Experience With a Vancomycin-sparing Empiric Antibiotic Guideline for Late-onset Sepsis in a Level-4 Neonatal Intensive Care Unit.

A vancomycin-sparing guideline for suspected late-onset sepsis helped reduce vancomycin usage in our level-4 neonatal intensive care unit. Significant reduction in overall vancomycin use, with its likely unit-wide beneficial downstream effects, may need to be measured against the rare case of methicillin-resistant Staphylococcus aureus infection and delayed effective therapy.

Cefazolin and Carbapenem Combination to Treat Persistent Methicillin-sensitive Staphylococcus aureus Bacteremia in Preterm Infants.

Encouraged by bacteremia clearance using antistaphylococcal beta-lactams plus carbapenem combination in adults with refractory methicillin-sensitive Staphylococcus aureus infection, we present our experience with 2 preterm infants and review 1 previously published case. Noted successful bacteremia clearance in all 3 must be weighed against possible adverse effects associated with carbapenem use.

Gut microbiome perturbation, antibiotic resistance, and Escherichia coli strain dynamics associated with international travel: a metagenomic analysis.

BACKGROUND: Culture-based studies have shown that acquisition of extended-spectrum ß-lactamase-producing Enterobacterales is common during international travel; however, little is known about the role of the gut microbiome before and during travel, nor about acquisition of other antimicrobial-resistant organisms. We aimed to identify (1) whether the gut microbiome provided colonisation resistance against antimicrobial-resistant organism acquisition, (2) the effect of travel and travel behaviours on the gut microbiome, and (3) the scale and global heterogeneity of antimicrobial-resistant organism acquisition. METHODS: In this metagenomic analysis, participants were recruited at three US travel clinics (Boston, MA; New York, NY; and Salt Lake City, UT) before international travel. Participants had to travel internationally between Dec 8, 2017, and April 30, 2019, and have DNA extractions for stool samples both before and after travel for inclusion. Participants were excluded if they had at least one low coverage sample (<1 million read pairs). Stool samples were collected at home before and after travel, sent to a clinical microbiology laboratory to be screened for three target antimicrobial-resistant organisms (extended-spectrum ß-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales), and underwent DNA extraction and shotgun metagenomic sequencing. We profiled metagenomes for taxonomic composition, antibiotic-resistant gene content, and characterised the Escherichia coli population at the strain level. We analysed pre-travel samples to identify the gut microbiome risk factors associated with acquisition of the three targeted antimicrobial resistant organisms. Pre-travel and post-travel samples were compared to identify microbiome and resistome perturbation and E coli strain acquisition associated with travel. FINDINGS: A total of 368 individuals travelled between the required dates, and 296 had DNA extractions available for both before and after travel. 29 travellers were excluded as they had at least one low coverage sample, leaving a final group of 267 participants. We observed a perturbation of the gut microbiota, characterised by a significant depletion of microbial diversity and enrichment of the Enterobacteriaceae family. Metagenomic strain tracking confirmed that 67% of travellers acquired new strains of E coli during travel that were phylogenetically distinct from their pre-travel strains. We observed widespread enrichment of antibiotic-resistant genes in the gut, with a median 15% (95% CI 10-20, p<1 × 10-10) increase in burden (reads per kilobase per million reads). This increase included antibiotic-resistant genes previously classified as threats to public health, which were 56% (95% CI 36-91, p=2 × 10-11) higher in abundance after travel than before. Fluoroquinolone antibiotic-resistant genes were aquired by 97 (54%) of 181 travellers with no detected pre-travel carriage. Although we found that visiting friends or relatives, travel to south Asia, and eating uncooked vegetables were risk factors for acquisition of the three targeted antimicrobial resistant organisms, we did not observe an association between the pre-travel microbiome structure and travel-related antimicrobial-resistant organism acquisition. INTERPRETATION: This work highlights a scale of E coli and antimicrobial-resistant organism acquisition by US travellers not apparent from previous culture-based studies, and suggests that strategies to control antimicrobial-resistant organisms addressing international traveller behaviour, rather than modulating the gut microbiome, could be worthwhile. FUNDING: US Centers for Disease Control and Prevention and National Institute of Allergy and Infectious Diseases.

Congenital Tuberculosis After In Vitro Fertilization: A Case for Tuberculosis Screening of Women Evaluated for Infertility.

We report a case of multidrug-resistant congenital tuberculosis (TB) in an infant conceived by in vitro fertilization and review 22 additional infant-mother pairs in the literature. Females evaluated for infertility should be screened for TB risk, and those at risk require a TB-specific diagnostic evaluation before receiving assisted reproductive treatment.

Travel-associated extensively drug-resistant typhoid fever: a case series to inform management in non-endemic regions.

BACKGROUND: Extensively drug-resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem and encourage preventive interventions as well as appropriate empiric antimicrobial use. METHODS: Cases were extracted from the GeoSentinel database, microbiologic laboratory records of two large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin and trimethoprim-sulfamethoxazole. RESULTS: Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1) and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only one patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhoea. Antimicrobial therapy was started on Day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2 days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR S. typhi phenotype, and whole genome sequencing on three isolates confirmed their belonging to the XDR variant of the H58 clade. CONCLUSIONS: XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for visiting friends and relatives travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology.

Utility of Methicillin-Resistant Staphylococcus aureus Nares Screening in Hospitalized Children with Acute Infectious Disease Syndromes.

Studies in adults support the use of a negative methicillin-resistant Staphylococcus aureus (MRSA) nares screening (MNS) to help limit empiric anti-MRSA antibiotic therapy. We aimed to evaluate the use of MNS for anti-MRSA antibiotic de-escalation in hospitalized children (<18 years). Records of patients admitted between 1 January 2015 and 31 December 2020 with a presumed infectious diagnosis who were started on anti-MRSA antibiotics, had a PCR-based MNS, and a clinical culture performed were retrospectively reviewed. A total of 95 children were included with a median age (range) of 2 (0-17) years. The top three diagnosis groups were skin and soft tissue infections (n = 38, 40%), toxin-mediated syndromes (n = 17, 17.9%), and osteoarticular infections (n = 14, 14.7%). Nasal MRSA colonization and growth of MRSA in clinical cultures was found in seven patients (7.4%) each. The specificity and the negative predictive value (NPV) of the MNS to predict a clinical MRSA infection were both 95.5%. About half (n = 55, 57.9%) had anti-MRSA antibiotics discontinued in-house. A quarter (n = 14, 25.5%) were de-escalated based on the negative MNS test alone, and another third (n = 21, 38.2%) after negative MNS test and negative culture results became available. A high NPV suggests that MNS may be useful for limiting unnecessary anti-MRSA therapy and thereby a useful antimicrobial stewardship tool for hospitalized children. Prospective studies are needed to further characterize the utility of MNS for specific infectious diagnoses.

A tale of caution: prolonged Bacillus clausii bacteraemia after probiotic use in an immunocompetent child.

INTRODUCTION: Bacillus clausii as a probiotic supplement is increasingly used in both adult and paediatric patient populations. There is limited awareness about potential adverse effects. CASE PRESENTATION: We report a case of prolonged (111 days) B. clausii bacteraemia after brief probiotic use in a 17-month-old immunocompetent child, without a definite focus of infection and in the absence of predisposing risk factors or underlying co-morbidities. We identified seven probiotic use-associated cases of prolonged B. clausii bacteraemia (mean duration [range] 64 days [14-93 days] where data were available) in the literature, all with underlying co-morbidities. CONCLUSION: B. clausii probiotic preparations may cause prolonged bacteraemia, rendering patients with underlying co-morbidities as well as those with unrecognized risk factors vulnerable for significant infectious complications.

Compassionate Use of Remdesivir in Children With Severe COVID-19.

OBJECTIVES: Remdesivir shortens time to recovery in adults with severe coronavirus disease 2019 (COVID-19), but its efficacy and safety in children are unknown. We describe outcomes in children with severe COVID-19 treated with remdesivir. METHODS: Seventy-seven hospitalized patients <18 years old with confirmed severe acute respiratory syndrome coronavirus 2 infection received remdesivir through a compassionate-use program between March 21 and April 22, 2020. The intended remdesivir treatment course was 10 days (200 mg on day 1 and 100 mg daily subsequently for children ≥40 kg and 5 mg/kg on day 1 and 2.5 mg/kg daily subsequently for children <40 kg, given intravenously). Clinical data through 28 days of follow-up were collected. RESULTS: Median age was 14 years (interquartile range 7-16, range <2 months to 17 years). Seventy-nine percent of patients had ≥1 comorbid condition. At baseline, 90% of children required supplemental oxygen and 51% required invasive ventilation. By day 28 of follow-up, 88% of patients had a decreased oxygen-support requirement, 83% recovered, and 73% were discharged. Among children requiring invasive ventilation at baseline, 90% were extubated, 80% recovered, and 67% were discharged. There were 4 deaths, of which 3 were attributed to COVID-19. Remdesivir was well tolerated, with a low incidence of serious adverse events (16%). Most adverse events were related to COVID-19 or comorbid conditions. Laboratory abnormalities, including elevations in transaminase levels, were common; 61% were grades 1 or 2. CONCLUSIONS: Among 77 children treated with remdesivir for severe COVID-19, most recovered and the rate of serious adverse events was low.

Characteristics and risk factors associated with critical illness in pediatric COVID-19.

BACKGROUND: While much has been reported regarding the clinical course of COVID-19 in children, little is known regarding factors associated with organ dysfunction in pediatric COVID-19. We describe critical illness in pediatric patients with active COVID-19 and identify factors associated with PICU admission and organ dysfunction. This is a retrospective chart review of 77 pediatric patients age 1 day to 21 years admitted to two New York City pediatric hospitals within the Northwell Health system between February 1 and April 24, 2020 with PCR + SARS-CoV-2. Descriptive statistics were used to describe the hospital course and laboratory results and bivariate comparisons were performed on variables to determine differences. RESULTS: Forty-seven patients (61%) were admitted to the general pediatric floor and thirty (39%) to the PICU. The majority (97%, n = 75) survived to discharge, 1.3% (n = 1) remain admitted, and 1.3% (n = 1) died. Common indications for PICU admission included hypoxia (50%), hemodynamic instability (20%), diabetic ketoacidosis (6.7%), mediastinal mass (6.7%), apnea (6.7%), acute chest syndrome in sickle cell disease (6.7%), and cardiac dysfunction (6.7%). Of PICU patients, 46.7% experienced any significant organ dysfunction (pSOFA > = 2) during admission. Patients aged 12 years or greater were more likely to be admitted to a PICU compared to younger patients (p = 0.015). Presence of an underlying comorbidity was not associated with need for PICU admission (p = 0.227) or organ dysfunction (p = 0.87). Initial white blood cell count (WBC), platelet count, and ferritin were not associated with need for PICU admission. Initial C-reactive protein was associated with both need for PICU admission (p = 0.005) and presence of organ dysfunction (p = 0.001). Initial WBC and presenting thrombocytopenia were associated with organ dysfunction (p = 0.034 and p = 0.003, respectively). CONCLUSIONS: Age over 12 years and initial CRP were associated with need for PICU admission in COVID-19. Organ dysfunction was associated with elevated admission CRP, elevated WBC, and thrombocytopenia. These factors may be useful in determining risk for critical illness and organ dysfunction in pediatric COVID-19.

Epidemiological and Clinical Characteristics of International Travelers with Enteric Fever and Antibiotic Resistance Profiles of Their Isolates: a GeoSentinel Analysis.

Enteric fever, caused by Salmonella enterica serovar Typhi (S Typhi) and S. enterica serovar Paratyphi (S Paratyphi), is a common travel-related illness. Limited data are available on the antimicrobial resistance (AMR) patterns of these serovars among travelers. Records of travelers with a culture-confirmed diagnosis seen during or after travel from January 2007 to December 2018 were obtained from GeoSentinel. Traveler demographics and antimicrobial susceptibility data were analyzed. Isolates were classified as nonsusceptible if intermediate or resistant or as susceptible in accordance with the participating site's national guidelines. A total of 889 travelers (S Typhi infections, n = 474; S Paratyphi infections, n = 414; coinfection, n = 1) were included; 114 (13%) were children of <18 years old. Most individuals (41%) traveled to visit friends and relatives (VFRs) and acquired the infection in South Asia (71%). Child travelers with S Typhi infection were most frequently VFRs (77%). The median trip duration was 31 days (interquartile range, 18 to 61 days), and 448 of 691 travelers (65%) had no pretravel consultation. Of 143 S Typhi and 75 S Paratyphi isolates for which there were susceptibility data, nonsusceptibility to antibiotics varied (fluoroquinolones, 65% and 56%, respectively; co-trimoxazole, 13% and 0%; macrolides, 8% and 16%). Two S Typhi isolates (1.5%) from India were nonsusceptible to third-generation cephalosporins. S Typhi fluoroquinolone nonsusceptibility was highest when infection was acquired in South Asia (70 of 90 isolates; 78%) and sub-Saharan Africa (6 of 10 isolates; 60%). Enteric fever is an important travel-associated illness complicated by AMR. Our data contribute to a better understanding of region-specific AMR, helping to inform empirical treatment options. Prevention measures need to focus on high-risk travelers including VFRs and children.

Gonococcal osteomyelitis in a pediatric patient with disseminated gonococcal infection: Implications for antimicrobial management.

We report a case of a female teenager with gonococcal septic arthritis of the right shoulder that also caused osteomyelitis of the humeral head. Infection with Neisseria gonorrhoeae is a frequently diagnosed sexually transmitted infection in the sexually active teenage population and disseminated gonococcal infection (DGI) is the most common systemic manifestation of acute gonorrhea. DGI commonly involves acute arthritis, tenosynovitis and dermatitis with less common complications of endocarditis, hepatitis and meningitis. In contrast, osteomyelitis has only rarely been reported as a result of gonococcal infection. Clinicians need to be aware of this unusual manifestation of DGI as a prolonged duration of antimicrobial treatment may be needed to assure complete resolution of this infection.

Acquisition and Long-term Carriage of Multidrug-Resistant Organisms in US International Travelers.

We performed prospective screening of stool for multidrug-resistant organisms from 608 US international travelers and identified an acquisition rate of 38% following travel. Carriage rates remained significantly elevated for at least 6 months post-travel. Travel-related diarrhea was a risk factor for acquisition, as well as for long-term carriage upon return.

Clinical Practices for Measles-Mumps-Rubella Vaccination Among US Pediatric International Travelers.

Importance: The US population is experiencing a resurgence of measles, with more than 1000 cases during the first 6 months of 2019. Imported measles cases among returning international travelers are the source of most US measles outbreaks, and these importations can be reduced with pretravel measles-mumps-rubella (MMR) vaccination of pediatric travelers. Although it is estimated that children account for less than 10% of US international travelers, pediatric travelers account for 47% of all known measles importations. Objective: To examine clinical practice regarding MMR vaccination of pediatric international travelers and to identify reasons for nonvaccination of pediatric travelers identified as MMR eligible. Design, Setting, and Participants: This cross-sectional study of pediatric travelers (ages ≥6 months and <18 years) attending pretravel consultation at 29 sites associated with Global TravEpiNet (GTEN), a Centers for Disease Control and Prevention-supported consortium of clinical sites that provide pretravel consultations, was performed from January 1, 2009, through December 31, 2018. Main Outcomes and Measures: Measles-mumps-rubella vaccination among MMR vaccination-eligible pediatric travelers. Results: Of 14 602 pretravel consultations for pediatric international travelers, 2864 travelers (19.6%; 1475 [51.5%] males; 1389 [48.5%] females) were eligible to receive pretravel MMR vaccination at the time of the consultation: 365 of 398 infants aged 6 to 12 months (91.7%), 2161 of 3623 preschool-aged travelers aged 1 to 6 years (59.6%), and 338 of 10 581 school-aged travelers aged 6 to 18 years (3.2%). Of 2864 total MMR vaccination-eligible travelers, 1182 (41.3%) received the MMR vaccine and 1682 (58.7%) did not. The MMR vaccination-eligible travelers who did not receive vaccine included 161 of 365 infants (44.1%), 1222 of 2161 preschool-aged travelers (56.5%), and 299 of 338 school-aged travelers (88.5%). We observed a diversity of clinical practice at different GTEN sites. In multivariable analysis, MMR vaccination-eligible pediatric travelers were less likely to be vaccinated at the pretravel consultation if they were school-aged (model 1: odds ratio [OR], 0.32 [95% CI, 0.24-0.42; P < .001]; model 2: OR, 0.26 [95% CI, 0.14-0.47; P < .001]) or evaluated at specific GTEN sites (South: OR, 0.06 [95% CI, 0.01-0.52; P < .001]; West: OR, 0.10 [95% CI, 0.02-0.47; P < .001]). The most common reasons for nonvaccination were clinician decision not to administer MMR vaccine (621 of 1682 travelers [36.9%]) and guardian refusal (612 [36.4%]). Conclusions and Relevance: Although most infant and preschool-aged travelers evaluated at GTEN sites were eligible for pretravel MMR vaccination, only 41.3% were vaccinated during pretravel consultation, mostly because of clinician decision or guardian refusal. Strategies may be needed to improve MMR vaccination among pediatric travelers and to reduce measles importations and outbreaks in the United States.