[Evaluation of systematic anti-meningococcal vaccination strategy in French military recruits]. / Evaluation de l'efficacité de la stratégie de vaccination systématique antiméningococcique chez les appelés de l'armée française.

The objective of the study was to assess the efficacy of meningococcal meningitidis vaccination among French military recruits, two years after the introduction of systematic vaccination. Protective efficacy (PE) was calculated using two epidemiological methods. The first was based on the incidence and density rates among vaccinated and unvaccinated subjects during the period when both groups were simultaneously available: PE = 100% (95% CI: 0-100%). The second was to compare the incidence density rates among vaccinated subjects with expected rates. The expected rates were calculated using a model involving adjustment of incidence rates observed before the introduction of vaccination. This second, more powerful method confirmed the efficacy of systematic vaccination for meningococcal meningitidis: PE = 100% (95% CI 30%-100%).

[Antibiotic sensitivity of aerobic gram-negative bacilli isolated from severe infections in 1992: results of a French multicenter study. Groupe d'Etude d'Infections à bacilles à Gram Négatif (GEIGN)]. / Sensibilité aux antibiotiques des bacilles à Gram négatif aérobies isolés d'infections sévères en 1992: résultats d'une étude multicentrique française. Groupe d'Etude d'Infections à bacilles à Gram Négatif (GEIGN).

OBJECTIVES: Antibiotic susceptibility of 649 gram-negative bacilli involved in severe infections and isolated in 18 teaching hospitals from January to December 1992 was evaluated. METHODS: Minimal Inhibitory Concentrations were determined by agar dilution method for piperacillin, piperacillin+ tazobactam and imipenem, and by a microdilution method for 11 other antibiotics (amoxicillin, amoxicillin + clavulanic acid, cefotaxime, ceftazidime, aztreonam, ticarcillin, ciprofloxacin, fosfomycin, tobramycin, gentamicin, amikacin). Criteria of Comité Français de l'Antibiogramme de la Société Française de Microbiologie were followed for interpretation. Betalactamases were identified by isoelectric focusing and overproduction of cephalosporinase was defined by the resistance phenotype. The main species isolated were Escherichia coli (45%), Pseudomonas aeruginosa (14%), Klebsiella pneumoniae (7.8%), Salmonella spp. (7.5%), Enterobacter cloacae (4%) and Klebsiella oxytoca (4%). Most of the strains were isolated from blood culture (72.3%), respiratory tract (11.4%) and intraabdominal infections (8.6%). Most of the enterobacteria isolates were susceptible to imipenem, aztreonam, amikacin and ciprofloxacin (percentages of susceptibility were respectively 99.3, 98, 98.3 and 96.3); in most of cases clavulanic acid did not entirely restore sensitivity to amoxicillin of penicillinase-producing strains. Among 89 P. aeruginosa strains, 82% were susceptible to imipenem and ceftazidime, 81% to the association piperacillin + tazobactam and 51% to ticarcillin. Resistance rates are very high for Acinetobacter baumannii except for imipenem. CONCLUSION: Production of TEM-type penicillinase and over-production of the chromosomal cephalosporinase are the most widely observed mechanisms of resistance (respectively 22% and 9% of 649 strains). Prevalence of extended spectrum betalactamases was low (1%) and essentially observed for K. pneumoniae.

[Prevention of hepatitis A and hepatitis B by vaccination]. / Prévention de l'hépatite A et de l'hépatite B par la vaccination.

In spite of low endemic levels in France, hepatitis A and hepatitis B remain major concerns for public health. Seroprevalence of antibodies against hepatitis A (anti-HAV), declining below 15% in the 20 years-aged subjects, highlights an increasing susceptibility to hepatitis A. Later in the life, HAV infections become more serious and expansive. Control measures against hepatitis B have nearly stopped HBV spread linked to blood transfusions and mothers to infants transmission. Now, common risk factors are first sexual exposure, then injecting drug use, especially among young people. Vaccination is recognized as the most effective process for prevention. Recombinant hepatitis B vaccines have taken the place of plasma-derived vaccines. Although non responder individuals and escape mutants of HBV may hamper vaccinal coverage, hepatitis vaccines are highly immunogenic in immunocompetent people, allowing simplified schedules and reduced HBsAg dosages for children. Inactivated HAV vaccines now licensed prove to be highly immunogenic after only one injection. Hepatitis B vaccination targeted on high risk groups remains imperative but inadequate for reducing hepatitis B occurrence. A universal hepatitis B vaccination program in childhood and early adolescence would nearly stop the spread of HBV in the populations before ten years. Likewise, hepatitis A vaccination of travelers to endemic areas, all individuals exposed to contaminations from fecal sources, and food handlers, could reduce the spread of HAV in the community but would not completely prevent outbreaks of hepatitis A. Advantages of universal immunization of babies are not proved yet. Implementation of preventive strategies first needs a comprehensive surveillance of viral hepatitis in France.

[Bactericidal activity of 6 antibiotics and 3 combinations against 6 strains of Salmonella isolated from blood]. / Activité bactéricide de six antibiotiques et de trois associations sur six souches de salmonelles isolées d'hémoculture.

The bactericidal activity of 6 antibiotics and 3 combinations was evaluated against 6 Salmonella strains isolated from blood: 3 sensitive to all antibiotics tested (1 Salmonella Typhi, 1 Salmonella Paratyphi A et 1 Salmonella Enteritidis) and 3 harbouring a TEM penicillinase (1 Salmonella Typhi, 1 Salmonella Virchow et 1 Salmonella Typhimurium). MICs of 6 antibiotics, ceftriaxone, cefotaxime, cefoperazone, ciprofloxacin, amikacin and chloramphenicol were determined by microdilution method in Mueller Hinton broth. The bactericidal activity of these antibiotics and 3 combinations (ciprocloxacin + ceftriaxone, ciprofloxacin + amikacin and ceftriaxone + amikacin) was determined by the killing curve method with 10(6) cfu/ml inocula and 4 x MIC for antibiotics concentrations. Chloramphenicol, only tested on typho-paratyphi strains, had only a bacteriostatic effect at 24 hours. Amikacin and ciprofloxacin had a faster and better bactericidal activity than cephalosporins. Combinations were either additive or synergistic. Those including amikacin had the best results, but any can be proposed for initial treatment of severe Salmonella infections in immunosuppressed patients.

[In vitro antibacterial activity of a new fluoroquinolone, enoxacin against hospital bacteria and regression curve]. / Activité antibactérienne in vitro d'une nouvelle fluoroquinolone, l'énoxacine sur les bactéries hospitalières et courbe de concordance.

Minimal inhibitory concentrations (MICs) of enoxacin (ENX), a new fluoroquinolone indicated for the treatment of urinary tract infections, was determined by agar dilution for 703 bacterial strains isolated in 1993 in 3 university hospitals in order to study its activity against urinary pathogens; in addition, antibiograms by agar diffusion were performed with 5 micrograms disks to calculate the regression curve and the breakpoints for sensitivity testing. Activity of ENX against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that of other fluoroquinolones (FQ) (MIC 50 and 90: 0.25-0.5 microgram/ml); like for other FQ, this activity was reduced against NAL intermediate and resistant (R) Enterobacteriaceae (8-64) MICs of ENX against P. aeruginosa were between 0.5 and 128 (2- > 128). ENX had also a good activity against NAL-S A. baumannii (0.06-2) but this activity is reduced against NAL-R Acinetobacter (0.5- > 128). ENX showed activity close to the currently available FQ against methicillin susceptible Staphylococci (0.5-8); the resistant strains (32- > 64) are usually methicillin resistant. ENX is less effective against Enterococci (4-128). The coefficient correlation of the regression curve is 0.906. For MIC breakpoints of 1 and 2 micrograms/ml, zone diameter breakpoints should be 22 and 19 mm.

[Comparative activity of azithromycin against 100 strains of Neisseria gonorrhoeae]. / Activité comparée de l'azithromycine sur cent souches de Neisseria gonorrhoeae.

Azithromycin is a new semisynthetic, acid stable C15 macrolid. In our study, we compared in vitro activity of azithromycin with 6 other antibiotics usually recommended for treatment of N. gonorrhoeae infections: erythromycin, ampicillin, amoxicillin, ceftriaxone, spectinomycin, ciprofloxacin. 100 strains have been selected: 95 clinical strains with different resistance patterns: 60 susceptible to beta-lactams, 25 PPNG, 10 chromosomal decreased susceptibility to beta-lactams. Among these strains, 13 had a decreased susceptibility to erythromycin (MIC: 2 and 4 mg/l) and 5 WHO reference strains: A: spectinomycin resistance, B: wild phenotype, C: chromosomal decreased susceptibility to penicillin and tetracycline, D: chromosomal resistance to penicillin and erythromycin+chromosomal decreased susceptibility to chloramphenicol, E: beta-lactamase producing strain (PPNG) and decreased susceptibility to tetracycline. MICs have been determined by GC agar dilution method. Azithromycin is more active than erythromycin on all N. gonorrhoeae patterns with a two log 10 difference for MIC50 and MIC90 (p < 0.0001). Because of pharmacokinetic properties and activity against Chlamydia trachomatis and urogenital mycoplasms often associated with N. gonorrhoeae, azithromycin is a good alternative for the treatment of genital infections.

[Prevention of hepatitis A and hepatitis B with vaccination]. / Prévention de l'hépatite A et de l'hépatite B par la vaccination.

In spite of low endemic levels in France, hepatitis A and hepatitis B remains major concerns for public health. Seroprevalence of antibodies against hepatitis A (anti-HAV), declining below 15% in the 20 years-aged subjects, highlights an increasing susceptibility to hepatitis A. Later in the life, HAV infections become more serious and expansive. Control measures against hepatitis B have nearly stopped HBV spread linked to blood transfusions and mothers to infants transmission. Now, common risk factors are first sexual exposure, then injecting drug use, especially among young people. Vaccination is recognized as the most effective process for prevention. Recombinant hepatitis B vaccines have taken the place of plasma-derived vaccines. Although non responder individuals and escape mutants of HBV may hamper vaccinal coverage, hepatitis vaccines are highly immunogenic in immunocompetent people, allowing simplified schedules and reduced HBsAg dosages for children. Inactivated HAV vaccines now licensed prove to be highly immunogenic after only one injection. Hepatitis B vaccination targeted on high risk groups remains imperative but inadequate for reducing hepatitis B occurrence. A universal hepatitis B vaccination program in childhood and early adolescence would nearly stop the spread of HBV in the populations before ten years. Likewise, hepatitis A vaccination of travelers to endemic areas, all individuals exposed to contaminations from fecal sources, and food handlers, could reduce the spread of HAV in the community but would not completely prevent outbreaks of hepatitis A. Advantages of universal immunization of babies are not proved yet. Implementation of preventive strategies first needs a comprehensive surveillance of viral hepatitis in France.

[Current status of immunization in the Armed Forces: need of continuous adaptation of vaccinations against cerebrospinal meningitis, typhoid and hepatitis A]. / Actualités des immunisations dans les armées: nécessité d'une adaptation continue des vaccinations contre la méningite cérébrospinale, la typhoïde et l'hépatite A.

The history of military medicine has always been closely linked with that of vaccinations. Doctors of Armed Forces, doctors of collectivities, have contributed to vaccination progresses in large amounts. But evolutions are often rapid here: epidemiological modifications, improvements in the existing vaccines or creation of new vaccines, diversification of military specificities. Three recent modifications in the vaccination schedule of the Armed Forces show this necessary adaptation: systematization of the meningococcal A+C vaccination during the incorporation, because of the modification of the disease's epidemiological profile; increase of the frequency in serogroup C with a mortality increase (9 cases of death out of 10 observed between 1991 and 1992); cancellation of antityphoid vaccination for recruits serving in home country. Indeed the disease has become rare in France, and this is often due to imported cases (3 cases in the Armed Forces in 1992); introduction in 1994 of vaccination against viral hepatitis A, systematic under the age of 25 years and after a serological selection above for servicemen having to serve overseas or for outside operations. These 3 examples show the necessity to have updated and adaptable vaccination schedules.

[In vitro activity of meropenem and seven other beta-lactam antibiotics against K.pneumoniae and enterobacteriaceae producing beta-lactamases with extended spectrum]. / Activité in vitro du méropénème et de sept autres bêtalactamines vis-à-vis de K.pneumoniae et d'entérobactéries produisant des bêtalactamases à spectre élargi.

Meropenem is a broad antibacterial spectrum carbapenem with a good activity on betalactam resistant Gram-negative bacilli. 120 non repetitive strains isolated from clinical samples from 1989 to 1992 were selected: 60 K. pneumoniae, 7 E. coli, 2 E. aerogenes and 1 S. marcescens with extended spectrum betalactamases (23 CTX-1, 18 SHV-2, 5 SHV-3, 16 SHV-4, 4 SHV-5, 3 CTX-1 + SHV-4, 1 CAZ-1), 10 K. pneumoniae with broad spectrum TEM-1 enzyme, and 40 K. pneumoniae with only SHV-1 chromosomal betalactamase. Determination of Minimal inhibitory concentrations (MIC) was done by agar dilution method for meropenem and 7 other betalactams (amoxicillin + clavulanic acid 2 mg/l, piperacillin + tazobactam 4 mg/l, cefoxitin, cefotetan, cefotaxime, ceftazidime, imipenem). All antibiotics except amoxicillin + clavulanic acid are active against strains with constitutive penicillinase. For strains with TEM-1 penicillinase, cephamycins, third generation cephalosporins and carbapenems are active. For strains with different extended spectrum betalactamases only cephamycins and carbapenems are efficious. There is no difference according to the period of isolation: 1989-90 or 1991-92. Meropenem has the best in vitro activity (MIC50 = 0.03 mg/l) for all strains independently of the nature of betalactamase.

[In vitro antibacterial activity of a new fluoroquinolone, fleroxacin, against hospital bacteria and regression curve]. / Activité antibactérienne in vitro d'une nouvelle fluoroquinolone, la fléroxacine, sur les bactéries hospitalières et courbe de concordance.

Minimal inhibitory concentrations (MICs) of fleroxacin (FLE) were determined by agar dilution for 1261 bacterial strains isolated in 1992 in 4 university hospitals; in addition, antibiograms by agar diffusion were performed with 5 micrograms disks. Activity of FLE against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that of other fluoroquinolones (FQ) (MIC 50 and 90: 0.12-0.25 micrograms/ml); like for other FQ, this activity was reduced against NAL intermediate and resistant (R) Enterobacteriaceae (4-32). MICs of FLE against P. aeruginosa were between 1 and 128 (8-128). FLE had also a good activity against NAL-S A. baumannii (0.12-0.5) but this activity is reduced against NAL-R Acinetobacter (64-128). FLE was highly active against Haemophilus (0.06-0.12), Gonococci (0.03-0.25), Meningococci (0.016-0.03) and B. catarrhalis (0.12-0.25). FLE showed activity close to the currently available FQ against methicillin susceptible Staphylococci (0.25-1); the resistant strains (32- > 128) are usually methicillin resistant. FLE is less effective against Enterococci (4-128), Streptococci (8-16) and Pneumococci (4-8). The coefficient correlation of the regression curve is 0.93; for MIC breakpoints of 1 and 4 micrograms/ml, zone diameter breakpoints should be 20 and 15 mm.

[Current status of resistance of bacteria to pefloxacin in hospital units. Cross resistance with ofloxacin and ciprofloxacin. Results of a multicenter study]. / Etat actuel de la résistance des bactéries à la péfloxacine à l'hôpital. Résistance croisée avec l'ofloxacine et la ciprofloxacine. Résultats d'une étude multicentrique.

The antibacterial activities of pefloxacin (PEF), ofloxacin (OFL), ciprofloxacin (CIP) were measured by agar diffusion (5 micrograms strength disks) against 6370 non duplicate clinical isolates collected in November 1991 in 40 hospitals from various areas in France. The MICs of PEF, OFL and CIP were determined by agar dilution against intermediate or resistant strains to one of the three antibiotics (inhibition zone < 16 mm for PEF, OFL, < 19 mm for CIP). In the Enterobacteriaceae the overall incidence of resistance to PEF (MIC > 4 mg/l) was 8% with important variations between the different species: E. coli 2%, Salmonella 0%, E. cloacae 9%, K. pneumoniae 21%, P. mirabilis 13%, P. vulgaris 3%, M. morganii 5%, Providencia 61%, S. marcescens 55%. Among S. aureus, the incidence of resistance was 3% for the methicillin-susceptible strains and 86% for the methicillin-resistant strains. The same applied to coagulase negative Staphylococci: methicillin-susceptible 9%, methicillin-resistant 62%. The frequency of the resistant strains was high among P. aeruginosa: 40% and A. baumanii: 83%. A high degree of correlation was observed between the MICs of PEF, OFL and CIP for all the bacterial species: r = 0.8 - 0.9. No major discrepancies were noted between the clinical categorizations of the activities of the three antibiotics for the different species except for P. aeruginosa: 4% of the strains were resistant to pefloxacin and susceptible to ciprofloxacin.

[In vitro bactericidal activity of seven antibiotics and four combinations against Neisseria meningitidis]. / Activité bactéricide in vitro de sept antibiotiques et de quatre associations sur Neisseria meningitidis.

The authors studied, with a time-kill curve method, in a derived Hafiz medium broth the bactericidal effect of 7 antibiotics and 4 associations against N. meningitidis. Their results show a better bactericidal effect for penicillin G, ampicillin and chloramphenicol. Pefloxacin and ceftriaxon are less efficient. The association ampicillin + chloramphenicol in vitro shows no antagonism and has a good bactericidal activity at the early stages of bactericidal killing with N. meningitidis.

[Value of the E-test for the determination of the susceptibility to antibiotics of Neisseria meningitidis]. / Intérêt de l'E-test dans la détermination de la sensibilité aux antibiotiques de Neisseria meningitidis.

The E-test was evaluated by comparison with the reference agar dilution method on 50 N. meningitidis strains belonging to serotypes A [13], B [17] and C [12] or not agglutinated, isolated in France and Djibouti from cerebrospinal fluid. All strains were sensible by the reference method to penicillin G, cefotaxime, chloramphenicol, ciprofloxacin, doxycyclin, rifampicin. For erythromycin, some strains were intermediate (7/50). N. meningitidis serogroup A ATCC 13077 was used as control. The E-test quantitative accuracy compared with agar dilution results was 80% (+/- 1 log2) or 97% (+/- 2 log2). The E-test generally showed lower inhibitory concentration values than the agar dilution method. Some technical problems appear in our experience: agar plates must be well dried; on 85 mm diameter agar plates only one strip can be tested. The E-test for determination of antibiotic resistance of N. meningitidis is an easy but expensive method, which give reliable results with agar dilution.

[Determination of the susceptibility of staphylococci and enterococci to plycopeptides by the E-test method]. / Détermination de la sensibilité aux glycopeptides des staphylocoques et entérocoques par la méthode E-test.

E-test was evaluated by comparison with the reference agar dilution method on 15 enterococci and 15 staphylococci with variable resistance to glycopeptides and isolated from clinical samples: 15 enterococci with 3 glycopeptide-resistant (2 E. facalis and 1 E. faecium), 1 glycopeptide intermediate E. gallinarum and 11 glycopeptide-sensible E. faecalis; 15 staphylococci with 4 teicoplanine-resistant (1 S. aureus, 1 S. epidermidis and 2 S. hominis), 3 teicoplanin-intermediate (1 S. epidermidis, 2 S. haemolyticus) and 8 teicoplanin sensible strains (6 S. aureus, 1 S. epidermidis and 1 S. hominis). Repeatability (10 determinations by strain) and exactitude were tested for all strains. Our data shows very good results for repeatability and exactitude with the reference method except in the case of coagulase negative staphylococci and teicoplanin. Some technical problems appear in our experience: for staphylococci, a 48 h incubation is necessary to detect teicoplanin-intermediate strains but 24 h is sufficient for enterococci. E-test is expensive, require a strict methodology, but is a good method to detect glycopeptide resistance for staphylococci and enterococci except for coagulase negative staphylococci and teicoplanine.

[Value of the score for Gram strains in the diagnosis of bacterial vaginosis]. / Valeur du score au Gram dans le diagnostic des vaginoses bactériennes.

The interpretation of Gram-stained slides of vaginal swab specimens is evaluated for the diagnosis of bacterial vaginosis and correlated with the isolation bacteria and clinical signs: thin homogeneous vaginal discharge, pH > or = 4.7, amine odor and presence of clue cells. Gram stained smears were scored following a morphotype classification: (a)-Lactobacillus morphotypes (scored 4 to 0), (b)-small Gram negative (G. vaginalis, scored 0 to 4), (c)-curved Gram variable rods (Mobiluncus morphotypes, scored 0 to 2). The scoring system (0 to 10) was a weighted combination of these morphotypes: a+b+c. The criterion for bacterial vaginosis was a score > or = 7, a score of 0 to 6 was considered as no bacterial vaginosis. Samples of 709 women, aged 18 to 84 (mean age = 39.7) were examined. The prevalence of G. vaginalis culture was 12.5%, and Mobiluncus infection occurred in 1.5%. The frequency of M. hominis was diagnosed in 2.8% of women. A score of 7 to 10 on Gram stain was observed in 9.7% in the population. Compared to G. vaginalis culture, Gram stained smear was more sensitive (0.71) than clinical signs of bacterial vaginosis (0.46). The specificity was similar with the two methods. The assessment of G. vaginalis morphotypes was highly correlated with the G. vaginalis culture (p < 0.001, OR = 248). The infection of T. vaginalis or Candida sp. was never associated with a score > or = 7. The Gram-stained smear is a cheap, fast and easy method. It provides good results for diagnosis of bacterial vaginosis.

Comparison of phenotypic methods and DNA hybridization for detection of methicillin-resistant Staphylococcus aureus.

One hundred thirty-eight Staphylococcus aureus isolates from patients with severe staphylococcal infections were collected in 15 French hospitals. Detection of the mec gene was performed by dot blot hybridization with a specific DNA probe. Dot blot results were used to characterize the isolates as methicillin susceptible (77 isolates) or resistant (61 isolates). The isolates were screened for methicillin resistance by an agar spread method on Mueller-Hinton plates containing oxacillin (2 and 10 micrograms/ml) and were incubated at 37 degrees C, with 10(8) CFU as the inoculum. MICs of oxacillin and methicillin were determined by the agar dilution method on Mueller-Hinton plates without NaCl, by using 10(5) CFU per spot, after 24 and 48h of incubation at 30 or 37 degrees C. Moderately elevated MICs were found for 20 isolates (14.5%). The mec gene was detected in six (30%) of the isolates expressing a low level of resistance to methicillin and/or oxacillin. As determined by comparison with probe hybridization results, the spread plate method with oxacillin at 2 micrograms/ml was more sensitive (sensitivity, 100%) and specific (specificity, 100%) than agar dilution with either methicillin or oxacillin in identifying methicillin resistance or susceptibility. Determinations of methicillin and oxacillin MICs by the agar dilution method had a specificity of 99 to 100% depending on the conditions of incubation, but the sensitivity was below 85% whatever the duration or temperature of incubation.