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Objective: To compare the efficacy and the safety of a single intramuscular dose of ceftriaxone, 50 mg/kg, vs. a 10-day course of amoxicillin/clavulanate (amox/clav) therapy, 80 mg/kg/day of amoxicillin: 10 mg/kg/day of clavulanate in three divided doses, in children with acute otitis media (AOM) and to evaluate the changes in nasopharyngeal flora after treatment., Methods: In a prospective, comparative, open randomized, multicenter trial, children were scheduled to return for visits on Days 12 to 14 (main end point) and Days 28 to 42 after the beginning of treatment for AOM. A nasopharyngeal swab for bacterial culture was obtained before the treatment and at Days 12 to 14., Results: Between February, 1995, and May, 1996, 513 children with a mean age of 14.2 +/- 6.7 months were enrolled. All the patients were evaluable for the safety and intent-to-treat analyses and 463 for the per protocol efficacy. At Days 12 to 14 clinical success was obtained in 186 of the 235 children (79%) given ceftriaxone and in 188 of the 228 children (82.5%) treated with amox/clav. Among the patients with clinical success on Days 12 to 14, the success was maintained at Days 28 to 42 for 108 of 183 (59%) patients in the ceftriaxone group and 103 of 187 (55%) patients in the amox/clav group. Before the antibiotic treatment the percentages of children carrying Streptococcus pneumoniae (59.1%), Haemophilus influenzae (39.4%), Moraxella catarrhalis (55.7%) and the rate of penicillin-resistant S. pneumoniae (52.2%) were comparable between the 2 groups. At Days 12 to 14 the carriage of S. pneumoniae and M. catarrhalis was significantly different between the patients treated with ceftriaxone, 43.9 and 42.2, respectively, and the patients treated with amox/clav, 17.4 and 11.1%, respectively. Among the children carrying S. pneumoniae at Days 12 to 14, the percentage of penicillin-resistant strains reached 63.4% in the ceftriaxone treatment group and 83.0% in the amox/clav treatment group, (P = 0.02). Adverse events (mainly diarrhea) related to the study medication were reported more frequently (P < 0.0001) in the amox/clav treatment group., Conclusions: In an area with a high rate of penicillin-resistant S. pneumoniae, a single dose of ceftriaxone is as efficient as a 10-day course of amox/clav in the treatment of AOM in young children. There was for the two regimens an increased rate of penicillin-resistant strains among the pneumococci carried, whereas the chance for a child to carry a penicillin resistant S. pneumoniae did not increase after treatment.

Objectives: A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure., Methods: The study included 186 children with a mean age of 17.5 +/- 13.1 months. Two-thirds of them attended a day-care center and 40.8% had a history of recurrent otitis media. The most frequently prescribed prior antibiotics were amoxicillin-clavulanic acid (43% of cases), an oral third generation cephalosporin (22.6%), erythromycin-sulfisoxazole (11.8%) and a first generation cephalosporin (10.2%). The average duration of antibiotic therapy was 6.9 +/- 2.65 days. Specimens for bacterial cultures included 188 samples of middle ear fluid obtained by tympanocentesis and 37 collected from otorrhea fluid., Results: One hundred forty-one samples (62.7%) from 126 children yielded 170 bacterial isolates. In 60 children (32.3%) the culture of the ear pus was sterile. Among the 170 bacterial isolates: 67 (39.4%) were Streptococcus pneumoniae (59 patients), of which 77.6% had reduced susceptibility to penicillin (PRSP with penicillin MIC > or = 0.125 mg/l); 61 (35.9%) were Haemophilus influenzae (56 patients) of which 49.2% were beta-lactamase producers; and 8 were Moraxella catarrhalis (8 patients), of which 87.5% were beta-lactamase producers. Thirty-six patients were infected by S. pneumoniae with penicillin MIC > or =1 mg/l. In our study attending day-care center (P = 0.04), temperature >38 degrees C with signs of otalgia (P = 0.02), age <2 years (P = 0.048) and prior antibiotic treatment with erythromycin-sulfisoxazole (P = 0.006) were independently predictive risk factors for patients infected with penicillin-resistant S. pneumoniae. Pneumococcal serogroups 23, 14 and 19 were predominant (25.4, 25.4 and 23.8%, respectively). Penicillin resistance was mainly associated with serogroups 23 and 14., Conclusions: Penicillin-resistant S. pneumoniae isolates are frequently responsible for therapeutic failure in cases of acute otitis media in the Paris region.

Two double-blind, double-dummy, randomized multicentre studies compared the safety and efficacy of 10-day regimens of cefaclor advanced formulation (cefaclor AF) (375 mg twice daily) with cefaclor (250 mg three times daily) in the treatment of proven group A beta-haemolytic streptococcal pharyngitis/tonsillitis. Of the 1,138 patients enrolled, 764 (cefaclor AF:392; cefaclor: 372) were evaluated for efficacy. All patients enrolled in the studies (570 treated with cefaclor AF and 568 treated with cefaclor) were evaluated for safety. Clinical and bacteriological evaluations were performed on treatment days 4-6, and after completion of treatment within 3-5 days and 2-3 weeks. In evaluable patients, the post-therapy clinical success and bacteriological cure rates for cefaclor AF were 96.7% and 93.6%, respectively; the rates were 98.1% and 94.1% for cefaclor. Sixteen cefaclor AF-treated patients and 14 cefaclor-treated patients withdrew early from the trial because of adverse events. There were no significant differences between treatment groups in the overall number of adverse events reported. Diarrhoea was the most frequently reported adverse event (5.6%) in cefaclor AF-treated patients, and headache/migraine was the most frequently reported adverse event (5.6%) in the cefaclor-treated patients. Cefaclor AF (375 mg twice daily) is as effective and safe as cefaclor capsules (250 mg three times daily) in the treatment of streptococcal pharyngitis/tonsillitis.

Antibiotic susceptibility testing of anaerobes by a same methodology allows the authors to draw up suggestions about the evolution of antibiotic resistance within the B. fragilis group. Cefoxitin resistance rates were stable until 1985 and were slowly increasing later. Until 1985 piperacillin was able to inhibit all tested strains. In 1987 the two groups noticed an increasing resistance to piperacillin (4 to 9%). During the 1970's clindamycin resistance was a minor event (less than 1%) then the resistance rate increased rapidly to 10% in 1980. MICs determinations from 1981 to 1985 demonstrated well that clindamycin resistance was stable at this 10% rate. Since 1987 the clindamycin resistance was again increasing and reached respectively 14 to 19% for the two groups of investigators. Metronidazole has kept a good activity against Bacteroides fragilis group strains but some strains with reduced susceptibility (MIC 2 to 8 mg/l) have been described since 1983. Three strains with MIC greater than 8 mg/l were recently described by one of the groups. Until 1987, the clavulanic amoxicillin combination was able to inhibit all strains of the B. fragilis group but only imipenem remained still active on all investigated strains with no change at all for the values of MIC50 and MIC90 determined by the investigators of this study. All these results emphasize the need for periodical surveys within the B. fragilis group in each country.

The in vitro activity of a new cephalosporin (CPX) was assessed against 260 strains of anaerobic bacteria. A comparison was done with two other oral cephalosporins cefaclor (CFA) and cefuroxime (CXM). MICs were determined by an agar-dilution method on wilkins chalgren agar. The three antibiotics had little activity against Bacteroïdes fragilis group. Cefpodoxime was more active than the two other cephalosporins against Fusobacterium and Bacteroïdes spp. At 4 mg/l concentration the percentages of susceptibility were respectively CFA 8% CXM 11% for all the Gram negative bacilli. Inversely, a better activity was detected against Gram positive anaerobes; the three cephalosporins inhibiting respectively CFA 65% CXM 75% CFX 46% of 94 tested strains. All Veillonella spp. and Propionibacteria were inhibited by cefpodoxime 4 mg/l. The activity of the three cephalosporins were similar weak against Gram negative anaerobes but greater against Gram positive strict anaerobes.

Two combined antibiotic treatments were compared in 35 cases of methicillin-sensitive Staph. aureus infection. Eighteen patients (including 17 with septicaemia) received penicillin M (methicillin or oxacillin) and gentamicin daily for a mean period of 11 days. Clinical and bacteriological cure was obtained in 14 cases; 2 of these 14 patients developed superinfection with gentamicin-resistant enterobacteria, 1 relapsed and 2 had renal impairment. Seventeen patients (including 15 with septicaemia) were given fosfomycin and penicillin M for a mean period of 17 days. Clinical and bacteriological cure was obtained in 16 patients; the patient with clinical and bacteriological failure died. There was no superinfection or relapse; 3 patients had hypokalaemia and 1 had renal damage caused by methicillin. The clinical and bacteriological results, therefore, were in favour of the fosfomycin-methicillin combination, but the only statistically significant difference between the two groups concerned the complications.

Nine cases of pleuro-pulmonary infection due to Pasteurella multocida were observed over an 11 year-period (1974-1984) occurring in seven men and two women, with a mean age of 65 (range: 47-80 years). There were 4 pneumonias and 5 cases of empyema, occurring on three occasions after septicemia. There was a background of depressed immunity in 7 cases: alcoholic cirrhosis (4 cases), blood dyscrasias (2 cases), breast cancer (1 case); and of a chronic broncho-pulmonary pathology in two cases. Animal inoculation was present in six cases but only one case of pneumonia followed injury by an animal (cat scratch). The clinical, radiological and epidemiological data of these nine cases were similar to those in the literature (forty-five published cases). There was a zero mortality in our (from 30%) in the literature. Pasteurella multocida is an opportunistic organism, noncommensal in man, producing pulmonary infections in subjects with generalised or localised diminished resistance, the portal of entry being airborne (indirect animal contact) or haematogenous. The organism is nearly always sensitive to Penicillin and other B-lactamines. The gravity of infections to Pasteurella multocida relates to the degree of decompensation or severity of the underlying disorder.

The activity of 5 aminoglycosides compounds (habekacin, amikacin, gentamicin, netilmicin and tobramycin) was studied by an agar dilution method, against 235 strains of Enterobacteriaceae and 146 other Gram negative bacilli. 79 to 98% of susceptible strains were observed, according to the aminoglycoside compound. Habekacin and amikacin were the most effective, specially against the more frequently resistant bacteria: Enterobacter, Serratia, Hafnia, Acinetobacter, Pseudomonas aeruginosa. In comparison with a previous study, no evolution was observed in the resistance to aminoglycosides.

The minimal inhibitory concentrations of three antimicrobial agents were determined by two fold dilution in Wilkins Chalgren agar for over 569 anaerobes isolated and collected from 20 French hospitals. Metronidazole, cefoxitin and clindamycin inhibited respectively 95, 97 and 91% of tested strains. No metronidazole resistant strains could be found among Bacteroides fragilis group, Fusobacterium and Clostridium other than C. perfringens. Cefoxitin was the most active against C. perfringens, Gram positive cocci and non sporulated bacilli. Clindamycin resistance was observed mainly with B. fragilis and Clostridium other than C perfringens. This phenomenon occurred in most hospitals where strains were isolated.

The activity of netilmicin and four other aminoglycosides was studied by a diffusion method against 1 028 bacterial strains isolated in hospital. Nearly all the strains of Gram-negative bacilli were susceptible to amikacin; with netilmicin, tobramycin, gentamicin and dibekacin the percentages of susceptible strains were smaller, without any statistically significant differences between them. Amikacin and netilmicin were the most effective compounds against staphylococci. Netilmicin seemed to be the most effective compound, in vitro, against streptococci. The MIC of gentamicin and netilmicin of 224 strains showed the superior activity of netilmicin against K. pneumoniae, Proteus, P. aeruginosa and S. aureus.

The MIC of two hundred and seven anaerobic bacterial strains was determined by an agar dilution method for five antibiotics (piperacillin, ampicillin, carbenicillin, cefalotin, metronidazole). 100% of the strains were susceptible to carbenicillin (MIC less than or equal to 128 mg/l), 97% to piperacillin (MIC less than or equal to 16), 86% to metronidazole (MIC less than or equal to 4), 70% to ampicillin (MIC less than or equal to 4) and 68% to cefalotin (MIC less than or equal to 8). Amongst bêta-lactam compounds, piperacillin and ampicillin determined the lowest MIC for Bacteroides fragilis, Fusobacterium, Clostridium and Gram-positive cocci. Amongst Bacteroides fragilis strains, the lowest MIC were obtained with metronidazole.

The minimum inhibitory concentrations (MIC) of piperacillin and three other antibiotics (amoxicillin, cefoxitin, metronidazole) against 165 strains of obligate anaerobes isolated in hospitals in 1985 and 1986 were determined by the Wilkins-Chalgren agar medium dilution method. Among the 67 strains of Bacteroides fragilis, 98.5% were sensitive to piperacillin (MIC less than or equal to 128 mg/l), 100% were sensitive to metronidazole (MIC less than or equal to 4 mg/l), 11.9% were resistant to cefoxitin (MIC greater than 32 mg/l) and 46% were resistant to amoxicillin (MIC greater than 16 mg/l). The MIC50 was about 4 mg/l with piperacillin, 8 mg/l with cefoxitin and 0.5 mg/l with metronidazole. All 32 strains of Clostridium perfringens were sensitive to the 4 antibiotics tested, with an MIC50 of about 0.06 mg/l with piperacillin, 0.125 mg/l with amoxicillin and 0.5 mg/l with cefoxitin and metronidazole. All other strains of Clostridium spp. (33 in all) were sensitive to piperacillin and metronidazole; the MIC's were about 0.06 mg/l with piperacillin, 0.25 mg/l with amoxicillin and metronidazole and 0.5 mg/l with cefoxitin. Seven strains (C. innocuum 5, C. difficile 1, C. ramosum 1) were resistant to cefoxitin. All 33 strains of Peptostreptococcus and Peptococcus were sensitive to the 4 antibiotics tested. Although metronidazole still is the most effective of anti-anaerobes agents, piperacillin has proved to be effective against most anaerobic bacteria, including B. fragilis. It is clearly superior to amoxicillin and relatively superior to cefoxitin, notably against this species.

The in vitro activities of amoxicillin, amoxicillin-clavulanic acid, piperacillin, cefoxitin, cefotetan, cefotaxime, cefmenoxime, ceftizoxime, latamoxef, clindamycin and metronidazole, were determined by agar dilution method for 196 clinical isolates of anaerobic bacteria. No metronidazole resistant strains could be found, 10% of tested strains were resistant to clindamycin. The majority of these strains was susceptible to amoxicillin-clavulanic acid and piperacillin; less than 10% were resistant to latamoxef, cefoxitin, cefotaxime and ceftizoxime; whereas 15 to 20% were resistant to amoxicillin, cefotetan and cefmenoxime.

Prophylactic systemic antibiotherapy with ceftriaxone (CRO) alone was tested in aplastic patients receiving total gut decontamination and treated in protected environment. To enter the study, the patients had to be afebrile when their polymorphonuclear (PMN) count fell under 500/cumm. Seventy eight therapeutic aplasias (after allogeneic or autologous bone marrow transplant conditioning regimens or high dose chemotherapy) form the basis of this report. The median duration of aplasia was 19 D (11-93 D). Forty-three patients received during 51 aplasias one single injection of CRO per day as soon as PMN count was under 500/cumm. In 23 cases (45%) the patients remained afebrile until the end of aplasia. There were 3 Staphylococcus epidermidis bacteremias (6%), 3 bacteriologically documented fevers (6%) and 1 Cryptococcus septicemia. Twenty-nine of these aplasias were part of a randomized study between group A (prophylactic CRO) and group B (non prophylactic CRO: 27 cases). In group A, there were significantly more aplasias without fever (34.5% vs 4%), and less bacteremias (10% vs 48%). Fever appeared later in group A (mean 12.5 D vs 6 D). No death was recorded during the whole study. Thus, in protected environment, prophylactic systemic antibiotherapy could still lessen the risk of bacterial infections. The side effects and the cost of such a procedure appeared to be diminished by a monoantibiotherapy.

Prophylactic systemic antibiotic therapy with ceftriaxone alone was tested in aplastic patients receiving total gut decontamination and treated in a protected environment. Only patients who were afebrile when their polymorphonuclear (PMN) count fell below 500/cumm were admitted to the study. Seventy-eight episodes of therapeutic aplasia (consecutive to allogeneic or autologous bone marrow transplant conditioning regimens or to high dose chemotherapy) form the basis of this report. The median duration of aplasia was 19 days (range 11-93 days). Twenty patients received, during 22 episodes of aplasia, one single injection of ceftriaxone per day as soon as their PMN count was below 500/mm3. In 13 cases (59%) the patients remained afebrile until the end of aplasia, and no bacteriemia was detected. The second part of the study was randomized between group A (prophylactic ceftriaxone: 29 cases) and group B (no prophylactic ceftriaxone: 27 cases). Patients in group A had significantly more episodes of afebrile aplasia (34.5% vs 4%) and less bacteriemias (10% vs 48%) than those in group B. Also fever developed later in group A (mean: 12.5 vs 6 days). No death was recorded throughout the study. Thus, in a protected environment prophylactic systemic antibiotic therapy could still lessen the risk of bacterial infection. Using one single antibiotic seemed to reduce the side-effects and cost of the prophylactic treatment.

Susceptibility to cefotiam of 494 bacterial strains was studied by MIC determination using an agar dilution assay. Activity of cefotiam was also compared with that of six other beta-lactams (ampicillin, mezlocillin, ticarcillin, cefalotin, cefotaxime, and moxalactam) using an agar diffusion method. Cefotiam showed a wide antibacterial spectrum including more than 70% of Enterobacteriaceae (except Serratia), beta-lactamase-producing and non-beta-lactamase-producing Haemophilus influenzae, non-enterococcus streptococci, and penicillinase-producing and non-penicillinase-producing staphylococci susceptible to methicillin. Conversely, cefotiam was inactive against Pseudomonas aeruginosa, Acinetobacter anitratum, Streptococcus faecalis, and methicillin-resistant Staphylococcus aureus.