Immunological effects and safety of live rotavirus vaccination after antenatal exposure to immunomodulatory biologic agents: a prospective cohort study from the Canadian Immunization Research Network.

BACKGROUND: People with inflammatory or autoimmune diseases are recommended to continue immunomodulatory biologic agents throughout pregnancy. However, concerns regarding potential immunosuppression in infants exposed to biologic agents have led to recommendations to avoid live vaccines in the first 6-12 months of life. We aimed to examine whether live rotavirus vaccine could be administered safely to infants exposed to biologic agents, assessed in the Canadian Special Immunization Clinic (SIC) Network. METHODS: In this prospective cohort study, infants exposed to biologic agents in utero were referred to one of six SIC sites in Canada for rotavirus vaccination recommendations. Children with other contraindications to rotavirus vaccination or older than 15 weeks were excluded. Clinical and laboratory evaluations were conducted according to a standard clinical pathway. Data were collected for relevant medical history, pregnancy outcomes, biologic agent exposure history, physical examination, laboratory results of the child, SIC recommendations for rotavirus vaccination, rotavirus vaccine series completion, and adverse events after immunisation. After parental consent, deidentified data were transferred to a central database for analysis. Children recommended for rotavirus vaccination were followed up for 8 months after series initiation to ascertain severe and serious adverse events, including severe diarrhoea, vomiting, and intussusception. FINDINGS: Between May 1, 2017, and Dec 31, 2021, 202 infants were assessed and 191 eligible infants were enrolled (97 [51%] were female and 94 [49%] were male). When including those exposed to multiple agents, the most common biologic agents to which infants were exposed were infliximab (67 [35%] of 191), adalimumab (49 [26%]), ustekinumab (18 [9%]), and vedolizumab (17 [9%]). Biologic agent exposure continued into the third trimester for 178 (93%) infants. No clinically significant abnormalities in lymphocyte subsets, quantitative immunoglobulins, or mitogen responses were detected. After SIC assessment, rotavirus vaccination was recommended for 187 (98%) of 191 infants, all of whom were followed up. By end of follow-up on Aug 19, 2022, 168 (90%) infants had initiated rotavirus vaccination; 150 (80%) completed the series. No serious adverse events after immunisation were reported, but three (2%) infants required medical attention, one for vomiting and change in stools who was subsequently diagnosed with gastroesophageal reflux disease, one for rash on labia unrelated to vaccination, and one for vomiting and diarrhoea associated with a milk allergy. INTERPRETATION: Findings from this study suggest that lymphocyte subsets and the safety of live rotavirus vaccination are generally not affected by in-utero exposure to biologic agents. Rotavirus vaccination can be offered to infants exposed to anti-TNF agents in utero. FUNDING: Public Health Agency of Canada and Canadian Institutes of Health Research through the Canadian Immunization Research Network.

Children hospitalized with skin and soft tissue infections: a guide to antibacterial selection and treatment.

Skin and soft tissue infections in children are an important cause for hospitalization. A thorough history and physical examination can provide clues to the pathogens involved. Collection of purulent discharge from lesions should be completed prior to initiating antimicrobial therapy, and results of bacteriologic studies (Gram stain and culture) should guide therapeutic decisions. The main pathogens involved in these infections are Staphylococcus aureus and group A beta-hemolytic streptococci, but enteric organisms also play a role especially in nosocomial infections. Increasing antibacterial resistance is becoming a major problem in the treatment of these infections worldwide. Specifically, the rise of methicillin-resistant S. aureus and glycopeptide-resistant S. aureus pose challenges for the future. Infections of the skin and soft tissues can be broadly classified based on the extent of tissue involvement. Superficial infections such as erysipelas, cellulitis, bullous impetigo, bite infections, and periorbital cellulitis may require hospitalization and parenteral antibacterials. Deeper infections such as orbital cellulitis, necrotizing fasciitis, and pyomyositis require surgical intervention as well as parenteral antibacterial therapy. Surgery plays a key role in the treatment of abscesses and for the debridement of necrotic tissue in deep infections. Intravenous immunoglobulin, as an adjunctive therapy, can be helpful in treating necrotizing fasciitis. For most infections an antistaphylococcal beta-lactam antibacterial is first-line therapy. Third-generation cephalosporins and beta-lactam/beta-lactamase inhibitor antibacterials as well as clindamycin or metronidazole are often required to provide broad-spectrum coverage for polymicrobial infections.Special populations, such as immunocompromised children, those with an allergy to penicillins, and those that acquire infections in hospitals, require specific antibacterial strategies. These usually involve broader antimicrobial coverage with increased Gram-negative (including antipseudomonal) and anerobic coverage. In patients with a true allergy to penicillins, clindamycin and vancomycin play an important role in treating Gram-positive infections. Newer antibacterial agents, such as linezolid and quinupristin/dalfopristin, are increasingly being studied in children for the treatment of skin and soft tissue infections. These agents hold promise for the future especially in the treatment of highly resistant, Gram-positive organisms such as methicillin-resistant S. aureus, vancomycin-resistant S. aureus, and vancomycin-resistant enterococci.

Invasive Streptococcus pneumoniae infection causing hemolytic uremic syndrome in children: Two recent cases.

INTRODUCTION: Streptococcus pneumoniae is an uncommon cause of hemolytic uremic syndrome (HUS) with a unique pathophysiology that differs from Shiga toxin-related HUS. METHODS: Case descriptions for each patient are provided. Each strain of S pneumoniae was subjected to a pulsed-field gel electrophoresis (PFGE) analysis, Shiga toxin assay and polymerase chain reaction to detect Shiga toxin genes. A review of the current literature was conducted. CASE PRESENTATIONS: Two patients with S pneumoniae-related HUS that presented to the Alberta Children's Hospital, Calgary, Alberta, within four weeks of each other in 2001 are described. Both presented with pneumonia and empyema with associated HUS. Both patients required dialysis, one patient for 10 days and the other for 18 days. Neither patient demonstrated evidence of Shiga toxin-related disease. S pneumoniae isolated from blood or pleural fluid was penicillin susceptible. One isolate was serotype 3 and the other was serotype 14. The two strains had different PFGE patterns. Both patients recovered well with no persistent renal dysfunction. CONCLUSIONS: S pneumoniaecontinues to be an uncommon but important cause of HUS. Most cases can be confirmed or at least considered probable without performing a renal biopsy.