Pharmacotherapeutic Considerations in the Treatment of Nontuberculous Mycobacterial Infections: A Primer for Clinicians.

Nontuberculous mycobacteria (NTM) can cause a variety of infections, including serious pulmonary disease. Treatment encompasses polypharmacy, with a targeted regimen of 2-5 active medications, depending on site of infection, species, and clinical characteristics. Medications may include oral, intravenous, and inhalational routes. Medication acquisition can be challenging for numerous reasons, including investigational status, limited distribution models, and insurance prior authorization. Additionally, monitoring and managing adverse reactions and drug interactions is a unique skill set. While NTM is primarily medically managed, clinicians may not be familiar with the intricacies of medication selection, procurement, and monitoring. This review offers insights into the pharmacotherapeutic considerations of this highly complex disease state, including regimen design, medication acquisition, safety monitoring, relevant drug-drug interactions, and adverse drug reactions.

A case study: lessons learned from online tutorial to improve practice readiness for family medicine residents in Palestine.

BACKGROUND: Geopolitical and socioeconomic challenges limit faculty development and clinical teaching in Palestine and many other developing countries. The first, and still only, Family Medicine (FM) residency program is a four-year program based out of An-Najah University in the West Bank. Training in primary care clinics occurs in the final two years and there are many challenges to adequate supervision in the clinical setting that were exacerbated during the pandemic. To improve the readiness for practice skills of 13 Palestinian FM residents a three-month tutorial program was organized in 2020. A nongovernmental organization (NGO) that has worked to support Family Medicine development in the region engaged experienced British and American General Practitioners trained as tutors to offer online tutorials. We examined the program as a case study to understand the factors that facilitated or impaired a positive virtual learning environment in a middle/low income country. METHODS: The tutors and residents were divided into groups and met virtually between June and September 2020. Evaluations and session reports collected during the program, the text of an online chat, and responses to an online survey two years later were collected. Using thematic analysis techniques, we evaluated the value for the residents at the time and two years later and identified factors that facilitated or impaired a positive virtual learning environment. RESULTS: Themes of knowledge, skills, attitudes, cultural disconnects, and tutorial logistics emerged. The group with the most stable tutor pairing, including one Arabic-speaker familiar with the context, was the most engaged. The all-female group formed a chat group to share real-time case questions during clinical practice and focused on skills (e.g. conducting a thorough medication review) and attitudes (e.g. open to sharing and discussing uncertainties). Other groups were less cohesive. CONCLUSIONS: Transnational tutorials that focused on clinical thinking and decision-making skills were most successful when the tutorial pair was stable, offered familiarity with the language and addressed cultural differences. Intrinsic factors such as lacking the motivation to participate and extrinsic factors such as unstable internet and rolling electric cuts, and clinical structures that made applying new skills challenging were more difficult to address but must be considered.

Efficacy of Cochleated Amphotericin B in Mouse and Human Mucocutaneous Candidiasis.

Candida albicans causes debilitating, often azole-resistant, infections in patients with chronic mucocutaneous candidiasis (CMC). Amphotericin B (AMB) resistance is rare, but AMB use is limited by parenteral administration and nephrotoxicity. In this study, we evaluated cochleated AMB (CAMB), a new oral AMB formulation, in mouse models of oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC) and in patients with azole-resistant CMC. OPC and VVC were modeled in Act1-/- mice, and mucosal tissue fungal burden was assessed after once-daily treatment with CAMB, vehicle, or AMB-deoxycholate (AMB-d). Four patients with azole-resistant CMC enrolled in a phase 2 CAMB dose-escalation study. The primary endpoint was clinical improvement at 2 weeks followed by optional extension for long-term CMC suppression to assess safety and efficacy. CAMB-treated mice had significantly reduced tongue and vaginal fungal burdens compared to vehicle-treated mice and exhibited comparable fungal burden reduction relative to AMB-d-treated mice. All CAMB-treated patients reached clinical efficacy by 2 weeks, three at 400 mg twice daily and one at 200 mg twice-daily dosing. All patients continued to the extension phase, with three having sustained clinical improvement of OPC and esophageal candidiasis (EC) for up to 60 months. One patient had a relapse of esophageal symptoms at week 24 and was withdrawn from further study. Clinical responses were not seen for onychomycosis or VVC. CAMB was safe and well-tolerated, without any evidence of nephrotoxicity. In summary, oral CAMB reduced tongue and vaginal fungal burdens during murine candidiasis. A proof-of-concept clinical trial in human CMC showed efficacy with good tolerability and safety. This study has been registered at ClinicalTrials.gov under identifier NCT02629419.

Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response, and immunothrombosis. Fostamatinib is a novel spleen tyrosine kinase inhibitor that we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with COVID-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. RESULTS: A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared with 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ±â€…0.3 vs -2.6 ±â€…0.4, P = .035) and the median length in the intensive care unit was 3 days in the fostamatinib group vs 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs 28, P = .027). There were trends toward more rapid reductions in C-reactive protein, D-dimer, fibrinogen, and ferritin levels in the fostamatinib group. CONCLUSION: For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared with placebo. These results warrant further validation in larger confirmatory trials. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov, NCT04579393.

I.V. minocycline revisited for infections caused by multidrug-resistant organisms.

PURPOSE: The evidence supporting the potential use of i.v. minocycline for serious infections caused by multidrug-resistant organisms (MDROs) is summarized. SUMMARY: Minocycline achieves good tissue penetration and excellent oral absorption. Minocycline achieves serum concentrations comparable to other tetracyclines, with peak serum concentrations ranging from 3 to 8.75 mg/L following i.v. administration of 200 mg. Minocycline retains antimicrobial activity against methicillin-sensitive and methicillin-resistant Staphylococcus aureus as well as many gram-negative pathogens, such as Acinetobacter species, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Stenotrophomonas maltophilia. Minocycline has been used to treat respiratory infections caused by Acinetobacter baumannii and bloodstream infections. The majority of these gram-negative infections were treated with combination therapy, with results similar to those seen with first-line agents. The ability to switch from parenteral to oral therapy and its favorable tissue penetration make minocycline an attractive option for severe respiratory or skin and skin structure infections. For A. baumannii infections, minocycline is the second most active agent in vitro and may be the only therapeutic option in certain cases. The overall clinical experience with minocycline supports its use to treat A. baumannii infections alone or in combination with other agents. Minocycline could be used to treat other MDRO gram-negative infections but only as an agent of last resort due to the limited data available. CONCLUSION: The available pharmacokinetic and clinical data support the use of i.v. minocycline for the treatment of MDRO infections, including infections due to S. aureus coagulase-negative and gram-negative pathogens.

6 essential elements for physician revenue cycle management.

To be effective, a professional fee billing operation requires the following elements: Capable management. An appropriate organizational model. Consolidated practice management systems. Transparency, standards, and controls. An appropriate coding and compliance model. ICD-10 preparedness.

National survey on continuous and extended infusions of antibiotics.

PURPOSE: A national survey was conducted to evaluate the use of continuous and extended infusions for administering ß-lactams and vancomycin. METHODS: The survey was sent to a random sample of 1000 acute care hospital pharmacists in the United States to evaluate the use of continuous and extended infusions of antibiotics. In addition, the same survey was sent to members of the Society of Infectious Diseases Pharmacists (SIDP) to assess the adoption of these infusion strategies. RESULTS: In the random-sample survey, 29 (11.2%) and 15 (5.8%) hospitals reported using continuous and extended infusions, respectively. Common rationales for adopting continuous and extended infusions were greater efficacy, equal or less toxicity, and cost savings. The SIDP survey revealed that 30 (50%) and 21 (35%) of responding pharmacists have initiated continuous and extended infusions, respectively. Common rationales for adopting continuous and extended infusions were greater efficacy, equal or less toxicity, and cost savings. Both surveys found that penicillins were the antibiotics most frequently administered as continuous and extended infusions. CONCLUSION: The results of a survey sent to a random sample of hospital pharmacists and to SIDP members indicated that the majority did not use either continuous or extended infusions of antibiotics. SIDP survey respondents more frequently reported the use of both continuous and extended infusions than the respondents of the random-sample survey, and the percentage of time above the minimum inhibitory concentration was the most frequently assessed pharmacokinetic-pharmacodynamic parameter for both groups.