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.

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.

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.

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.

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.

A quality improvement initiative to increase Tdap (tetanus, diphtheria, acellular pertussis) vaccination coverage among direct health care providers at a children's hospital.

OBJECTIVES: Health care providers (HCP) are at high risk of acquiring and transmitting pertussis to susceptible family members, co-workers, and patients. Public health authorities recommend administering a single dose of Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccine to all adults, including HCP, to increase adult immunity to pertussis. We set a quality improvement goal to increase Tdap vaccination coverage among HCP who provided direct patient care at a children's hospital from 58% to 90% over 18 months. DESIGN: A multidisciplinary working group comprised of Occupational Health Program (OHP) staff and representatives of various medical services drew from a variety of qualitative methods and previous studies of vaccination programs in the healthcare system to understand barriers to Tdap vaccination within the institution and to develop interventions to increase vaccination rates. INTERVENTIONS: Interventions included changes to OHP processes, a general education campaign, improved access to vaccine, and personal engagement of HCP by task force members. RESULTS: Overall vaccination rates increased to 90% over 15 months, a rate that has been sustained by systematically assessing new employees' vaccination status and vaccinating those without documentation of previous Tdap vaccination. CONCLUSIONS: Tdap vaccination coverage in our institution was significantly increased by an intensive, multipronged educational campaign, and by improving processes of screening and vaccination of HCP. The use of direct engagement of vaccine hesitant populations to increase vaccination rates warrants further study.

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.

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).

Epidemiology of Diarrheal Illness in Pediatric Oncology Patients.

BACKGROUND: Diarrhea is common in children with cancer, but this has not been systematically studied to date. METHODS: Remnant stool samples collected between January 2010 and June 2011 from pediatric oncology patients with diarrhea were tested for bacterial, viral, and parasitic enteropathogens using a combination of standard-of-care (SOC) diagnostic tests, including broad-range, real-time polymerase chain reaction (PCR) assays for adenoviruses, astroviruses, and sapoviruses and 2 commercially available multiplexed PCR assays. Corresponding demographic and clinical data were abstracted from patients' medical records. RESULTS: One hundred fourteen episodes of diarrhea in 93 patients (median age, 3.7 years; range, 0.2-18.8) were included in the study. No patients died, but morbidity was significant. A total of 158 potential pathogens were detected in 114 diarrhea episodes, with >1 organism in one third of these; the most common were Clostridium difficile, noroviruses, adenoviruses, and astroviruses. Clostridium difficile, in combination with norovirus or adenovirus, was most common when >1 pathogen was detected. When both studies were obtained, SOC and broadly multiplexed PCR tests were concordant in 64 episodes (56%). Forty-five pathogens (28%) were identified retrospectively by broadly multiplexed PCR assays only. A total of 19 (13%) were detected by SOC real-time PCR assays but not by either commercially available multiplexed PCR assay. CONCLUSIONS: Most pediatric oncology patients in this study had 1 or more potential infectious causes for their diarrhea. Additional studies are warranted to understand the natural history of gastroenteritis in this patient population. Although broadly multiplexed PCR assays offer some advantages over conventional testing, there may be disadvantages to their use for the diagnosis of infectious gastroenteritis that are unique to pediatric oncology patients.

Comparative Evaluation of Broad-Panel PCR Assays for the Detection of Gastrointestinal Pathogens in Pediatric Oncology Patients.

Broadly multiplexed molecular amplification assays offer an unprecedented ability to diagnose gastrointestinal infection in immunocompromised patients. However, little data are available to compare the performance of such systems in this population. A total of 436 stool samples were collected from 199 predominantly immunocompromised pediatric oncology patients. Remnant samples were tested in parallel with the use of the premarket (investigational use only) versions of two broadly multiplexed PCR assays (BioFire and Luminex), and the results of samples corresponding to the first episode per patient were compared with those from laboratory-developed molecular assays, culture, and antigen detection. Overall performance of the multiplexed systems was comparable, with BioFire and Luminex detecting 94 and 99 positives (P = 0.34), respectively. Stratifying by analyte, BioFire assay detected 51 samples positive for Clostridium difficile, whereas Luminex assay detected 60 (P = 0.01). Biofire and Luminex detected 28 and 38 norovirus-positive samples (P = 0.002), respectively. Astrovirus- and adenovirus-positive samples were detected in higher numbers by in-house PCR than by BioFire; the same was observed for adenovirus with Luminex. Differences observed with other analytes were minimal, did not reach statistical significance, or lacked the numbers needed to detect a difference between systems. Broadly multiplexed PCR offers an effective means of detecting a variety of gastrointestinal pathogens in pediatric oncology patients, with assay performance comparable among the tests examined.

Infections Caused by Rapidly Growing Mycobacteria spp in Children and Adolescents With Cancer.

BACKGROUND: Rapidly growing mycobacteria (RGM) infections in pediatric oncology patients have not been completely characterized. METHODS: We reviewed medical records of oncology patients at St. Jude Children's Research Hospital (St. Jude) from 1990 to 2010 with RGM infections and summarized the results of previously published cases. RESULTS: Twenty-five St. Jude patients had 27 episodes of infection. Approximately half of the cases occurred in patients with hematological malignancies and in males; infections were more common in white patients. Most patients were not neutropenic or lymphopenic. The most common causative species were Mycobacterium chelonae, Mycobacterium abscessus, and Mycobacterium fortuitum. Most isolates were susceptible to amikacin and clarithromycin; all were susceptible to at least 1 of these. Treatment regimens varied considerably, particularly with respect to the duration of antimicrobial chemotherapy. Two St. Jude patients died; both had pulmonary infections. The literature search identified an additional 58 cases of infection. Localized catheter-associated infections were more common than bloodstream infections in the current series than in previous reports, and outbreaks were not recognized. Otherwise, the demographic and clinical characteristics of patients were similar. CONCLUSIONS: Localized catheter-associated infections were most common in this largest reported single center experience reported to date. Pulmonary infection is uncommon in children but, as in adults, has a high mortality rate. Relatively short-term antimicrobial treatment and surgical debridement of infected tissue, if present, may be as effective for catheter-associated infections as prolonged antimicrobial use and may reduce adverse drug effects in these patients, who are vulnerable to drug-drug interactions and toxicity.

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.

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 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.

Safety and immunogenicity of an intranasal Sendai virus-based human parainfluenza virus type 1 vaccine in 3- to 6-year-old children.

Human parainfluenza virus type 1 (hPIV-1) is the most common cause of laryngotracheobronchitis (croup), resulting in tens of thousands of hospitalizations each year in the United States alone. No licensed vaccine is yet available. We have developed murine PIV-1 (Sendai virus [SeV]) as a live Jennerian vaccine for hPIV-1. Here, we describe vaccine testing in healthy 3- to 6-year-old hPIV-1-seropositive children in a dose escalation study. One dose of the vaccine (5 × 10(5), 5 × 10(6), or 5 × 10(7) 50% egg infectious doses) was delivered by the intranasal route to each study participant. The vaccine was well tolerated by all the study participants. There was no sign of vaccine virus replication in the airway in any participant. Most children exhibited an increase in antibody binding and neutralizing responses toward hPIV-1 within 4 weeks from the time of vaccination. In several children, antibody responses remained above incoming levels for at least 6 months after vaccination. Data suggest that SeV may provide a benefit to 3- to 6-year-old children, even when vaccine recipients have preexisting cross-reactive antibodies due to previous exposures to hPIV-1. Results encourage the testing of SeV administration in young seronegative children to protect against the serious respiratory tract diseases caused by hPIV-1 infections.

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.

Clinical and demographic characteristics of seasonal influenza in pediatric patients with cancer.

BACKGROUND: Changes in oncology care and the diagnosis and management of influenza over the past several decades may have altered the epidemiology and outcomes of influenza in pediatric oncology patients. METHODS: The clinical features and outcomes of 102 pediatric patients undergoing cancer therapy during 107 episodes of influenza between January 2002 and April 2009 were retrospectively ascertained. RESULTS: Median age at the time of influenza was 7.2 years (interquartile range: 3.8-11.2 years); 46% of patients were male. Nineteen patients (18%) were recipients of hematopoietic stem cell transplants. Patients' median absolute neutrophil and lymphocyte counts were 1300/µL (interquartile range: 500-2967/µL) and 360/µL (interquartile range: 180-836/µL), respectively. Twelve patients (11%) had coinfections with influenza and one or more other respiratory pathogens. Influenza prompted patients' hospitalization during 64% of episodes, and 75% received antiviral therapy. Complications occurred in 30% of infections and serious complications occurred in 7%. Three patients died, but no deaths were directly attributable to influenza. Most patients had delays in cancer therapy; the median delay was 5 days. Neutropenia, concurrent infection, increasing age and having received hematopoietic stem cell transplant increased the risk of serious complications. CONCLUSIONS: Advances in the management of pediatric cancer and influenza have not altered the epidemiology and outcome of influenza in oncology patients. Clinical features identify subgroups of patients with influenza who are at risk of poor outcomes and those with a good prognosis.

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.

Phylogenetic lineage and pilus protein Spb1/SAN1518 affect opsonin-independent phagocytosis and intracellular survival of Group B Streptococcus.

Opsonin-independent phagocytosis of Group B Streptococcus (GBS) is important in defense against neonatal GBS infections. A recent study indicated a role for GBS pilus in macrophage phagocytosis (Maisey et al Faseb J 22 2008 1715-24). We studied 163 isolates from different phylogenetic backgrounds and those possessing or lacking the gene encoding the pilus backbone protein, Spb1 (SAN1518, PI-2b) and spb1-deficient mutants of wild-type (WT) serotype III-3 GBS 874391 in non-opsonic phagocytosis assays using J774A.1 macrophages. Numbers of GBS phagocytosed differed up to 23-fold depending on phylogenetic background; isolates possessing spb1 were phagocytosed more than isolates lacking spb1. Comparing WT GBS and isogenic spb1-deficient mutants showed WT was phagocytosed better compared to mutants; Spb1 also enhanced intracellular survival as mutants were killed more efficiently. Complementation of mutants restored phagocytosis and resistance to killing in J774A.1 macrophages. Spb1 antiserum revealed surface expression in WT GBS and spatial distribution relative to capsular polysaccharide. spb1 did not affect macrophage nitric oxide and TNF-alpha responses; differences in phagocytosis did not correlate with N-acetyl d-glucosamine (from GBS cell-wall) according to enzyme-linked lectin-sorbent assay. Together, these findings support a role for phylogenetic lineage and Spb1 in opsonin-independent phagocytosis and intracellular survival of GBS in J774A.1 macrophages.

Oseltamivir-resistant influenza A and B viruses pre- and postantiviral therapy in children and young adults with cancer.

BACKGROUND: Immunocompromised patients are highly susceptible to influenza infection and can have prolonged viral shedding, which is a risk factor for the development of antiviral resistance. METHODS: We investigated the emergence of oseltamivir-resistant influenza variants in children and young adults with cancer during the 2002-2008 influenza seasons. The demographic and clinical features of influenza infections in 12 patients who had viral isolates obtained before and after oseltamivir therapy was initiated were studied. Antiviral susceptibilities were determined by the fluorescence-based neuraminidase (NA) enzyme inhibition assay and by sequencing genes encoding NA and matrix M2 proteins. RESULTS: The mean age of patients was 10.5 (range, 1.1-23.0) years. Ten patients had hematologic malignancies, 4 were recipients of hematopoietic stem cell transplants, and all patients were receiving immunosuppressive therapy. Eleven patients had prolonged respiratory symptoms and 8 had prolonged viral shedding. Serial viral isolates were available for 8 of 12 patients. Oseltamivir-resistant influenza viruses were isolated from 4 children (3 influenza A [H3N2] and 1 influenza B virus): before the initiation of antiviral therapy in 2 patients and during therapy in the other 2 patients. Three resistant influenza A (H3N2) viruses shared a common E119V NA mutation. One patient was infected with oseltamivir-resistant influenza B virus (IC50, 731.86 ± 155.12 nM) that harbored a N294S NA mutation, the first report of this mutation in influenza B viruses. CONCLUSIONS: Oseltamivir-resistant influenza viruses can exist before or rapidly emerge during antiviral therapy in immunocompromised individuals, and this has important implications for therapy and infection control.