Optimizing the use of Paxlovid in clinical practice.

On December 22, 2021, the United States Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for nirmatrelvir/ritonavir (Paxlovid) for the treatment of mild to moderate coronavirus disease 2019 (COVID-19). The drug is authorized for use in patients 12 years of age and older weighing at least 40 kg who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and who are at high risk for progression to severe COVID-19. Nirmatrelvir, an orally bioavailable protease inhibitor that prevents SARS-CoV-2 replication by cleaving the two viral polyproteins, is packaged with ritonavir, a cytochrome P450 (CYP)3A4 inhibitor and pharmacokinetic boosting agent that increases nirmatrelvir concentrations. Although Paxlovid has demonstrated clinical efficacy in unvaccinated patients with COVID-19, its role in the treatment of other populations is less clear. This manuscript reviews what is known about Paxlovid and explores how this drug may be used in the future to treat patients with SARS-CoV-2 infection.

Cefiderocol to treat complicated urinary tract infection.

On November 14, 2019, the U.S. Food and Drug Administration (FDA) approved cefiderocol, a siderophore-cephalosporin conjugate antibiotic, for the treatment of adults with complicated urinary tract infections (cUTIs), including kidney infections caused by susceptible Gram-negative microorganisms, who have limited or no alternative treatment options. The approval was based on substantial preclinical and clinical data, including in vitro and in vivo work, as well as pharmacokinetic and pharmacodynamic studies that established cefiderocol as an effective agent for the treatment of cUTI. This paper reviews that work and looks ahead to determine how cefiderocol might be used by clinicians in the future.

Plazomicin for the treatment of patients with complicated urinary tract infection.

In June 2018, the United States Food and Drug Administration (FDA) approved plazomicin, a novel neoglycoside, for the treatment of adults with complicated urinary tract infections who have limited or no alternative treatment options. This approval was based on substantial preclinical and clinical work, and marks an important advance in the treatment of multidrug-resistant bacterial pathogens. This manuscript reviews the in vivo and in vitro work that led to the approval of plazomicin and examines how the drug may be used in the years ahead to treat patients with aggressive and life-threatening infections.

Meropenem/vaborbactam fixed combination for the treatment of patients with complicated urinary tract infections.

On August 29, 2017, the United States Food and Drug Administration (FDA) approved meropenem/ vaborbactam fixed combination for the treatment of adults with complicated urinary tract infections (cUTI). The decision was based on substantial preclinical and clinical data, including two recent trials involving hundreds of adults with cUTI. Meropenem/ vaborbactam represents a powerful new treatment option to address antibiotic-resistant pathogens, including Klebsiella pneumoniae carbapenemase-producing bacteria. In this paper, we examine the work that led to FDA approval, with special emphasis on molecular pharmacology, pharmacokinetics, metabolism, efficacy and drug safety. We also look ahead, to explore how this promising new antimicrobial agent might be used in the near future to confront other drug-resistant infections..

Factors influencing pursuit and satisfaction of academic dentistry careers: perceptions of new dental educators.

New dental educators (n = 280) with zero to five years full-time teaching experience were surveyed to ascertain their perceptions regarding salary, work environment, and workload to determine the impact of these factors on faculty recruitment and retention. Work environment was the most frequently reported factor for considering and maintaining an academic dentistry position. Educational resources, facilities, salary, and benefits were ranked as moderately important for considering an academic position. Mentoring, startup funds for research, and external private practice opportunities were also reported as moderately important for maintaining a position. Other factors of concern to new faculty included quality of administration and leadership, reputation of program, professional development opportunities, faculty autonomy, and reasonable criteria for tenure and promotion. These findings suggest that resources, strategies, and formal mentoring programs that provide direction and guidance in the areas of teaching, promotion, and tenure for new educators should be considered for implementation in our dental schools.

Seizure activity and unresponsiveness after hydroxycut ingestion.

A 22-year-old man was hospitalized after unexplained seizure-like activity and unresponsiveness. A urine toxicology screen was negative for salicylates, acetaminophen, alcohol, and drugs of abuse. Medical history was insignificant with the exception of recent (within 2 wks) ingestion of Hydroxycut is a dietary supplement purported to be energy enhancing, muscle building, and fat burning. The agent contains ephedra alkaloids and caffeine, which are both central nervous system stimulants; the etiology of seizure was attributed to their consumption. Due to a significant number of reported adverse events, the United States Food and Drug Administration (FDA) proposed regulations for dietary supplements containing ephedra alkaloids and requested an independent review of case reports linked to these products. Because herbal products are not subject to the same rigorous FDA regulations required for prescription and over-the-counter products, consumers unknowingly risk adverse effects when taking these products. Questioning patients about consumption of herbal products should be part of routine medical visits.

Zanamivir in the treatment and prevention of influenza.

OBJECTIVE: To evaluate the efficacy of zanamivir in the prevention and treatment of influenza. DATA SOURCES: Medical literature was accessed through MEDLINE (1966-June 1999). Key search terms included zanamivir, GG167, and influenza. Additional information was obtained from GlaxoWellcome, Inc. DATA SYNTHESIS: Zanamivir is the first in a new class of drugs to be developed for the treatment of influenza. An evaluation of clinical trials using inhaled zanamivir was conducted to determine its efficacy. CONCLUSIONS: Zanamivir appears to shorten the median duration of influenza symptoms by up to 2.5 days when compared with placebo. It was well tolerated in clinical trials, with mild adverse effects occurring in a small percentage of subjects.

Dapsone-induced methemoglobinemia.

OBJECTIVE: To report a case of methemoglobinemia in a patient receiving dapsone for prophylaxis of Pneumocystis carinii pneumonia (PCP). CASE SUMMARY: A 69-year-old white woman was hospitalized to rule out sepsis. Two years prior to this admission, the patient received an orthotopic liver transplant after which she required hemodialysis three times weekly. Because of intolerance to trimethoprim/ sulfamethoxazole and aerosolized pentamidine, she was prescribed dapsone therapy on hospital day 13, that was continued for 11 days. On hospital day 45 the patient received a cadaveric kidney transplant, and dialysis treatments were scheduled only as needed. One week after the transplant, dapsone therapy was resumed. Nine days into this course of dapsone, the patient developed dyspnea and oxygen desaturation of unknown etiology. The patient was evaluated for and diagnosed with methemoglobinemia. She received two doses of intravenous methylene blue and one dose of oral activated charcoal due to fluctuating methemoglobin concentrations. DISCUSSION: The elimination of dapsone is not completely understood. Several case reports of dapsone-induced methemoglobinemia are present in the literature. Most have occurred in patients who have accidentally or deliberately overdosed. Cases of methemoglobinemia in patients receiving therapeutic doses of dapsone are discussed. CONCLUSIONS: The growing numbers of immunosuppressed patients due to transplantation of HIV may result in increased dapsone use for the prevention of PCP. Clinicians should be aware of the adverse effects associated with dapsone therapy, and patients with dyspnea and hypoxemia of unclear etiology should be evaluated for methemoglobinemia.

Treatment of Rocky Mountain spotted fever in children.

RMSF is a potentially life-threatening disease that requires prompt diagnosis and empiric initiation of an appropriate antimicrobial agent. For the clinician treating young children with RMSF, there are few options. The safety and efficacy of fluoroquinolones and orally administered parenteral chloramphenicol have not been established in the pediatric population. Therefore, widespread and casual use of these agents is not recommended. Doxycycline is the most favorable agent for the treatment of RMSF in children younger than 9 years of age because of its documented effectiveness, broader margin of safety, reduced risk of drug-related adverse effects in young children, and convenient dosing schedule. For patients with RMSF reinfection, up to five courses of doxycycline may be administered with minimal risk of dental staining.