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Since the introduction of the varicella vaccine to the routine immunization schedule, we have observed a 70% reduction in the rate of varicella-associated invasive group A streptococcal infections (IGASI). In the mean time, the clinical presentation of IGASI and microbiological characteristics of GAS strains have changed significantly., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: This study aims to analyze the epidemiology of Group A streptococci (GAS) emm-types causing invasive and noninvasive infections in French children., Methods: From September 2009 to May 2011, we analyzed GAS isolates from 585 pharyngitis, 125 invasive infections and, for the first time in France, 32 healthy carriers. M protein gene (emm) typing of the isolates was carried out by a new rapid technique, combining 3 multiplex-polymerase chain reactions (PCRs) coupled to high-resolution melting (HRM) curves, able to detect 13 major emm-types (emm 1, 3, 4, 6, 11, 12, 22, 28, 75, 77, 87, 89 and 102)., Results: GAS belonging to emm-type 1 were more frequently found among invasive infections than among pharyngitis (24.0% vs. 11.5%, P < 0.001); emm 4 and 89 were more common in pharyngitis than in invasive infections (emm-type 4, 17.4% vs. 6.4%, P = 0.002 and emm-type 89, 9.9% vs. 2.4%, P = 0.006, respectively) and emm 3 and 4 were more common in cases of pharyngitis associated with scarlet fever (21.6% vs. 6.0%, P < 0.001 and 29.3% vs. 14.5%, P < 0.001, respectively)., Conclusion: HRM method enables the rapid emm-typing of a large number of isolates in epidemiological studies. Comparison of GAS causing invasive and noninvasive infections in the same population of children displays an unbalanced repartition of emm-types.

In industrialized countries, group A streptococcal infections were a source of concern, mainly due to the occurrence of rheumatic fever and its cardiac complications. At present, the incidence of rheumatic fever is decreasing in these countries, giving way to an increasing occurrence of invasive streptococcal group A infections with high level of morbidity and mortality. Streptococcal necrotizing fasciitis, a specific entity, emerged these last decades, often in association with chickenpox. The introduction of the varicella vaccine in the province of Quebec routine immunization program, was followed by a significant decrease in the number of necrotizing fasciitis or other skin and soft-tissues infections in our pediatric population. However, in our experience at the CHU Sainte-Justine, this immunization program has not been helpful to reduce the overall incidence of invasive group A streptococcal infections. Conversely, an increase in the number of pleuro-pulmonary and osteo-articular infections was observed., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Group A Streptococcus (GAS) is a human pathogen responsible for a wide range of clinical manifestations. An increase of GAS invasive infections has been described since the mid 1980s. To study the French epidemiology of invasive infections (i) we characterized all GAS invasive strains received at the French National Reference Center for streptococci (CNR-Strep) between 2007 and 2011; (ii) we analyzed the epidemiological data on the corresponding strains. For each strain, emm genotype, superantigen genes and antibiotics susceptibility were determined. Among the 2 603 non redundant invasive GAS strains, 65.1 % (n=1 695) were isolated from blood culture. A streptococcal toxic shock syndrome (STSS) was described in 16.4 % (n=428) of cases, mostly associated with necrotizing fasciitis (NF), pleuropulmonary or osteoarticular infections (p ≤0.001). The case fatality rate was 10.6 %. A total of 102 different emm genotypes were identified. Three emm genotypes predominated, reaching nearly 60 % of the strains: emm 1 (26.7 %), emm 28 (16.4 %), and emm 89 (12.8 %). The proportion of each emm genotype varied according to the year and the age of patients. Among those < 15 years old, the three main genotypes were emm 1 (36.8 %), emm 12 (12.9 %) and emm 4 (9.5 %). The distribution of superantigen genes (SpeA, SpeC and Ssa) was restricted to several emm genotypes. Between 2007 and 2011, the rate of macrolides resistant GAS strains decreased from 7.8 to 5.5 %. emm 1 strains are still the most common especially in most severe clinical manifestations including STSS and NF., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

We aimed to assess the independent effect of clinical spectrum, bacterial inoculum size and physician characteristics on the sensitivity of a rapid antigen detection test (RADT) for group A streptococcus (GAS) in children. Double throat swabs were collected from 1,482 children with pharyngitis and 294 asymptomatic children in a French prospective, office-based, multicenter (n = 17) study, from October 2009 to May 2011. Patient- and physician-level factors potentially affecting RADT sensitivity were studied by univariate and multivariate multilevel analysis, with laboratory throat culture as the reference test. In children with pharyngitis and asymptomatic children, the prevalence of GAS was 38 % (95 % confidence interval 36-41 %) and 11 % (7-14 %), respectively. Overall, RADT sensitivity was 87 % (84-90 %). On stratified and multivariate multilevel analysis, RADT sensitivity was higher for children with pharyngitis than asymptomatic children (89 % vs. 41 %), children <9 than ≥ 9 years old (88 % vs. 79 %) and those with heavy than light inoculum (94 % vs. 53 %). RADT sensitivity was influenced by the physician performing the test (range 56-96 %, p = 0.01) and was higher for physicians with hospital-based clinical activity in addition to office-based practice (adjusted odds ratio 3.4 [95 % confidence interval 1.9-6.3], p < 0.001); inter-physician variations in RADT sensitivity were largely explained by this variable (proportional change in variance >99 %). The sensitivity of the RADT is independently affected by patient- and physician-level factors. Physicians who base their diagnosis of GAS pharyngitis on the results of a RADT alone should consider diagnostic accuracy monitoring and adequate training when needed.

We investigated mechanisms of the false-positive test results on rapid-antigen detection test (RADT) for group A Streptococcal (GAS) pharyngitis. Most RADT false-positives (76%) were associated with polymerase chain reaction-positive GAS results, suggesting that RADT specificity could be considered close to 100%. Finding that 61% of GAS culture-negative but RADT-positive cases were positive on both GAS polymerase chain reaction and Staphylococcus aureus testing, we posit bacterial inhibition as causative., (Copyright © 2013 Mosby, Inc. All rights reserved.)

We studied the macrolide resistance and serotypes of 585 group A streptococcus (GAS) isolates collected from French children with pharyngitis. Nineteen isolates (3.2%) were erythromycin-resistant and harbored the following resistance genes: 31.6% mef(A), 15.8% erm(A), and 52.6% erm(B). The 19 isolates included 7 different emm types (4, 1, 11, 2, 28, 12, and 77) and 7 corresponding multilocus sequence types. The current fall in macrolide consumption has led to a very low rate of GAS macrolide resistance., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

M/emm typing, based either on serotyping of the M protein or on sequencing of the emm gene, is a major tool for epidemiological studies of group A streptococci (GAS). In order to simplify M/emm typing, we designed two multiplex polymerase chain reaction (PCR) formats capable of identifying the most frequent GAS M/emm types involved in invasive infections and antimicrobial resistance. A heptaplex PCR procedure was first developed in a conventional format coupled with gel electrophoresis to identify emm types 1, 3, 4, 6, 12, 28, and 89, based on the size of the amplification products. The other method, designed to identify the same seven emm types, together with emm11, was based on a real-time PCR format coupled with high-resolution melting (HRM) analysis, allowing the rapid typing of large strain collections.

Invasive group A streptococcal (GAS) infections cause significant morbidity and mortality. A national survey was initiated to assess the burden of invasive GAS infections in France, describe their clinical characteristics, and assess the molecular characteristics of GAS strains responsible for these infections. The survey was conducted in 194 hospitals, accounting for 51% of acute care hospital admissions in France. Clinical data, predisposing factors, and demographic data were obtained, and all GAS isolates were emm sequence typed. We identified 664 cases of invasive GAS infections, with an annual incidence of 3.1 per 100,000 population. The case-fatality ratio was 14% and rose to 43% in the case of streptococcal toxic shock syndrome. Bacteremia without identified focus (22%) and skin/soft tissue infections (30%) were the most frequent clinical presentations. Necrotizing fasciitis was frequent in adults (18%) and uncommon in children (3%). The 3 predominant emm types were emm1, emm89, and emm28, accounting for 33%, 16%, and 10% of GAS isolates, respectively. The emm1 type was associated with fatal outcomes and was more frequent in children than in adults. Six clusters of cases were identified, with each cluster involving 2 invasive cases due to GAS strains which shared identical GAS emm sequence types. Four clusters of cases involved eight postpartum infections, one family cluster involved a mother and child, and one cluster involved two patients in a nursing home. Invasive GAS infection is one of the most severe bacterial diseases in France, particularly in persons aged ≥ 50 years or when associated with toxic shock syndrome.

Background: Acute bacterial parotitis is a rare infectious disease in infants under 3 months of age., Objectives: To describe the clinical characteristics and the course of acute bacterial parotitis in infants less than 3 months old., Patients and Methods: Infants under 3 months of age, hospitalized at Robert Debré university hospital, Paris, France, between January 2005 and December 2009 for acute bacterial parotitis, were included in a retrospective study., Results: Five infants less than 3 months of age were included in this study, for a frequency of 2.5/1000 hospitalizations in this age group. All were born at term, 4 of 5 were male. Three of the 5 patients had specific clinical signs of parotitis on admission. One patient had septic shock on admission. The ultrasound confirmed the parotitis in all cases. No parotid abscess was demonstrated on imaging. All patients had at least one abnormal inflammatory biological test (WBC, CRP, PCT). Bacteria were identified in 4 of 5 cases: Staphylococcus aureus was isolated in the pus culture of the Stenon duct in 2 patients and a group B Streptococcus was isolated from blood culture of 2 other patients. The duration of intravenous antibiotic therapy varied from 4 to 13 days, and the total duration of antibiotic therapy was between 10 and 16 days. No surgical procedures were needed., Conclusion: Acute bacterial parotitis in infants under 3 months of age might be associated with localized infections due to S. aureus, but also with a more severe clinical presentation due to group B streptococcus infection. Early diagnosis and appropriate antibiotic therapy might prevent the progression to serious complications., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Invasive group A streptococcal (GAS) infections have a broad and evolving clinical spectrum, associated with various GAS genotypes and/or virulence factors that are only poorly described in children. We aimed to assess the clinical and molecular characteristics of invasive GAS infections in 28 children admitted from 2000 to 2007 at a large French pediatric tertiary care center. The GAS isolates were characterized molecularly by emm-typing and by the determination of the main virulence factors: speA, speB, speC, smeZ-1, ssa, sic, and silC. The median age of the children was 2.9 years. Osteoarticular infection (OAI) was the main clinical manifestation (n=15/28, 53%). emm-1 predominated (n=10/28), followed by emm-12, 3, and 4. No significant correlation was found between emm type and clinical manifestations, but emm-1 predominated in cases of OAI (n=7/15) and was associated with speA, speB, smeZ-1, and sic virulence factor genes. In this pediatric study, we describe a predominance of OAI associated with emm-1 GAS. Further larger international pediatric studies, including host immunity evaluation, are needed in order to better assess the pathogenesis of GAS infection in children.

Since the 1980s, infections due to Streptococcus pyogenes or group A streptococci (GAS) were marked by the increase in invasive infections and the emergence of clones which were resistant to macrolides. Those challenges led the French national reference center for streptococci to enhance the epidemiological survey and the characterization of GAS strains, in collaboration with the National Institute for Public Health Surveillance. Active surveillance is of major importance for implementation of therapeutic and prophylactic guidelines and for evaluation of future streptococcal vaccines., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

An increase in the incidence of Group A streptococcal necrotizing fasciitis has recently been observed in Montréal, Canada. Clinical features of children hospitalized for invasive Group A streptococcal infections and various virulence factor genes of the bacteria were concomitantly analyzed. It was determined that varicella and presence of speC gene in group A streptococcal strains were associated with necrotizing fasciitis.

Objective: The group B streptococcal meningitis (GBS) remains an important cause of child's morbidity and mortality. The purposes of this work were to appreciate the GBS place among the bacterial meningitis, to define clinical and biological factors associated with death and to study the immediate complications., Patients and Methods: This study concerned 276 GBS meningitis listed by the observatory of GPIP/ACTIV on the child's bacterial meningitis in France from January, 2001 to December, 2005. This report is one of the biggest series of child's GBS meningitis published to this day., Results: The GBS was the third germ in frequency responsible for bacterial meningitis at every age (13 %) : 65 % of the GBS meningitis affected infants less than one month of age, 29 % infants between 1 month and 3 months of age and only 6 % infants more than 3 months of age. The male/female ratio in GBS meningitis was nearly equal (51 % vs 49 %). There was no variation of the GBS meningitis number according to the season. The serotype III was mostly involved in this cohort (81 %) followed by the serotype I (13 %). Statistically we observed a significant decline in the number of early onset meningitis from 2001 to 2004 whereas the number of late meningitis and the total meningitis cases were stable. The biological results mostly present in child's GBS meningitis were a high CSF protein level (95 %), a CSF neutrophil count more than fifteen percent (90 %), a low CSF glucose level (83.5 %), leukopenia (49 %) or a normal blood level leukocyte (38 %). Eighty three percent of the children affected by GBS meningitis were term infants. However, the prematurity seemed to be a risk factor to develop late meningitis (age between 7 days and 3 months) and very late meningitis (after 3 months) but no early onset meningitis. Prematurity, convulsions, shock, coma, assisted ventilation, high CSF protein level, weak CSF cell level and leukopenia seemed to be factors associated with death in the GBS meningitis. The mortality of the GBS meningitis was still 14 % and the immediate complications were observed in 62 % of cases, the most frequent being convulsions (45 %)., Conclusion: The GBS meningitis in children remains a frequent problem in pediatrics despite intra partum antibioprophylaxy and thus must encourage to strengthen the prevention of these meningitis.

Background and Method: Group A streptococcal (GAS) invasive infections have been increasingly reported in recent years but meningitis due to GAS remains a rare affection. In children some scarce case reports have been described. The aim of this study was to describe and analyze the clinical and biological data on GAS meningitis recorded in the Bacterial Meningitis (BM) French Surveillance Network (GPIP/ACTIV)., Results: From 2001 through end 2006, 2539 children suffering from proven bacterial meningitis were recorded in the data base. Among them 10 children presented GAS infections. The mean age was 6 years (9 months to 14.1 years) and the sex ratio (male/female) 4/1. Seven out of the 10 patients had a history of community acquired infection before the onset of GAS meningitis : 3 had previous acute otitis media, 1 otitis media with mastoiditis, 2 sinusitis and 1 soft tissue infection. In the 3 remaining children no risk factors of invasive GAS infection could be identified. All but 1 patient survived. The patient who died had no risk factors for invasive infectious disease. He presented with fulminant septicaemia and died 6hours after hospital admission despite appropriate supportive care and prompt antibiotic treatment. The cerebrospinal fluid examination revealed high white blood cells counts (>500/mm(3)) in 8 patients and Gram stained smear showed gram-positive cocci in 6 patients. All the patients received antibiotic regimen including 3(rd) generation cephalosporins before definite bacterial identification and all the strains were susceptible to the first line antibiotic treatment chosen., Conclusion: GAS is an uncommon organism causing meningitis in children. In our study upper respiratory tract infection is the most common predisposing factor for GAS meningitis but even apparently healthy children can suffer from this severe form of bacterial meningitis.

Clinical features and molecular characterization of 109 group B streptococci causing neonatal invasive infections were determined over an 18-month period in France. Sixty-four percent of the strains were from late-onset infections, and 75% were capsular type III. The hypervirulent clone ST-17 was recovered in 80% of meningitis cases.

We found 31 different emm-toxin genotypes among 74 group A streptococcal isolates causing invasive infections in French children. The predominant emm types were emm1 (25%), emm3 (8%), emm4 (8%), emm6 (7%), and emm89 (9%). Sixteen percent of isolates harbored the streptococcal invasive locus, half of them belonging to emm4.

Within the scope of its health products control mission, the French Health Products Safety Agency (Afssaps) collaborating with two expert's sites, has assessed the 16 tests available on the French market in 2002 for rapid diagnosis of the Streptococcus A tonsillitis. The purpose of this study was to verify the reliability and rapidity of these tests and to give some information to the users about their analytical criteria and practicability characteristics. The analytical study has been performed on a same panel of four reference strains of Streptococcus pyogenes dilutions to determine the limit of detection of all the reagents in the same condition of methodology. The limit of detection has been calculated with the results expressed in colony forming unit by ml (CFU/ml). The practicability study has permitted to analyze the quality of the presentation, the easiness of the final reading and of performing tests. A score has been established for each rapid test. A classification of the analytical sensitivity (limit of detection) and practicability (score) of these 16 devices has been established. The limit of detection of the reagents giving the best results allows the detection of the lowest bacterial concentration of the panel which is 10(5) CFU/ml. Regarding practicability, the results suggest that, the immunochromatographic strip methods have the best score in a view with the use by a non medical laboratory.

We studied the antimicrobial susceptibility of 322 Streptococcus pyogenes throat isolates from French children and their serotype and genomic diversity. A total of 22.4% were erythromycin resistant, and 69.4, 4.2, and 26.4% of these isolates harbored ermB, ermA, and mefA, respectively. Increasing resistance in France is mainly associated with a few emm type 28 clones.

Objective: Current guidelines recommend that only tonsillopharyngitis due to group A beta-haemolytic streptococcus (GABHS) diagnosed by rapid diagnostic test should be treated with antibiotics. Empirical antibiotic therapy must be based on epidemiological surveillance of resistance of GABHS to antibiotics. The aim of our study was to assess the activity of antimicrobial agents currently recommended for the treatment of GABHS tonsillopharyngitis. Method The activity of penicillin G, amoxicillin, cefaclor, cefpodoxime, cefuroxime, erythromycin, clarithromycin and clindamycin was determined against 93 consecutive GABHS isolates collected in 2002. MIC50 and MIC90 of antibiotics tested were determined by agar dilution method according to CA-SFM guidelines. Macrolide resistance genes (ermA, ermB, mef) were detected by PCR. Genetic diversity of erythromycin-resistant isolates was analysed by pulsotypic method after digestion by SmaI (Finger-printing II, Biorad)., Results: The activity of beta-lactam agents tested was similar and no resistant strain was detected (0%). Nevertheless, this study shows an increasing emergence of erythromycin-resistant GABHS strains reaching 14% in 2002 (vs. 6.2% in a previous study carried out in 1996-1999)., Conclusion: The empirical antibiotic therapy of tonsillopharyngitis must consider, on the one hand, the high risk of GABHS eradication failure associated with in vitro resistance to erythromycin and clarithromycin, and on the other hand, the sustained susceptibility of GABHS to beta-lactam agents. These results reinforce the recommendations to use beta-lactam agents as first line treatment of GABHS tonsillopharyngitis.

We studied the telithromycin, erythromycin, azithromycin, and clindamycin susceptibilities of serotype III macrolide-resistant group B streptococci, together with genetic mechanisms of resistance and genomic diversity. ermB, ermA, and mefA were found in, respectively, 57, 32, and 9% of isolates. The telithromycin MIC at which 90% of isolates were inhibited was 0.5 micro g/ml. Macrolide resistance was associated with dissemination of resistance determinants among isolates of different genetic backgrounds.

Unlabelled: Despite the fact that group A streptococci (GAS) remain susceptible to penicillin V (pen V), an increasing rate of bacteriological treatment failures has occurred. A recent study has suggested that the major variables associated with pen V treatment failures were the number of days ill prior to initiation of treatment (<2 days) and age <6 years. In order to study the link between pen V treatment failures and individual variables, we reviewed the files of all children enrolled in four randomised multicentre trials of oral antibiotic therapy, carried out from 1993 to 1999. A standard protocol and follow-up examination were used in these four studies: cultures were obtained 4 days and 1 month after completion of treatment. Total DNA restriction fragment length polymorphism was used to compare pre- and post-treatment GAS isolates. We enrolled 1560 children aged 3 to 12 years, 685 received a 10 day pen V regimen (45 mg/kg per day divided into three doses/day), among them 536 were assessable for bacteriological efficacy at the first and second follow-up visit. We found the only variable associated with penicillin treatment failure was the age of the child when infected. The rate of failure was statistically more important for children younger than 6 years (35.5%, 95% CI 29.9--41.1) than for older children (21.9%, 95% CI 16.9-26.9)., Conclusion: in this study only young age (<6 years) increases penicillin V treatment failures for group A streptococcal tonsillopharyngitis. This may lead to different antibiotic regimens and follow-up modalities for these targeted patients.

The mechanisms of resistance to macrolides in seven group A streptococcal (Streptococcus pyogenes) isolates that were the cause of pharyngitis in children who were unsuccessfully treated with azithromycin (10 mg/kg of body weight/day for 3 days) were evaluated. All posttreatment strains were found to be genetically related to the pretreatment isolates by random amplified polymorphism DNA analysis and pulsed-field gel electrophoresis. Two isolates had acquired either a mef(A) or an erm(B) gene, responsible for macrolide efflux and ribosomal modification, respectively. Three isolates displayed mutations in the gene encoding the L4 ribosomal protein that is part of the exit tunnel within the 50S subunit of the bacterial ribosome. In the two remaining posttreatment strains, the mechanisms of macrolide resistance could not be elucidated.

Background: Three-day, 10 mg/kg/day azithromycin (AZM) studies in pediatric acute group A streptococcal tonsillopharyngitis have shown contradictory bacteriologic results. This study investigates the efficacy and tolerability of two dosages of 3-day azithromycin (20 mg/kg/day and 10 mg/kg/day) compared with 10-day penicillin V., Methods: This was a prospective, comparative, randomized, multicenter trial. Children were scheduled to return for visits at 14 days (main end point) and 1 month after the onset of treatment for clinical and bacteriologic assessment. Molecular tools were used to compare pre- and posttreatment group A beta-hemolytic Streptococcus (GABHS) isolates., Results: Between November, 1997, and July, 1998, 501 patients (169 AZM 10 mg, 165 AZM 20 mg, 167 penicillin V) between 2 and 12 years old were enrolled; 500 were assessable for safety, 469 for intent to treat analysis and 420 for efficacy in the per protocol analysis. Before treatment 25 (7.9%) of 315 GABHS stains isolated from patients receiving AZM were resistant to this compound. On Day 14 pretreatment GABHS were eradicated from 78 (57.8%) of the 135 children receiving the AZM 10 mg regimen, 131 (94.2%) of the 139 receiving AZM 20 mg and 123 (84.2%) of the 146 taking penicillin. One month after the outset of treatment, bacteriologic relapses were observed in 40.5% (n = 30) of the children receiving AZM 10 mg, 14.8% (n = 18) of children taking AZM 20 mg and 13.2% (n = 15) of those treated with penicillin V. AZM 20 mg/kg/day was statistically superior to AZM 10 mg/kg/day microbiologically on Day 14 (P = 0.0001) and Day 30 (P = 0.0001) and clinically on Day 14 (P = 0.0035). AZM 20 mg/kg/day was statistically equivalent both microbiologically and clinically to standard therapy with penicillin V at all endpoints. The incidence of treatment-related adverse events was similar in the two azithromycin groups [AZM 10 mg, 31 of 169 (18.3%); AZM 20 mg, 37 of 164 (23%)] but significantly higher than those observed in the penicillin V group [5 of 166 (3%); P < 0.0001]. Most treatment-related adverse events were gastrointestinal and of mild-to-moderate severity. Fourteen patients withdrew from the trial because of adverse events (1 in the penicillin V group, 7 in the AZM 10 mg group and 6 in the AZM 20 mg group)., Conclusion: This is the first study to demonstrate a daily dose-dependent difference in microbiologic efficacy of a regimen; 3-day AZM 20 mg/kg/day is a more effective regimen than 3-day AZM 10 mg/kg/day for pediatric GABHS tonsillopharyngitis.

We examined the genetic diversity of serotype V group B streptococcus (GBS) isolates in the Paris area and compared them with the predominant American serotype V clone. Pulsed-field gel electrophoresis yielded 11 patterns for 64 French GBS. One pattern was obtained with 60% of the isolates tested and was indistinguishable from that of the predominant American clone.

Background: Macrolide resistance among Streptococcus pyogenes strains is increasing in many European countries. Greece was not considered a country with high prevalence of macrolide-resistant S. pyogenes strains, and until now the genetic mechanism of resistance was unknown., Methods: During the 25-month period from December, 1998, to December, 2000, pharyngeal cultures for S. pyogenes were performed on 743 Greek children with the clinical diagnosis of pharyngitis. The children were 1 to 16 years old (median age, 7 years) and were living in Central and Southern Greece. S. pyogenes isolates were tested for their susceptibility to erythromycin, clarithromycin, azithromycin, clindamycin, penicillin G, amoxicillin/clavulanate and cefprozil. The erythromycin-resistant isolates were further studied for their genetic mechanism of resistance by means of PCR., Results: Of a total of 275 S. pyogenes isolates recovered, 105 (38%) were erythromycin-resistant (MIC > or = 1 microgram/ml) [corrected], with 54, 45 and 1% of them carrying mef(A), erm(A) [subclass erm(TR)] and erm(B) gene, respectively. The prevalence of erythromycin-resistant strains was 29 and 42% during the time periods December, 1998, to December, 1999, and January, 2000, to December, 2000, respectively. All erythromycin-resistant isolates were also resistant to clarithromycin and azithromycin. The isolates carrying the erm(A) gene were inducibly resistant to clindamycin. The 275 S. pyogenes isolates had ceprozil MICs < or = 0.032 microgram/ml., Conclusions: The current high (38%) prevalence of erythromycin-resistant S. pyogenes in Central and Southern Greece requires continuous surveillance and careful antibiotic policy.

Three hundred and three strains of group A streptococci (GAS) isolated from adults with pharyngitis were tested to evaluate their phenotype of resistance to macrolides-lincosamides and to search for macrolide resistance genes. MICs of clarithromycin were determined. The overall rate of resistance to both erythromycin and clarithromycin was 9.6%. Constitutive, inducible and M phenotypes of resistance were detected in 4.3, 2 and 3.3% of strains, respectively. All constitutive phenotypes harboured ermB genes, whereas inducible phenotypes had the ermTR gene and M phenotypes had the mefA gene. In France, the current resistance rate of GAS to erythromycin and clarithromycin remains low.

Material and Methods: In this randomized open study, 325 children aged two to 15 years with acute tonsillitis and a positive test of GA beta H streptococcal antigen were treated with josamycin 50 mg.kg-1.day-1 b.i.d for 5 days, or penicillin 50,000 to 100,000 IU/day t.i.d for 10 days. Clinical assessments and throat cultures for GA beta HS isolation were performed at the inclusion visit (V1), at the end of treatment visit (V2: day 12 for all patients) and at the follow-up visit (V3: day 30). In case of positive GA beta HS culture, the bacterial DNA by RFLP was performed to differentiate between the persistence (presence of original strain at V2), relapse (eradication at V2 and acquisition of same strain at V3) and reinfection (eradication at V2 and acquisition of different strain at V3)., Results: Two hundred and twenty-three patients were included in the bacteriological and clinical criteria per protocol analysis. At V2, eradication rates were comparable: 82% in josamycin and 80% in penicillin patients; clinical cure rates were 90% and 89%. At V3, relapse of GAS assessed only on clinically and bacteriologically cured patients at V2 occurred in 12% of josamycin patients and 12.8% of penicillin patients. Tolerance was good; 14% and 10% of josamycin and penicillin patients respectively experienced an adverse event., Conclusion: In this non-inferiority study, the efficacy of a 5-day course of josamycin is comparable to reference treatment in GA beta HS tonsillitis in children.

A total of 1,500 recent throat isolates of Streptococcus pyogenes collected between 1996 and 1999 from children throughout France were tested for their susceptibility to erythromycin, azithromycin, josamycin, clindamycin, and streptogramin B. The erythromycin-resistant isolates were further studied for their genetic mechanism of resistance, by means of PCR. The clonality of these strains was also investigated by means of serotyping and ribotyping. In all, 6.2% of the strains were erythromycin resistant, and 3.4 and 2.8% expressed the constitutive MLS(B) and M resistance phenotypes and harbored the ermB and mefA genes, respectively; ermTR was recovered from one isolate which also harbored the ermB gene. Ten serotypes and 8 ribotypes were identified, but we identified 17 strains by combining serotyping with ribotyping. Among the eight ribotypes, the mefA gene was recovered from six clusters, one being predominant, while the ermB gene was recovered from four clusters, of which two were predominant.

In the evaluation of treatment failure in group A streptococcal pharyngitis, it is essential to distinguish persistence or relapse with homologous streptococcal strains from the acquisition of new, unrelated strains. Randomly amplified polymorphic DNA analysis and restriction fragment length polymorphism analysis of total DNA were used as epidemiological tools to compare 122 pre- and post-treatment Streptococcus pyogenes isolates obtained from 61 patients. The results obtained by molecular typing showed that bacteriological failures were due to the original strains in 43 cases (70%) and to new strains in 18 cases (30%). In the present study, restriction fragment length polymorphism analysis of total DNA appeared to be more discriminative than randomly amplified polymorphic DNA analysis. Thus, molecular analysis of DNA is an effective way to distinguish recurrence from persistence or relapse and will be useful in assessing the efficacy of new antibiotic treatments.

Objective: To compare the efficacy and safety of amoxicillin (50 mg/kg/day divided twice daily) for 6 days and penicillin V (45 mg/kg/day divided into three doses/day) for 10 days in children with group A streptococcal (GAS) tonsillopharyngitis., Methods: In a prospective, comparative, open, randomized, multicenter trial, children were scheduled to return for visits 4 days (main end point) and 1 month after the completion of treatment for clinical and bacteriologic assessment. Total DNA restriction fragment length polymorphism was used to compare pre- and posttreatment GAS isolates., Results: Between September, 1993, and February, 1995, 321 children (161 amoxicillin, 160 penicillin V) were enrolled, among whom 318 (160 amoxicillin, 158 penicillin V) were evaluable for safety, and 277 were evaluable for efficacy. Four days after the completion of treatment, pretreatment GAS were eradicated from 118 of the 141 children receiving amoxicillin (83.7%) and 116 of the 136 (85.3%) taking penicillin. One month after the outset of treatment, bacteriologic relapses were observed in 9.9% (n = 11) of the children receiving amoxicillin and 5.7% (n = 6) of those treated with penicillin V, bacteriologic recurrences in 5 and 3 patients, respectively. Adverse events related to the study medications were reported in 4 patients in the amoxicillin group and 8 in the penicillin V group. Drug-related adverse events leading to treatment discontinuation occurred in 3 patients, all in the penicillin V group. Compliance, based on diary cards and the weight of study drugs returned, was significantly better in the amoxicillin group. CONCLUSIONS. The efficacy and safety of amoxicillin (50 mg/kg/day twice daily) for 6 days were not statistically different from those of penicillin (45 mg/kg/d three times a day) for 10 days in the treatment of GAS tonsillopharyngitis.

A 10-day course of penicillin is the antibiotic regimen currently recommended by the American Heart Association (AHA) as treatment for patients with tonsillitis caused by group A beta-haemolytic streptococci (GABHS), with the aim of preventing both the suppurative and non-suppurative complications of this infection. This prospective, multicentre, randomized, double-blind, double-dummy clinical trial was undertaken in order to compare the efficacy of, tolerability of and compliance with a 5-day course of cefotiam hexetil (CTM) 200 mg bd with that of a 10-day course of penicillin V (PEV) 1 megaunit (600 mg) tds, to investigate the significance of recovering GABHS during or after treatment and to evaluate the potential economic advantages of short-term regimens. Two hundred and fifty ambulatory adult patients with a presumptive diagnosis (based on a positive rapid antigen detection test) of GABHS tonsillitis were recruited in 60 centres; the diagnosis was subsequently confirmed by a positive culture of a throat swab. At the time of entry into the trial there was no statistically significant difference between the groups in terms of clinical symptoms. In an intention-to-treat analysis, both the clinical and bacteriological response rates at days 10 and 30 were comparable for each group i.e. 106 of 119 (89.1%) patients and 90 of 109 (82.6%) patients respectively in the CTM group and 103 of 117 (88.0%) patients and 92 of 107 (86.0%) patients respectively in the PEV group. The times until defervescence and resolution of symptoms were also similar. Of the 115 patients in each group who were assessed at day 90, there were three clinical relapses in the CTM group and seven in the PEV group. No non-suppurative complications of GABHS infection were detected. Tolerance was significantly better in the CTM group than in the PEV group, 14 of 119 (11.8%) patients and 26 of 117 (22.2%) patients in the former and latter groups respectively reporting adverse events. In three cases in each group treatment was discontinued prematurely because of adverse events; none of these in the CTM group was serious but one patient in the PEV group experienced a severe allergic reaction. Compliance in both groups was good during the first 5 days of therapy but, by the end of each course, 93.6% of patients in the CTM group had completed treatment, compared with 73.0% in the PEV group.(ABSTRACT TRUNCATED AT 400 WORDS)

In a prospective randomized multicenter study, 308 children, ages 2 to 15 years, were randomized to receive either cefuroxime axetil suspension (N = 152; 20 mg/kg/day twice daily) for 4 days, penicillin suspension (N = 156; 45 mg/kg/day divided three times daily) for 10 days, of whom 97 and 103, respectively, had culture-proved group A beta-hemolytic Streptococcus infection. Two to 4 days after completion of the treatment, group A beta-hemolytic Streptococcus were eradicated from 85 of 97 (87.6%) children taking cefuroxime and from 90 of 103 (87.4%) taking penicillin; respective clinical cure rates were 94.8% and 96.1%. Clinical signs and symptoms resolved significantly more rapidly with cefuroxime (P < 0.05). At 28 to 32 days posttreatment the eradication of the primary isolate was confirmed in 94.4 and 91.9% of cefuroxime axetil and penicillin-treated patients, respectively. Drug-related adverse events (mainly gastrointestinal and cutaneous reactions) were reported in 2.1 and 2.7% of the cefuroxime- and penicillin-treated patients, respectively. Results indicated that a 4-day treatment with cefuroxime axetil was as effective and well-tolerated as the conventional 10-day treatment with penicillin in children with acute group A beta-hemolytic Streptococcus pharyngitis.

Pneumococci is the number one pathogen causing pneumonia and bacteraemia in children in France. After H. influenzae, it is the second most frequent cause of conjunctivitis and otitis as well as purulent meningitis in 3-month to 3-year-old children (a situation which will undoubtedly be modified by Hib H. influenzae b vaccinations). It also predominates in bronchial superinfections and occult bacteraemia. Penicillin G. has been given for pneumococci infections for years leading the development of resistant strains (20.1% of the strains isolated in France in 1992 were resistant to beta-lactamines. Other resistances include macrolides (44% of the strains), tetracyclins (28%), cotrimoxazol (32%), chloramphenicol (25%) and erythromycin-sulphisoxazol (20%). Thus no other family of oral antibiotics can be successfully substituted for beta-lactamines for routine treatment. Lifestyle and health care organization is a major factor of risk which could explain why the incidence of resistant strains is greater in high density urban populations or in countries were young children are cared for in groups. Therapeutic strategies for easily accessible localizations (septicaemias, pneumonia) can be easily established on the basis of minimal inhibiting concentrations, but for certain sites (otitis, meningitis) more problems are raised. For example, the probability of resistance to penicillin R in acute otitis has been estimated at 75% for children living in the Paris area. We therefore recommend amoxillin (150 to 200 mg/kg/day) or pristinamycin or possibly ceftriaxon (50 mg/kg/day during 3 days). Similar probabilistic strategies are established for purulent meningitis and other childhood pneumococci infections.

Objectives: Epidemiological surveys which are not frequently carried out in medical practice should provide useful information for the choice of antibiotics to be prescribed in community-acquired infections particularly with the recent development of therapeutic difficulties due to resistant strains. We therefore analyzed the prevalent pharyngeal flora in a general patient population., Methods: The study was conducted during a single 24-hour period in 1991 by 43 general practitioners and included 645 subjects consulting for benign affections. No patient selection was made. Two pharyngeal swabs were obtained from each subject and cultured in aerobic and anaerobic conditions. Internationally accepted methods for identifying bacteria in pharyngeal samples all performed by one well-equipped laboratory. Beta-lactamase activity was determined with the nitrocephine technique, both directly and after culture., Results: Patient age varied from 16 to 45 years; most (68.5%) consulted for reasons other than ear-nose-throat affections. Only 41 patients (4.3%) consulted for sore throat and 65.4% had not received antibiotics for at least 6 months. Haemophilus influenzae was found in 59.6% of the patients, 20% of the strains were beta-lactamase producers as were 83.7% of the Moraxella catarrhalis strains identified., Conclusion: These factors are indicators of potential risk of therapeutic failure when using beta-lactams unstable to beta-lactamases for the treatment of pharyngeal infections.

In the evaluation of treatment failure in Streptococcus pyogenes pharyngitis it is necessary to distinguish between persistence of the original streptococcus and acquisition of a new strain. We used the analysis of restriction fragment length polymorphism (RFLP) of total DNA and of ribosomal DNA (rDNA) regions (ribotypes) as epidemiological tools to compare 43 pre- and post-treatment S. pyogenes strains obtained from 20 patients. In 16 cases pre- and post-treatment strains gave indistinguishable RFLP patterns of total DNA, strongly suggesting relapse with the same strain. However, in four cases different patterns were obtained for the pre- and post-treatment isolates, indicating recurrence due to the acquisition of a new strain. Ribotyping did not improve discrimination among strains. Thus, analysis of DNA RFLP is a promising method for distinguishing recurrence from relapse in failures of pharyngitis treatment.

Analysis of restriction fragment length polymorphism (RFLP) of total DNA and of ribosomal DNA (ribotyping) was used to document four cases of Streptococcus agalactiae mother-to-infant transmission potentially associated with ingestion of infected mother's milk. Twenty strains were analyzed. Ten strains were mother-baby pairs, five from the milk of five mothers, four from their neonates with late-onset infection, and one from a colonized neonate. All mothers had early postpartum mastitis. Ten unrelated strains were studied for comparison. In each case, the two strains of each mother-baby pair produced identical RFLP patterns of total DNA. The 10 unrelated strains generated 10 different patterns, one of which, though, was observed in one of the mother-baby pairs. Ribotyping was less discriminative than total DNA RFLP analysis (6 different patterns vs. 13). These data extend the evidence for breast milk transmission in S. agalactiae late-onset neonatal infection.

Restriction fragment length polymorphism (RFLP) analysis of total DNA and of ribosomal DNA (rDNA) regions (ribotyping) were used to document Streptococcus pyogenes vertical mother-to-infant transmission and to investigate the spread of S. pyogenes in an obstetric unit. Two isolates from a newborn, two isolates from his mother (patient 1), and two isolates from two other mothers (patients 2 and 3) were studied. RFLP of total DNA, both after HindIII and PvuII digestions and ethidium bromide staining, gave indistinguishable patterns for the strains isolated from the neonate, his mother, and patient 2. Strains from patient 3 and six unrelated strains studied for comparison showed different patterns. In our system, ribotyping was less discriminative than total DNA RFLP analysis. DNA RFLP analysis therefore provides a valuable molecular tool for studying S. pyogenes epidemiology.

Morbidity and mortality among neonates with group B streptococcal infections remain high. As delays in bacterial killing may be responsible for these poor results, there is a need for studies into killing kinetics. We investigated antimicrobial sensitivity and killing effect time lags for penicillin, ampicillin and mezlocillin, alone and in combination with gentamicin or amikacin, against 20 strains of group B streptococci isolated in cultures of blood and cerebrospinal fluid from neonates. A culture of each strain (10(5) germs/ml) was exposed to the antibiotics individually or in combination. Antibiotics were used in the concentrations achieved clinically. Surviving bacteria were counted after 2 h 30, 4 h 30 and 24 h. incubation. Mean killing curves showed that the time interval until onset of a killing effect was 24 hours with either penicillin or ampicillin alone, against 4 h 30 with penicillin-amikacin or ampicillin-gentamicin. The most rapid killing effect (2 h 30) was observed with mezlocillin alone and ampicillin-amikacin. No antagonism was found between mezlocillin and aminoglycosides. Choice of the best antibiotic treatment for group B streptococcal infections should be based on both the rapidity of the in vitro killing effect and the antibiotic's diffusion into the site of the infection.