[Present status of the resistance of the Pneumococcus to macrolide antibiotics. Experience of the Grenoble University Medical Center].
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Biomedical subjects
Publications and source records attributed to M Micoud.
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Authors report a prospective clinical an bacteriological study in 32 patients, almost with a chronic bronchopulmonary disease. A group of 16 patients was treated with the association clavulanic acid-amoxicillin (ACA) and the 16 others with josamycin (J) for an acute exacerbation of bronchitis. Pus and numeration of bacteria in expectorations were the criteria of efficacity. Better results of ACA group were assessed with 14 cures (87%) against 4 (25%) (p less than 0.001) and no failure against 4 in J group (p less than 0.05). They conclude therapy with ACA is more effective and recommended in serious acute exacerbations in chronic bronchopulmonary diseases.
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Ofloxacin diffusion into cerebrospinal fluid (CSF) was evaluated in nine patients with bacterial meningitis. Patients were under treatment with i.v. amoxicillin (100 mg/kg/day), and during the first five days they were also given oral ofloxacin, 200 mg b.i.d. On days 2 and 5, blood and CSF samples were collected for assays by both HPLC and microbiological techniques. Samples were obtained 2 h (n = 2), 4 h (n = 1), 6 h (n = 2), 8 h (n = 2) and 12 h (n = 2) after the ofloxacin dose respectively. Concentration in CSF was 50 to 60% of that in serum and there was no significant difference between results with the two assay techniques.
The authors studied the tolerance and efficacy of the new stabilized 17D yellow fever vaccine produced by Pasteur Vaccins, on 50 international travellers at the University Hospital of Grenoble (France), comparing it with the standard 17D yellow fever vaccine. The short-term and long-term tolerance in all the travellers was excellent. The serological efficacy was estimated by seroneutralization assay with the vaccine virus Rockefeller 17D, which is the most sensitive and the most specific method. The seroconversion rate was 93.8%, the same as the rate obtained with the standard yellow fever vaccine in 50 other travellers. The authors studied also the serological response to the standard yellow fever vaccine associated with other vaccines (diphtheria, tetanus, oral or injectable poliomyelitis, and oral cholera): the seroconversion rates were similar to those obtained with the yellow fever vaccine alone, thus demonstrating that these associated vaccines do not interfere with immunization against yellow fever.
In a prospective study 128 community acquired pneumoniae were treated with a macrolide (josamycin) by oral route. Patients improved in 94 p. 100 (113). Complications were as following: 2 deaths, 2 sequels, 3 failures. Authors discuss macrolides effectiveness in acute pneumoniae, particularly pneumococcal ones. They conclude macrolides are a good choice in first intention in acute pneumoniae of adults.
One hundred febrile episodes in neutropenic (PMN less than 500/mm3) patients were treated with Timentin alone or in combination with amikacin. The overall response rate in 87 episodes was 82.9% with Timentin alone and 84.5% with the combination. Eleven out of 15 patients with septicaemia were cured by Timentin alone and 12 out of 13 by the combination, a response rate of 73.3% and 92.4% respectively (not-statistically significant P = 1.307). The rates of superinfection were low. Few side effects occurred. Timentin is a useful antibiotic in the treatment of febrile neutropenic patients and was, in this study, as effective alone as in combination with an aminoglycoside in the initial therapy.
Effectiveness of cefotetan, a new generation semisynthetic cephamycin, was studied in a clinical trial in elderly patients. Cefotetan was used as single drug therapy. A single daily injection of 2 g was given to each of 33 elderly subjects (mean age 70.2 years, range 69-92 years). The infections were severe: pneumonia in 13 cases, septicemia in 12, upper urinary tract infections in 3 and miscellaneous infections in the remaining cases. The regimen used proved clinically effective (93% successes) and achieved residual serum levels greater than the MICs of all the Gram negative bacteria and most of the Gram positive cocci isolated. In addition to being efficient, the single daily injection regimen causes minimal damage to peripheral veins, provides optimal comfort to the patient, and saves both material and time.
Imipenem and cilastatin in combination have a broad spectrum in vitro with a strong killing activity on most bacteria. Using a multicenter study design, we investigated 41 patients with moderate or severe infections: septicemia in 18 cases (Gram negative rods in 10, Gram positive cocci in 7 and combination of both in 1), pneumonia in 7, osteitis in 4, soft tissue infection in 7, infection of the genitourinary tract in 6 and miscellaneous infections in the remaining cases (1 abscess of the pancreas, 1 typhoid fever, 1 presumptive endocarditis). All of the bacteria were susceptible to imipenem/cilastatin: MICs ranged from 0.02 to 0.8 mg/l and MBCs from 0.015 to more than 10 mg/l. All patients except one recovered or improved under imipenem/cilastatin. The patient who failed to respond had septicemia due to a methicillin-resistant Staphylococcus aureus with a MBC and MIC above 10 and 0.5 mg/l respectively. Tolerance was outstanding: only 4 patients had adverse effects requiring withdrawal of the drug.
16 patients with bacterial meningitis following a neurosurgical procedure were given a combination of ceftriaxone and fosfomycin. 8 microorganism were isolated: 2 Staphylococcus epidermidis, 1 Staphylococcus aureus, 1 Neisseria meningitidis, 1 Streptococcus pneumoniae, 1 Haemophilus influenzae, 1 Serratia marcescens and 1 Aeromonas hydrophila. No pathogen was identified in the remaining cases. All of the isolated strains were susceptible to both antibiotics. In vitro, neither synergy nor antagonism were observed between the two antimicrobial agents. The acute infectious episode resolved in all patients. One relapse only was observed, in a patient with meningitis related to a ventricular shunt, and successfully treated by the same therapeutic schedule associated with removal of the tubing. Lastly, CSF concentrations of both antibiotics were assayed and found to be comparable with those reported by most author.
Nine patients with typhoid fever were given ofloxacin in a daily dosage of 400 mg for ten days. All patients recovered with no relapses. No case of Salmonella typhi carriage was recorded. Diffusion of ofloxacin into mesenteric lymph nodes was studied in four patients. Mean concentration was 1.46 micrograms/g after four 200 mg doses. According to our results, ofloxacin could be considered as one of the alternatives for treating typhoid fever.
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We treated 10 patients with bacterial meningitis by 150 mg/kg/day cefmenoxime divided into six intravenous infusions. CSF samples were taken one hour after an IV on the second and fifth days. CSF cefmenoxime determined by microbiologic assay was 8.3 mg/l on days 2 and 5. Every patient recovered without sequelae. In our opinion, these results may support use of cefmenoxime in bacterial meningitis.
Pneumococcal vaccine effectiveness was assessed in a randomized trial among 1,686 old people (mean age: 74, standard deviation: 4 years) living in 24 geriatric hospitals and 26 homes for the aged in our district; 937 were vaccinated with Merck-Sharp and Dohme pneumococcal vaccine (14 serotypes). The 749 others composed the reference group. This study was performed during 2 years, since December 1980. Both groups were randomized after a two-criteria stratification: by clinical risk assessed before the study, and by type of homes for the aged. Forty pneumonias were diagnosed, with 13 proved pneumococcal etiology. The incidence of pneumonia was significantly reduced in the vaccinated group (p less than 10(-4) but the mortality rate was not modified. We concluded in favor of the effectiveness of pneumococcal vaccine: etiological fraction 77.1% (51.2%-89.3% confidence limits, 95% risk) in the population we studied. The incidence of pneumococcal-proved pneumonia was not significantly reduced.
An epidemiological survey was conducted after the observation of 4 cases of acute brucellosis in an horticultural school. Of a total number of 215 attendants, eventually exposed to a single contamination, 65 cases of brucellosis were thus identified. The source of contamination was probably a practical lesson where the pupils studied a bovine gravid uterus. More stringent regulations are needed in order to avoid further similar epidemics.
The complications of varicella have been studied in 103 cases of hospitalized children. The patients have been divided into two groups: group I comprises 94 previously healthy children; group II is made up of 9 children who have been treated by corticotherapy for a long time. The frequency of the complications is not statistically different between the two groups. On the other hand, all the fatal complications are observed in group II (3 deaths out of 9 patients). This investigation is in accordance with published data which allows us to characterize a high risk population for life threatening varicella: patients with congenital or acquired cell immunity deficiency. This group requires special therapy: vaccination, specific immunoglobulins and acyclovir.
Cerebrospinal fluid levels of fosfomycin were measured in 10 patients with bacterial meningitis. Fosfomycin 200 mg/kg/day was administered in three 4-hour intravenous infusions. The antibiotic was associated with amoxicillin in 9 patients and with cefotaxime in one. Cerebrospinal fluid was obtained on the 2nd and 5th days of treatment, 2 hours after the end of the infusion. The mean CSF fosfomycin levels were 31 mg/l on the 2nd day and 37.2 mg/l on the 5th day. These levels were higher than the MIC 90 for most bacteria encountered in meningitis. Fosfomycin could be used to treat some cases of bacterial meningitis, but always in association with another antibiotic.