The Penn Medicine COVID-19 Therapeutics Committee-Reflections on a Model for Rapid Evidence Review and Dynamic Practice Recommendations During a Public Health Emergency.

The Penn Medicine COVID-19 Therapeutics Committee-an interspecialty, clinician-pharmacist, and specialist-front line primary care collaboration-has served as a forum for rapid evidence review and the production of dynamic practice recommendations during the 3-year coronavirus disease 2019 public health emergency. We describe the process by which the committee went about its work and how it navigated specific challenging scenarios. Our target audiences are clinicians, hospital leaders, public health officials, and researchers invested in preparedness for inevitable future threats. Our objectives are to discuss the logistics and challenges of forming an effective committee, undertaking a rapid evidence review process, aligning evidence-based guidelines with operational realities, and iteratively revising recommendations in response to changing pandemic data. We specifically discuss the arc of evidence for corticosteroids; the noble beginnings and dangerous misinformation end of hydroxychloroquine and ivermectin; monoclonal antibodies and emerging viral variants; and patient screening and safety processes for tocilizumab, baricitinib, and nirmatrelvir-ritonavir.

Community-Based COVID-19 Vaccine Clinics in Medically Underserved Neighborhoods to Improve Access and Equity, Philadelphia, 2021-2022.

Vaccination remains key to reducing the risk of COVID-19-related severe illness and death. Because of historic medical exclusion and barriers to access, Black communities have had lower rates of COVID-19 vaccination than White communities. We describe the efforts of an academic medical institution to implement community-based COVID-19 vaccine clinics in medically underserved neighborhoods in Philadelphia, Pennsylvania. Over a 13-month period (April 2021-April 2022), the initiative delivered 9038 vaccine doses to community members, a majority of whom (57%) identified as Black. (Am J Public Health. 2022;112(12):1721-1725. https://doi.org/10.2105/AJPH.2022.307030).

Factors Associated With COVID-19 Vaccine Receipt by Health Care Personnel at a Major Academic Hospital During the First Months of Vaccine Availability.

Importance: Several COVID-19 vaccines have been authorized in the US, yet preliminary evidence suggests high levels of vaccine hesitancy and wide racial, ethnic, and socioeconomic disparities in uptake. Objective: To assess COVID-19 vaccine acceptance among health care personnel (HCP) during the first 4 months of availability in a large academic hospital, compare acceptance with previously measured vaccine hesitancy, and describe racial, ethnic, and socioeconomic disparities in vaccine uptake. Design, Setting, and Participants: This cross-sectional study included 12 610 HCP who were offered COVID-19 vaccination at a major academic hospital in Philadelphia between December 16, 2020, and April 16, 2021. Exposures: For each HCP, data were collected on occupational category, age, sex, race and ethnicity (Asian or Pacific Islander, Black or African American [Black], Hispanic, White, and multiracial), and social vulnerability index (SVI) at the zip code of residence. Main Outcomes and Measures: Vaccine uptake by HCP at the employee vaccination clinic. Results: The study population included 4173 men (34.8%) and 7814 women (65.2%) (623 without data). A total of 1480 were Asian or Pacific Islander (12.4%); 2563 (21.6%), Black; 452 (3.8%), Hispanic; 7086 (59.6%), White; and 192 (1.6%), multiracial; 717 had no data for race and ethnicity. The mean (SD) age was 40.9 (12.4) years, and 9573 (76.0%) received at least 1 vaccine dose during the first 4 months of vaccine availability. Adjusted for age, sex, job position, and SVI, Black (relative risk [RR], 0.69; 95% CI, 0.66-0.72) and multiracial (RR, 0.80; 95% CI, 0.73-0.89) HCP were less likely to receive vaccine compared with White HCP. When stratified by job position, Black nurses (n = 189; 62.8%), Black HCP with some patient contact (n = 466; 49.9%), and Black HCP with no patient contact (n = 636; 56.3%) all had lower vaccine uptake compared with their White and Asian or Pacific Islander counterparts. Similarly, multiracial HCP with some (n = 26; 52.0%) or no (n = 48; 58.5%) patient contact had lower vaccine uptake. In contrast, Black physicians were just as likely to receive the vaccine as physicians of other racial and ethnic groups. Conclusions and Relevance: In this cross-sectional study, more than two-thirds of HCP at a large academic hospital in Philadelphia received a COVID-19 vaccine within 4 months of vaccine availability. Although racial, ethnic, and socioeconomic disparities were seen in vaccine uptake, no such disparities were found among physicians. Better understanding of factors driving these disparities may help improve uptake.

Use of antiepileptic drugs in patients with kidney disease.

The number of medications used to treat different types of seizures has increased over the last 10-15 years. Most of the newer antiepileptic drugs (AEDs) are likely to be unfamiliar to many nephrologists. For both the older and newer AEDs, basic pharmacokinetic information, recommendations for drug dosing in patients with reduced kidney function or who are on dialysis, and adverse renal and fluid-electrolyte effects are reviewed. Newer AEDs are less likely to have significant drug-drug interactions than older agents, but are more likely to need dosage adjustment in patients with reduced kidney function. The most common renal toxicities of these drugs include metabolic acidosis, hyponatremia, and nephrolithiasis; interstitial nephritis and other adverse effects are less common. Little is known about the clearance of most of the newer AEDs with high-efficiency hemodialyzers or with peritoneal dialysis. Monitoring of drug levels when available, careful clinical assessment of patients taking AEDs, and close collaboration with neurologists is essential to the management of patients taking AEDs.

The safety of heparins in end-stage renal disease.

In patients on chronic dialysis, unfractionated heparin (UFH) is the most commonly used agent for anticoagulation of the hemodialysis extracorporeal circuit, for hemodialysis catheter "locking" between dialysis treatments, and for nondialysis indications such as venous thromboembolic disease, peripheral vascular disease, and acute coronary artery disease. Potentially serious complications of UFH, such as hemorrhage, osteoporosis, and thrombocytopenia, have led to consideration of other options for anticoagulation, including low molecular weight heparin (LMWH) and direct thrombin inhibitors (DTIs). LMWH can be used for anticoagulation of the hemodialysis circuit, but whether this has significant benefit compared to UFH remains to be proven. Because of the somewhat unpredictable risk of severe bleeding complications when LMWH is used for other indications in dialysis patients, UFH rather than LMWH is preferred for treatment of thromboembolic disease in these patients. DTIs have been used for anticoagulation in dialysis patients with heparin-induced thrombocytopenia (HIT), with argatroban being the preferred agent if heparin-free hemodialysis cannot be performed. UFH still remains the preferred anticoagulant in the vast majority of dialysis patients requiring systemic anticoagulation and for anticoagulation of the extracorporeal hemodialysis circuit.

Tigecycline: a new glycylcycline antimicrobial agent.

PURPOSE: The pharmacology, spectrum of activity, pharmacokinetics, clinical efficacy, adverse events, dosage and administration, drug interactions, and place in therapy of tigecycline are reviewed. SUMMARY: Tigecycline is the first of a new class of antimicrobials, the glycylcyclines, to receive approved labeling from the Food and Drug Administration. Similar to tetracyclines, glycylcyclines contain the central four-ring carbocyclic skeleton, with a substitution at the D-9 position. This substitution confers expanded broad-spectrum activity and defense against antimicrobial efflux pumps and ribosomal protection mechanisms. Tigecycline covers a broad spectrum of gram-positive (including resistant isolates), gram-negative (including extended-spectrum beta-lactamase producing organisms), and anaerobic pathogens. It does not exhibit activity against Pseudomonas aeruginosa and Proteus species. Clinical efficacy has been demonstrated in complicated skin and skin structure infections and intraabdominal infections. Tigecycline is administered intravenously and exhibits linear pharmacokinetics. The drug does not undergo extensive metabolism and works independently of the cytochrome P-450 isoenzyme system and therefore does not affect medications metabolized by these enzymes. Tigecycline is administered as a 100-mg i.v. loading dose followed by 50 mg i.v. every 12 hours. Hepatic dosage adjustment is necessary for severe disease; however, no dosage adjustments are necessary for patients with renal impairment. CONCLUSION: Tigecycline is an alternative agent available for the treatment of resistant gram-negative and gram-positive infections, especially in patients with a history of a penicillin allergy or antimicrobial-related toxicities.

Limiting the emergence of extended-spectrum Beta-lactamase-producing enterobacteriaceae: influence of patient population characteristics on the response to antimicrobial formulary interventions.

BACKGROUND: Effective methods to control the emergence of extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) remain unclear. Variations in the patient populations at different hospitals may influence the effect of antimicrobial formulary interventions. METHODS: To examine variations across hospitals in the response to antimicrobial interventions (ie, restriction of ceftazidime and ceftriaxone) designed to curb the spread of ESBL-EK, we conducted a 5-year quasi-experimental study. This study was conducted at 2 hospitals within the same health system: Hospital A is a 625-bed academic medical center, and Hospital B is a 344-bed urban community hospital. All adult patients with a healthcare-acquired clinical culture of ESBL-EK from July 1, 1997 through December 31, 2002 were included. RESULTS: After the interventions, the use of ceftriaxone decreased by 86% at Hospital A and by 95% at Hospital B, whereas the use of ceftazidime decreased by 95% at Hospital A and by 97% at Hospital B. The prevalence of ESBL-EK at Hospital A decreased by 45% (P < .001), compared with a 22% decrease at Hospital B (P = .36). The following variables were significantly more common among ESBL-EK-infected patients at Hospital B: residence in a long-term care facility (adjusted odds ratio, 3.77 [95% confidence interval, 1.70-8.37]), advanced age (adjusted odds ratio, 1.04 [95% confidence interval, 1.01-1.06]), and presence of a decubitus ulcer (adjusted odds ratio, 4.13 [95% confidence interval, 1.97-8.65]). CONCLUSIONS: The effect of antimicrobial formulary interventions intended to curb emergence of ESBL-EK may differ substantially across institutions, perhaps as a result of differences in patient populations. Variability in the epidemiological profiles of ESBL-EK isolates at different hospitals must be considered when designing interventions to respond to these pathogens.

Highly active antiretroviral therapy and the kidney: an update on antiretroviral medications for nephrologists.

Highly active antiretroviral therapy has dramatically altered the treatment and life expectancy of individuals who are infected with HIV. More than 20 antiretroviral drugs and drug combinations now are available in the United States. Nephrologists need to have an understanding of the pharmacokinetics of antiretroviral medications and the proper dosing of these medications in patients with impaired kidney function. It is also important for nephrologists to be aware of drug-drug interactions that can occur between antiretroviral medications and other medications that they may prescribe, including immunosuppressive medications that are used for renal transplantation, as this becomes more common in HIV-infected patients. Adverse reactions that affect the kidneys and cause fluid-electrolyte complications occur with certain antiretroviral agents, although most are relatively free of nephrotoxicity. This article reviews the clinical pharmacology and dosing modifications of the newer antiretroviral medications in patients with reduced kidney function; important drug-drug interactions involving these medications, particularly with other medications that are likely to be prescribed by nephrologists; and renal toxicities of antiretroviral agents.

Telithromycin: the first ketolide for the treatment of respiratory infections.

PURPOSE: The pharmacology, mechanisms of resistance, in vitro activity, clinical efficacy, pharmacokinetics, indications, adverse effects, dosage and administration, and place in therapy of telithromycin in the treatment of respiratory infections are reviewed. SUMMARY: Telithromycin is the first ketolide to be approved in the United States for use against common respiratory pathogens. The unique structure of telithromycin allows for enhanced binding to bacterial ribosomal RNA, thereby blocking protein synthesis. Its spectrum of activity includes pathogens implicated in common respiratory infections (Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumonia, and Chlamydia pneumoniae) and multidrug-resistant isolates of pneumococcus. Clinical efficacy has been documented in several multicenter, comparative trials for the treatment of community-acquired pneumonia, acute exacerbation of chronic bronchitis, acute maxillary sinusitis, and pharyngitis tonsillitis. Although studies have demonstrated that the clinical efficacy of telithromycin is comparable to macrolides, telithromycin is unique in that it provides activity against penicillin- and macrolide-resistant respiratory pathogens. The recommended dosage of telithromycin is 800 mg p.o. once daily. The most common adverse events resulting from telithromycin use include diarrhea, nausea, headache, dizziness, vomiting, loose stools, dysgeusia, and dyspepsia. The drug's adverse-event profile is comparable to that of similar agents. Telithromycin is a strong inhibitor of cytochrome P-450 isoenzyme 3A4; therefore, it can affect the efficacy and toxicity profile of medications that are metabolized by this isoenzyme. CONCLUSION: Telithromycin is a reasonable addition to the current treatment options for upper-respiratory-tract infections. Its use should be restricted to infections caused by penicillin- and macrolide-resistant pathogens.

Fluoroquinolone utilization in the emergency departments of academic medical centers: prevalence of, and risk factors for, inappropriate use.

BACKGROUND: Resistance to fluoroquinolone (FQ) antibiotics has risen markedly in recent years and has been associated with increasing FQ use; however, few data exist regarding FQ use patterns. Designing strategies to limit FQ resistance by optimizing FQ use depends on identifying patterns of inappropriate FQ use. Use of FQs in emergency departments (EDs) has not been studied. METHODS: We studied 100 consecutive ED patients who received an FQ and were subsequently discharged. Appropriateness of the indication for use was judged according to existing institutional guidelines. A case-control study was conducted to identify the prevalence of, and risk factors for, inappropriate FQ use. RESULTS: Of 100 total patients, 81 received an FQ for an inappropriate indication. Of these cases, 43 (53%) were judged inappropriate because another agent was considered first line, 27 (33%) because there was no evidence of infection based on the documented evaluation, and 11 (14%) because of inability to assess the need for antimicrobial therapy. Although the prevalence of inappropriate use was similar across various clinical scenarios, there was a borderline significant association between the hospital in which the ED was located and inappropriate FQ use. Of the 19 patients who received an FQ for an appropriate indication, only 1 received both the correct dose and duration of therapy. CONCLUSIONS: Inappropriate FQ use in EDs is extremely common. Efforts to limit emergence of FQ resistance must address the high level of inappropriate FQ use in EDs. Future studies should evaluate the impact of interventions designed to reduce inappropriate FQ use in this setting.