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J Grosset

Publications and source records attributed to J Grosset.

At least 91 records · Page 5Linked to original sources
PubMed1993

Automated interpretation of disk diffusion antibiotic susceptibility tests with the radial profile analysis algorithm.

An original algorithm referred to as the radial profile analysis algorithm was implemented on a Macintosh Quadra 700 computer to provide an automatic determination of the inhibition zone diameters of antibiotic susceptibility tests performed with the disk diffusion method. After digitization of the petri plate image, each antibiotic disk is recognized and labeled. Pixels of the local zone around each disk are then used for generating a profile pattern that is subjected to decision rules. The resulting estimate of the inhibition zone diameter is then automatically compared with conventional breakpoints for classifying the tested strain in one of the clinical categories of antibiotic susceptibility. The program is also able to request a human reading for some rare plates difficult to interpret. The algorithm accuracy was tested by comparing the results with a combination of independent human measurements performed on the tested plates. The test sample was composed of 98 strains, and 2,552 tests of 40 distinct antibiotics were subjected to the analysis. The difference between the automatic and human diameter estimates was less than 4 mm in 90% of the tests. The agreement between the automatic and human clinical categorizations amounted to 95.5%, and severe (major and very major) disagreements were found in 5.6% of the tests performed with staphylococci but only 0.3% of the tests with gram-negative rods. We conclude that the radial profile analysis algorithm is a solid backbone for an automatic system dedicated to the clinical interpretation of disk diffusion antibiotic susceptibility tests.

Algorithms↗
PubMed1993

Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice.

To identify alternative regimens for preventive therapy of tuberculosis, the pharmacokinetics and antimicrobial activities of rifampin (RMP), rifabutin (RBT), and rifapentine (RPT) were compared in BCG-vaccinated and M. tuberculosis-infected immunocompetent mice. RPT showed the highest serum peak level (Cmax) and the longest half-life (t1/2), whereas RBT displayed the lowest Cmax and the shortest t1/2. On weight-to-weight basis, both RPT and RBT were more bactericidal than RMP. The activity of RMP was significantly reduced when the frequency of administration was reduced from six to three times weekly, whereas significant bactericidal activity was still observed in mice treated with RPT, 10 mg/kg up to once fortnightly, or RBT, 10 mg/kg twice weekly. Because the bactericidal activity of RBT, 10 mg/kg six times/wk for 6 wk, or RPT, 10 mg/kg two times/wk for 12 wk, was comparable to that of RMP, 10 mg/kg six times/wk for 12 wk in mice, the two regimens are appropriate for clinical trials of preventive therapy of tuberculosis.

Animals↗
PubMed1993

A simple and rapid technique for the detection of rifampin resistance in Mycobacterium leprae.

The rifampin resistance of Mycobacterium leprae is due to missense mutations in the rpoB gene encoding the beta-subunit of the essential enzyme RNA polymerase. A rapid and very simple method has been developed to detect rifampin resistance in small numbers of M. leprae present in biopsies. It involves polymerase chain reaction amplification of a defined region of the rpoB gene followed by single-strand conformational polymorphism analysis (PCR-SSCP). The reliability of the method has been tested on a sample of known drug-resistant and susceptible isolates of M. leprae.

Alleles↗
PubMed1992

Activities of WIN-57273, minocycline, clarithromycin, and 14-hydroxy-clarithromycin against Mycobacterium avium complex in human macrophages.

The activities of the fluoroquinolone WIN-57273, 14-OH clarithromycin (a human metabolite of clarithromycin), and minocycline against two virulent strains of Mycobacterium avium complex were evaluated in a model of intracellular infection and compared with that of clarithromycin. Human monocyte-derived macrophages were infected at day 6 of culture. Intracellular CFU at 60 min and intracellular and supernatant CFU on days 4 and 7 were counted after inoculation. The concentrations used, which were equal to peak levels in serum, were 3 micrograms of WIN-57273 per ml (MICs for the two strains, 1 microgram/ml), 4 microgram of 14-OH clarithromycin per ml (MICs, 8 and 2 micrograms/ml, respectively, at pH 7.4), 4 micrograms of minocycline per ml (MICs, 64 and 32 micrograms/ml, respectively), and 4 micrograms of clarithromycin per ml (MICs, 2 and 0.5 micrograms/ml, respectively, at pH 7.4). On day 7, compared with controls, WIN-57273, minocycline (P less than 0.02), clarithromycin, or different combinations of clarithromycin and the other drugs (P less than 0.001) slowed the intracellular replication of strain MO-1. 14-OH clarithromycin (P less than 0.02), clarithromycin (P less than 0.02), 14-OH clarithromycin plus clarithromycin (P less than 0.01), clarithromycin plus minocycline, or clarithromycin plus minocycline plus 14-OH clarithromycin (P less than 0.001) slowed the intracellular replication of strain LV-2. WIN-57273 was less effective than clarithromycin against strain MO-1 (P less than 0.05). Clarithromycin plus 14-OH clarithromycin plus minocycline (P less than 0.02) was more effective than clarithromycin alone against strain LV-2. Thus, clarithromycin plus minocycline, which corresponds in humans to three active molecules, may exhibit a better efficacy than clarithromycin in this model.

Anti-Infective Agents↗
PubMed1992

Sparfloxacin, ethambutol, and cortisol receptor inhibitor RU-40 555 treatment for disseminated Mycobacterium avium complex infection of normal C57BL/6 mice.

Sparfloxacin (50 mg/kg of body weight given subcutaneously each day), alone or in combination with ethambutol (50 mg/kg given subcutaneously each day), was examined for its therapeutic efficacy against experimental infection induced with the Mycobacterium avium complex in normal C57BL/6 mice. In addition, the potential anti-infective role of RU-40 555 (100 mg/kg given intraperitoneally each day), a drug that inhibits the cortisol receptors, was examined in the same model. Treatments were started 24 h after intravenous bacterial challenge and were continued for 21 days. Compared with controls, sparfloxacin or ethambutol decreased the CFU counts in spleens and lungs (P < 0.001). The sparfloxacin plus ethambutol combination was more effective than sparfloxacin alone in spleens (P < 0.001) but not in lungs. The sparfloxacin plus ethambutol plus RU-40 555 combination was more effective than the sparfloxacin plus ethambutol combination in spleens and lungs (P < 0.001). Thus, in this model, RU-40 555 enhanced the antibacterial activities of the antibiotics tested. Results of the study showed that normal C57BL/6 mice infected with the M. avium complex can be used for the evaluation of antimicrobial agents.

Animals↗
PubMed1992

Selection of resistant mutants of Mycobacterium avium in beige mice by clarithromycin monotherapy.

Beige mice were inoculated intravenously with 10(7.90) CFU of Mycobacterium avium 101. Among the untreated control mice, when the mean CFU per spleen increased to a level greater than 10(8), small numbers of organisms resistant to clarithromycin (CLARI) were isolated from some of the spleens; the frequency of CLARI-resistant mutants was estimated to be between 10(-8) and 10(-9). In mice treated with 200 mg of CLARI per kg of body weight six times weekly, however, CLARI-resistant organisms were isolated from the spleens of all mice examined after treatment for 8 weeks; the mean CFU per spleen and the frequency of resistant mutants were significantly greater than those of control mice and increased further after treatment for 16 weeks. The MICs of CLARI against the resistant organisms isolated from both control and treated mice were > or = 512 micrograms/ml.

Animals↗
PubMed1992

Antagonism between isoniazid and the combination pyrazinamide-rifampin against tuberculosis infection in mice.

Mice that had been inoculated intravenously with 6.30 log10 Mycobacterium tuberculosis H37Rv 14 days earlier were administered one of three combinations of drugs, i.e., isoniazid (INH)-rifampin (RMP)-pyrazinamide (PZA), INH-RMP, and RMP-PZA, during an initial 2-month period to mimic the initial phase of chemotherapy for human tuberculosis and during a later 4-month period to mimic the continuation phase of chemotherapy. At the end of the initial phase, all three combined regimens were found to have been highly effective in terms of the number of CFUs in the spleens of infected mice. The bactericidal activities of INH-RMP-PZA and INH-RMP were similar, whereas that of RMP-PZA was significantly greater. The spleens of all of the mice that had been treated initially with INH-RMP-PZA were culture negative by the end of 6 months of treatment, regardless of the regimen employed during the continuation phase. However, after an additional period of 6 months without treatment, the proportion of spleen culture positivity, or relapse rate, was significantly smaller in the subgroup treated with RMP-PZA during the continuation phase than in the subgroups treated with INH-RMP-PZA or INH-RMP; the relapse rate did not differ significantly between the latter two subgroups. These results suggest that antagonism occurs between INH and the combination RMP-PZA during both the initial and continuation phases of chemotherapy, compromising the benefit conferred by the addition of PZA to the combined regimen. The preliminary pharmacokinetic analysis suggested that the pharmacological interaction between INH and RMP was very likely to be involved in the mechanism of antagonism, as concomitant treatment with INH had significantly reduced the peak serum level and the area under the serum concentration-time curve of RMP in mice.

Animals↗
PubMed1992

Nosocomial bronchopneumonia in the critically ill. Histologic and bacteriologic aspects.

To provide a comprehensive description of the histologic and bacteriologic characteristics of human nosocomial bronchopneumonia (BPN), the lungs of 83 critically ill patients decreased after a period of mechanical ventilation were examined in the immediate postmortem period. In addition, the accuracy of the protected minibronchoalveolar lavage (BAL) technique in the diagnosis of nosocomial BPN was evaluated. In each patient, a surgical pneumonectomy was performed at the bedside within 30 min following death. Each pulmonary lobe was sampled and bacteriologically analyzed using semiquantitative cultures in 50 patients and quantitative cultures in 33 patients. The entire lung was histologically analyzed using 5 to 10 slices per lung segment. In 69 patients, the bacteriologic result of a protected mini-BAL performed within 48 h preceding death was compared with histologic and bacteriologic results of study of the lung tissue itself. Histologic lesions of BPN were found in 43 of the 83 lungs examined. These lesions were (1) severe in the majority of patients (confluent BPN, n = 23; lung abscess, n = 6), (2) preferentially found in dependent lung segments, (3) often associated with nonspecific alveolar damage, (4) associated with positive lung cultures in 65% of patients (53% with gram-negative bacteria), (5) polymicrobial in 28% of patients, (6) characterized by a lobar bacterial burden greater than 10(3) cfu/g in 32% of cases. Using semiquantitative bacteriologic analysis, the sensitivity and the specificity of the protected mini-BAL in the diagnosis of nosocomial BPN were found to be 70 and 69%, respectively. Protected mini-BAL identified 77% of causative microorganisms of BPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗
PubMed1992

Combined chemotherapy including rifabutin for rifampicin and isoniazid resistant pulmonary tuberculosis. G.E.T.I.M. (Group for the Study and Treatment of Resistant Mycobacterial Infection).

A prospective multicentre open study has been conducted in France in order to assess the efficacy and tolerability of an antimycobacterial regimen including rifabutin in the treatment of patients with pulmonary tuberculosis due to rifampicin and isoniazid resistant bacilli. Patients were treated with daily rifabutin (450-600 mg), associated with companion drugs to which the organisms remained susceptible; in most cases the regimen included a fluoroquinolone. The duration of treatment was initially scheduled for a minimum period of 12 months after sputum culture conversion. Thirty nine patients were enrolled, 23 of whom were treated for at least 12 months. Culture conversion was obtained at the end of the twelfth month in 14 out of 23 patients. Twenty one out of 39 patients experienced adverse events. These were, however, serious enough to discontinue treatment in only four patients. These results suggest that an antimycobacterial combination including rifabutin might contribute to the treatment of multi-resistant pulmonary tuberculosis.

Adult↗
PubMed1991

Rifabutin in combination with clofazimine, isoniazid and ethambutol in the treatment of AIDS patients with infections due to opportunist mycobacteria. Groupe d'Etude et de Traitement des Infections à Mycobacteries Résistantes.

96 AIDS patients with fever and either acid-fast bacilli on microscopic examination of bacteriological samples or mycobacteria isolated by culture were treated with a daily 4-drug combination of 7-10 mg/kg rifabutin, 5 mg/kg isoniazid, 20 mg/kg ethambutol and 100 mg clofazimine. 46 patients were excluded from efficacy assessment: 13 died before or within the first days of treatment, 5 had negative initial cultures, 14 had initial cultures positive for M. tuberculosis, 4 for M. kansasii, 1 for M. flavescens, 1 for M. gordonae, 7 were lost to follow-up and 1 received no rifabutin. In the 50 remaining patients, 31 had disseminated disease due to M. avium intracellulare complex (MAIC) and 19 had apparently localised disease, due to MAIC in 15 cases and to M. xenopi in 4 cases. Side-effects led to withdrawal of isoniazid in 1 case (hepatic enzymes increased) and rifabutin in another (thrombocytopenia). After 1 month of treatment, fever decreased from 38.4 +/- 0.6 degrees C to 37.7 +/- 0.5 degrees C (p less than 0.01) and patients stopped losing weight. After 3 months treatment, only 37 patients were alive and still under treatment. Cultures became negative in 16 of 23 patients with available bacteriological data (9 of 14 patients with disseminated disease and 7 of 9 patients with localised disease), relapse occurred before death in 4 patients. 34 patients died before treatment was completed. Death was considered to be related to mycobacterial infection in 5 cases. We conclude that the 4-drug combination is safe and, in some cases, it appears to be effective.

Acquired Immunodeficiency Syndrome↗
PubMed1991

In vitro and in vivo activities of sparfloxacin (AT-4140) against Mycobacterium tuberculosis.

The in vitro and in vivo activities of sparfloxacin (AT-4140) against M. tuberculosis are reported. The MICs of sparfloxacin for 50% and 90% of 18 clinical isolates were, respectively, 0.25 and 0.5 mg/l, one or two dilutions lower than that of ciprofloxacin and ofloxacin. In mice infected intravenously with 0.1 mg M. tuberculosis H37Rv strain, the minimal effective dosage of sparfloxacin, as assessed by survival rate, spleen enlargement and gross lung lesions, was 12.5 mg/kg. The activities of various regimens were in the following rank order: INH 25 mg/kg = sparfloxacin 50-100 mg/kg greater than ofloxacin 300 mg/kg greater than (or =) sparfloxacin 25 mg/kg greater than sparfloxacin 12.5 mg/kg greater than (or =) ofloxacin 200 mg/kg greater than ofloxacin 100 mg/kg greater than (or =) negative control. Therefore, on a weight to weight basis, sparfloxacin was six to eight-fold more active against M. tuberculosis infection in mice than ofloxacin. In addition, WIN 57273, a new broad-spectrum fluoroquinolone, at a dosage of 100 mg/kg daily, was inactive against M. tuberculosis infection.

Animals↗
PubMed1991

Activities of pefloxacin and ofloxacin against mycobacteria: in vitro and mouse experiments.

The minimal inhibitory concentrations for 90% of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/l. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacterial agents. Mycobacterium avium-intracellulare was resistant to both compounds with MIC90s greater than 16 mg/l. The maximum serum levels (Cmax) of both compounds increased proportionally with increasing dose size. The terminal elimination half-life (T1/2) of pefloxacin was longer than that of ofloxacin, but the T1/2 of both compounds in mice were much shorter than in man. The area under the concentration curve (AUC) of pefloxacin was double than that of ofloxacin. In the mouse, pefloxacin at doses up to 150 mg/kg daily was inactive against M. tuberculosis infection: in terms of survival rate the minimal effective dose of ofloxacin against M. tuberculosis infection was 150 mg/kg daily when given by gavage or by incorporation into the mouse diet at a concentration of 0.1%, but in terms of cfu counts, ofloxacin 150 mg/kg daily only displayed a moderate degree of activity similar to ethambutol 100 mg/kg daily. The therapeutic effects of ofloxacin against M. tuberculosis infection were dose-related: 300 mg/kg daily by gavage or 0.4% in mouse diet displayed much better therapeutic effects than lower dosages. Since the AUC in mice treated with ofloxacin 150 mg/kg daily is close to that in man treated with a clinically tolerated dose--600 mg daily--such a dosage may be only moderately effective against human tuberculosis.

Animals↗
PubMed1991

Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages.

The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infected with the M. avium complex at day 6 of culture. The intracellular CFU was counted 60 min after inoculation. The intracellular and supernatant CFU was counted on days 4 and 7 after inoculation. The concentrations used, which were equal to peak levels in serum, were 10 micrograms of rifapentine per ml (MICs for the two strains, 4 and 16 micrograms/ml), 4 micrograms of clarithromycin per ml (MICs, 8 and 4 micrograms/ml), 1 microgram of azithromycin per ml (MICs, 32 and 16 micrograms/ml), 4 micrograms of temafloxacin per ml (MICs, 2 and 16 micrograms/ml), and 1 microgram of sparfloxacin per ml (MICs, 0.5 and 2 micrograms/ml). Compared with controls on day 7 after inoculation, clarithromycin (P less than 0.001), sparfloxacin (P less than 0.001), and azithromycin (P less than 0.001 for the first strain, P less than 0.02 for the second) slowed intracellular replication. Rifapentine (P less than 0.001) and temafloxacin (P less than 0.001) slowed intracellular replication of the first strain but not of the second strain. Azithromycin plus sparfloxacin was as effective as sparfloxacin alone. In this macrophage model, sparfloxacin or clarithromycin (difference not significant) exhibited a better efficacy than rifapentine, azithromycin, or temafloxacin against intracellular M. avium complex infection.

4-Quinolones↗
PubMed1991

Effect of pH on the in vitro potency of clarithromycin against Mycobacterium avium complex.

Employing 7H11 agar medium at pH 6.6, the MICs of clarithromycin for 50% (MIC50) and 90% (MIC90) of 19 strains of Mycobacterium avium complex were 8 and 16 micrograms/ml, respectively. However, the MICs were 2 to 3 log2 dilutions lower in the 7H11 medium adjusted to pH 7.4, and the MICs on 10% OADC (oleic acid-albumin-dextrose-catalase)-enriched Mueller-Hinton agar at pH 7.3 were also 2 log2 dilutions lower than those measured on 7H11 agar at pH 6.6. Therefore, clarithromycin is more active at a physiologic than at an acidic pH.

Clarithromycin↗
PubMed1991

Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome. A controlled clinical trial.

Disseminated Mycobacterium avium infection is common in patients with acquired immune deficiency syndrome (AIDS), but no drug studies have been reported establishing antimicrobial activity against this organism in a controlled, randomized trial. Clarithromycin, a new macrolide, has activity against M. avium in vitro and in animals, but it has not been studied in humans. In this randomized, double-blind, placebo-controlled trial, we measured the ability of clarithromycin to reduce M. avium bacteremia in patients with AIDS and disseminated infection. Of 23 patients initially enrolled, 15 men with late-stage AIDS qualified for the study. One group received clarithromycin alone for 6 wk, then placebo plus rifampin, isoniazid, ethambutol, and clofazimine for 6 wk. The other group received placebo alone, then clarithromycin plus the other four drugs. Colony-forming units (CFU) of M. avium per milliliter of blood were determined by quantitative cultures taken at baseline and every 2 wk thereafter. Minimum inhibitory concentration of clarithromycin for 90% of the strains isolated from patients at baseline, as measured on 7H11 agar at pH 6.6, was 8 micrograms/ml. Eight eligible patients with initial positive cultures who were initially receiving clarithromycin alone had marked declines in blood M. avium CFU; in six cases, CFU decreased to zero. When seven patients were switched to placebo plus the other four drugs, CFU rose in four patients and remained undetectable in three. The five eligible patients initially treated with placebo had progressive CFU increases; when three were switched to clarithromycin plus the four drugs, their CFU declined.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

Ofloxacin for the treatment of leprosy.

Among the major commercially available fluoroquinolones, ciprofloxacin was inactive against M. leprae in mice; pefloxacin was active, 50 mg/kg daily showed bacteriostatic activity but 150 mg/kg daily displayed bactericidal activity; ofloxacin was more active than pefloxacin, 50 mg/kg daily exerted the same level of bactericidal effect as pefloxacin 150 mg/kg daily, and ofloxacin 150 mg/kg displayed profound killing activity. Two clinical trials with 6 months of pefloxacin and/or ofloxacin in 31 previously untreated lepromatous patients have been completed. Pefloxacin 400 mg twice daily or 800 mg once daily or ofloxacin 400 mg once daily were equally effective; definite clinical improvement with drastically decrease of morphological index to the baseline were observed in all patients at 2 months after beginning of treatment; about 99.99%, or 4 "logs", of organisms viable on Day 0 were killed by 22 doses of either pefloxacin or ofloxacin. The side effects from the two trials were rare and mild, and the patients tolerated extremely well the combinations of pefloxacin/ofloxacin plus multidrug therapy (MDT) regimen for multibacillary leprosy recommended by WHO. The amount of rifampicin-resistant mutants in lepromatous patients before treatment are no more than 4 "logs", thus, all rifampicin-resistant mutants may be eliminated by 22 doses of either pefloxacin or ofloxacin. It is, therefore, possible that the combination of ofloxacin and rifampicin may considerably shorten the required duration of MDT.

Animals↗