Medscape CME Activity

We investigated the clinical outcomes and molecular mechanisms of fluconazole-resistant (FR) Candida glabrata bloodstream infections. Among 1,158 isolates collected during multicenter studies in South Korea during 2008–2018, 5.7% were FR. For 64 patients with FR bloodstream infection isolates, the 30-day mortality rate was 60.9% and the 90-day mortality rate 78.2%; these rates were significantly higher than in patients with fluconazole-susceptible dose-dependent isolates (30-day mortality rate 36.4%, 90-day mortality rate 43.8%; p<0.05). For patients with FR isolates, appropriate antifungal therapy was the only independent protective factor associated with 30-day (hazard ratio 0.304) and 90-day (hazard ratio 0.310) mortality. Sequencing of pleiotropic drug-resistance transcription factor revealed that 1–2 additional Pdr1p amino acid substitutions (except genotype-specific Pdr1p amino acid substitutions) occurred in 98.5% of FR isolates but in only 0.9% of fluconazole-susceptible dose-dependent isolates. These results highlight the high mortality rate of patients infected with FR C. glabrata BSI isolates harboring Pdr1p mutations.

In Karachi, Pakistan, a South Asian megacity with a high prevalence of tuberculosis (TB) and low HIV prevalence, we assessed the effectiveness of fluoroquinolone-based preventive therapy for drug-resistant (DR) TB exposure. During February 2016–March 2017, high-risk household contacts of DR TB patients began a 6-month course of preventive therapy with a fluoroquinolone-based, 2-drug regimen. We assessed effectiveness in this cohort by comparing the rate and risk for TB disease over 2 years to the rates and risks reported in the literature. Of 172 participants, TB occurred in 2 persons over 336 person-years of observation. TB disease incidence rate observed in the cohort was 6.0/1,000 person-years. The incidence rate ratio ranged from 0.29 (95% CI 0.04–1.3) to 0.50 (95% CI 0.06–2.8), with a pooled estimate of 0.35 (95% CI 0.14–0.87). Overall, fluoroquinolone-based preventive therapy for DR TB exposure reduced risk for TB disease by 65%.

After Zika virus (ZIKV) infection in Costa Rica was confirmed in January 2016, the national surveillance system was enhanced to monitor associated birth defects. To characterize the ZIKV outbreak among live-born infants during March 2016–March 2018, we conducted a descriptive analysis. Prevalence of ZIKV-associated birth defects was 15.3 cases/100,000 live births. Among 22 infants with ZIKV-associated birth defects, 11 were designated as confirmed (positive for ZIKV) and 11 were designated as probable cases (negative for ZIKV or not tested, but mother was expsed to ZIKV during pregnancy). A total of 91% had microcephaly (head circumference >2 SDs below mean for age and sex), 64% severe microcephaly (head circumference >3 SDs below mean for age and sex), 95% neurodevelopmental abnormalities, 82% brain anomalies, 41% eye abnormalities, and 9% hearing loss. Monitoring children for >1 year can increase identification of ZIKV-associated abnormalities in addition to microcephaly.

We retrospectively analyzed epidemiologic, clinical, and biologic characteristics of 368 Plasmodium ovale wallikeri and 309 P. ovale curtisi infections treated in France during January 2013–December 2018. P. ovale wallikeri infections displayed deeper thrombocytopenia and shorter latency periods. Despite similar clinical manifestations, P. ovale wallikeri–infected patients were more frequently treated with artemisinin-based combination therapy. Although the difference was not statistically significant, P. ovale wallikeri–infected patients were 5 times more frequently hospitalized in intensive care or intermediate care and had a higher proportion of severe thrombocytopenia than P. ovale curtisi–infected patients. Rapid diagnostic tests that detect aldolase were more efficient than those detecting Plasmodium lactate dehydrogenase. Sequence analysis of the potra gene from 90 P. ovale isolates reveals an insufficient polymorphism for relapse typing.

Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000–2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000–2009 to 0.22 cases per 100,000 admissions in 2010–2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.

We describe trends in acute rheumatic fever (ARF), rheumatic heart disease (RHD), and RHD deaths among population groups in New Zealand. We analyzed initial primary ARF and RHD hospitalizations during 2000–2018 and RHD mortality rates during 2000–2016. We found elevated rates of initial ARF hospitalizations for persons of Māori (adjusted rate ratio [aRR] 11.8, 95% CI 10.0–14.0) and Pacific Islander (aRR 23.6, 95% CI 19.9–27.9) ethnicity compared with persons of European/other ethnicity. We also noted higher rates of initial RHD hospitalization for Māori (aRR 3.2, 95% CI 2.9–3.5) and Pacific Islander (aRR 4.6, 95% CI 4.2–5.1) groups and RHD deaths among these groups (Māori aRR 12.3, 95% CI 10.3–14.6, and Pacific Islanders aRR 11.2, 95% CI 9.1–13.8). Rates also were higher in socioeconomically disadvantaged neighborhoods. To curb high rates of ARF and RHD, New Zealand must address increasing social and ethnic inequalities.

HIV-infected children and adolescents are at increased risk for tuberculosis (TB). Antiretroviral therapy (ART) reduces TB risk in HIV-infected adults, but its effectiveness in HIV-infected children and adolescents is unknown. We analyzed data from 7 integrated pediatric HIV/TB centers in 6 countries in sub-Saharan Africa. We used a Bayesian mixed-effect model to assess association between ART and TB prevalence and used adaptive lasso regression to analyze risk factors for adverse TB outcomes. The study period encompassed 57,525 patient-years and 1,160 TB cases (2,017 cases/100,000 patient-years). Every 10% increase in ART uptake resulted in a 2.33% reduction in TB prevalence. Favorable TB outcomes were associated with increased time in care and early ART initiation, whereas severe immunosuppression was associated with death. These findings support integrated HIV/TB services for HIV-infected children and adults and demonstrate the association of ART uptake with decreased TB incidence in high HIV/TB settings.

In 2015, an outbreak of presumed waterborne toxoplasmosis occurred in Gouveia, Brazil. We conducted a 3-year prospective study on a cohort of 52 patients from this outbreak, collected clinical and multimodal imaging findings, and determined risk factors for ocular involvement. At baseline examination, 12 (23%) patients had retinochoroiditis; 4 patients had bilateral and 2 had macular lesions. Multimodal imaging revealed 2 distinct retinochoroiditis patterns: necrotizing focal retinochoroiditis and punctate retinochoroiditis. Older age, worse visual acuity, self-reported recent reduction of visual acuity, and presence of floaters were associated with retinochoroiditis. Among patients, persons >40 years of age had 5 times the risk for ocular involvement. Five patients had recurrences during follow-up, a rate of 22% per person-year. Recurrences were associated with binocular involvement. Two patients had late ocular involvement that occurred >34 months after initial diagnosis. Patients with acquired toxoplasmosis should have long-term ophthalmic follow-up, regardless of initial ocular involvement.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) can acquire phage-encoded immune modulators, such as the immune evasion cluster (IEC), which protects bacteria from components of the human innate immune system, and the enzyme TarP, which protects against antibody-mediated immune recognition. We used whole-genome sequencing and epidemiologic investigations to study the effects of IEC- and tarP-harboring phages on household transmission of LA-MRSA in North Denmark Region during 2004–2011. We reviewed information about all patients throughout Denmark who experienced LA-MRSA infection during 2007–2018 to determine whether IEC is associated with increased spread into the general population. Horizontal acquisition of IEC in the human host was associated with increased household transmission of LA-MRSA and spillover into the community and healthcare settings, whereas we found no evidence to suggest that IEC-positive LA-MRSA isolates have become self-sustainable in the general population. By contrast, TarP did not seem to influence household transmission of LA-MRSA.

Healthcare-associated Legionnaires’ disease (HCA LD) can cause nosocomial outbreaks with high death rates. We compared community-acquired LD cases with HCA LD cases in Europe during 2008−2017 using data from The European Surveillance System. A total of 29 countries reported 40,411 community-acquired and 4,315 HCA LD cases. Of the HCA LD cases, 2,937 (68.1%) were hospital-acquired and 1,378 (31.9%) were linked to other healthcare facilities. The odds of having HCA LD were higher for women, children and persons <20 years of age, and persons >60 years of age. Out of the cases caused by Legionella pneumophila with a known serotype, community-acquired LD was more likely to be caused by L. pneumophila serogroup 1 (92.3%) than was HCA LD (85.1%). HCA LD patients were more likely to die. HCA LD is associated with specific patient demographics, causative strains, and outcomes. Healthcare facilities should consider these characteristics when designing HCA LD prevention strategies.

Shiga toxin–producing Escherichia coli (STEC) cause substantial and costly illnesses. Leafy greens are the second most common source of foodborne STEC O157 outbreaks. We examined STEC outbreaks linked to leafy greens during 2009–2018 in the United States and Canada. We identified 40 outbreaks, 1,212 illnesses, 77 cases of hemolytic uremic syndrome, and 8 deaths. More outbreaks were linked to romaine lettuce (54%) than to any other type of leafy green. More outbreaks occurred in the fall (45%) and spring (28%) than in other seasons. Barriers in epidemiologic and traceback investigations complicated identification of the ultimate outbreak source. Research on the seasonality of leafy green outbreaks and vulnerability to STEC contamination and bacterial survival dynamics by leafy green type are warranted. Improvements in traceability of leafy greens are also needed. Federal and state health partners, researchers, the leafy green industry, and retailers can work together on interventions to reduce STEC contamination.

Q fever osteoarticular infection in children is an underestimated disease. We report 3 cases of Q fever osteomyelitis in children and review all cases reported in the literature through March 2018. A high index of suspicion is encouraged in cases of an unusual manifestation, prolonged course, relapsing symptoms, nonresolving or slowly resolving osteomyelitis, culture-negative osteomyelitis, or bone histopathology demonstrating granulomatous changes. Urban residence or lack of direct exposure to animals does not rule out infection. Diagnosis usually requires use of newer diagnostic modalities. Optimal antimicrobial therapy has not been well established; some case-patients may improve spontaneously or during treatment with a β-lactam. The etiology of treatment failure and relapse is not well understood, and tools for follow-up are lacking. Clinicians should be aware of these infections in children to guide optimal treatment, including choice of antimicrobial drugs, duration of therapy, and methods of monitoring response to treatment..

Nine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms. All isolates but 1 had low MICs for the 8 antifungal drugs tested. When treated, patients received mainly azole therapy. Two of 7 patients with a known outcome died. We performed multilocus sequence analysis of N. obscura clinical strains and several strains of Nannizziopsis spp. isolated from reptiles. The human strains were clearly differentiated from the animal strains. N. obscura might be endemic to West Africa and responsible for undetected infections, which might become reactivated when immunosuppression occurs. N. obscura infection is probably underestimated because only sequencing enables proper identification.

US guidelines have recommended testing children emigrating from high tuberculosis-incidence countries with interferon-gamma release assays (IGRAs) or tuberculin skin tests (TSTs). We describe the Harris County (Texas) Public Health Refugee Health Screening Program’s testing results during 2010–2015 for children <18 years of age: 5,990 were evaluated, and 5,870 (98%) were tested. Overall, 364 (6.2%) children had >1 positive test: 143/1,842 (7.8%) were tested with TST alone, 129/3,730 (3.5%) with IGRA alone, and 92/298 (30.9%) with both TST and IGRA. Region of origin and younger age were associated with positive TST or IGRA results. All children were more likely to have positive results for TST than for IGRA (OR 2.92, 95% CI 2.37–3.59). Discordant test results were common (20%) and most often were TST+/IGRA– (95.0%), likely because of bacillus Calmette-Guérin vaccination. Finding fewer false positives supports the 2018 change in US immigration guidelines that recommends using IGRAs for recently immigrated children.

We investigated sporadic Creutzfeldt-Jakob disease (sCJD) among physicians in Germany by analyzing occupational information of patients with sCJD recorded by the German CJD Surveillance Unit (1993–2005; 1,250 patients, of whom 4 [0.32%] were physicians) and the National Reference Center for Human Spongiform Encephalopathies (2006–2016; 1,491 patients, of whom 13 [0.87%] were physicians). Among the physicians, we did not identify any neurologists, neurosurgeons, psychiatrists, or pathologists. A cumulative sum test showed an increase in reported physicians over time. Data for 2017–2018 indicated an increased rate of physicians among all notified sCJD cases (5/239 [2.1%]) when we used the total population of Germany as control group. Our data suggest the possibility of an increased risk for sCJD among physicians in Germany. However, we can only speculate about the reasons, and larger multinational studies are needed to replicate the finding and to clarify whether this finding is a general or a country-specific phenomenon.

Orientia tsutsugamushi, spotted fever group rickettsioses, and typhus group rickettsioses (TGR) are reemerging causes of acute febrile illness (AFI) in Southeast Asia. To further delineate extent, we enrolled patients >4 weeks of age with nonmalarial AFI in Sabah, Malaysia, during 2013–2015. We confirmed rickettsioses (past or acute, IgG titer >160) in 126/354 (36%) patients. We confirmed acute rickettsioses (paired 4-fold IgG titer rise to >160) in 38/145 (26%) patients: 23 O. tsutsugamushi, 9 spotted fever group, 4 TGR, 1 O. tsutsugamushi/spotted fever group, and 1 O. tsutsugamushi/TGR. PCR results were positive in 11/319 (3%) patients. Confirmed rickettsioses were more common in male adults; agricultural/plantation work and recent forest exposure were risk factors. Dizziness and acute hearing loss but not eschars were reported more often with acute rickettsioses. Only 2 patients were treated with doxycycline. Acute rickettsioses are common (>26%), underrecognized, and untreated etiologies of AFI in East Malaysia; empirical doxycycline treatment should be considered.

Atypical manifestations that can be severe and difficult to diagnosis develop in 5%–20% of patients with cat-scratch disease. To clarify the epidemiology of atypical cat-scratch disease in the United States, we analyzed data from the 2005–2014 MarketScan national health insurance claims databases by using the International Classification of Diseases, 9th Revision, Clinical Modification, codes for cat-scratch disease and selected atypical manifestations: retinitis/neuroretinitis, conjunctivitis, neuritis, encephalitis, hepatosplenic disease, osteomyelitis, erythema nodosum, and endocarditis. Atypical cat-scratch disease accounted for 1.5% of all cases, resulting in an average annual incidence of 0.7 cases/100,000 population. Atypical cat-scratch disease was associated with increased risk for hospitalization (risk ratios 8.77, 95% CI 6.56–11.72) and occurred most often in female patients 10–14 years of age. Ocular (48.7%), hepatosplenic (24.6%), and neurologic (13.8%) manifestations were most common among patients. A more comprehensive understanding of atypical cat-scratch disease can improve patient diagnosis and potentially elucidate pathophysiology of the disease.

Debates on whether statin use reduces the effectiveness of influenza vaccines against critical illness and death among persons >65 years of age continue. We conducted a study of 9,427,392 persons >65 years of age who did and did not receive influenza vaccinations during 12 consecutive influenza seasons, 2000–01 through 2011–12. Using data from Taiwan’s National Health Insurance Research Database, we performed propensity score-matching to compare vaccinated persons with unvaccinated controls. After propensity score-matching, the vaccinated group had lower risks for in-hospital death from influenza and pneumonia and for hospitalization for pneumonia and influenza, circulatory conditions, and critical illnesses compared with the unvaccinated group. We stratified the 2 groups by statin use and analyzed data by interaction analysis and saw no statistically significant difference. We found that influenza vaccine effectively reduced risks for hospitalization and death in persons >65 years of age, regardless of statin use.

Data are limited on the incidence and management of streptococcal toxic shock syndrome (TSS) and nonstreptococcal TSS in children. We aimed to define the clinical patterns of TSS at Nationwide Children’s Hospital in Ohio as they relate to published criteria, diagnostic decisions, and treatment options. Through retrospective chart reviews, we identified 58 patients with TSS (27 streptococcal, 31 nonstreptococcal) during January 2010–September 2017. We observed clinical and laboratory findings that are not part of TSS criteria, such as pyuria in streptococcal TSS (50% of patients) and pulmonary involvement (85%) and coagulopathy (92%) in nonstreptococcal TSS patients. Recommended treatment with clindamycin and intravenous immunoglobulin was delayed in streptococcal TSS patients without rash (3.37 days vs. 0.87 days in patients with rash), leading to prolonged hospitalization and complications. Incorporation of additional TSS signs and symptoms would be helpful in TSS diagnosis and management.

Blastomycosis is a systemic disease caused by Blastomyces spp. fungi. To determine its epidemiology in blastomycosis-endemic Minnesota, USA, we evaluated all cases reported to public health officials during 1999–2018. We focused on time to diagnosis, exposure activities, and exposure location. A total of 671 cases and a median of 34 cases/year were reported. Median time to diagnosis was 31 days; 61% of patients were not tested for blastomycosis until they were hospitalized. The case-fatality rate was 10%, and patients who died were 5.3 times more likely to have a concurrent medical condition. Outdoor activities and soil exposure were reported by many patients, but no specific activity or exposure was common to most. Almost one third of patients were probably exposed in geographic areas other than their home county. Providers should consider alternative etiologies for patients with pneumonia not responding to antibacterial treatment, and public health officials should increase awareness in blastomycosis-endemic areas.

Invasive Cronobacter infections among infants are associated with severe neurologic disabilities and death. Early Cronobacter reports typically featured hospitalized and preterm infants and recognized contaminated powdered infant formula (PIF) as a transmission vehicle. To clarify recent epidemiology, we reviewed all cases of bloodstream infection or meningitis among infants that were reported to the Centers for Disease Control and Prevention and in the literature (1961–2018; n = 183). Most infants were neonates (100/150 [67%]); 38% (42/112) died, and 79% (81/102) had reported recent PIF consumption. In the final quarter of the study period (2004–2018), case counts were significantly higher (global average 8.7 cases/year); among US cases, significantly higher proportions occurred among full-term (56% [27/48]) and nonhospitalized (78% [42/54]) infants. PIF contamination, most commonly from opened containers, was identified in 30% (21/71) of investigations. Our findings reaffirm the need to promote safer alternatives for infant feeding, particularly among neonates.

Tickborne diseases are rare in Washington, USA, and the ecology of these pathogens is poorly understood. We integrated surveillance data from humans and ticks to better describe their epidemiology and ecology. During 2011–2016, a total of 202 tickborne disease cases were reported in Washington residents. Of these, 68 (34%) were autochthonous, including cases of Lyme disease, Rocky Mountain spotted fever, tickborne relapsing fever, and tularemia. During May 2011–December 2016, we collected 977 host-seeking ticks, including Ixodes pacificus, I. angustus, I. spinipalpis, I. auritulus, Dermacentor andersoni, and D. variabilis ticks. The prevalence of Borrelia burgdorferi sensu stricto in I. pacificus ticks was 4.0%; of B. burgdorferi sensu lato, 3.8%; of B. miyamotoi, 4.4%; and of Anaplasma phagocytophilum, 1.9%. We did not detect Rickettsia rickettsii in either Dermacentor species. Case-patient histories and detection of pathogens in field-collected ticks indicate that several tickborne pathogens are endemic to Washington.