Choanephora infundibulifera Rhinosinusitis in Man with Acute Lymphoblastic Leukemia, Tennessee, USA.

Choanephora infundibulifera is a member of the Mucorales order of fungi. The species is associated with plants as a saprophyte or parasite and may be responsible for spoilage or disease but is an uncommon cause of human infection. We describe C. infundibulifera rhinosinusitis in a young man with leukemia in Tennessee, USA.

Promoting penicillin allergy de-labeling for children attending a hematology clinic.

BACKGROUND: Up to 10% of children are reported to be allergic to penicillin, but many allergy labels are unverified and may require formal testing. Inaccurate drug allergy labels are associated with a range of adverse clinical outcomes. Patients with hematological disorders may experience frequent and severe infections; those who have been incorrectly labeled penicillin allergic may benefit from allergy de-labeling (ADL) efforts to facilitate access to beta-lactam antibiotics. We developed a multidisciplinary, pharmacist-driven process that enabled non-allergist trained providers to assess and de-label penicillin allergies in a pediatric hematology center. METHODS: Volunteers, including physicians, advanced practice providers, nurses, and pharmacists, were trained in skin testing and oral challenge procedures. Patients were identified by review of electronic medical records for penicillin or penicillin-derivative allergy. Patient and family interviews were conducted in cases where a true penicillin allergy was deemed uncertain based on chart review. If allergy could not be de-labeled by chart review or interview alone, patients were offered skin and/or oral challenge testing. RESULTS: Fifty-nine patients were initially labeled as penicillin allergic. Allergy labels of 11 (19%) were removed by chart review only, and 15 (25%) after conducting interviews. A total of two (3%) patients were ineligible due to contraindications, and five (9%) declined participation. Twenty-six patients (44%) underwent allergy testing (50% skin testing, 50% oral challenge) of which 23 (88%) were negative. CONCLUSIONS: ADL was possible in most patients previously identified as penicillin allergic. Testing was well tolerated with no serious adverse effects.

Simultaneous Presentation of B-Acute Lymphoblastic Leukemia and Streptococcus agalactiae Meningitis in a 3-Year-old Girl.

Infection is a major cause of treatment-related morbidity and mortality in pediatric acute lymphoblastic leukemia (ALL). Most children with ALL who develop life-threatening bacterial infections do so during induction therapy. We describe a rare case of ALL presenting simultaneously with Streptococcus agalactiae group B Streptococcus bacteremia and meningitis in a 3-year-old girl. She received appropriate antimicrobial therapy and a 2-drug early induction regimen consisting of vincristine and dexamethasone, leading to slow neurologic recovery and a favorable initial response to anti-neoplastic therapy as evidenced by minimal residual disease of 1.12% on day 15 of induction.

Healthcare-Associated Infections Caused by Mycolicibacterium neoaurum.

Mycolicibacterium neoaurum is a rapidly growing mycobacterium and an emerging cause of human infections. M. neoaurum infections are uncommon but likely underreported, and our understanding of the disease spectrum and optimum management is incomplete. We summarize demographic and clinical characteristics of a case of catheter-related M. neoaurum bacteremia in a child with leukemia and those of 36 previously reported episodes of M. neoaurum infection. Most infections occurred in young to middle-aged adults with serious underlying medical conditions and commonly involved medical devices. Overall, infections were not associated with severe illness or death. In contrast to other mycobacteria species, M. neoaurum was generally susceptible to multiple antimicrobial drugs and responded promptly to treatment, and infections were associated with good outcomes after relatively short therapy duration and device removal. Delays in identification and susceptibility testing were common. We recommend using combination antimicrobial drug therapy and removal of infected devices to eradicate infection.

Persistent Infections with Diverse Co-Circulating Astroviruses in Pediatric Oncology Patients, Memphis, Tennessee, USA.

Human astroviruses are a major cause of pediatric gastroenteritis, especially in immunocompromised children. We conducted a retrospective study to demonstrate that diverse astrovirus genotypes can co-circulate in pediatric oncology patients. A subset of cases is associated with long-term virus shedding (range 17-183 days).

The Effectiveness of Trivalent Inactivated Influenza Vaccine in Children with Acute Leukemia.

OBJECTIVE: The objective of this study was to determine the effectiveness of trivalent inactivated influenza vaccine (TIV) for the prevention of laboratory-confirmed influenza and influenza-like illnesses (ILI) among children and adolescents receiving therapy for acute leukemia. STUDY DESIGN: A retrospective review of the demographic and clinical characteristics of 498 patients at a pediatric cancer center who received therapy for acute leukemia during 3 successive influenza seasons (2010-2011 through 2012-2013). RESULTS: In 498 patient seasons with a known immunization history (median age, 6 years; range, 1-21), 354 patients (71.1%) were immunized with TIV and 98 (19.7%) received a booster dose of vaccine. Vaccinated and unvaccinated patients had generally similar demographic characteristics. There were no differences in the overall rates of influenza or ILI between vaccinated and unvaccinated patients overall, or in any individual season. There was no difference in the rates of influenza or ILI between patients who received 1 dose of vaccine and those who received 2 doses. Time to first influenza infection and time to first ILI in vaccinated and unvaccinated patients were not different. CONCLUSION: TIV did not protect children and adolescents with acute leukemia against laboratory-confirmed influenza or ILI. Future prospective studies should assess TIV effectiveness in high-risk subpopulations and alternative strategies to prevent influenza should be considered in this population.

Distinguishing Benign Mediastinal Masses from Malignancy in a Histoplasmosis-Endemic Region.

OBJECTIVE: To describe the characteristics of benign and malignant mediastinal masses, which may predict their etiology and facilitate the safe and timely management of patients, especially those residing in histoplasmosis-endemic regions. STUDY DESIGN: We conducted a retrospective review of the health records of 131 patients aged <19 years who were referred to 2 tertiary care children's hospitals between 2005 and 2010 for evaluation of mediastinal masses. RESULTS: Most patients (79%) had benign masses, including 98 with confirmed or suspected histoplasmosis. Overall, compared with patients with malignant masses, patients with benign masses were younger and more likely to be African American, to complain of cough, and to have pulmonary nodules by chest computed tomography. In addition, patients with malignant disease were more likely to complain of malaise and to have neck swelling, abnormal extrathoracic lymphadenopathy, lymphopenia, anterior mediastinal involvement, and/or pleural effusion. Positive histoplasmosis serologic tests were specific but insensitive for a benign etiology. No single clinical, laboratory, or radiologic feature was sufficiently sensitive and specific for distinguishing between benign and malignant masses; however, the presence of lymphopenia, anterior mediastinal involvement, or enlarged cervical lymph nodes on computed tomography had a sensitivity of 93%, specificity of 95%, positive predictive value of 86%, and negative predictive value of 97% for cancer. Sixty-four patients (49%) underwent invasive testing, including 37 (36%) of those with benign masses. CONCLUSION: Patients in this series who had involvement of the anterior mediastinum, lymphopenia, or enlarged cervical lymph nodes had a high likelihood of cancer. Expectant management of patients lacking these characteristics may be safe and reduce unnecessary invasive testing.

The Impact of Vaccine Concerns on Racial/Ethnic Disparities in Influenza Vaccine Uptake Among Health Care Workers.

OBJECTIVES: We explored whether collective concerns about the safety, effectiveness, and necessity of influenza vaccines mediate racial/ethnic disparities in vaccine uptake among health care workers (HCWs). METHODS: We used a self-administered Web-based survey to assess race/ethnicity (exposure), concerns about influenza vaccination (mediator; categorized through latent class analysis), and influenza vaccine uptake (outcome) for the 2012 to 2013 influenza season among HCWs at St. Jude Children's Research Hospital in Memphis, Tennessee. We used mediation analysis to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the total, direct, and indirect effects of race/ethnicity on influenza vaccine uptake. RESULTS: Non-Hispanic Blacks had lower influenza vaccine uptake than non-Hispanic Whites (total effect: PR = 0.87; 95% CI = 0.75, 0.99), largely mediated by high concern about influenza vaccines (natural indirect effect: PR = 0.89; 95% CI = 0.84, 0.94; controlled direct effect: PR = 0.98; 95% CI = 0.85, 1.1). Hispanic and Asian HCWs had modestly lower uptake than non-Hispanic Whites, also mediated by high concern about influenza vaccines. CONCLUSIONS: Racial/ethnic disparities among HCWs could be attenuated if concerns about the safety, effectiveness, and necessity of influenza vaccines were reduced.

Distinguishing Osteomyelitis From Ewing Sarcoma on Radiography and MRI.

OBJECTIVE: The purpose of this study was to determine whether clinical and imaging features can distinguish osteomyelitis from Ewing sarcoma (EWS) and to assess the accuracy of percutaneous biopsy versus open biopsy in the diagnosis of these diseases. MATERIALS AND METHODS: Three radiologists reviewed the radiographs and MRI examinations of 32 subjects with osteomyelitis and 31 subjects with EWS to determine the presence of 36 imaging parameters. Information on demographic characteristics, history, physical examination findings, laboratory findings, biopsy type, and biopsy results were recorded. Individual imaging and clinical parameters and combinations of these parameters were tested for correlation with findings from histologic analysis. The diagnostic accuracy of biopsy was also determined. RESULTS: On radiography, the presence of joint or metaphyseal involvement, a wide transition zone, a Codman triangle, a periosteal reaction, or a soft-tissue mass, when tested individually, was more likely to be noted in subjects with EWS (p ≤ 0.05) than in subjects with osteomyelitis. On MRI, permeative cortical involvement and soft-tissue mass were more likely in subjects with EWS (p ≤ 0.02), whereas a serpiginous tract was more likely to be seen in subjects with osteomyelitis (p = 0.04). African Americans were more likely to have osteomyelitis than EWS (p = 0). According to the results of multiple regression analysis, only ethnicity and soft-tissue mass remained statistically significant (p ≤ 0.01). The findings from 100% of open biopsies (18/18) and 58% of percutaneous biopsies (7/12) resulted in the diagnosis of osteomyelitis, whereas the findings from 88% of open biopsies (22/25) and 50% of percutaneous biopsies (3/6) resulted in a diagnosis of EWS. CONCLUSION: Several imaging features are significantly associated with either EWS or osteomyelitis, but many features are associated with both diseases. Other than ethnicity, no clinical feature improved diagnostic accuracy. Compared with percutaneous biopsy, open biopsy provides a higher diagnostic yield but may be inconclusive, especially for cases of EWS. Our findings underscore the need for better methods of diagnosing these disease processes.

Mucormycosis in children with cancer and hematopoietic cell transplant-A single center cohort study.

Although mucormycosis is an important cause of morbidity and mortality in children with cancer, our understanding of the typical characteristics of these infections is incomplete. We reviewed all cases of mucormycosis diagnosed at a single pediatric cancer center over 5 decades to identify the clinical features of mucormycosis in pediatric oncology patients and to identify risk factors for mortality. There were 44 cases of mucormycosis diagnosed between 1970-2019. Most patients (89%) had hematological malignancies and a history of prolonged and severe neutropenia (91%). In this series, hyperglycemia and exposure to corticosteroids were common. Pulmonary (36%) and disseminated infections (32%) were most common; rhino-orbital-cerebral infections were relatively infrequent (11%). Rhizopus spp. was the most common etiological agent (40%) followed by Mucor spp. (31%), and Cunninghamella spp. (19%). Overall mortality was 44% and 51% and attributable mortality was 39% and 41% at the end of antifungal therapy and end of follow up, respectively. Attributable mortality fell to 18% in 2010-2019, from 58-60% in previous decades; adjunctive surgery was associated with decreased mortality. Mortality remains unacceptably high despite aggressive antifungal therapy and adjunctive surgery, suggesting novel therapeutic strategies are needed.

The safety of cefepime and ceftazidime in pediatric oncology patients.

BACKGROUND: Concern has been raised about possible increased mortality associated with the use of cefepime. There are limited data available on the pragmatic use of beta-lactam antibiotics, especially in children. PROCEDURE: This retrospective study included 532 pediatric oncology patients. The outcomes of patients treated with cefepime for suspected serious bacterial infections were compared to those of patients treated with ceftazidime. Primary outcomes included 30- and 90-day all-cause mortality. RESULTS: The demographic and clinical characteristics of 337 patients treated with ceftazidime were similar to those of 195 patients receiving cefepime. Thirty-day and 90-day all cause mortality rates were comparable (30-day OR for cefepime: 3.48, 95% CI 0.31-38.84, P = 0.3; 90-day OR: 0.99, 95% CI 0.29-3.42, P = 1.0). There were also no differences in infection-related mortality rates, secondary infections, or adverse drug events. Deaths occurring within 30 days of hospitalization were judged to be attributable to infection, but not the result of treatment failure or adverse drug events. Deaths occurring between 30 and 90 days were associated with progressive or new malignancy. Secondary infection was significantly associated with mortality. CONCLUSIONS: The use of cefepime in pediatric oncology patients is not associated with increased mortality when compared to ceftazidime, however the small number of deaths in this study limits the strength of this conclusion. Previous associations between antimicrobial therapy and increased all-cause mortality may have been confounded by patients' demographic characteristics and co-morbid conditions. All-cause mortality may be an insensitive outcome for studies examining the efficacy and safety of these agents.

Pediatric Infectious Diseases Milestones: A Step in the Right Direction to Evaluate Subspecialty Learners.

We share the work of the ACGME Pediatric Infectious Diseases Working Group in creating the Pediatric Infectious Diseases-Specific Milestones and discuss key considerations that lead to the reformation of competencies to better assess learners in Pediatric Infectious Diseases.

Safety and immunogenicity of live attenuated and inactivated influenza vaccines in children with cancer.

BACKGROUND: The safety and immunogenicity of live, attenuated influenza vaccine (LAIV) has not been compared to that of the standard trivalent inactivated vaccine (TIV) in children with cancer. METHODS: Randomized study of LAIV versus TIV in children with cancer, age 2-21 years, vaccinated according to recommendations based on age and prior vaccination. Data on reactogenicity and other adverse events and blood and nasal swab samples were obtained following vaccination. RESULTS: Fifty-five eligible subjects (mean age, 10.4 years) received vaccine (28 LAIV/27 TIV). Both vaccines were well tolerated. Rhinorrhea reported within 10 days of vaccination was similar in both groups (36% LAIV vs 33% TIV, P > .999). Ten LAIV recipients shed virus; the latest viral shedding was detected 7 days after vaccination. Immunogenicity data were available for 52 subjects, or 26 in each group. TIV induced significantly higher postvaccination geometric mean titers against influenza A viruses (P < .001), greater seroprotection against influenza A/H1N1 (P = .01), and greater seroconversion against A/H3N2 (P = .004), compared with LAIV. No differences after vaccination were observed against influenza B viruses. CONCLUSIONS: As expected, serum antibody response against influenza A strains were greater with TIV than with LAIV in children with cancer. Both vaccines were well tolerated, and prolonged viral shedding after LAIV was not detected. CLINICAL TRIALS REGISTRATION: NCT00906750.

Priming the immune system for heart disease: a perspective on group A streptococci.

Although immune responses against group A streptococci and the heart have been correlated with antibodies and T cell responses against cardiac myosin, there is no unifying hypothesis about carditis caused globally by many different serotypes. Our study identified disease-specific epitopes of human cardiac myosin in the development of rheumatic carditis in humans. We found that immune responses to cardiac myosin were similar in rheumatic carditis among a small sample of worldwide populations, in which immunoglobulin G targeted human cardiac myosin epitopes in the S2 subfragment hinge region within S2 peptides containing amino acid residues 842-992 and 1164-1272. An analysis of rheumatic carditis in a Pacific Islander family confirmed the presence of potential rheumatogenic epitopes in the S2 region of human cardiac myosin. Our report suggests that cardiac myosin epitopes in rheumatic carditis target the S2 region of cardiac myosin and are similar among populations with rheumatic carditis worldwide, regardless of the infecting group A streptococcal M serotype.

Development, Implementation, and Outcomes of a Global Infectious Disease Training Course.

BACKGROUND: Skilled healthcare professionals are critical for providing quality healthcare for children with cancer globally. Training curricula addressing the knowledge needs in infection care and prevention (ICP) in cancer are scarce. PROGRAM DESCRIPTION: We implemented a 10-week blended course in ICP. The distance learning had four 2-week modules: Infectious Complications, Quality in Infection Care, Quality in Infection Prevention, and Sustainability, Research, and Dissemination. Each module had pre- and post-tests and weekly webinars. The 2-week in-person learning had lectures, group exercises, clinical observations, hospital and laboratory tours, and ended in an annual conference. An individual project developed during the distance learning was presented in the in-person workshop. Course attendance criteria were English language proficiency and participants' role in ICP at their institutions. PROGRAM EVALUATION AND RESULTS: Twenty-two students from 17 hospitals in 10 countries completed the course, developed a project, and answered surveys covering knowledge assessments and satisfaction, and 6-month course and 1-year project follow-ups. Pretest and post-test scores revealed knowledge improvement (P < .001). Participants rated the distance learning as outstanding (63%) or good (28%); and the in-person as outstanding (87%). In the follow-up survey, graduates felt more comfortable at managing infections and participated more in quality improvement and academics at their institutions. Seventeen participants (77%) took steps to implement their study projects, and 9 were successful. Collaboration and networking of trainees were notable outcomes. DISCUSSION: The ICP course is a resource to improve knowledge, engage graduates in network collaborations, and a reliable model to develop other thematic healthcare global training programs.

Efficacy and safety of cefepime in pediatric patients: a systematic review and meta-analysis.

OBJECTIVES: We systematically reviewed clinical trials on the safety and efficacy of cefepime in pediatric patients in view of recent reports, which suggested that cefepime is associated with increased 30-day all-cause mortality rates. STUDY DESIGN: We searched the Cochrane Central Registry of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and other published and unpublished sources. Randomized clinical trials of cefepime in patients<19 years of age were selected. RESULTS: Sixteen clinical trials were included. All-cause mortality rates did not differ between cefepime and comparator groups (risk difference, 0.00; 95% CI, -0.01-0.02). The risks of overall clinical failure (relative risk, 0.93; 95% CI, 0.82-1.04; P>.05) and failure in microbiologically confirmed infections (relative risk, 0.91; 95% CI, 0.68-1.22; P>.05) were not greater in subjects treated with cefepime. Rates of adverse events were similar in each group in all trials except 1. All studies had significant methodological flaws. CONCLUSIONS: Comparisons of the safety and efficacy of cefepime relative with other antimicrobial agents in pediatric patients are limited by small numbers of trials and enrolled subjects and poor study methodology. This review, however, suggests that cefepime therapy in pediatric patients is not associated with an increased risk of adverse outcomes.

L-Ficolin/mannose-binding lectin-associated serine protease complexes bind to group B streptococci primarily through N-acetylneuraminic acid of capsular polysaccharide and activate the complement pathway.

Group B streptococci (GBS) are the most common cause of neonatal sepsis and meningitis. Most infants who are colonized with GBS at birth do not develop invasive disease, although many of these uninfected infants lack protective levels of capsular polysaccharide (CPS)-specific antibody. The lectin pathway of complement is a potential mechanism for initiating opsonization of GBS with CPS-specific antibody-deficient serum. In this study, we determined whether mannose-binding lectin (MBL)/MBL-associated serine protease (MASP) complexes and L-ficolin/MASP complexes bind to different strains of GBS to activate the lectin pathway, and we identified the molecules recognized by lectins on the GBS surface. We found that MBL did not bind to any GBS examined, whereas L-ficolin bound to GBS cells of many serotypes. L-ficolin binding to GBS cells correlated with the CPS content in serotypes Ib, III (restriction digestion pattern types III-2 and III-3), and V but not with the group B-specific polysaccharide (GBPS) content or with the lipoteichoic acid (LTA) content. L-ficolin bound to purified CPS and GBPS in a concentration-dependent manner but not to purified LTA. All strains to which L-ficolin/MASP complexes bound consumed C4. When N-acetylneuraminic acid (NeuNAc) was selectively removed from GBS cells by treatment with neuraminidase, the reduction in L-ficolin binding was correlated with the amount of NeuNAc removed. Additionally, L-ficolin was able to bind to wild-type strains but was able to bind only weakly to unencapsulated mutants and a mutant strain in which the CPS lacks NeuNAc. We concluded that L-ficolin/MASP complexes bind to GBS primarily through an interaction with NeuNAc of CPS.

Tularemia with vesicular skin lesions may be mistaken for infection with herpes viruses.

The original reports of human infection with Francisella tularensis noted vesicular skin rash as a manifestation. We present 2 cases of tularemia initially diagnosed as herpes simplex or varicella zoster infection. Clinicians must recognize the cutaneous manifestations of tularemia and be able to distinguish these from lesions seen with herpes viruses.

Identification of clinical coryneform bacterial isolates: comparison of biochemical methods and sequence analysis of 16S rRNA and rpoB genes.

We compared the relative levels of effectiveness of three commercial identification kits and three nucleic acid amplification tests for the identification of coryneform bacteria by testing 50 diverse isolates, including 12 well-characterized control strains and 38 organisms obtained from pediatric oncology patients at our institution. Between 33.3 and 75.0% of control strains were correctly identified to the species level by phenotypic systems or nucleic acid amplification assays. The most sensitive tests were the API Coryne system and amplification and sequencing of the 16S rRNA gene using primers optimized for coryneform bacteria, which correctly identified 9 of 12 control isolates to the species level, and all strains with a high-confidence call were correctly identified. Organisms not correctly identified were species not included in the test kit databases or not producing a pattern of reactions included in kit databases or which could not be differentiated among several genospecies based on reaction patterns. Nucleic acid amplification assays had limited abilities to identify some bacteria to the species level, and comparison of sequence homologies was complicated by the inclusion of allele sequences obtained from uncultivated and uncharacterized strains in databases. The utility of rpoB genotyping was limited by the small number of representative gene sequences that are currently available for comparison. The correlation between identifications produced by different classification systems was poor, particularly for clinical isolates.

Infections caused by coryneform bacteria in pediatric oncology patients.

BACKGROUND: Invasive infections caused by coryneform bacteria are uncommon but have been reported with increasing frequency in recent decades, especially in immunocompromised persons. Because pediatric experience is limited, we examined the epidemiology and clinical characteristics of these infections in children undergoing cancer therapy. METHODS: Using strict case definitions, 17 coryneform bacterial infections were identified in 16 children during a 13-year period; there were 12 episodes of bacteremia and 5 skin or soft tissue infections. RESULTS: The median age of children with bloodstream infections was 11.2 years, and that of children with skin or soft tissue infections was 3.5 years. Most were receiving cancer therapy at the time of their infections, were outpatients at the onset of their infections, had central venous catheters, and were not neutropenic. No patient died as a result of infection and most had relatively mild signs and symptoms. All patients responded promptly to antimicrobial therapy and, although 3 infections relapsed, there was only 1 serious complication. The most common species isolated were Corynebacterium striatum, C. amycolatum, and Microbacterium species. CONCLUSIONS: The epidemiologic and clinical features of coryneform bacterial infections in immunocompromised children differ in several important respects from the previously reported characteristics of these infections in adults.