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.

Early impact of 13-valent pneumococcal conjugate vaccine on community-acquired pneumonia in children.

BACKGROUND: Pneumococcal serotypes 1, 3, 5, 7F, and 19A were the most implicated in community-acquired pneumonia (CAP) after implementation of 7-valent pneumococcal conjugate vaccine (PCV7). In France, the switch from PCV7 to 13-valent pneumococcal conjugate vaccine (PCV13) occurred in June 2010. An active surveillance network was set up to analyze the impact of PCV13 on CAP. METHODS: An observational prospective study performed in 8 pediatric emergency departments from June 2009 to May 2012 included all children between 1 month and 15 years of age with chest radiography-confirmed pneumonia. Three 1-year periods were defined: pre-PCV13, transitional, and post-PCV13. RESULTS: During the 3-year study period, among the 953 274 pediatric emergency visits, 5645 children with CAP were included. CAP with pleural effusion and documented pneumococcal CAP were diagnosed in 365 and 136 patients, respectively. Despite an increase (4.5%) in number of pediatric emergency visits, cases of CAP decreased by 16% (2060 to 1725) between pre- and post-PCV13 periods. The decrease reached 32% in infants in the same periods (757 to 516; P < .001). Between pre- and post-PCV13 periods, the proportion of CAP patients with a C-reactive protein level >120 mg/dL decreased from 41.3% to 29.7% (P < .001), the number of pleural effusion cases decreased by 53% (167 to 79; P < .001) and the number of pneumococcal CAP cases decreased by 63% (64 to 24; P = .002). The number of additional PCV13 serotypes identified decreased by 74% (27 to 7). CONCLUSIONS: Our data suggest a strong impact of PCV13 on CAP, pleural effusion, and documented pneumococcal pneumonia, particularly cases due to PCV13 serotypes.

Evidence of a clonal expansion of Streptococcus pneumoniae serotype 19A in adults as in children assessed by the DiversiLab® system.

Streptococcus pneumoniae serotype 19A was the main serotype responsible for invasive pneumococcal disease (IPD) in the Paris area in 2007 and 2009 in both adults and children. To verify if a particular clone is emerging, we determined the populational structure of S. pneumoniae isolates. Eighty-four S. pneumoniae strains responsible for invasive infections isolated from 52 adults and 32 children hospitalized in Parisian hospitals were analyzed. Capsular typing was performed by polymerase chain reaction (PCR) using the semi-automated repetitive sequence-based (rep-PCR) DiversiLab® System. Multilocus sequence typing (MLST) was also performed on 26 strains (ten selected strains after cluster analysis and 16 control strains). In 2007 and 2009, S. pneumoniae serotype 19A represented, respectively, 28.6 % and 25 % of the serotypes involved in IPDs in children and 13 % and 13.7 % in adults. The rep-PCR DiversiLab® analysis showed that the 84 S. pneumoniae serotype 19A isolates were distributed in five clusters and four unique rep-PCR types. Overall, 77/84 (91.6 %) S. pneumoniae 19A serotypes grouped into three main genetically related clusters (71/77 belonged to the cluster I). The five other strains exhibited different profiles. Using MLST, we demonstrated that most strains of the main cluster belonged to clonal complex (CC) 230, sequence type (ST) 276. However, for the other strains, the DiversiLab® method cannot be used to predict to which ST a strain belongs. The DiversiLab® method allowed us to identify the clonal expansion of S. pneumoniae serotype 19A strains isolated from both children and adults in 2007 and 2009.

Invasive pneumococcal disease in HIV-infected adults in France from 2000 to 2011: antimicrobial susceptibility and implication of serotypes for vaccination.

PURPOSE: Invasive pneumococcal diseases (IPD) remain frequent and severe events in human immunodeficiency virus (HIV)-infected subjects despite the use of antiretroviral therapy and the availability of vaccines. Our aim was to assess the antibiotic susceptibilities and serotypes of strains responsible for IPD in HIV-infected patients. METHODS: We retrospectively analyzed all Streptococcus pneumoniae strains isolated from normally sterile sites between 2000 and 2011 in HIV-infected patients from a single reference center in Paris. The minimum inhibitory concentrations were determined by the E-test, and serotyping was performed by the antiserum agglutination method. RESULTS: Among our study group, 41 HIV-infected adults presented 43 IPD during the study period. Of these 41 patients, 78 % were men, and the median age was 43 (range 23-62) years. the median CD4 cell count was 184/mm(3) (6-1,090/mm(3)), 51 % were receiving antiretroviral therapy, and 24 % had plasma HIV-RNA levels of <400 copies/mL. Only two patients had received the pneumococcal polysaccharide 23-valent vaccine (PPV23). Isolates were susceptible to penicillin G, amoxicillin, and cotrimoxazole in 44, 70, and 59 % of cases, respectively, and were significantly less susceptible to these antibiotics than isolates in the French general population during the same period. Among the 27 strains serotyped, 18 different serotypes were observed, of which 19A, 14, 7F, and 6A were the most frequent. Serotype distribution was similar to that in the French general population. The PPV23 vaccine and the 13-valent conjugate vaccine (PCV13) would have theoretically covered 78 and 70 % of cases, respectively. CONCLUSIONS: In our HIV-infected patient cohort, S. pneumoniae isolates demonstrated higher levels of resistance to beta-lactamines and cotrimoxazole than in the French general population. HIV-infected patients should benefit from the herd protection effect expected from the large-scale vaccination of children by PCV13.

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.

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).

Point prevalence survey of antibiotic use in French hospitals in 2009.

OBJECTIVES: To evaluate the feasibility of a point prevalence survey for monitoring antibiotic use in a voluntary sample of French hospitals. METHODS: Demographic and medical data were collected for all inpatients. Additional characteristics regarding antimicrobial treatment, type of infection and microbiological results were collected only for patients receiving antimicrobials. RESULTS: Among 3964 patients in 38 hospitals, 343 (8.7%) received antimicrobial prophylaxis and 1276 (32.2%) antimicrobial therapy. The duration of surgical antimicrobial prophylaxis was >1 day in 41 out of 200 (21%) of the cases. Among patients with antimicrobial therapy, 959 (75.2%) received ß-lactams (including 34.8% penicillins with ß-lactam inhibitors, 22.1% third-generation cephalosporins and 7.8% carbapenems) and 301 (23.6%) received fluoroquinolones (50% orally). A total of 518 (40.6%) patients were treated with more than one drug and 345 (27.2%) were treated for >7 days. Patients treated for hospital-acquired infections (39.2%) were more likely to receive combinations (47.6% versus 34.4%, P < 0.01), carbapenems (14.4% versus 2.6%, P < 0.01), glycopeptides (14.4% versus 3.7%, P < 0.01) and antifungals (17% versus 5.3%, P < 0.01) for a longer duration (7.8 versus 6 days, P < 0.01). Fifty-six patients (4.4%) were treated for >7 days and did not have any microbiological sample drawn. The time allocated for the survey represented 18.3-25.0 h for 100 patients. CONCLUSIONS: The data provide directions for further interventions, such as better use of diagnostic tools, decreasing the treatment duration and the use of combinations. In addition, the survey shows that, although cumbersome, it is feasible to improve the representativeness of national data in European surveys.

Epidemiology of Streptococcus pneumoniae in France before introduction of the PCV-13 vaccine.

The purpose of this article was to describe the serotype incidence and antibiotic susceptibility of Streptococcus pneumoniae strains isolated from adults and children with invasive disease (IPD) or acute otitis media (AOM) before introduction of the 13-valent pneumococcal vaccine. During 2009, 494 strains of S. pneumoniae isolated were collected. Complete serotyping by latex antisera and molecular methods was performed. The most frequent serotypes isolated from children with IPD were 1 (26.2%), 19A (25%) and 7F (14.3%). Serotype 19A was predominant (42.1%) in children ≤ 2 years, whereas serotype 1 was predominant (63.3%) after the age of 5. Serotype 19A was the most frequently isolated serotype from AOM (62.3%). In adults, serotypes responsible for IPD were 7F (19.4%), 19A (13.7%), 1 (8.4%) and 3 (7.5%). The serotype 19A was predominant in adults older than 65 years (19.1%). The emergence of serotype 12F was observed in adults. Between 2007 and 2009, the introduction of PCV-7 has resulted in a significant decrease of IPD caused by serotypes included in the vaccine, in children as well as in adults, confirming the herd effect. Serotype coverage of PCV-13 was 70% and 80.9% for adult and children's IPD, respectively. PCV-13 will be more efficient in preventing invasive diseases among children and adults.

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.

Rebound in the incidence of pneumococcal meningitis in northern France: effect of serotype replacement.

AIM: To determine whether the recent emergence of nonvaccine pneumococcal serotypes has affected the incidence of pneumococcal meningitis in children a few years after the introduction of the heptavalent pneumococcal conjugate vaccine. METHODS: We conducted a multicentre retrospective cohort study from 2005 to 2008 in all hospitals with paediatric units in northern France. It included all patients < 18 years of age who were admitted for laboratory-confirmed pneumococcal meningitis during the study period. Data were collected from medical files and laboratory records at each hospital and compared with the regional hospital discharge codes. We assessed global and age-specific incidence rates of pneumococcal meningitis from 2005 through 2008, compared them with those from the prevaccine era (2000-2002) and evaluated pneumococcal serotypes. RESULTS: In all, 41 cases were found during the study period. The incidence rate of pneumococcal meningitis varied from 0.8/100,000 children < 18 years in 2005 to 1.8/100,000 children in 2008 (2.2-fold increase, p = 0.06); and from 1.8 to 11.9/100,000 children < 2 years (6.5-fold increase, p = 0.004). This increase was caused by nonvaccine pneumococcal serotypes. CONCLUSION: The incidence of pneumococcal meningitis in infants has rebounded in northern France during the pneumococcal conjugate vaccine programme, with the emergence of nonvaccine pneumococcal serotypes.

Pharmacokinetics and milk penetration of difloxacin after a long-acting formulation for subcutaneous administration to lactating goats.

The single-dose disposition kinetics of difloxacin were determined in clinically normal lactating goats (n=6) after intravenous (IV) and subcutaneous (SC) administration and subcutaneous administration of a long-acting poloxamer 407 gel formulation (P407). Difloxacin concentrations were determined by HPLC with fluorescence detection. Minimum inhibitory concentrations of difloxacin against 14 strains of Staphylococcus aureus isolated from mastitic goats' milk in Spain were determined to compute pharmacodynamic surrogate markers. The concentration-time data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Following SC and P407 administration, difloxacin achieved maximum milk concentrations of 1.34+/-0.12 and 2.97+/-1.18 mg/L, respectively, at 4.00+/-0.00 h (SC) and 3.60+/-0.89 h (P407) after administration. The absolute bioavailabilities after SC and P407 administration were 81.74+/-15.60% and 72.58+/-20.45%, respectively. Difloxacin penetration from the blood into the milk was good and high concentrations were found in milk secretions. From these data, a 15 mg/kg dose of difloxacin P407 would appear to be effective against Staphylococcus aureus isolated from mastitic goats' milk with minimum inhibitory concentrations

Short communication: Fluoroquinolone susceptibility of Staphylococcus aureus strains isolated from caprine clinical mastitis in southeast Spain.

The antibiotic susceptibility of 32 strains of Staphylococcus aureus isolated from the mastitic milk of dairy goats was evaluated. The antibiotics tested were 3 fluoroquinolones that have been developed especially for use in veterinary medicine: danofloxacin, marbofloxacin, and orbifloxacin. Minimum inhibitory concentration (MIC) tests were performed according to the microdilution broth method. The MIC(90) (concentration at which 90% inhibition is achieved) values obtained were 0.5, 1, and 1 mg/L for danofloxacin, marbofloxacin, and orbifloxacin, respectively. Danofloxacin was the most active fluoroquinolone tested against Staph. aureus strains isolated from milk; however, specific testing is required before using these drugs as therapy for the control of clinical mammary infections in goats.

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.

[Antibiotics susceptibility of Streptococcus and Enterococcus: data of Onerba network]. / Sensibilité aux antibiotiques chez les streptocoques (hors pneumocoque) et les entérocoques: données Onerba.

This work was aimed to analyze trends in susceptibility to antibiotics among the main species of beta-hemolytic streptococci involved in community-acquired infections in human (Streptococcus pyogenes and Streptococcus agalactiae), or in animals (Streptococcus suis and Streptococcus uberis) and also among the main enterocci species, Enterococcus faecalis and Enterococcus faecium. Data were recorded since 1996 through the Onerba networks. S. pyogenes, as the other beta-hemolytic streptococci studied remained fully susceptible to beta-lactam antibiotics. However, susceptibility to macrolides is clearly decreasing in S. pyogenes. In 2002, only 62 to 65% of the strains according to the network considered, were susceptible to erythromycin. A similar trend was observed for S. agalactiae with only 75% of erythromycin susceptibility in 2002, and for both species isolated from animals S. suis and S. uberis, with respectively 35 and 76% of strains susceptible to erythromycin. In enterococci, susceptibility to beta-lactams remained stable between 2000 and 2004. Indeed, the susceptibility to aminopenicillins remained high in E. faecalis (about 98%), whereas the proportion of E. faecium isolates susceptible to these antibiotics were lower than 60%. From 1999 to 2004, various studies conducted in French hospitals showed that the vancomycin resistance among enterococci accounted for less than 2%. However, the recent emergence of glycopeptide resistant enterococci clusters in French hospitals is a matter of concern and emphasizes the need for an ongoing surveillance. Such trend in macrolide resistance among S. pyogenes or S. agalactiae should consequently lead to propose other alternatives in case of beta-lactam allergy, and for pharyngitis, to rethink the place of the culture for susceptibility testing.

[Epidemiology of acute bacterial meningitis in adult patients in France]. / Actualisation de l'épidémiologie des méningites bactériennes aiguës chez l'adulte en France.

In 2006, the number of bacterial meningitis cases was estimated at 1375 (2.23/100,000). The leading pathogens involved in adult meningitis were, according to frequency, Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes, Streptococcus agalactiae, and Haemophilus influenzae. The overall mortality rate averaged 20%, higher among patients with pneumococcal meningitis or in individuals over 65 years of age. Sequels were observed in 30% of cases and more frequent after pneumococcal meningitis. A decrease in susceptibility to antibiotics was reported for N. meningitidis, S. pneumoniae and H. influenzae. Generalized vaccination of children less than two years of age with H. influenzae type b conjugate vaccine has lead to a dramatic decrease in adult H. influenza meningitis. The few cases involved almost exclusively non-typeable strains, presenting in 12% of cases, a modified penicillin binding protein leading to a decreased susceptibility to aminopenicillins. Decreased susceptibility to amoxicillin was observed in 30% of meningococcal isolates, but all strains remained susceptible to parenteral third generation cephalosporins. Resistances to rifampicin or to ciprofloxacin, recommended in meningococcal meningitis prophylaxis, were unusual, but had to be documented. Finally, the proportion of pneumococcal strains with decreased susceptibility to beta-lactams has decreased since 2002. In adult meningitis, pneumococcal isolates with decreased susceptibility to penicillin, amoxicillin, and cefotaxime or ceftriaxone accounted for 37, 18, and 4% of cases respectively. It should be noted that for these isolates, no parenteral third generation cephalosporins MIC was above 2mg/l. Resistance to rifampin was very unusual and all pneumococcal isolates were fully susceptible to glycopeptides.

Impact of infant pneumococcal vaccination on invasive pneumococcal diseases in France, 2001-2006.

Vaccination with the 7-valent pneumococcal conjugate vaccine (PCV) has been recommended in France since 2003 for children under the age of two years who are at risk due to medical or living conditions. From 2006, the recommendation has been extended to all children under two years. The impact of PCV introduction on the incidence of pneumococcal meningitis and bacteraemia and on the serotype distribution in French children and other age-groups was assessed using laboratory surveillance data. The coverage with three doses of PCV was 44% in children aged 6-12 months in 2006. From 2001/2002 to 2006, the incidence of pneumococcal meningitis decreased from 8.0 to 6.0 cases per 100,000, and the incidence of pneumococcal bacteraemia decreased from 21.8 to 17.5 cases per 100,000 in children under the age of two years. For the vaccine strains, the incidence of pneumococcal meningitis and bacteraemia decreased from 20,4 to 6.0 cases per 100,000, while the incidence of pneumococcal meningitis and bacteraemia due to non-vaccine strains increased from 9.4 to 17.5 cases per 100,000 in this time period. The incidence in older children and adults did not decrease. Further expansion of PCV coverage is expected to increase the impact of the vaccination in both children and adults. However, the fact that cases caused by vaccine serotypes have been partially substituted by cases of non-vaccine serotypes is likely to reduce the overall benefit of PCV in France, should this early observation be confirmed in the future.

Disposition kinetics and pharmacokinetics--pharmacodynamic integration of difloxacin against Staphylococcus aureus isolates from rabbits.

The pharmacokinetics of difloxacin were studied following intravenous (IV), subcutaneous (SC) and oral administration of 5mg/kg to healthy white New Zealand rabbits (n = 6). Difloxacin concentrations were determined by HPLC assay with fluorescence detection. Minimal inhibitory concentrations (MICs) assay of difloxacin against different strains of S. aureus from different european countries was performed in order to compute the main pharmacodynamic surrogate markers. The plasma difloxacin clearance (Cl) for the IV route was (mean +/- SD) 0.41 +/- 0.05 L/h kg. The steady-state volume of distribution (V(ss)) was 1.95 +/- 0.17 L/kg. The terminal half-life [Formula: see text] was (mean+/-SD) 4.19+/-0.34 h, 7.53 +/- 1.32 h and 8.00 +/- 0.45 h after IV, IM and oral, respectively. From this data, it seems that a 5 mg/kg dose difloxacin would be effective by SC and oral routes in rabbits against bacterial isolates with MIC0.1 microg/mL.

[Pneumococcal meningitis in children in France: 832 cases from 2001 to 2007]. / Méningites à pneumocoque de l'enfant en France : 832 cas de 2001 à 2007.

BACKGROUND: Pneumococcal meningitis represents one major cause of morbidity and mortality in children in France. The GPIP/ACTIV (Groupe de Pathologie Infectieuse Pédiatrique and Association Clinique et Thérapeutique Infantile du Val de Marne) set up an active surveillance network to analyze the clinical and biological features of pneumococcal meningitis and the impact of 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: From 2001 to 2007, 252 French pediatric wards working with 168 microbiology laboratories enrolled all children (0-18 years old) with bacterial meningitis. Risk factors, signs and symptoms, vaccination status, cerebrospinal fluid analysis, treatments and case fatality rate were recorded. RESULTS: Within the 7 years study period, 832 pneumococcal meningitis were reported among 2951 bacterial meningitis. In 2001 as in 2007, excluding the neonatal period, pneumococal meningitis represented nearly 1/3 of bacterial meningitis without significant decline in the number of reported cases (less than 30% for children under 2 years old). The peak of incidence was at 5 months of age and 61.7% of cases occured in children 2 to 24 months old. PCV7 vaccinated patients represented 154 cases from 2003 to 2007. In the vaccinated population, serotypes were identified in 136 cases. Few vaccine serotypes (VT) were identified (n=18). The most important was serotype 19F (n=8) followed by 6B (n=4) and 14 (n=3). Three vaccine failures (case occurring after complete vaccination) were observed (serotypes 6B, 4 and 19F). Remaining cases (n=118) were mainly due to non vaccine serotypes (NVT): serotypes 19A, 15B/C and 7F. In 2007, the serotype 19A, more often intermediary strains to cytoxin, represented about 20% of cases. Among non vaccinated children, VT decreased between 2001 and 2007 (59/92 in 2001 vs 15/39 in 2007). Case fatality rate was stable around 11.4%. CONCLUSION: In France, probably because of the insufficient vaccination coverage and the slow implementation of the PCV7, the expected decline in the number of cases of pneumococcal meningitis has not been observed. The impact of PCV7 appeared clearly since only few cases of VT pneumococcal meningitis were reported in vaccinated children.