Septicaemia caused by phenotypic variants of group A streptococci.

Clinical isolates (115) of Streptococcus pyogenes responsible for septicaemia were investigated to determine whether invasiveness may be correlated with a large variety of strains, or concerns only particular phenotypes. Irrespective of their clinical origin, the strains studied displayed seven of the ten biotypes described within this species. As already observed in a series of strains isolated from pharyngitis, a restricted association between M-types and biotypes was demonstrated; each M-type corresponded to a sole biotype. However, the proportion of biotypes 3, 5 and 7 was higher in the septicaemia series than in the pharyngitis series, with a larger variety of M-types and with more non-typable strains. Despite these differences, the restricted associations between these characters were concordant in both series. These results demonstrate that streptococcal septicaemias appear to be caused by a wide variety of strains, suggesting that multiple factors may be involved in the invasiveness of the bloodstream during streptococcal infections.

[Development of resistance to beta-lactams and other antibiotics of pneumococci isolated from acute otitis media in France: statement of the National Reference Center 1995-1996]. / Evolution de la résistance aux bêtalactamines et aux autres antibiotiques des pneumocoques isolés d'otites moyennes aiguës en France: bilan du Centre national de référence 1995-1996.

POPULATION AND METHODS: During 1995 and 1996, 393 and 566 strains of Streptococcus pneumoniae, isolated from acute otitis media, were respectively sent to the National Reference Center for Pneumococci by its corresponding centers. RESULTS: The resistance rates for 1995 and 1996 were respectively: for penicillin: 65.4 and 70.3% (18.6 and 24.9% of intermediately resistant strains, 46.8 and 45.4% of fully resistant strains), for erythromycin: 57.5 and 68.5%, for tetracycline: 43.2 and 42.6%, for trimethoprim-sulfamethoxazole: 47.5 and 50.9%. Minimal inhibitory concentrations (MICs) of various betalactams were determined against a representative sample of strains (n = 99). CONCLUSION: Amoxicillin, cefpodoxime and cefuroxime MICs remained low against numerous penicillin resistant strains, indicating that these three oral antibiotics (in combination with clavulanate for amoxicillin) have a useful potential for the treatment of acute otitis media when risk factors for pneumococcal penicillin-resistant infections are detected.

[Changes in the sensitivity of pneumococci to antibiotics. Therapeutic consequences]. / Evolution de la sensibilité des pneumocoques aux antibiotiques. Conséquences thérapeutiques.

Streptococcus pneumoniae has a prominent role in infectious bronchopulmonary diseases. This organism is normally sensitive to a vast number of antibiotics. However, in recent years, acquired resistance against tetracyclines, macrolides, and, more recently, penicillins, has emerged. Since 1987, there is indeed a regular increase in the frequency of strains that have a lower sensitivity to penicillin G (less than 1% before 1986; 12% in 1990). However, this percentage of strains with a lower sensitivity is much more important among non-invasive as opposed to invasive organisms that are isolated from blood, pleural and spinal fluid cultures (3.3% in 1990). Among strains with abnormal sensitivity to penicillin G, there are very selective serotypes or serogroups: 4 types or groups (23, 19, 6 and 14) represent 80% of these strains. More than 80% of the strains of MIC greater than 2 mg/l are among only one stereotype, 23F. This abnormal sensitivity to penicillin G implies a modification of sensitivity to all beta-lactams, but MIC increase to a variable extent depending on the antiinfectious agent. The most efficient agents against strains of lower sensitivity are amoxicillin, imipenem and parenteral third generation cephalosporins. On the other hand, for all oral first, second and third generation cephalosporins, MIC increase to levels for which seric levels that are reached hardly demonstrate convincing efficiency. Even if resistance levels are less marked as shown by strains isolated from pulmonary infections as compared to what is seen in ENT, the trend in the development of abnormal sensitivity of pneumococci to beta-lactam agents urges the clinician to take into account these data in the therapeutic coverage of bronchopulmonary infections.

[Streptococcus pneumoniae: serotypes, invasive and antibiotic resistant strains. Current situation in France]. / Streptococcus pneumoniae: sérotypes, souches invasives et résistantes aux antibiotiques. Situation actuelle en France.

OBJECTIVES: Anti-pneumococcal antibiotic therapy has reduced morbidity and mortality of pneumococcal infections, but this success has retarded wide application of vaccination. The emergence and worldwide diffusion of antibiotic-resistant strains raises an important public health problem. The current situation requires determining the respective roles of antibiotic therapy and vaccine immunoprophylaxy. The aim of this work was to examine the data collected by the French National Pneumococci Registry. METHODS: The Nation Surveillance Network for Pneumococcal Infections was initiated in France in 1984. With this registry, it has been possible to follow regularly the evolution of serotypes and their sensitivity to antibiotics in 34,130 strains received from 1984 to 1996 and to compare these results with the clinical data. RESULTS: Serotyping the invasive strains has shown that the relative frequency of these serotypes has been stable: the 23-valence pneumococca vaccine provided good serotype coverage from 1984 to 1996 (87.2% of the invasive strains isolated in 1996 belonged to the vaccine types). Penicillin-resistant pneumococci comprised 3.8% of the strains, isolated in 1987 and 42.8% of those isolated in 1996. Two-thirds of these penicillin-resistant pneumococci had high-level resistance and an equivalent percentage were multiresistant. The consequences of resistant strains on antibiotic therapy for pneumonia, acute otitis and meningitis is discussed. CONCLUSION: Bacterio-clinical surveillance networks provide regular epidemiological data aimed at better use of antibiotics and the promotion of vaccination campaigns. In the future, the vaccination of children under 2 years of age with new conjugated polysaccharide vaccines should be an essential step in the global strategy against pneumococcal infections. The vaccinal formula of such a pediatric vaccine would contain 10 valences, defined according to the serotype results we have obtained: 1, 3, 4, 6, 7, 9, 14, 18, 19, 13. This vaccine would cover 86.1% of the invasive strains and 90.7% of the strains isolated from children with acute otitismedia.

[Epidemiology and antimicrobial resistance of Streptococcus pneumoniae strains isolated in Ile de France area during 2001]. / Epidémiologie et résistance aux antibiotiques de Streptococcus pneumoniae en Ile de France en 2001.

OBJECTIVE: The authors wanted to assess the level of Streptococcus pneumoniae antibiotic resistance in Ile de France. METHOD: In 2001, 637 clinical strains of S. pneumoniae were prospectively collected from 32 microbiology laboratories. RESULTS: Fifty one percent of strains were isolated from children under 15 years of age and 49% from adults. In children, 76% of strains came from otitis media, 20% from blood culture, in adults most strains (92%) came from blood culture. The overall prevalence of non-susceptible penicillin pneumococci was 61% higher in children (73%) than in adults (50%). Among the non-susceptible penicillin pneumococci 21.8% were resistant (CMI > 1 mg/l). Strains with decreased susceptibility to amoxicillin and cefotaxime were 38% and 17% respectively. Resistant strains to these two drugs (CMI > 2 mg/l) were rare 2.6% and 0.4% respectively. Among other antimicrobial agents, rate of resistance was 63% to erythromycin, 47% to cotrimoxazole, 40% to tetracycline, and 23% to chloramphenicol. The most frequent serogroups were serogroups 19 and 14, respectively 23% and 18%. Serotypes included in heptavalent vaccine covered 90% of children strains under 2 years of age. CONCLUSIONS: The prevalence of resistance to penicillin was high in children particularly in otitis media pus (76%).

[In vitro antibacterial activity of pristinamycin against penicillin resistant Streptococcus pneumoniae]. / Activité antibactérienne in vitro de la pristinamycine sur Streptococcus pneumoniae résistant à la pénicilline.

Pristinamycin, a member of streptogramin family, is the association of two groups (components I and pristinamycin II A) which have a high synergistic activity. Given the increasing rates of penicillin resistance in Streptococcus pneumoniae in many countries, and in particular of strains exhibiting multiple resistance to commonly used antibiotics, it was interesting to study the in vitro activity of pristinamycin against penicillin resistant S. pneumoniae (47 strains) and compare it with that of erythromycin. All strains were isolated from otitis media. Minimal inhibitory concentrations (MICs) were determined by an agar dilution technique using Mueller-Hinton medium supplemented with 5% horse blood. An inoculum of 10(4)-10(5) CFU per spot was delivered by a Steers replicator. This study showed that, among the 47 penicillin resistant strains, 29 (61.7%) were resistant to erythromycin but none of them were resistant to pristinamycin. The good in vitro activity of pristinamycin against S. pneumoniae could be of particular interest in cases of infections with multiresistant strains.

[Pneumococcal serotyping in France. Development (1978-1982) and vaccine covering]. / Sérotypie pneumococcique en France. Evolution (1978-1982) et couverture vaccinale.

From 09/1977 till 08/1982, 2,449 pneumococcus strains coming from Paris or province hospitals were typed according to the Danish system with antisera from the Copenhagen Statens Serum Institut by counter-immunoelectrophoresis for the first 900 and by capsular swelling afterwards. For the whole, the first 14 types or groups are in order: 19 (348), 6 (261), 23 (231), 3 (205), 1 (158), 14 (104), 9 (103), 18 (94), 7 (82), 11 (82), 15 (82), 4 (74), 8 (63), 10 (55), and make up 79.3% of the whole. For the 687 strains isolated from haemocultures or from cerebrospinal fluids, the first 14 types or groups are in order: 1 (95), 19 (69), 6 (56), 23 (49), 4 (47), 3 (44), 7 (42), 18 (40), 9 (35), 5 (32), 14 (30), 8 (27), 15 (18), 24 (13), and make up 86.9% of these strains. The annual variations for these 687 strains are slight as regards the 14 most frequent groups and types: the type I is always first, except for one year. The definition of serotypes in the groups for 261 strains isolated from cerebrospinal fluids or from haemocultures, in 1981 and 1982, allowed a study of the "vaccinal covering". It is 64.75% for the marketed tetradecavalent vaccine and 82.75% for a 23 valency vaccine defined according to international serotype statements.

In-vitro bacteriostatic activity of levofloxacin and three other fluoroquinolones against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae.

The purpose of this study was to investigate the in-vitro bacteriostatic activity of levofloxacin in comparison with that of ofloxacin, sparfloxacin and ciprofloxacin against 205 strains of Streptococcus pneumoniae (101 penicillin-susceptible, 51 penicillin-intermediate and 53 penicillin-resistant). The isolates were provided between September 1996 and October 1996 by French hospitals participating in the National Co-operative Survey of Pneumococcal Infections. The determination of MICs (mg/L) was made by the agar dilution method. The MIC50 and MIC90 values of the four fluoroquinolones for the three classes of S. pneumoniae (penicillin-susceptible, penicillin-intermediate and penicillin-resistant) were not significantly different. In contrast, the differences in in-vitro activity observed among the four fluoroquinolones against the 205 strains allowed them to be separated into three groups: sparfloxacin (MIC50/90 0.25 mg/L); ciprofloxacin and levofloxacin (MIC50 0.5 and 1 mg/L respectively, MIC90 1 mg/L); and ofloxacin (MIC50 1 mg/L, MIC90 2 mg/L). A total of 204 of the strains had a levofloxacin MIC between 0.25 mg/L and 1 mg/L, and only one of the 205 strains was highly resistant (MIC 16 mg/L). Whatever the level of susceptibility to penicillin, the relative bacteriostatic activity was, in descending order of activity, sparfloxacin, levofloxacin/ciprofloxacin and ofloxacin. These results suggest levofloxacin has potential for the treatment of pneumococcal infections.

In-vitro killing activity of combinations of beta-lactam agents with aminoglycosides against penicillin-resistant pneumococci.

Streptococcus pneumoniae has developed resistance to almost every antibacterial agent used in clinical practice, including the most active beta-lactams. This has led to the proposed use of drug combinations. The aim of this study was to determine the efficacy of combinations of beta-lactam agents (cefotaxime or imipenem) with aminoglycosides (gentamicin, netilmicin or amikacin) against pneumococci showing high-level resistance to penicillin and streptomycin and/or kanamycin. All tested combinations were bactericidal and synergic despite the weak concentrations of antibiotics used. Our results suggest that combinations of beta-lactam agents with aminoglycosides may be useful for treating infections by penicillin-resistant pneumococci located outside the central nervous system.

In-vitro antibacterial activity of RP 59500, a semisynthetic streptogramin, against Streptococcus pneumoniae.

The in-vitro activity of the new streptogramin RP 59500 was determined against 100 strains of Streptococcus pneumoniae. In all, 48 erythromycin-sensitive strains and 52 erythromycin-resistant strains were tested by an agar dilution method (MIC determination), 20 strains (eight erythromycin-sensitive and 12 erythromycin-resistant) were tested by a broth microdilution technique (MIC and MBC determination) and ten strains (two erythromycin-sensitive and eight erythromycin-resistant) were tested for bactericidal kinetics. The study showed that RP 59500 had good bacteristatic and bactericidal activity against both erythromycin-sensitive and erythromycin-resistant strains. On the basis of these results, and because the number of erythromycin-resistant strains of S. pneumoniae isolated in France has increased steadily since 1985, RP 59500 might be useful for the treatment of pneumococcal infections and warrants further investigation.

[Piezo-electric activity of dental tissues]. / L'activité piézo-électrique des tissus dentaires

The appearance of electrical charges on dental samples submitted to 10 daN compression strains was confirmed. In a first series of experiments a correlation was determined between the charges measured and the importance of the organic element at the studied locations. In a second series of measurements carried out on dental specimens after extraction of their organic content there was an almost complete disappearance of the piezoelectric phenomenon. Thus the piezoelectric phenomenon appears essentially in the organic stroma and perhaps also in certain non centro-symmetrical crystals the existence of which has to be demonstrated.

Antimicrobial resistance in Streptococcus pneumoniae: an epidemiological survey in France, 1970-1990.

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.

[Results of bacteriological technics and demonstration of pneumococcal antigens by counterimmunoelectrophoresis in 40 cases of Streptococcus pneumoniae pneumonia]. / Résultats des techniques bactériologiques et de la mise en évidence d'antigènes pneumococciques par contre-immunoélectrophorèse dans quarante-cinq pneumonies à Streptococcus pneumoniae.

This study is conducted on 45 patients with Streptococcus pneumoniae pneumonias. Counter-immunoelectrophoresis (CIE) (detection of pneumococcal polysaccharides antigens in serum and/or urine and/or pleural fluid) and conventional bacteriological technics (blood culture and/or thoracentesis and/or transtracheal function) have been performed in all cases. Streptococcus pneumoniae has been identified with conventional bacteriological technics in 27 patients. Pneumococcal antigens have been identified in 28 patients. Both technics have been positive in 10 patients. The detection of antigens has been positive in 7 on 8 pleural fluids. The CIE is very useful in patients who has been treated by antibiotics before bacteriological examination of samples (6 CIE + and 1 bacteriological technic +). The association of the two technics is very useful. The percentage of cases with CIE / and bacteriology - is 40% (18 cases). The percentage of cases with bacteriology + and CIE - is 37.7% (17 cases).

[Failure of anti-pneumococcal vaccination and prophylactic antibiotic therapy in 2 splenectomized subjects]. / Echec de la vaccination anti-pneumococcique et de l'antibiothérapie prophylactique chez deux sujets splénectomisés.

Asplenic patients are at high risk for the development of fulminant pneumococcal bacteremia. The mortality rate in those infected patients remains high. Therefore pneumococcal polysaccharide vaccine has been recommended, but despite penicillin prophylaxis pneumococcal sepsis can occur in vaccinated patients. We have observed two cases (one fatal) of overwhelming postsplenectomy pneumococcal sepsis in vaccinated patients who received long-term antibiotic prophylaxis. Both exhibited a poor antibody response to polyvalent vaccine.