The Landscape of Candidemia During the Coronavirus Disease 2019 (COVID-19) Pandemic.

BACKGROUND: The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 coinfection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis. METHODS: We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention's Emerging Infections Program during April-August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher's exact tests. RESULTS: Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid-organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 coinfection, whereas intensive care unit-level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All-cause in-hospital fatality was 2 times higher among those with COVID-19 (62.5%) than without (32.1%). CONCLUSIONS: One-quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19.

Treatment Practices for Adults With Candidemia at 9 Active Surveillance Sites-United States, 2017-2018.

BACKGROUND: Candidemia is a common opportunistic infection causing substantial morbidity and mortality. Because of an increasing proportion of non-albicans Candida species and rising antifungal drug resistance, the Infectious Diseases Society of America (IDSA) changed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment for adults with candidemia. We describe candidemia treatment practices and adherence to the updated guidelines. METHODS: During 2017-2018, the Emerging Infections Program conducted active population-based candidemia surveillance at 9 US sites using a standardized case definition. We assessed factors associated with initial antifungal treatment for the first candidemia case among adults using multivariable logistic regression models. To identify instances of potentially inappropriate treatment, we compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results from initial blood cultures. RESULTS: Among 1835 patients who received antifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment. Cirrhosis (adjusted odds ratio = 2.06; 95% confidence interval, 1.29-3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole). More than one-half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non-albicans species. Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate. CONCLUSIONS: A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non-albicans or fluconazole-resistant species. Reasons for nonadherence to IDSA guidelines should be evaluated, and clinician education is needed.

Burden of Candidemia in the United States, 2017.

BACKGROUND: Candidemia is a common healthcare-associated bloodstream infection with high morbidity and mortality. There are no current estimates of candidemia burden in the United States (US). METHODS: In 2017, the Centers for Disease Control and Prevention conducted active population-based surveillance for candidemia through the Emerging Infections Program in 45 counties in 9 states encompassing approximately 17 million persons (5% of the national population). Laboratories serving the catchment area population reported all blood cultures with Candida, and a standard case definition was applied to identify cases that occurred in surveillance area residents. Burden of cases and mortality were estimated by extrapolating surveillance area cases to national numbers using 2017 national census data. RESULTS: We identified 1226 candidemia cases across 9 surveillance sites in 2017. Based on this, we estimated that 22 660 (95% confidence interval [CI], 20 210-25 110) cases of candidemia occurred in the US in 2017. Overall estimated incidence was 7.0 cases per 100 000 persons, with highest rates in adults aged ≥ 65 years (20.1/100 000), males (7.9/100 000), and those of black race (12.3/100 000). An estimated 3380 (95% CI, 1318-5442) deaths occurred within 7 days of a positive Candida blood culture, and 5628 (95% CI, 2465-8791) deaths occurred during the hospitalization with candidemia. CONCLUSIONS: Our analysis highlights the substantial burden of candidemia in the US. Because candidemia is only one form of invasive candidiasis, the true burden of invasive infections due to Candida is higher. Ongoing surveillance can support future burden estimates and help assess the impact of prevention interventions.

Candida Bloodstream Infections Among Persons Who Inject Drugs - Denver Metropolitan Area, Colorado, 2017-2018.

Candidemia, a bloodstream infection caused by Candida species, is typically considered a health care-associated infection, with known risk factors including the presence of a central venous catheter, receipt of total parenteral nutrition or broad-spectrum antibiotics, recent abdominal surgery, admission to an intensive care unit, and prolonged hospitalization (1,2). Injection drug use (IDU) is not a common risk factor for candidemia; however, in the context of the ongoing opioid epidemic and corresponding IDU increases, IDU has been reported as an increasingly common condition associated with candidemia (3) and methicillin-resistant Staphylococcus aureus bacteremia (4). Little is known about the epidemiology of candidemia among persons who inject drugs. The Colorado Department of Public Health and Environment (CDPHE) conducts population-based surveillance for candidemia in the five-county Denver metropolitan area, encompassing 2.7 million persons, through CDC's Emerging Infections Program (EIP). As part of candidemia surveillance, CDPHE collected demographic, clinical, and IDU behavior information for persons with Candida-positive blood cultures during May 2017-August 2018. Among 203 candidemia cases reported, 23 (11%) occurred in 22 patients with a history of IDU in the year preceding their candidemia episode. Ten (43%) of the 23 cases were considered community-onset infections, and four (17%) cases were considered community-onset infections with recent health care exposures. Seven (32%) of the 22 patients had disseminated candidiasis with end-organ dysfunctions; four (18%) died during their hospitalization. In-hospital IDU was reported among six (27%) patients, revealing that IDU can be a risk factor in the hospital setting as well as in the community. In addition to community interventions, opportunities to intervene during health care encounters to decrease IDU and unsafe injection practices might prevent infections, including candidemia, among persons who inject drugs.

The cost-effectiveness of sofosbuvir-based regimens for treatment of hepatitis C virus genotype 2 or 3 infection.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) genotype 2 or 3 can be treated with sofosbuvir without interferon. Because sofosbuvir is costly, its benefits should be compared with the additional resources used. OBJECTIVE: To estimate the cost-effectiveness of sofosbuvir-based treatments for HCV genotype 2 or 3 infection in the United States. DESIGN: Monte Carlo simulation, including deterministic and probabilistic sensitivity analyses. DATA SOURCES: Randomized trials, observational cohorts, and national health care spending surveys. TARGET POPULATION: 8 patient types defined by HCV genotype (2 vs. 3), treatment history (naive vs. experienced), and cirrhosis status (noncirrhotic vs. cirrhotic). TIME HORIZON: Lifetime. PERSPECTIVE: Payer. INTERVENTION: Sofosbuvir-based therapies, pegylated interferon-ribavirin, and no therapy. OUTCOME MEASURES: Discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: The ICER of sofosbuvir-based treatment was less than $100,000 per QALY in cirrhotic patients (genotype 2 or 3 and treatment-naive or treatment-experienced) and in treatment-experienced noncirrhotic patients but was greater than $200,000 per QALY in treatment-naive noncirrhotic patients. RESULTS OF SENSITIVITY ANALYSIS: The ICER of sofosbuvir-based therapy for treatment-naive noncirrhotic patients with genotype 2 or 3 infection was less than $100,000 per QALY when the cost of sofosbuvir was reduced by approximately 40% and 60%, respectively. In probabilistic sensitivity analyses, cost-effectiveness conclusions were robust to uncertainty in treatment efficacy. LIMITATION: The analysis did not consider possible benefits of preventing HCV transmission. CONCLUSION: Sofosbuvir provides good value for money for treatment-experienced patients with HCV genotype 2 or 3 infection and those with cirrhosis. At their current cost, sofosbuvir-based regimens for treatment-naive noncirrhotic patients exceed willingness-to-pay thresholds commonly cited in the United States. PRIMARY FUNDING SOURCE: National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases.

Tuberculosis and poverty: the contribution of patient costs in sub-Saharan Africa--a systematic review.

BACKGROUND: Tuberculosis (TB) is known to disproportionately affect the most economically disadvantaged strata of society. Many studies have assessed the association between poverty and TB, but only a few have assessed the direct financial burden TB treatment and care can place on households. Patient costs can be particularly burdensome for TB-affected households in sub-Saharan Africa where poverty levels are high; these costs include the direct costs of medical and non-medical expenditures and the indirect costs of time utilizing healthcare or lost wages. In order to comprehensively assess the existing evidence on the costs that TB patients incur, we undertook a systematic review of the literature. METHODS: PubMed, EMBASE, Science Citation Index, Social Science Citation Index, EconLit, Dissertation Abstracts, CINAHL, and Sociological Abstracts databases were searched, and 5,114 articles were identified. Articles were included in the final review if they contained a quantitative measure of direct or indirect patient costs for treatment or care for pulmonary TB in sub-Saharan Africa and were published from January 1, 1994 to Dec 31, 2010. Cost data were extracted from each study and converted to 2010 international dollars (I$). RESULTS: Thirty articles met all of the inclusion criteria. Twenty-one studies reported both direct and indirect costs; eight studies reported only direct costs; and one study reported only indirect costs. Depending on type of costs, costs varied from less than I$1 to almost I$600 or from a small fraction of mean monthly income for average annual income earners to over 10 times average annual income for income earners in the income-poorest 20% of the population. Out of the eleven types of TB patient costs identified in this review, the costs for hospitalization, medication, transportation, and care in the private sector were largest. CONCLUSION: TB patients and households in sub-Saharan Africa often incurred high costs when utilizing TB treatment and care, both within and outside of Directly Observed Therapy Short-course (DOTS) programs. For many households, TB treatment and care-related costs were considered to be catastrophic because the patient costs incurred commonly amounted to 10% or more of per capita incomes in the countries where the primary studies included in this review were conducted. Our results suggest that policies to decrease direct and indirect TB patient costs are urgently needed to prevent poverty due to TB treatment and care for those affected by the disease.

The Estimated Health and Economic Benefits of Three Decades of Polio Elimination Efforts in India.

OBJECTIVE: In March 2014, India, the country with historically the highest burden of polio, was declared polio free, with no reported cases since January 2011. We estimate the health and economic benefits of polio elimination in India with the oral polio vaccine (OPV) during 1982-2012. METHODS: Based on a pre-vaccine incidence rate, we estimate the counterfactual burden of polio in the hypothetical absence of the national polio elimination program in India. We attribute differences in outcomes between the actual (adjusted for under-reporting) and hypothetical counterfactual scenarios in our model to the national polio program. We measure health benefits as averted polio incidence, deaths, and disability adjusted life years (DALYs). We consider two methods to measure economic benefits: the value of statistical life approach, and equating one DALY to the Gross National Income (GNI) per capita. RESULTS: We estimate that the National Program against Polio averted 3.94 million (95% confidence interval [CI]: 3.89-3.99 million) paralytic polio cases, 393,918 polio deaths (95% CI: 388,897- 398,939), and 1.48 billion DALYs (95% CI: 1.46-1.50 billion). We also estimate that the program contributed to a $1.71 trillion (INR 76.91 trillion) gain (95% CI: $1.69-$1.73 trillion [INR 75.93-77.89 trillion]) in economic productivity between 1982 and 2012 in our base case analysis. Using the GNI and DALY method, the economic gain from the program is estimated to be $1.11 trillion (INR 50.13 trillion) (95% CI: $1.10-$1.13 trillion [INR 49.50-50.76 trillion]) over the same period. CONCLUSION: India accrued large health and economic benefits from investing in polio elimination efforts. Other programs to control/eliminate more vaccine-preventable diseases are likely to contribute to large health and economic benefits in India.

Cost-effectiveness of rapid hepatitis C virus (HCV) testing and simultaneous rapid HCV and HIV testing in substance abuse treatment programs.

AIMS: To evaluate the cost-effectiveness of rapid hepatitis C virus (HCV) and simultaneous HCV/HIV antibody testing in substance abuse treatment programs. DESIGN: We used a decision analytic model to compare the cost-effectiveness of no HCV testing referral or offer, off-site HCV testing referral, on-site rapid HCV testing offer and on-site rapid HCV and HIV testing offer. Base case inputs included 11% undetected chronic HCV, 0.4% undetected HIV, 35% HCV co-infection among HIV-infected, 53% linked to HCV care after testing antibody-positive and 67% linked to HIV care. Disease outcomes were estimated from established computer simulation models of HCV [Hepatitis C Cost-Effectiveness (HEP-CE)] and HIV [Cost-Effectiveness of Preventing AIDS Complications (CEPAC)]. SETTING AND PARTICIPANTS: Data on test acceptance and costs were from a national randomized trial of HIV testing strategies conducted at 12 substance abuse treatment programs in the United States. MEASUREMENTS: Lifetime costs (2011 US$) and quality-adjusted life years (QALYs) discounted at 3% annually; incremental cost-effectiveness ratios (ICERs). FINDINGS: On-site rapid HCV testing had an ICER of $18,300/QALY compared with no testing, and was more efficient than (dominated) off-site HCV testing referral. On-site rapid HCV and HIV testing had an ICER of $64,500/QALY compared with on-site rapid HCV testing alone. In one- and two-way sensitivity analyses, the ICER of on-site rapid HCV and HIV testing remained <$100,000/QALY, except when undetected HIV prevalence was <0.1% or when we assumed frequent HIV testing elsewhere. The ICER remained <$100,000/QALY in 91% of probabilistic sensitivity analyses. CONCLUSIONS: On-site rapid hepatitis C virus and HIV testing in substance abuse treatment programs is cost-effective at a <$100,000/quality-adjusted life year threshold.

Hepatitis C screening trends in a large integrated health system.

BACKGROUND: As new hepatitis C virus (HCV) therapies emerge, only 1%-12% of individuals are screened in the US for HCV infection. Presently, HCV screening trends are unknown. METHODS: We utilized the Kaiser Permanente Mid-Atlantic States' (KPMAS) data repository to investigate HCV antibody screening between January 1, 2003 and December 31, 2012. We identified the proportion screened for HCV and 5-year cumulative incidence of screening, the screening positivity rate, the provider types performing HCV screening, patient-level factors associated with being screened, and trends in screening over time. RESULTS: There were 444,594 patients who met the inclusion criteria. Overall, 15.8% of the cohort was ever screened for HCV. Adult primary care and obstetrics and gynecology providers performed 75.9% of all screening. The overall test positivity rate was 3.8%. Screening was more frequent in younger age groups (P <.0001) and those with a documented history of illicit drug use (P <.0001). Patients with missing drug use history (46.7%) were least likely to be screened (P <.0001). While the rate of HCV screening increased in the later years of the study among those enrolled in KPMAS 2009-2012, only 11.8% were screened by the end of follow-up. CONCLUSION: Screening for HCV is increasing but remains incomplete. Targeting screening to those with a history of injection drug will not likely expand screening, as nearly half of patients have no documented drug use history. Routine screening is likely the most effective approach to expand HCV screening.

The hepatitis C cascade of care: identifying priorities to improve clinical outcomes.

BACKGROUND: As highly effective hepatitis C virus (HCV) therapies emerge, data are needed to inform the development of interventions to improve HCV treatment rates. We used simulation modeling to estimate the impact of loss to follow-up on HCV treatment outcomes and to identify intervention strategies likely to provide good value for the resources invested in them. METHODS: We used a Monte Carlo state-transition model to simulate a hypothetical cohort of chronically HCV-infected individuals recently screened positive for serum HCV antibody. We simulated four hypothetical intervention strategies (linkage to care; treatment initiation; integrated case management; peer navigator) to improve HCV treatment rates, varying efficacies and costs, and identified strategies that would most likely result in the best value for the resources required for implementation. MAIN MEASURES: Sustained virologic responses (SVRs), life expectancy, quality-adjusted life expectancy (QALE), costs from health system and program implementation perspectives, and incremental cost-effectiveness ratios (ICERs). RESULTS: We estimate that imperfect follow-up reduces the real-world effectiveness of HCV therapies by approximately 75%. In the base case, a modestly effective hypothetical peer navigator program maximized the number of SVRs and QALE, with an ICER compared to the next best intervention of $48,700/quality-adjusted life year. Hypothetical interventions that simultaneously addressed multiple points along the cascade provided better outcomes and more value for money than less costly interventions targeting single steps. The 5-year program cost of the hypothetical peer navigator intervention was $14.5 million per 10,000 newly diagnosed individuals. CONCLUSIONS: We estimate that imperfect follow-up during the HCV cascade of care greatly reduces the real-world effectiveness of HCV therapy. Our mathematical model shows that modestly effective interventions to improve follow-up would likely be cost-effective. Priority should be given to developing and evaluating interventions addressing multiple points along the cascade rather than options focusing solely on single points.

The cost-effectiveness of improved hepatitis C virus therapies in HIV/hepatitis C virus coinfected patients.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of strategies to treat hepatitis C virus (HCV) in HIV/HCV coinfected patients in the United States. PARTICIPANTS: Simulated cohort of HIV/HCV genotype 1 coinfected, noncirrhotic, HCV treatment-naive individuals enrolled in US HIV guideline-concordant care. DESIGN/INTERVENTIONS: Monte Carlo simulation comparing five strategies: no treatment; dual therapy with pegylated-interferon (PEG) and ribavirin (RBV); 'PEG/RBV trial' in which all patients initiate dual therapy and switch to triple therapy upon failure; 'IL28B triage' in which patients initiate either dual therapy or triple therapy based on their IL28B allele type; and PEG/RBV and telaprevir (TPV) triple therapy. Sensitivity analyses varied efficacies and costs and included a scenario with interferon (IFN)-free therapy. MAIN MEASURES: Sustained virologic response (SVR), life expectancy, discounted quality-adjusted life expectancy (QALE), lifetime medical costs, and incremental cost-effectiveness ratios (ICERs) in $/quality-adjusted life years (QALY) gained. RESULTS: 'PEG/RBV trial,' 'IL28B triage,' and 'triple therapy' each provided 72% SVR and extended QALE compared with 'dual therapy' by 1.12, 1.14, and 1.15 QALY, respectively. The ICER of 'PEG/RBV trial' compared with 'dual therapy' was $37 500/QALY. 'IL28B triage' and 'triple therapy' provided little benefit compared with 'PEG/RBV trial,' and both had ICERs exceeding $300 000/QALY. In sensitivity analyses, IFN-free treatment attaining 90% SVR had an ICER less than $100 000/QALY compared with 'PEG/RBV trial' when its cost was $109 000 or less (125% of the cost of PEG/RBV/TVR). CONCLUSION: HCV protease inhibitors are most efficiently used in HIV/HCV coinfection after a trial of PEG/RBV, sparing protease inhibitors for those who attain rapid virologic response and SVR. The cost-effectiveness of IFN-free regimens for HIV/HCV coinfection will depend on the cost of these therapies.