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Background: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown., Methods: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression., Results: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%)., Conclusions: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Discussion remains on how to advise women with a past medical history of surgically corrected anorectal malformations (ARMs) regarding vaginal delivery. The aim of this review is to evaluate and review the reported obstetrical complications and outcomes after vaginal delivery for these women., Data Sources: A systematic search was performed from inception up to 25 July 2022 in PubMed, Embase.com and Clarivate Analytics/Web of Science Core Collection, with backward citation tracking., Study Eligibility Criteria/appraisal: All articles reported on the outcomes of interest in women with a past medical history of surgically corrected anorectal malformation and had a vaginal delivery were included with the exception of editorial comments or invitational commentaries. Screening, data extraction and risk of bias assessment was done by two authors independently with a third and fourth reviewer in case of disagreement. Tool for Quality assessment depended on the type of article. As low quality evidence was expected no meta-analysis was performed., Results: Only five of the 2377 articles screened were eligible for inclusion with a total of 13 attempted vaginal deliveries in eight women. In three patients complications were reported: failed vaginal delivery requiring urgent cesarean section in two patients, and vaginal tearing in one patient., Conclusion: High quality evidence regarding outcomes and complications after vaginal delivery in women with a history of surgically corrected anorectal malformation is lacking. Therefore, based upon this systematic review no formal recommendation can be formulated regarding its safety. Future studies are essential to address this problem., Trial Registration: CRD42020201390. Date: 28-07-2020s., (© 2023. The Author(s).)

Objective: To reduce both inappropriate testing for and diagnosis of healthcare-onset (HO) Clostridioides difficile infections (CDIs)., Design: We performed a retrospective analysis of C. difficile testing from hospitalized children before (October 2017-October 2018) and after (November 2018-October 2020) implementing restrictive computerized provider order entry (CPOE)., Setting: Study sites included hospital A (a ∼250-bed freestanding children's hospital) and hospital B (a ∼100-bed children's hospital within a larger hospital) that are part of the same multicampus institution., Methods: In October 2018, we implemented CPOE. No testing was allowed for infants aged ≤12 months, approval of the infectious disease team was required to test children aged 13-23 months, and pathology residents' approval was required to test all patients aged ≥24 months with recent laxative, stool softener, or enema use. Interrupted time series analysis and Mann-Whitney U test were used for analysis., Results: An interrupted time series analysis revealed that from October 2017 to October 2020, the numbers of tests ordered and samples sent significantly decreased in all age groups ( P < .05). The monthly median number of HO-CDI cases significantly decreased after implementation of the restrictive CPOE in children aged 13-23 months ( P < .001) and all ages combined ( P = .003)., Conclusion: Restrictive CPOE for CDI in pediatrics was successfully implemented and sustained. Diagnostic stewardship for CDI is likely cost-saving and could decrease misdiagnosis, unnecessary antibiotic therapy, and overestimation of HO-CDI rates.

Background: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy has been on acute infections with limited data on the effect of distant infection., Aim: We examined placental pathology and neonatal outcomes in distant SARS-CoV-2 infection earlier in pregnancy compared to acute infections late in pregnancy/at birth and to non-SARS-CoV-2 infected patients with other placental pathologies/clinical presentations., Methods: Placentas birthed to unvaccinated patients with SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) testing and serology testing results from time of delivery were included in this study. A total of 514 singleton placentas between April 18, 2020, and July 26, 2021, were included: 77 acute SARS-CoV-2 infection (RT-PCR positive and serology negative); 222 distant SARS-CoV-2 infection (RT-PCR negative but serology IgG-positive); and 215 non-SARS-Cov-2 infected (RT-PCR negative, serology negative, and history negative) with other placental pathologies: preeclampsia/hypertension, intrauterine growth restriction (IUGR), diabetes, chorioamnionitis, and meconium. Placental pathology findings, Apgar scores, and neonatal birth weights were compared., Results: Placentas from the acute group had significantly more villous agglutination (10.4%, P = 0.015) and eosinophilic T-cell vasculitis (5.2%, P = 0.004) compared to placentas from the distant group (2.7% and 0%) and non-SARS-CoV-2 placentas (1.9% and 0.9%). One acute case showed SARS-CoV-2 placentitis and resulted in preterm delivery at 25 weeks. Both the preeclampsia/hypertension and the IUGR groups showed significantly more maternal vascular malperfusion findings compared to the acute (6.5%, 6.5% and 1.3%) and distant (7.7%, 7.7%, and 3.2%) groups. Fetal vascular malperfusion findings such as thrombosis of fetal vessels (17.4% P = 0.042) and intramural fibrin deposition (21.7% P = 0.026) were significantly higher in the IUGR group compared to acute (7.8%; 2.6%) and distant (3.6%; 8.1%) infection. Many neonates born to patients infected with SARS-CoV-2 had birth weights outside of 95% confidence range of observed birth weights. There was no association of Apgar scores with infection status or placental pathology., Conclusion: Acute and distant SARS-CoV-2 infections present differing placental pathology., Relevance for Patients: SARS-CoV-2 infection during pregnancy has demonstrable effects on the placenta with potential significant impacts for maternal and fetal health. Prevention of maternal SARS-CoV-2 infection, primarily through vaccination, remains the best mitigation strategy to prevent sequelae of maternal SARS-CoV-2 infection., Competing Interests: The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright: © 2022 Author(s).)

Background: Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear., Methods: This multinational observational cohort study enrolled patients aged >120 days and <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-β-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard., Results: Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%- 97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%)., Conclusions: T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC., Clinical Trials Registration: NCT02220790., Competing Interests: Potential conflicts of interest. B. T. F. receives funding from the Food and Drug Administration, Pfizer, and Merck and serves as a paid chair of a data and safety monitoring board (DSMB) for Astellas. R. H. serves on advisory boards for Quidel and Inflammatix; receives ASM Press book royalties (personal payments); and serves as a member of the board of directors for the Clinical Laboratories Standards Institute and as immediate past president for the Pan-American Society for Clinical Virology (both unpaid). T. E. Z. provides consultant services for T2 Biosystems and Nabriva Therapeutics. D. E. Y.’s institution receives funding from Merck, Astellas, Marion Merrel Dow Fund, Viracor-Eurofins (laboratory testing services to institution for investigator-initiated research), and Chimerix. D. E. Y. is now employed by the National Institute of Allergy and Infectious Diseases, NIH, which has paid for conference registration and fees, but this research was conducted while he was employed by Children’s Mercy Kansas City and the University of Missouri–Kansas City School of Medicine. D. E. Y. also reports serving as unpaid technical advisor to nonprofit organizations Cover the Globe and Maipelo Trust, which provide human immunodeficiency virus services to migrant or displaced children and families in Botswana. A. R. H. has patent 10,160,974 issued (Engineered cytokine- and chemokine-expressing Candida albicans strains and methods of use; no royalties collected); reports grant support from the NIH (grant K08DE026189 from the National Institute of Dental and Craniofacial Research and NIH pass-through via Duke grants [DOMINIC]); and reports serving on the Central Review Board for Non-Invasive Diagnosis of Pediatric Pulmonary Invasive Mold infections (DOMINIC) (unpaid). L. D. I. received institutional support for contracted clinical research from Astellas, Merck, Takeda, Ansun Biopharma, and Viracor-Eurofins; is a paid consultant for Takeda and paid chair of a DSMB for Merck; and serves as president of The International Society for Heart and Lung Transplantation. W. J. M. receives support from Adagio Therapeutics, Ansun Biopharma, Astellas, AstraZeneca, Eli Lilly, Enanta Pharmaceuticals, Janssen, Karius, Merck, Genentech, Gilead, Moderna, Melinta, Nabriva, Tetraphase, and Seqirus; reports consulting fees from Seqirus (to institution), the US Attorney’s Office, Southern District of Illinois (to self), McQuade Blasko Law Offices (to self), Finley Law Firm (to self), Doherty & Progar (to self), Phelan, Tucker, Mullen, Walker, Tucker, Gelman (to self), and Bailes, Craig, Yon & Sellards (to self); and reports participation on DSMB or advisory boards for Adagio Therapeutics and ProventionBio (payments to self). E. R. receives funding from Merck Sharp & Dohme (MSD), Merck, Pfizer, and Gilead; reports consulting fees from MSD and Pfizer (paid to institution); reports honoraria for lectures paid to their institution from Pfizer, MSD, and Gilead; reports travel support/payment of registration from Vianex, Pfizer, and MSD; and reports participation on advisory board(s) for MSD and Pfizer. P. K. S. reports grants from Astellas and Merck (to institution for work as clinical trial site). D. B. was a consultant for Teleflex. D. B. reports consulting fees from Precision Health (consulting agreement as of August 2021), for providing advice on the selection of polymerase chain reaction panels for outpatients in long-term care facilities and educating the Medical Science Liason team on their use) and Karius Diagnostics (where D. B. has been employed full time since 28 June 2021, as medical director in the Medical Affairs Division); Karius offers metagenomic next-generation sequencing for pathogens from plasma). As a full-time Karius employee, D. B. has the option to purchase stocks in the future during the initial public offering (the timing of the initial public offering is not yet known). D. B. continue to have a faculty appointment at Johns Hopkins All Children’s Hospital and hospital privileges (per diem). N. H. was a consultant for Moderna; receives funding from NIH, the Centers for Disease Control and Prevention, Quidel, and Sanofi; and serves as a Pediatric Infectious Diseases Society board member. G. M. receives funding from Astellas. P. S. P. receives support from Pfizer (research grant), Grifols, CSL Behring, Takeda, and Gilead (education and research grants); reports payment/honoraria from Pfizer and Gilead and payment for expert testimony from Gilead; reports participation on DSMB or an advisory board for Pfizer. C. M. S. reports receiving an NIH grant for the BIOPIC study, during the conduct of the study. M. G. reports NIH funding, outside the submitted work; receives royalties for being a textbook editor for Elsevier; reports personal consulting fees from ITB-Med; reports a personal honorarium for a lecture from Medscape; reports personal payments for serving on an advisory board for ATARA Biotherapeutics; and serves on the DSMB and as a consultant for Bristol Myers Squibb. S. B. H. reports honoraria for lectures on coronavirus disease 19 in Texas and office infection control from the Centers for Disease Control and Prevention. W. J. S. serves on the scientific advisory board of Sfunga (personal payments). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The effect of SARS-CoV-2 infection on placental function is not well understood. Analysis of placentas from women who tested positive at delivery showed SARS-CoV-2 genomic and subgenomic RNA in 22 out of 52 placentas. Placentas from two mothers with symptomatic COVID-19 whose pregnancies resulted in adverse outcomes for the fetuses contained high levels of viral Alpha variant RNA. The RNA was localized to the trophoblasts that cover the fetal chorionic villi in direct contact with maternal blood. The intervillous spaces and villi were infiltrated with maternal macrophages and T cells. Transcriptome analysis showed an increased expression of chemokines and pathways associated with viral infection and inflammation. Infection of placental cultures with live SARS-CoV-2 and spike protein-pseudotyped lentivirus showed infection of syncytiotrophoblast and, in rare cases, endothelial cells mediated by ACE2 and Neuropilin-1. Viruses with Alpha, Beta, and Delta variant spikes infected the placental cultures at significantly greater levels., Competing Interests: O.E. is a scientific advisor and equity holder in Freenome, Owkin, Volastra Therapeutics, and One Three Biotech. R.E.S. is on the scientific advisory board of Miromatrix Inc and is a consultant and speaker for Alnylam Inc., (© 2022 The Author(s).)

Background: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis., Methods: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups., Results: Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days., Conclusions: In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents., Clinical Trials Registration: NCT01869829., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The risk of vertical and perinatal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, which causes COVID-19), the most appropriate management, and the neonate's risk of developing COVID-19 during the perinatal period are unknown. Therefore, we aimed to elucidate best practices regarding infection control in mother-newborn dyads, and identify potential risk factors associated with transmission., Methods: In this observational cohort study, we identified all neonates born between March 22 and May 17, 2020, at three New York Presbyterian Hospitals in New York City (NY, USA) to mothers positive for SARS-CoV-2 at delivery. Mothers could practice skin-to-skin care and breastfeed in the delivery room, but had to wear a surgical mask when near their neonate and practice proper hand hygiene before skin-to-skin contact, breastfeeding, and routine care. Unless medically required, neonates were kept in a closed Giraffe isolette in the same room as their mothers, and were held by mothers for feeding after appropriate hand hygiene, breast cleansing, and placement of a surgical mask. Neonates were tested for SARS-CoV-2 by use of real-time PCR on nasopharyngeal swabs taken at 24 h, 5-7 days, and 14 days of life, and were clinically evaluated by telemedicine at 1 month of age. We recorded demographics, neonatal, and maternal clinical presentation, as well as infection control practices in the hospital and at home., Findings: Of 1481 deliveries, 116 (8%) mothers tested positive for SARS-CoV-2; 120 neonates were identified. All neonates were tested at 24 h of life and none were positive for SARS-CoV-2. 82 (68%) neonates completed follow-up at day 5-7 of life. Of the 82 neonates, 68 (83%) roomed in with the mothers. All mothers were allowed to breastfeed; at 5-7 days of life, 64 (78%) were still breastfeeding. 79 (96%) of 82 neonates had a repeat PCR at 5-7 days of life, which was negative in all; 72 (88%) neonates were also tested at 14 days of life and none were positive. None of the neonates had symptoms of COVID-19., Interpretation: Our data suggest that perinatal transmission of COVID-19 is unlikely to occur if correct hygiene precautions are undertaken, and that allowing neonates to room in with their mothers and direct breastfeeding are safe procedures when paired with effective parental education of infant protective strategies., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This paper reviews recent advances in three selected areas of pediatric invasive candidiasis: epidemiology, diagnosis, and treatment. Although the epidemiological trends of pediatric invasive candidiasis illustrate a declining incidence, this infection still carries a heavy burden of mortality and morbidity that warrants a high index of clinical suspicion, the need for rapid diagnostic systems, and the early initiation of antifungal therapy. The development of non-culture-based technologies, such as the T2Candida system and (1→3)-β-d-glucan detection assay, offers the potential for early laboratory detection of candidemia and CNS candidiasis, respectively. Among the complications of disseminated candidiasis in infants and children, hematogenous disseminated Candida meningoencephalitis (HCME) is an important cause of neurological morbidity. Detection of (1→3)-β-d-glucan in cerebrospinal fluid serves as an early diagnostic indicator and an important biomarker of therapeutic response. The recently reported pharmacokinetic data of liposomal amphotericin B in children demonstrate dose⁻exposure relationships similar to those in adults. The recently completed randomized clinical trial of micafungin versus deoxycholate amphotericin B in the treatment of neonatal candidemia provides further safety data for an echinocandin in this clinical setting.

Study Design: Single-institution, retrospective case series., Objective: To determine whether the microbiology of deep surgical site infections (SSIs) after spinal fusion surgery for deformity has changed over the last decade at our institution., Summary of Background Data: SSI after pediatric spinal deformity surgery results in significantly increased patient morbidity and health care costs. Although risk factors are multifactorial, prophylactic and treatment antibiotic coverage is based in part on historical epidemiologic data, which may evolve over time., Methods: This study represents a retrospective review of clinical and microbiology records of patients less than 21 years old who underwent spinal deformity surgery at a single institution between 2000 and 2012. Patients were included who underwent index surgery at our institution and developed a deep SSI. Patients with growth-preserving spine constructs were excluded., Results: The overall incidence of deep SSI was 3.6% (39/1094). The incidence of deep SSI following primary surgery was 3.3% (34/1034) and 8.3% (5/60) following revision surgery. The incidence of deep SSI varied by primary diagnosis: idiopathic (1.0%), neuromuscular (14.3%), syndromic (5.3%), congenital (5.7%), and kyphosis (0.0%). The most common inciting pathogens were Staphylococcus epidermidis (26%), methicillin-sensitive Staphylococcus aureus (MSSA, 18%), Propionibacterium acnes (P. acnes; 18%), and Escherichia coli (18%). Sixteen of the 18 (89%) gram-negative infections occurred in neuromuscular patients (P = 0.006). Between 2000 and 2006 and between 2007 and 2012, MSSA occurred in 2/18 (11%) and 5/21 (24%) of cases (P = 0.41), methicillin-resistant S. aureus occurred in 1/18 (6%) and 3/21 (14%) (P = 0.61), and P. acnes occurred in 3/18 (17%) and 4/21 (19%) (P = 1.0)., Conclusion: The epidemiology of deep SSI following spinal fusion for deformity in pediatric patients at our institution has not changed significantly during 13 years. Prophylactic antibiotic coverage for both gram-positive and gram-negative organisms may be indicated for patients with primary neuromuscular diagnoses., Level of Evidence: 4.

Background: Fungal infections of the central nervous system (FICNS) are important causes of morbidity and mortality among immunocompromised pediatric patients. Standard diagnostic modalities lack the sensitivity for detecting and therapeutically monitoring these life-threatening diseases. Current molecular methods remain investigational. (1→3)-β-d-glucan (BDG) is a cell wall component found in several fungal pathogens, including Candida and Aspergillus spp. Detecting BDG in cerebrospinal fluid (CSF) may be an important approach for detecting and therapeutically monitoring FICNS. To date, there has been no study that has investigated the effectiveness of CSF BDG as a diagnostic and therapeutic marker of FICNS in children., Methods: Serial BDG levels were measured in serum and CSF samples obtained from pediatric patients (aged 0-18 years) with a diagnosis of probable or proven Candida or Aspergillus CNS infection., Results: Nine cases of FICNS were identified in patients aged 1 month to 18 years. Two patients were infected with an Aspergillus species, and 7 patients were infected with a Candida species. All the patients at baseline had detectable BDG in their CSF. Among 7 patients who completed therapy for an FICNS, all elevated CSF BDG levels decreased to <31 pg/mL. At the time of this writing, 1 patient was still receiving therapy and continued to have elevated BDG levels. One patient died from overwhelming disseminated candidiasis. The lengths of therapy for these 9 children ranged from 2 weeks to 28 months., Conclusion: The BDG assay is useful in diagnosing and therapeutically monitoring Candida and Aspergillus CNS infections in pediatric patients., (© The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Skeletal infections secondary to Candida albicans are uncommon and described primarily in adults. Nearly all 22 pediatric cases of C. albicans osteomyelitis described to date have occurred in neonates with specific risk factors or in children with a severe immunodeficiency. We report an unusual presentation of C. albicans osteomyelitis and arthritis in a 1-year-old boy without an immunodeficiency, which led to a delayed diagnosis. He most likely developed C. albicans arthritis and osteomyelitis during the neonatal period with a subsequent indolent and subacute presentation. Our literature search found no prior or recent reviews of C. albicans osteomyelitis in pediatric patients. On the basis of this patient and the case reports previously published, we discuss an approach to the evaluation and management of pediatric patients with Candida osteomyelitis.

We report our experience with a 9-month-old infant treated with intravenous polymyxin B for multidrug-resistant Klebsiella pneumoniae bacteremia. Serial blood samples were obtained at steady state and serum drug concentrations were determined using a validated liquid chromatography-mass spectrometry method. The elimination half-lives of polymyxin B1 and isoleucine-polymyxin B1 were found to be 3.1 and 4.7 hours, respectively.

Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against M. pneumoniae. We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of M. pneumoniae pneumonia. BALB/c mice were inoculated intranasally with M. pneumoniae and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], interleukin 1beta [IL-1beta], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1alpha, MIG, KC, MCP-1, and IP-10). BAL M. pneumoniae concentrations in mice treated with tigecycline (MpTige) tended to be reduced compared with mice treated with placebo (MpPl); however this did not reach statistical significance. The lung HPS was significantly lower, as well as the parenchymal-pneumonia subscore, in the MpTige mice than in the MpPl mice. MpTige mice had significantly lower BAL cytokine concentrations of IL-1beta, IL-12 (p40/p70), IFN-gamma, and TNF-alpha; of the chemokines, MIG, MIP-1alpha, and IP-10 were statistically lower in MpTige mice. While tigecycline treatment demonstrated a modest microbiologic effect, it significantly improved lung histologic inflammation and reduced pulmonary cytokines and chemokines.

Unlabelled: Alternative antimicrobial regimens are needed for treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated pulmonary exacerbations in children with cystic fibrosis (CF). There are no published pharmacokinetic (PK) and pharmacodynamic (PD) data for linezolid in children with CF., Objectives: (1) To determine the PK and PD profile of linezolid among children with CF; (2) to characterize the effect of linezolid on MRSA infection; (3) to determine the effect of age and CF transmembrane regulator (CFTR) gene mutations on drug clearance., Hypotheses: Linezolid clearance is enhanced in children with CF requiring a higher dosage regimen. Age and CFTR gene mutations affect drug clearance., Methods: This was a retrospective cohort study; medical records of children with MRSA-associated pulmonary exacerbations treated with linezolid (10 mg/kg/dose IV every 8h) were reviewed. Linezolid peak and trough concentrations in serum were determined by high performance liquid chromatography, PK profiles determined using standard noncompartmental method, and PD indices were evaluated., Results: 10 children (mean +/- SD, 10.2 +/- 5.5 years) received 14 courses of linezolid at 10 +/- 0.4 mg/kg/dose every 8h for 15.4 +/- 3.2 days. Seven had homozygous DeltaF508 CFTR mutation. Peak and trough linezolid concentrations varied widely (range, 8.4-20.5 and 0.1-11.5 mcg/mL respectively). The PK profile of children <10 years differed significantly from older patients (>or=10 years). The PK indices of children with homozygous DeltaF508 differed marginally from those with heterozygous CFTR mutations, but there were too few subjects to allow separation of age and CFTR mutations effect. No patient achieved the target PD ratio of AUC/MIC >80. MRSA persisted in sputum or throat culture after treatment with linezolid., Conclusions: Additional PK and PD data are needed to optimize linezolid therapy in children with cystic fibrosis; it is likely that higher doses will be needed., ((c) 2009 Wiley-Liss, Inc.)

Background: Systemic steroids have been advocated in addition to antimicrobial therapy for severe Mycoplasma pneumoniae pneumonia. We evaluated the efficacy of clarithromycin, dexamethasone, and combination therapy for M. pneumoniae respiratory infection., Methods: Mice infected with M. pneumoniae were treated with clarithromycin, dexamethasone, combined clarithromycin/dexamethasone, or placebo daily; mice were evaluated at baseline and after 1, 3, and 6 days of therapy. Outcome variables included M. pneumoniae culture, lung histopathologic score (HPS), and bronchoalveolar lavage cytokine, chemokine, and growth factor concentrations., Results: Clarithromycin monotherapy resulted in the greatest reductions in M. pneumoniae concentrations. After 3 days of treatment, combination therapy significantly reduced lung HPS compared with placebo, clarithromycin, and dexamethasone alone, whereas, after 6 days of therapy, clarithromycin alone and combination therapy significantly reduced lung HPS compared with placebo. Concentrations of interleukin (IL)-12 p40, RANTES, macrophage chemotactic protein-1, and cytokine-induced neutrophil chemoattractant were significantly lower in mice treated with clarithromycin alone and/or combination therapy compared with dexamethasone alone and/or placebo; combination therapy resulted in a significantly greater reduction than clarithromycin alone for IL-12 p40 and RANTES., Conclusions: Although monotherapy with clarithromycin had the greatest effect on reducing concentrations of M. pneumoniae, combination therapy had the greatest effect on decreasing levels of cytokines and chemokines as well as pulmonary histologic inflammation.

Three women aged 17, 12 and 13 years presented with intermittent abdominal pain. Secondary sexual characteristics, i.e. mammae and pubic hair, were developed, but menarche had not occurred. All were found to have imperforate hymen. After incision, the symptoms disappeared. Imperforate hymen causes clinical symptoms from the time of menarche. Pubertal girls presenting with abdominal symptoms must be examined, including observation of secondary sexual characteristics and inspection of the external genitalia. This examination is often omitted because the patient and the physician are embarrassed. However, it is essential and should be carried out in a considerate manner. Excision of the hymen must be performed under general anaesthesia using a technique that will prevent secondary stenosis.

Mycoplasma pneumoniae is a leading cause of pneumonia and is associated with asthma. Evidence links M. pneumoniae respiratory disease severity with interleukin-12 (IL-12) concentrations in respiratory secretions. We evaluated the effects of IL-12 therapy on microbiologic, inflammatory, and pulmonary function indices of M. pneumoniae pneumonia in mice. BALB/c mice were inoculated with M. pneumoniae or SP4 broth. Mice were treated with intranasal IL-12 or placebo daily for 8 days, starting on day 1 after inoculation. Mice were evaluated at baseline and on days 1, 3, 6, and 8 after therapy. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine concentrations determined by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, and granulocyte-macrophage colony-stimulating factor), and plethysmography, both before and after methacholine treatment. M. pneumoniae-infected mice treated with IL-12 (MpIL12 mice) were found to have significantly higher BAL M. pneumoniae concentrations than those of M. pneumoniae-infected mice treated with placebo (MpP mice) (P < 0.001). MpIL12 mice had higher BAL concentrations of IL-12, IFN-gamma, TNF-alpha, and IL-6, with differences in IL-12 and IFN-gamma concentrations reaching statistical significance (P < 0.001). Airway obstruction was statistically elevated in MpIL12 mice compared to that in MpP mice (P = 0.048), while airway hyperreactivity was also elevated in MpIL12 mice but did not reach statistical significance (P = 0.081). Lung parenchymal pneumonia subscores were significantly higher in MpIL12 mice (P < 0.001), but no difference was found for overall HPS, even though a strong trend was noticed (P = 0.051). Treatment of experimental M. pneumoniae pneumonia with intranasal IL-12 was associated with more severe pulmonary disease and less rapid microbiologic and histological resolution.

Mycoplasma pneumoniae is a leading cause of pneumonia and is associated with asthma. Evidence links M. pneumoniae respiratory disease severity with interleukin-12 (IL-12) concentration in respiratory secretions. We evaluated the microbiologic, inflammatory, and pulmonary function indices of M. pneumoniae pneumonia in IL-12 (p35) knockout (KO) mice and wild-type (WT) mice to determine the role of IL-12 in M. pneumoniae respiratory disease. Eight-week-old wild-type BALB/c mice and 8-week-old IL-12 (p35) KO BALB/c mice were inoculated once intranasally with 10(7) CFU of M. pneumoniae. Mice were evaluated at days 2, 4, and 7 after inoculation. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic scores (HPS), BAL cytokine concentrations determined by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor) and plethysmography, before and after methacholine, to assess airway obstruction (AO) and airway hyperreactivity (AHR). IL-12 (p35) KO mice infected with M. pneumoniae were found to have significantly lower BAL M. pneumoniae concentrations compared with M. pneumoniae-infected WT mice. Lung HPS and the parenchymal pneumonia subscores (neutrophilic alveolar infiltrate), as well as AO, were significantly lower in infected KO mice. No difference was found for AHR. Infected KO mice had significantly lower BAL concentrations of IFN-gamma than WT mice; a trend toward lower BAL concentrations was observed for IL-10 (P = 0.065) and TNF-alpha (P = 0.078). No differences were found for IL-1beta, IL-2, IL-4, IL-5, or IL-6. The lack of IL-12 in experimental M. pneumoniae pneumonia was associated with less severe pulmonary disease and more rapid microbiologic and histologic resolution.

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. We evaluated the efficacy of LBM415, a novel peptide deformylase inhibitor antimicrobial agent, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were intranasally inoculated once with 10(7) CFU of M. pneumoniae. Groups of mice were treated with LBM415 (50 mg/kg of body weight) or placebo subcutaneously daily for 13 days, starting 24 h after inoculation. Groups of mice were evaluated at the baseline; at days of treatment 1, 3, 6, and 13; and at 7 days after treatment. The MIC of LBM415 against M. pneumoniae was <0.005 microg/ml. LBM415-treated mice had significantly lower bronchoalveolar lavage fluid M. pneumoniae concentrations than placebo-treated mice on days 6 and 13 of treatment. Compared with placebo treatment, therapy with LBM415 significantly decreased lung histopathology scores at days 3, 6, and 13 of treatment and at 7 days after treatment. Airway obstruction was significantly lower in LBM415-treated mice than in placebo-treated mice on days 1, 3, and 6 of treatment and after 7 days of therapy, while airway hyperresponsiveness was significantly lower only on day 3 of therapy. The bronchoalveolar lavage fluid concentrations of tumor necrosis factor alpha, gamma interferon (IFN-gamma), interleukin-6 (IL-6), IL-12, KC (functional IL-8), monocyte chemotactic protein 1, macrophage inflammatory protein 1alpha, monokine induced by IFN-gamma, and IFN-inducible protein 10 were significantly reduced in LBM415-treated mice compared with the levels in placebo-treated mice. There were no differences in the bronchoalveolar lavage fluid concentrations of granulocyte-macrophage colony-stimulating factor, IL-1beta, IL-2, IL-4, IL-5, and IL-10 between the two groups of mice. LBM415 therapy had beneficial microbiologic, histologic, respiratory, and immunologic effects on acute murine M. pneumoniae pneumonia.

Forty infants with suspected gastroesophageal reflux (GOR) underwent continuous 24 hour esophageal pH-metry and sonography of the gastroesophageal junction. In 29 out of 40 cases (72.5%) GOR was confirmed by the 24 hour pH-monitoring, because of a percentage of total time of reflux of 10% or more. The positive and negative predictive value of sonography versus the result of continuous 24 hour pH-monitoring was 80% and 50% respectively. Sonography cannot be considered a faithful diagnostic tool in screening for GOR in infants.

In a randomized study three methods of obtaining cells for Papanicolaou smears were tested: the classical Ayre spatula, the Ayre spatula plus the endocervical cytobrush and the cervexbrush. Endocervical cells were identified in 67.8% of smears obtained with the Ayre spatula alone, in 89.1% of smears obtained with the Ayre spatula plus the endocervical cytobrush and in 85.6% of smears obtained with the cervexbrush. The use of the Ayre spatula alone for obtaining cervical cells for Papanicolaou smears is discouraged.

Three methods of cervical Pap smear have been studied: the classical spatula, the combination of spatula and cytobrush, and the Cervex-Brush. Thirty-two percent of the spatula smears did not provide endocervical cylinder cells. Significantly better results can be achieved by performing the smear with a combination of spatula and cytobrush (11% without cylinder cells), or with Cervex-Brush (15% without cylinder cells). Cervical smears using a spatula alone are therefore discouraged.