Clavulanate combinations with mecillinam, cefixime or cefpodoxime against ESBL-producing Enterobacterales frequently associated with blaOXA-1 in a paediatric population with febrile urinary tract infections.

OBJECTIVES: Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of ß-lactamases and Enterobacterales' genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. MATERIALS AND METHODS: In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates' ST and their type of ß-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. RESULTS: All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant ß-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). CONCLUSIONS: Despite the frequent association of ESBL genes with inhibitor-resistant ß-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.

Staphylococcus capitis isolated from bloodstream infections: a nationwide 3-month survey in 38 neonatal intensive care units.

To increase the knowledge about S. capitis in the neonatal setting, we conducted a nationwide 3-month survey in 38 neonatal intensive care units (NICUs) covering 56.6% of French NICU beds. We demonstrated 14.2% of S. capitis BSI (S.capBSI) among nosocomial BSIs. S.capBSI incidence rate was 0.59 per 1000 patient-days. A total of 55.0% of the S.capBSIs were late onset catheter-related BSIs. The S. capitis strains infected preterm babies (median gestational age 26 weeks, median birth weight 855 g). They were resistant to methicillin and aminoglycosides and belonged to the NRCS-A clone. Evolution was favorable in all but one case, following vancomycin treatment.

Assessment of SARS-CoV-2 infection by Reverse transcription-PCR and serology in the Paris area: a cross-sectional study.

BACKGROUND: Several studies indicated that children seem to be less frequently infected with SARS-CoV-2 and are potentially less contagious than adults. To examine the spread of SARS-CoV-2, we combined both Reverse transcription-PCR testing and serology in children in the most affected region in France, Paris, during the COVID-19 epidemic. METHODS: From 14 April 2020 to 12 May 2020, we conducted a cross-sectional, prospective, multicentre study. Healthy controls and pauci-symptomatic children from birth to age 15 years were enrolled by 27 ambulatory paediatricians. A nasopharyngeal swab was taken for detection of SARS-CoV-2 by Reverse transcription-PCR and a microsample of blood for micromethod serology. RESULTS: Among the 605 children, 322 (53.2%) were asymptomatic and 283 (46.8%) were symptomatic. Reverse transcription-PCR and serology results were positive for 11 (1.8%) and 65 (10.7%) children, respectively, with no significant difference between asymptomatic and pauci-symptomatic children. Only three children were Reverse transcription-PCR-positive without any antibody response detected. The frequency of Reverse transcription-PCR SARS-CoV-2 positivity was significantly higher for children with positive than negative serology results (12.3% vs 0.6%, p<0.001). Contact with a person with confirmed COVID-19 increased the odds of Reverse transcription-PCR positivity (OR 7.8, 95% CI 1.5 to 40.7) and serology positivity (OR 15.1, 95% CI 6.6 to 34.6). CONCLUSION: In an area heavily affected by COVID-19, after the peak of the first epidemic wave and during the lockdown, the rate of children with Reverse transcription-PCR SARS-CoV-2 positivity was very low (1.8%), but that of serology positivity was higher (10.7%). Most children with positive Reverse transcription-PCR results also had positive serology results. TRIAL REGISTRATION NUMBER: NCT04318431.

Group A Streptococcal Paronychia and Blistering Distal Dactylitis in Children: Diagnostic Accuracy of a Rapid Diagnostic Test and Efficacy of Antibiotic Treatment.

Among 174 children with blistering distal dactylitis or paronychia, 36.2% had a positive group A Streptococcus (GAS) rapid detection antigen. For GAS, the outcome for patients who received amoxicillin was favorable in all cases without any surgical procedures; 44.6% of cases due to Staphylococcus aureus infection (38.7%) required surgery.

Diversity and trends in population structure of ESBL-producing Enterobacteriaceae in febrile urinary tract infections in children in France from 2014 to 2017.

BACKGROUND: The population structure of extraintestinal pathogenic Escherichia coli evolves over time, notably due to the emergence of antibiotic-resistant clones such as ESBL-producing Enterobacteriaceae (ESBL-E). OBJECTIVES: To analyse by WGS the genetic diversity of a large number of ESBL-E isolated from urinary tract infections in children from paediatric centres across France between 2014 and 2017 and collected by the National Observatory of febrile urinary tract infection (FUTI) caused by ESBL-E. METHODS: A total of 40 905 Enterobacteriaceae-positive urine cultures were identified. ESBL-E were found in 1983 samples (4.85%). WGS was performed on 251 ESBL-E causing FUTI. STs, core genome MLST (cgMLST), serotype, fimH allele, ESBL genes and presence of papGII key virulence factor were determined. RESULTS: E. coli and Klebsiella pneumoniae were found in 86.9% (218/251) and 11.2% (28/251) of cases, respectively. Several STs predominate among E. coli such as ST131, ST38, ST69, ST73, ST95, ST405, ST12 and ST1193, while no ST emerged in K. pneumoniae. E. coli ST131, ST38 and ST1193 increased during the study period, with a heterogeneity in papGII prevalence (64.5%, 35% and 20% respectively). Most isolates harboured the CTX-M type (97%) with a predominance of blaCTX-M-15. blaCTX-M-27, an emerging variant in E. coli, is found in various STs. cgMLST enabled discrimination of clusters within the main STs. CONCLUSIONS: The predominance of ST131, and the emergence of other STs such as ST38 and ST1193 combined with ESBL genes deserves close epidemiological surveillance considering their high threat in infectious disease. cgMLST could be a discriminant complementary tool for the analyses.

Antimicrobial treatment practices among Ugandan children with suspicion of central nervous system infection.

Acute central nervous system (CNS) infections in children in sub-Saharan Africa are often fatal. Potential contributors include late presentation, limited diagnostic capacity and inadequate treatment. A more nuanced understanding of treatment practices with a goal of optimizing such practices is critical to prevent avoidable case fatality. We describe empiric antimicrobial treatment, antibiotic resistance and treatment adequacy in a prospective cohort of 459 children aged two months to 12 years hospitalised for suspected acute CNS infections in Mbarara, Uganda, from 2009 to 2012. Among these 459 children, 155 had a laboratory-confirmed diagnosis of malaria (case-fatality rate [CFR] 14%), 58 had bacterial infections (CFR 24%) and 6 children had mixed malaria and bacterial infections (CFR 17%). Overall case fatality was 18.1% (n = 83). Of 219 children with laboratory-confirmed malaria and/or bacterial infections, 182 (83.1%) received an adequate antimalarial and/or antibiotic on the day of admission and 211 (96.3%) within 48 hours of admission. The proportion of those receiving adequate treatment was similar among survivors and non-survivors. All bacterial isolates were sensitive to ceftriaxone except one Escherichia coli isolate with extended-spectrum beta-lactamase (ESBL). The observed high mortality was not a result of inadequate initial antimicrobial treatment at the hospital. The epidemiology of CNS infection in this setting justifies empirical use of a third-generation cephalosporin, however antibiotic resistance should be monitored closely.

Aetiology and Outcomes of Suspected Infections of the Central Nervous System in Children in Mbarara, Uganda.

Infections of the central nervous system (CNS) are severe conditions, leading to neurological sequelae or death. Knowledge of the causative agents is essential to develop guidelines for case management in resource-limited settings. Between August 2009 and October 2012, we conducted a prospective descriptive study of the aetiology of suspected CNS infections in children two months to 12 years old, with fever and at least one sign of CNS involvement in Mbarara Hospital, Uganda. Children were clinically evaluated on admission and discharge, and followed-up for 6 months for neurological sequelae. Pathogens were identified from cerebrospinal fluid (CSF) and blood using microbiological and molecular methods. We enrolled 459 children. Plasmodium falciparum (36.2%) and bacteria in CSF (13.3%) or blood (3.3%) were the most detected pathogens. Viruses were found in 27 (5.9%) children. No pathogen was isolated in 207 (45.1%) children. Patterns varied by age and HIV status. Eighty-three (18.1%) children died during hospitalisation, and 23 (5.0%) during follow-up. Forty-one (13.5%) children had neurological sequelae at the last visit. While malaria remains the main aetiology in children with suspected CNS infections, no pathogen was isolated in many children. The high mortality and high rate of neurological sequelae highlight the need for efficient diagnosis.

Prevalence of Bordetella infection in a hospital setting in niamey, niger.

Bordetella pertussis still poses an important health threat in developing countries. In Niger, notified pertussis cases are few despite the low diphtheria-tetanus-pertussis/pentavalent vaccine coverage. We aimed to estimate the prevalence of B. pertussis in children aged <5 years consulting at a pediatric ward. A 5-month study in 2011 recruited 342 children with respiratory symptoms at the National Hospital of Niamey. Nasopharyngeal aspirates were tested by culture and real-time polymerase chain reaction. Overall, 34 (11.2%) of the 305 available nasopharyngeal aspirates tested by real-time polymerase chain reaction were positive for a Bordetella spp., with an estimated prevalence of 8.2 cases per 1000 children aged <5. None was notified to the surveillance network. A single specimen was positive on culture. This study, the first to provide laboratory-confirmed data on pertussis in Niger, highlights the need to sensitize health care personnel to actively notify clinical cases and to integrate laboratory diagnosis in the existing surveillance system.

Diagnostic and prognostic value of procalcitonin and C-reactive protein in malnourished children.

BACKGROUND: Early recognition of bacterial infections is crucial for their proper management, but is particularly difficult in children with severe acute malnutrition (SAM). The objectives of this study were to evaluate the accuracy of C-reactive protein (CRP) and procalcitonin (PCT) for diagnosing bacterial infections and assessing the prognosis of hospitalized children with SAM, and to determine the reliability of CRP and PCT rapid tests suitable for remote settings. METHODS: From November 2007 to July 2008, we prospectively recruited 311 children aged 6 to 59 months hospitalized with SAM plus a medical complication in Maradi, Niger. Blood, urine, and stool cultures and chest radiography were performed systematically on admission. CRP and PCT were measured by rapid tests and by reference quantitative methods using frozen serum sent to a reference laboratory. RESULTS: Median CRP and PCT levels were higher in children with bacteremia or pneumonia than in those with no proven bacterial infection (P < .002). However, both markers performed poorly in identifying invasive bacterial infection, with areas under the curve of 0.64 and 0.67 before and after excluding children with malaria, respectively. At a threshold of 40 mg/L, CRP was the best predictor of death (81% sensitivity, 58% specificity). Rapid test results were consistent with those from reference methods. CONCLUSIONS: CRP and PCT are not sufficiently accurate for diagnosing invasive bacterial infections in this population of hospitalized children with complicated SAM. However, a rapid CRP test could be useful in these settings to identify children most at risk for dying.

Infections in children admitted with complicated severe acute malnutrition in Niger.

BACKGROUND: Although malnutrition affects thousands of children throughout the Sahel each year and predisposes them to infections, there is little data on the etiology of infections in these populations. We present a clinical and biological characterization of infections in hospitalized children with complicated severe acute malnutrition (SAM) in Maradi, Niger. METHODS: Children with complicated SAM hospitalized in the intensive care unit of a therapeutic feeding center, with no antibiotics in the previous 7 days, were included. A clinical examination, blood, urine and stool cultures, and chest radiography were performed systematically on admission. RESULTS: Among the 311 children included in the study, gastroenteritis was the most frequent clinical diagnosis on admission, followed by respiratory tract infections and malaria. Blood or urine culture was positive in 17% and 16% of cases, respectively, and 36% had abnormal chest radiography. Enterobacteria were sensitive to most antibiotics, except amoxicillin and cotrimoxazole. Twenty-nine (9%) children died, most frequently from sepsis. Clinical signs were poor indicators of infection and initial diagnoses correlated poorly with biologically or radiography-confirmed diagnoses. CONCLUSIONS: These data confirm the high level of infections and poor correlation with clinical signs in children with complicated SAM, and provide antibiotic resistance profiles from an area with limited microbiological data. These results contribute unique data to the ongoing debate on the use and choice of broad-spectrum antibiotics as first-line treatment in children with complicated SAM and reinforce the call for an update of international guidelines on management of complicated SAM based on more recent data.

Role of the central venous catheter in bloodstream infections caused by coagulase-negative staphylococci in very preterm neonates.

BACKGROUND: Pathogenesis of coagulase-negative staphylococcal bloodstream infections among preterm neonates is debated: central venous catheters (CVCs) are considered the major cause and the cornerstone of prevention measures. The role of other means of transmission is unknown. METHODS: We developed a specific quantitative polymerase chain reaction assay targeting the dnaJ gene from Staphylococcus epidermidis and Staphylococcus capitis to detect DNA from CVC used in preterms. Performance of the polymerase chain reaction was tested against 2 control groups of CVC yielding positive (n = 24) or negative (n = 63) conventional cultures. We also explored retrospectively the DNA load of CVC having a negative conventional bacterial culture and obtained from 34 very preterm neonates with catheter-related bloodstream infections (CR-BSIs) established by usual clinical and biologic criteria. RESULTS: The molecular approach allowed detection of corresponding DNA from all the positive control catheters. Among the 34 episodes of CR-BSI yielding a negative conventional CVC culture, 8 (23.5%) had a positive polymerase chain reaction signal (5 S. epidermidis and 3 S. capitis). This percentage did not significantly differ according to the staphylococcal species, the delay between the CVC insertion and the beginning of the sepsis or between the blood culture collection and the CVC removal. These results conform to the previously published 70% of CR-BSI for whom the origin could be questioned. CONCLUSIONS: CVC removal in preterms is often performed in cases of CR-BSI; our study supports the hypothesis that in some cases the responsibility of CVC is questionable.

Nosocomial pertussis outbreak among adult patients and healthcare workers.

We describe a pertussis outbreak among adult patients in a French general hospital following transmission from a healthcare worker. This index case transmitted pertussis to other healthcare workers, who, in turn, contaminated other staff and two immunosuppressed patients. This raises questions about infection control.

Halofantrine efficacy in non-immune children with imported acute Plasmodium falciparum malaria Infection.

UNLABELLED: A rising incidence of imported acute malaria has been observed in non-immune traveller children returning from the tropics to France. Halofantrine efficacy has been poorly assessed in non-immune children. In order to assess halofantrine efficacy in non-immune children with acute uncomplicated Plasmodium falciparum malaria, we collected data of children with positive blood smears in an open prospective study. Children with neurological manifestations, vomiting and congenital long QT were excluded. All children were hospitalised and received halofantrine (24 mg/kg divided into three doses per day) on an empty stomach. Persistent fever after day 3 defined failure. Relapse was defined by a positive blood smear with or without systemic symptoms within a 1 month follow-up period. In total, 52 children were enrolled. No failure was observed, but relapses occurred in 14/52. On univariate analysis, the mean age of children with relapse was significantly lower (P<0.05). Moreover, diarrhoea was more frequently associated with relapses (P<0.04). Age and diarrhoea were significant independent factors contributing to relapses. CONCLUSION: This study shows that with a relapse rate of 27%, this regimen with a 1-day course of halofantrine is not to be recommended.