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Biomedical subjects

H Monteil

Publications and source records attributed to H Monteil.

At least 145 records · Page 8Linked to original sources

Urinary tract infections with tissue penetration in children: cefotaxime compared with amoxycillin/clavulanate.

In children, the site of urinary tract infection (acute pyelonephritis or cystitis) cannot usually be accurately determined from the clinical presentation. The severity of the urinary tract infection (risk of renal scars) is best correlated with its estimated degree of tissue penetration clinically (fever, general condition) and on laboratory tests (sedimentation rate, C-reactive protein). The duration of parenteral antibiotic therapy, especially in children (taking account of difficult venous access and the cost of hospitalization) needs to be specified beyond the initial period required for sterilization of the urine (usually less than 48 h). We conducted a study in children older than one year to compare the efficacy and tolerance of two treatment regimens for urinary tract infection with tissue penetration: cefotaxime 100 mg/kg/d in four divided iv doses for 14 days (group I) and amoxycillin/clavulanate 100 mg/kg/d in four divided iv doses for seven days with conversion to the oral route at a dosage of 50 mg/kg/d for seven days (group II). The randomised protocol included ten patients in each group, comparable with respect to sex, age and history. Clinical efficacy (time until the patient became afebrile), bacteriological efficacy (sterilization of the urine), and biological efficacy (time to normalization of the indices of the acute inflammatory response) were identical for both groups regardless of the duration of iv antibiotic treatment (seven days for amoxycillin/clavulanate; 14 days for cefotaxime). The only side effect was diarrhoea, which affected three patients and did not require modification of the oral treatment regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxicillin↗

Clinical pharmacokinetics of cefotiam.

Cefotiam, a semisynthetic parenteral cephalosporin of the aminothiazole group, exhibits interesting properties: stability against hepatic metabolism and excellent solubility, accounting for an apparent volume of distribution 2 to 3 times higher than that of most other cephalosporins. Its degree of protein binding is about 40%. High concentrations of cefotiam are observed in several tissues (kidney, heart, ear, prostate and genital tract) as well as in fluids and secretions (bile, ascitic fluid). In healthy subjects, the serum elimination half-life is about 1 hour. The pharmacokinetics are linear only for doses lower than 1g. Cefotiam is mostly (and rapidly) eliminated in unchanged form in urine; 50 to 70% of the dose is recovered during the 12 hours following administration, and only severe renal failure, with creatinine clearance less than 5 ml/min, significantly alters the elimination half-life. Although the drug has no proven nephrotoxicity in man, a reduction of the dose is recommended when creatinine clearance is less than 30 ml/min.

Aging↗

[Lyme disease and Borrelia burgdorferi infections in Europe].

Lyme disease is endemic in Europe. The strains of the causative agent, Borrelia burgdorferi, seem to be antigenically more heterogeneous than the North American isolates. The only documented vector for this bacterium in Europe is ixodes ricinus, but other vectors might be involved as observed in the United States. The tick hosts are not yet well documented in Europe. Human infection occurs principally during summer months. The clinical aspect of the disease has particular features in Europe: at the early stage of the disease, a single and large erythema chronicum migrans is observed on the skin; complications often include meningoradiculonevritis (Bannwarth's syndrome) and later, acrodermatitis chronica atrophians; arthritis is less frequent in Europe than in the USA. The culture of B. burgdorferi from the lesions is difficult. The diagnosis of the disease is performed on the basis of serological tests: immunofluorescence assay where the important thing is to define a cutoff titer; ELISA tests using either whole cells or supernatant of sonicated cells or flagellar antigen; passive haemagglutination for IgG; IgM solid phase haemadsorption; Western blot (immunoblot) seems interesting to perform on a research basis to determine to which protein antigens patients are responding with antibody. Once antibody production begins, it is usually in the form of IgM antibody to flagellin protein (41 kD), with time, both IgM and IgG antibodies to a variety of other antigens appear. Prophylaxis is based on health services and public education because a prompt removal of the tick diminishes risk of infection with B. burgdorferi (4 p. cent of cases after tick bite). The treatment includes aminopenicillins or tetracyclines at the early stage. The second and third stages of borreliosis are treated by high doses aminopenicillins or cetriaxone.

Acrodermatitis↗

[Cefpiramide, a new cephalosporin with high hepatic elimination; experimental evaluation of its biliary passage and disposition in the liver].

The biliary elimination and hepatic disposition of cefpiramide were studied using an isolated and perfused rabbit liver model. Five experiments were performed, each lasting 3 hours. After addition of 10 mg of cefpiramide to the circulating blood, the biliary concentration reached a mean peak of 741 +/- 15 micrograms/ml between the 30th and 60th minute; the cumulated biliary elimination of the drug amounted 4042 +/- 1099 micrograms, corresponding to 40.4% of the injected dose. The hepato-biliary clearance was 54.5 ml/hr and the biliary elimination rate constant 0.2019(hr-1). At the end of the perfusion, 21.7% of the dose was still present in the circulating blood and 1.4% is found in the liver. Control experiments showed that 36.2% of the cefpiramide added into the experimental device was submitted to degradation. Thus, it was possible to calculate the rate of liver biotransformation of cefpiramide, which accounted for 0.3%. These experimental results confirm the major role of the liver in the elimination of cefpiramide and prove that the drug is not submitted to hepatic metabolisation.

Animals↗

Pharmacokinetics of teicoplanin in children.

A single dose of 6 mg/kg teicoplanin was infused over 10 min in six children of mean age 7 years, and a single dose of 6 mg/kg was infused over 20 min in four neonates of mean age 8.5 days. Serum sampling was performed at 0 and 10 min and at 1, 4, 12 and 24 h and thereafter 24-hourly, up to ten days. Urine was collected for each 24 h throughout the study in children. Teicoplanin was assayed by high performance liquid chromatography. Tolerability of teicoplanin was excellent both in children and in neonates. For all the patients the serum concentrations of teicoplanin followed an open two-compartment model. Mean Cmax was 48.6 +/- 16.7 mg/l (10 min) in children, and 19.6 +/- 1.05 mg/l (20 min) in neonates, and mean t1/2 beta was 20.5 +/- 5.5 h and 30.3 +/- 6.3 h, respectively. On the basis of the results dosage recommendations for children and neonates are made.

Adolescent↗

HPLC quantitation of the six main components of teicoplanin in biological fluids.

Teicoplanin, a new glycopeptide antibiotic belonging to the same class as vancomycin, is a mixture of six main components, designated A3, A2-1, A2-2, A2-3, A2-4 and A2-5. An assay method by higher performance liquid chromatography (HPLC) has been devised to separate and monitor each of these components in blood and urine.

Anti-Bacterial Agents↗

High hepatic excretion in humans of cefpiramide, a new cephalosporin.

After intravenous administration of 1 g of cefpiramide, the biliary elimination of the drug was studied by using high-performance liquid chromatography. In five healthy volunteers, a mean peak concentration of 339 +/- 107 (standard error of the mean) micrograms/ml was measured in aspirated duodenal fluid during h 2 after administration, and 1.2% of the dose given was recovered over a 4-h period. A maximal concentration of 1,161 +/- 392 micrograms/ml was reached during h 2 in T-tube bile from 10 recently cholecystectomized patients, with a 24-h biliary recovery of 23.1%; urinary recovery over the same period averaged 49.4%. In 10 patients undergoing cholecystectomy, the concentrations in serum, choledochal bile, gallbladder bile, and gallbladder wall 1 h after cefpiramide administration were 157 +/- 21, 1,726 +/- 501, and 84 +/- 33 micrograms/ml and 23 +/- 4 micrograms/g, respectively. These figures represent the highest biliary concentrations attained so far with a beta-lactam antibiotic and are therefore a good prerequisite for treatment of biliary tract infections with cefpiramide.

Anti-Bacterial Agents↗

[Evaluation of the biliary excretion of a ticarcillin-clavulanic acid combination in man].

The association of a beta-lactamase inhibitor, clavulanic acid (CA) (0.2 g) to ticarcillin (TIC) (3 g) enhances the activity of the latter on resistant strains. The aim of the present study was to assess their biliary elimination in man. Serum, urine and bile concentrations of TIC and CA were measured in biological samples collected in 10 cholecystectomized patients provided with a T-tube, during 12 hours after the IV administration of 3.2 g of claventin. Concerning TIC, a mean biliary peak of 177 +/- 49 (SEM) micrograms/ml was reached during the 2nd hour; the total biliary output (0-12 h) (AB) was 8.8 +/- 2.6 mg (0.28% of the administered dose), the hepato-biliary clearance CL HB 0.34 ml/min and the biological half-life, TB 1/2 1.2 h. The mean biliary peak of CA was 2.7 +/- 0.5 micrograms/ml and occurred during the first hour. AB amounted to 98.5 +/- 34.7 micrograms (0.04% of dose), CLHB to 0.10 ml/min and TB 1/2 1.2 h. In per-operatively sampled serum, choledochal bile, gallbladder bile and gall-bladder wall, the following concentrations were measured 1 hour after the IV administration of 3.2 g of Claventin. TIC: 105 +/- 11; 386 +/- 66; 72 +/- 20 micrograms/ml and 36 +/- 11 micrograms/g. CA: 3.6 +/- 0.7; 5.9 +/- 1.5; 0.3 +/- 0.3 micrograms/ml and 0.1 +/- 0.1 micrograms/g. The biliary pharmacokinetic profiles allow to favorably consider the prophylactic use of Claventin in the surgery of the biliary tract as well as its therapeutic administration in biliary tract infections.

Adult↗

[Aztreonam treatment of severe infections caused by gram-negative aerobic bacilli].

Twenty nine patients of an intensive care unit (9 women and 20 men), aged 63.9 +/- 15.8 years, with a mean body weight of 62.5 +/- 11.8 kg were treated during 9.4 +/- 2.1 days by aztreonam (2 x 1 g/24 h) administered by short infusion (30 min) for a severe infection due to a Gram-negative bacilli. The primary (n = 25) or nosocomial (n = 4) infection sites were a peritonitis (14), a septicaemia (6), a cholecystitis (6), a pyelonephritis (5), a cholangitis (2), a subphrenic abscess (1) or a pneumonia (2). The isolated Gram-negative bacilli were all susceptible to aztreonam, their MIC being less than or equal to 0.5 micrograms/ml, except for a Pseudomonas aeruginosa (MIC = 4 micrograms/ml). Aztreonam was administered as a single therapy to 7 patients and in association with metronidazole (18) and/or penicillin G (14) to 22 patients; in fact, anaerobes were isolated in ten patients. The mean serum concentrations of aztreonam, as measured by HPLC, before and after the 7th administration respectively were 83.2 +/- 17.5 and 6.1 +/- 5.5 micrograms/ml for peak and through levels. The treatment of the 29 infections was a success in all the cases. No complication occurred due to the presence of Gram positive cocci (n = 4) in the first bacteriological sample, or due to the emergence (n = 12) of Gram positive cocci, except for one case of sepsis of the abdominal wall by Staphylococcus aureus. Aztreonam (2 x 1 g/24 h) may be a suitable alternative for the treatment of severe infections of intensive care units, mostly due to Gram-negative bacilli.

Aged↗

[The role of ciprofloxacine metabolites in its biliary and urinary elimination in man].

The purpose of the present work was the investigation of the urinary and biliary eliminations of M1, M2, M3 and M4, the four metabolites of ciprofloxacin in twelve recently cholecystectomized patients provided with a T-drain. The four metabolites were measured by HPLC under isocratic conditions for M2 and M4, and by gradient elution for M1 and M3. After a single oral dose of 500 mg of ciprofloxacin, the 24th urinary elimination of the parent compound and its metabolites respectively amounted to 130.1 +/- 15.6; 13 +/- 11; 46.6 +/- 8.2; 13 +/- 3.7 and 0 mg, representing 26.02; 0.54; 1.32; 2.60 and 0% of the administered dose (total: 192.4 mg; 38.5%). During the same investigation period, the biliary elimination respectively reached 1,587 +/- 222; 241 +/- 38; 11,042 +/- 2,489; 144 +/- 51 and 19 +/- 13 micrograms (total: 13 mg) corresponding to 0.32; 0.05; 2.21; 0.03 and 0% (total: 2.61%) of the dose. The urinary and biliary elimination of ciprofloxacin as metabolites respectively represents 12.5 and 2.3% of the dose (total: 14.8%). The important amount of M2 recovered in bile (7 times more than ciprofloxacin itself) let suggest a hepatic biotransformation of ciprofloxacin.

Administration, Oral↗

Experimental and clinical evaluation of the biliary pharmacokinetic profile of cefpiramide, a new cephalosporin with high hepatic elimination.

Biliary elimination of cefpiramide was studied experimentally and in human subjects using chromatography (HPLC). During a 3-h perfusion of five isolated rabbit liver preparations, 40.4% of cefpiramide added to the circulating blood was eliminated in the bile and only 0.3% was metabolized in the liver. In five healthy subjects, after a single intravenous administration of 1 g of cefpiramide, a maximal concentration of 339 +/- 107 micrograms/ml was reached during the 2nd hour in the collected duodenal fluid, and 1.23 +/- 0.20% of the given dose was recovered within 4 h. In ten cholecystectomized patients provided with a T-tube, intravenous injection of 1 g of cefpiramide resulted during the 2nd hour in a biliary peak concentration of 1161 +/- 392 micrograms/ml. The total amount of antibiotic eliminated in the bile over 24 h averaged 231.5 +/- 39.1 mg, corresponding to 23.2 +/- 3.9% of the administered dose. Hepatic clearance was 3.13 ml/h. Intraoperative specimens sampled simultaneously 1 h after intravenous administration of 1 g of the antibiotic in ten patients undergoing cholecystectomy showed cefpiramide concentrations of 157 +/- 21 micrograms/ml in serum, 1726 +/- 501 micrograms/ml in choledocal bile, 84 +/- 33 micrograms/ml in gall-bladder bile and 22.6 +/- 4.2 micrograms/g in gall-bladder wall. These data emphasize the excellent biliary tropism of cefpiramide, and compare favourably with results concerning 19 other beta-lactams previously studied under the same conditions. They constitute a good prerequisite for possible beneficial treatment of biliary tract infections.

Adult↗

Identification of Pseudomonas, Flavobacterium, and Alcaligenes with the API 20 NE system.

The API 20 NE system is designed for the rapid identification of Gram negative rods other than Enterobacteriaceae. It has been compared to conventional methods in the characterization of 404 strains representative of 23 species belonging to 3 genera: Pseudomonas (236 strains), Flavobacterium (133 strains) and Alcaligenes (35 strains). The system consists of 9 enzymatic tests and 12 carbohydrate assimilation tests. A 7-digit numerical profile is obtained by an octal coding of the test results. The strains are identified by comparing the numerical profile to those of species listed in a profile index. The API 20 NE tests showed 99-100% correlation with corresponding conventional methods except in indole production (96.5%) for which we observed 14 false negative reactions in testing F. meningosepticum and CDC groups IIb and IIf. The API 20 NE system presented 94.1% identification to the species level and 96.3% to the genus level in agreement with conventional biochemical methods. Among the correctly identified strains, 7.4% (30) gave an erroneous or unlisted numerical profile in the first version of the Profile Index and required the use of the computer. Among the misidentified strains 2%, (8) were assigned to the right genus but wrong species, 0.7% (3) were placed in the wrong genus and 1% (4) gave a doubtful profile with one or more tests compared to the profiles listed.

Alcaligenes↗

High biliary elimination of ceftriaxone in man.

Biliary elimination of ceftriaxone was studied in man using chromatography (HPLC). After a single i.v. administration of 2 g of ceftriaxone to 6 normal subjects, a peak concentration of 565 +/- s.e.m. 347 micrograms/ml was reached during the 1st h in the collected duodenal fluid, and 1.4 +/- 0.5% of the given dose was recovered within 4 h. In 10 cholecystectomized patients provided with a T-drain, a maximal biliary concentration of 1,078 +/- 158 micrograms/ml was measured during the 2nd h after i.v. injection of 2 g of ceftriaxone and the 24-h recovery was 9.5 +/- 2.9%. Intraoperative samples obtained in 12 patients undergoing cholecystectomy 1 h after i.v. administration of 2 g of the antibiotic, gave the following results: serum concentration 199 +/- 10 micrograms/ml, choledochal bile = 5,259 +/- 1,085 micrograms/ml, gallbladder bile 4,533 +/- 809 micrograms/ml. These data indicate an excellent biliary elimination of ceftriaxone in comparison with other beta-lactams previously studied under the same conditions and point to be a promising therapeutic potential in biliary tract infections.

Adult↗

[Ceftriaxone, a cephalosporin with high hepatic elimination. Evaluation of its biliary clearance in man. Therapeutic value].

The biliary elimination of ceftriaxone, a cephalosporin derivative, was quantitatively studied in man with the help of high pressure liquid chromatography (HPLC). In 6 healthy volunteers a mean peak concentration of 565 +/- 347 (SEM) micrograms/ml was observed in the aspirated duodenal fluid within the first hour after i.v. administration of 2 g ceftriaxone, and 1.4 +/- 0.5% of the dose was recovered during the 4 hours investigation period. In 10 cholecystectomized patients provided with a T-drain, the biliary concentration peak (1078 +/- 158 micrograms/ml) was reached within 1 hour after administration and the total 24 hours recovery amounted to 9.5 +/- 2.9% of the dose given. In 12 patients undergoing cholecystectomy, serum, and choledochal (CB) and gallbladder bile (GB) were peroperatively collected 1 hour after i.v. administration of 2 g ceftriaxone; the respective concentrations were: 199 +/- 10 (serum), 5259 +/- 1085 (CB), and 4533 +/- 809 (GB) micrograms/ml. These data point to excellent biliary elimination of ceftriaxone compared with the other beta-lactams previously studied, and afford evidence of its high therapeutic potential in biliary tract infections.

Aged↗

Hospital routine analysis of penicillins, third-generation cephalosporins and aztreonam by conventional and high-speed high-performance liquid chromatography.

A high-performance liquid chromatographic procedure for the measurement of fifteen beta-lactam antibiotics in body fluids is described, with special reference to high-speed techniques. The procedure involves a unique sample preparation before analysis for all the following fifteen compounds: benzylpenicillin, ampicillin, cloxacillin, ticarcillin, mezlocillin, azlocillin, piperacillin, cefotaxime and its desacetyl metabolite, cefsulodin, cefoperazone, cefmenoxime, ceftazidime, ceftriaxone and the monobactam aztreonam; thus all biological samples arriving at the laboratory can be treated in batch. Of these fifteen antibiotics, eleven can be chromatographed with the same type of mobile phase, which consists of a mixture of ammonium acetate and acetonitrile in various ratios. Three others need ionpairing chromatography because of their polarity, and ticarcillin requires citric acid. High-speed high-performance liquid chromatography seems to be particularly suitable for the routine analysis of beta-lactam antibiotics because columns equilibrate more rapidly, retention times are much shorter, detection limits are lower and the longer lifetime of columns reduces analysis costs.

Aztreonam↗