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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.

Objective: Meningococcal disease due to Neisseria meningitidis of serogroup W135 (N. meningitidis W135) is increasing in France. Clinical and outcome data concerning these infections in children are scarce., Patients: We report 5 cases of children hospitalised in our unit between June 2000 and December 2002 for N. meningitidis W135 infection., Case Reports: Among these 5 children aged 19 months to 11 years, 3 presented with a primary meningitis and 4 with primary or secondary extra-meningeal involvement, articular in 3 cases, pericardial in 2 cases and ocular in one case. The outcome was favourable without after effects in 4 cases, marked by a resistant prolonged post-meningococcal inflammatory syndrome., Comments: Extra-meningeal septic and/or non septic complications are frequent and a prolonged post meningococcal inflammatory syndrome is reported. In N. meningitidis W135 infections a careful clinical evaluation of potential extra-meningeal complications and a long term follow up of children are needed.

Objective: To review the bacteriological features and treatment of suppurative cervical lymphadenitis in children in order to achieve optimal treatment., Patients and Methods: Forty-five children were hospitalized. Time of hospitalization was evenly distributed over Year and between Years. Age ranged from 2.5 Months to 13.5 Years (median 1 Year 10 Months). Twenty-nine patients had received prior antibiotic treatment. Bacteriological samples were sterile in 15 out of 45 children and were positive for Staphylococcus (all meti-S) in 20. Cefotoxim and fosfomycin were prescribed and was sufficient in 14 children (with needle aspiration). Surgical drainage was performed in the other cases., Conclusion: Staphylococcus aureus is the predominant causal agent for acute suppurative lymphadenitis in children. Antibiotic therapy in the outpatient setting does not always prevent abscess formation and surgical drainage may be required.

EPIDEMIOLOGY OF THE BACTERIA RESPONSIBLE: Acute otitis media (AOM) is the most common bacterial infection in childhood below the age of 5 years. Bacteria may be isolated from middle ear fluid in about two-thirds of patients. The prevalence of bacteria varies from one country to the next. The most common pathogens recovered are Streptococcus pneumoniae, Haemophilus influenzae (20-50%) and less frequently Moraxella catarrhalis (10%). However, several recent reports suggest an increasing rate of isolation of M. catarrhalis approaching 20%. Concomitant isolation of two or more organisms occurs in up to 10% of cases. The role of Group A Streptococci and Staphylococcus aureus in AOM has decreased since the use of antibiotics. EPIDEMIOLOGY OF ANTIMICROBIAL RESISTANCE: The recent spread of penicillin resistant S. pneumoniae and amoxycillin resistant H. influenzae varies considerably from one country to an other and appears related to the use of antibiotics and socio-economic conditions. A follow up of bacterial epidemiology and antibiotic resistance is necessary in each region of the world to define accurate strategies of acute otitis antibiotherapy.

Objective: We studied the microbiological epidemiology of tympanostomy tube otorrhea, rifamycin and ofloxacin sensitivity of pathogens isolated from these otorrheas, and the bactericidal power of the rifamycine-ofloxacin combination., Material and Methods: A prospective study was conducted in 1997 with cultures of otorrhea aspirates, in vitro study of pathogen resistance to rifamycin and ofloxacin, bacteriocidal study of the rifamycin-ofloxacin combination., Results: One hundred eight aspirates were obtained from 98 children (mean age 5 years). Ten aspirates were sterile, 32 had more than one pathogen. The more frequent pathogens were Pseudomonas aeruginosa (Pa) (n=35), Staphylococcus aureus (Sa) (n=27), Haemophilus influenae (Hi) (n=12) and Streptococcus pneumoniae (Sp) (n=9). All Hi, all Sp, 86.3% of the Sa (MIC(90) 0.25 mg/l) and none of the Pa were rifamycin sensitive. All Hi, 97.7% of the Pa (MIC(90) 0.5 mg/l), 73,1% of the Sa (MIC(90) 0.24 mg/l) and none of the Sp were ofloxacin sensitive. The rifamycin-ofloxacin combination led to a 4 log CFU/ml decrease in 6 hours for Sp, and in 24 hours for Pa, Hi and Sa., Conclusion: The rifamycin-ofloxacin combination is bactericidal for bacteria causing tympanostomy tube otorrhea. Otic drops with this combination should be considered as the first line treatment for such otorrhea.

AN EMERGING PATHOGEN: Escherichia coli O157:H7 became an important pathogen starting in the early 1980s. It has caused epidemics and sporadic cases of often bloody diarrhea which may progress to severe hemolytic and uremic syndromes or thrombotic thrombocytopenic purpura., Transmission: E. coli O157:H7 is mainly transmitted in food. Water and inter-human transmission as well as direct animal-to-man transmission has also been documented., Virulence: E. coli O157:H7 can adhere tightly to the enterocyte brush border (eae gene) and produce verotoxins or Shiga-like toxins and hemolysine (ehxA gene)., Diagnosis: Diagnosis of E. coli O157:H7 infections is based on evidencing the germ in stools and/or by identifying the genes coding for verotoxins or by serology which increased serum titre of specific antilipopolysaccharide antibodies., Treatment and Prevention: Anti-diarrheal drugs and antibiotics have little place in the treatment of bloody diarrhea. This public health problem, requires careful identification of animal reservoirs and improved population education in food hygiene.

Objectives: The aim of this study was to analyze the epidemiological evolution of causal germs in meningitis in children aged 1 day to 15 years and determine the relationship between pretreatment concentrations of bacteria in cerebral spinal fluid (CSF), patient age, bacterial species and bacteriological eradication., Patients and Methods: A quantitative analysis of germs was performed in 212 children with bacterial meningitis (mean age 19.8 months)., Results: Bacterial counts ranged from 2.10(1) to 4.10(9) CFU/ml in CSF. Among the 212 patients, 52 (24.5%) had counts 10(7)/ml. Infants had significantly higher counts than the other age groups. Mean counts for Hoemophilus influenzoe serotype B were not different from those for Streptococcus pneumoniae but were significantly higher than for Neisseria meningitidis. Compared with initial germ counts, 98.5% of the CSF specimens were sterile at 24 and 48 hours and 100% at 72 hours., Conclusion: Germ counts were higher in infants.

PROBABILITY-BASED ANTIBIOTIC THERAPY: In children, the risk of an unfavorable course of bacterial infections requires careful selection of the initial antibiotic prescription based on the disease state, bacterial epidemiology and the child's age. ACUTE COMMUNITY ACQUIRED PNEUMONIA: Before the age of 5 years, antibiotics active against Haemophilus influenzae such as amoxicillin or clavulanic acid can be given orally. In children over 5, amoxicillin or a macrolide are effective. SEVERE EAR, NOSE AND THROAT INFECTIONS: For sore throats, clinical and bacterial results of a 4-day antibiotic regimen using a second generation cephalosporin are equivalent (with better compliance) to a 10-day regimen of penicillin V. For acute middle ear infections, a combination of amoxicillin-clavulanic acid is usually prescribed as initial treatment. COMMUNITY ACQUIRED BACTERIAL MENINGITIS: The most recent consensus established the indication for cefotaxime or ceftriaxone. The increasing number of peni-R pneumococci and the major drop in the frequency of Haemophilus infections have led to new therapeutic propositions currently under investigation. ACUTE SKIN INFECTIONS: For impetigo, general antibiotics-oxacillin or a derivative-are required due to the risk of contagion. BONE AND JOINT INFECTIONS: For these urgent situations, in vitro sensitivity and antibiotic penetration into the infected tissue are the determining factors. BACTERIAL DIARRHEA: Antibiotics are not required in case of acute diaarhea with little or no fever. Antibiotics could be discussed for cholera-like diarrhea and are required in case of invasive bacterial diarrhea, shigelosis, cholera, and Clostridium difficile as well as diarrhea with fever and blood loss in infants or salmonella-induced diarrhea with signs of extradigestive complications. URINARY TRACT INFECTIONS: The choice of the antibiotic and the duration of treatment depend on the clinical presentation: lower tract infection, acute pyeloephritis, or prophylaxis. The causal germ must be identified for adapted antibiotic treatment.

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.

The haemolytic uraemic syndrome, first described in 1955 by Gasser, is the number one cause of acute renal failure in infants. There are three types of the haemolytic uraemic syndrome: the seasonal epidemic form with prodromic diarrhoea and generally favourable outcome which usually occurs in infants, a less typical form without signs of digestive tract involvement and no seasonal prevalence which occurs more readily in older children and sometimes in families has a less favourable prognosis, and finally drug- or disease-related forms. Currently, overall mortality due to haemolytic uraemic syndrome has been reduced to about 4%, usually as a result of damage to the central nervous system. Several microorganism, including Shigella dysenteriae, Salmonella typhi, Campylobacter jejuni, Streptococcus pneumoniae, Rickittsiae and certain viruses (Coksackiae, Influenzae, Epstein-Barr) have been identified as causative agents. In 1983, digestive tract infection due to an Escherichia coli strain producing verotoxin was identified as capable of producing haemolytic uraemic syndrome and more rarely thrombopenic thrombotic purpura. The germ produces two exotoxins (whose effect is accentuated by the E. coli lipopolysaccharide endotoxin) which lead to the glomerular microangiopathy causing haemolytic uraemic syndrome. Diagnosis is based on identification (monoclonal antibodies, ELISA, PCR) of the verotoxins themselves or the two encoding genes in stool samples. Symptomatic treatment is essential but the effectiveness of antibiotics is still debated. Theoretically, antibiotics could worsen the syndrome by increasing endotoxin release from lysed bacteria, but inversely they could also prevent the syndrome if given early enough. Further research is required to acquire precise epidemiological data and identify animal reservoirs of verotoxin producing E. coli.

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.

The advances achieved in the field of oral cephalosporins consist of improved bioavailability and enhanced intrinsic activity of the compounds. Oral absorption is facilitated either by creating prodrugs or by modifying the compound itself with addition of the alpha-amino group at position 7 on the cephem ring or of a vinyl group at position 3. Antibacterial activity and resistance to beta-lactamases are facilitated by the presence of an amino-2-thiazole heterocycle at position 7, associated with a methoxy-imino group or an oxy-imino-acetoxy group.

The prognosis and sequelae of patients with Haemophilus influenzae meningitis were related to concentrations of bacteria in the cerebrospinal fluid (CSF). Rapid bacterial killing and rapid reduction of organisms in vivo in CSF are critical to the outcome. In our patients colony counts of Haemophilus influenzae in CSF were 10(2)/ml - 10(9)/ml (mean 10(5)/ml). Killing kinetics were determined for amoxicillin and cefotaxime, alone and in combination with amikacin, against 35 clinical strains of Haemophilus influenzae (43% beta-lactamase-positive) at concentrations of these antibiotics comparable to those attained in the CSF following systemic administration. Antibiotics concentrations were: amoxicillin: 5 mg/ml, cefotaxime: 3.8 mg/l, amikacin: 1.8 mg/l. Mean killing curves with beta-lactamase-negative strains showed that a bactericidal effect was observed at 18 h for amoxicillin, at 5 h for cefotaxime, at 5 h for amoxicillin plus amikacin and at 2 h 30 for cefotaxime plus amikacin. Against beta-lactamase-positive strains a bactericidal effect was observed at 5 h for cefotaxime, at 2 h 30 for cefotaxime plus amikacin and at 18 h for amoxicillin plus amikacin. The finding of significantly increased killing rates of Haemophilus influenzae by amikacin at low concentration in the presence of either ampicillin or cefotaxime suggests that combined therapy may be beneficial in the treatment of meningitis caused by Haemophilus influenzae.

Antimicrobial sensitivity and time-kill curves were determined for ticarcillin, azlocillin, piperacillin, cefsulodin, ceftazidime, gentamicin, tobramycin and amikacin alone or in combination against 40 strains of Pseudomonas aeruginosa isolated from blood cultures and tracheal aspirates in pediatric intensive care units. The antibiotics were used in concentrations obtainable with the usual therapeutic dosage. No bactericidal effect was observed with each of the beta-lactam antibiotics tested alone. For ticarcillin-sensitive strains the most rapid bacterial inoculum size decrease was observed at 2.5 h with the piperacillin-amikacin combination, and a bactericidal effect was obtained within 4.5 h when amikacin was combined with ticarcillin, azlocillin, piperacillin, ceftazidime or cefsulodin. For ticarcillin-resistant strains a bactericidal effect was obtained within 4.5 h when amikacin was combined with piperacillin, azlocillin, ceftazidime or cefsulodin.

A retrospective study was conducted of 587 bacteriological samples collected from 387 children with acute otitis media treated as outpatients over a period of 30 months, to determine relative frequency of the causative germs and their resistance to antibiotics. The most frequently involved bacteria were staphylococci (16 p.cent) of which 70 p.cent were Staph. Epidermidis, and Haemophilus (17 p.cent), résistance to ampicillin being present in 19 p.cent. These results, which differ from those in the published literature, suggest that paracentesis with systematic bacteriological typing is the treatment of choice in acute otitis media.