Inborn Errors of Immunity in Children With Invasive Pneumococcal Disease: A Multicenter Prospective Study.

BACKGROUND: In settings with universal conjugate pneumococcal vaccination, invasive pneumococcal disease (IPD) can be a marker of an underlying inborn error of immunity. The aim of this study was to determine the prevalence and characterize the types of immunodeficiencies in children presenting with IPD. METHODS: Multicenter prospective audit following the introduction of routinely recommended immunological screening in children presenting with IPD. The minimum immunological evaluation comprised a full blood examination and film, serum immunoglobulins (IgG, IgA and IgM), complement levels and function. Included participants were children in whom Streptococcus pneumoniae was isolated from a normally sterile site (cerebrospinal fluid, pleura, peritoneum and synovium). If isolated from blood, features of sepsis needed to be present. Children with predisposing factors for IPD (nephrotic syndrome, anatomical defect or malignancy) were excluded. RESULTS: Overall, there were 379 episodes of IPD of which 313 (83%) were eligible for inclusion and 143/313 (46%) had an immunologic evaluation. Of these, 17/143 (12%) were diagnosed with a clinically significant abnormality: hypogammaglobulinemia (n = 4), IgA deficiency (n = 3), common variable immunodeficiency (n = 2), asplenia (n = 2), specific antibody deficiency (n = 2), incontinentia pigmenti with immunologic dysfunction (n = 1), alternative complement deficiency (n = 1), complement factor H deficiency (n = 1) and congenital disorder of glycosylation (n = 1). The number needed to investigate to identify 1 child presenting with IPD with an immunologic abnormality was 7 for children under 2 years and 9 for those 2 years old and over. CONCLUSIONS: This study supports the routine immune evaluation of children presenting with IPD of any age, with consideration of referral to a pediatric immunologist.

Candidemia in Children: A 16-year Longitudinal Epidemiologic Study.

BACKGROUND: Candida species are the most common cause of systemic fungal infections in children. Risk factors for candidemia vary in different patient populations, posing challenges for clinical prediction of infection. We describe the epidemiology and clinical disease of candidemia in children admitted to a tertiary pediatric hospital. METHODS: Retrospective audit of children ≤18 years of age with candidemia at a tertiary pediatric hospital over a 16-year period. RESULTS: There were 139 episodes of candidemia in 124 children. A central venous catheter was present in 94% of episodes, prior antibiotic exposure in 86% and parenteral nutrition in 43%. During the study period, the proportion of candidemia due to non-albicans Candida spp. increased primarily due to a rise in C. krusei. Colonization with Candida spp. in the 30 days before developing candidemia was identified in 40% of episodes and the species was concordant in 60%. Infection at other sites was rare, including pulmonary dissemination (9/38, 24%), renal fungal disease (9/114, 8%), fungal endophthalmitis (8/102, 8%) and hepatosplenic nodules (5/92, 5%). Overall, 8/127 (6%) isolates were fluconazole-resistant (7 C. krusei and 1 C. glabrata) and 7/127 (6%) had intermediate susceptibility to fluconazole. The overall 30-day mortality was 12% and significant risk factors for mortality on multivariate analysis were male sex, liver disease and mucositis. CONCLUSIONS: Our study outlines low rates of disseminated candidiasis and low mortality associated with candidemia at our institution. Additionally, it suggests that prior colonization may be an important risk factor, however, this should be validated in large prospective controlled studies.

Effect of Surgical Skin Antisepsis on Surgical Site Infections in Patients Undergoing Gynecological Laparoscopic Surgery: A Double-Blind Randomized Clinical Trial.

Importance: Gynecological laparoscopies are one of the most common surgical procedures worldwide. Limited evidence exists on rates of surgical site infections in patients undergoing gynecological laparoscopies and strategies to prevent these infections. Objective: To compare rates of port-site infections, organ or space infections, and any type of surgical site infections among patients who underwent gynecological laparoscopies and received 1 of 3 types of skin preparation solutions. Design, Setting, and Participants: A double-blind randomized clinical trial was conducted between February 28, 2017, and November 26, 2018, at a tertiary university-affiliated referral center. A total of 661 patients 18 years or older who underwent an elective operative laparoscopy for treatment of nonmalignant gynecological disorders were randomly assigned in a 1:1:1 ratio to have their skin cleaned before surgery with alcohol-based chlorhexidine, alcohol-based povidone-iodine, or water-based povidone-iodine. Statistical analysis was performed from February 28, 2017, to November 26, 2018. Analyses were performed on a modified intention-to-treat basis. Interventions: A total of 221 patients were randomized to have their skin prepared preoperatively with water-based povidone-iodine, 220 were randomized to alcohol-based povidone-iodine, and 220 were randomized to alcohol-based chlorhexidine. The patients were blinded to the solution used to clean their skin. Patients were followed up 1 and 4 weeks after surgery by a physician who was blinded to the skin preparation solution used at surgery. Evidence of infection according to Centers for Disease Control and Prevention criteria were documented. Main Outcomes and Measures: The primary outcome of this study was port-site infection 30 days after surgery. Secondary outcomes were organ or space infections and any type of surgical site infections; the study also aimed to prospectively describe rates of surgical site infections in gynecological laparoscopies. Results: Of the 661 patients, 640 (96.8%; mean [SD] age, 36.2 [10.6] years) were examined after surgery by a physician at the study site and were included in the modified intention-to-treat analysis. The overall rate of port-site infection was 10.2% (65 of 640), rate of organ or space infection was 6.6% (42 of 640), and rate of any surgical site infection was 16.3% (104 of 640). The odds ratio for port-site infection for alcohol-based chlorhexidine vs water-based povidone-iodine was 1.13 (95% CI, 0.61-2.08), for alcohol-based chlorhexidine vs alcohol-based povidone-iodine was 1.34 (95% CI, 0.71-2.52), and for water-based povidone-iodine vs alcohol-based povidone-iodine was 1.19 (95% 0.62-2.27). Conclusions and Relevance: Surgical site infections were more common than expected among patients who underwent gynecological laparoscopies. No skin preparation solution provided an advantage compared with the other solutions in reducing infection rates. Trial Registration: http://anzctr.org.au Identifier: ACTRN12617000475347.

Changing Epidemiology and Predisposing Factors for Invasive Pneumococcal Disease at Two Australian Tertiary Hospitals.

BACKGROUND: Invasive pneumococcal disease (IPD) is associated with significant morbidity and mortality in children. Universal pneumococcal conjugate vaccination has changed the epidemiology of IPD. In vaccinated children, IPD can be a marker of an underlying immunodeficiency. METHODS: This is a retrospective audit of children younger than 18 years with IPD admitted to 2 tertiary pediatric hospitals in Australia between 2011 and 2017. Data on predisposing conditions, immunologic evaluation, pneumococcal serotype, antibiotic susceptibility and treatment were collected. RESULTS: During the 7-year period, there were 131 presentations with IPD in 127 children; 3 children had recurrent IPD. Patients presented with sepsis (41%), empyema (29%), meningitis (18%), mastoiditis (12%), pneumonia (10%) and septic arthritis (4%). In 19 (15%) presentations, risk factors for IPD were present, including malignancy, hematologic disorder, chronic liver disease, chronic kidney disease and cochlear implant. Pneumococcal serotypes were determined in 78/131 (60%) of presentations: the most frequent serotypes were 19A (19%), 3 (13%), 7F (10%) and 19F (8%) and non-vaccine serotypes 22F (8%), 35B (6%), 15A (4%) and 38 (4%). Overall, 11% of isolates were non-susceptible to ceftriaxone. Only 36 patients (32%) had an immunologic evaluation, and 4 patients had proven or probable immunodeficiency. CONCLUSION: Although pneumococcal conjugate vaccine serotypes 19A, 3, 19F and 7F remain frequent causes of IPD, non-vaccine serotypes are emerging. Our data support vancomycin treatment for children with pneumococcal meningitis given 11% of our isolates were not susceptible to ceftriaxone. It is important to consider underlying conditions predisposing to IPD in a population with high rates of pneumococcal vaccination.

Compliance with screening for and recommended management of maternal group B streptococcus carriage in pregnancy.

BACKGROUND: Universal screening of pregnant women at 35-37 weeks gestation is recommended for detection of anogenital group B streptococcus carriage. Intrapartum chemoprophylaxis is prescribed to carriers to prevent transmission to babies, reducing early-onset neonatal group B streptococcal sepsis. AIMS: To review compliance with, and the effects of education on group B streptococcus screening and intrapartum chemoprophylaxis practices at The Royal Women's Hospital, Melbourne, Australia. MATERIALS AND METHODS: A retrospective audit of women delivering in February 2016 and February-March 2017 was conducted. In February 2017, updated early-onset group B streptococcal disease prevention guidelines were released and promoted with targeted education of clinical staff. Compliance was considered appropriate if practices followed up-to-date local protocols. RESULTS: Screening rate for group B streptococcus was 84.4% (599/710) and carriage rate 19.5% (109/558), while intrapartum antibiotic prophylaxis was optimal in 83% of those labouring greater than four hours (39/47). There was no significant difference in compliance between 2016 and 2017. Of 113 women with unknown group B streptococcal status at delivery, only five of 33 (15%) with clinical risk factors for early-onset neonatal disease received intrapartum prophylaxis. CONCLUSIONS: Compliance remained stable, with no change during or after implementation of new protocols. Compliance with protocols was low for cases with unknown group B streptococcal status at delivery but with the presence of one or more clinical risk factors for early-onset group B streptococcal sepsis.

Diagnostic Yield of Timing Blood Culture Collection Relative to Fever.

BACKGROUND: Conventional practice involves obtaining a blood culture during or immediately after a fever to increase diagnostic yield. There are no data to support this practice in children. METHODS: Retrospective single-center case-control study of children (0-18 years) who had blood cultures performed as part of routine care. Cases had an a priori defined pathogen isolated from blood culture (n = 410) and were age-matched with contemporaneous controls with a sterile blood culture (n = 410). The predictive value of fever (before and after blood culture), C-reactive protein and hematologic indices were analyzed by multivariate regression and area under the receiver operating characteristic curves (AUCs) in neonatal, general pediatric and pediatric oncology patients. RESULTS: One thousand one hundred seventy-two (6.7%) of 17,607 blood cultures were positive, of which 410 (35%) cultured pathogen(s). Three hundred and twenty four (79%) cases and 275 (67.1%) controls had a fever (≥37.5°C) during the 12 hours pre- or post-collection. Fever 2-6 hours before a blood culture was neither sensitive nor specific for predicting bacteremia in neonatal or pediatric patients and marginally predictive in oncology patients (AUC 0.59-0.63). Cultures obtained 2-6 hours before fever were nonpredictive in neonates (AUC 0.56-0.59), marginally predictive in pediatric patients (AUC 0.64-0.67) and moderately predictive in oncology patients (AUC 0.70). C-reactive protein was marginally predictive in neonates (AUC 0.60). Hematologic indices were nonpredictive in all groups. CONCLUSIONS: Fever before obtaining blood culture was neither sensitive nor specific for culture positivity; timing of pediatric blood cultures relative to fever is unimportant. Bacteremia precedes a fever, but this is of limited clinical applicability.

Antibiotic-resistant Gram-negative bacteremia in pediatric oncology patients--risk factors and outcomes.

BACKGROUND: Infection with antibiotic-resistant (AR) Gram-negative (GN) bacteria is associated with increased morbidity and mortality. The aim of this study was to determine risk factors and outcomes associated with GN bacteremia with acquired resistance to antibiotics used in the empiric treatment of febrile neutropenia in pediatric oncology patients at our institution. METHODS: All episodes of GN bacteremia in oncology patients at the Royal Children's Hospital Melbourne, from 2003 to 2010 were retrospectively reviewed. Information regarding age, diagnosis, phase of treatment, inpatient status, previous AR GN infection, treatment with inotropes or ventilatory support, admission to intensive care unit, and hospital and intensive care unit length of stay were obtained from electronic records. RESULTS: A total of 280 episodes of GN bacteremia in 210 patients were identified. Of these, 42 episodes in 35 patients were caused by an AR GN organism. Factors independently associated with AR GN bacteremia were high-intensity chemotherapy (odds ratio 3.7, 95% confidence interval: 1.2-11.4), hospital-acquired bacteremia (odds ratio 4.3, 95% confidence interval: 2.0-9.6) and isolation of AR GN bacteria from any site within the preceding 12 months (odds ratio 9.9, 95% confidence interval: 3.8-25.5). Episodes of AR GN bacteremia were associated with longer median hospital length of stay (23.5 days versus 14.0 days; P = 0.0007), longer median intensive care unit length of stay (3.8 days versus 1.6 days; P = 0.02) and a higher rate of invasive ventilation (15% versus 5.2%; P = 0.03). No significant difference in infection-related or all-cause mortality between the 2 groups was identified. CONCLUSIONS: In pediatric oncology patients, AR GN bacteremia is associated with an increased rate of adverse outcomes and is more likely in patients who have received high-intensity chemotherapy, have been in hospital beyond 48 hours and who have had previous AR GN infection or colonization.

Nontuberculous mycobacterial infection in children: a prospective national study.

BACKGROUND: The epidemiology and management of nontuberculous mycobacterial (NTM) infection in Australian children is unknown. METHODS: From July 2004 to June 2007, clinicians identified children with NTM infection as part of a nationwide active surveillance network. Following notification, detailed data were collected. RESULTS: From 192 reports, data were received on 153 cases (response rate: 79.7%). Of these, 102 met inclusion criteria. The median age was 2.9 years. Predisposing conditions were infrequent and included chronic respiratory disease (n = 12) and immunosuppression (n = 6). Lymphadenitis was the most frequent presentation (n = 68) with pulmonary and disseminated disease infrequent (n = 14 and 3, respectively). NTM was isolated in 68 cases with Mycobacterium avium-intracellulare complex most frequently isolated (33/68; 48.5%). Surgery was performed in 78 cases and 42 children were treated with antimycobacterial therapy. Twenty-five subjects received surgery and antimycobacterial therapy. Follow-up data were available for 77 children with recurrence observed in 18 cases. Complete excision was associated with a higher rate of treatment success when compared with all other therapies (OR: 9.48 [95% CI: 2.00-44.97], P = 0.001). Mycobacterium lentiflavum infection accounted for 4.4% of culture confirmed cases and had a lower rate of treatment success than other species (0% vs. 78.2%; P = 0.016). CONCLUSIONS: The incidence of NTM infection in Australian children is 0.84 of 100,000 (95% CI: 0.68-1.02). Infection occurs most often in young children without predisposing conditions. Despite therapy, there was recurrence in 23.4% of cases.