prospective data detailing DRPs and a survey assessing baseline characteristics and patient-related outcomes were used to generate a predictive model to identify patients at risk of having six or more DRPs; the cutoff of six DRPs provided a threshold for identifying a subset of high-risk patients on whom the transplant pharmacists could focus their efforts. DRPs were categorized as nonadherence, overdosing or underdosing, duplication of therapy, preventable adverse drug reaction, missing medication, erroneous medication, conflicting provider information, undermonitoring or lack of monitoring, and wrong medication received. In total, 865 unique DRPs were identified, and the most common were erroneous medication, missing medication, and nonadherence, accounting for 38%, 21%, and 16% of the DRPs, respectively. A nine-variable model with a sensitivity of 62.5% and specificity of 66.7% (area under the receiver operating characteristic curve of 0.720) was developed to identify patients at risk of having six or more DRPs. The model included the following variables: age, Medicaid for prescription insurance, current employment status, medication affordability, difficulty or lack of difficulty obtaining medications from the pharmacy, negative impact of medications on quality of life, medication nonadherence, poor rating of current health status, and moderate or poor medication understanding. CONCLUSION: These results demonstrated that a straightforward, 5-minute survey completed by renal transplant recipients prior to their clinic visit may be capable of effectively determining those at risk of having six or more DRPs, potentially allowing use as a screening tool for transplant pharmacists' workflow prioritization. External validation is needed before this tool can be used in the outpatient setting.

Effectiveness of an Evidence-Based Induction Therapy Protocol Revision in Adult Kidney Transplant Recipients.

STUDY OBJECTIVE: Induction immunosuppression significantly improves graft outcomes after kidney transplantation, but protocols vary among transplant centers due to the lack of data identifying an optimal induction agent. The objective of this study was to assess the effectiveness of an evidence-based protocol change in induction therapy in adult kidney transplant recipients. DESIGN: Retrospective cohort study. SETTING: Large tertiary care academic medical center. PATIENTS: A total of 349 patients transplanted between August 2011 and December 2013 were included in the study. A protocol revision in 2012 reserved the use of lymphocyte-depleting induction therapy to a select group of traditionally high-risk patients based on the findings of a previous randomized controlled trial performed at this center. MEASUREMENTS AND MAIN RESULTS: The primary outcome was biopsy-proved acute rejection and graft loss. The use of nondepleting induction therapy increased significantly after the protocol revision, with no significant differences in rejection or infection rates identified between protocols. When comparing graft survival between the protocol cohorts, there was no significant difference. A cost-minimization analysis indicated that the revised protocol was associated with considerable medication cost savings. CONCLUSION: A protocol targeting the use of lymphocyte-depleting induction to a select group of high-risk recipients appears to have equivalent efficacy and safety and is less costly compared with a more traditional induction protocol.