Growth on blood agar discriminates Mycobacterium avium and Mycobacterium intracellulare.

Mycobacterium intracellulare and Mycobacterium avium (MAC) require specialized culture and identification procedures. To simplify the diagnosis, we inoculated reference strains, and 85 M. avium and 12 M. intracellulare clinical isolates, on egg-based and sheep blood agar. After 5 days of culture, there were significantly more colonies on sheep blood than on egg-based agar for M. avium (ratio: 250.5 +/- 209) but not for M. intracellulare (ratio: 0.44 +/-0.11). Using a ratio > or = 20, the sensitivity of the identification of an MAC isolate as M. avium was 97.65%, the specificity was 100%, and the positive predictive value was 100%. Differential growth on egg-based and blood agar is an aid to the identification of MAC isolates.

[Acquired rifampicin resistance during M. kansasii infection in a patient with AIDS]. / Résistance acquise à la rifampicine au cours d'une infection à M. kansasii chez un patient atteint de SIDA.

A man with AIDS and M. kansasii lung infection received rifampicin and isoniazid for 9 months, combined with ethambutol for four months. The treatment was effective with sputum culture negativation, but relapse occurred. The minimal inhibitory concentration of rifampicin for the M. kansasii strain was respectively 0.2 microgram/ml at the onset and 128 micrograms/ml after the treatment, giving evidence of acquired resistance. A new treatment was initiated but is was ineffective.

[Pulmonary mycobacteriosis due to a non-chromogenic, slow-growing, unclassified mycobacterium]. / Mycobactériose pulmonaire due à une mycobactérie non chromogène, à croissance lente, non classée.

A case is reported of a bilateral atypical mycobacterial infection, occurring in a 44 year old male with antecedent silicosis. Successful surgical resection was performed after 17 months of failed chemotherapy. The atypical mycobacterium which is unclassified is intermediate between Mycobacterium avium-intracellulare. Mycobacterium terrae complex and Mycobacterium gastri. It has some similarities with the newly described species, Mycobacterium malmöense.

[Treatment with clarithromycin of 173 HIV+ patients with disseminated Mycobacterium avium intracellulare infection]. / Traitement de 173 malades VIH+ atteints d'infection disséminée à M. avium intracellulare par une association incluant la clarithromycine.

No treatment was established for disseminated M. avium intracellulare (MAC) infection, a common disease of end stage of AIDS. An open study was conducted to assess in 173 AIDS patients, the activity of clarithromycin. Initial bacteriologic eradication from blood was observed in 136/147 evaluable patients (93%). Acquired resistance to clarithromycin associated with relapse appeared to develop after 2 to 7 months of drug treatment in 31/136 patients with initial success. Early bacteriological relapse was associated with clinical deterioration. Side effects of drug treatment were elevated liver enzymes (26%) and impaired hearing (4%). Side effects conducted to stop treatment in 14 cases (8%) to modified treatment in 8 cases (5%). Our study gave new argues for activity of clarithromycin in disseminated MAC infection.

[Relationships between "Mycobacterium simiae" and the "M. avium-intracellulare-scrofulaceum" complex (author's transl)]. / Relations entre Mycobacterium simiae et le complexe M. avium-intracellulare-scofulaceum.

The 24 strains of Mycobacterium simiae described in this report were isolated from 12 black Africans, 6 from white Europeans, 5 from primates and 1 from a leprosy infected Armadillo. These strains form 3 groups having the similar morphologic and cultural properties as M. intracellulare. Two groups were similar with respect to pigmentation, urease activity and niacin production but differed serologically, the second group being of M. intracellulare serotype 18. The third group was less homogenous and was intermediate to M. simiae and M. intracellulare. Thus M. simiae belong to the M. avium-intracellulare-simiae-scrofulaceum (MAISS) complex. Two cases of well characterized pulmonary disease progressed like M. avium mycobacteriosis.

The role of low dosage prothionamide with and without 4,4'-diamino diphenyl sulphone for use with isoniazid in the treatment of experimental mouse tuberculosis.

To determine whether or not low dosage prothionamide (PTH), with or without diamino diphenyl sulphone (DDS), can replace PAS or thiacetazone as the companion drug to isoniazid (INH) in the treatment of tuberculosis, two experiments have been performed in mice. In experiment I the 2-month effectiveness of 25mg/kg INH alone, INH+PTH (25mg/kg) or INH+PTH+DDS (10mg/kg) was investigated. Both PTH-containing regimens were equally effective in preventing the selection of INH-resistant mutants but PTH did not appear to add much to the bactericidal activity of INH. In experiment II the one year effectiveness of similar regimens supplemented by an initial month of streptomycin (SM) was investigated. Again PTH appeared very effective whereas DDS seemed ineffective. Therefore it seems that PTH is likely to be a good companion drug for INH when used in man at the dosage of 5mg/kg which is more or less equivalent to 25mg/kg in the mouse.

[Sterilizing activity of the main drugs on the mouse experimental tuberculosis (author's transl)]. / Activité stérilisante des différents antibiotiques dans la tuberculose expérimentale de la souris.

In a first experiment mice infected intravenously with 10(6) Mycobacterium tuberculosis were randomly treated either with isoniazid (INH) + rifampicin (RMP) 25 mg/kg or with INH + RMP + pyrazinamide (PZA) or with INH + RMP + PZA + streptomycin (SM). The decrease of the viable counts (CFU) in the lungs was similar with all three regimens. In a second experiment, mice were treated for six months either with INH + RMP 25 mg/kg or INH + RMP 10 mg/kg. After a follow-up of six months, mice were killed and their lungs and spleen cultivated. Positive cultures were obtained in 7.5 p. cent of the mice treated with the high dose of RMP and 36.5 p. cent in the mice treated with the low dose (p less than 0.05). A third experiment demonstrated that, during the first two months of treatment, adding PZA to INH + RMP 10 mg/kg increased significantly the overall effectiveness of INH + RMP 10 mg/kg combination. A fourth experiment demonstrated that after three initial months of INH + RMP 10 mg/kg, RMP alone was as effective as RMP + INH or RMP + INH + PZA. It may be concluded that RMP and PZA are both active on the intracellular population of Mycobacterium tuberculosis and that RMP is the only drug to act on persisting Mycobacterium tuberculosis in extracellular lesions.

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.

[Analysis of restriction fragment length polymorphism (RFLP) of Mycobacterium tuberculosis strains isolated from patients with several episodes of tuberculosis]. / Analyse du polymorphisme de longueur des fragments de restriction (RFLP) de souches de Mycobacterium tuberculosis isolées de malades ayant fait plusieurs épisodes de tuberculose.

Analysis of restriction fragment length polymorphism (RFLP), using a DNA probe directed against the insertion sequence IS6110, was applied to strains of Mycobacterium tuberculosis successively isolated from four patients. In order to determine the cause of recurrence in these patients, the RFLP patterns of the corresponding isolated were analyzed. The profils obtained from the strains isolated from each of the patients were identical, thus suggesting that a relapse, rather than an exogenous reinfection with a new strain, was the cause of recurrence. The RFLP patterns of successive isolated remained unchanged during periods of time ranging from 5 months to 7 years, and were not modified after development of rifampin resistance. These results demonstrate the stability of the polymorphism detected by the IS6110 probe. Therefore, RFLP analysis is a powerfull epidemiologic tool to distinguish relapse from exogenous reinfection.

[Resistance of Enterobacteria to cefotaxime and lamoxactam at the Pitié-Salpêtrière Hospital in 1982]. / Situation de la résistance des Entérobactéries au céfotaxime et au lamoxactam au groupe hospitalier Pitié-Salpêtrière en 1982.

Systematic collection of data on every Enterobacteriaceae clinical isolate cultured in the Central Bacteriology Laboratory allowed comparison of the percentage of cefotaxim (CTX) and moxalactam ( MOX ) intermediate or resistant (IR) strains among the 8 199 Enterobacteriaceae isolated in 1982 and the 5 032 Enterobacteriaceae isolated in 1980. In 1982, IR rates were 2% to CTX and 0.6% to MOX . Among the 166 strains IR to CTX, 28% were also IR to MOX . Two strains only were IR to MOX but not to CTX. No E. coli, P. mirabilis or Klebsiella strains IR to CTX or MOX were isolated. On the opposite, percentages of strains IR to CTX or MOX were respectively 2.5 and 0 for indole positive Proteus, 6 and 3.6 for Enterobacter, 7.4 and 0.5 for Serratia and 17.2 and 2.5 for Citrobacter. Strains IR to CTX or MOX represented 3.3%, 2.5% and 1% of Enterobacteriaceae isolated from pus, urine and blood cultures, and 4.7%, 2.2% and 1.3% of those isolated in urology, surgery and medicine. Between 1980 and 1982, there was a simultaneous increase in the consumption of CTX and MOX (10 fold) and in the percentage of Enterobacteriaceae IR to CTX (2 fold); this last involved Serratia (9 fold) more than Citrobacter (3 fold) and spared Enterobacter.

[Sensitivity to fosfomycin of bacteria isolated at the Pitié-Salpétrière Hospital in 1982 and 1983]. / Sensibilité à la fosfomycine des bactéries isolées au Groupe Hospitalier Pitié-Salpêtrière en 1982 et 1983.

Susceptibility of 16 056 strains isolated in 1982 and 1983 to fosfomycin (FOS) was tested with Mueller-Hinton medium and discs 50 micrograms FOS + 25 micrograms glucose-6-phosphate (G6P) (cutoff diameter 14 mm). For 3 411 strains, inhibition zone diameters were recorded. Almost all E. coli, Citrobacter, Salmonella and S. aureus were susceptible to FOS as well as 70% of Serratia, E. cloacae, P. mirabilis and 50% of Klebsiella and Enterobacter sp. Only 27% of P. aeruginosa, 20% of indole positive Proteus and 8% of Acinetobacter were sensitive to FOS. E. coli, Citrobacter and S. aureus seem to exhibit the highest susceptibilities to FOS. Sensitivity rates of E. cloacae, Serratia, P. aeruginosa, and especially Klebsiella seemed slightly underestimated by the disk diffusion method, but differentiation between susceptible and resistant strains was facilitated by rating as susceptible those strains with inhibition zone diameters between 12 and 14 mm. This method also seemed to underrate the sensitivity of susceptible Enterobacteriaceae, probably because of inadequate G6P concentrations at this point of the disk.

Survey of the phenotypes of susceptibility to beta-lactams in Enterobacteriaceae at the Pitie-Salpetriere Hospital.

The phenotypes of susceptibility to ampicillin, carbenicillin, cephalothin, cefamandole, cefoxitin and cefotaxime were determined by the disc-diffusion method in 10,994 Enterobacteriaceae consecutively isolated from in-patients during 18 months. The susceptible phenotypes were much more frequent among Escherichia coli, Proteus mirabilis and Klebsiella (67.4 to 84.8%) than among Serratia, Enterobacter and Citrobacter (8.8 to 35.5%). In all species the most common resistance phenotypes were to ampicillin and carbenicillin: E. coli (28%), Pr. mirabilis (15.2%), Klebsiella (23.8%), indole-positive Proteus (33.3%), Serratia (74.4%), Enterobacter (61.4%) and Citrobacter (74.8%). Among E. coli 4.6% of the strains were resistant to ampicillin and cephalothin but susceptible to carbenicillin. Among E. coli, Pr. mirabilis and Klebsiella the strains susceptible only to cefotaxime represented 0.3 to 5% and no cefotaxime-resistant strain was isolated; whereas among Serratia, Enterobacter and Citrobacter the former represented 28.3 to 58.3% and the latter 7.5 to 18.5%. Some important differences in the distribution of the phenotypes according to the type of ward were observed.

[Lymph-node tuberculosis in patients infected or not with HIV: general characteristics, clinical presentation, microbiological diagnosis and treatment]. / Caractéristiques épidémiologiques, cliniques, biologiques et thérapeutiques de la tuberculose ganglionnaire observée chez des patients infectés ou non par le VIH.

Lymph node tuberculosis is the most frequent form of extrapulmonary tuberculosis, especially in immunocompromised patients. We have studied patients with proven lymph node tuberculosis in the Department of Infectious Diseases at Pitié-Salpêtrière Hospital, Paris, between January 1997 and January 2002. Clinical presentation, microbiological diagnosis and treatment were analyzed in 13 HIV infected and 19 non-HIV infected patients. A risk factor for tuberculosis was present in all cases (HIV infection, immigration, life in community, poverty, past history of tuberculosis and IVDU). The median duration between the onset of symptoms and diagnosis was longer for HIV infected (2 months) compared with non-HIV infected patients (1 month). At the time of the diagnosis, general symptoms were present in >50% of patients of both groups. In HIV infected patients, abdominal lymph node involvement was more frequent (P < 0.05). All the non-HIV infected and 85% of HIV infected patients had peripheral adenopathies. A pulmonary tuberculosis was noted in more than half of the cases (53% non-HIV and 69% HIV patients). Inflammatory parameters and liver function tests were frequently abnormal in both groups. Hyponatremia was more frequent in HIV patients (P < 0.05). TB skin testing was more frequently positive and phlyctenular in non-HIV infected patients (P < 0.05). In this study, direct examination of the needle aspirate from infected lymph nodes was rarely positive; cultures were more frequently positive after biopsy compared to needle-aspiration. The median duration of treatment was 9 months for the two groups (6-24 months). Three HIV infected patients were infected by mycobacteria resistant to at least one antibiotic (isoniazid, 1; rifampicin, 1; isoniazid, streptomycin, etambutool, 1). All the patients recovered.

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)

The management of thirty immunocompromised patients with tuberculosis.

Between 1978 and 1981, 30 of 870 bacteriologically confirmed cases of tuberculosis occurred in immunocompromised hosts. One year after the diagnosis, 11 patients were dead, only 2 of them of tuberculosis. In the other 19 patients, the course of tuberculosis under standard chemotherapy was the same as in nonimmunocompromised hosts. Among the 24 patients still alive more than 2 months after the diagnosis of tuberculosis, the treatment of the underlying disease was changed in 14 patients to avoid worsening of the course of tuberculosis; 5 patients died and 4 kidney transplant carriers rejected their transplants. The treatment of the underlying disease was not changed in 10 patients: all of these remained alive 1 yr later, and 2 were kidney transplant carriers who did not reject their transplants. We conclude that the clinical response of the immunocompromised tuberculous host was good and that treatment of the underlying disease should not be modified.

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.

[A case of pulmonary mycobacteriosis due to Mycobacterium intracellulare (author's transl)]. / Un cas de mycobactériose pulmonaire humaine par Mycobacterium intracellulare.

An M. intracellulare, rough strain (serotype 7) has been isolated from sputum of a sixty-year old patients. This patient was a political prisoner in Germany between 1942-1945 and had contracted pulmonary tuberculosis with the cavity in the upper lobe of the right lung. A strain of mycobacterium susceptible to antituberculous drugs was isolated from his sputum in 1973. Since 1979, the isolation of M. Intracellulare has been accompanied by clinical signs of pulmonary mycobacteriosis, i.e. persistence of the cavity in spite of antituberculous treatments reapparition of cough with sputum, general weakness. Intradermo-reaction with specific sensitin gives a strong positive reaction, contrasting with a weak reaction with PPD tuberculin. As the antibiogram of the strain shows a susceptibility to cotrimoxazole and erythromycin, the patient underwent a therapy with the combination sulfamethaxozale-trimethoprime and erythromycin, for 4 months. At the end of this treatment, he seems to have recovered completely. The radiological aspect of the lungs remains unchanged. Although the source of contamination remains unknown, one thinks on the basis of bibliographica data, that it can be found in human beings, or seldom in animals (a pig, a bird) or in nature (a pond).