Changes in the sensitivity of urinary pathogens to quinolones between 1987 and 1990 in France.
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Biomedical subjects
Publications and source records attributed to G Aubert.
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The constant development of clinical bacteriology and the consequence this has on the way an infected patient is approached and treated require that be examined a bacteriology laboratory's contribution in choosing and monitoring an antibiotic treatment. In the economic context of hospitals, one of the aims is to rationalize the prescription of biological investigations, as well as that of antibiotic treatments. The patient's history, his clinical state as well as the place where he has been admitted must be taken into account to establish, together with microbiologists, a hierarchy of the biological investigations required and to adapt the antibiotic treatment. In the laboratory, both the bacteriostatic and bactericidal sensitivity to antibiotics may be assessed in vitro. The best therapeutic antibiotic concentrations may be obtained by monitoring the pharmacokinetics of antibiotics.
Emergence of resistance to fluoroquinolones was observed in two clinical isolates of Pseudomonas aeruginosa after ciprofloxacin or norfloxacin monotherapy. In the first case, the resistant variants exhibited quinolone-imipenem cross-resistance (MIC of norfloxacin and ciprofloxacin: 16 mg/L; MIC of imipenem: 8 mg/L), although the patient had never received imipenem treatment, while the strain from the second case remained imipenem-susceptible (MIC of norfloxacin or ciprofloxacin: 8 mg/L; MIC of imipenem: 2 mg/I). The frequency of in-vitro emergence of variants resistant to imipenem and fluoroquinolones was studied for the two strains, with imipenem or fluoroquinolones as selecting agents. Ciprofloxacin and three other quinolones (norfloxacin, temafloxacin and tosufloxacin) selected imipenem-resistant variants in a similar way to imipenem for the first strain, but not for the other. In contrast, imipenem did not select quinolone-resistant variants from either strain. For both strains, killing curves demonstrated that a bactericidal effect could be obtained with a drug combination (2 x MIC of ciprofloxacin and 2 x MIC of imipenem) without any selection of resistant mutants after 24 h, thereby suggesting the possible use of this combined regimen for treating severe P. aeruginosa infection.
A number of therapeutic alternatives to continuous positive airway pressure (CPAP) and surgery have been proposed to treat sleep apnea syndrome. Nasopharyngeal intubation may provide an immediate, simple and cost-effective means of bypassing upper airway obstruction during sleep. Tolerance is good in small children but is lower, between 30 and 40%, in adults. Clinical improvement is reported by more than half of the patients treated with this device and is confirmed by polysomnography. However, in most of these subjects, breathing during sleep is only partially corrected and sleep remains fragmented. Nasopharyngeal intubation should be proposed in infants, in patients who do not tolerate CPAP or as a therapeutic substitute for CPAP during holidays or traveling. The tongue retaining device and variants of orthodontic appliances have been proposed in order to increase upper airway patency. Tolerance is low, efficacy is usually incomplete and limited to patients with moderate forms of SAS, and long-term follow-ups are scarce. Sleep position training has been advocated as a means of reducing time spent in the supine position. Long-term efficacy has not been proven. Weight loss by caloric restriction or surgical procedures produces a variable improvement of sleep architecture and breathing during sleep. It should be proposed to all patients with SAS, as cure has been achieved in a few patients with the adjunction of weight loss and another treatment modality.
Two hundred and ninety-four serum specimens from 248 subjects, whose complement fixation (CF) titres to Mycoplasma pneumoniae were known, were further investigated by IgG immunoblotting. After analysis of M. pneumoniae proteins by SDS-PAGE, nine polypeptides (p) with mol. wts of 180-43 Kda were selected for immunoblotting studies. Antibodies to M. pneumoniae measured by immunoblotting appeared progressively with age; most subjects more than 19 years old gave positive results. For most of the polypeptides, there was an increase in the frequency of band detection when the CF titres were higher. Furthermore, paired serum specimens from 10 patients with M. pneumoniae infection, as demonstrated by a rise in CF antibody titre, were tested for IgG blotting patterns. Generally, p180 (the P1 adhesin of M. pneumoniae), p172 and p84 were shown to be the dominant targets of the immune response to this organism and may have diagnostic value.
A panel of 68 serum specimens from 41 subjects exhibiting various immunological patterns to Mycoplasma pneumoniae as determined by detection of a 180 kDa protein in immunoblotting was used to compare five commercially available tests based on different methods: complement fixation test (CFT), microparticle agglutination (MAG), indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (Elisa), and latex agglutination (LA). The tests were performed according to the manufacturers' instructions. For the determination of immunity to M pneumoniae, the five tests were in good accordance with immunoblotting: sensitivity was 100% for all the five assays, specificity ranged from 95.6% (MAG) to 82.6% (Elisa) and overall agreement ranged from 98.2% (MAG) to 92.8% (Elisa). The comparisons of antibody rates obtained by the four quantitative tests (CFT, MAG, IFA, Elisa) showed correlation coefficients ranging from 0.87 (CFT-IFA) to 0.67 (CFT-Elisa). Six significant antibody rises demonstrated by immunoblotting patterns were detected by all the tests but Elisa in one case. As a whole, the commercial assays gave satisfactory results for routine determination of immune status to M pneumoniae: CFT was the cheapest test and MAG and LA were the easiest to perform.
The serum kinetics of vancomycin was studied in two patients aged 3 and 15 years during antibiotic therapy for catheter related sepsis associated with Staphylococcus epidermidis. Vancomycin was administered, simultaneously, by parenteral conventional doses (30 mg/kg/day div q 8 h) and using the antibiotic-lock technique in the infected catheter at a high concentration (150 mg/ml) during one hour, 3 hours after each infusion. Pharmacokinetics data did not show any significant change in the serum kinetics of the antibiotic. The results suggest that delivering a high concentration of vancomycin in the infected catheter using the lock technique may be useful to sterilize infected catheter without toxic effect.
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Tosufloxacin tosylate (TOSU) and temafloxacin hydrochloride (TEMA) were tested in vitro against 248 clinical isolates of various species of streptococci recovered in a hospital microbiology laboratory (Bellevue Regional Teaching Hospital). Species included S. pneumoniae (n = 20), group A streptococci (n = 22), group B streptococci (n = 30), group G streptococci (n = 17), group D S. bovis (n = 19), Enterococcus faecium (n = 45), Enterococcus faecalis (n = 28), S. sanguis (n = 21), S. milleri (n = 29) and S. mitis (n = 17). Activities of each of the two study drugs were evaluated comparatively with two other fluoroquinolones, i.e., ciprofloxacin (CIP) and pefloxacin (PEF). Activities of each of these four antibiotics, expressed as the MIC 90%, varied as follows according to the species of streptococci: TOSU, 0.25 to 1 mg/l, TEMA 0.5 to 2 mg/l, CIP, 1 to 4 mg/l and PEF 8 to 32 mgl. Overall, TOSU and TEMA exhibited the greatest activity of the various species. The size of the inoculum had no significant effect on MIC values.
Combinations of one of the new fluoroquinolones (ciprofloxacin, temafloxacin or tosufloxacin) with a betalactam (amoxicillin, piperacillin, or imipenem) were tested in vitro using the checkboard method against 28 strains of Streptococcus faecalis recovered in 1990 from a variety of specimens. No instance of antagonism (FIC greater than 2) was recorded. Effects of the two agents were usually additive (0.5 less than FIC less than or equal to 1). An indifferent effect (1 less than FIC less than or equal to 2) was seen in 32.1% of cases (9 strains) with the amoxicillin-tosufloxacin combination. Synergy (FIC less than or equal to 0.5) was uncommon with combinations including imipenem: effects were synergistic for only three strains with imipenem and either ciprofloxacin or tosufloxacin and for six strains with the imipenem-temafloxacin combination. Synergy was more common with combinations including ciprofloxacin and either piperacillin (10 strains, 35.7%) or amoxicillin (13 strains, 46.4%).
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The cerebral penetration of ceftriaxone in patients who underwent surgery for cerebral tumours was investigated. Seventeen patients received 2 g of ceftriaxone given intravenously 2 to 13 h before blood and brain samples were taken. Antibiotic levels were determined by an agar-well diffusion method. Cerebral ceftriaxone concentrations ranged from 0.3 to 12 micrograms/g, with a mean value of 1.63 micrograms/g. These values were less than 2% of corresponding serum concentrations, but enough to inhibit 75% of bacterial strains recently isolated from brain abscesses in our unit.
A case of pneumonia related to 2 serogroups (1 and 8) of Legionella pneumophila (Lp) in a 10-day-old boy is described together with the epidemiological survey in the maternity ward which made it possible to establish its nosocomial origin. Rodshaped bacteria reacting with an Lp genus-specific monoclonal antibody and serogroup 1 and 8 polyclonal sera were detected in bronchoalveolar lavages (BAL) collected on day 13. Serogroups 1 and 8 were recovered from cultures of BAL collected on days 12 and 13. Fourfold or more antibody rises to serogroups 1, 5, 8 and 10 of Lp were observed in sequential serum specimens. Water samples collected from the tank and mixer of the maternity ward grew serogroups 1 and 8 of Lp. Serogroup 1 was detected in large amounts in water samples taken at several points of the hot water supply system and from the oxygen nebulizers and the feeding-bottle heater. Analysis of the Lp serogroup 1 strains isolated from the water by subgroup-specific monoclonal antibodies revealed the presence of 4 different subgroups, one of which was identical to the Lp 1 subgroup isolated from the neonate's BAL. This latter subgroup, reactive with McKinney monoclonal antibody Mab 2, has been described as highly virulent. No other case of legionellosis was recorded in the maternity ward.
In the course of an Escherichia coli cholecystitis, demonstrated by positive blood cultures, the authors observed a therapeutic failure with amoxicillin/clavulanate, probably related to the isolation in blood cultures, nine days after the beginning of the treatment, of a beta-lactam resistant E. coli strain (MICs of the amoxicillin combined with clavulanate was 64 mg/l and ceftazidim 16 mg/l). The strains which were recovered before and after treatment were shown to have the same biotype and the same electrophoretic profile for bacterial esterases. The second strain exhibited a high level production of the mediated chromosomal cephalosporinase. In the agar diffusion test, this mutant was more easily detected by ceftazidim than by other third generation cephalosporins. In the middle-stay unit where the patient was cured, cephalosporinase high producing mutants of E. coli were recovered in 0.6 p. cent of the strains versus 5, 1 p. cent for strains with cephalosporinase phenotype and 46.6 p. cent for strains with penicillinase phenotype. This report illustrates the importance of associating two synergistic antibiotics to prevent the emergence of beta-lactam resistant mutants in the course of severe E. coli infections.
Study of the penetration of ceftriaxone into the brain of patients who underwent surgery for cerebral tumors. Seventeen patients received 2 g of ceftriaxone intravenously 2 h to 13 h before blood and brain samples were taken. Ceftriaxone levels in serum and in non tumoral cerebral tissue were determined by the agar well diffusion technique. Hemoglobin concentration was measured in cerebral samples in order to subtract ceftriaxone due to blood contamination. True ceftriaxone levels in cerebral tissue ranged from 0.3 to 12 mcg/g, mean 1.63 mcg/g. The ceftriaxone level ratio in brain and serum was low, mean about 2%, but cerebral ceftriaxone concentrations would be sufficient to inhibit more than 75% of bacteria isolated in recent cerebral abscesses. These results allow to do further therapeutic studies of ceftriaxone in cerebral abscesses due to identified and susceptible bacteria or in random treatment in association with antibiotics directed on anaerobic organisms and resistant hospital strains.
The minimum inhibitory concentrations (MIC) of 5 fluoroquinolones, fleroxacin (FLE), ciprofloxacin (CIP), ofloxacin (OFL), enoxacin (ENO) and norfloxacin (NOR) have been determined by the agar dilution method towards 140 strains of Pseudomonas aeruginosa (Pa) and 146 Enterobacteriaceae showing different sensitivities to pefloxacin (PEF). The strains were isolated in 1988 at the Bellevue Hospital. The modal MIC is 0.12 for CIP, 0.25 for NOR, 0.5 for OFL, and 1 for FLE and ENO when used on Pa strains which are sensitive to PEF (n = 35) (MIC less than or equal to 1mg/1). The modal MIC is 0.25 - 0.5 for CIP, 0.5 for NOR, 1 for OFL and ENO, and 2 for FLE when used on Pa strains which are of intermediate sensitivity to PEF (n = 70) (1 less than MIC less than or equal to 4). The modal MIC is 2 for CIP, 8 for NOR and OFL, 8 - 16 for ENO, and 32 for FLE when used on Pa strains which are resistant to PEF (n = 35) (MIC greater than 4). The modal MIC is 0.015 for CIP, 0.06 for OFL, 0.12 for FLE, NOR and ENO when used on Escherichia coli strains which are sensitive to PEF (n = 47). The modal MIC is 0.5 for CIP, 1 for OFL and NOR, and 2 FLE and ENO, when used on Escherichia coli strains which are of intermediate sensitivity to PEF (n = 38). The modal MIC is 1 for CIP, 4 for OFL and NOR, 16 for FLE, and 32 for ENO when used on E coli strains which are resistant to PEF (n = 15). The 26 Serratia marcescens and 20 Citrobacter with MIC greater than or equal to 8 for PEF all have MICs greater than 1 and modal MICs greater than or equal to 4 for all the fluoroquinolones studied. CIP always showed greater activity than the other quinolones whatever the sensitivity shown towards PEF.