Long-Term Evaluation of Changes in Kidney Function after Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Patients Living with HIV.

Tenofovir is one of the most widely used medications for HIV treatment and is administered as either tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). Use of TAF is preferred as it is associated with fewer negative impacts on renal function; however, long-term follow-up beyond 96 weeks is limited. A retrospective chart review of patients ≥18 years who received TDF-containing anti-retroviral therapy (ART) for ≥6 months and then switched to a TAF-containing regimen between 1 December 2015 and 1 January 2020 is presented. The primary objective was to evaluate changes in kidney function as measured by eGFR and Scr. The secondary objective was to evaluate changes in lipids. Among the 142 patients identified, the median age was 66 years old with a median follow-up of 3.6 years. The change in kidney function was a median increase in Scr of 0.1 mg/dL and a decrease in eGFR of -8 mL/min/1.73 m2. The change in lipid panels at the end of the medication use evaluation endpoint was a decrease in total cholesterol, LDL, HDL, and triglycerides of -2.5, -0.1, -0.6, and -9 mmol/L, respectively. There was no clinically meaningful difference in kidney function as measured by eGFR or Scr, nor was there any clinically meaningful difference in lipid panels in patients switched from TDF to TAF-containing ART. Our observations suggest that the favorable impact of TAF on kidney function is sustained for at least 44 months after conversion from TDF.

Impact of early home psychotropic medication reinitiation on surrogate measures of intensive care unit delirium.

INTRODUCTION: Intensive care unit (ICU) delirium is a major contributing factor to increased mortality, length of stay, and cost of care. Psychotropic medications may often require extensive tapering to prevent withdrawal symptoms; during ICU admission, home psychotropics are frequently held which may precipitate acute drug withdrawal and subsequent delirium. METHODS: This is a single-center, observational, retrospective chart review. The primary endpoint was the total number of new-start antipsychotics used to treat ICU delirium. Secondary endpoints included use of restraints, ICU length of stay, and hospital length of stay. RESULTS: A total of 2334 charts were reviewed for inclusion; 55 patients were categorized into each group. There was no statistically significant difference in the requirement for new-start antipsychotics (P = 1.0), restraint use (P = .057), or ICU length of stay (P = .71). There was a statistically significant decrease in hospital length of stay (P = .048). DISCUSSION: Early reinitiation was associated with a decrease in hospital length of stay but was not associated with a decrease in the number of new-start antipsychotics, use of restraints, or ICU length of stay.

Metformin-Induced Hemolytic Anemia in a Patient With Glucose-6-Phosphate Dehydrogenase Deficiency.

Metformin, an oral antidiabetic agent, is considered the preferred first-line therapy for patients with type II diabetes. Between 2010 and 2012, it has been estimated that 14 million Americans were administered an oral antidiabetic agent, suggesting the extensive use of metformin among the diabetic population. There have been few case reports implicating metformin in causing hemolytic anemia. We present a case of a 53-year-old white male who developed hemolytic anemia after the initiation of treatment with metformin 500 mg twice daily. The patient experienced a 1.5 g/dL decrease in hemoglobin from baseline and a 2.8 mg/dL increase in total bilirubin within 1 day of treatment. Laboratory results confirmed that the patient was also glucose-6-phosphate dehydrogenase deficient. The hemolytic anemia resolved on discontinuation of metformin. Although this adverse effect seems to be rare, it is important to consider its seriousness. Clinicians should be advised to closely monitor patients newly started on metformin.

Treatment of skin and soft tissue infections in the elderly: A review.

BACKGROUND: Skin and soft tissue infections (SSTIs) have become the second most common type of infection among persons residing in long-term care facilities. OBJECTIVE: The purpose of this article was to review the latest information on SSTIs among the elderly, including age-related changes, challenges, and treatment strategies in the era of emerging bacterial resistance. METHODS: Relevant information was identified through a search of MEDLINE (1970-April 2010), International Pharmaceutical Abstracts (1970-April 2010), and Google Scholar using the terms skin and soft tissue infection, skin and skin structure infection, cellulitis, treatment guidelines, and elderly. Additional publications were found by searching the reference lists of the identified articles. Trials published since 1970 were selected for this review if they prospectively evaluated mostly adults (≥18 years of age), included >50 patients, and reported diagnostic criteria as well as clinical outcomes in patients treated for simple or complicated SSTIs. RESULTS: Fifty-eight of 664 identified studies were selected and included in this review. A search of the literature did not identify any prospective clinical trials that were conducted exclusively in the elderly. Information on the treatment of SSTIs in the elderly was based solely on clinical studies that were conducted in adults in general. As recommended by the Infectious Diseases Society of America (IDSA) 2008 update, SSTIs should be suspected in elderly patients who have skin lesions and present with a decline in functional status, with or without fever. Patients who present with symptoms of systemic toxicity should be hospitalized for further evaluation. Current challenges in the management of SSTIs include the rapid emergence of community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA), the emergence of macrolide-resistant streptococci within the past decade, and the lack of a reliable algorithm to differentiate potentially life-threatening SSTIs that require aggressive interventions and prompt hospitalization from those that can be managed in an outpatient setting. S aureus was the most common cause of SSTIs, being isolated in 42.8% (5015/11,723) of wounds, followed by streptococci. Common SSTIs in the elderly such as shingles, diabetic foot infections, infected pressure ulcers, and scabies, and their treatment were also discussed. Based on reviews of published trials, treatment of simple SSTIs generally consisted of administration of agents with activity against S aureus and Streptococcus species such as a penicillinase-resistant ß-lactam, a first-generation cephalosporin, or clindamycin. Broadening of the antimicrobial spectrum to include gram-negative and anaerobic organisms should be implemented for complicated SSTIs such as diabetic foot infections and infected pressure ulcers. Local rates of MRSA, CA-MRSA, and macrolide-resistant streptococci should be considered when selecting empiric therapy. CONCLUSIONS: A search of the literature did not identify any prospective clinical trials on the treatment of SSTIs in the elderly; therefore, it is recommended to follow treatment based on the current IDSA guidelines. More research and publications are needed to establish proper selection of antimicrobial agents, treatment strategies, and duration of therapy of SSTIs in the elderly population.

Telavancin: a lipoglycopeptide antimicrobial for the treatment of complicated skin and skin structure infections caused by gram-positive bacteria in adults.

BACKGROUND: Telavancin, a lipoglycopeptide antibiotic, is a semisynthetic derivative of vancomycin. It was approved by the US Food and Drug Administration (FDA) in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. OBJECTIVE: This article summarizes the pharmacology, in vitro and in vivo activity, pharmacokinetic properties, and clinical efficacy and tolerability of telavancin. METHODS: Relevant information was identified through a search of MEDLINE (1966-August 2010), Iowa Drug Information Service (1966-August 2010), International Pharmaceutical Abstracts (1970-August 2010), and Google Scholar using the terms telavancin, lipoglycopeptide, and TD-6424. Abstracts and posters from scientific meetings, as well as documents submitted by the manufacturer of telavancin to the FDA as part of the approval process, were consulted. In vivo and in vitro experimental and clinical studies and review articles that provided information on the activity, mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of telavancin were reviewed. RESULTS: In vitro, telavancin has potent activity against S aureus, including methicillin-resistant strains; Streptococcus pneumoniae; and vancomycin-susceptible enterococci with MICs generally <1 µg/mL. Telavancin appears to have a dual mechanism of action, inhibiting cell wall formation and disrupting the cell membrane. In Phase III studies (ATLAS 1 and ATLAS 2), telavancin was found to be noninferior to vancomycin, with clinical cure rates of 88.3% and 87.1%, respectively, in clinically evaluable patients in the treatment of cSSSIs (difference, 1.2%; 95% CI, -2.1 to 4.6; P = NS). The effectiveness of telavancin in the treatment of hospital-acquired pneumonia was assessed in 2 Phase III studies (ATTAIN 1 and ATTAIN 2). Preliminary findings were that the effectiveness of telavancin was not significantly different from that of vancomycin, with cure rates of 82.7% and 80.9% in the clinically evaluable population, respectively (difference, 1.8%; 95% CI, -4.1 to 7.7; P = NS). The most commonly (>10%) reported adverse events included taste disturbances, nausea, headache, vomiting, foamy urine, constipation, and insomnia. CONCLUSION: In clinical trials, the effectiveness of telavancin was not significantly different from that of vancomycin in the treatment of cSSSIs, and telavancin was generally well tolerated.