SPILF update on bacterial arthritis in adults and children.

In 2020 the French Society of Rhumatology (SFR) published an update of the 1990 recommendations for management of bacterial arthritis in adults. While we (French ID Society, SPILF) totally endorse this update, we wished to provide further information about specific antibiotic treatments. The present update focuses on antibiotics with good distribution in bone and joint. It is important to monitor their dosage, which should be maximized according to PK/PD parameters. Dosages proposed in this update are high, with the optimized mode of administration for intravenous betalactams (continuous or intermittent infusion). We give tools for the best dosage adaptation to conditions such as obesity or renal insufficiency. In case of enterobacter infection, with an antibiogram result "susceptible for high dosage", we recommend the requesting of specialized advice from an ID physician. More often than not, it is possible to prescribe antibiotics via the oral route as soon as blood cultures are sterile and clinical have symptoms shown improvement. Duration of antibiotic treatment is 6 weeks for Staphylococcus aureus, and 4 weeks for the other bacteria (except for Neisseria: 7 days).

Invasive pneumococcal infections in France: Changes from 2009 to 2021 in antibiotic resistance and serotype distribution of Streptococcus pneumoniae based on data from the French Regional Pneumococcal Observatories network.

OBJECTIVE: The 23 French Regional Pneumococcal Observatories (ORPs) analyzed antibiotic resistance and serotypes of Streptococcus pneumoniae strains isolated from invasive infections in France over a 12-year period. METHODS: Between 2009 and 2021, the ORPs analyzed 19,319 strains, including 1,965 in children and 17,354 in adults. Strains were assessed for their resistance to penicillin G, amoxicillin and cefotaxime. Serotypes were identified in collaboration with the National Reference Centre. RESULTS: During this period, the number of strains collected yearly decreased significantly. The decrease was particularly pronounced up until 2013, especially in children (-61.0%). However, penicillin non-susceptible strains (PNSPs) increased in children (24.7% in 2009 vs 45.0% in 2021, p < 0.0001) and in adults (27.1% in 2009 vs 31.3% in 2021, p < 0.05), as well as resistance (I + R) to amoxicillin (children: 12.5% in 2009 vs 19.4% in 2021, p < 0.05; adults: 13.4% in 2009 vs 14.5% in 2021, NS) and resistance (I + R) to cefotaxime (children: 8.0% in 2009 vs 13.1% in 2021, p < 0.05; adults: 7.1% in 2009 vs 11.9% in 2021, p < 0.0001). All in all, the proportion of strains belonging to serotypes present in the PCV13 vaccine has fallen sharply, from 64.8% in 2009 to 23.6 % in 2021. At the same time, serotypes such as 8, 10A, 11A, 15B/C and 9N, not included in PCV13, were increasing. CONCLUSION: During the study period, data collected by the network highlighted an increase of invasive PNSPs in children and non-vaccine serotypes. Surveillance of resistance and serotypes remains instrumental, particularly to monitor the evolution of vaccine efficacy.

2010 French SPILF-AFSSAPS guiding criteria for Streptococcuspneumoniae acute community-acquired pneumonia: Evaluation in patients of the PACSCAN-ESCAPED cohort.

OBJECTIVE: To assess the proportion of patients meeting the 2010 SPILF-AFSSAPS guiding criteria for Streptococcuspneumoniae in patients consulting at the emergency departments of four French university hospitals for acute community-acquired pneumonia (CAP) suspicion. PATIENTS AND METHODS: The PACSCAN study prospectively included 319 patients. Medical history, clinical, biological, and radiological presentations were collected. An adjudication committee retrospectively classified the diagnostic certainty based on the initial chest CT scan data and the follow-up data up to Day 28. S. pneumoniae was looked for according to the clinician's choice of blood culture, pneumococcal urinary antigen test, nasopharyngeal PCR, and/or sputum microbiological examination. RESULTS: All patients (100%) met at least one criterion for S. pneumoniae CAP and six (2%) met all criteria. The distribution of criteria ranged from 32% (chest pain criterion) to 86% (age≥40years criterion). These figures were respectively 100%, 3%, 38%, and 82% when the study population was restricted to the 139 patients with definite or probable CAP, according to the adjudication committee. Taking into account the microbiological results, the criteria taken one by one or combined did not make it possible to differentiate the 19 S. pneumoniae CAP from the other CAPs. CONCLUSION: The 2010 SPILF-AFSSAPS guiding criteria for S. pneumoniae CAP are found in very variable proportions and do not, in their current form, make it possible to accurately guide towards a pneumococcal etiology in patients included in the PACSCAN study.

Community-acquired bacterial meningitis in adults: in-hospital prognosis, long-term disability and determinants of outcome in a multicentre prospective cohort.

OBJECTIVES: To identify factors associated with unfavourable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM). METHODS: In a prospective multicentre cohort study (COMBAT; February 2013 to July 2015), all consecutive cases of CABM in the 69 participating centres in France were enrolled and followed up for 12 months. Factors associated with unfavourable outcome were identified by logistic regression and long-term disability was analysed. RESULTS: Among the 533 individuals enrolled, (Streptococcus pneumoniae 53.8% (280/520 isolates identified), Neisseria meningitidis 21.3% (111/520), others 24.9% (129/520)), case fatality rate was 16.9% (90/533) and unfavourable outcome occurred in 45.0% (225/500). Factors independently associated with unfavourable outcome were: age >70 years (adjusted odds ratio (aOR) 4.64; 95% CI 1.93-11.15), male gender (aOR 2.11; 95% CI 1.25-3.57), chronic renal failure (aOR 6.65; 95% CI 1.57-28.12), purpura fulminans (aOR 4.37; 95% CI 1.38-13.81), localized neurological signs (aOR 3.72; 95% CI 2.29-6.05), disseminated intravascular coagulation (aOR 3.19; 95% CI 1.16-8.79), cerebrospinal fluid (CSF) white-cell count <1500 cells/µL (aOR 2.40; 95% CI 1.42-4.03), CSF glucose concentration (0.1-2.5 g/L: aOR 1.92; 95% CI 1.01-3.67; <0.1 g/L: aOR 2.24; 95% CI 1.01-4.97), elevated CSF protein concentration (aOR 1.09; 95% CI 1.03-1.17), time interval between hospitalization and lumbar puncture >1 day (aOR 2.94; 95% CI 1.32-6.54), and S. pneumoniae meningitis (aOR 4.99; 95% CI 1.98-12.56), or meningitis other than N. meningitidis (aOR 4.54; 95% CI 1.68-12.27). At 12 months, 26.7% (74/277) had hearing loss, 32.8% (87/265) depressive symptoms, 31.0% (86/277) persistent headache, and 53.4% had a physical health-related quality of life (142/266) <25th centile of the distribution of the score in the general French population (p < 0.0001). CONCLUSIONS: The burden of CABM (death, disability, depression, impaired quality of life and hearing loss) is high. Identification of cases from the first symptoms may improve prognosis. CLINICALTRIAL: Gov identification number: NCT01730690.

Community-acquired pneumonia in the emergency department: an algorithm to facilitate diagnosis and guide chest CT scan indication.

OBJECTIVE: The aim was to create and validate a community-acquired pneumonia (CAP) diagnostic algorithm to facilitate diagnosis and guide chest computed tomography (CT) scan indication in patients with CAP suspicion in Emergency Departments (ED). METHODS: We performed an analysis of CAP suspected patients enrolled in the ESCAPED study who had undergone chest CT scan and detection of respiratory pathogens through nasopharyngeal PCRs. An adjudication committee assigned the final CAP probability (reference standard). Variables associated with confirmed CAP were used to create weighted CAP diagnostic scores. We estimated the score values for which CT scans helped correctly identify CAP, therefore creating a CAP diagnosis algorithm. Algorithms were externally validated in an independent cohort of 200 patients consecutively admitted in a Swiss hospital for CAP suspicion. RESULTS: Among the 319 patients included, 51% (163/319) were classified as confirmed CAP and 49% (156/319) as excluded CAP. Cough (weight = 1), chest pain (1), fever (1), positive PCR (except for rhinovirus) (1), C-reactive protein ≥50 mg/L (2) and chest X-ray parenchymal infiltrate (2) were associated with CAP. Patients with a score below 3 had a low probability of CAP (17%, 14/84), whereas those above 5 had a high probability (88%, 51/58). The algorithm (score calculation + CT scan in patients with score between 3 and 5) showed sensitivity 73% (95% CI 66-80), specificity 89% (95% CI 83-94), positive predictive value (PPV) 88% (95% CI 81-93), negative predictive value (NPV) 76% (95% CI 69-82) and area under the curve (AUC) 0.81 (95% CI 0.77-0.85). The algorithm displayed similar performance in the validation cohort (sensitivity 88% (95% CI 81-92), specificity 72% (95% CI 60-81), PPV 86% (95% CI 79-91), NPV 75% (95% CI 63-84) and AUC 0.80 (95% CI 0.73-0.87). CONCLUSION: Our CAP diagnostic algorithm may help reduce CAP misdiagnosis and optimize the use of chest CT scan.

Proposal for shorter antibiotic therapies.

OBJECTIVES: Reducing antibiotic consumption has now become a major public health priority. Reducing treatment duration is one of the means to achieve this objective. Guidelines on the therapeutic management of the most frequent infections recommend ranges of treatment duration in the ratio of one to two. The Recommendation Group of the French Infectious Diseases Society (SPILF) was asked to collect literature data to then recommend the shortest treatment durations possible for various infections. METHODS: Analysis of the literature focused on guidelines published in French and English, supported by a systematic search on PubMed. Articles dating from one year before the guidelines publication to August 31, 2015 were searched on the website. RESULTS: The shortest treatment durations based on the relevant clinical data were suggested for upper and lower respiratory tract infections, central venous catheter-related and uncomplicated primary bacteremia, infective endocarditis, bacterial meningitis, intra-abdominal, urinary tract, upper reproductive tract, bone and joint, skin and soft tissue infections, and febrile neutropenia. Details of analyzed articles were shown in tables. CONCLUSION: This work stresses the need for new well-conducted studies evaluating treatment durations for some common infections. Following the above-mentioned work focusing on existing literature data, the Recommendation Group of the SPILF suggests specific study proposals.

Susceptibility and PK/PD relationships of Staphylococcus aureus strains from ovine and caprine with clinical mastitis against five veterinary fluoroquinolones.

Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of veterinary fluoroquinolones as enrofloxacin, its metabolite ciprofloxacin, danofloxacin, difloxacin and marbofloxacin against Staphylococcus aureus strains (n=24) isolated from milk of sheep and goats affected by clinical mastitis were evaluated. The authors have used the MIC and MPC, as well as the pharmacokinetic-pharmacodynamic relationships in plasma and milk. MIC values were significantly different between drugs, unlike MPC values. Lower MIC values were obtained for danofloxacin and difloxacin, middle and higher values for enrofloxacin, ciprofloxacin and marbofloxacin. However, differences in MPC values were not found between drugs. At conventional doses, the AUC24/MIC and AUC24/MPC ratios were close to 30-80 hours and 5-30 hours, with exception of danofloxacin, in plasma and milk. The time inside the mutant selection window (TMSW) was close to 3-6 hours for enrofloxacin, ciprofloxacin and marbofloxacin, near to 8 hours for danofloxacin and 12-22 hours for difloxacin. From these data, the mutant selection window could be higher for danofloxacin and difloxacin compared with the other fluoroquinolones tested. The authors concluded that enrofloxacin and marbofloxacin, at conventional doses, could prevent the selection of bacterial subpopulations of S aureus, unlike danofloxacin and difloxacin, where higher doses could be used.

Demonstration of the herd effect in adults after the implementation of pneumococcal vaccination with PCV13 in children.

The purpose of this investigation was to describe the evolution of serotypes and antibiotic susceptibility of Streptococcus pneumoniae strains isolated from both adults and children from the same population area with invasive pneumococcal disease (IPD) or acute otitis media (AOM), 5 years after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). From 2009 to 2015, 839 strains of S. pneumoniae strains were collected (481 from adults and 358 from children). Serotyping by latex antisera and molecular methods was performed. Antimicrobial susceptibility was tested. Compared to 2009, the total number of strains isolated in 2015 decreased in children (263 vs. 53, respectively) and in adults (220 vs. 131, respectively). Serotype coverage of PCV13 for IPD decreased significantly in adults from 67.7% (149/220) to 25.2% (33/131) and in children from 75.1% (61/81) to 18.5% (5/27). Especially, serotypes 1, 7F and 19A decreased significantly in children, while serotypes 7F and 19A decreased significantly in adults. PCV13 serotypes involved in AOM decreased significantly over the 5-year period, from 85.7% (156/182) to 38.5% (10/26), and were more susceptible to penicillin, amoxicillin and cefotaxime, p < 0.05. Serotypes 8, 9N and 10A seemed to emerge in adults, whereas any serotype prevalence was observed in children. Between 2009 and 2015, the introduction of PCV13 has resulted in a significant decrease of the number of S. pneumoniae strains isolated from IPD in children as in adults. It highlights a strong herd effect of vaccination in adults.

Impact of the 13-valent pneumococcal conjugate vaccine on the incidence of pneumococcal meningitis in children.

The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of pneumococcal meningitis (PM) in children is unknown. To determine this impact, a descriptive multicentre retrospective cohort study was conducted from 2008 to 2013 in northern France. All laboratory-confirmed PM in children aged <18 years in all hospitals of the area with paediatric units were included. Two independent databases were used for exhaustive identification of cases: medical plus laboratory records at each hospital and discharge codes. The corrected incidence of PM was determined by a capture-recapture analysis using these two databases. Sixty-two cases were found over the 6-year period. A decrease of the PM corrected incidence was observed in the global population (P = 0·07), significant only for children aged <2 years, from 11·9/100 000 in 2008 in 1·9/100 000 in 2013 [6·4 fold-decrease, 95% confidence interval (CI) 1·4-41, P = 0·01] between years 2008 and 2013. When comparing the pre- and post-PCV13 periods, this decrease was still statistically significant for children aged <2 years [7·32/100 000 (95% CI 4·39-10·25) to 2·78/100 000 (95% CI 0·96-4·60), P = 0·01]. Only three (5%) cases of PM caused by vaccine serotypes could have been prevented. After the introduction of the PCV13 vaccine, a decrease in the incidence of PM cases in children in northern France was observed.

Antibiotic use and good practice in 314 French hospitals: The 2010 SPA2 prevalence study.

OBJECTIVES: We aimed to assess antibiotic prescriptions to identify potential targets for improvement. METHODS: We conducted a point prevalence survey (November 2010) of antibiotic use in 314 voluntary hospitals recruited by the French Infectious Diseases Society (SPILF) and the National Observatory for Epidemiology of Bacterial Resistance to Antimicrobials (ONERBA). Data were entered online, immediately analyzed and exported. RESULTS: The prevalence of antibiotic use was 19.5% (9059/46,446patients). A higher prevalence was observed in the infectious disease (58.4%), hematology (58%), and intensive care (48.7%) units. The three most frequently used antibiotic classes were aminopenicillins (23.8%), fluoroquinolones (17.9%), and 3rd-generation cephalosporins (16.7%). A monotherapy was prescribed to 64% of patients. The reasons for the antibiotic prescription were written in the medical records of 74% of patients and 62% were consistent with the local guidelines. CONCLUSION: Our results are similar to that of other studies. Various local targets for improvement have been identified to help hospitals define a better antibiotic stewardship.

Decline in antibiotic resistance and changes in the serotype distribution of Streptococcus pneumoniae isolates from children with acute otitis media; a 2001-2011 survey by the French Pneumococcal Network.

Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.

Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001-2012.

CONTEXT AND AIMS: Vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) was recommended in France in 2003 for children <2 years. The 13-valent conjugate vaccine (PCV13) replaced PCV7 in 2010. We assessed the impact of PCVs vaccination on the incidence of invasive pneumococcal diseases (IPD) in French children (0-15 years) and adults (>15 years). METHODS: IPD rates were calculated using cases reported from 2001 to 2012 to Epibac, a laboratory network. The distribution of serotypes was assessed from invasive isolates serotyped at the National reference Centre for Pneumococci. IPD incidence rates were compared between the pre-PCV7 (2001-2002), late PCV7 (2008-2009) and post PCV13 (2012) periods. RESULTS: The PCVs coverage increased from 56% in the 2004 birth-cohort to 94% in the 2008 and following birth-cohorts. Following PCV7 introduction, IPD incidence decreased by 19% between 2001-2002 and 2008-2009 in children <2 years, but increased in children aged 2-15 years and adults, despite a sharp decline in PCV7-IPD in all age-groups. After PCV13 introduction, IPD incidence decreased by 34% in children <5 years, by 50% in those aged 5-15 years and 15% in adults from 2008-2009 to 2012. The incidence of PCV13-Non PCV7-IPD decreased by 74% in children <5 years and by 60% in those aged 5-15 years. CONCLUSIONS: Vaccination with PCV13 was rapidly followed by a decrease in the incidence of all-type IPD in children, in relation with a sharp decrease in the incidence of PCV13-Non PCV7-IPD. Moreover, all-type IPD decreased after PCV13 introduction in older non-vaccinated age-groups, with a shift in the distribution of serotypes. Considering the whole 2001-2012 period, the vaccination with PCV7 and PCV13 resulted in a decline in the incidence of IPD in children up to the age of 5 but not in older children and adults.