Food and Drug Administration Approval of Artesunate for Severe Malaria: Enough to Achieve Best Practice?

Intravenous artesunate has been the global standard of care for severe malaria for over 2 decades. Yet, until recently, artesunate has only been available to patients through an expanded-access protocol from the Centers for Disease Control and Prevention. In May 2020, the Food and Drug Administration approved artesunate, allowing US hospitals to stock the drug and ensuring prompt treatment for this life-threatening infection. However, because of artesunate's high cost and the infrequency of severe malaria in the United States, hospitals may be reluctant to stock the drug. As US health systems weigh the decision to stock artesunate, we propose a hospital tier framework to inform this decision and support clinicians caring for patients who present with severe malaria.

Antifungal drug price increases in the United States, 2000-2019.

BACKGROUND: Antifungal drugs treat a variety of conditions, ranging from localised dermatologic disease to life-threatening systemic infections. Some common antifungal drugs experienced large price increases in recent years, however, factors contributing to these price increases are poorly understood. We sought to examine trends in antifungal drug prices and determine underlying drivers of price changes. METHODS: Antifungal drug products in the United States were identified using the Food and Drug Administration (FDA) Label database. For each product, we determined the wholesale acquisition cost per unit over time between 2000 and 2019, adjusting for inflation, and examined variables that could impact price: route of administration, number of FDA indications, the quantity of professional guideline recommendations, use for prophylaxis, number of FDA-approved manufacturers, and whether it was compounded. Price trajectories were clustered into four groups: (1) stable, 2) moderate, (3) high, and (4) extreme price increases. RESULTS: Of 139 identified drug products, one outlier was removed due to exorbitant price increases. Cluster 1 (n = 31) demonstrated the most stable prices with a 25% mean price increase. Clusters 2 (n = 97), 3 (n = 7), and 4 (n = 3) demonstrated moderate, high, and extreme price increases with 52%, 318%, and 900% mean price increases, respectively. Atypical routes of administration and compounding were over-represented in clusters 3 and 4. There was no correlation between the number of manufacturers and price changes. CONCLUSIONS: Antifungal drugs exhibited large, inflation-adjusted price increases. Atypical routes of administration and compounding were over-represented within clusters exhibiting extraordinary price increases. Our data support policies aiming to curb large price increases for medically important drugs.

Hospital pharmacy acquisition of nonstocked antimicrobials-current processes and areas for improvement.

BACKGROUND: The delivery of prompt and appropriate antimicrobial therapy for life-threatening infections is an important antimicrobial stewardship measure and a priority for hospitals. OBJECTIVES: To better understand U.S. hospital pharmacy stocking processes and acquisition of nonstocked antimicrobials and to identify strategies for improving this process. METHODS: This mixed-methods study recruited infectious diseases and antimicrobial stewardship pharmacists. Semistructured interviews with pharmacists in Minnesota were conducted via video conferencing software from January 21, 2021, to March 17, 2021. Audio recordings of the interviews guided survey development and were also transcribed, coded, and qualitatively analyzed. Surveys were distributed throughout the United States via an e-mail listserv, and responses were collected between August 5, 2021, and September 15, 2021. RESULTS: Ten interviews and 78 surveys were included in the analysis. Formulary and stocking practices varied based on institution. Stocking decisions were most frequently based on the frequency of use, clinical utility, and cost of antimicrobials. Nonstocked antimicrobials were often ordered from the wholesale distributor but, if needed urgently, acquired from another local institution. Antibacterial agents were the most frequently needed nonstocked antimicrobials, especially those targeting multidrug-resistant gram-negative bacteria. When acquiring nonstocked antimicrobials, barriers include process inefficiencies, cost, availability, and safety concerns. Improved information sharing between local institutions may help improve this process. CONCLUSION: In this exploratory study, antimicrobial stocking practices varied within U.S. hospitals. Acquisition of nonstocked, urgently needed antimicrobials from neighboring hospitals may be common; however, this process lacks guidance and is often inefficient. Establishing better mechanisms for information sharing may improve this process and should be explored.

Travel-associated chikungunya acquired in Myanmar in 2019.

Eighteen cases of chikungunya virus infection in travellers returning from Myanmar were reported to the GeoSentinel Surveillance Network, its subnetwork EuroTravNet and TropNet in 2019, reflecting an ongoing local outbreak. This report reinforces the importance of travellers as sentinels of emerging arboviral outbreaks and highlights the importance of vigilance for imported cases, due to the potential for dissemination of the virus into areas with competent local vectors and conducive environmental conditions.

Trends in Pricing and Generic Competition Within the Oral Antibiotic Drug Market in the United States.

BACKGROUND: In recent years, the price of many older generic drugs, including numerous antibiotics, has increased substantially. We sought to analyze recent price changes and extent of generic competition within a cohort of commonly prescribed off-patent oral antibiotics. METHODS: We extracted oral antibiotics recommended for common outpatient conditions in the Infectious Diseases Society of America Practice Guidelines. We determined all US Food and Drug Administration-approved manufacturers for each formulation and strength in 2013 and 2016 and the yearly national average drug acquisition cost (NADAC) price between 2013 and 2016. Wilcoxon signed rank test was used to compare changes in drug prices and number of manufacturers from 2013 to 2016. Spearman correlation coefficient was used to assess the association between drug prices and number of manufacturers. RESULTS: Twenty-two antibiotics (81 formulations and strengths) were analyzed. There was no change in the median NADAC price or the number of manufacturers between 2013 and 2016. However, 11 (14%) formulations increased in price by 90% or more, and 13 (16%) had 2 or fewer manufacturers during all 4 years. Antibiotic prices were negatively associated with the number of available manufacturers. CONCLUSIONS: While prices and the number of manufacturers for common oral antibiotics were overall stable between 2013 and 2016, reduced manufacturer competition was associated with increased prices. A subset of antibiotics exhibited substantial price increases, and most, but not all, had limited manufacturer competition. Policy solutions are needed to ensure availability of low-cost, essential generic antibiotics.

Incentives for Bushmeat Consumption and Importation among West African Immigrants, Minnesota, USA.

The knowledge, attitudes, and practices surrounding bushmeat consumption and importation in the United States are not well described. Focus groups of West African persons living in Minnesota, USA, found that perceived risks are low and unlikely to deter consumers. Incentives for importation and consumption were multifactorial in this community.

High-cost generic drugs--implications for patients and policymakers.

Some older generic drugs have become very expensive, owing to factors including drug shortages, supply disruptions, and consolidations in the generic-drug industry. But generics manufacturers that legally obtain a market monopoly can also unilaterally raise prices.

Strongyloides hyperinfection following hematopoietic stem cell transplant in a patient with HTLV-1-associated T-cell leukemia.

Strongyloides stercoralis has the potential to cause accelerated autoinfection in immunocompromised hosts. Screening tests for strongyloidiasis may be falsely negative in the setting of immunosuppression. We report a case of Strongyloides hyperinfection syndrome in a patient with human T-lymphotropic virus type 1-associated T-cell leukemia early after hematopoietic stem cell transplant. The diagnosis was made by stool ova and parasite examination, despite a negative screening enzyme-linked immunosorbent assay. Because of anticipated prolonged neutropenia, an extended course of treatment was utilized.

Perceived barriers to success for resident physicians interested in immigrant and refugee health.

BACKGROUND: Cross-cultural care is recognized by the ACGME as an important aspect of US residency training. Resident physicians' preparedness to deliver cross-cultural care has been well studied, while preparedness to provide care specifically to immigrant and refugee populations has not been. METHODS: We administered a survey in October 2013 to 199 residents in Internal Medicine, Pediatrics, and Medicine/Pediatrics at the University of Minnesota, assessing perceived knowledge, attitudes, and experience with immigrant and refugee patients. RESULTS: Eighty-three of 199 residents enrolled in Internal Medicine, Pediatrics and Medicine/Pediatrics programs at the University of Minnesota completed the survey (42 %). Most (n = 68, 82 %) enjoyed caring for immigrants and refugees. 54 (65 %) planned to care for this population after residency, though 45 (54 %) were not comfortable with their knowledge regarding immigrant and refugee health. Specific challenges were language (n = 81, 98 %), cultural barriers (n = 76, 92 %), time constraints (n = 60, 72 %), and limited knowledge of tropical medicine (n = 57, 69 %). 67 (82 %) wanted more training in refugee and immigrant health. CONCLUSIONS: The majority of residents enjoyed caring for immigrant and refugee patients and planned to continue after residency. Despite favorable attitudes, residents identified many barriers to providing good care. Some involved cultural and language barriers, while others were structural. Finally, most respondents felt they needed more education, did not feel comfortable with their knowledge, and wanted more training during residency. These data suggest that residency programs consider increasing training in these specific areas of concern.

Factors Associated With Adherence to First-line Antiviral Therapy Among Commercially Insured Patients With Chronic Hepatitis B.

Background: Nonadherence to antiviral therapy can lead to poor clinical outcomes among patients with chronic hepatitis B (CHB). We used a claims database to evaluate risk factors for nonadherence to antiviral therapy among commercially insured patients with CHB in the United States. Methods: We obtained data for commercially insured adult patients with CHB prescribed entecavir or tenofovir disoproxil fumarate (TDF) in 2019. Primary outcomes were adherence to entecavir and adherence to TDF. Enrollees with a proportion of days covered (PDC) ≥80% were considered adherent. We presented adjusted odds ratios (AORs) from multivariate logistic regressions. Results: Eighty-three percent (n = 640) of entecavir patients were adherent, and 81% (n = 687) of TDF patients were adherent. Ninety-day supply (vs 30-day supply; AOR, 2.21; P < .01), mixed supply (vs 30-day supply; AOR, 2.19; P = .04), and ever using a mail order pharmacy (AOR, 1.92, P = .03) were associated with adherence to entecavir. Ninety-day supply (vs 30-day supply; AOR, 2.51; P < .01), mixed supply (vs 30-day supply; AOR, 1.82; P = .04), and use of a high-deductible health plan (vs no high-deductible health plan; AOR, 2.29; P = .01) were associated with adherence to TDF. Out-of-pocket spending of >$25 per 30-day supply of TDF was associated with reduced odds of adherence to TDF (vs <$5 per 30-day supply of TDF; AOR, 0.34; P < .01). Conclusions: Ninety-day and mixed-duration supplies of entecavir and TDF were associated with higher fill rates as compared with 30-day supplies among commercially insured patients with CHB.

Costs of malaria treatment in the United States.

We estimated inpatient and outpatient payments for malaria treatment in the USA. The mean cost per hospitalized patient was significantly higher than for non-hospitalized patients (e.g. $27 642 vs $1177 among patients with private insurance). Patients with severe malaria payed two to four times more than those hospitalized with uncomplicated malaria.

Cost-effectiveness of treatment strategies for populations from strongyloidiasis high-risk areas globally who will initiate corticosteroid treatment in the United States.

BACKGROUND: The risk of developing strongyloidiasis hyperinfection syndrome appears to be elevated among individuals who initiate corticosteroid treatment. Presumptive treatment or treatment after screening for populations from Strongyloides stercoralis-endemic areas has been suggested before initiating corticosteroids. However, potential clinical and economic impacts of preventative strategies have not been evaluated. METHODS: Using a decision tree model for a hypothetical cohort of 1000 individuals from S. stercoralis-endemic areas globally initiating corticosteroid treatment, we evaluated clinical and economic impacts of two interventions, 'Screen and Treat' (i.e. screening and ivermectin treatment after a positive test), and 'Presumptively Treat,' compared to current practice (i.e. 'No Intervention'). We evaluated the cost-effectiveness (net cost per death averted) of each strategy using broad ranges of pre-intervention prevalence and hospitalization rates for chronic strongyloidiasis patients initiating corticosteroid treatment. RESULTS: For the baseline parameter estimates, 'Presumptively Treat' was cost-effective (i.e. clinically superior with cost per death averted less than a threshold of $10.6 million per life) compared to 'No Intervention' ($532 000 per death averted) or 'Screen and Treat' ($39 000 per death averted). The two parameters contributing the most uncertainty to the analysis were the hospitalization rate for individuals with chronic strongyloidiasis who initiate corticosteroids (baseline 0.166%) and prevalence of chronic strongyloidiasis (baseline 17.3%) according to a series of one-way sensitivity analyses. For hospitalization rates greater than 0.022%, 'Presumptively Treat' would remain cost-effective. Similarly, 'Presumptively Treat' remained preferred at prevalence rates of 4% or above; 'Screen and Treat' was preferred for prevalence between 2% and 4%, and 'No Intervention' was preferred for prevalence less than 2%. CONCLUSIONS: The findings support decision-making for interventions for populations from S. stercoralis endemic areas before initiating corticosteroid treatment. Although some input parameters are highly uncertain and prevalence varies across endemic countries, 'Presumptively Treat' would likely be preferred across a range for many populations given plausible parameters.