The antimicrobial resistance of Streptococcus pneumoniae was surveyed in 1970-1990 at Saint Joseph and Broussais hospitals in Paris (3,279 isolates) and in 1984-1990 at the National Reference Center for Pneumococci (NRCP) in Créteil (8,128 isolates). All isolates were tested for susceptibility and serotyped. At St. Joseph and Broussais hospitals, the rate of resistance to tetracycline increased from 14% in 1970 to 46.5% in 1978 and then decreased to approximately 20% in 1988-1990. Resistance to chloramphenicol appeared in 1972; its frequency remained at less than 10% until 1990. Resistance to macrolides was first detected in 1976, increased to 20% in 1984, and reached 29% in 1990. Among strains submitted to the NRCP, resistance to penicillin (MIC, greater than or equal to 0.1 mg/L) remained infrequent (less than or equal to 1.1%) between 1984 and 1986 but then increased steadily, reaching 12% in 1990. The frequency of high-level resistance to penicillin (MIC, greater than 1 mg/L) among penicillin-resistant pneumococci increased from 13% in 1988 to 48% in 1990. Compared with other serotypes, the penicillin-resistant serotype isolated most frequently (23F, 49.3%) was more often highly resistant to penicillin and was more often multiresistant.
We evaluated the in vitro killing activities of ceftriaxone, imipenem, vancomycin, gentamicin, fosfomycin, and rifampin, alone and in combination, against 26 Streptococcus pneumoniae strains (penicillin G MICs, >0.125 to 2 ,ug/ml) isolated from the cerebrospinal fluid of children with meningitis. The antibiotics were tested at clinically achievable concentrations in cerebrospinal fluid. After 5 h of incubation, imipenem was the most effective drug. None of the combinations had synergistic activity. Killing by 1I-lactam antibiotics or vancomycin was enhanced by the addition of gentamicin, reduced by the addition of rifampin, and unafected by the addition of fosfomycin.Pneumococcal meningitis in children is associated with considerable morbidity and mortality. As in many other parts of the world, there has recently been an increase in the prevalence of Streptococcus pneumoniae strains with diminished susceptibility to penicillin G in France; these strains represented about 12% of all S. pneumoniae strains isolated from cerebrospinal fluid (CSF) in France in 1992 (12). Clinical failure of S. pneumoniae meningitis therapy with delayed sterilization of CSF has been reported with such strains (11, 12, 16, 33), leading to recommendations that standard P-lactam antimicrobial agents be replaced by broad-spectrum cephalosporins in this setting (16,33). However, S. pneumoniae strains resistant to broad-spectrum cephalosporins have recently been reported in the United States and Spain, together with clinical treatment failure in cases of infection caused by strains for which the ceftriaxone or cefotaxime MIC is .0.5 jxg/ml (4,5,17,29). New strategies such as the use of antimicrobial combinations are now being evaluated as first-line empiric treatment for meningitis (8,9,32).The aim of the study described here was to determine the comparative in vitro bactericidal activities of candidate antibiotics for use in childhood meningitis caused by S. pneumoniae strains with diminished susceptibilities to penicillin G. We used the time-killing curve method with clinically achievable CSF antibiotic concentrations and experimental conditions mimicking clinical conditions, such as a large inoculum (3) in the stationary growth phase (7).We studied 26 S. pneumoniae strains (serotype 23, n = 18; serotype 14, n = 3; serotype 9, n = 2; serotype 19, n = 1; serotype 6, n = 1; serotype 15, n = 1) for which penicillin G MICs were increased (MICs, >0.125 to 2 p.g/ml). These strains represented all the strains isolated from the CSF of children with meningitis and collected by the French reference laboratory between 1987 and 1992. France), ceftriaxone (Roche, Neuilly-sur-Seine, France), imipenem (Merck, Sharp and Dohme-Chibret, Paris, France), gentamicin (Schering-Plough, Levallois-Perret, France), fosfomycin (Sanofi, Gentilly, France), and rifampin (Ciba-Geigy, Rueil-Malmaison, France) were determined by the dilution method on Mueller-Hinton agar supplemented with 5% sheep blood. The replicator prong delivered approximately 104 CFU per spot on...
Between January 1997 and April 2002, 73 consecutive invasive strains of Streptococcus pneumoniae were isolated from children under 16 years of age in four hospitals in suburban Paris. Their genetic diversity was investigated by serotyping and analysis of pulsed-field gel electrophoresis restriction patterns. Antibiotic susceptibility patterns were analysed by disk susceptibility testing and determination of minimal inhibitory concentrations. The genetic basis of macrolide resistance was investigated by polymerase chain reaction. Studies of penicillin and vancomycin tolerance were performed for each strain. Despite the high prevalence (45.2%) of penicillin-nonsusceptible Streptococcus pneumoniae, resistance to amoxicillin (1.4%) was rare, and no strain was resistant to cefotaxime. Overall, 4.1% of pneumococcal strains were resistant to penicillin. Penicillin or vancomycin tolerance was not detected in any of the 73 strains studied. Of the erythromycin-resistant strains (48%), all but one carried the ermB gene. No strains showing a decreased susceptibility to ciprofloxacin (MIC, >4 mg/l) or overexpressing an efflux pump inhibited by reserpine were isolated. The serotypes found, in order of frequency, were as follows: 18C, 14, 6B, 19F, 19A, 9V, 23F, 1, 7F, 9A, 38. Strains of penicillin-nonsusceptible Streptococcus pneumoniae belonged predominantly to serotypes 14, 6B, 9V, 9A, 23F, 19F and 19A. The seven-valent conjugated vaccine covered 85.5% of the serogroups isolated in children under 2 years of age and 65.6% of the serogroups identified in children over 2 years of age. The genetic analysis showed a high identity for some serotypes, such as 14/9V, 6B and 23F. The use of the seven-valent conjugated vaccine is a critical measure to prevent invasive pneumococci infections in children in the Ille de France area.
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