Commonly Reported Mosquito-Borne Viruses in the United States: A Primer for Pharmacists.

Mosquito-borne diseases are a public health concern. Pharmacists are often a patient's first stop for health information and may be asked questions regarding transmission, symptoms, and treatment of mosquito borne viruses (MBVs). The objective of this paper is to review transmission, geographic location, symptoms, diagnosis and treatment of MBVs. We discuss the following viruses with cases in the US in recent years: Dengue, West Nile, Chikungunya, LaCrosse Encephalitis, Eastern Equine Encephalitis Virus, and Zika. Prevention, including vaccines, and the impact of climate change are also discussed.

Clinical Evaluation of Meropenem-Vaborbactam Combination for the Treatment of Urinary Tract Infection: Evidence to Date.

As antimicrobial resistance continues to grow, one of the biggest threats includes the members of the Enterobacterales order presenting with carbapenem resistance (CRE). Meropenem-vaborbactam, along with other beta-lactam/beta-lactamase agents, has been developed to help combat this growing concern and is currently approved to treat complicated urinary tract infections (cUTI), as well as acute pyelonephritis (AP), in the USA. Vaborbactam is a novel beta-lactamase inhibitor designed specifically to optimize and restore the activity of meropenem against resistant Enterobacterales. Vaborbactam inhibits a number of beta-lactamases, including in vitro activity against extended-spectrum beta-lactamases (ESBL) and the Klebsiella pneumoniae carbapenemase (KPC) group. KPC represents one of the most clinically relevant carbapenemase in the USA, accounting for the majority of carbapenemase-producing CRE. Meropenem-vaborbactam has been studied in the two Phase 3, noninferiority trials, TANGO I and TANGO II. TANGO I compared meropenem-vaborbactam against piperacillin-tazobactam in patients with cUTIs and was found to be noninferior for overall success and microbial eradication. TANGO II expanded to other disease states (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia [HAP/VAP], complicated intra-abdominal infection [cIAI], cUTI/AP) and was found to be noninferior against best available therapy (BAT) with respect to clinical cure at the end of treatment and the test of cure. Meropenem-vaborbactam maintained the established safety profile of meropenem alone, with headache as the most common adverse event in both phase 3 studies. Overall, clinical efficacy has been demonstrated and suggests the use of meropenem-vaborbactam for the treatment of cUTI is an option.

Real-world impact of switching from tenofovir disoproxil fumarate to tenofovir alafenamide.

Although tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) have been evaluated in various clinical trials, limited safety and efficacy data exist in real-world settings. The goal of this retrospective analysis is to assess changes in virological suppression, immunological status, renal function, weight and body mass index (BMI) amongst people living with HIV who switched from a TDF-based to a TAF-based regimen. Of 130 patients included in the final analysis, 53 patients experienced an increase in their viral load upon switching from TDF to TAF therapy whilst 62 patients remained undetectable. For those who experienced a viral blip, 33 (62%) resuppressed by the time of last follow-up, 15 (28%) patients did not have additional labs beyond the last follow-up and concern for failure occurred in 5 (9%) patients. No differences in immunological function, renal function, weight or BMI were observed from before switching to the last follow-up. Although a loss of virological suppression was found upon switching to TAF at subsequent follow-up visits, resuppression ultimately occurred in most patients.

The race to a COVID-19 vaccine: opportunities and challenges in development and distribution.

The unprecedented toll of severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus 2019 disease (COVID-19), jumpstarted the race towards the development and distribution of effective treatment and prevention options. With an urgent need to slow viral transmission, lessen disease severity, and reduce mortality, biopharmaceutical companies rapidly began investigating potential COVID-19 vaccinations. While typical vaccine development can take upwards of 10-15 years, COVID-19 vaccines were developed in less than a year after the identification of COVID-19. To accomplish this feat, clinical development, manufacturing scale-up and distribution are occurring in parallel for the four COVID-19 vaccine front-runners. This remarkable opportunity will forever change the drug development process and would not be possible without tremendous dedication from the public and private sectors, researchers, and clinical trial volunteers. However, many challenges still lie ahead. Comprehensive plans for equitable vaccine education, distribution, administration and post-marketing surveillance must be implemented successfully to overcome vaccine hesitancy, supply-chain obstacles and healthcare provider shortages in an already overburdened healthcare system. We are moving forward at a remarkable pace but worldwide immunity through vaccination will take time to achieve. Thus, current prevention efforts of masking, hand hygiene and social distancing must remain in effect for the foreseeable future. We must remain diligent and not fatigue in our efforts. Ending the COVID-19 pandemic cannot rest on the promise of vaccination alone - it will require a continued, robust and multi-faceted approach to disease treatment and prevention.

Impact of Pharmacist-Driven Antiretroviral Stewardship and Transitions of Care Interventions on Persons With Human Immunodeficiency Virus.

BACKGROUND: Persons with human immunodeficiency virus (HIV) experience high rates of medication-related errors when admitted to the inpatient setting. Data are lacking on the impact of a combined antiretroviral (ARV) stewardship and transitions of care (TOC) program. We investigated the impact of a pharmacist-driven ARV stewardship and TOC program in persons with HIV. METHODS: This was a retrospective, quasi-experimental analysis evaluating the impact of an HIV-trained clinical pharmacist on hospitalized persons with HIV. Patients included in the study were adults following up, or planning to follow up, at the University of Illinois (UI) outpatient clinics for HIV care and admitted to the University of Illinois Hospital. Data were collected between July 1, 2017 and December 31, 2017 for the preimplementation phase and between July 1, 2018 and December 31, 2018 for the postimplementation phase. Primary and secondary endpoints included medication error rates related to antiretroviral therapy (ART) and opportunistic infection (OI) medications, all-cause readmission rates, medication access at time of hospital discharge, and linkage to care rates. RESULTS: A total of 128 patients were included in the study: 60 in the preimplementation phase and 68 in the postimplementation phase. After the implementation of this program, medication error rates associated with ART and OI medications decreased from 17% (10 of 60) to 6% (4 of 68) (P = .051), 30-day all-cause readmission rates decreased significantly from 27% (16 of 60) to 12% (8 of 68) (P = .03), and linkage to care rates increased significantly from 78% (46 of 59) to 92% (61 of 66) (P = .02). CONCLUSIONS: A pharmacist-led ARV stewardship and TOC program improved overall care of persons with HIV through reduction in medication error rates, all-cause readmission rates, and an improvement in linkage to care rates.

Trimethoprim-Sulfamethoxazole Associated Drug-Induced Liver Injury in Pediatrics: A Systematic Review.

BACKGROUND: Drug-induced liver injury (DILI) is a rare but known adverse event associated with trimethoprim-sulfamethoxazole (TMP-SMX) in adults. No studies to date have looked at the risk of this association in children. We systematically reviewed the evidence for a potential association between TMP-SMX and DILI in the pediatric population. METHODS: PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, Scopus and Web of Science was searched using a combination of terms to identify reports of TMP-SMX exposure, liver injury and pediatrics (≤18 years old). We included any studies with hepatic adverse events occurring after exposure to TMP-SMX. Bibliographies were reviewed for additional relevant references. The Narajno scale was used to assess causality in case studies. RESULTS: A total of 22 studies were identified: 3 randomized trials, 1 prospective observational study, 8 retrospective observational studies and 10 case reports. Among the randomized trials and prospective studies, only mild, transient hepatic function abnormalities were reported. Retrospective observational studies reported 1 fatal DILI and statistically significant increased odds of DILI with TMP-SMX use compared with nonuse. Among the 10 case reports, severe liver outcomes and mild hepatic function abnormalities were both reported. Naranjo scores suggested reported hepatic adverse events were probably because of exposure in 5, possible in 4, and doubtful in 1 case report. CONCLUSIONS: Evidence regarding DILI associated with TMP-SMX exposure in pediatrics is limited. Observational population studies show mild hepatic abnormalities. Case reports suggest more severe manifestations of DILI. Additional studies may reveal the association between TMP-SMX and DILI in pediatrics.

Omadacycline: A Review of the Clinical Pharmacokinetics and Pharmacodynamics.

Omadacycline is a novel aminomethylcycline antibiotic (antibacterial). Omadacycline has had chemical structure modifications at the C9 and C7 positions of the core tetracycline rings that allow stability in the efflux pump and ribosomal protection protein mechanisms of tetracycline resistance. The systemic exposure (i.e., maximum plasma concentrations [Cmax] and area under the plasma concentration-time curve [AUC]) after intravenous (IV) administration were linear and predictable over the dose range of 25 and 600 mg in healthy subjects. The oral bioavailability of omadacycline was 34.5% under fasted conditions (no food intake 6 h before and 4 h after dosing). Both AUC and Cmax values significantly decreased (41-61%) when a high-fat meal, with and without dairy, were administered 2 h before oral dosing of omadacycline. Similar to other tetracyclines, it is advisable to avoid concurrent administration of divalent- or trivalent cation-containing products (e.g., antacids and iron-containing preparations) for at least 4 h after oral administration of omadacycline. Omadacycline has a large volume of distribution (190 L) and low plasma protein binding (21.3%) that was concentration independent. Systemic exposure of omadacycline in epithelial lining fluid (ELF) and alveolar macrophages was greater than in plasma in healthy adult subjects. Omadacycline is excreted unchanged in the feces (81.1%) and urine (14.4%), and has a low potential for drug-drug interactions since it was not a substrate, inhibitor, or inducer of major cytochrome-metabolizing enzymes or organic anion transporters (OATs). No clinically significant differences in the pharmacokinetics of omadacycline have been observed for age, sex, and renal or hepatic impairment. Pharmacokinetic-pharmacodynamic studies have confirmed that the AUC from time zero to 24 h (AUC24)/minimum inhibitory concentration (MIC) ratio was the best index for correlating unbound plasma and total-drug ELF concentrations with the efficacy of omadacycline. A population pharmacokinetic model was developed with data from healthy subjects and infected patients and used to establish interpretive criteria for in vitro susceptibility testing and dosing regimens of omadacycline for treating acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia.

Mycobacterium conceptionense Pneumonitis in Patient with HIV/AIDS1.

Approximately 21 human cases of infection with Mycobacterium conceptionense have been reported. However, most cases were outside the United States, and optimal treatment remains uncertain. We report a case of M. conceptionense pneumonitis in a patient with HIV/AIDS in the United States. The patient was cured with azithromycin and doxycycline.

Omadacycline: a novel aminomethylcycline.

Tetracyclines have come a long way since they became available almost seven decades ago, with numerous enhancements allowing new agents to overcome bacterial mechanisms of resistance. However, these enhancements come with toxicities and pharmacokinetic disadvantages such as the gastrointestinal side-effects and poor oral bioavailability seen with the glycylcylcines. Omadacycline, a new and improved tetracycline, has demonstrated a broad spectrum of in vitro activity, has oral and intravenous formulations, improved safety compared to glycylcyclines, as well as clinical efficacy and safety for two types of infections: acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. This review will summarize salient points about its pharmacologic properties, available clinical efficacy, and safety data and omadacycline's place in therapy.

ZTI-01 (fosfomycin for injection) in the treatment of hospitalized patients with complicated urinary tract infections.

Fosfomycin is a bactericidal antibiotic available since the 1970s whose intravenous formulation has been available in many countries outside the USA. Given the rise in drug-resistant bacteria, its introduction into the US market has become a necessity for addressing these organisms. This review provides an overview of the microbiology, clinical pharmacology and initial clinical experiences of the intravenous fosfomycin product (ZTI-01) that is undergoing clinical development in the USA for the treatment of complicated urinary tract infections and acute pyelonephritis.

Pharmacokinetic evaluation of meropenem and vaborbactam for the treatment of urinary tract infection.

INTRODUCTION: Meropenem/vaborbactam (M/V) represents the first carbapenem and ß-lactamase inhibitor combination approved for treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a novel boronic acid, ß-lactamase inhibitor with a high affinity for serine ß-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration for the treatment of cUTIs in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, K. pneumoniae, and Enterobacter cloacae species complex. Areas covered: Relevant literature regarding microbiology, pharmacokinetics, pharmacodynamics, and clinical trials evaluating efficacy, safety, and tolerability will be discussed. Expert opinion: Current treatment options for KPC-producing infections such as aminoglycosides, polymyxins, fosfomycin, and tigecycline are associated with concerns regarding efficacy, toxicities, optimal dosing, and/or development of resistance. Additionally, resistance to the new combination product of ceftazidime/avibactam has also emerged. Current clinical evidence supporting the use of M/V for KPC-producing infections is limited to an open-label, randomized, phase III study in a small number of patients with serious infections due to carbapenem-resistant Enterobacteriaceae. Although M/V is not approved for KPC-producing infections, we believe that M/V will become a preferred agent for KPC-producing Enterobacteriaceae infections.