Live Biotherapeutic Products for the Prevention of Recurrent Clostridioides difficile Infection.

OBJECTIVE: To review the efficacy, safety, and role of live biotherapeutic products (LBPs) in the prevention of recurrent Clostridioides difficile infection (rCDI). DATA SOURCES: A literature search was performed using PubMed and Google Scholar (through February 2024) with search terms RBX2660, SER-109, and fecal microbiota. Other resources included abstracts presented at recent conferences, national clinical practice guidelines, and manufacturers' websites. STUDY SELECTION AND DATA EXTRACTION: All relevant studies, trial updates, conference abstracts, and guidelines in the English language were included. DATA SYNTHESIS: Two LBPs were recently approved by the Food and Drug Administration for the prevention of recurrence in adults following antibiotic treatment for rCDI. Fecal microbiota, live-jslm is administered rectally as a retention enema, whereas fecal microbiota spores, live-brpk is given orally after bowel preparation. Several phase 2 and phase 3 clinical trials have established the safety and efficacy of these LBPs in reducing rates of rCDI compared with placebo. Patients with severe immunosuppression and those with inflammatory bowel disease were largely excluded from these trials. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: Live biotherapeutic products offer a similar mechanism to conventional fecal microbiota transplant (FMT) in preventing rCDI through microbiota restoration. The primary advantages of LBPs over FMT are their standardized composition and donor stool screening processes for transmissible pathogens. Bezlotoxumab is also available for the prevention of Clostridioides difficile infection; however, there are no clinical data available to compare the efficacy of LBPs with bezlotoxumab, and the benefit of simultaneous use of these preventative therapies is unclear. CONCLUSIONS: Live biotherapeutic products provide a safe and effective option for the prevention of rCDI and represent an improvement over conventional FMT. Additional studies are needed to further determine their place in therapy relative to bezlotoxumab and in the setting of immunosuppression and inflammatory bowel disease.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

Lenacapavir: A Novel Long-Acting Capsid Inhibitor for HIV.

OBJECTIVE: To review the efficacy, safety, and role of lenacapavir (LEN) in the treatment of HIV-1 infection. DATA SOURCES: A literature search was performed using PubMed and Google Scholar (through March 2023) with the search term LEN and GS-6207. Other resources included abstracts presented at recent conferences, the manufacturer's Web site, and prescribing information. STUDY SELECTION AND DATA EXTRACTION: All relevant articles, trial updates, and conference abstracts in the English language were included. DATA SYNTHESIS: Lenacapavir represents a new class of antiretrovirals (ARVs) with a novel mechanism of action as a capsid inhibitor and a unique twice-a-year subcutaneous administration schedule. Lenacapavir when combined with other ARVs has proven to benefit heavily treatment-experienced (HTE) patients with HIV-1 infection in achieving viral suppression and immune restoration. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: Lenacapavir is a new treatment option that patients who are HTE can consider adding as part of an ARV regimen. CONCLUSIONS: Lenacapavir is an effective and well-tolerated option for HTE patients which is a valuable addition to the arsenal of ARVs.

The Essential Role of Senior Care Pharmacists in Antimicrobial Stewardship: An Updated Position Statement on Behalf of the American Society of Consultant Pharmacists and the Society of Infectious Diseases Pharmacists.

Senior care pharmacists are well-positioned to lead and drive antimicrobial stewardship (AMS) initiatives, not only through audit and data collection, but also through communication, collaboration, and cooperation with prescribers and nurses to influence prescribing behaviors. Senior care pharmacists are in a unique position to take a leadership role within the interprofessional team to achieve AMS goals. They should engage with the interprofessional team to promote the judicious and appropriate use of antimicrobials at their practice sites. This position statement is an update of the 2017 version by the American Society of Consultant Pharmacists (ASCP) Antimicrobial Stewardship and Infection and Prevention Control Committee and the Society of Infectious Diseases Pharmacists (SIDP).

Comparing Safety and Effectiveness of Antiretroviral Therapy in a Diverse Population of Older People With HIV.

Background Advances in antiretroviral therapy (ART) enable people with HIV to live longer, healthier lives. However, older people with HIV (OPWH) are more susceptible to long-term toxicity and drug interactions associated with ART. Racial and ethnic minorities have specific social determinants of health, which increase their risks of negative outcomes. Objective To determine if there were differences in the safety and effectiveness of ART in White, Black, and Hispanic OPWH. Methods A retrospective observational study was conducted on patients receiving care between January 1, 2017, and December 31, 2022, at two affiliated HIV clinics in South Florida. The primary effectiveness endpoint was the percentage of OPWH with undetectable viral load (< 50 copies/mL) throughout the study. Secondary safety endpoints were changes in median metabolic, hepatic, and renal parameters. A two-way analysis of variance or the Chi-square test was used to determine differences between groups. Results A total of 116 White, 42 Black, and 40 Hispanic OPWH were included. Upon enrollment, most patients (90.7%) were receiving ART. Of these, the percentage with undetectable viral load was lower among Black (61.8%) compared with White (85.8%; P < 0.01) or Hispanic (83.3%; P < 0.05) patients. Similarly, throughout the study after the first visit, the percentage with undetectable viral load was lower among Black (61.6%) compared with White (84.7%; P < 0.05) or Hispanic (83.3%; P = 0.12) patients. However, there were no significant differences in the percentage of virally suppressed (< 200 copies/mL) participants throughout the study after the first visit between Black (88.5%), White (94.9%), and Hispanic (96.7%) patients. Additionally, no significant changes in safety endpoints were observed among the groups throughout the study. Conclusion Fewer Black OPWH had undetectable viral load upon enrollment and throughout the study compared with White or Hispanic OPWH, suggesting the need to provide more targeted interventions for Black patients.

AACP faculty affairs standing committee report of strategies for faculty self-advocacy and promotion.

OBJECTIVES: The 2020-2021 American Association of Colleges of Pharmacy Faculty Affairs Standing Committee (FASC) was charged with identifying how faculty can self-advocate and promote themselves in a social influence context. FINDINGS: The FASC identified social influence and persuasion theories and strategies that can be used by faculty to initiate self-advocacy discussions and collaborations. Social influence and persuasion theories can provide a framework for research and scholarship or for beginning discussions regarding self-advocacy. SUMMARY: This FASC report describes the Committee charge, background information, and an overview of social influence theories and how these theories can be applied in academic pharmacy. The report concludes with a summary of issues for follow-up to the Committee's work.

Envisioning the Future of Student Success: Report of the 2022-2023 AACP Student Affairs Standing Committee.

Over the past several years, traditional metrics have indicated declining student success within colleges and schools of pharmacy. Though students may be less well-prepared for professional school than in years past, once candidates are admitted to our institutions, we have a responsibility to effectively support their progression through the program. The 2022-2023 Student Affairs Committee was convened to evaluate and advance the construct of student success within Doctor of Pharmacy programs. The Student Affairs Committee was charged with identifying environmental factors affecting the ability of pharmacy students to be successful; determining how colleges and schools of pharmacy are currently meeting needs related to student progress; conducting a literature review to determine what academic support measures minimize attrition; and developing innovative suggestions and recommendations that better support student success. To accomplish this work, we conducted an extensive literature review and synthesis of evidence, engaged in professional networking across the Academy, and administered a wide-ranging student success survey to all colleges and schools of pharmacy. In this report, we explore the complex and interacting systems that affect learning behavior and academic success and offer a novel, comprehensive description of how the Academy is currently responding to challenges of academic and student success. Additionally, we envision the future of student success, offering 7 recommendations to the American Association of Colleges of Pharmacy and 5 suggestions to members of the Academy to advance this vision.

Cabotegravir: The First Long-Acting Injectable for HIV Preexposure Prophylaxis.

OBJECTIVE: Review the pharmacology, pharmacokinetics, efficacy, safety, and role of long-acting injectable cabotegravir (CAB-LA) in HIV preexposure prophylaxis (PrEP). DATA SOURCES: A literature search was performed using PubMed and Google Scholar (2012 to April 2022) with the search terms cabotegravir, preexposure prophylaxis, and PrEP. Other resources included abstracts presented at recent conferences, the manufacturer's Web site, prescribing information, and review articles. STUDY SELECTION AND DATA EXTRACTION: All English-language articles of studies assessing the efficacy and safety of CAB-LA for PrEP were included. DATA SYNTHESIS: CAB-LA is the first long-acting injectable therapy approved for HIV-1 PrEP in both men and women. It is a suspension given intramuscularly every other month. CAB-LA has been shown to be more effective than daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in preventing HIV-1 infection among high-risk individuals. Two phase 3 trials were stopped early on the basis of superior efficacy of CAB-LA. The most common adverse effects were injection site reactions (ISRs), although they tended to decrease over time, and few participants in clinical trials discontinued use due to ISRs. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: CAB-LA may be particularly useful for individuals with known adherence problems to oral therapy, those with renal impairment, and those with decreased bone mineral density. However, CAB-LA is more expensive than generic TDF/FTC and may be associated with weight gain. CONCLUSIONS: CAB-LA is the first long-acting injectable agent for HIV PrEP. It is more effective than oral TDF/FTC, is well-tolerated aside from ISRs, and has few clinically significant drug-drug interactions.

PreHevbrio: A New 3-Antigen Hepatitis B Vaccine for Adults.

OBJECTIVE: The main objective of this article is to review the immunogenicity and safety of the 3-antigen recombinant hepatitis B vaccine (3A-HepB) in adults. DATA SOURCES: A literature search was performed using PubMed and Google Scholar (2000 to June 2022) with the search terms hepatitis B vaccine and 3-antigen. Other resources included the Centers for Disease Control and Prevention, conference abstracts of liver meetings, the prescribing information, and the manufacturer's website. STUDY SELECTION AND DATA EXTRACTION: All English-language articles of studies assessing the immunogenicity and safety of 3A-HepB in humans were included. DATA SYNTHESIS: The 3A-HepB is licensed to prevent infection caused by all known subtypes of the hepatitis B virus in adults. It contains 3 hepatitis B surface antigens. The 3A-HepB has been shown to be noninferior to a single-antigen hepatitis B vaccine (1A-HepB). It is administered intramuscularly as a 3-dose series at 0, 1, and 6 months. The most commonly reported local reactions were injection site pain and tenderness, and the most commonly reported systemic reactions were headache, fatigue, and myalgia. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The introduction of 3A-HepB represents another step toward reducing the rates of new hepatitis B infections. However, clinical trials are needed to assess the immunogenicity of 3A-HepB in individuals at high-risk of nonresponse or low response to 1A-HepB, such as those with renal or hepatic impairment and those with altered immunocompetence. CONCLUSIONS: The 3A-HepB represents another vaccine to prevent hepatitis B in adults. It is safe and immunogenic but is associated with more adverse reactions than 1A-HepB.

An Exploratory Study of Arab American Pharmacy Educators' Work Experience with Diversity, Equity, and Inclusion.

Objective. To explore the experience of members of Arab American Pharmacy Educators (AAPE) regarding diversity, equity, and inclusion in their workplace.Methods. A cross-sectional questionnaire was distributed electronically to 51 AAPE members. Eligible participants were those who identify with Arab heritage and have worked at US schools or colleges of pharmacy. Following the initial invitation, three reminders were sent to complete the questionnaire.Results. A total of 31 (61% response rate) AAPE members completed the questionnaire. The majority of participants reported an overall positive academic experience. However, some participants reported being subject to negative stereotypes and discrimination, which may have hindered their ability to teach, practice, conduct research, and fully engage in service to their schools or colleges, profession, and community.Conclusion. Some AAPE members reported negative stereotypes and discrimination at US schools or colleges of pharmacy. Findings from this study can have implications for faculty representing different minority groups, especially for those pharmacy educators who are not of Western European descent and anyone who is perceived as the "other."

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in Non-Hospital Care Settings in 2021.

The scope of antimicrobial stewardship programs has expanded beyond the acute hospital setting. The need to optimize antimicrobial use in emergency departments, urgent, primary, and specialty care clinics, nursing homes, and long-term care facilities prompted the development of core elements of stewardship programs in these settings. Identifying the most innovative and well-designed stewardship literature in these novel stewardship areas can be challenging. The Southeastern Research Group Endeavor (SERGE-45) network evaluated antimicrobial stewardship-related, peer-reviewed literature published in 2021 that detailed actionable interventions specific to the nonhospital setting. The top 13 publications were summarized following identification using a modified Delphi technique. This article highlights the selected interventions and may serve as a key resource for expansion of antimicrobial stewardship programs beyond the acute hospital setting.

Ibrexafungerp: A new triterpenoid antifungal.

PURPOSE: The pharmacology, microbiology, pharmacokinetics, pharmacodynamics, efficacy, safety, and role of ibrexafungerp in the treatment of fungal infections are reviewed. SUMMARY: Ibrexafungerp is the first triterpenoid antifungal. Similarly to echinocandins, it inhibits the synthesis of 1,3-ß-d-glucan. However, it binds to a different site on the enzyme than echinocandins, resulting in limited cross-resistance. Ibrexafungerp exerts concentration-dependent fungicidal activity against Candida species and retains in vitro activity against most fluconazole-resistant strains. It is also active against Aspergillus species. Ibrexafungerp has been shown to be safe and effective in the treatment of vulvovaginal candidiasis caused by Candida albicans in phase 2 and phase 3 clinical trials. It is approved for vulvovaginal candidiasis in adult and postmenarchal pediatric females and is given as two 150-mg tablets orally, administered 12 hours apart. Ibrexafungerp is contraindicated in pregnancy. The most commonly reported adverse reactions were diarrhea, nausea, abdominal pain, dizziness, and vomiting. Ibrexafungerp should be avoided with strong or moderate CYP3A inducers, and the dose should be reduced with strong CYP3A inhibitors. Ibrexafungerp may be useful for patients who are not able to receive fluconazole or prefer oral therapy for the treatment of vulvovaginal candidiasis. However, it is more expensive than the 150-mg tablet of generic fluconazole, which is the current standard of care for vulvovaginal candidiasis. Clinical trials are ongoing for recurrent and complicated vulvovaginal candidiasis as well as invasive candidiasis and pulmonary aspergillosis. CONCLUSION: Ibrexafungerp is an alternative to fluconazole for the treatment of vulvovaginal candidiasis in nonpregnant females. It has the potential to be useful for recurrent and complicated vulvovaginal candidiasis as well as certain invasive fungal infections.

Impact of the Antimicrobial Stewardship Mandate on Multidrug-Resistant Organisms and Clostridioides difficile Infection Among Long-term Care Facility Residents.

Objective To determine whether the long-term care facility (LTCF) Centers for Medicare & Medicaid Services (CMS) Antimicrobial Stewardship (AMS) mandate was associated with a change in the combined rate of LTCF-acquired multidrug-resistant organism infection or colonization (MDRO-I/C) and Clostridioides difficile infection (CDI). Design Retrospective quasi-experimental study. Setting A 233-bed community hospital. Participants LTCF residents 75 years of age and older with MDRO-I/C or CDI admitted to the hospital before the AMS mandate in 2015 through 2016 or after the mandate in 2018 through 2019. Intervention LTCF CMS AMS mandate. Main Outcomes Measures Rates of LTCF-acquired MDRO-I/C and CDI. MDRO-I/C were defined by a culture positive for methicillin-resistant Staphylococcus aureus or extended-spectrum beta-lactamase-producing Enterobacterales. CDI was defined by a positive test for C. difficile using a multistep algorithm of toxin, glutamate dehydrogenase, and nucleic acid amplification tests. These specimens must have been collected within 48 hours of hospital admission. Results There were 33 residents with either LTCF-acquired MDRO-I/C or CDI out of a total of 205 hospitalized residents with MDRO-I/C or CDI in 2015 and 2016, resulting in a rate of 16.10%. In comparison, there were 38 residents with either LTCF-acquired MDRO-I/C or CDI out of a total of 253 hospitalized residents with MDRO-I/C or CDI in 2018 and 2019 resulting in a rate of 15.02%. The difference in the combined rate of LTCF-acquired MDRO-I/C and CDI was -1.08% (P = 0.75). Conclusion The AMS mandate was not associated with a significant change in the combined rate of LTCF-acquired MDRO-I/C and CDI, suggesting a need for more robust AMS programs in LTCFs.

A Continuing Education Activity Durably Addressed Knowledge Gaps Related to Penicillin Allergies Among Pharmacists and Pharmacy Technicians.

Background: Penicillin allergy is one of the most frequent self-reported allergies; however, only about 10% of reported allergies are accurate. Objectives: Through the creation of a continuing pharmacy education (CPE) activity, we sought to assess knowledge gaps and comfort levels in the management of penicillin allergies. Methods: A 1-hour enduring-content CPE activity was offered as an interactive course from September 20, 2019, to September 20, 2020. Participants completed 3 surveys (pre-survey, post-survey, and follow-up survey). Participants were pharmacists and pharmacy technicians who completed, at a minimum, the activity and both pre- and post-surveys. The primary outcome was the percentage of participants scoring >80% on knowledge-based questions on the post-survey compared with the pre-survey. Secondary outcomes included pre-post comparisons on knowledge-based questions, participants' self-report of an allergy, and comfort levels dispensing cephalosporins in a patient with a self-reported penicillin allergy. Results: A total of 389 participants completed the CPE activity, with 176 included for analysis. Significantly more participants scored >80% on knowledge-based questions on the post-survey compared with the pre-survey (71.6% vs 22.7%, P < .001). There was no significant difference between the percentage of participants scoring >80% on the post-survey and the follow-up survey (71.6% vs 65%, P = .119). The majority of participants (74%) felt comfortable dispensing a cephalosporin in a patient with a penicillin allergy on the pre-survey, with similar percentages on the post- and follow-up surveys (77% and 90%, respectively). Conclusion: A targeted continuing education program improved overall knowledge, which was sustained for up to 2 months.

Invasive Fungal Rhinosinusitis Caused by Curvularia in a Patient With Type 1 Diabetes Mellitus: A Case Report.

Invasive fungal rhinosinusitis (IFRS) is a serious illness requiring early diagnosis, surgical debridement, and administration of antifungals. We report a case of an acute IFRS caused by Curvularia in a patient with diabetes mellitus. An 18-year-old female presented to the emergency department with an acute onset of fever, headache, facial discomfort, and a blood glucose reading of 500 mg/dL. The patient was admitted for the management of hyperosmolar hyperglycemia. Her past medical history includes uncontrolled type 1 diabetes mellitus and a recent toothache. A computed tomography scan of the facial maxillary region revealed sinus disease with bony erosion. Empiric therapy with liposomal amphotericin B 400 mg i.v. every 24 hours, piperacillin/tazobactam 4.5 g i.v. every 6 hours and vancomycin 1 g i.v. every 12 hours was started. A functional endoscopic sinus surgery revealed invasive rhinosinusitis and cultures were positive for fungal elements. The patient was discharged on liposomal amphotericin B 400 mg i.v. daily and cefuroxime 500 mg orally twice daily. However, she was readmitted for the management of acute kidney injury and was discharged on itraconazole capsules 200 mg orally twice daily. Sinus cultures grew Curvularia and itraconazole was prescribed for 6 weeks, but the patient discontinued treatment after 3 weeks and had no signs or symptoms of rhinosinusitis when she was last seen in the clinic. The possibility of IFRS should be explored in patients with diabetes and signs and symptoms of rhinosinusitis.

Antibiotic Approvals in the Last Decade: Are We Keeping Up With Resistance?

OBJECTIVE: To review the spectrum of activity, efficacy, safety, and role in therapy of all antibiotics and related biologics approved by the Food and Drug Administration (FDA) in the last decade. DATA SOURCES: A literature search was performed using PubMed and Google Scholar (2010 to end May 2021) with the search terms' name of the antibiotic or the biologic. Data were also obtained from the prescribing information, FDA, and ClinicalTrials.gov websites. STUDY SELECTION: All relevant English-language, late phase clinical trials assessing the safety and efficacy of the identified drugs were included. Review articles and references of retrieved articles were evaluated for relevant data. DATA SYNTHESIS: Antibiotic resistance is a public health crisis, and antibiotic development is imperative to outpace the ability of bacteria to develop resistance. Only 17 new systemic antibiotics and 1 related biologic have been approved by the FDA since 2010. Among these drugs, 14 were approved for common bacterial infections, 1 was approved for Clostridioides difficile infection (CDI), 1 was licensed to prevent CDI recurrence, and 2 were approved for drug-resistant tuberculosis. Very few antibiotics are in clinical development. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The arrival of these new antibiotics was welcomed with great enthusiasm, particularly when they met previously unmet medical needs. Unfortunately, the majority of them represent modifications to existing chemical structures rather than new drug classes. Despite the availability of these antibiotics, managing patients with deep-seated infections and those with extensively resistant gram-negative organisms remains challenging. CONCLUSIONS: The number of new antibiotics and their indications are not keeping up with resistance and the needs of the patients.

Assessment of antimicrobial stewardship programs within governmental hospitals in Qatar: a SWOC analysis.

OBJECTIVES: Antimicrobial resistance is a worldwide public health issue that requires emergent action. Antimicrobial stewardship programs (ASPs) have been proposed as a strategy to minimise resistance. Although ASPs were implemented in governmental hospitals in Qatar since 2015, a formal evaluation of these programs has not been conducted. We aimed to assess the status of ASPs in Qatar and to identify strengths, weaknesses, opportunities and challenges (SWOC) to further enhance ASPs within Hamad Medical Corporation (HMC). METHODS: Lead stakeholders of ASPs in HMC filled a questionnaire adapted from the 2019 Centers for Disease Control Prevention checklist for ASPs. Notes were taken by research team to assist in formulating a SWOC analysis. KEY FINDINGS: All hospitals (12/12) had an infectious diseases physician and pharmacist designated as an ASP leader (major strength identified). Almost all hospitals lack a financial statement and information technology resources to support ASPs (major weaknesses identified). Nine hospitals had an antibiotic pre-authorisation policy and adopted a prospective audit with feedback strategy. Among hospitals surveyed, 11 hospitals tracked antibiotic use by measuring the defined daily dose, and only four hospitals tracked rates of Clostridioides difficile infection. Qatar's rich economy supports the allocation of financial resources and budgeting to improve ASPs despite the increased emergence of resistant organisms and the limited resources currently available to expand ASPs across the country's healthcare settings. CONCLUSIONS: Although ASPs were implemented in all governmental hospitals in Qatar, national efforts and more resources are needed to further develop and improve these programs.

Cabotegravir-Rilpivirine: The First Complete Long-Acting Injectable Regimen for the Treatment of HIV-1 Infection.

OBJECTIVE: To review the efficacy and safety of cabotegravir (CAB) with rilpivirine (RPV) in the treatment of HIV-1 infection. DATA SOURCES: A literature search was performed using PubMed and Google Scholar (2010 to January 2021) with the search terms cabotegravir and rilpivirine. Other resources included abstracts presented at recent conferences and the manufacturer's website and prescribing information. STUDY SELECTION: All English-language articles of studies assessing the efficacy and safety of CAB with RPV were included. DATA SYNTHESIS: The combination of CAB, a new integrase strand transfer inhibitor, and RPV, an established nonnucleoside reverse transcriptase inhibitor, is the first long-acting dual therapy approved for the treatment of HIV-1 infection in adults who have achieved viral suppression on a standard antiretroviral therapy (ART). This regimen demonstrated comparable maintenance of viral suppression evaluated up to 160 weeks, with low rates of virological failure. CAB and RPV are available as suspension given intramuscularly in 2 separate injections every 4 weeks. Common adverse effects include injection site reactions, pyrexia, fatigue, and headache. CAB and RPV are also available as tablets given orally for bridging therapy. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This long-acting dual therapy represents an attractive option with a high barrier to resistance for adults who have achieved viral suppression on standard ART and who prefer monthly injections over daily oral therapy. CONCLUSIONS: CAB-RPV is the first complete long-acting injectable that provides a convenient way to maintain viral suppression with no negative effects on renal and bone health and few drug interactions.

Imipenem/cilastatin/relebactam: A new carbapenem ß-lactamase inhibitor combination.

PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, efficacy, safety, and current regulatory status of imipenem/cilastatin/relebactam are reviewed. SUMMARY: Imipenem/cilastatin/relebactam is a newly approved anti-infective combination of a well-established ß-lactam and a new ß-lactamase inhibitor for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, and complicated intra-abdominal infections (cIAIs) caused by susceptible gram-negative bacteria in patients 18 years of age or older with limited or no alternative treatment options. The antibiotic is also indicated for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The antibiotic is active in vitro against a wide range of pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales (CRE) such as Klebsiella pneumoniae carbapenemase. The addition of relebactam does not restore the activity of imipenem against metallo-ß-lactamase (MBL)-producing Enterobacterales and carbapenem-resistant Acinetobacter baumannii. Two phase 3 clinical trials of imipenem/cilastatin/relebactam were conducted. In the RESTORE-IMI 1 trial, the efficacy and safety of imipenem/cilastatin/relebactam was found to be comparable to that of imipenem/cilastatin plus colistin for the treatment of infections caused by imipenem-nonsusceptible gram-negative bacteria in patients with HABP/VABP, cUTIs, and cIAIs, with a significantly lower incidence of nephrotoxicity reported with the new antibiotic. The RESTORE-IMI 2 trial demonstrated the noninferiority of imipenem/cilastatin/relebactam to piperacillin/tazobactam for the treatment of HABP/VABP. Commonly reported adverse events in clinical trials included anemia, elevated liver enzymes, electrolyte imbalances, nausea, vomiting, diarrhea, headache, fever, phlebitis and/or infusion-site reactions, and hypertension. CONCLUSION: Imipenem/cilastatin/relebactam is a new ß-lactam/ß-lactamase inhibitor combination with activity against MDR gram-negative bacteria, including many CRE but excluding MBL-producing Enterobacterales and carbapenem-resistant Acinetobacter baumannii. It is approved for the treatment of cUTIs, cIAIs, and HABP/VABP.