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This is a single-center US case series of 18 infants <90 days old who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These infants had a mild febrile illness without significant pulmonary disease. One-half of the infants were hospitalized; 1 had bacterial urinary tract co-infection. Nasopharyngeal viral loads were notably high. Latinx ethnicity was overrepresented., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We report the complete genome sequence of Clostridium innocuum ATCC 14501, which was isolated in 1962 from an appendiceal abscess. At that time, the isolated strain was designated C. innocuum , given its suspected lack of virulence, but recent reports suggest that C. innocuum is an emerging pathogen., (Copyright © 2020 Cherny et al.)

Here, we report the complete genome sequence of Clostridium innocuum strain LC-LUMC-CI-001. As recently as 2018, C. innocuum was generally considered a benign gastrointestinal microorganism. This strain was isolated from the stool of a patient with recurrent Clostridioides difficile infection-like illnesses., (Copyright © 2020 Cherny et al.)

Fidaxomicin is an oral narrow-spectrum novel 18-membered macrocyclic antibiotic that was initially approved in 2011 by the US FDA for the treatment of Clostridioides difficile infections (CDI) in adults. In February 2020, the FDA approved fidaxomicin for the treatment of CDI in children age >6 months. In adults, fidaxomicin is as efficacious as vancomycin in treating CDI and reduces the risk of recurrent CDI. An investigator-blinded, randomized, multicenter, multinational clinical trial comparing the efficacy and safety of fidaxomicin with vancomycin in children was recently published confirming similar findings as previously reported in adults. Fidaxomicin is the first FDA-approved treatment for CDI in children and offers a promising option for reducing recurrent CDI in this population.

Background: Clostridioides (Clostridium) difficile colonization is common among infants. Serological sequelae of infant C. difficile colonization are poorly understood., Methods: In this prospective cohort study of healthy infants, stools serially collected between ages 1-2 and 9-12 months were tested for non-toxigenic and toxigenic C. difficile (TCD). Cultured isolates underwent whole-genome sequencing. Serum collected at 9-12 months underwent measurement of IgA, IgG, and IgM against TCD toxins A and B and neutralizing antibody (NAb) titers against toxin B. For comparison, antitoxin IgG and NAb were measured in cord blood from 50 mothers unrelated to study infants., Results: Among 32 infants, 16 (50%) were colonized with TCD; 12 were first colonized >1 month before serology measurements. A variety of sequence types were identified, and there was evidence of putative in-home (enrolled siblings) and outpatient clinic transmission. Infants first colonized with TCD >1 month prior had significantly greater serum antitoxin IgA and IgG against toxins A (P = .02 for both) and B (P = .009 and .008, respectively) compared with non-TCD-colonized infants, and greater IgG compared with unrelated cord blood (P = .005). Five of 12 (42%) colonized infants had detectable NAb titers compared with zero non-TCD-colonized infants (P = .02). Breastfeeding was not associated with differences in serological measurements., Conclusions: TCD colonization is associated with a humoral immune response against toxins A and B, with evidence of toxin B neutralization in vitro. The extent and duration of protection against CDI later in life afforded by natural C. difficile immunization events require further investigation., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We investigated the effect of annual winter visitor restrictions on hospital respiratory virus transmission. The healthcare-associated (HA) viral respiratory infection (VRI) transmission index (number of HA VRIs per 100 inpatient community-associated VRIs) was 59% lower during the months in which visitor restrictions were implemented. These data prompt consideration for instituting year-round visitor restrictions., (© The Author(s) 2019. 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.)

Fecal microbiota transplantation (FMT) is efficacious for treatment of recurrent Clostridioides difficile infections (rCDIs). Pediatric experience with FMT for rCDIs is increasing, particularly at large centers. While retrospective studies suggest that FMT is generally safe in the short term, particularly in immunocompetent patients and with rigorous donor screening, additional large prospective studies are needed. This particularly includes those at high risk for infectious complications, such as immunocompromised hosts. Further, long-term implications of altering the intestinal microbiome with FMT are not well understood. The role of FMT in children, particularly in high-risk patients, will require continual reexamination with future availability of pediatric safety and efficacy data. This review summarizes key points for infectious diseases physicians to consider when evaluating a child for FMT., (© The Author(s) 2019. 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: National guidelines recommend oral vancomycin over oral metronidazole as first-line treatment for nonsevere Clostridioides difficile infection (CDI) in adults. Guidelines recommend metronidazole for children with nonsevere CDI, emphasizing that comparative effectiveness studies comparing the relative efficacy of vancomycin and metronidazole are lacking in children., Method: We conducted an observational study of hospitalized children with nonsevere CDI treated with metronidazole versus vancomycin using an inverse probability of treatment-weighted propensity-score analysis. All of the following criteria had to be present for children with positive CDI testing for study eligibility: (1) ≥3 new-onset unformed stools within a 24-hour period; (2) 2-17 years of age; (3) hospitalization for ≥48 hours for CDI; (4) no laxative use ≤48 hours; (5) no alternate etiology for diarrhea; (6) no previous episode of CDI ≤3 months; (7) no concurrent non-CDI-targeted antibiotic therapy, and (8) no severe or fulminant CDI., Results: One hundred ninety-two patients met eligibility criteria; 141 (73.4%) received oral metronidazole and 51 (26.6%) children received oral vancomycin. Baseline characteristics were similar between the 2 groups in the weighted cohort. Of 141 patients, 101 (71.7%) children receiving metronidazole had clinical improvement by day 5, whereas 44 of 51 (86.3%) cases resolved with vancomycin (odds ratio, 0.40; 95% confidence interval, 0.17-0.97; P = .04). The odds of CDI recurrence within 12 weeks were similar between the groups., Conclusions: Our study suggests that children with nonsevere CDI have earlier resolution of clinical symptoms when prescribed vancomycin compared with metronidazole. Large interventional studies are necessary to evaluate the reproducibility of our findings., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Clostridioides (Clostridium) difficile infection (CDI) in pediatric solid organ transplant (SOT) recipients is a growing problem, though CDI risk factors in this population are poorly understood. Our objective was to characterize CDI risk factors in pediatric SOT recipients., Methods: This retrospective case-control study, performed at a single freestanding academic children's hospital, included all SOT recipients age 1-22 years who were tested for C. difficile by toxin B gene PCR between August 2009 and August 2017. CDI risk factors were assessed by comparing PCR-positive and PCR-negative cases by generalized linear mixed models., Results: Between August 2009 and August 2017, 409 SOTs were performed of which 138 (33.7%), 134 (32.8%), 131 (32.0%), and 6 (1.5%) were kidney, liver, heart, and small intestine transplants, respectively. Of 205 SOT recipients were tested for CDI, with 723 C. difficile PCR tests performed among these patients. 68/205 (33%) patients developed CDI at least once during the study period. Median (interquartile range) time to diagnosis of first CDI following SOT was 8.9 (1.2, 19.6) months. CDI was independently associated with calcineurin inhibitor use at time of C. difficile testing (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.08, 5.24, P = 0.03) and systemic antibiotic exposure within 30 days of C. difficile testing (OR 1.74, 95% CI 1.08, 2.79, P = 0.02)., Conclusions: CDI is a common, relatively late post-transplant complication and independently associated with calcineurin inhibitor and systemic antibiotic exposure. The potential impact of specific immunosuppressive drug and antibiotic selection on CDI risk reduction requires further investigation., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Whole-genome sequencing (WGS) is a highly sensitive method for identifying genetic relatedness and transmission of Clostridioides difficile strains. Previous studies suggest that as few as 3 core genome single-nucleotide variants (SNVs) discriminate between genetically distinct isolates. Because a single C. difficile colony is selected from culture for WGS, significant within-host genetic diversity could preclude identification of transmission events. To evaluate the likelihood of missed transmission events using WGS of single colonies from culture, we examined within-host genetic diversity among C. difficile isolates collected from children. We performed WGS using an Illumina MiSeq instrument on 8  C. difficile colonies randomly selected from each culture performed on stool collected from 10 children (8 children diagnosed with C. difficile infection and 2 children with asymptomatic carriage); 77/80 (96%) isolate sequences were successfully assembled. Among 8/10 (80%) children, all isolates were the same sequence type (ST). The other 2 children each had mixed infection with two STs, although one ST predominated. Among 9/10 (90%) children, isotypic isolates differed by ≤2 SNVs; an isotypic isolate in the remaining child differed by 3 to SNVs relative to the other isolates from that child. Overall, among the 77 isolates collected from 10 stool cultures, 74/77 (96%) were clonal (i.e., same ST and ≤2 core genome SNVs) to other isolates in stool culture. In summary, we identified rare C. difficile within-host genetic diversity in children, suggesting that WGS of a single colony from stool is likely to appropriately characterize isolate clonality and putative transmission events in the majority of cases., (Copyright © 2019 American Society for Microbiology.)

Objective: To characterize healthcare provider diagnostic testing practices for identifying Clostridioides (Clostridium) difficile infection (CDI) and asymptomatic carriage in children., Design: Electronic survey., Methods: An 11-question survey was sent by e-mail or facsimile to all pediatric infectious diseases (PID) members of the Infectious Diseases Society of America's Emerging Infections Network (EIN)., Results: Among 345 eligible respondents who had ever responded to an EIN survey, 196 (57%) responded; 162 of these (83%) were aware of their institutional policies for CDI testing and management. Also, 159 (98%) respondents knew their institution's C. difficile testing method: 99 (62%) utilize NAAT without toxin testing and 60 (38%) utilize toxin testing, either as a single test or a multistep algorithm. Of 153 respondents, 10 (7%) reported that formed stools were tested for C. difficile at their institution, and 76 of 151 (50%) reported that their institution does not restrict C. difficile testing in infants and young children. The frequency of symptom- and age-based testing restrictions did not vary between institutions utilizing NAAT alone compared to those utilizing toxin testing for C. difficile diagnosis. Of 143 respondents, 26 (16%) permit testing of neonatal intensive care unit patients and 12 of 26 (46%) treat CDI with antibiotics in this patient population., Conclusions: These data suggest that there are opportunities to improve CDI diagnostic stewardship practices in children, including among hospitals using NAATs alone for CDI diagnosis in children.

Background: Implementing matrix-assisted laser desorption ionization-time of flight and multiplex polymerase chain reaction has been associated with decreased mortality and hospital length of stay in adults, but the impact in pediatrics is less understood., Methods: This pre-post quasi-experimental study compared antibiotic prescribing for positive blood cultures in patients ≤21 years of age collected in 2012 (preintervention) and in 2015 (after matrix-assisted laser desorption ionization-time of flight/multiplex polymerase chain reaction). Time to effective and optimal antimicrobial therapy was evaluated using Cox proportional hazards regression. Time to ideal optimal therapy was estimated as the earliest potential initiation of optimal therapy. Antibiotic use and clinical outcomes were measured., Results: There were 242 and 192 positive monomicrobial blood cultures in 2012 and 2015, respectively. Postintervention, time to optimal therapy (73.8 vs. 48.8 hours; P < 0.001) and organism identification (55.6 vs. 29.5 hours; P < 0.001) were reduced, and patients were more likely to receive optimal therapy by 7 days (hazard ratio, 1.85; P < 0.001). In the ideal scenario in 2015, there was an 8.8-hour delay in initiating optimal therapy based on the time that sufficient microbiologic data were available. Postintervention, time to effective therapy (2.8 vs. 2.7 hours; P = 0.782) and clinical outcomes did not differ. Unnecessary antibiotic duration for probable contaminants (skin flora) (43.1 vs. 29.7 hours; P = 0.027), vancomycin for methicillin-sensitive Staphylococcus aureus (54.0 vs. 41.3 hours; P = 0.008) and nonpenicillin/ampicillin antibiotics for group A Streptococcus, group B Streptococcus and Enterococcus faecalis (87.2 vs. 33.4 hours; P < 0.001) were reduced postintervention., Conclusions: Rapid diagnostics reduced time to optimal antimicrobial therapy and unnecessary antibiotic use without worse clinical outcomes.

Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.

Restriction endonuclease analysis (REA) and PCR ribotyping are two typing systems that have been frequently utilized for molecular epidemiologic characterization of Clostridioides (Clostridium) difficile. To correlate typing data obtained from each method, we performed both REA and PCR ribotyping on a large and diverse set of historical and contemporary C. difficile infection clinical isolates. Eighty isolates were selected from each reference laboratory in the United States (Microbiology Reference Laboratory, Hines VA Medical Center) and United Kingdom (Clostridium difficile Network for England and Northern Ireland laboratory, University of Leeds). The 160 isolates were assigned to 82 unique ribotypes and 51 unique REA groups (116 unique REA types). In general, concordance between typing methods was good. Dendrogram analysis of PCR ribotype band patterns demonstrated close genetic relationships among strain types with discordant REA and ribotype assignments. While REA typing was more discriminatory, several REA types in this study were further discriminated by PCR ribotyping, indicating that discriminatory value of these typing methods may be strain dependent. These data will assist with molecular epidemiologic surveillance of strains identified by these two commonly used C. difficile typing systems., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Traditional antibiograms can guide empiric antibiotic therapy, but they may miss differences in resistance across patient subpopulations. In this retrospective descriptive study, we constructed and validated antibiograms using International Classification of Disease, Tenth Revision (ICD-10) codes and other discrete data elements to define a cohort of previously healthy children with urinary tract infections. Our results demonstrate increased antibiotic susceptibility. This methodology may be modified to create other syndrome-specific antibiograms.

Background: Fidaxomicin is an approved therapy for Clostridium difficile-associated diarrhea (CDAD) in adults. The safety of fidaxomicin in children has not been reported., Methods: In this study (ClinicalTrials.gov identifier NCT01591863), pediatric patients with CDAD received twice-daily oral fidaxomicin at a dose of 16 mg/kg per day (up to 200 mg) for 10 days in an open-label study. Plasma and fecal samples were collected for pharmacokinetic assessments. The primary outcome measure was safety, which was assessed by adverse-event (AE), laboratory, and physical examination/vital-sign monitoring. Efficacy was determined through early and sustained clinical response rates (clinical response without recurrence of CDAD)., Results: The study enrolled 40 patients (11 months to 17 years of age), many with underlying comorbidity, including neoplasm (23.7%), gastrointestinal disorder (78.9%), and history of CDAD (60.5%). Plasma fidaxomicin and OP-1118 (the major fidaxomicin metabolite) 3- to 5-hour postdose concentrations were 0.6 to 87.4 and 2.4 to 882.0 ng/mL, respectively, and no age-related trends were seen. Fecal fidaxomicin concentrations within 24 hours of the last dose averaged 3228 µg/g, and higher concentrations and greater variability in the youngest age group were found. AEs were reported in 73.7% of the patients; most of them were mild (44.7%) to moderate (21.1%) and were considered treatment-related in 15.8% of the patients. Overall, the early clinical response rate was 92.1%. The rate of sustained clinical response (clinical response without recurrence through 28 days after treatment) was 65.8% overall., Conclusions: Fidaxomicin was well tolerated in children with CDAD and has a pharmacokinetic profile in children similar to that in adults. The clinical response rate was high.

Background: Although pediatric Clostridium difficile infections (CDIs) are increasing, C. difficile transmission patterns among children are poorly understood., Methods: We performed whole genome sequencing (WGS) on C. difficile isolates collected from children diagnosed with CDI between December 2012 and December 2013 at a single academic medical center. Genome sequences of isolates from CDIs diagnosed ≥8 weeks after study initiation were compared to all study isolate genome sequences. Among patients with isogenic isolates (≤2-3 core genome single nucleotide variants [SNVs] identified by pairwise SNV analyses), common inpatient and/or outpatient healthcare exposures were investigated., Results: Among 131 CDIs in 107 children, WGS identified 104 genetically distinct isolates. Of 84 incident CDIs occurring ≥8 weeks after study initiation, only 10 (11.9%) were caused by a strain isogenic to another cohort CDI isolate (putative transmission events). Proportions of each CDI class putatively associated with transmission were hospital-onset healthcare facility-associated (HCFA), 2/16 (12.5%); community-onset HCFA, 1/17 (5.9%); indeterminate, 1/11 (9.1%); community-associated (CA), 5/40 (12.5%); and recurrent, 1/21 (4.8%). Transmission events among CA and HCFA CDIs were similarly infrequent (5/40 [12.5%] vs 3/33 [9.1%]; P = .64). Shared healthcare facility exposures were only identified among 7/10 putative transmission events. Potential community transmission (same postal code) was not identified., Conclusions: WGS identified a highly diverse group of C. difficile isolates among children with CDI, including those with HCFA CDI. Clostridium difficile transmission among symptomatic children was very uncommon. Among putatively transmitted cases, investigation of shared healthcare exposures often did not identify a potential transmission source.

Antimicrobial stewardship can be challenging in children with bloodstream infections (BSIs) caused by Gram-negative bacilli (GNB). This retrospective cohort study explored how data elements in the electronic health record could potentially optimize empiric antibiotic therapy for BSIs caused by GNB, via the construction of customized antibiograms for categorical GNB infections and identification of opportunities to minimize organism-drug mismatch and decrease time to effective therapy. Our results suggest potential strategies that could be implemented at key decision points in prescribing at initiation, modification, and targeting of therapy., (Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Clostridium difficile strain DH/NAP11/106, a relatively antibiotic-susceptible strain, is now the most common cause of C. difficile infection (CDI) among adults in the USA., Objectives: To identify mechanisms underlying the evolution and transmission of an MDR DH/NAP11/106 clone., Methods: WGS (Illumina MiSeq), restriction endonuclease analysis (REA) and antibiotic susceptibility testing were performed on 134 C. difficile isolates collected from paediatric patients with CDI over a 2 year period., Results: Thirty-one of 134 (23%) isolates were REA group DH. Pairwise single-nucleotide variant (SNV) analyses identified a DH clone causing seven instances of CDI in two patients. During the 337 days between the first and second CDI, Patient 1 (P1) received 313 days of antibiotic therapy. Clindamycin and rifaximin resistance, and reduced vancomycin susceptibility (MIC 0.5-2 mg/L), were newly identified in the relapsed isolate. This MDR clone was transmitted to Patient 2 (P2) while P1 and P2 received care in adjacent private rooms. P1 and P2 each developed two additional CDI relapses. Comparative genomics analyses demonstrated SNVs in multiple antibiotic resistance genes, including rpoB (rifaximin resistance), gyrB and a gene encoding PBP; gyrB and PBP mutations did not consistently confer a resistance phenotype. The clone also acquired a 46 000 bp genomic element, likely a conjugative plasmid, which contained ermB (clindamycin resistance). The element shared 99% identity with the genomic sequence of Faecalibacterium prausnitzii, an enteric commensal., Conclusions: These data highlight the emergence of MDR in C. difficile strain DH/NAP11/106 through multiple independent mechanisms probably as a consequence of profound antibiotic pressure.

Clostridium difficile PCR ribotype 106 (also identified as restriction endonuclease analysis [REA] group DH) recently emerged as the most common strain causing C. difficile infection (CDI) among US adults. We previously identified this strain predominating our pediatric cohort. Pediatric clinical CDI isolates previously characterized by REA underwent antibiotic resistance testing and whole genome sequencing. Of 134 isolates collected from children, 31 (23%) were REA group DH. We performed a comparative genomics analysis to identify DH-associated accessory genes. We identified five DH-associated genes that are associated with virulence in other bacterial species but not previously known to contribute to CDI. These genes are associated with intestinal mucosal adhesion (collagen-binding surface protein), sporulation (sporulation integral membrane protein YtvI), and protection from oxidative stress and foreign DNA (DNA phosphorothioation-dependent restriction proteins, sulfurtransferase, and DNA sulfur modification proteins). The association of these genes was validated in a cohort of 623 publicly available C. difficile sequences, 10 (1.6%) of which were monophyletic to REA group DH through in silico multilocus sequence typing and core genome phylogenetic analysis. Further investigation is required to determine the contribution of these genes to the emergence and virulence of this epidemic strain., (Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Transitioning from administration of monthly palivizumab to a single dose at discharge was associated with substantial pharmacy cost savings. With the concurrent adoption of private hospital rooms and visitor restriction policies, hospital-wide and neonatal intensive care unit healthcare-associated respiratory syncytial virus infections decreased following these changes. Infect Control Hosp Epidemiol 2018;39:485-487.

Background: Prompt central venous catheter (CVC) removal is currently recommended in children with Staphylococcus aureus central line-associated bloodstream infection (CLABSI). Our objective was to examine the outcome of attempted line salvage in children with S. aureus CLABSI and assess predictors of success., Methods: A single-institution, retrospective cohort study was performed of all children with S. aureus CLABSI between 2012 and 2015. Patients with and without immediate CVC removal (≤ 2 days after first positive culture) were compared. The primary outcome was failed CVC salvage (removal after 3+ days)., Results: Seventy-seven children met criteria for S. aureus CLABSI. Immediate CVC removal was performed in 27.3% of patients. Among the 72.7% patients in whom CVC salvage was attempted, 78.6% were successful and 21.4% required delayed CVC removal. Malignancy, short gut syndrome, neutropenia, methicillin-resistant S. aureus, and line type were not associated with salvage failure. No associated morbidity or mortality occurred in patients with a failed salvage attempt. New or recurrent bacteremia occurred in five patients, but three were successfully salvaged a second time., Conclusions: CVC salvage was feasible in the majority of children with S. aureus CLABSI and was not associated with significant complications or attributable mortality as reported in adults.

We report here the complete genome sequence of Clostridioides difficile strain DH/NAP11/106/ST-42, which is now the most common strain causing C. difficile infection among U.S. adults. This strain was isolated from the stool from a hospitalized pediatric patient with frequent relapses of C. difficile infection., (Copyright © 2017 Ozer et al.)

Background.: Although Clostridium difficile infections (CDIs) are increasingly diagnosed in children, many children diagnosed with CDI lack classic risk factors. Frequent use of highly sensitive tcdB polymerase chain reaction (PCR) testing in low-risk patients leads to CDI misdiagnosis and unnecessary CDI antibiotic use in children with C difficile carriage., Methods.: For this quasi-experimental study, we developed and implemented an educational intervention (EI) to inform healthcare providers (HCPs) about tcdB PCR test limitations. We provided HCP didactic education and built an electronic notification into the tcdB PCR test order that describes scenarios in which carriage is more likely than CDI. Segmented regression analysis assessed changes in level (ie, overall rates) and trend of C difficile testing rate ([TR] number of tests performed per 1000 patient encounters) and test positivity rate ([PR] number of positive tests per 1000 patient encounters) between the pre- (August 2009-August 2013) and postintervention (February 2014-July 2015) periods., Results.: Hospital-wide, absolute TR reduction was 0.71 (P[level] = .0067; P[trend] = .0042) and absolute PR reduction was 0.14 (P[level] = .22; P[trend] = .018). In the outpatient setting, absolute TR reduction was 0.30 (P[level] = .0015; P[trend] < .001) and absolute PR reduction was 0.09 (P[level] = .0069; P[trend] = .046). The incidence density of healthcare facility-associated CDI did not significantly change after the EI. The EI was associated with avoidance of 574 tests and 113 positive tests (and subsequent antibiotic courses) during the postintervention period, which saved approximately $250 000 in patient charges related to CDI testing and treatment., Conclusions.: Healthcare provider education can cost-effectively reduce the frequency of C difficile testing and CDI misdiagnosis by improving test utilization among low-risk children., (© The Author 2016. 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.)

Because nucleic acid amplification tests (NAATs) do not distinguish Clostridium difficile infection (CDI) and asymptomatic C. difficile carriage, the diagnostic predictive value of NAATs is limited when used in patients with a low probability of CDI. In this issue of the Journal of Clinical Microbiology , Truong et al. (J. Clin. Microbiol., 55:1276-1284, 2017, https://doi.org/10.1128/JCM.02319-16) report significant reductions in hospital-onset CDI and oral vancomycin utilization at their institution following implementation of a novel intervention that leveraged their clinical bioinformatics resources to prevent C. difficile testing of stools from patients without clinically significant diarrhea and in patients with recent laxative use., (Copyright © 2017 American Society for Microbiology.)

The rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinolone-resistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P = 0.003); rifaximin, 1.6% and 6.7% (P = 0.11); clindamycin, 18.9% and 25.3% (P = 0.29); and moxifloxacin, 2.5% and 36% (P = <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P = <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

This Review summarizes the latest advances in the treatment and prevention of Clostridium difficile infection (CDI), which is now the most common health-care-associated infection in the USA. As traditional, standard CDI antibiotic therapies (metronidazole and vancomycin) are limited by their broad spectrum and further perturbation of the intestinal microbiota, which result in unacceptably high recurrence rates, novel therapeutic strategies for CDI are needed. Emerging CDI therapies are focused on limiting further perturbation of the intestinal microbiota and/or restoring the microbiota to its pre-morbid state, reducing colonization of the intestinal tract by toxigenic strains of C. difficile and bolstering the host immune response against C. difficile toxins. Fidaxomicin is associated with reduced CDI recurrences, and other emerging narrow-spectrum CDI antibiotic therapies might eventually demonstrate a similar benefit. Prevention of intestinal colonization of toxigenic strains of C. difficile can be achieved through restoration of the intestinal microbiota with faecal microbiota transplantation, as well as by colonizing the gut with nontoxigenic C. difficile strains. Finally, emerging immunological therapies, including monoclonal antibodies and vaccines against C. difficile toxins, might protect against CDI and subsequent CDI recurrences. The available clinical data for these emerging therapies, and their relative advantages and disadvantages, are described.

Background: Most children with Clostridium difficile infection (CDI) experience community onset of CDI symptoms., Methods: We retrospectively compared hospital-onset healthcare facility-associated CDI cases to community-associated (CA) CDI cases diagnosed by Cepheid Xpert tcdB polymerase chain reaction (PCR) at an academic children's hospital over a 1-year period. Saved stools from CDI cases additionally underwent anaerobic stool culture and multiplex gastrointestinal pathogen PCR testing., Results: Compared with 25 hospital-onset healthcare facility-associated CDI cases, the 74 CA-CDI cases were more frequently <2 years old (18% vs. 0%, P = 0.034) and less frequently had antibiotic exposure in the past 30 days (26% vs. 88%, P < 0.0001), proton pump inhibitor exposure (16% vs. 36%, P = 0.036) or a gastrostomy tube (11% vs. 32%, P = 0.013). Among children diagnosed with CA-CDI, 19 (26%) had no identified CDI risk factors (immunocompromised; gastrostomy tube; recent antibiotic, proton pump inhibitor or inpatient/outpatient healthcare exposures). Clinical testing for viral pathogens was uncommon among children thought to have CA-CDI. Multiplex PCR testing of saved stool samples failed to identify C. difficile among 23% of cases diagnosed with CA-CDI by the Cepheid Xpert tcdB PCR assay. CDI antibiotic therapy was provided to nearly all patients testing positive by tcdB PCR irrespective of CDI risk factors., Conclusions: Many children diagnosed with CA-CDI by PCR lack CDI risk factors and have discordant results when additional CDI testing methods are performed, suggesting overdiagnosis of CDI in children with community-onset diarrhea. More selective CDI testing of low-risk pediatric patients is needed to more accurately diagnose CDI and limit unnecessary CDI antibiotic treatment in children.

Clostridium difficile strain BI/NAP1/027 is associated with increased C. difficile infection (CDI) rates and severity, and the efficacy of some CDI therapies may be strain dependent. Although cultured C. difficile isolates can be reliably subtyped by various methods, the long turnaround times, high cost, and limited availability of strain typing preclude their routine use. Nucleic acid amplification tests identify BI/NAP1/027 rapidly from stool, but the emergence of closely related strains compromises test specificity. Although detection of epidemiologically significant pathogens is generally useful for infection control programs, specific data supporting use of rapid detection of BI/NAP1/027 as an infection control tool are still awaited., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Severe and severe complicated Clostridium difficile infections (SCDI/SCCDI) were retrospectively assessed in a pediatric cohort. Underlying medical conditions and concomitant medical therapy preclude accurate classification of children with SCDI/SCCDI, using current CDI severity definitions. Revised CDI definitions in children should focus on more objective, age-appropriate, and CDI-specific markers of severity., (© The Author 2014. 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.)

The 2014-2015 Ebola virus disease (EVD) epidemic and international public health emergency has been referred to as a "black swan" event, or an event that is unlikely, hard to predict, and highly impactful once it occurs. The Chicago Ebola Response Network (CERN) was formed in response to EVD and is capable of receiving and managing new cases of EVD, while also laying the foundation for a public health network that can anticipate, manage, and prevent the next black swan public health event. By sharing expertise, risk, and resources among 4 major academic centers, Chicago created a sustainable network to respond to the latest in a series of public health emergencies. In this respect, CERN is a roadmap for how a region can prepare to respond to public health emergencies, thereby preventing negative impacts through planning and implementation., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To identify risk factors for recurrent Clostridium difficile infection (RCDI) in children., Study Design: A nested case-control study was performed to identify RCDI risk factors using a pediatric cohort of inpatients and outpatients diagnosed with Clostridium difficile infection by tcdB polymerase chain reaction (PCR) at an academic children's hospital between December 9, 2012, and June 30, 2014. Strict inclusion criteria were adopted to limit selection bias related to inappropriate inclusion of patients with probable C difficile colonization., Results: Thirty children with RCDI were compared with 94 children with non-RCDI. Statistically significant associations were identified between RCDI and malignancy (OR 2.8, 95% CI 1.0-7.4, P = .044), tracheostomy tube dependence (OR 5.2, 95% CI 1.1-24.7, P = .037), and tcdB PCR cycle threshold (OR 0.87, 95% CI 0.78-0.97, P = .01) using multivariable logistic regression modeling. The receiver operator characteristic curve for PCR cycle threshold as a predictor of RCDI demonstrated area under the curve = 0.67. The highest predictive rate (75%) for RCDI was demonstrated at cycle threshold cutpoint ≤ 20. The difference between sensitivity (64%) and specificity (68%) was minimized at cycle threshold cutpoint ≤ 23. Compared with controls with non-RCDI, children excluded because of probable C difficile colonization had a similar cycle threshold value (27.5 vs 27.2, P = .77)., Conclusions: Malignancy and tracheostomy tube dependence were identified as RCDI risk factors. Although RCDI was associated with positivity at a lower tcdB PCR cycle threshold, the clinical utility of cycle threshold as a tool to predict recurrence was limited. Better methods to predict RCDI are needed to prioritize pediatric populations to target for RCDI prevention efforts., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The molecular epidemiology of pediatric Clostridium difficile infection (CDI) is poorly understood. We aimed to identify the restriction endonuclease analysis (REA) groups causing CDI and to determine risk factors and outcomes associated with CDI caused by epidemic strains in children., Design: Retrospective cohort study., Patients: Inpatients and outpatients >1 year old receiving care between December 2012 and December 2013., Setting: An academic children's hospital in Chicago, Illinois., Methods: C. difficile PCR-positive stools were cultured, and C. difficile isolates were typed by REA. REA of isolates from patients with multiple CDIs was performed to differentiate relapse (infection with same strain) from reinfection (different strains) irrespective of time between CDIs., Results: A total of 189 CDIs occurred among 145 patients. REA groups were widely distributed. The BI/NAP1/027 strain caused CDI in only 1 patient. DH/NAP11/106, the predominant epidemic strain identified, was associated with the use of third- or fourth-generation cephalosporins (risk ratio [RR], 3.2; 95% confidence interval [CI], 1.1-9.9; P=.04). CDI relapse commonly occurred up to 20 weeks later. Compared with CDI caused by non-DH/NAP11/106 strains, CDI caused by DH/NAP11/106 was more likely to result in multiple CDI relapses (40% vs 8%; P=.05) among children with multiple CDIs., Conclusions: REA identified the exceedingly low prevalence of BI/NAP1/027 and the high prevalence of DH/NAP11/106, a common epidemic strain in the United Kingdom that is less often reported in the United States. CDI relapse commonly occurred up to 20 weeks from the previous CDI. Defining recurrent CDI as that occurring only within 8 weeks of the original infection may lead to misclassification of some recurrent CDIs as new CDIs in children.

To assess national variability in methods of identifying and preventing Clostridium difficile infection (CDI) in pediatric populations, an anonymous survey was sent to hospital epidemiologists at US children's hospitals. Data from 30 hospitals indicate substantial variability in surveillance, testing, and infection control strategies, which may limit reliable interfacility comparison of CDI rates. In addition, only 60% of respondents perform surveillance for community-associated CDI., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Background/aims: P450c17 deficiency is an uncommon steroidogenic disorder that typically presents as a sexually infantile adolescent phenotypic female with hypertension and hypokalemia. Although cortisol synthesis is impaired, elevated corticosterone and deoxycorticosterone ordinarily prevent adrenal insufficiency. Thus, diagnosis prior to puberty is rare. We report novel clinical features of an infant with complete P450c17 deficiency due to two novel mutations in CYP17A1., Methods: A 10-week-old, 46,XY phenotypic female presented with hypotension, developed hypokalemic hypertension post-resuscitation, then hyperkalemic hyponatremia upon weaning salt supplements. All CYP17A1 exons of the proband and parents were PCR-amplified and sequenced. Cosyntropin, GnRH agonist, and hCG tests were performed., Results: Sequencing demonstrated compound heterozygosity for two novel CYP17A1 mutations, C327dupT and C362G>A (W121X), both generating premature stop codons in exon 2 and predicting non-functional enzymes. Plasma corticosterone was very elevated, deoxycorticosterone normal, cortisol detectable, and aldosterone low-normal at baseline. Responses to cosyntropin of corticosterone and progesterone were elevated, deoxycorticosterone and aldosterone normal, cortisol subnormal, and 17α-hydroxycorticosteroid intermediates undetectable. GnRH agonist/hCG testing showed no androgenic response., Conclusion: This is the first report of P450c17 deficiency presenting in a 46,XY female infant with hypotensive shock, a state exacerbated by the atypical absence of deoxycorticosterone elevation., (Copyright © 2011 S. Karger AG, Basel.)

Background: After heart transplant (HTX), the heart is completely denervated. While sympathetic reinnervation is likely to occur, there is conflicting evidence regarding parasympathetic reinnervation. Accordingly, it is unclear if atropine is efficacious as a chronotropic agent in HTX patients undergoing dobutamine stress echocardiography (DSE), since cholinergic cardiac stimulation is required for atropine to exert its effect. The purpose of this study was to demonstrate that atropine can sufficiently increase the heart rate (HR) in HTX patients undergoing DSE., Methods: A retrospective review was performed on 68 HTX patients who underwent DSE as part of their routine annual HTX follow-ups. Dobutamine was administered in the standard fashion of 10, 20, 30, 40, 50 mcg/kg per minute with blood pressure and electrocardiographic monitoring. If target HR was not attained, atropine was administered to aid in achieving 85% of maximum age-predicted HR., Results: Mean patient age was 58 +/- 10 years. Mean period since transplant was 9 +/- 4 years. Forty-seven (69%) patients received dobutamine only, and 21 (31%) required additional atropine to reach target HR. Of the 21 patients who received atropine, 10 (48%) reached target HR. Neither time from transplant, age, gender, resting HR, medications, nor atherosclerotic risk factors predicted responsiveness to atropine. Those responding to dobutamine had a significantly greater resting HR than those receiving additional atropine., Conclusions: The adjunctive use of atropine in HTX patients during DSE aids in reaching 85% of maximum predicted HR in some patients. Furthermore, resting HR may predict the additional need of atropine during DSE.