Risk of Hemolytic Uremic Syndrome Related to Treatment of Escherichia coli O157 Infection with Different Antimicrobial Classes.

Treatment of Shiga toxin-producing Escherichia coli O157 (O157) diarrhea with antimicrobials might alter the risk of hemolytic uremic syndrome (HUS). However, full characterization of which antimicrobials might affect risk is lacking, particularly among adults. To inform clinical management, we conducted a case-control study of residents of the FoodNet surveillance areas with O157 diarrhea during a 4-year period to assess antimicrobial class-specific associations with HUS among persons with O157 diarrhea. We collected data from medical records and patient interviews. We measured associations between treatment with agents in specific antimicrobial classes during the first week of diarrhea and development of HUS, adjusting for age and illness severity. We enrolled 1308 patients; 102 (7.8%) developed confirmed HUS. Antimicrobial treatment varied by age: <5 years (12.6%), 5-14 (11.5%), 15-39 (45.4%), ≥40 (53.4%). Persons treated with a ß-lactam had higher odds of developing HUS (OR 2.80, CI 1.14-6.89). None of the few persons treated with a macrolide developed HUS, but the protective association was not statistically significant. Exposure to "any antimicrobial" was not associated with increased odds of HUS. Our findings confirm the risk of ß-lactams among children with O157 diarrhea and extends it to adults. We observed a high frequency of inappropriate antimicrobial treatment among adults. Our data suggest that antimicrobial classes differ in the magnitude of risk for persons with O157 diarrhea.

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.

Identifying Vaccine-associated Rash Illness Amidst a Large Measles Outbreak: Minnesota, 2017.

Characteristics of vaccine-associated rash illness (VARI) and confirmed measles cases were compared during a measles outbreak. Although some clinical differences were noted, measles exposure and identification of the vaccine strain were helpful for public health decision-making. Rapid, vaccine strain-specific diagnostic assays will more efficiently distinguish VARI from measles.

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.

The Changing Epidemiology of Candidemia in the United States: Injection Drug Use as an Increasingly Common Risk Factor-Active Surveillance in Selected Sites, United States, 2014-2017.

BACKGROUND: Injection drug use (IDU) is a known, but infrequent risk factor on candidemia; however, the opioid epidemic and increases in IDU may be changing the epidemiology of candidemia. METHODS: Active population-based surveillance for candidemia was conducted in selected US counties. Cases of candidemia were categorized as IDU cases if IDU was indicated in the medical records in the 12 months prior to the date of initial culture. RESULTS: During 2017, 1191 candidemia cases were identified in patients aged >12 years (incidence: 6.9 per 100 000 population); 128 (10.7%) had IDU history, and this proportion was especially high (34.6%) in patients with candidemia aged 19-44. Patients with candidemia and IDU history were younger than those without (median age, 35 vs 63 years; P < .001). Candidemia cases involving recent IDU were less likely to have typical risk factors including malignancy (7.0% vs 29.4%; relative risk [RR], 0.2 [95% confidence interval {CI}, .1-.5]), abdominal surgery (3.9% vs 17.5%; RR, 0.2 [95% CI, .09-.5]), and total parenteral nutrition (3.9% vs 22.5%; RR, 0.2 [95% CI, .07-.4]). Candidemia cases with IDU occurred more commonly in smokers (68.8% vs 18.5%; RR, 3.7 [95% CI, 3.1-4.4]), those with hepatitis C (54.7% vs 6.4%; RR, 8.5 [95% CI, 6.5-11.3]), and in people who were homeless (13.3% vs 0.8%; RR, 15.7 [95% CI, 7.1-34.5]). CONCLUSIONS: Clinicians should consider injection drug use as a risk factor in patients with candidemia who lack typical candidemia risk factors, especially in those with who are 19-44 years of age and have community-associated candidemia.

Testing for Coccidioidomycosis among Community-Acquired Pneumonia Patients, Southern California, USA1.

We conducted a cohort study to identify characteristics associated with testing for, and testing positive for, coccidioidomycosis among patients with community-acquired pneumonia in southern California, USA. Limited and delayed testing probably leads to underdiagnosis among non-Hispanic black, Filipino, or Hispanic patients and among high-risk groups, including persons in whom antimicrobial drug therapy has failed.

Recognition of Azole-Resistant Aspergillosis by Physicians Specializing in Infectious Diseases, United States.

Infections caused by pan-azole-resistant Aspergillus fumigatus strains have emerged in Europe and recently in the United States. Physicians specializing in infectious diseases reported observing pan-azole-resistant infections and low rates of susceptibility testing, suggesting the need for wider-scale testing.

Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga Toxin-Producing Escherichia coli Infection: A Centers for Disease Control and Prevention FoodNet Study.

Background: Postdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin-producing Escherichia coli (STEC) infection is a serious condition lacking specific treatment. Host immune dysregulation and genetic susceptibility to complement hyperactivation are implicated in non-STEC-related HUS. However, genetic susceptibility to D+HUS remains largely uncharacterized. Methods: Patients with culture-confirmed STEC diarrhea, identified through the Centers for Disease Control and Prevention FoodNet surveillance system (2007-2012), were serotyped and classified by laboratory and/or clinical criteria as having suspected, probable, or confirmed D+HUS or as controls and underwent genotyping at 200 loci linked to nondiarrheal HUS or similar pathologies. Genetic associations with D+HUS were explored by multivariable regression, with adjustment for known risk factors. Results: Of 641 enrollees with STEC O157:H7, 80 had suspected D+HUS (41 with probable and 32 with confirmed D+HUS). Twelve genes related to cytokine signaling, complement pathways, platelet function, pathogen recognition, iron transport, and endothelial function were associated with D+HUS in multivariable-adjusted analyses (P ≤ .05). Of 12 significant single-nucleotide polymorphisms (SNPs), 5 were associated with all levels of D+HUS (intergenic SNP rs10874639, TFRC rs3804141, EDN1 rs5370, GP1BA rs121908064, and B2M rs16966334), and 7 SNPs (6 non-complement related) were associated with confirmed D+HUS (all P < .05). Conclusions: Polymorphisms in many non-complement-related genes may contribute to D+HUS susceptibility. These results require replication, but they suggest novel therapeutic targets in patients with D+HUS.

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea.

These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea.

These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.

Trends in Hospitalizations Related to Invasive Aspergillosis and Mucormycosis in the United States, 2000-2013.

BACKGROUND: Invasive aspergillosis (IA) and mucormycosis contribute to substantial mortality, especially among immunocompromised persons, including those with hematopoietic stem cell transplant (HSCT), hematologic malignancy (HM), and solid organ transplant (SOT). METHODS: Using International Classification of Diseases, Ninth Revision codes available in the National Inpatient Sample, a hospital discharge database, we estimated IA-related hospitalizations (IA-RH), mucormycosis-RH (M-RH), HSCT-RH, HM-RH, and SOT-RH during 2000-2013. United States census data were used to calculate overall M-RH and IA-RH rates and present trends; estimated annual numbers of HSCT-RH, HM-RH, and SOT-RH served as denominators to calculate M-RH and IA-RH rates occurring with these conditions. Weighted least-squares technique was used to test for linear trends and calculate average annual percentage change (APC). RESULTS: There were an estimated 169 110 IA-RH and 9966 M-RH during 2000-2013. Overall, IA-RH and M-RH rates per million persons rose from 32.8 to 46.0 (APC = +2.9; P < .001) and 1.7 to 3.4 (APC = +5.2%; P < .001), respectively, from 2000 to 2013. Among HSCT-RH, there was no significant change in M-RH rate, but a significant decline occurred in IA-RH rate (APC = -4.6%; P = .004). Among HM-RH, the rate of M-RH increased (APC = +7.0%; P < .001), but the IA-RH rate did not change significantly (APC = +1.2%; P = .073). Among SOT-RH, M-RH (APC = +6.3%; P = .038) and IA-RH rates (APC = +4.1%; P < .001) both increased. CONCLUSIONS: Overall IA-RH and M-RH rates increased during 2000-2013, with a doubling of M-RH. Mucormycosis-related hospitalization occurring in conjunction with certain comorbidities increased, whereas IA-RH rates among patients with the comorbidities, decreased, remained stable, or increased to a lesser extent than M-RH.

Safety and Improved Clinical Outcomes in Patients Treated With New Equine-Derived Heptavalent Botulinum Antitoxin.

Background: Botulism is a rare, life-threatening paralytic illness. Equine-derived heptavalent botulinum antitoxin (HBAT), the only currently available treatment for noninfant botulism in the United States, was licensed in 2013. No reports have systematically examined safety and clinical benefit of HBAT among botulism patients. Methods: From March 2010 through March 2013, we collected data prospectively and through medical record reviews of patients with confirmed or suspected botulism who were treated with HBAT under an expanded-access Investigational New Drug program. Results: Among 249 HBAT-treated patients, 1 (<1%) child experienced an HBAT-related serious adverse event (hemodynamic instability characterized by bradycardia, tachycardia, and asystole); 22 (9%) patients experienced 38 nonserious adverse events reported by physicians to be HBAT related. Twelve (5%) deaths occurred; all were determined to be likely unrelated to HBAT. Among 104 (42%) patients with confirmed botulism, those treated early (≤2 days) spent fewer days in the hospital (median, 15 vs 25 days; P < .01) and intensive care (10 vs 17 days; P = .04) than those treated later. Improvements in any botulism sign/symptom were detected a median of 2.4 days and in muscle strength a median of 4.8 days after HBAT. Conclusions: HBAT was safe and provided clinical benefit in treated patients. HBAT administration within 2 days of symptom onset was associated with shorter hospital and intensive care stays. These results highlight the importance of maintaining clinical suspicion for botulism among patients presenting with paralytic illness to facilitate early HBAT treatment before laboratory confirmation might be available. Clinical consultation and, if indicated, HBAT release, are available to clinicians 24/7 through their state health department in conjunction with CDC.

Clinical Characteristics and Ancillary Test Results Among Patients With Botulism-United States, 2002-2015.

Background: Botulism is classically described as a bilateral, symmetric, descending flaccid paralysis in an afebrile and alert patient without sensory findings. We describe the reported spectrum of clinical findings among persons >12 months of age in the United States during 2002-2015. Methods: The Centers for Disease Control and Prevention collects clinical findings reported by physicians treating suspected cases of botulism nationwide. We analyzed symptoms and signs, and neuroimaging and cerebrospinal fluid (CSF) results. A case was defined as illness compatible with botulism with laboratory confirmation or epidemiologic link to a confirmed case, and presence or absence of at least 1 sign or symptom recorded. Physicians' differential diagnoses were evaluated. Results: Clinical information was evaluated for 332 botulism cases; data quality and completeness were variable. Most had no fever (99%), descending paralysis (93%), no mental status change (91%), at least 1 ocular weakness finding (84%), and neuroimaging without acute changes (82%). Some had paresthesias (17%), elevated CSF protein level (13%), and other features sometimes considered indicative of alternative diagnoses. Five of 71 (7%) cases with sufficient information were reported to have atypical findings (eg, at least 1 cranial nerve finding that was unilateral or ascending paralysis). Illnesses on the physician differential included Guillain-Barré syndrome (99 cases) and myasthenia gravis (76 cases) and, rarely, gastrointestinal-related illness (5 cases), multiple sclerosis (3 cases), sepsis (3 cases), and Lyme disease (2 cases). Conclusions: Our analysis illustrates that classic symptoms and signs were common among patients with botulism but that features considered atypical were reported by some physicians. Diagnosis can be challenging, as illustrated by the broad range of illnesses on physician differentials.

Sporotrichosis-Associated Hospitalizations, United States, 2000-2013.

To determine frequency and risk for sporotrichosis-associated hospitalizations, we analyzed the US 2000-2013 National (Nationwide) Inpatient Sample. An estimated 1,471 hospitalizations occurred (average annual rate 0.35/1 million persons). Hospitalizations were associated with HIV/AIDS, immune-mediated inflammatory diseases, and chronic obstructive pulmonary disease. Although rare, severe sporotrichosis should be considered for at-risk patients.

Notes from the Field: Probable Mucormycosis Among Adult Solid Organ Transplant Recipients at an Acute Care Hospital - Pennsylvania, 2014-2015.

On September 17, 2015, the Pennsylvania Department of Health (PADOH) notified CDC of a cluster of three potentially health care-associated mucormycete infections that occurred among solid organ transplant recipients during a 12-month period at hospital A. On September 18, hospital B reported that it had identified an additional transplant recipient with mucormycosis. Hospitals A and B are part of the same health care system and are connected by a pedestrian bridge. PADOH requested CDC's assistance with an on-site investigation, which started on September 22, to identify possible sources of infection and prevent additional infections.

Implementation of Nationwide Real-time Whole-genome Sequencing to Enhance Listeriosis Outbreak Detection and Investigation.

Listeria monocytogenes (Lm) causes severe foodborne illness (listeriosis). Previous molecular subtyping methods, such as pulsed-field gel electrophoresis (PFGE), were critical in detecting outbreaks that led to food safety improvements and declining incidence, but PFGE provides limited genetic resolution. A multiagency collaboration began performing real-time, whole-genome sequencing (WGS) on all US Lm isolates from patients, food, and the environment in September 2013, posting sequencing data into a public repository. Compared with the year before the project began, WGS, combined with epidemiologic and product trace-back data, detected more listeriosis clusters and solved more outbreaks (2 outbreaks in pre-WGS year, 5 in WGS year 1, and 9 in year 2). Whole-genome multilocus sequence typing and single nucleotide polymorphism analyses provided equivalent phylogenetic relationships relevant to investigations; results were most useful when interpreted in context of epidemiological data. WGS has transformed listeriosis outbreak surveillance and is being implemented for other foodborne pathogens.

Invasive Fungal Infections Acquired from Contaminated Food or Nutritional Supplements: A Review of the Literature.

Fungi are an integral part of the natural environment and, therefore, play many roles in relation to food: some fungi are used in food production, some are food sources themselves, and some are agents of food spoilage. Some fungi that contaminate food can also be harmful to human health. The harmful but noninfectious health consequences of mycotoxins have been well-characterized, but the extent to which fungi in food pose a risk for invasive infections is unknown. We conducted a literature review to identify cases of invasive fungal infections (IFIs) believed to have resulted from ingestion or inhalation of food, beverages, or dietary supplements (excluding Saccharomyces infections). We identified 11 publications describing cases or small outbreaks of IFIs related to foods or beverages and three describing IFIs related to dietary supplements. These food-associated IFIs were predominantly mold infections, and the few yeast infections were associated with dairy products. Suspected foodborne IFIs appear to be rare, but are increasingly described in the electronically searchable literature. They are associated with a variety of foods, are due to a variety of fungal pathogens, and primarily occur in persons with immunosuppressive conditions or other predisposing factors. Various guidelines for high-risk patients recommend avoidance of certain food products that may contain high levels of fungi, but further work is needed to evaluate the effectiveness of these restrictive diets in preventing fungal infections. The relationships between food spoilage, food insecurity, and IFI risk are another area that may warrant further exploration.

Epidemiology of Histoplasmosis Outbreaks, United States, 1938-2013.

Histoplasmosis has been described as the most common endemic mycosis in the United States. However, histoplasmosis is not nationally notifiable. Its presumed geographic distribution is largely derived from skin test surveys performed during the 1940s, and information about its local features comes primarily from outbreak investigations. We conducted a literature review to assess epidemiologic features of histoplasmosis outbreaks in the United States. During 1938-2013, a total of 105 outbreaks involving 2,850 cases were reported in 26 states and the territory of Puerto Rico. Common exposure settings were chicken coops and buildings or other structures undergoing renovation or demolition. Birds, bats, or their droppings were reported to be present in 77% of outbreak settings, and workplace exposures were reported in 41% of outbreaks. The continued occurrence of histoplasmosis outbreaks, particularly work-related ones involving known disturbance of bird or bat droppings, highlights the need to increase awareness of the disease.

Histoplasmosis-Associated Hospitalizations in the United States, 2001-2012.

We examined trends in histoplasmosis-associated hospitalizations in the United States using the 2001-2012 National (Nationwide) Inpatient Sample. An estimated 50 778 hospitalizations occurred, with significant increases in hospitalizations overall and in the proportion of hospitalizations associated with transplant, diabetes, and autoimmune conditions often treated with biologic therapies; therefore, histoplasmosis remains an important opportunistic infection.