Antibiotic therapy for osteoarticular infections in 2023: Proposals from the Pediatric Infectious Pathology Group (GPIP).

Most osteoarticular infections (OAI) occur via the hematogenous route, affect children under 5 years of age old, and include osteomyelitis, septic arthritis, osteoarthritis and spondylodiscitis. Early diagnosis and prompt treatment are needed to avoid complications. Children with suspected OAI should be hospitalized at the start of therapy. Surgical drainage is indicated in patients with septic arthritis or periosteal abscess. Staphylococcus aureus is implicated in OAI in children at all ages; Kingella kingae is a very common causative pathogen in children from 6 months to 4 years old. The French Pediatric Infectious Disease Group recommends empirical antibiotic therapy with appropriate coverage against methicillin-sensitive S. aureus (MSSA) with high doses (150 mg/kg/d) of intravenous cefazolin. In most children presenting uncomplicated OAI with favorable outcome (disappearance of fever and pain), short intravenous antibiotic therapy during 3 days can be followed by oral therapy. In the absence of bacteriological identification, oral relay is carried out with the amoxicillin/clavulanate combination (80 mg/kg/d of amoxicillin) or cefalexin (150 mg/kg/d). If the bacterial species is identified, antibiotic therapy will be adapted to antibiotic susceptibility. The minimum total duration of antibiotic therapy should be 14 days for septic arthritis, 3 weeks for osteomyelitis and 4-6 weeks for OAI of the pelvis, spondylodiscitis and more severe OAI, and those evolving slowly under treatment or with an underlying medical condition (neonate, infant under 3 months of old, immunocompromised patients). Treatment of spondylodiscitis and severe OAI requires systematic orthopedic advice.

Antibiotic treatment of neuro-meningeal infections.

In France, conjugated pneumococcal vaccination has considerably modified the profile of pneumococcal meningitis by eliminating the most virulent strains resistant to beta-lactams. Over recent years, the nationwide pediatric meningitis network of the Pediatric Infectious Disease Group (GPIP) and the National Reference Centre of Pneumococci have not recorded any cases of meningitis due to pneumococcus resistant to third-generation cephalosporins (C3G), even though in 2021, strains with a less favorable profile appeared to emerge. These recent data justify renewal of the 2016 recommendations and limitation of vancomycin to the secondary phase of treatment of pneumococcal meningitis when the MIC of the isolated strain against injectable C3Gs is >0.5 mg/L. The only major change proposed by the GPIP in this 2023 update of its recommendations is discontinuation of the recommendation of a combination of ciprofloxacin and cefotaxime in Escherichia coli meningitis in newborns and young infants. The nationwide observatory of meningitis in children is a valuable tool because of its completeness and its continuity over the past 15 years. The maintenance of epidemiological surveillance will allow us to adapt new therapeutic regimens to the evolution of pneumococcal susceptibility profiles and to future serotype-specific changes. Community-acquired cerebral abscesses are rare diseases, of which the management requires a rigorous approach: high-quality imaging, bacteriological sampling prior to antibiotic therapy whenever possible, and antibiotic treatment including metronidazole in addition to cefotaxime. Multidisciplinary collaboration, including infectious disease and neurosurgical advice, is always called for.

The principles of curative antibiotic treatments.

Knowledge of infectious diseases and their treatments is constantly evolving. New infectious agents are regularly discovered, due mainly to improvement of identification techniques, especially the development of molecular biology and mass spectrometry. While changes in the epidemiology of infectious diseases are not always predictable or readily understood, several factors regularly enter into consideration, such as not only the natural history of diseases and the impact of vaccinations, but also the excessive and irrational use of antibiotics. Antibiotic resistance is now recognized as one of the major challenges for humanity, especially since few new molecules have been put on the market in recent years. These molecules are reserved for serious infections caused by bacteria resistant to other antibiotics and should be prescribed only by infectious disease specialists trained in their use. Rationalization of antibiotic therapy is therefore one of the keys to reducing antibiotic resistance and the spread of resistant bacteria. In this guide, with regard to each clinical situation, the bacterial target(s) of antibiotic treatment, the preferred antibiotic choice, and the therapeutic alternatives will be specified. Comments on diagnosis and treatment of the infection will be added if necessary.

Antimicrobial treatment of urinary tract infections in children.

Urinary tract infections are the most frequently proven bacterial infections in pediatrics. The treatment options proposed in this guide are based on recommendations published by the Groupe de Pathologie Infectieuse de Pédiatrique (GPIP-SFP). Except in rare situations (newborns, neutropenia, sepsis), a positive urine dipstick for leukocytes and/or nitrites should precede a urine culture examination and any antibiotic therapy. After rising steadily between 2000 and 2012, the proportion of Escherichia coli strains resistant to extended-spectrum ß-lactamases (E-ESBL) has remained stable over the last ten years (between 7% and 10% in pediatrics). However, in many cases no oral antibiotic is active on E-ESBL leading either to prolonged parenteral treatment, or to use of a non-orthodox combination such as cefixime + clavulanate. With the aim of avoiding penem antibiotics and encouraging outpatient management, this guide favors initial treatment of febrile urinary tract infections (suspected or actual E-ESBL infection), with amikacin. Amikacin remains active against the majority of E-ESBL strains. It could be prescribed as monotherapy for patients in pediatric emergency departments or otherwise hospitalized patients.

Definitions and implications of the pharmacokinetic-pharmacodynamic parameters of antibiotics in pediatric clinical practice.

Knowledge of infectious diseases and their treatments is constantly evolving. New infectious agents are regularly discovered, mainly due to improvement of identification techniques, especially the development of molecular biology and mass spectrometry. While changes in the epidemiology of infectious diseases are not always predictable or readily understood, several factors regularly enter into consideration, such as not only the natural history of diseases, the impact of vaccinations, but also the excessive and irrational use of antibiotics. Antibiotic resistance is now recognized as one of the major challenges for humanity, especially since few new molecules have been put on the market in recent years. These molecules are reserved for serious infections caused by bacteria resistant to other antibiotics and should only be prescribed by infectious diseases specialists trained in their use. Rationalization of antibiotic therapy is therefore one of the keys to reducing antibiotic resistance and the spread of resistant bacteria. In this guide, for each clinical situation, the bacterial target(s) of antibiotic treatment, the preferred antibiotic choice, and the therapeutic alternatives will be specified. Comments on the diagnosis and treatment of the infection will be added if necessary.

Procalcitonin at 12-36 hours of fever for prediction of invasive bacterial infections in hospitalized febrile neonates.

Aim: We aimed to investigate the performance of procalcitonin (PCT) assay between 12 and 36 h after onset of fever (PCT H12-H36) to predict invasive bacterial infection (IBI) (ie, meningitis and/or bacteremia) in febrile neonates. Methods: We retrospectively included all febrile neonates hospitalized in the general pediatric department in a teaching hospital from January 2013 to December 2019. PCT assay ≤ 0.6 ng/ml was defined as negative. The primary outcome was to study the performance of PCT H12-H36 to predict IBI. Results: Out of 385 included neonates, IBI was ascertainable for 357 neonates (92.7%). We found 16 IBI: 3 meningitis and 13 bacteremia. Sensitivity and specificity of PCT H12-H36 in the identification of IBI were, respectively, 100% [95% CI 82.9-100%] and 71.8% [95% CI 66.8-76.6%], with positive and negative predictive values of 14.3% [95% CI 8.4-22.2%] and 100% [95% CI 98.8-100%] respectively. Of the 259 neonates who had a PCT assay within the first 12 h of fever (< H12) and a PCT assay after H12-H36, 8 had IBI. Two of these 8 neonates had a negative < H12 PCT but a positive H12-H36 PCT. Conclusions: PCT H12-H36 did not miss any IBI whereas < H12 PCT could missed IBI diagnoses. PCT H12-H36 might be included in clinical decision rule to help physicians to stop early antibiotics in febrile neonates.

Relay oral therapy in febrile urinary tract infections caused by extended spectrum beta-lactamase-producing Enterobacteriaceae in children: A French multicenter study.

OBJECTIVES: We need studies assessing therapeutic options for oral relay in febrile urinary tract infection (FUTI) due to ESBL-producing Enterobacteriaceae (ESBL-E) in children. Amoxicillin-clavulanate/cefixime (AC-cefixime) combination seems to be a suitable option. We sought to describe the risk of recurrence at 1 month after the end of treatment for FUTI due to ESBL-E according to the oral relay therapy used. MATERIALS AND METHODS: We retrospectively identified children <18 years who were included in a previous prospective observational multicentric study on managing FUTI due to ESBL-E between 2014 and 2017 in France. We collected whether children who received cotrimoxazole, ciprofloxacin or the AC-cefixime combination as the oral relay therapy reported a recurrence within the first month after the end of treatment. Then, we analyzed the susceptibility drug-testing of the strains involved. RESULTS: We included 199 children who received an oral relay therapy with cotrimoxazole (n = 72, 36.2%), ciprofloxacin (n = 38, 19.1%) or the AC-cefixime combination (n = 89, 44.7%). Nine (4.5%) patients had a recurrence within the first month after the end of treatment, with no difference between the 3 groups of oral relay (p = 0.8): 4 (5.6%) cotrimoxazole, 2 (5.3%) ciprofloxacin and 3 (3.4%) AC-cefixime combination. Phenotype characterization of 249 strains responsible for FUTI due to ESBL-E showed that 97.6% were susceptible to the AC-cefixime combination. CONCLUSIONS: The AC-cefixime combination represents an interesting therapeutic option for oral relay treatment of FUTI due to ESBL-E as the recurrence rate at 1 month after the end of treatment was the same when compared to cotrimoxazole and ciprofloxacin.

Pediatric Infectious Disease Group (GPIP) position paper on the immune debt of the COVID-19 pandemic in childhood, how can we fill the immunity gap?

Since the beginning of the COVID-19 pandemic, reduced incidence of many viral and bacterial infections has been reported in children: bronchiolitis, varicella, measles, pertussis, pneumococcal and meningococcal invasive diseases. The purpose of this opinion paper is to discuss various situations that could lead to larger epidemics when the non-pharmaceutical interventions (NPI) imposed by the SARS-CoV-2 epidemic will no longer be necessary. While NPIs limited the transmission of SARS-CoV-2, they also reduced the spread of other pathogens during and after lockdown periods, despite the re-opening of schools since June 2020 in France. This positive collateral effect in the short term is welcome as it prevents additional overload of the healthcare system. The lack of immune stimulation due to the reduced circulation of microbial agents and to the related reduced vaccine uptake induced an "immunity debt" which could have negative consequences when the pandemic is under control and NPIs are lifted. The longer these periods of "viral or bacterial low-exposure" are, the greater the likelihood of future epidemics. This is due to a growing proportion of "susceptible" people and a declined herd immunity in the population. The observed delay in vaccination program without effective catch-up and the decrease in viral and bacterial exposures lead to a rebound risk of vaccine-preventable diseases. With a vaccination schedule that does not include vaccines against rotavirus, varicella, and serogroup B and ACYW Neisseria meningitidis, France could become more vulnerable to some of these rebound effects.

Multisystem inflammatory syndrome in children rose and fell with the first wave of the COVID-19 pandemic in France.

AIM: This study determined the influence of the COVID-19 pandemic on the occurrence of multisystem inflammatory syndrome in children (MIS-C) and compared the main characteristics of MIS-C and Kawasaki disease (KD). METHODS: We included patients aged up to 18 years of age who were diagnosed with MIS-C or KD in a paediatric university hospital in Paris from 1 January 2018 to 15 July 2020. Clinical, laboratory and imaging characteristics were compared, and new French COVID-19 cases were correlated with MIS-C cases in our hospital. RESULTS: There were seven children with MIS-C, from 6 months to 12 years of age, who were all positive for the virus that causes COVID-19, and 40 virus-negative children with KD. Their respective characteristics were as follows: under 5 years of age (14.3% vs. 85.0%), paediatric intensive care unit admission (100% vs. 10.0%), abdominal pain (71.4% vs. 12.5%), myocardial dysfunction (85.7% vs. 5.0%), shock syndrome (85.7% vs. 2.5%) and mean and standard deviation C-reactive protein (339 ± 131 vs. 153 ± 87). There was a strong lagged correlation between the rise and fall in MIS-C patients and COVID-19 cases. CONCLUSION: The rise and fall of COVID-19 first wave mirrored the MIS-C cases. There were important differences between MIS-C and KD.

Recurrent Acute Septic Arthritis Caused by Kingella kingae in a 16-Month-Old Boy.

We describe the first case of 2 consecutive acute septic arthritis infections of both knees caused by the same virulent strain of Kingella kingae belonging to the virulent sequence type complex 14, in a 16-month-old boy. Both infections occurred after viral upper respiratory tract infections.

Bone and joint infections in infants under three months of age.

AIM: Studies on bone and joint infections (BJI) in infants under three months are rare. We described the clinical and paraclinical features and outcomes of infants hospitalised with BJI under three months of age. METHODS: The French National Hospital Discharge Database provided data on BJIs in infants under three months of age from January 2004 to 2015 in three Parisian Paediatric teaching hospitals. RESULTS: We included 71 infants under three months of age with BJI, the median age was 25 days, and the interquartile range (IQR) was 17-43 days. The most common infection sites were the hip (32%) and knee (32%). Symptoms included pain (94%), limited mobility (87%) and/or fever (52%). There were 11 (15.5%) cases of nosocomial BJI. A pathogen was identified in 51 infants (71.8%), including Streptococcus agalactiae (45%), Staphylococcus aureus (22%) and Escherichia coli (18%). The initial median C-reactive protein test rate was 31 mg/L (IQR 17-68). Of the 34 infants followed for more than one year, four developed severe orthopaedic conditions such as epiphysiodesis, limb length discrepancy, bone necrosis and/or impaired limb function. CONCLUSION: Streptococcus agalactiae was the most common cause of BJI in infants under three months. Orthopaedic sequelae were rare, but severe, and required long-term follow-up.

Febrile urinary-tract infection due to extended-spectrum beta-lactamase-producing Enterobacteriaceae in children: A French prospective multicenter study.

OBJECTIVES: To assess the management of febrile urinary-tract infection (FUTIs) due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) in children, the Pediatric Infectious Diseases Group of the French Pediatric Society set up an active surveillance network in pediatric centers across France in 2014. MATERIALS AND METHODS: We prospectively analysed data from 2014 to 2016 for all children < 18 years old who received antibiotic treatment for FUTI due to ESBL-E in 24 pediatric centers. Baseline demographic, clinical features, microbiological data and antimicrobials prescribed were collected. RESULTS: 301 children were enrolled in this study. The median age was 1 year (IQR 0.02-17.9) and 44.5% were male. These infections occurred in children with history of UTIs (27.3%) and urinary malformations (32.6%). Recent antibiotic use was the main associated factor for FUTIs due to ESBL-E, followed by a previous hospitalization and travel history. Before drug susceptibility testing (DST), third-generation cephalosporins (3GC) PO/IV were the most-prescribed antibiotics (75.5%). Only 13% and 24% of children received amikacine alone for empirical or definitive therapy, respectively, whereas 88.7% of children had isolates susceptible to amikacin. In all, 23.2% of children received carbapenems in empirical and/or definitive therapy. Cotrimoxazole (24.5%), ciprofloxacin (15.6%) and non-orthodox clavulanate-cefixime combination (31.3%) were the most frequently prescribed oral options after obtaining the DST. The time to apyrexia and length of hospital stay did not differ with or without effective empirical therapy. CONCLUSIONS: We believe that amikacin should increasingly take on a key role in the choice of definitive therapy of FUTI due to ESBL-E in children by avoiding the use of carbapenems.

Compliance with the current recommendations for prescribing antibiotics for paediatric community-acquired pneumonia is improving: data from a prospective study in a French network.

BACKGROUND: Lower respiratory tract infection is a common cause of consultation and antibiotic prescription in paediatric practice. The misuse of antibiotics is a major cause of the emergence of multidrug-resistant bacteria. The aim of this study was to evaluate the frequency, changes over time, and determinants of non-compliance with antibiotic prescription recommendations for children admitted in paediatric emergency department (PED) with community-acquired pneumonia (CAP). METHODS: We conducted a prospective two-period study using data from the French pneumonia network that included all children with CAP, aged one month to 15 years old, admitted to one of the ten participating paediatric emergency departments. In the first period, data from children included in all ten centres were analysed. In the second period, we analysed children in three centers for which we collected additional data. Two experts assessed compliance with the current French recommendations. Independent determinants of non-compliance were evaluated using a logistic regression model. The frequency of non-compliance was compared between the two periods for the same centres in univariate analysis, after adjustment for confounding factors. RESULTS: A total of 3034 children were included during the first period (from May 2009 to May 2011) and 293 in the second period (from January to July 2012). Median ages were 3.0 years [1.4-5] in the first period and 3.6 years in the second period. The main reasons for non-compliance were the improper use of broad-spectrum antibiotics or combinations of antibiotics. Factors that were independently associated with non-compliance with recommendations were younger age, presence of risk factors for pneumococcal infection, and hospitalization. We also observed significant differences in compliance between the treatment centres during the first period. The frequency of non-compliance significantly decreased from 48 to 18.8 % between 2009 and 2012. The association between period and non-compliance remained statistically significant after adjustment for confounding factors. Amoxicillin was prescribed as the sole therapy significantly more frequently in the second period (71 % vs. 54.2 %, p < 0.001). CONCLUSIONS: We observed a significant increase in the compliance with recommendations, with a reduction in the prescription of broad-spectrum antibiotics, efforts to improve antibiotic prescriptions must continue.

Oral Ambulatory Treatment of Acute Osteomyelitis in Children: A Case-Control Study.

The treatment of acute hematogenous osteomyelitis has evolved in recent years to a shorter parenteral treatment with an early switch to the oral route. Current publications recommend a 2- to 4-day parenteral treatment before the oral switch. We retrospectively analyzed a series of 45 children aged 1 to 11 years and treated in our department for acute osteomyelitis without severity criterion. Nineteen of 45 patients were treated by an exclusive ambulatory oral treatment by amoxicillin and clavulanic acid. Twenty six of 45 patients had a 2- to 4-day parenteral treatment before the oral switch. The minimum follow-up was 6 months. The primary endpoint was a clinical, radiographic, and biologic healing, 6 months after the beginning of the treatment. The secondary endpoints evaluated were the length of hospitalization, the total duration of treatment, and the type of antibiotic used. On the primary endpoint, we did not find any significant difference between the 2 treatments (P = 0.38). On the duration of treatment, we found a significant difference (P = 0.049) in favor of oral treatment. The ambulatory oral treatment by amoxicillin and clavulanic acid seems to be a valid alternative to the classical parenteral then oral sequence in the treatment of acute hematogenous osteomyelitis in children without severity criterion.

An innovative pedagogic course combining video and simulation to teach medical students about pediatric cardiopulmonary arrest: a prospective controlled study.

UNLABELLED: Compliance by residents in pediatrics to pediatric resuscitation guidelines is low. In many French faculties, a 1-h traditional lecture is still used to educate medical students about pediatric cardiopulmonary arrest (CPA). We developed an innovative pedagogic course combining a 23-min video and 3-h simulation exercises to improve knowledge and skills of medical students. A prospective controlled study was conducted. Medical student knowledge was tested before, just after, and 6-12 months after the innovative course and compared to that of a cohort who attended the traditional lecture. A high-fidelity mannequin simulator simulating cardiopulmonary arrest was used to assess and compare the skills of the study and control groups. Costs of the courses were evaluated; 809 of 860 (94 %) medical students were assessed for knowledge. Six to 12 months after the courses, the median score was significantly higher for the innovative group than that for the traditional lecture group (p < 0.001). In terms of skills, student in the innovative group scored higher on the performance score than the control group (p < 0.01). The innovative course was 24 times more expensive. CONCLUSION: Combination of video and simulation allows better retention of knowledge than a traditional lecture and leads to better compliance to resuscitation guidelines. WHAT IS KNOWN: • Compliance by residents to pediatric resuscitation guidelines is low. • We developed an innovative pedagogic course combining an educational video and simulation. What is new: • Knowledge retention after the innovative course was better than after a traditional lecture. • Sixty-six students tested on their skills demonstrated better compliance to resuscitation guidelines.