Bloodstream Infections With Candida auris Among Children in Colombia: Clinical Characteristics and Outcomes of 34 Cases.

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and healthcare-associated outbreaks. Here, we describe 34 cases of pediatric C. auris bloodstream infections (BSIs) identified during July 2014-October 2017 in 2 hospitals in Colombia. METHODS: We conducted a retrospective review of microbiology records for possible C. auris cases in 2 hospitals in Barranquilla and Cartagena. BSIs that occurred in patients aged <18 years confirmed as C. auris were included in this analysis. RESULTS: We identified 34 children with C. auris BSIs. Twenty-two (65%) patients were male, 21% were aged <28 days, 47% were aged 29-365 days, and 32% were aged >1 year. Underlying conditions included preterm birth (26%), being malnourished (59%), cancer (12%), solid-organ transplant (3%), and renal disease (3%). Eighty-two percent had a central venous catheter (CVC), 82% were on respiratory support, 56% received total parenteral nutrition (TPN), 15% had a surgical procedure, and 9% received hemodialysis. Preinfection inpatient stay was 22 days (interquartile range, 19-33 days), and in-hospital mortality was 41%. CONCLUSIONS: Candida auris affects children with a variety of medical conditions including prematurity and malignancy, as well as children with CVCs and those who receive TPN. Mortality was high, with nearly half of patients dying before discharge. However, unlike most other Candida species, C. auris can be transmitted in healthcare settings, as suggested by the close clustering of cases in time at each of the hospitals.Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and healthcare-associated outbreaks. This report describes 34 cases of pediatric C. auris bloodstream infections, identified in two hospitals in Colombia, South America.

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.

Population-Based Active Surveillance for Culture-Confirmed Candidemia - Four Sites, United States, 2012-2016.

PROBLEM/CONDITION: Candidemia is a bloodstream infection (BSI) caused by yeasts in the genus Candida. Candidemia is one of the most common health care-associated BSIs in the United States, with all-cause in-hospital mortality of up to 30%. PERIOD COVERED: 2012-2016. DESCRIPTION OF SYSTEM: CDC's Emerging Infections Program (EIP), a collaboration among CDC, state health departments, and academic partners that was established in 1995, was used to conduct active, population-based laboratory surveillance for candidemia in 22 counties in four states (Georgia, Maryland, Oregon, and Tennessee) with a combined population of approximately 8 million persons. Laboratories serving the catchment areas were recruited to report candidemia cases to the local EIP program staff. A case was defined as a blood culture that was positive for a Candida species collected from a surveillance area resident during 2012-2016. Isolates were sent to CDC for species confirmation and antifungal susceptibility testing. Any subsequent blood cultures with Candida within 30 days of the initial positive culture in the same patient were considered part of the same case. Trained surveillance officers collected clinical information from the medical chart for all cases, and isolates were sent to CDC for species confirmation and antifungal susceptibility testing. RESULTS: Across all sites and surveillance years (2012-2016), 3,492 cases of candidemia were identified. The crude candidemia incidence averaged across sites and years during 2012-2016 was 8.7 per 100,000 population; important differences in incidence were found by site, age group, sex, and race. The crude annual incidence was the highest in Maryland (14.1 per 100,000 population) and lowest in Oregon (4.0 per 100,000 population). The crude annual incidence of candidemia was highest among adults aged ≥65 years (25.5 per 100,000 population) followed by infants aged <1 year (15.8). The crude annual incidence was higher among males (9.4) than among females (8.0) and was approximately 2 times greater among blacks than among nonblacks (13.7 versus 5.8). Ninety-six percent of cases occurred in patients who were hospitalized at the time of or during the week after having a positive culture. One third of cases occurred in patients who had undergone a surgical procedure in the 90 days before the candidemia diagnosis, 77% occurred in patients who had received systemic antibiotics in the 14 days before the diagnosis, and 73% occurred in patients who had had a central venous catheter (CVC) in place within 2 days before the diagnosis. Ten percent were in patients who had used injection drugs in the past 12 months. The median time from admission to candidemia diagnosis was 5 days (interquartile range [IQR]: 0-16 days). Among 2,662 cases that were treated in adults aged >18 years, 34% were treated with fluconazole alone, 30% with echinocandins alone, and 34% with both. The all-cause, in-hospital case-fatality ratio was 25% for any time after admission; the all-cause in-hospital case-fatality ratio was 8% for <48 hours after a positive culture for Candida species. Candida albicans accounted for 39% of cases, followed by Candida glabrata (28%) and Candida parapsilosis (15%). Overall, 7% of isolates were resistant to fluconazole and 1.6% were resistant to echinocandins, with no clear trends in resistance over the 5-year surveillance period. INTERPRETATION: Approximately nine out of 100,000 persons developed culture-positive candidemia annually in four U.S. sites. The youngest and oldest persons, men, and blacks had the highest incidences of candidemia. Patients with candidemia identified in the surveillance program had many of the typical risk factors for candidemia, including recent surgery, exposure to broad-spectrum antibiotics, and presence of a CVC. However, an unexpectedly high proportion of candidemia cases (10%) occurred in patients with a history of injection drug use (IDU), suggesting that IDU has become a common risk factor for candidemia. Deaths associated with candidemia remain high, with one in four cases resulting in death during hospitalization. PUBLIC HEALTH ACTION: Active surveillance for candidemia yielded important information about the disease incidence and death rate and persons at greatest risk. The surveillance was expanded to nine sites in 2017, which will improve understanding of the geographic variability in candidemia incidence and associated clinical and demographic features. This surveillance will help monitor incidence trends, track emergence of resistance and species distribution, monitor changes in underlying conditions and predisposing factors, assess trends in antifungal treatment and outcomes, and be helpful for those developing prevention efforts. IDU has emerged as an important risk factor for candidemia, and interventions to prevent invasive fungal infections in this population are needed. Surveillance data documenting that approximately two thirds of candidemia cases were caused by species other than C. albicans, which are generally associated with greater antifungal resistance than C. albicans, and the presence of substantial fluconazole resistance supports 2016 clinical guidelines recommending a switch from fluconazole to echinocandins as the initial treatment for candidemia in most patients.

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.

Trends in antifungal use in US hospitals, 2006-12.

Background: Although trends in antibiotic use have been characterized, less is known about antifungal use. Data on antifungal use are important for understanding practice patterns, assessing emergence of antifungal resistance and developing antifungal stewardship programmes. We estimated national trends in inpatient antifungal use in the USA. Methods: Using billing data for antifungals from the Truven Health MarketScan® Hospital Drug Database during 2006-12, we estimated the proportion of discharges at which antifungals were given and days of therapy (DOT)/1000 patient days (PDs) by antifungal drug type, year, patient and facility characteristics. We created national estimates using weights generated from Centers for Medicare and Medicaid Services data and assessed trends over time. Results: Overall, 2.7% of all inpatients and 7.7% of those in ICUs received antifungals. The estimated DOT/1000 PDs for any antifungal was 35.0 for all inpatients and 73.7 for ICU patients. Azoles accounted for 80% of all antifungal use (28.5/1000 PDs), followed by echinocandins (5.0/1000 PDs). By multivariable trend analysis, DOT/1000 PDs for azoles (-21%) and polyenes (-47%) decreased between 2006 and 2012, whereas echinocandins increased 11% during 2006-10 and declined after 2011. Unspecified septicaemia, HIV and antineoplastic therapy were among the top primary diagnosis codes for patients who received antifungals. Conclusions: Antifungals were most frequently used in ICU settings and fluconazole accounted for a large, but declining, proportion of antifungal use. Antifungal stewardship efforts may have the most impact if focused in ICUs, among certain patient groups (e.g. HIV and malignancy) and on stopping empirical antifungal therapy for unspecified sepsis when not indicated.

Neonatal and Pediatric Candidemia: Results From Population-Based Active Laboratory Surveillance in Four US Locations, 2009-2015.

INTRODUCTION: Candida is a leading cause of healthcare-associated bloodstream infections in the United States. Infants and children have unique risk factors for candidemia, and the Candida species distribution in this group is different that among adults; however, candidemia epidemiology in this population has not been described recently. METHODS: We conducted active population-based candidemia surveillance in 4 US metropolitan areas between 2009 and 2015. We calculated incidences among neonates (0-30 days old), infants (0-364 days old), and noninfant children (1-19 years old), documented their clinical features and antifungal drug resistance. RESULTS: We identified 307 pediatric candidemia cases. Incidence trends varied according to site, but overall, the incidence in neonates decreased from 31.5 cases/100000 births in 2009 to 10.7 to 11.8 cases/100000 births between 2012 and 2015, the incidence in infants decreased from 52.1 cases/100000 in 2009 to 15.7 to 17.5 between 2012 and 2015, and the incidence in noninfant children decreased steadily from 1.8 cases/100000 in 2009 to 0.8 in 2014. Common underlying conditions were prematurity in neonates (78%), surgery in nonneonate infants (38%), and malignancy in noninfant children (28%). Most neonate cases were caused by C albicans (67%), whereas non-C. albicans species accounted for 60% of cases in nonneonate infants and noninfant children. Fluconazole and echinocandin resistance rates were low overall. Thirty-day crude mortality was 13%. CONCLUSIONS: The incidence of candidemia among neonates and infants declined after 2009 but remained stable from 2012 to 2015. Antifungal drug resistance is uncommon. Reasons for the lack of recent declines in neonatal and infant candidemia deserve further exploration. In this article, we describe the epidemiology of candidemia in children in the United States and on the basis of data collected as part of US Centers for Disease Control and Prevention active population-based surveillance. Trends in incidence, clinical characteristics, species distribution, and resistance rates are presented.

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.

Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses.

BACKGROUND: Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. METHODS: To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012-2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). RESULTS: Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9-36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. CONCLUSIONS: C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

Notes from the Field: Fungal Bloodstream Infections Associated with a Compounded Intravenous Medication at an Outpatient Oncology Clinic - New York City, 2016.

On May 24, 2016, the New York City Department of Health and Mental Hygiene notified CDC of two cases of Exophiala dermatitidis bloodstream infections among patients with malignancies who had received care from a single physician at an outpatient oncology facility (clinic A). Review of January 1-May 31, 2016 microbiology records identified E. dermatitidis bloodstream infections in two additional patients who also had received care at clinic A. All four patients had implanted vascular access ports and had received intravenous (IV) medications, including a compounded IV flush solution containing saline, heparin, vancomycin, and ceftazidime, compounded and administered at clinic A.

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa.

BACKGROUND: In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ µl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies. METHODS: We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions. RESULTS: In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment). CONCLUSIONS: In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved.

Implementation and Operational Research: Evaluation of a Public-Sector, Provider-Initiated Cryptococcal Antigen Screening and Treatment Program, Western Cape, South Africa.

BACKGROUND: Screening for serum cryptococcal antigen (CrAg) may identify those at risk for disseminated cryptococcal disease (DCD), and preemptive fluconazole treatment may prevent progression to DCD. In August 2012, the Western Cape Province (WC), South Africa, adopted provider-initiated CrAg screening. We evaluated the implementation and effectiveness of this large-scale public-sector program during its first year, September 1, 2012-August 31, 2013. METHODS: We used data from the South African National Health Laboratory Service, WC provincial HIV program, and nationwide surveillance data for DCD. We assessed the proportion of eligible patients screened for CrAg (CrAg test done within 30 days of CD4 date) and the prevalence of CrAg positivity. Incidence of DCD among those screened was compared with those not screened. RESULTS: Of 4395 eligible patients, 26.6% (n = 1170) were screened. The proportion of patients screened increased from 15.9% in September 2012 to 36.6% in August 2013. The prevalence of positive serum CrAg was 2.1%. Treatment data were available for 13 of 24 CrAg-positive patients; 9 of 13 were treated with fluconazole. Nine (0.8%) incident cases of DCD occurred among the 1170 patients who were screened for CrAg vs. 49 (1.5%) incident cases among the 3225 patients not screened (P = 0.07). CONCLUSIONS: Relatively few eligible patients were screened under the WC provider-initiated CrAg screening program. Unscreened patients were nearly twice as likely to develop DCD. CrAg screening can reduce the burden of DCD, but needs to be implemented well. To improve screening rates, countries should consider laboratory-based reflexive screening when possible.

Whole-Genome Sequencing to Determine Origin of Multinational Outbreak of Sarocladium kiliense Bloodstream Infections.

We used whole-genome sequence typing (WGST) to investigate an outbreak of Sarocladium kiliense bloodstream infections (BSI) associated with receipt of contaminated antinausea medication among oncology patients in Colombia and Chile during 2013-2014. Twenty-five outbreak isolates (18 from patients and 7 from medication vials) and 11 control isolates unrelated to this outbreak were subjected to WGST to elucidate a source of infection. All outbreak isolates were nearly indistinguishable (<5 single-nucleotide polymorphisms), and >21,000 single-nucleotide polymorphisms were identified from unrelated control isolates, suggesting a point source for this outbreak. S. kiliense has been previously implicated in healthcare-related infections; however, the lack of available typing methods has precluded the ability to substantiate point sources. WGST for outbreak investigation caused by eukaryotic pathogens without reference genomes or existing genotyping methods enables accurate source identification to guide implementation of appropriate control and prevention measures.

Cardiothoracic surgical site phaeohyphomycosis caused by Bipolaris mould, multiple US states, 2008-2013: a clinical description.

Bipolaris mould surgical site infections (SSIs) are exceedingly rare. We describe 21 cases of Bipolaris SSIs in pediatric and adult cardiothoracic surgery patients at ten hospitals in Texas, Arkansas, and Florida during 2008-2013. Median case-patient age was 55 years (range: 3 days-82 years), and 19 (90%) were male. Ten (48%) had coronary artery bypass or valve surgery, and seven (33%) had heart transplantation. Fifteen (71%) had more than one cardiothoracic procedure (median: 3, range: 1-11). Thirteen (62%) case-patients (all 5 pediatric patients, and 8 (50%) of 16 adult patients) had delayed sternal closure (chest closed >1 day [median = 8 days; range: 2-22] following the initial cardiothoracic procedure). Thirteen (62%) had mediastinitis. Median time from initial surgery to positive Bipolaris culture was 20 days (range: 6-497). Sixteen (76%) case-patients died.

Efficient Identification of HIV Serodiscordant Couples by Existing HIV Testing Programs in South Brazil.

OBJECTIVE: To examine the feasibility of identifying HIV negative at risk individuals in HIV serodiscordant couples, during voluntary HIV testing in South Brazil. METHODS: We surveyed HIV testers at 4 public testing sites in Rio Grande do Sul. We obtained information on risk behaviors and sexual partnerships. HIV testing and testing for recent infection were performed; HIV prevalence and risk behaviors were assessed among subjects who reported having a steady partner who was HIV positive (serodiscordant group) and compared with the general testing population. RESULTS: Among 3100 patients, 490 (15.8%) reported being in a steady relationship with an HIV positive partner. New HIV infections were diagnosed in 23% of the serodiscordant group (vs. 13% in the general population, p = 0.01); among newly positive subjects, recent HIV infections were more frequent (23/86, 26.7%) among testers with positive partners than among the general testing group (52/334; 15.6%; p = 0.016). Less than half of the serodiscordant testers reported having used a condom during the last sexual intercourse with their HIV-positive partner. Participants with inconsistent condom use with steady partner were four times more likely to test positive for HIV compared to those who reported always using condoms with the steady partner (OR: 4.2; 95% CI: 2.3 to 7.5). CONCLUSION: It is highly feasible to identify large numbers of HIV susceptible individuals who are in HIV serodiscordant relationships in South Brazil testing sites. Condom use within HIV serodiscordant couples is low in this setting, suggesting urgent need for biomedical prevention strategies to reduce HIV transmission.

Cryptococcal antigen screening and early antifungal treatment to prevent cryptococcal meningitis: a review of the literature.

BACKGROUND: Screening individuals with AIDS for serum cryptococcal antigen (CrAg), followed by treatment of CrAg positives with antifungals, may prevent cryptococcal meningitis. This review examined data on CrAg screening and treatment in resource-limited settings. METHODS: We searched articles published during 2007-2014 on the effectiveness and cost-effectiveness of CrAg screening and treatment on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. We rated overall quality of individual articles, summarized the body of evidence, the expected impact, and cost-effectiveness for each outcome. RESULTS: We identified 2613 articles. Eight met all inclusion criteria. Five studies addressed mortality and/or morbidity outcomes; all were observational and had small sample sizes; 3 lacked a comparison group. Ratings of study quality ranged from "medium" to "weak," and the quality of the overall body of evidence for mortality and morbidity outcomes was rated as "fair." The intervention's expected impact on mortality and morbidity was rated as "moderate." The 4 cost-effectiveness studies included in the analysis showed that CrAg screening and treatment interventions are highly cost-effective. No studies addressed retention in care, quality of life, or HIV transmission. CONCLUSIONS: Although limited, the body of evidence regarding CrAg screening and treatment suggests that the intervention may have an impact on preventing cryptococcal meningitis and death in persons with AIDS. Additional research is needed to quantify the intervention's effectiveness and identify optimal treatment dosing and implementation best practices.

Notes from the field: Fatal gastrointestinal mucormycosis in a premature infant associated with a contaminated dietary supplement--Connecticut, 2014.

In October 2014, a hospital in Connecticut notified CDC and the Connecticut Department of Public Health of a fatal case of gastrointestinal mucormycosis in a preterm infant. The infant, born at 29 weeks' gestation and weighing 1,400 grams (about 3 pounds), had developed signs and symptoms initially consistent with necrotizing enterocolitis approximately 1 week after birth. Exploratory laparotomy revealed complete ischemia of the gastrointestinal tract from the esophagus to the rectum; a portion of necrotic cecum was sent for microscopic examination. Following surgery, the infant developed multiple areas of vascular occlusion, including a large clot in the aorta, findings not usually associated with necrotizing enterocolitis. The infant died soon after. Histopathology results from the resected cecum revealed an angioinvasive fungal infection consistent with mucormycosis. Gastrointestinal mucormycosis is an extremely rare fungal infection caused by mold in the order Mucorales. It occurs predominantly in low birth weight infants, patients with diarrhea and malnutrition, and those receiving peritoneal dialysis; mortality is 85%. Local investigation revealed that the infant had received a dietary supplement, ABC Dophilus Powder, for 7 days, beginning on day 1 of life.

Atraumatic splenic rupture: an unusual manifestation of acute HIV infection.

A 27-year-old white male, who had sex with other men, presented to the emergency department with 3 days of left shoulder and abdominal pain. He reported no history of trauma to the abdomen. On abdominal imaging, he was found to have hemoperitoneum from a ruptured spleen; he underwent splenectomy. Causes of atraumatic splenic rupture can be divided into six main categories: infectious, neoplastic, inflammatory, congenital or structural, iatrogenic, and idiopathic. Work-up of the atraumatic splenic rupture revealed that his HIV antibody was newly positive. He had a documented negative HIV antibody 3 weeks prior to the current admission. CD4 cell count, obtained after splenectomy, was 904 cells per microliter and the HIV-1 plasma RNA level was 4657 copies per milliliter. Spleen pathology demonstrated an enlarged spleen with increase in the number of small to intermediate size lymphoid cells in the red pulp, and reactive follicular lymphoid hyperplasia, with numerous secondary lymphoid follicles and reactive germinal centers in the white pulp. T-cell receptor (TCR) gene rearrangement studies demonstrated a positive TCR beta gene rearrangement, without a TCR gamma gene rearrangement, consistent with a clonal CD8(+) T-cell population. The case gives rare insight into what happens in the spleen during acute HIV infection and encourages HIV testing in those presenting with atraumatic splenic rupture. Counseling patients with acute HIV to avoid potential trauma should also be considered.

Pandemic (H1N1) 2009 infection in patients with hematologic malignancy.

To assess outcomes of patients with hematologic malignancy and pandemic (H1N1) 2009 infection, we reviewed cases during June-December 2009 at the University of California San Francisco Medical Center. Seventeen (63%) and 10 (37%) patients had upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI), respectively. Cough (85%) and fever (70%) were the most common signs; 19% of patients had nausea, vomiting, or diarrhea. Sixty-five percent of URTI patients were outpatients; 35% recovered without antiviral therapy. All LRTI patients were hospitalized; half required intensive care unit admission. Complications included acute respiratory distress syndrome, pneumomediastinum, myocarditis, and development of oseltamivir-resistant virus; 3 patients died. Of the 3 patients with nosocomial pandemic (H1N1) 2009, 2 died. Pandemic (H1N1) 2009 may cause serious illness in patients with hematologic malignancy, primarily those with LRTI. Rigorous infection control, improved techniques for diagnosing respiratory disease, and early antiviral therapy can prevent nosocomial transmission and optimize patient care.