rifampin and Mycobacterium-Infections

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Topics: Africa, Western; Anti-Bacterial Agents; Buruli Ulcer; Clarithromycin; Humans; Macrolides; Mycobacterium Infections; Mycobacterium ulcerans; Neglected Diseases; Polymerase Chain Reaction; Rifampin; Skin Diseases, Bacterial; Streptomycin

Rifampin was initially approved for the treatment of tuberculosis. Because of its low toxicity, broad-spectrum activity, and good bioavailability, rifampin is now commonly administered as combination antimicrobial therapy for the treatment of various infections caused by organisms other than mycobacteria. This review summarizes the most recent clinical studies on the use of rifampin combinations for treating four common non-mycobacterial infections: acute bacterial meningitis, infective endocarditis and bacteraemia, pneumonia, and biofilm-related infections.. We performed a literature search of clinical studies published in English from January 2005 to June 2016 using the PubMed database with the search terms "rifampin" with "meningitis" or "infective endocarditis and bacteraemia" or "pneumonia" or "prosthetic joint infections.. Current evidence to support a rifampin combination therapy as a treatment for non-mycobacterial infections was largely based on in vitro/in vivo studies and non-comparable retrospective case series. Additionally, controlled clinical trials that directly compared outcomes resulting from rifampin treatment versus treatment without rifampin were limited.. Rifampin combination therapy appears promising for the treatment of non-mycobacterial infections. However, further definitive clinical trials are necessary to validate its use because the risk of adverse drug-drug interactions and of the emergence of rifampin resistance during treatment may outweigh the potential benefits.

Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Mycobacterium Infections; Rifampin

Rifabutin is a spiro-piperidyl-rifamycin structurally closely related to rifampicin that shares many of its properties. We attempted to address the reasons why this drug, which was recently recognized as a WHO Essential Medicine, still had a far narrower range of indications than rifampicin, 24 years after its launch. In this comprehensive review of the classic and more recent rifabutin experimental and clinical studies, the current state of knowledge about rifabutin is depicted, relying on specific pharmacokinetics, pharmacodynamics, antimicrobial properties, resistance data and side effects compared with rifampicin. There are consistent in vitro data and clinical studies showing that rifabutin has at least equivalent activity/efficacy and acceptable tolerance compared with rifampicin in TB and non-tuberculous mycobacterial diseases. Clinical studies have emphasized the clinical benefits of low rifabutin liver induction in patients with AIDS under PIs, in solid organ transplant patients under immunosuppressive drugs or in patients presenting intolerable side effects related to rifampicin. The contribution of rifabutin for rifampicin-resistant, but rifabutin-susceptible, Mycobacterium tuberculosis isolates according to the present breakpoints has been challenged and is now controversial. Compared with rifampicin, rifabutin's lower AUC is balanced by higher intracellular penetration and lower MIC for most pathogens. Clinical studies are lacking in non-mycobacterial infections.

Topics: Antibiotics, Antitubercular; Clinical Trials as Topic; Humans; Microbial Sensitivity Tests; Mycobacterium Infections; Mycobacterium tuberculosis; Rifabutin; Rifampin

We present a case of Mycobacterium bovis infection of a total knee arthroplasty. This infection developed after use of bacillus Calmette-Guérin immunotherapy used to treat superficial bladder cancer. The patient presented with joint stiffness. Radiographs and inflammatory markers were normal. Six weeks after arthroscopy for synovectomy and biopsy, cultures showed M bovis infection of the knee joint. The patient was switched to antitubercular chemotherapy treatment, which resulted in the successful retention of implants. Seven and a half years later, the patient is symptom-free with high function in the joint. To our knowledge, this is the first time that this type of joint infection did not lead to removal.

Topics: Administration, Intravesical; Aged; Antitubercular Agents; Arthroplasty, Replacement, Knee; BCG Vaccine; Cancer Vaccines; Humans; Isoniazid; Male; Mycobacterium bovis; Mycobacterium Infections; Prosthesis-Related Infections; Rifampin; Urinary Bladder Neoplasms

The goals of tuberculosis control are to cure active disease, prevent relapse, reduce transmission and avert the emergence of drug resistance. However, since the 1960s, there have been few developments in available therapies. Currently available agents are complicated by numerous side-effects, drug interactions and the need for a long duration of therapy. Rifampicin-containing regimes lead to hepatic enzyme induction which can complicate or preclude the use of protease inhibitors and non-nucleoside reverse transcriptase inhibitors in patients infected with the human immunodeficiency virus. Furthermore, emerging drug resistance has complicated management for many patients and clinicians. Therefore, new chemotherapeutic agents are urgently needed. Existing antimicrobials are emerging as potent antituberculous agents. Recent studies have demonstrated the antituberculous activity of newer fluoroquinolones including levofloxacin, moxifloxacin, and gatifloxacin. Their use as first line antituberculous agents is currently under investigation. Furthermore, the oxazolidinones linezolid and PNU-100480 have been shown to have antituberculous activity in addition to their antibacterial effects. Several other agents are currently being developed for the treatment of tuberculosis. These agents include diarylquinolones (R207910), nitroimidazopyrans (PA-824, OPC-67683), ethambutol analogues (SQ109), cerulenin, trans-cinnamic acid, macrolides, pyrroles (LL3858), long-acting rifamycins and inhaled interferon-gamma. Furthermore, vaccines are being explored for pre-exposure and post-exposure use. This review will describe therapeutic developments in the management of tuberculosis, highlighting mechanisms of action of new pharmacological agents and their potential for clinical use.

Topics: Acetamides; Antitubercular Agents; Drug Design; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Linezolid; Mycobacterium Infections; Mycobacterium tuberculosis; Oxazolidinones; Protease Inhibitors; Reverse Transcriptase Inhibitors; Rifampin; Vaccines

In the treatment of tuberculosis the patients normally receive a two month daily treatment with Isoniazid, Rifampicin, Pyrazinamid and Ethambutol, followed by a daily treatment with Isoniazid and Rifampicin for four month. The atypical mycobacterial infections can be addressed as a local infection and are amendable to surgical therapy, eventually followed by a daily treatment with antibiotics for four to twelve weeks. In Germany it is obligatory to inform the local public health department about typical mycobacterial infections. Hygiene procedures following German law are discussed in this review.

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antitubercular Agents; Disease Notification; Drug Therapy, Combination; Ethambutol; Female; Germany; Humans; Immunocompromised Host; Isoniazid; Male; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Patient Isolation; Pyrazinamide; Rifampin; Streptomycin; Time Factors; Tuberculosis, Lymph Node

Tuberculosis and other mycobacterial diseases are frequent coinfections in AIDS patients with an increased related mortality. In this review we have updated the treatment of the main mycobacterial diseases (tuberculosis and Mycobacterium avium disease), under the scope of pharmacological interactions between antimycobacterial drugs, specially rifampicin and clarithromycin, and anti-retroviral drugs. Antimycobacterial treatment schemes, their duration, primary and secondary chemoprophylaxis and the optimal time to start the anti-retroviral therapy are analized. Finally, the immnune reconstitution inflammatory syndrome and its treatment are discussed.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Retroviral Agents; Clarithromycin; Drug Interactions; Humans; Mycobacterium Infections; Rifampin; Tuberculosis

We report a case of human infection caused by Mycobacterium lentiflavum and review the literature for infections caused by this bacterium. The patient was a 19-month-old boy with involvement of a cervical lymph node. Surgical removal of the lymphadenopathy was both diagnostic and curative.

Topics: Abscess; Amoxicillin-Potassium Clavulanate Combination; Humans; Infant; Isoniazid; Lymph Nodes; Male; Mycobacterium; Mycobacterium Infections; Pyrazinamide; Rifampin; Tuberculosis, Lymph Node

Topics: Clofazimine; Cost-Benefit Analysis; Dapsone; Drug Therapy, Combination; Global Health; Humans; International Cooperation; Leprostatic Agents; Leprosy; Mycobacterium Infections; Mycobacterium leprae; Prevalence; Rifampin; World Health Organization

Topics: Adolescent; Aged; Anti-Infective Agents; Antibiotics, Antitubercular; Ciprofloxacin; Drug Therapy, Combination; Ethambutol; Humans; Male; Middle Aged; Mycobacterium Infections; Nontuberculous Mycobacteria; Rifampin

The nontuberculous mycobacteria are responsible for considerable morbidity in the immunocompromised and immunocompetent host, especially in the older patient with chronic fibrotic or cavitary disease of the lung. Mycobacterium szulgai is a slow growing mycobacterium infrequent in nature and man. Except from a snail and a tropical fish, it has been isolated only from humans and nearly always represents a true pathogen. Three-drug therapy using in vitro susceptibilities as a guide for 12 to 18 months increases the likelihood of success. We present a patient who developed M szulgai pulmonary infection 30 years after an episode of pulmonary tuberculosis. After successful therapy for his M szulgai infection, this patient developed chronic pulmonary histoplasmosis. We review the 25 years of clinical experience with this mycobacteria; particular emphasis is on the presentation and treatment of this very unusual infection.

Topics: Anti-Bacterial Agents; Ciprofloxacin; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Lung Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium; Mycobacterium Infections; Radiography; Rifampin

Topics: Anti-Infective Agents; Ciprofloxacin; Humans; Isoniazid; Microbial Sensitivity Tests; Mycobacterium Infections; Ofloxacin; Rifampin

The reemergence of tuberculosis in the industrialized countries has hastened the development of new laboratory techniques. Hence, well-known shortcomings of traditional techniques such as the lack of a rapid and specific detection system, the delayed availability of species identification and drug susceptibility results, and the lack of a reliable method for determining strain identity for epidemiological purposes, have become immediate targets for implementing molecular biology techniques. In particular, nucleic acid amplification techniques, restriction fragment-length polymorphism and single-strand conformation polymorphism analyses have dramatically improved diagnostic timeliness and accuracy of mycobacteriology laboratory results. Our paper reviews recent developments and comments on the diagnostic applications of the new tools as compared to traditional techniques.

Topics: Amino Acid Sequence; Drug Resistance; Humans; Molecular Sequence Data; Mycobacterium; Mycobacterium Infections; Mycobacterium tuberculosis; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Random Amplified Polymorphic DNA Technique; Rifampin; Switzerland; Tuberculosis

We describe two cases of pulmonary infection due to Mycobacterium xenopi (M. xenopi). Both cases were men, ages 61 and 54 yr. In the first patient, lung infection due to M. xenopi occurred after gastrectomy. The second patient had an inactive M. tuberculosis infection. Both had pulmonary symptoms including cough, sputum and fever. Each chest X-ray showed an infiltrative shadow with a cavity in a unilateral, upper lobe. Isolates from both patients were studied not only by microbiological characteristics but also by DNA-DNA hybridization. All isolates were susceptible to streptomycin and kanamycin. In the first case, the patient had initially received rifampicin, isoniazid and ethambutol despite in vitro susceptibility patterns, however, there was no response and a new infiltrative shadow appeared in the contralateral lobe. With a multiple drug regimen based on in vitro susceptibility, clinical and roentgenographic improvements were achieved. The second patient showed a favorable response to the initial chemotherapy. Pulmonary infection due to M. xenopi can generally be successfully treated with drugs to which the organisms show in vitro sensitivity. We also reviewed the other two cases reported in Japan.

Topics: Bacterial Typing Techniques; Clarithromycin; Cycloserine; DNA Probes; Drug Resistance, Microbial; Gastrectomy; Humans; Isoniazid; Kanamycin; Male; Middle Aged; Mycobacterium Infections; Respiratory Tract Infections; Rifampin; Streptomycin; Tuberculosis, Pulmonary

Two patients with a history of intravenous drug abuse developed a pancreatic abscess due to mycobacterial infection as their initial evident opportunistic infection in association with the acquired immunodeficiency syndrome (AIDS). This presentation of mycobacterial infection has been previously reported in nine patients. The two patients reported here are the second and third reported cases in association with AIDS. As this entity should be considered a cause of a pancreatic lesion in immunosuppressed patients, fluid drained from a pancreatic abscess should have histologic stains and cultures for mycobacteria.

Topics: Abscess; Acquired Immunodeficiency Syndrome; Adult; Amikacin; Female; Gentamicins; Humans; Isoniazid; Middle Aged; Mycobacterium Infections; Nafcillin; Pancreatic Diseases; Penicillins; Rifampin; Tomography, X-Ray Computed; Ultrasonography

Topics: Acquired Immunodeficiency Syndrome; Antitubercular Agents; Dermatitis; Humans; Lung Diseases; Lung Diseases, Obstructive; Lymphadenitis; Male; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin; Risk Factors; Tuberculin Test

A 64-year-old alcoholic man had a chronic cavitary pulmonary infiltrate. Initial sputum smears and cultures yielded abundant acid-fast organisms subsequently identified as Mycobacterium terrae. Treatment with rifampin and ethambutol resulted in progressive clinical and roentgenographic resolution with an apparent cure after 18 months of therapy.

Topics: Chronic Disease; Ethambutol; Humans; Klebsiella Infections; Lung Diseases; Male; Middle Aged; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Radiography; Rifampin; Time Factors

Topics: Adrenal Cortex Hormones; Ambulatory Care; Aminosalicylic Acid; Antitubercular Agents; BCG Vaccine; Drug Resistance, Microbial; Ethambutol; Humans; Isoniazid; Mycobacterium Infections; Mycobacterium tuberculosis; Rifampin; Sputum; Streptomycin; Tuberculin Test; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Drug Resistance, Microbial; Humans; Methods; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Rifampin; Tuberculosis, Pulmonary

Rifapentine is undergoing development for the treatment of pulmonary tuberculosis. This study was conducted to characterize the single-dose pharmacokinetics of rifapentine and its 25-desacetyl metabolite and to assess the effect of food on the rate and extent of absorption in participants infected with human immunodeficiency virus (HIV). Twelve men and four women, mean age, 38.6 +/- 6.9 years, received a single 600-mg oral dose of rifapentine in an open-label, randomized two-way, complete crossover study. Each volunteer received rifapentine following a high-fat breakfast or during a fasting period. Serial blood samples were collected for 72 h and both rifapentine and its metabolite were assayed by a validated high-performance liquid chromatography method. Pharmacokinetics of rifapentine and 25-desacetylrifapentine were determined by noncompartmental methods. Mean (+/- the standard deviation) maximum concentrations of rifapentine in serum and areas under the curve from time zero to infinity following a high-fat breakfast were 14.09 +/- 2.81 and 373.63 +/- 78.19 micrograms/ml, respectively, and following a fasting period they were 9.42 +/- 2.67 and 256.10 +/- 86.39 micrograms. h/ml, respectively. Pharmacokinetic data from a previously published healthy volunteer study were used for comparison. Administration of rifapentine with a high-fat breakfast resulted in a 51% increase in rifapentine bioavailability, an effect also observed in healthy volunteers. Although food increased the exposure of these patients to rifapentine, the infrequent dosing schedule for the treatment of tuberculosis (e.g., once- or twice-weekly dosing) would be unlikely to lead to accumulation. Additionally, autoinduction has been previously studied and has not been demonstrated with this compound, unlike with rifabutin and rifampin. Rifapentine was well tolerated by HIV-infected study participants. The results of our study suggest that no dosage adjustments may be required for rifapentine in HIV-infected patients (Centers for Disease Control and Prevention classification A1, A2, B1, or B2) undergoing treatment for tuberculosis.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Cross-Over Studies; Female; Food; HIV Seropositivity; HIV-1; Humans; Male; Middle Aged; Mycobacterium Infections; Rifampin; Tuberculosis

In this study the results of treatment of 37 patients with non-tuberculous mycobacterial disease were analyzed. The responsible strains were indentified as M. kansasi in 16 patients, M. avium-intracellulare in 10 patients, M. avium intracellulare and M. xenopi in 3 patients, M. xenopi and M. chalone in 7 patients. Patients with M. kansasi infection had been treated for 12 months. Sputum culture became negative in all patients after 2 months of treatment mainly with ryfamipcin (R) and etambutol (E). Thirteen patients infected with M. avium-intracellulare or M. avium-intracellulare and M. xenopi had been treated for 24 months according to the drug sensitivity tests. Sputum conversion was achieved only in 4 out of 11 patients. In 3 patients sputum examination was positive inspite for the regression of chest X-ray lesions. In 2 cases despite the resistance in vitro to all drugs, during treatment with H, R, E and aminoglicoside-sputum culture become negative. Four patients died due to the progression of non-tuberculous mycobacterial infection. In a group of 7 patients infected with M. xenopi sputum--negative results were observed after 2 months of treatment. One patient infected with M. chaelone had been treated for 6 months with clarithromycine, and sputum culture become negative after 2 months of the treatment.

Topics: Adult; Aged; Antitubercular Agents; Drug Resistance; Drug Therapy, Combination; Ethambutol; Female; HIV Seronegativity; Humans; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Respiratory Tract Infections; Retrospective Studies; Rifampin; Sputum; Treatment Outcome

The success of short-course chemotherapy for tuberculosis, the similarity between Mycobacterium tuberculosis and M. kansasii and the effectiveness of rifampin against the latter organism prompted a comparison of the diseases due to these organisms to assess the feasibility of a prospective trial of short-course chemotherapy in patients with mycobacteriosis kansasii. The two groups of patients were matched for age, sex and time of diagnosis. The patients with mycobacteriosis kansasii more frequently had underlying obstructive pulmonary disease. The clinical course of mycobacteriosis kansasii was more indolent, with a slower rate of improvement according to the chest x-ray films and a longer time before sputum smears and cultures became negative. M. kansasii was significantly more resistant to all the antibiotics, including rifampin. Although these differences from tuberculosis suggest that an equally short course of therapy may not be effective for patients with mycobacteriosis kansasii, the outcome was good in compliant patients who were given the three most effective major drugs for 12 months after the sputum smears and cultures had become negative. Therefore, a trial of modified short-course chemotherapy is recommended for patients with mycobacteriosis kansasii.

Topics: Clinical Trials as Topic; Drug Administration Schedule; Drug Resistance, Microbial; Female; Humans; Male; Middle Aged; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Prospective Studies; Rifampin; Time Factors; Tuberculosis, Pulmonary

Topics: Animals; Antitubercular Agents; Capreomycin; Clinical Trials as Topic; Drug Combinations; Ethambutol; Mycobacterium Infections; Phenylthiourea; Rabbits; Rifampin; Tuberculosis

Multidrug-resistant (MDR) tuberculosis (TB) is defined by the resistance of Mycobacterium tuberculosis, the causative organism, to the first-line antibiotics rifampicin and isoniazid. Mitigating or reversing resistance to these drugs offers a means of preserving and extending their use in TB treatment. R-loops are RNA/DNA hybrids that are formed in the genome during transcription, and they can be lethal to the cell if not resolved. RNase HI is an enzyme that removes R-loops, and this activity is essential in M. tuberculosis: knockouts of

Topics: Anti-Bacterial Agents; Antitubercular Agents; Cell Death; Humans; Isoniazid; Moxifloxacin; Mycobacterium Infections; Mycobacterium tuberculosis; Rifampin; RNA; Streptomycin; Tuberculosis, Multidrug-Resistant

Topics: Aged; Aged, 80 and over; Antitubercular Agents; Arthritis, Infectious; BCG Vaccine; Ethambutol; Fatal Outcome; Humans; Isoniazid; Male; Mycobacterium bovis; Mycobacterium Infections; Rifampin; Treatment Outcome; Urinary Bladder Neoplasms

Therapeutic treatment options for opportunistic non-tuberculous mycobacterial (NTM) infection and/or serious mycobacterial infections such as tuberculosis (TB) and leprosy are limited due to the spread of antimicrobial resistance mechanism. Plant-derived natural compounds as prospective efflux pump inhibitors may present a promising adjunct to conventional chemotherapy by enhancing mycobacterial susceptibility to antibiotics. This study served to evaluate the antimicrobial and resistance-modifying profile of a range of plant-derived flavonoids against the mycobacterial model strains:

Topics: Anti-Infective Agents; Bacterial Proteins; Biological Transport; Ethidium; Flavonoids; Membrane Transport Proteins; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Rifampin

Mycobacterium colombiense (M. colombiense) is a member of the Mycobacterium avium complex (MAC). To our knowledge, this is the third case report of an M. colombiense infection. An 80-year-old man, immunocompromised by myelodysplastic syndrome (MDS), developed a skin rash with exfoliation and eruption on his face and scalp. Mycobacteria were detected in pus samples. Broad-range polymerase chain reaction (PCR) revealed the mycobacteria to be M. colombiense. The lesions resolved after daily administration of rifampicin, ethambutol, and clarithromycin. In conclusion, broad-range PCR identified this rare mycobacterium, allowing for the administration of appropriate combination antibiotic therapy.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Clarithromycin; Ethambutol; Humans; Immunocompromised Host; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Myelodysplastic Syndromes; Rifampin; Treatment Outcome

To treat organ transplant patients with mycobacterial infection, physicians need to pay attention to interaction between drugs used against mycobacteria and immunosuppressants. The purpose of this report is to describe the clinical features of and treatment for mycobacterial infection in lung transplant (LTx) recipients.. To investigate the incidence, treatment, and outcome for mycobacterial infection, we retrospectively reviewed 100 LTx recipients in our program since 2000.. Four recipients (4.0%) developed mycobacterial infection. Three recipients took tacrolimus, and 1 received cyclosporine with mycophenolate mofetil and a steroid for immunosuppression. Tuberculosis (TB) was isolated from 2 recipients, and non-tuberculous mycobacteriosis (NTM) was detected in the other 2. We treated the patients with levofloxacin + isoniazid + pyrazinamide + ethambutol (EB) for TB and clarithromycin (CLM) + EB for NTM to avoid interaction of calcineurin inhibitors (CNI: 8-10 ng/mL in trough level) with rifampicin (RFP). In treating the patients with NTM, we were able to maintain an adequate blood concentration of CNI by decreasing the dosage from one-half to one-quarter. All mycobacterial infections were controlled with treatment. In 1 patient with chronic obstructive pulmonary disease (COPD) infected with TB in the native lung, the forced expiratory volume in 1 second (FEV1) unexpectedly increased from 1890 mL before infection to 2320 mL possibly due to organization of the native lung.. We were able to manage the mycobacterial infections using drugs other than RFP without any cases of acute rejection under adequate immunosuppression. Organization of the native lung with TB infection unexpectedly resulted in improvement of FEV1 in a COPD patient.

Topics: Adult; Anti-Bacterial Agents; Calcineurin Inhibitors; Cyclosporine; Drug Interactions; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Lung Transplantation; Male; Middle Aged; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Mycophenolic Acid; Nontuberculous Mycobacteria; Postoperative Complications; Retrospective Studies; Rifampin; Tacrolimus; Tuberculosis

Mycobacterium genavense infection was diagnosed in an adult ferret with ptosis of the left eye, a proliferative lesion of the conjunctiva of the nictitating membrane, conjunctival swelling, and tumefaction of the periorbital tissues with a watery ocular discharge and the presence of a retrobulbar mass. The diagnosis was based on characteristic cytology of the retrobulbar mass and left mandibular lymph node that revealed granulomatous inflammation. Ziehl-Neelsen staining showed the presence of positive acid-fast bacilli in the cytoplasm of the macrophages. The diagnosis was confirmed by sequence analysis of the 16S rRNA gene amplified by using a multiplex polymerase chain reaction from a fresh lymph node biopsy. Therapy with marbofloxacin, rifampicin, and clarithromycin was recommended for 6 months and after this period, the veterinarian who was treating the ferret reported the disappearance of clinical signs. Six months after the end of the antibiotic treatment, the symptoms described previously reoccurred. Confirmatory laboratory tests were not performed but a recurrence of M genavense infection was suspected and the veterinarian, in agreement with the owner, euthanized the ferret.

Topics: Animals; Anti-Bacterial Agents; Clarithromycin; Conjunctivitis, Bacterial; Female; Ferrets; Fluoroquinolones; Mycobacterium; Mycobacterium Infections; Polymerase Chain Reaction; Rifampin; RNA, Ribosomal, 16S

A series of rhodanine incorporated quinoline derivatives were efficiently synthesized using reusable DBU acetate as ionic liquid and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743) both in active and dormant state. Compounds 3e, 3f, 3g, 3h and 3i exhibited very good antitubercular activity. The active compounds were studied for cytotoxicity against HUVEC, THP-1, macrophages, A549, PANC-1 and HeLa cell lines using modified MTT assay and were found to be noncytotoxic. Inactivity of all these compounds against Gram positive and Gram negative bacteria indicates their specificity towards the MTB. Further, the synthesized compounds have been screened for their in vitro antifungal activity. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of Zmp1 enzyme, which in turn helped to establish a structural basis of inhibition of mycobacteria. The results of present study clearly indicate the identification of some novel, selective and specific inhibitors against MTB that can be explored further for potential antitubercular drug.

Topics: Animals; Antitubercular Agents; Bacterial Proteins; Cell Line; Humans; Metalloproteases; Molecular Docking Simulation; Mycobacterium bovis; Mycobacterium Infections; Mycobacterium tuberculosis; Quinolines; Rhodanine

Mycobacterium abscessus is a fast-growing, multidrug-resistant organism that has emerged as a clinically significant pathogen in cystic fibrosis (CF) patients. The intrinsic resistance of M. abscessus to most commonly available antibiotics seriously restricts chemotherapeutic options. Herein, we report the potent activity of a series of indolecarboxamides against M. abscessus. The lead compounds, 6 and 12, exhibited strong activity in vitro against a wide panel of M. abscessus isolates and in infected macrophages. High resistance levels to the indolecarboxamides appear to be associated with an A309P mutation in the mycolic acid transporter MmpL3. Biochemical analyses demonstrated that while de novo mycolic acid synthesis remained unaffected, the indolecarboxamides strongly inhibited the transport of trehalose monomycolate, resulting in the loss of trehalose dimycolate production and abrogating mycolylation of arabinogalactan. Our data introduce a hereto unexploited chemical structure class active against M. abscessus infections with promising translational development possibilities for the treatment of CF patients.

Topics: Anti-Bacterial Agents; Biological Transport; Cell Line; Cord Factors; Humans; Indoles; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Mycolic Acids

The resurgence of mycobacterial infections and the emergence of drug-resistant strains urgently require a new class of agents that are distinct than current therapies. A group of 5-ethynyl (6-10), 5-(2-propynyloxy) (16, 18, 20, 22, 24), 5-(2-propynyloxy)-3-N-(2-propynyl) (17, 19, 21, 23, 25) and 5-hydroxymethyl-3-N-(2-propynyl) (30-33) derivatives of pyrimidine nucleosides were synthesized and evaluated against mycobacteria [Mycobacterium tuberculosis (Mtb), Mycobacterium bovis (BCG) and Mycobacterium avium], gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and gram-negative bacteria (Escherichia coli, Salmonella typhimurium and Pseudomonas aeruginosa) alone and in combination with existing drugs in in vitro assays. Although several compounds exhibited marked inhibitory activity at a higher concentration against Mtb, M. bovis, S. aureus and E. faecalis, they displayed unexpected synergistic and additive interactions at their lower concentrations with antitubercular drugs isoniazid and rifampicin, and antibacterial drug gentamicin. The active analogues were also found to inhibit intracellular Mtb in a human monocytic cell line infected with H37Ra. Oral administration of 5-hydroxymethyl-3-N-(2-propynyl)-3'-azido-2',3'-dideoxyuridine (32) and 5-hydroxymethyl-3-N-(2-propynyl)-2',3'-dideoxyuridine (33) at a dose of 100mg/kg for two weeks showed promising in vivo effects in mice infected with Mtb (H37Ra). No in vitro cytotoxicity of the test compounds was observed up to the highest concentration tested (CC50>300μg/mL).

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Cell Line; Dose-Response Relationship, Drug; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Mice; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium Infections; Nucleosides; Pyrimidines; Structure-Activity Relationship

A 4-year-old spayed female ferret presented with a 2-month history of anorexia, vomiting and occasional diarrhea. Abdominal ultrasonography revealed thickening of the gastric wall and enlarged abdominal lymph nodes. Biopsy samples from the thickened gastric wall, enlarged abdominal lymph nodes and liver were taken during an exploratory laparotomy. Based on the histopathological examination, mycobacterium infection was diagnosed. The bacterial species could not be identified by additional diagnostic tests of feces, including fecal smear, culture and polymerase chain reaction (PCR). The ferret was treated with prednisolone and multiple antimicrobials, including rifampicin, azithromycin and enrofloxacin, but did not improve with treatment and died 220 days after the first presentation.

Topics: Animals; Anti-Infective Agents; Azithromycin; Enrofloxacin; Fatal Outcome; Female; Ferrets; Fluoroquinolones; Hematocrit; Histological Techniques; Laparotomy; Leukocyte Count; Mycobacterium Infections; Prednisolone; Rifampin

Biological agents such as tumor necrosis factor-α inhibitors are known to cause mycobacterium infections. Here, we report a disseminated non-tuberculosis case caused by TNF-α inhibitor therapy and a probable paradoxical response to antimycobacterial therapy.. A 68-year-old man with relapsing polychondritis was refractory to glucocorticoid therapy; adalimumab was therefore administered in combination with oral glucocorticoids. Treatment with 40 mg of adalimumab led to rapid improvement of his clinical manifestations. The administration of tacrolimus (1 mg) was started as the dosage of oral glucocorticoids was tapered. However, the patient developed an intermittent high fever and productive cough 15 months after starting adalimumab treatment. A chest computed tomography scan revealed new granular shadows and multiple nodules in both lung fields with mediastinal lymphadenopathy, and Mycobacterium intracellulare was isolated from 2 sputum samples; based on these findings, the patient was diagnosed with non-tuberculosis mycobacteriosis. Tacrolimus treatment was discontinued and oral clarithromycin (800 mg/day), rifampicin (450 mg/day), and ethambutol (750 mg/day) treatment was initiated. However, his condition continued to deteriorate despite 4 months of treatment; moreover, paravertebral and subcutaneous abscesses developed and increased the size of the mediastinal lymphadenopathy. Biopsy of the mediastinal lymphadenopathy and a subcutaneous abscess of the right posterior thigh indicated the presence of Mycobacterium avium complex (MAC), and the diagnosis of disseminated non-tuberculosis mycobacteriosis was confirmed. Despite 9 months of antimycobacterial therapy, the mediastinal lymphadenopathy and paravertebral and subcutaneous abscesses had enlarged and additional subcutaneous abscesses had developed, although microscopic examinations and cultures of sputum and subcutaneous abscess samples yielded negative results. We considered this a paradoxical reaction similar to other reports in tuberculosis patients who had discontinued biological agent treatments, and increased the dose of oral glucocorticoids. The patient's symptoms gradually improved with this increased dose and his lymph nodes and abscesses began to decrease in size.. Clinicians should consider the possibility of a paradoxical response when the clinical manifestations of non-tuberculosis mycobacteriosis worsen in spite of antimycobacterial therapy or after discontinuation of tumor necrosis factor-α inhibitors. However, additional evidence is needed to verify our findings and to determine the optimal management strategies for such cases.

Topics: Adalimumab; Administration, Oral; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Clarithromycin; Ethambutol; Glucocorticoids; Humans; Male; Mycobacterium; Mycobacterium Infections; Polychondritis, Relapsing; Rifampin; Tacrolimus; Treatment Outcome; Tumor Necrosis Factor-alpha

Our laboratory of microbiology use the VersaTREK/ESP Culture System II for the isolation of mycobacteria. In this study, we evaluate this system for the analysis carried out between April 2009 and March 2010.. The Myco bottles are supplemented with growth supplements and an antimicrobial agent solution prior to inoculation with the specimen. The technology of the VersaTREK/ESP Culture System II is based on the detection of headspace pressure changes within a sealed bottle. It monitors changes in either gas production or gas consumption due to microbial growth. A special algorithm has been developed for detection of very slow growing mycobacteria. The bottles are incubated during 42 days. Meanwhile a solid medium is inoculated too. All specimen types can be analysed with this system.. Compared to solid culture, the time needed for detection of positive cultures was significantly shorter for the VersaTREK with a good recovery rate. For isolates recovered in both systems, mean time of detection is respectively 19.1 and 35.6 days for liquid and solid cultures. Mycobacteria identification may be determined using nucleic acid probs directly in Myco VersaTREK or in the solid medium. The susceptibility test of Mycobacteria tuberculosis complex is obtained between six and 13 days for rifampin, isoniazid, ethambutol, streptomycin and pyrasinamide.. This system offers a faster diagnosis and is an alternative to other instruments using liquid culture.

Topics: Algorithms; Antitubercular Agents; Automation; Bacteriological Techniques; Culture Media; Ethambutol; Humans; Isoniazid; Manometry; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Mycobacterium tuberculosis; Pyrazinamide; Rifampin; Staining and Labeling; Streptomycin; Time Factors

Topics: Aged; Antitubercular Agents; Diagnosis, Differential; DNA Probes; Drug Therapy, Combination; Ethambutol; Fingers; Humans; Male; Mycobacterium Infections; Postoperative Care; Rifampin; Tenosynovitis

Bacillus Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis that has been widely used for the treatment of superficial transitional cell carcinoma of the bladder. We describe a rare case of supra-renal mycotic aortic aneurysm secondary to BCG instillation in a 75-year-old male. Patients presenting with systemic symptoms post-instillation, possibly with an aneurysm, should raise suspicion of BCG dissemination, which requires early instigation of anti-mycobacterial drugs.

Topics: Administration, Intravesical; Aged; Aneurysm, Infected; Antibiotics, Antitubercular; Aorta, Abdominal; Aortic Aneurysm, Abdominal; BCG Vaccine; Carcinoma, Transitional Cell; England; Ethambutol; Fatal Outcome; Humans; Isoniazid; Male; Mycobacterium bovis; Mycobacterium Infections; Rifampin; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

After a laboratory-confirmed case of Mycobacterium haemophilum skin infection in a recently tattooed immunocompetent adult was reported, we investigated to identify the infection source and additional cases. We found 1 laboratory-confirmed and 1 suspected case among immunocompetent adults who had been tattooed at the same parlor.

Topics: Adult; Anti-Bacterial Agents; Ciprofloxacin; Clarithromycin; Contact Tracing; Drug Therapy, Combination; Humans; Male; Mycobacterium haemophilum; Mycobacterium Infections; Rifampin; Skin Diseases, Bacterial; Tattooing; Treatment Outcome; Washington

The in vitro activities of DC-159a against seven species of Mycobacterium were compared with moxifloxacin, gatifloxacin, levofloxacin, and rifampin. DC-159a was the most active compound against quinolone-resistant multidrug-resistant M. tuberculosis (MIC(90), 0.5 microg/ml) as well as drug-susceptible isolates (MIC(90), 0.06 microg/ml). The anti-tubercle bacilli activity of DC-159a was 4- to 32-fold more potent than those of currently available quinolones. DC-159a also demonstrated the highest activities against clinically important nontuberculous mycobacteria.

Topics: Aminopyridines; Antitubercular Agents; Aza Compounds; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Gatifloxacin; Humans; In Vitro Techniques; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Mycobacterium; Mycobacterium avium Complex; Mycobacterium chelonae; Mycobacterium fortuitum; Mycobacterium Infections; Mycobacterium kansasii; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Ofloxacin; Quinolines; Rifampin; Species Specificity

Topics: Aged, 80 and over; Antibiotics, Antitubercular; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Facial Dermatoses; Female; Granuloma; Humans; Isoniazid; Mycobacterium Infections; Pyrazinamide; Rifampin; Skin Diseases, Bacterial

The optimal treatment regimen for Mycobacterium avium complex (MAC) lung disease has not yet been fully established. We evaluated the efficacy of standardized combination antibiotic therapy and the factors that might affect unfavorable microbiologic responses in patients with MAC pulmonary disease.. This retrospective study reviewed data from 96 patients (56 females; median age 59 years) treated with newly diagnosed MAC lung disease between January 2003 and December 2006.. All patients received standardized combination antibiotic therapy, consisting of clarithromycin, rifampicin, and ethambutol. Streptomycin was additionally given in 72 patients (75%) for a median duration of 4.5 months. The overall favorable microbiologic response rate was 79% (76/96); 20 patients (21%) had unfavorable microbiologic responses, including failure to sputum conversion (n = 13), relapse (n = 3), and MAC-related death (n = 4). A positive sputum acid-fast bacillus smear at the start of treatment was an independent predictor of an unfavorable microbiologic response.. Standardized combination antibiotic therapy consisting of clarithromycin, rifampicin, and ethambutol with or without initial use of streptomycin is effective in treating patients with newly diagnosed MAC lung disease.

Topics: Aged; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium; Mycobacterium Infections; Retrospective Studies; Rifampin; Streptomycin; Treatment Outcome

Mucosal immunization has been suggested to be the best option for preventing Mycobacterium tuberculosis infection. The purpose of this study was to develop albumin microspheres containing Mycobacterium tuberculosis antigens and to determine if oral administration of the microspheres can induce antigen-specific mucosal and systemic immune responses. Albumin microspheres containing Mycobacterium tuberculosis dead cells and cell lysate were prepared. The physico-chemical characteristics of the formulations were determined and the microspheres were administered to animal models to evaluate the induction of immune responses to the antigens. The results showed that the particle sizes, zeta potential and dissolution pattern of the microspheres were ideal for oral delivery of vaccines. In vivo studies showed high production of antigen-specific antibody production in serum, nasal, salivary and faecal samples. From the results of the study, it can be concluded that oral administration of Mycobacterium tuberculosis microspheres was successful in inducing antigen-specific systemic and mucosal immune responses.

Topics: Administration, Oral; Albumins; Chemistry; Drug Delivery Systems; Emulsions; Humans; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Mycobacterium Infections; Mycobacterium tuberculosis; Nanoparticles; Polyesters; Pressure; Rifampin; Solvents; Tuberculosis Vaccines

Bacillus Calmette-Guérin (BCG) vaccine has a good safety profile in immune competent children and considerable risks such as disseminated BCG disease in individuals with immune deficiencies. However, some complications including local subcutaneous infection, regional suppurative lymphadenitis may occur after BCG vaccination in immune competent children. A 17-month-old female child was admitted with a painless protruding mass on the anterior chest wall. There was no evidence of previous tuberculous infection and contact with a tuberculosis patient. Chest-computed tomography revealed an oval shaped low attenuated 1.8 x 1.0 cm mass at subcutaneous and muscle layers just below sternum, but the pulmonary parenchyma seemed to be normal. We excised the mass and the histopathologic examination revealed granulomatous lesions that suggestive of mycobacterial disease process. We considered that the chest wall abscess was a complication of BCG vaccination occurred by hematogenous dissemination of the inoculated mycobacteria. She recovered without any complications and was treated with isoniazid (150 mg/day) and rifampin (150 mg/day) for 6 months as an outpatient, not directly observed therapy but monthly follow-up.

Topics: Abscess; Antitubercular Agents; BCG Vaccine; Female; Humans; Infant; Isoniazid; Mycobacterium Infections; Rifampin; Thoracic Wall; Tomography, X-Ray Computed; Treatment Outcome

Screening of new agents for anti-tubercular activity is a challenging task due to the virulent and slow growing nature of mycobacteria. In this study, we explored the use of Mycobacterium smegmatis as an alternate model to virulent strains. We observed that the effect of standard anti-tubercular drugs was similar in mice infected with M. smegmatis and Mycobacterium tuberculosis. The total duration of the experiment, including incubation time, was 10 days in the M. smegmatis-infected mice model compared with 2 months in M. tuberculosis-infected mice. This model of anti-tubercular screening is a simple, easy to carry out, less time-consuming, safer and economical alternative for preliminary in vivo screening of potential anti-tubercular agents.

Topics: Animals; Antitubercular Agents; Colony Count, Microbial; Disease Models, Animal; Drug Discovery; Female; Fluoroquinolones; Gatifloxacin; Isoniazid; Lung; Male; Mice; Mycobacterium Infections; Mycobacterium smegmatis; Mycobacterium tuberculosis; Rifampin; Spleen

Buruli ulcer caused by Mycobacterium ulcerans is an infection of the subcutaneous tissue leading to chronic necrotising skin ulcers. The pathogenesis is associated with the cytocidal and immunosuppressive activities of a macrolide toxin. Histopathological hallmark of progressing disease is a poor inflammatory response despite of clusters of extracellular bacilli. While traditionally wide excision of the infected tissue was the standard treatment, provisional WHO guidelines now recommend an eight week pre-treatment with streptomycin and rifampicin.. We conducted a detailed immunohistochemical analysis of tissue samples from Buruli patients who received antibiotic treatment. Cellular immune response along with bacterial load and distribution were monitored. We demonstrate that this treatment leads to the development of highly organized cellular infiltration surrounding areas of coagulative necrosis. Diffuse infiltrates, granulomas and dense lymphocyte aggregation close to vessels were observed. Mycobacterial material was primarily located inside mononuclear phagocytes and microcolonies consisting of extracellular rod-shaped mycobacteria were no longer found. In observational studies some patients showed no clinical response to antibiotic treatment. Corresponding to that, one of five lesions analysed presented with huge clusters of rod-shaped bacilli but no signs of infiltration.. Results signify that eight weeks of antibiotic treatment reverses local immunosuppression and leads to an active inflammatory process in different compartments of the skin. Structured leukocyte infiltrates with unique signatures indicative for healing processes developed at the margins of the lesions. It remains to be analysed whether antibiotic resistance of certain strains of M. ulcerans, lacking patient compliance or poor drug quality are responsible for the absent clinical responses in some patients. In future, analysis of local immune responses could serve as a suitable surrogate marker for the efficacy of alternative treatment strategies.

Topics: Anti-Bacterial Agents; Buruli Ulcer; Child; Ghana; Granuloma; Humans; Immunohistochemistry; Lymphocytes; Mycobacterium; Mycobacterium Infections; Rifampin; Streptomycin

Clarithromycin resistance in Helicobacter pylori has increased the incidence of eradication failure. Clarithromycin is a key drug in the current treatment regimens for H. pylori infection, and it is also used for nontuberculous mycobacteriosis (NTM). The rate of H. pylori infection in 15 patients with NTM who were on longterm clarithromycin, rifampicin, and other drug therapy was examined, using the [(13)C] urea breath test. H. pylori was detected in 5 of the 15 patients (33.3%), which was significantly lower than the prevalence of H. pyloriin subjects who had routine upper gastrointestinal endoscopy in Japan (P = 0.0006). Thus, H. pylori resistance to clarithromycin is suggested to be low in patients with longterm administration, and the possibility exists of a combination of clarithromycin and rifampicin as a second-line therapy for the eradiation of H. pylori.

Topics: Aged; Aged, 80 and over; Clarithromycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Male; Middle Aged; Mycobacterium Infections; Rifampin

Disseminated mycobacterial disease was diagnosed in an eight-year-old domestic shorthaired cat, with involvement of the skin, lungs, lymph nodes and one eye. Mycobacterium simiae was cultured from skin biopsies on solid agar and in liquid media. This organism is known to cause pulmonary, cutaneous or disseminated infection in human patients with acquired immunodeficiency syndrome but has never been encountered as a pathogen in companion animals. Combination treatment with rifampicin, enrofloxacin and clarithromycin resulted in complete clinical remission within six months, with no side effects. No recurrence was observed in a 22-month follow-up period.

Topics: Animals; Anti-Infective Agents; Antitubercular Agents; Bacteremia; Cat Diseases; Cats; Clarithromycin; Diagnosis, Differential; Diagnostic Techniques, Ophthalmological; Drug Therapy, Combination; Enrofloxacin; Fluoroquinolones; Male; Mycobacterium; Mycobacterium Infections; Quinolones; Radiography; Rifampin; Tuberculosis, Ocular

Tuberculous otitis media (TOM) is a rare cause of chronic suppurative infection of the middle ear. Due to that the symptoms and signs are often indistinguishable from those of nontuberculosis chronic otitis media and the fact that the index of suspicion is low, there is frequently a considerable delay prior to diagnosis. This can lead to irreversible complications such as facial nerve paralysis and labyrinthitis. Medical therapy with antituberculous drugs is usually effective. We report three cases with TOM diagnosticated and followed up in our Service from january 1993 to july 2001. Their charts were retrospectively reviewed for relevant historical data, physical findings, complementary studies, treatment and clinical response. We performed a review of the literature, emphasizing that TOM should be considered in the differential diagnosis of chronic otitis media.

Topics: Adult; Aged; Amoxicillin; Antitubercular Agents; Cerebrospinal Fluid Otorrhea; Drug Combinations; Ear Diseases; Female; Humans; Isoniazid; Male; Mycobacterium Infections; Mycobacterium tuberculosis; Otitis Media; Penicillins; Proteus Infections; Proteus mirabilis; Pyrazinamide; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tuberculosis

Mycobacterial infection is a serious opportunistic infection in renal transplant recipients. The incidence is higher in developing than in developed Western countries. This study is a single-centre retrospective review of the records of 2502 renal transplant recipients in Belgium. Fourteen cases of mycobacterial infection (9 Mycobacterium tuberculosis and 5 atypical mycobacterial infection) were diagnosed. The time interval between transplantation and diagnosis was 64 +/- 80 months (mean +/- SD, range 5-188) for M. tuberculosis and 92 +/- 75 months (range 14-209) for atypical mycobacterial infection. The localisation of M. tuberculosis was pulmonary/pleural in 67% and extrapulmonary in 33%. The atypical mycobacterial infections were located in skin, tendons, and joints. Eight patients received IV prednisolone pulse therapy for acute rejection long before the time of mycobacterial infection. The initial antimycobacterial therapy consisted of a combination of isoniazid, rifampicin, and ethambutol in all patients. In patients with M. tuberculosis infection, a good response to antimycobacterial therapy was obtained. In patients with atypical mycobacterial infection, initial treatment was successful in 3 out of 5 patients, in 1 patient recurrence was diagnosed and in another patient, who is still under treatment at present, the initial treatment was adjusted after identification of the atypical mycobacterium and its antibiogram. The incidence of mycobacterial infection after renal transplantation did not increase with newer immunosuppressive therapy. The major risk factor is the total dose of corticosteroids. All patients responded well without major reductions in immunosuppressive therapy. Chemoprophylaxis for high-risk patients still is recommended.

Topics: Adult; Aged; Belgium; Female; Humans; Immunosuppression Therapy; Isoniazid; Kidney Transplantation; Male; Middle Aged; Mycobacterium Infections; Mycobacterium tuberculosis; Opportunistic Infections; Retrospective Studies; Rifampin; Treatment Outcome

Mycobacterium tuberculosis infects one-third of the world's population and causes two million deaths annually. The unusually low permeability of its cell wall contributes to the ability of M. tuberculosis to grow within host macrophages, a property required for pathogenesis of infection. Mycobacterium marinum is an established model for discovering genes involved in mycobacterial infection. Mycobacterium marinum mutants with transposon insertions in the beta-ketoacyl-acyl carrier protein synthase B gene (kasB) grew poorly in macrophages, although growth in vitro was unaffected. Detailed analyses by thin-layer chromatography, nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, infrared spectroscopy, and chemical degradations showed that the kasB mutants synthesize mycolic acids that are 2-4 carbons shorter than wild type; the defect was localized to the proximal portion of the meromycolate chain. In addition, these mutants showed a significant (approximately 30%) reduction in the abundance of keto-mycolates, with a slight compensatory increase of both alpha- and methoxy-mycolates. Despite these small changes in mycolate length and composition, the kasB mutants exhibited strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensin and lysozyme. The abnormalities of the kasB mutants were fully complemented by expressing M. tuberculosis kasB, but not by the closely related gene kasA. These studies identify kasB as a novel target for therapeutic intervention in mycobacterial diseases.

Topics: Animals; Anti-Bacterial Agents; Cell Line; Cell Wall; Cerulenin; Chromatography, Gas; Chromatography, Thin Layer; Colony Count, Microbial; Defensins; DNA Transposable Elements; Drug Resistance, Bacterial; Genetic Complementation Test; Macrophages; Magnetic Resonance Spectroscopy; Mice; Muramidase; Mutagenesis, Insertional; Mycobacterium Infections; Mycobacterium marinum; Mycolic Acids; Permeability; Phagosomes; Rifampin; Sodium Dodecyl Sulfate; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrophotometry, Infrared

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antitubercular; Female; Helicobacter Infections; Humans; Male; Middle Aged; Mycobacterium Infections; Respiratory Tract Infections; Rifampin

RCR-heteroduplex (GDA) and chip methods were used to detect rifampricin-resistant (RR) and rifampicin-sensitive (RS) Mycobacterium tuberculosis (MTB) in the samples from patients (sputum) and in the clinical isolates of MTB from these patients (MB/BacT liquid medium and Lowenstein Jensen's (LJ) solid medium. The efficiency of detecting RR and RS of MTB (from the sputum) is 100 and 92.3% in the chip and GDA tests, respectively. Correlations between GDA (sputum) and drug test (LJ) were 91.7%, that of chip (sputum) and drug test LJ, 88.5%, chip (sputum) and chip clinical isolates (LJ), 100%. The efficacy of GDA and chip in the detection of RR of MTB strains is under discussion.

Topics: Antitubercular Agents; Drug Resistance, Microbial; Humans; Molecular Biology; Mycobacterium Infections; Mycobacterium tuberculosis; Point Mutation; Rifampin; Tuberculosis

We describe a case of Mycobacterium haemophilum in an immunocompromised patient with systemic lupus erythematosus (SLE). Mycobacterium haemophilum is a recently described pathogen which has not been previously described either in SLE patients or patients on Mycophenolate Mofetil. Mycobacterium haemophilum can be difficult to diagnose, as it may not have the granulomas characteristic of atypical mycobacterial infections. Combination therapy with at least two drugs for several months is required and the outcome depends on the patient's underlying immunocompromised state. Our report highlights the need for early diagnosis and treatment of Mycobacterium haemophilum in immunocompromised patients with SLE.

Topics: Adult; Anti-Bacterial Agents; Antirheumatic Agents; Clarithromycin; Cyclophosphamide; Ethambutol; Female; Humans; Immunosuppressive Agents; Isoniazid; Leg; Lupus Erythematosus, Systemic; Muscle, Skeletal; Mycobacterium haemophilum; Mycobacterium Infections; Mycophenolic Acid; Rifampin

Topics: Antibiotics, Antitubercular; Ethambutol; Evidence-Based Medicine; Humans; Mycobacterium Infections; Opportunistic Infections; Practice Guidelines as Topic; Rifampin; United Kingdom

It is generally accepted that qualitative drug susceptibility tests established and validated for Mycobacterium tuberculosis are not applicable to opportunist (non-tuberculous) mycobacteria. Previous studies have shown that in vitro antimicrobial susceptibilities for opportunist mycobacteria, performed by the method of modal resistance (MR), correlate poorly with clinical response. Minimum inhibitory concentration (MIC) determination may provide better correlation with predicted clinical response than the conventional MR results.. To determine the relationship between quantitative in vitro sensitivity results for opportunist mycobacteria and their in vivo response to treatment.. MICs were performed radiometrically with the Bactec TB-460 system; 35 M. avium complex isolates, 29 isolates of M. malmoense and 16 isolates of M. xenopi were tested.. Susceptibility results were analysed in comparison with therapeutic outcome by Fisher's exact probability test. Only one significant association was found; in vitro resistance to ethambutol correlated with treatment failure for M. malmoense infections (P = 0.027). There were no other significant correlations between in vitro results and treatment outcome.. Prediction of treatment outcome from in vitro susceptibility tests continues to be a problem in infections with opportunist mycobacteria.

Topics: Antitubercular Agents; Ethambutol; Humans; In Vitro Techniques; Lung Diseases; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Opportunistic Infections; Predictive Value of Tests; Rifampin; Treatment Outcome

Tuberculous otitis media can provide a diagnostic challenge even to the most astute and experienced clinician. The rarity of the condition and its propensity to masquerade as commoner otological conditions further delays diagnosis and treatment. We present the case of a 22-year-old female who presented with chronic aural discharge, unilateral hearing loss and recurrent hemifacial paralysis. The paper highlights the difficulty in diagnosis and stresses the need for a high index of suspicion in cases resistant to the common methods of treatment.

Topics: Adult; Antitubercular Agents; Diagnosis, Differential; Drug Therapy, Combination; Ear Diseases; Facial Paralysis; Female; Hearing Loss; Hearing Loss, Conductive; Humans; Isoniazid; Mycobacterium Infections; Otitis Media; Pyrazinamide; Rifampin; Tinnitus; Tuberculosis

Rifampin is the most potent drug used in the treatment of disease due to Mycobacterium kansasii. A 69-bp fragment of rpoB, the gene that encodes the beta subunit of the bacterial RNA polymerase, was sequenced and found to be identical in five rifampin-susceptible clinical isolates of M. kansasii. This sequence showed 87% homology with the Mycobacterium tuberculosis gene, with an identical deduced amino acid sequence. In contrast, missense mutations were detected in the same fragment amplified from five rifampin-resistant isolates. A rifampin-resistant strain generated in vitro also harbored an rpoB gene missense mutation that was not present in the parent isolate. All mutations detected (in codons 513, 526, and 531) have previously been described in rifampin-resistant M. tuberculosis isolates. Rifampin MICs determined by E-test were <1 mg/liter for all rifampin-susceptible isolates and >256 mg/liter for all rifampin-resistant ones. In addition, four of the five rifampin-resistant isolates were also resistant to rifabutin. We have thus shown a strong association between rpoB gene missense mutations and rifampin resistance in M. kansasii. Although our results are derived from a small number of isolates and confirmation with larger numbers would be useful, they strongly suggest that mutations within rpoB form the molecular basis of rifampin resistance in this species.

Topics: Amino Acid Sequence; Antibiotics, Antitubercular; Base Sequence; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Mycobacterium Infections; Mycobacterium kansasii; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; Rifampin

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Brucellosis; Doxycycline; Humans; Male; Middle Aged; Mycobacterium Infections; Rifampin; Spleen

Mycobacterium genavense infection was diagnosed in two adult ferrets. Disseminated mycobacteriosis was diagnosed in a castrated 5-year-old sable ferret with generalised peripheral lymph node enlargement and a proliferative lesion of the conjunctiva of the nictitating membrane. The diagnosis was based on characteristic cytology and sequence analysis of the 16S rRNA gene amplified using the polymerase chain reaction from fresh biopsy material. Therapy with rifampicin, clofazimine and clarithromycin probably cured the infection. An entire 4-year-old female ferret with conjunctival swelling, serous ocular discharge and swelling of the subcutaneous tissues of the nasal bridge was diagnosed as having M genavense infection on the basis of typical cytology, histopathology and sequence analysis of 16S rRNA amplicons from formalin-fixed paraffin-embedded tissue. This patient was treated successfully using rifampicin. Both ferrets subsequently died as a result of other disease conditions, 10 and 4 months following initiation of therapy, respectively. This is the first report documenting M genavense as a cause of disseminated mycobacterial disease in ferrets. Conjunctival involvement may be a feature of disseminated mycobacteriosis in the ferret. The possibility that these infections were the consequence of a ferret retrovirus infection should be considered further.

Topics: Animals; Clarithromycin; Clofazimine; Conjunctivitis, Bacterial; Diagnosis, Differential; DNA Primers; Drug Therapy, Combination; Fatal Outcome; Female; Ferrets; Male; Mycobacterium; Mycobacterium Infections; Polymerase Chain Reaction; Rifampin; RNA, Bacterial

The usefulness of the lymphocyte transformation test (LTT) for the analysis of adverse reactions to antituberculous drugs was evaluated. - The LTT was performed with isoniazid and rifampicin in 15 tuberculosis and 2 MOTT (Mycobacteria other than tuberculosis)-infection patients who suffered drug reactions, in 23 patients without any adverse reactions, in 7 controls previously exposed to antituberculous drugs, and in 14 controls who had never been exposed. 4/15 of the hepatotoxic reactions only showed a positive LTT with rifampicin, 3/15 only with isoniazid, and in 8/15 the LTT was negative. In an anaphylactoid shock reaction the LTT was extremely exaggerated for both rifampicin and isoniazid. In patients without any side effects only one slightly increased LTT due to isoniazid was observed. Two healthy controls with previous contact to these drugs showed a positive LTT for isoniazid, one of those with both rifampicin and isoniazid. The LTT was negative in all control persons without any former contact to antituberculous medications. In most cases hepatotoxicity seems to be a pure toxic reaction without the participation of cellular immune mechanisms. LTT can be useful for identifying the drug responsible for immunological side effects.

Topics: Adult; Anaphylaxis; Anti-Bacterial Agents; Antitubercular Agents; Bromodeoxyuridine; Cells, Cultured; Chemical and Drug Induced Liver Injury; DNA Replication; Drug Eruptions; Drug Hypersensitivity; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunity, Cellular; Isoniazid; Kidney Diseases; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Middle Aged; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Mycobacterium kansasii; Nervous System Diseases; Rifampin; Tuberculosis

Topics: Adolescent; Adult; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; Humans; Isoniazid; Male; Mycobacterium Infections; Organ Transplantation; Postoperative Complications; Pyrazinamide; Retrospective Studies; Rifampin; Rural Population; Socioeconomic Factors; Time Factors; Turkey

The aim of this study was to investigate the clinical and radiological particularities of pulmonary tuberculosis depending on the age of the child.. The medical records of all children with pulmonary tuberculosis diagnosed between 1985 to 1996 were reviewed. They were divided into three age groups according to age: < 3 years, 3-5 year and 6-15 years.. Of the 173 children identified, 51.4% were male. Forty percent were < 3 years if age, 33.1% between 3 and 5 years and 26.1% between 6 and 15 years old. The frequency of diagnosis derived from a case contact investigation was higher in children < 3 years of age (38.6%) and children aged 3-5 years (52.6%) than in children between 6-15 years old (21.7%, p < 0.05 for both). In the other cases, diagnosis was the result of investigation of an ill child, investigation of a child after pulmonary tuberculosis was diagnosed in a sibling and routine tuberculin skin test reactivity. An adult source of tuberculosis was identified in 68.6% of the children < 3 years old, 59.6% of children aged 3-5, but only in 37% of the children aged 6-15 years (p < 0.05 for both). The case contact was a family member in 92.7% of the children < 6 years of age and in 66.7% of children aged 6-15 years (p < 0.01). Culture of Mycobacterium tuberculosis was positive in 47.1% of children < 3 years old and 43.9% of children aged 6-15 years, but only in 27.5% of children aged 3.5 years (p < 0.05). Pulmonary parenchymal disease was more frequently found in children < 3 years (67.5%) than in children aged 6-15 years (39.4%, p < 0.05).. Investigation of an adult source is essential when a child is diagnosed of pulmonary tuberculosis. Pulmonary tuberculosis is more intense and the source of adult contact is more frequently found in children < 3 years old.

Topics: Adolescent; Age Distribution; Anti-Bacterial Agents; Antibiotics, Antitubercular; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Isoniazid; Male; Mycobacterium Infections; Retrospective Studies; Rifampin; Tuberculosis, Pulmonary

Topics: Actinomycetales Infections; Adult; AIDS-Related Opportunistic Infections; Ciprofloxacin; Clarithromycin; Diagnostic Errors; Drug Therapy, Combination; Humans; Mycobacterium Infections; Pneumonia, Bacterial; Rhodococcus equi; Rifampin; Vancomycin

Pyrolysis mass spectrometry (Py-MS) yields data reflecting overall cell composition. The changes in composition induced by treatment with rifampicin and ethambutol, alone and in combination, were investigated for a collection of seven strains of Mycobacterium malmoense from pulmonary infections. Two strains, both from patients that had responded to therapy with this combination, showed large changes in composition from control, untreated cultures. The difference was particularly marked for the ethambutol treated cultures. Four strains, all from patients who had failed to respond to therapy with this combination, showed minimal changes in composition for all treatments. The remaining strain also showed minimal treatment-induced change, but, for this patient, therapy with the combination had proved successful. Minimum inhibitory concentrations (MICs) were determined radiometrically. All strains showed MICs < 0.5 microgram/mL for rifampicin (sensitive) and of 8 micrograms/mL for ethambutol (resistant). MIC results did not correlate with clinical response, whereas the Py-MS results correlated with clinical response for six of the seven isolates. Py-MS may have a role in predicting effective therapy for this problem group.

Topics: Ethambutol; Humans; Lung Diseases; Mass Spectrometry; Microbial Sensitivity Tests; Mycobacterium Infections; Opportunistic Infections; Rifampin

We describe a case of osteomyelitis due to Mycobacterium haemophilum in a cardiac transplant recipient and review the two other reported cases of M. haemophilum infection in cardiac transplant patients. Our patient had an excellent response to a prolonged course of therapy with clarithromycin and rifampin. We examine in detail the interactions between these two antibiotics and cyclosporine, including the apparently offsetting effects of clarithromycin/rifampin combination therapy on blood levels of cyclosporine.

Topics: Adult; Clarithromycin; Cyclosporine; Drug Interactions; Drug Therapy, Combination; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Mycobacterium haemophilum; Mycobacterium Infections; Osteomyelitis; Rifampin

Topics: Adrenal Cortex Hormones; Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Antitubercular Agents; Ciprofloxacin; Clarithromycin; Clofazimine; Drug Therapy, Combination; Ethambutol; HIV Infections; Humans; Isoniazid; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections; Nontuberculous Mycobacteria; Practice Guidelines as Topic; Pyrazinamide; Pyridoxine; Radiography; Rifabutin; Rifampin; Tuberculosis, Meningeal; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Topics: Antibiotics, Antitubercular; Antitubercular Agents; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Multiple; Ethambutol; HIV Infections; Humans; Isoniazid; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium bovis; Mycobacterium Infections; Pyrazinamide; Rifampin

In vitro studies have shown that rifampicin is an effective antibiotic for mycobacteria infections. Two species of tropical fish, the Firemouth Cichild Cichlasoma meeki and the Congo Tetra Phenacogrammus interruptus, were used to determine whether oral application of rifampicin might serve as an effective treatment for mycobacteriosis in tropical fish. Fish of the two species were infected with M. marinum under controlled conditions. Six or twelve weeks after infection, treatment was begun with medicated fish food containing rifampicin in combination with tetracyclin. Histological examination of epithelial cell granuloma in the anterior and posterior kidneys, as well as in liver and spleen, showed that antibiotic treatment could somewhat reduce the intensity of, but could not successfully eliminate infection. In addition, after treatment, acid-resistant rods could still be isolated from histological samples and M. marinum could be cultured from organ samples.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Fish Diseases; Fishes; Mycobacterium; Mycobacterium Infections; Perches; Rifampin; Tropical Climate

A patient with indolent, non-Hodgkin's lymphoma developed a pretibial soft tissue abscess caused by a fastidious mycobacterium. Because the organism could not be definitively identified by standard microbiologic testing, whole cell fatty acid analysis and 16S rDNA sequencing were performed. These procedures identified the organism as Mycobacterium haemophilum. We review the diagnostic considerations with regard to this pathogen.

Topics: Abscess; Aged; Ciprofloxacin; DNA, Bacterial; DNA, Ribosomal; Drug Therapy, Combination; Fatty Acids; Humans; Lymphoma, Non-Hodgkin; Male; Mycobacterium haemophilum; Mycobacterium Infections; Rifampin

Topics: Actinomycetales Infections; Drug Therapy, Combination; Erythromycin; HIV Infections; HIV-1; Humans; Mycobacterium Infections; Rhodococcus equi; Rifampin

Topics: Drug Therapy, Combination; Ethambutol; HIV Seropositivity; Humans; Immunosuppressive Agents; Isoniazid; Kidney Transplantation; Mycobacterium Infections; New York; Postoperative Complications; Pyrazinamide; Rifampin; Transplantation, Homologous

Intact, non-growing Mycobacterium leprae, M. avium and M. microti oxidized a wide range of 1-14C-labelled fatty acids (C8 to C24) to 14CO2. Laurate (C12) was oxidized most rapidly, and its oxidation by M. leprae was inhibited by the antileprosy agents Dapsone, clofazamine and rifampicin. Key enzymes of beta-oxidation were detected in extracts from all three mycobacteria. All these activities (both in intact mycobacteria and the enzymes) were stimulated in M. avium grown in Dubos medium plus palmitate but activities in M. microti or M. avium grown either in Dubos medium with added liposomes or triolein, or in vivo were similar to those detected in the same strain grown in Dubos medium alone. M. avium could be grown in medium in which 95% of its fatty acyl elongase activity is acetyl-CoA dependent. In this medium growing M. avium organisms oxidized [1-14C]palmitate to 14CO2 but simultaneously elongated palmitate to C24 acids and even longer. Acetyl-CoA-dependent elongase activity is similar but clearly not identical to reversed beta-oxidation, but the exact point(s) of difference have not yet been identified.

Topics: Acetyl Coenzyme A; Clofazimine; Dapsone; Fatty Acids; Laurates; Mycobacterium; Mycobacterium avium; Mycobacterium Infections; Mycobacterium leprae; Oxidation-Reduction; Rifampin

Treatment of nontuberculous mycobacterial infection should be carried out by the chemotherapeutic regimens most suitable for each species. We performed in-vitro susceptibility tests for various species and determined the probability in which the mycobacteria of each species are inhibited by blood concentrations attainable by the dosages usually used. From such determinations, the following regimens have been recommended: 1) M. avium-M. intracellulare complex, Rifampicin + Enviomycin + Ethambutol; 2) M. kansasii, Ofloxacin + Enviomycin + Rifampicin; 3) M. szulgai, Enviomycin - Ethambutol + Isoniazid; 4) M. fortuitum, Ofloxacin. The effectiveness of the treatment of the infection caused by M. avium complex is less than 15% even using the above regimen, while it is high in the treatment of infections caused by M. kansasii and M. szulgai. There are no effective regimens for the treatment of infection caused by M. chelonae or M. simiae. The above recommendations are useful in practice, because, at present, reliable susceptibility testing of nontuberculous mycobacteria is not yet done commonly.

Topics: Drug Resistance, Microbial; Drug Therapy, Combination; Enviomycin; Ethambutol; Humans; Isoniazid; Mycobacterium; Mycobacterium Infections; Ofloxacin; Rifampin; Viomycin

We describe a patient with hairy cell leukemia and protracted fever. The patient's condition deteriorated during treatment with alfa Interferon 2b, and his fever persisted. A slight widening of the upper mediastinum appeared after 2.5 months. Mediastinoscopy with lymph node biopsy revealed granulomatous infiltrates with acid-fast bacilli. Cultures of the lymph node material later showed growth of Mycobacterium malmoense. The patient was treated with rifampicin, doxycycline, etambutol and cycloserin for sixteen months and remains afebrile and is gaining weight. His general condition is still improving. An aggressive diagnostic approach is necessary in febrile patients with hairy cell leukemia.

Topics: Adult; Bone Marrow; Cycloserine; Doxycycline; Ethambutol; Humans; Leukemia, Hairy Cell; Male; Mycobacterium Infections; Rifampin

Three treatment protocols using rifabutine for mycobacterial infections resistant to rifampicin were prepared by a study group (GETIM) and were accepted by the ethical committee concerned. A prospective study has been carried out since April 1986. Thirty-five cases of tuberculosis with bacilli resistant to rifampicin received daily treatment with 5 to 7 mg/kg of rifabutine combined with several other drugs which were still active in vitro. Sixteen cases of M. xenopi infection occurred in individuals without apparent immune deficiency and they were treated with a daily combination of 5 to 7 mg/kg of rifabutine, 20 mg/kg of ethambutol, 3 to 5 mg/kg of isoniazid and 400 mg of ofloxacin (or 800 mg of pefloxacin). Twenty-one cases of M. avium-intracellulare infection, also in patients without any evident immune deficiency, and fifty-nine cases in patients suffering from the acquired immunodeficiency syndrome (AIDS), were treated with a similar combination in which the fluoroquinolone was replaced with 100 mg of clofazimine. During the first three months of treatment there were few major problems of toxicity or acceptability in the different combinations of drugs with the exception of three cases of leukopenia with thrombocytopenia. The proportion of negative cultures on the third month was 8 out of 24 (33%) for the cases of pulmonary tuberculosis and 10 out of 13 (77%) for the cases of M. xenopi infection, and 6 out of 11 (55%) and 9 out of 13 (69%), respectively, for infections by M. avium-intracellulare in subjects without immune deficiency and in subjects suffering from AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Drug Resistance, Microbial; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Ofloxacin; Rifabutin; Rifampin; Rifamycins; Tuberculosis, Pulmonary

A case of intra-abdominal disease caused by Mycobacterium simiae in a Nepalese adult female is reported. She was treated successfully with combination chemotherapy, despite multiple drug resistance in vitro.

Topics: Abdomen; Adult; Ascitic Fluid; Drug Therapy, Combination; Female; Humans; Isoniazid; Kanamycin; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Ofloxacin; Pyrazinamide; Rifampin

Topics: Child, Preschool; Clofazimine; Consanguinity; Drug Therapy, Combination; Ethambutol; Female; Hepatomegaly; Humans; Immunity, Cellular; Joint Diseases; Mycobacterium Infections; Rifampin; Skin Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

The authors present results of in-vivo and in-vitro studies of combined effect of gentamycin , amikacin and rifampicin , ethambutol, isoniazide on selected standard strains of Mycobacterium sp. (Myc. H37Rv, Myc. An5, Myc. wells, Myc. kirchberg, Myc. kansasii, Myc. intracellulare, and Myc. fortuitum). In in-vitro studies the synergistic effect of gentamycin and amikacin with the tuberculostatic drugs was demonstrable on all Mycobacterium strains. The weakest effect was seen on Myc. fortuitum colonies. In-vivo studies have also shown this synergistic effect on all studied strains, and a much weaker effect when used in monotherapy. The authors have shown the possibility of using combination of gentamycin and amikacin with RMP, EMB, INH in treating Myc. intracellulare infections.

Topics: Amikacin; Anti-Bacterial Agents; Antitubercular Agents; Ethambutol; Gentamicins; Humans; Isoniazid; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin; Species Specificity

The activities of some commonly used antituberculosis drugs were investigated within unstimulated peritoneal macrophages and in 7H-9 medium without Tween 80 using Mycobacterium microti OV254 as the target organism. In macrophage cultures, serial concentrations of isoniazid, rifampin, pyrazinamide, or streptomycin were added after a 2.5-h phagocytosis period. Viable counts were carried out at daily intervals for 5 or 6 days. The patterns of susceptibility to the four drugs were similar for M. microti and Mycobacterium tuberculosis. To ensure comparability with daily drug replacements in the macrophage experiments, the period of exposure to drugs in 7H-9 medium was kept to only 3 days. With in vitro culture at pH 6.4, drug penetration, measured as the ratio of MICs in macrophages to MICs in 7H-9 medium, was approximately 5 for isoniazid, 5 for rifampin, and 10 for streptomycin. With in vitro culture at pH 7.4, drug penetration was 100 for streptomycin, and at pH 5.6 it was 1 for pyrazinamide. Pyrazinamide was only bacteriostatic in macrophages but weakly bactericidal during the first day of exposure in vitro.

Topics: Animals; Antitubercular Agents; Culture Media; Hydrogen-Ion Concentration; In Vitro Techniques; Isoniazid; Macrophages; Mice; Mice, Inbred BALB C; Mycobacterium Infections; Pyrazinamide; Rifampin; Streptomycin; Time Factors

Topics: Adult; Corneal Transplantation; Ethambutol; Eye Injuries; Humans; Keratitis; Male; Minocycline; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Scleral Diseases; Skin Tests

Two cases of Mycobacterium avium-intracellulare complex (MAC) infections are described, and the diagnosis, clinical features, and management of MAC infections are reviewed. In case 1, a four-year-old boy was diagnosed as having both acquired immunodeficiency syndrome (AIDS) and disseminated MAC infection. He was treated with a combination of isoniazid, ethambutol hydrochloride, rifabutin, and clofazimine. Results of susceptibility testing showed that the MAC was susceptible to rifabutin and ethambutol with intermediate susceptibility to isoniazid. The child developed severe adverse effects that necessitated the discontinuation of rifabutin therapy. Despite therapy, blood cultures remained positive for MAC. The child died of disseminated human immunodeficiency virus and MAC infection. In case 2, a 20-month-old girl was found to have a prevertebral retropharyngeal mass caused by MAC. The child did not have evidence of immunologic deficiency. She was treated with streptomycin, ethambutol, clofazimine, and rifabutin. Streptomycin was discontinued after three months. After seven months the mass decreased in size, allowing for surgical resection. Intraoperative cultures were negative for mycobacteria. Ethambutol, rifabutin, and clofazimine were continued for a total of 12 months, at which time the child was determined to be clinically and radiologically cured. Empiric multidrug antituberculous therapy should be initiated in patients with suspected disseminated nontuberculous mycobacterial infection because final isolation, identification, and susceptibility testing may take several weeks. Clofazimine and rifabutin, in combination with isoniazid and ethambutol, may be useful in the treatment of some MAC infections. At least four drugs are given, and regimens often consist of six drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Anti-Infective Agents; Child, Preschool; Ethambutol; Female; Humans; Infant; Isoniazid; Male; Microbial Sensitivity Tests; Mycobacterium avium; Mycobacterium Infections; Rifabutin; Rifampin; Rifamycins; Streptomycin

Topics: Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Male; Middle Aged; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Tuberculosis, Pulmonary

Topics: Animals; Antitubercular Agents; Drug Synergism; Drug Therapy, Combination; Erythromycin; Ethambutol; In Vitro Techniques; Isoniazid; Mice; Mycobacterium; Mycobacterium Infections; Rifampin

A 38-year-old woman presented with small, ulcerated, red or bluish nodules on the right hand, clinically resembling mycobacterial granulomas; these appeared a few months after a bite by a rat, while the patient was collecting frogs in a pond in the Belgian Ardennes. The histopathologic picture was compatible with a diagnosis of mycobacterial infection and rare acid-fast bacilli could be found. Repeated bacteriologic investigations were performed and these led to the identification of a strain displaying characteristics of Mycobacterium gordonae. The skin condition responded well to rifampicin (300 mg/day) within 6 months.

Topics: Adult; Female; Granuloma; Humans; Microbial Sensitivity Tests; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin; Skin Diseases, Infectious

Mycobacterium malmoense was isolated in four different sputum samples of a 45-year-old alcoholic smoker. The biochemical and culture characteristics of this species are described and compared with a reference strain (ATCC 29571). The isolated strain was sensitive in vitro to rifampicine, ethionamide, kanamycine and erythromycin. Therapy consisted of right-upper-lobe lobectomy and a two-year antimicrobial therapy. There was no sign of relapse at the end of the treatment period.

Topics: Bronchoalveolar Lavage Fluid; Erythromycin; Humans; Isoniazid; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Pneumonectomy; Rifampin; Sputum; Switzerland

Inadequate débridement, extensive scarring, and breakdown of the wound have been commonly encountered after surgical débridement has been employed as the initial treatment of infection with Mycobacterium marinum involving the deep structures of the hand. Because of our disappointment with the results of this form of treatment, from 1982 to 1986 we treated twenty-four patients who had such an infection with rifampicin and ethambutol after a diagnostic biopsy was done. Surgical treatment was deferred until it was determined that the infection had not been controlled by the chemotherapy. The clinical outcome for these patients could be divided into three patterns: eleven patients (Group I) had a good result with no complications, three patients (Group II) had delayed healing of the wound, and ten patients (Group III) did not have a good response to conservative treatment and required one or more surgical débridements. Complications were sometimes associated with use of the drugs, and loss of visual acuity was a concern in three patients. In twenty-one (87 per cent) of the patients, at follow-up the function of the treated hand was equal to that of the other hand. Persistent pain, a discharging sinus, and previous local injection of steroids were unfavorable prognostic factors. If these factors are present, surgical débridement is advised.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Debridement; Ethambutol; Female; Hand; Humans; Male; Middle Aged; Mycobacterium Infections; Physical Therapy Modalities; Prognosis; Prospective Studies; Rifampin; Tenosynovitis; Wound Healing; Wrist

Topics: Humans; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Tetracyclines

Topics: Ethambutol; Humans; Male; Middle Aged; Mycobacterium Infections; Rifampin

Fourteen wild strains and 14 relapse or treatment failure isolates of Mycobacterium kansasii were tested and found to be highly susceptible to sulfamethoxazole (SMX), with 26 of 28 isolates having minimal inhibitory concentrations (MIC) of less than or equal to 4 micrograms/ml), using a broth microdilution method. Treatment failure isolates frequently exhibited resistance to rifampin (RMP) (greater than 2 micrograms/ml), isoniazid (INH) (greater than 4 micrograms/ml), and ethambutol (EMB) (greater than 4 micrograms/ml) not seen among the wild strain isolates. Eight patients with cavitary disease caused by RMP-resistant M. kansasii were treated with SMX-containing regimens that also included high dose INH (900 mg), EMB (25 mg/kg), and an aminoglycoside (either streptomycin or amikacin). Patients were treated initially in the hospital for 4 to 10 wk. In 7 of the 8 patients, sputum cultures became negative in a mean of 10 wk (range, 7 to 14 wk). Acquired drug resistance to INH, RMP, and EMB can be demonstrated in M. kansasii, and SMX in combination with other agents chosen on the basis of MIC determinations are effective in the treatment of disease caused by RMP-resistant M. kansasii.

Topics: Adult; Aged; Antitubercular Agents; Dose-Response Relationship, Drug; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Recurrence; Rifampin; Sputum; Sulfonamides

The effect of recombinant murine interferon-gamma (IFN-gamma) on the growth of Listeria monocytogenes for 4 h and Mycobacterium microti for up to 3 days in monolayers of peritoneal macrophages from BALB/c mice was examined by serial viable counts of cell-associated bacteria. Macrophages pretreated with 10 u IFN-gamma per ml were bacteriostatic and with 100 u or 1000 u per ml were bactericidal against L. monocytogenes. Addition of IFN-gamma 3 days before infection caused monolayers to be bactericidal against M. microti mainly during the first 15 min after infection. This was just evident with 10 u IFN-gamma per ml and greater with 100 u or 1000 u per ml. If IFN-gamma was added when phagocytosis of M. microti was complete, about 2 h after infection, its action was only bacteriostatic, the viable counts remaining stationary while those of unexposed monolayers increased. IFN-gamma 100 u per ml added before infection did not alter the bactericidal activity of rifampicin 10 mg/l, nor did it alter the killing curves for isoniazid 1 mg/l or for rifampicin 10 mg/l if added after completion of phagocytosis.

Topics: Animals; Bacterial Infections; Cells, Cultured; Drug Therapy, Combination; Interferon-gamma; Isoniazid; Listeriosis; Lymphokines; Macrophages; Mice; Mice, Inbred BALB C; Mycobacterium Infections; Recombinant Proteins; Rifampin

The antimycobacterial activities of two newer ansamycins, isobutylpiperazinylrifamycin SV (R-76-1) and cyclopentylrifamycin SV (DL 473), were compared with those of rifampin (RMP) both in vitro and in vivo. In terms of minimal inhibitory concentrations against a number of cultivable mycobacteria, R-76-1 was about eight times more active in vitro than RMP; whereas DL 473 was only slightly more active than RMP. Therapeutic activities of R-76-1 versus RMP and DL 473 versus RMP were compared, respectively, in the experimental infection of mice with Mycobacterium lepraemurium by different treatment schedules (immediate and delayed) and dosage regimens. R-76-1 appeared to have been three times more effective than RMP; DL 473 was also more effective than RMP in that an equivalent therapeutic effect could be obtained by fewer doses of DL 473 than of RMP, and in that DL 473 exerted a more prolonged activity than RMP. With the kinetic method and a dosage of 0.001% in the diet, R-76-1 demonstrated a bactericidal-type effect against M. leprae whereas RMP did not; with the proportional bactericidal method, R-76-1 possessed about three times the bactericidal activity of RMP against M. leprae. When drugs were administered once in 4 weeks, the RMP dose required to prevent multiplication of M. leprae in the foot pads of half of the mice was in the range of 1.25 to 2.5 mg/kg; whereas that of DL 473 was less than 0.625 mg/kg. With the proportional bactericidal method, even a single dose of 1.25 mg DL 473 per kg was active against M. leprae; whereas the smallest single active dose of RMP was 10 mg/kg. DL 473 in single doses of 5 mg/kg and 10 mg/kg was significantly more effective than RMP in equal doses and, among the intermittent regimens administered four times, once every 4 weeks, no significant differences of bactericidal activity were observed between RMP at 20 mg/kg and DL 473 at 0.625 mg/kg. A preliminary clinical trial of R-76-1 in 20 patients with lepromatous leprosy showed that the compound, administered in a dosage of 150 mg daily, was very effective.

Topics: Animals; Humans; Leprostatic Agents; Leprosy; Mice; Microbial Sensitivity Tests; Mycobacterium Infections; Mycobacterium leprae; Mycobacterium lepraemurium; Rifampin; Rifamycins

We describe four patients with Mycobacterium marinum infections who did not respond to two- to six-week courses of therapy with tetracycline, minocycline, and doxycycline. All four patients had prompt responses to therapy with either rifampin alone (two patients) or rifampin in combination with ethambutol. Results of antimicrobial sensitivity tests may be helpful in guiding therapy. Rifampin may be the drug of choice for treatment of these infections.

Topics: Adult; Aged; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Male; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin; Tetracycline

Topics: Antitubercular Agents; Child; Child, Preschool; Contraceptives, Oral; Drug Interactions; Drug Labeling; Drug Synergism; Humans; Isoniazid; Mycobacterium Infections; Outpatients; Pyrazinamide; Rifampin; Tuberculin; United States; United States Food and Drug Administration

Infections with Mycobacterium marinum are uncommon in children but should be considered by a physician confronted with chronic, poorly healing skin lesions. A case of such an infection in a 4-year-old child is presented. Presenting signs and symptoms, differential diagnosis, and treatment of these infections are discussed.

Topics: Axilla; Child, Preschool; Combined Modality Therapy; Drainage; Elbow; Ethambutol; Female; Humans; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Skin Diseases, Infectious; Wrist

Topics: Bacterial Infections; Humans; Kinetics; Leprosy; Mycobacterium Infections; Rifampin; Tuberculosis, Pulmonary

Thirty seven patients whose sputum cultures had yielded positive isolates of Mycobacterium malmoense during the years 1978-1983 have been reviewed. Significant pulmonary infection was present in 34 patients (92%), 3 of whom had only single isolates cultured from their sputum. The significance of isolates in the remaining 3 patients was not established. There was pre-existing pulmonary disease in 22 patients and another 4 were taking immuno-suppressive drugs. Various drug regimens were used to treat the condition but the best responses were seen in 5 patients (13.5%) who received 3 standard drugs given for between 18-24 months. Relapse occurred in 3 of another 5 who were treated with the same combination but given for less than 18 months. Omission of ethambutol from this standard regimen was associated with an unfavourable course in another 7 patients. Regimens which included the second line drugs ethionamide and cycloserine were given to 10 patients. The responses in this group were poor and were probably related to drug toxicity and poor patient compliance. Four of these patients eventually underwent successful resectional surgery.

Topics: Adult; Aged; Antitubercular Agents; Drug Resistance, Microbial; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Lung Diseases; Male; Middle Aged; Mycobacterium Infections; Patient Compliance; Rifampin; Sputum; Tuberculosis, Pulmonary

We report a 6 year experience (1979-1984) of isolating Mycobacterium malmoense in the north-east of England. Eleven subjects were involved of whom 10 had active infection--9 pulmonary, one cervical adenitis. The 11 new isolates represent 0.7% of all new mycobacterial isolates during this period and 10% of new non-tuberculous isolates. In all but 2 cases there was pre-existing pulmonary disease and/or a recognised predisposing factor to mycobacterial infection. The organisms were generally insensitive to isoniazid but sensitive to both rifampicin and ethionamide. The results of chemotherapy are described.

Topics: Adult; Drug Therapy, Combination; England; Ethionamide; Female; Humans; Infant; Lung Diseases; Lymphadenitis; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Rifampin; Tuberculosis, Pulmonary

Topics: Adult; Arthritis, Infectious; Drug Combinations; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Male; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin

Topics: Adult; Drug Therapy, Combination; Ethambutol; Female; Humans; Leg Dermatoses; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin

The effects of various chemotherapeutic regimens were investigated in ddY mice infected intravenously with a mouse-virulent strain, 31F093T, of Mycobacterium avium-intracellulare. Evaluation of therapeutic effects was based on serial counts of viable bacilli in the lung, the spleen, and the kidney, as well as on weight and extent of gross diseases of the organs, and on histopathologic examination. Kanamycin alone was effective against the infection. The combination of ethambutol and rifampin with kanamycin (KM-EMB-RMP) decreased counts in the lung. In another 3-drug regimen (kanamycin, ethionamide, and cycloserine), the effect was similar. Two 4-drug regimens, KM-EMB-RMP-CEX and KM-EMB-RMP-MINO, as well as a 5-drug regimen, KM-EMB-RMP-CS-INH, were also compared with the above 3-drug regimens, and only the 5-drug regimen decreased counts in the lung more than the 3-drug regimens did. Even the 5-drug regimen, however, could not eradicate the mycobacteria in the organs of mice, which demonstrates the inveteracy of M. avium-intracellulare infection. The control mice consistently showed grossly visible disease of the lung at 6 wk of infection, and the histopathologic findings were granuloma (3 to 6 wk of infection) and diffuse proliferative change beyond 9 weeks of infection, which was persistent and slowly progressive. The spleens and livers showed extensive granulomatous changes. The subacuteness of grossly visible lung disease with significant multiplication of bacilli in the organ of the control mice in the present murine model should prove useful in evaluating experimental chemotherapy of M. avium-intracellulare infection.

Topics: Animals; Antitubercular Agents; Chronic Disease; Cycloserine; Disease Models, Animal; Drug Therapy, Combination; Ethambutol; Kanamycin; Liver; Lung; Male; Mice; Mycobacterium avium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Spleen; Time Factors

Topics: Ethambutol; Female; Humans; Infant; Isoniazid; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Skin Diseases, Infectious

Thirty-five patients (88% male) with pulmonary infection caused by Mycobacterium kansasii have been reviewed. Sixty-six per cent had pre-existing lung disease, chronic bronchitis and emphysema accounting for half of the disorders. Unilateral lesions were present in 69% of patients whose chest radiographs were reviewed and 90% had cavitating disease. The development of unilateral or bilateral disease appeared to be independent of any delay in starting treatment. Five patients died while receiving treatment, but none of these deaths was due to M kansasii infection. The remaining 30 patients were successfully treated with drug regimens, all of which included rifampicin and 86% of which included ethambutol. There was 100% sputum conversion, with no relapses after a mean follow-up period of five-and-a-half years. Rifampicin and ethambutol given for a mean period of 15 months appeared to be a non-toxic, effective combination.

Topics: Adult; Aged; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Tuberculosis, Pulmonary

Topics: Adult; Female; Humans; Isoniazid; Kidney Transplantation; Leg Dermatoses; Mycobacterium Infections; Rifampin; Skin Diseases, Infectious

Topics: Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Male; Melanoma; Middle Aged; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin; Tuberculosis, Pulmonary

Topics: Humans; Minocycline; Mycobacterium; Mycobacterium Infections; Nontuberculous Mycobacteria; Rifampin; Skin Diseases; Tuberculin Test

Specific pathogen-free B6D2 mice were infected with 10(6) or 10(8) viable Mycobacterium bovis (BCG Pasteur) or Mycobacterium simiae and the in vivo growth curves were correlated with the levels of delayed hypersensitivity developed against a cytoplasmic protein antigen (CPA) injected into a hind footpad at increasing time intervals after infection. Half of the heavily infected, anergic mice were placed on a regimen of 10 mg of rifampin, 5 mg of amikacin and 2 mg of clofazimine per 100 ml of drinking water 2 or 8 weeks into the infection. The number of viable mycobacteria recovered from the lungs and spleens of the treated mice (compared with the corresponding drug-free controls) were reduced by up to 10,000-fold over a 3-month treatment period. Spleen cells were harvested at increasing time intervals from the drug-treated and control mice and T-cell enriched suspensions were tested for blastogenic responsiveness to phytohaemagglutinin (PHA) and to the specific CPA mitogen. The early (day 14) peak in tritiated thymidine ([3H]-TdR) uptake was followed by a sharp drop to near background levels. Cell-mixing experiments demonstrated the presence of a suppressor T-cell population in the heavily infected spleens of the M. simiae-infected mice. The suppressor-cell effect was substantially reduced following combined drug therapy although the specific CPA-mediated response was less affected than the non-specific PHA-mediated response.

Topics: Amikacin; Animals; Clofazimine; Drug Therapy, Combination; Lymphocyte Activation; Mice; Mycobacterium; Mycobacterium Infections; Rifampin; Spleen; T-Lymphocytes, Regulatory

Topics: Adult; Ethambutol; Female; Hand; Humans; Male; Middle Aged; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Tendons

A case of renal infection with Mycobacterium chelonei is described. The infection probably occurred via haematogenous spread from an infected arteriovenous shunt in a uraemic woman. Prolonged treatment with intravenous cefoxitin combined with oral erythromycin and rifampicin eradicated the organism from the urine. Although renal function stabilised for one year, gradual deterioration to end-stage renal failure occurred.

Topics: Adult; Cefoxitin; Drug Therapy, Combination; Erythromycin; Female; Humans; Kidney Diseases; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin

The medical and surgical therapy of 82 cases of atypical mycobacterial adenitis from Dallas and 298 cases from the literature was reviewed. The 92% cure rate in 149 patients with total surgical excision alone was comparable to the 95% cure rate in 156 patients when excision was followed by antituberculous drug therapy. With incision and drainage in 63 patients the cure rate was 16% whether drugs were given or not. Ten patients were initially treated with antituberculous drugs alone and only one was cured. It is concluded that total surgical excision is definitive therapy for this disease and that antituberculous drugs should be used only when surgery cannot be performed or when complete excision is not possible.

Topics: Antitubercular Agents; Child, Preschool; Drainage; Female; Humans; Infant; Infant, Newborn; Lymphadenitis; Male; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Rifampin; Suction

The effectiveness of hyperbaric oxygenation (HBO), heat, and rifampin for treating mice infected with Mycobacterium ulcerans was analyzed. Four hundred mice were innouclated in the hind footpads with 10(8) organisms. The seven treatment groups (50 mice each) were HBO (2.5 ATA for 1.5 h, twice a day), rifampin (RIF) (20 mg/kg body weight/d), heat (mice maintained at 37 degrees C), and all combinations of the three treatments. The severity of infection in the treated mice was compared weekly for 20 weeks with that of infected controls. The most effective treatments were RIF/HEAT and RIF/HBO/HEAT, RIF/HBO/HEAT treatment was further evaluated to determine the effectiveness of treating mice at various stages of infection. Three hundred mice were inoculated in the hind footpads, and, as the infection progressed, they were separated into groups (50 mice/group) according to the severity of infection. The treatment groups were compared to positive controls. The effectiveness of therapy was indirectly proportional to the severity of infection.

Topics: Animals; Hot Temperature; Hyperbaric Oxygenation; Mice; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Skin Ulcer

Topics: Aminosalicylic Acid; Animals; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Isoniazid; Mice; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Streptomycin

Topics: Diabetes Complications; Drug Therapy, Combination; Ethambutol; Female; Hand Dermatoses; Humans; Middle Aged; Mycobacterium Infections; Rifampin; Skin Diseases, Infectious

A patient prviously suspected of having a mycobacterial infection was found to have a Mycobacterium gordonae infection of his prosthetic aortic valve. Following replacement of his infected prosthesis and systemic therapy for two years, the patient has apparently been cured.

Topics: Aortic Valve; Endocarditis, Bacterial; Ethambutol; Heart Valve Prosthesis; Humans; Isoniazid; Male; Middle Aged; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin

Mycobacterium szulgai, a scotochromogenic mycobacterium, is a newly recognized pathogen of man and has been reported to cause pulmonary infections, olecranon bursitis and cervical adenitis. We isolated M. szulfai from granulomatous tissue removed at surgery from a young florist with the carpal tunnel syndrome. The organism was susceptible to ethambutol and rifampin but resistant to isoniazid. Cure was achieved by debridement and chemotherapy with ethambutol and rifampin. Neither the source in our patient nor the natural habitat of M. szulgai is known. Because it resembles M. gordonae and M. flavescens, common scotochromogenic mycobacteria in tapwater, care must be taken to avoid dismissing M. szulgai as a contaminant when it is isolated from tissue.

Topics: Adult; Carpal Tunnel Syndrome; Debridement; Ethambutol; Hand; Humans; Male; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin; Tenosynovitis

Two outbreaks of postoperative wound infections by organisms of the Mycobacterium fortuitum complex have focused attention on this notoriously drug resistant organism. In this report 2 cases are presented which developed infections with this organism, one of which responded to systemic antimicrobials despite discouraging in vitro sensitivities. Surgical debridement must remain the choice of treatment; however, systemic antibiotics may prove effective in some cases.

Topics: Adult; Antitubercular Agents; Drug Resistance, Microbial; Ethambutol; Ethionamide; Humans; Isoniazid; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium; Mycobacterium Infections; Rifampin; Surgical Wound Infection

Five cases of Mycobacterium marinum skin infections were successfully treated with 2 gm of tetracycline hydrochloride daily for periods from four to 12 weeks. In each case, the isolated M marinum was sensitive in vitro to tetracycline at levels from 25 to 50 microgram/ml. Tetracycline is recommended as treatment for extensive or sporotrichoid M marinum infections.

Topics: 4-Aminobenzoic Acid; Adult; Ethambutol; Granuloma; Humans; Isoniazid; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium; Mycobacterium Infections; Rifampin; Skin Diseases, Infectious; Streptomycin; Tetracycline

In 1971, rifampin was approved for treatment of pulmonary tuberculosis and asymptomatic carriers of Neisseria meningitidis. At present, the approved indications remain the same. However, rifampin in conjunction with at least one other antituberculous drug may be of great value in therapy of extrapulmonary tuberculosis and infections due to other susceptible mycobacteria. In addition, results of clinical trials in leprosy have been highly encouraging. Rifampin appears to induce light chain proteinuria in a majority of patients and has been implicated in suppression of both humoral and cell-mediated immune responses. However, these effects appear to have been of little consequence to treated patients. A variety of possibly immunologically mediated reactions to rifampin has been closely associated with irregular administration of the drug. These reactions and hepatic toxcity may be preventable in many patients. Rifampin or one of its congeners, alone or in combination with other antibiotics, may prove useful in treatment of various infectious, and possibly malignant, diseases.

Topics: Animals; Antibody Formation; Antineoplastic Agents; Antiviral Agents; Chemical and Drug Induced Liver Injury; Drug Interactions; Drug Resistance, Microbial; Drug Therapy, Combination; Forecasting; Humans; Immunity, Cellular; Immunosuppressive Agents; Leprosy; Liver; Meningococcal Infections; Mycobacterium Infections; Rifampin; Tuberculosis; Tuberculosis, Pulmonary

Two patients with Mycobacterium kansasii infection of the lung had organisms sensitive to rifampicin. Following treatment, essentially with rifampicin alone, the patients began to excrete organisms completely resistant to rifampicin. The ability of M. kansasii to acquire resistance to rifampicin during treatment has been clearly demonstrated. This reinforces the need to treat this infection with an adequate multiple drug regimen.

Topics: Drug Resistance, Microbial; Humans; Male; Mycobacterium; Mycobacterium Infections; Rifampin; Species Specificity

Topics: Adult; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; Humans; Isoniazid; Lung Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin; Texas

After seven months' continuous treatment for suspected tuberculosis with rifampicin and ethambutol a nine-year-old boy developed polyarthritis, rash and hepatitis in association with anti-native DNA antibodies and positive antinuclear factor. Six weeks after withdrawal of the antituberculosis drugs and conservative management, the boy was clinically well and ten months later he remained well clinically and liver function tests, anti-DNA antibody and antinuclear factor tests were normal.

Topics: Antibodies; Antibodies, Antinuclear; Antibody Specificity; Child; DNA; Ethambutol; Humans; Male; Mycobacterium Infections; Rifampin

Topics: Adult; Ethambutol; Female; Hand; Humans; Isoniazid; Male; Middle Aged; Mycobacterium Infections; Rifampin; Synovectomy

Rifampicin (RMP) and two riminophenazine compounds (B663 and B1912) suppressed the growth of Mycobacterium marinum in vitro and in a mouse footpad infection. At appropriate concentrations and dietary dosage, all three drugs showed bactericidal activity in vitro and in vivo. On the basis of minimum inhibitory concentration, RMP was considerably more active than the other two substances in vitro. However, the rate of bactericidal effect was similar for all three drugs. In vivo, the minimum bactericidal dietary dosages of RMP, B663 and B1912 were 0.03, 0.03 and less than or equal to 0.01%, respectively. Results suggest that these drugs may be of value for the treatment of clinical M. marinum infections.

Topics: Animals; Clofazimine; Mice; Mycobacterium; Mycobacterium Infections; Phenazines; Rifampin

The clinical response of atypical mycobacterial cervical adenitis to standard antituberculous therapy has been disappointing. Surgical procedures in the anterior cervical triangle are difficult and often complete excision is impossible. In each of four children with atypical mycobacterial cervical adenitis in this study, the institution of rifampin therapy was followed by complete resolution. Previously rifampin, a well-tolerated, orally administered drug, had been used effectively with Mycobacterium tuberculosis. The place of this drug as a major alternative to surgical excision in cases of atypical mycobacterial cervical adentis is reviewed.

Topics: Antigens; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Long-Term Care; Lymphadenitis; Male; Mycobacterium Infections; Neck; Rifampin; Skin Tests

Four patients with Mycobacterium kansaii pulmonary infection were followed without treatment for 10 to 14 years after diagnosis. Although spontaneous resolution of active disease occurred 5 years after diagnosis in one patient, slowly progressive disease in the absence of significant symptoms was documented in 3 patients during a 12-to-14-year follow-up period. Administration of antituberculous drugs resulted in rapid resolution of signs of active disease in these patients. These observations added to our limited knowledge of the natural history of M. kansasii disease.

Topics: Adult; Ethambutol; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Isoniazid; Lung Diseases; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Radiography; Rifampin; Vital Capacity

Topics: Ethambutol; Fascia; Humans; Inflammation; Isoniazid; Male; Middle Aged; Mycobacterium Infections; Rifampin; Tendinopathy

Chemotherapy of pulmonary disease due to Mycobacterium kansaii has not always been successful, and resectional surgery has been used frequently in the treatment of this infection. To ascertain the impact of new antimicrobial agents on the treatment of M. kansaii infection, we reviewed the clinical courses of 59 patients treated between 1971 and 1974. Over-all, 92 per cent of patients converted their sputum cultures while receiving drugs, with only one patient undergoing surgical resection. Regimens containing rifampin were universally effective in both initial and retreatment cases; however, they offered no significant advantage over monrifampin regimens in initial treatment cases. In vitro resistance to isoniazid and ethambutol did not adversely affect the results of treatment with these drugs. Owing to the effectiveness of current chemotherapy, parameters such as age, underlying lung disease, or extent of disease were not related to the outcome of therapy. Because 90 per cent of the conversions in successful regimens occur within 4 to 6 months of beginning therapy, patients whose cultures remain positive should be considered for alternate drugs. Because the frequency of relapse after current chemotherapy is not yet clear, and because rifampin appears to be particularly advantageous in retreatment programs, rifampin should be reserved for this role. The total course of treatment should probably span at least 18 months, or 6 months beyond any cultural or radiographic evidence of activity.

Topics: Adult; Drug Resistance, Microbial; Ethambutol; Female; Humans; Isoniazid; Lung Diseases; Male; Mycobacterium; Mycobacterium Infections; Recurrence; Rifampin; Sputum; Streptomycin; Time Factors

Topics: Aged; Aortic Valve Stenosis; Chemical and Drug Induced Liver Injury; Humans; Isoniazid; Liver; Lung Diseases; Lung Diseases, Obstructive; Male; Mycobacterium Infections; Rifampin

A white child with a long history of illness from the age of six was thought at first to have Hodgkin's disease. There followed an acute illness with lesions involving glands, lungs, bone and skin. Mycobacterium avium-intracellulare group (Battey) was isolated from various lesions at the age of thirteen. After six years of continuous treatment the patient, now eighteen, is living a normal life.

Topics: Adolescent; Bone Diseases; Bone Neoplasms; Child; Diagnosis, Differential; Ethambutol; Hodgkin Disease; Humans; Isoniazid; Kanamycin; Male; Mycobacterium; Mycobacterium avium; Mycobacterium Infections; Radiography; Rifampin; Time Factors

Topics: Animals; Mice; Mycobacterium; Mycobacterium Infections; Rifampin; Skin Ulcer

Topics: Anti-Bacterial Agents; Diagnosis, Differential; Ethambutol; Female; Granuloma; Humans; Middle Aged; Mycobacterium; Mycobacterium Infections; Rifampin; Skin Diseases, Infectious; Water Microbiology

Topics: Adult; Diagnosis, Differential; Female; Humans; Isoniazid; Mycobacterium; Mycobacterium Infections; Rifampin; Tuberculosis, Urogenital; Urinary Tract Infections

Topics: Capreomycin; Child; Drug Resistance, Microbial; Ethambutol; Ethionamide; Humans; Isoniazid; Kanamycin; Lung Diseases; Lymphadenitis; Mycobacterium; Mycobacterium Infections; Rifampin; Skin Diseases, Infectious; Sputum; Streptomycin

Topics: Ethambutol; Female; Humans; Isoniazid; Middle Aged; Minnesota; Mycobacterium; Mycobacterium Infections; Radiography, Abdominal; Rifampin; Streptomycin; Urinary Tract Infections; Urography; Urologic Diseases

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Cornea; Edema; Eye Foreign Bodies; Humans; Keratitis; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Ophthalmic Solutions; Ophthalmoscopy; Rifampin; Species Specificity; Visual Acuity

Topics: Adolescent; Adrenal Cortex Hormones; Anemia; Antibodies; BCG Vaccine; Biopsy; Bone Marrow Diseases; Ethambutol; Female; Fever; Hepatomegaly; Humans; Immunity, Cellular; Immunoglobulins; Immunologic Deficiency Syndromes; Iron; Isoniazid; Leukocyte Count; Lymph Nodes; Lymphocytes; Lymphopenia; Mycobacterium bovis; Mycobacterium Infections; Rifampin; Splenic Diseases; Splenomegaly; Tuberculin Test

Topics: Adolescent; Adult; Aged; Aminosalicylic Acids; Antitubercular Agents; Child; Cycloserine; Ethambutol; Ethionamide; Female; Follow-Up Studies; Humans; Isoniazid; Lung Diseases; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Pneumonectomy; Pyrazinamide; Rifampin; Sputum; Streptomycin

Topics: Adult; Aged; Aminosalicylic Acids; Australia; Ethambutol; Female; Humans; Isoniazid; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium; Mycobacterium Infections; Mycobacterium tuberculosis; Rifampin; Streptomycin; Tuberculosis

Topics: Debridement; Ethambutol; Female; Hand Dermatoses; Hand Injuries; Humans; Inflammation; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Radiography; Rifampin; Synovectomy; Water Microbiology

Topics: Adolescent; Adult; Amputation, Surgical; Debridement; Diagnosis, Differential; Ethambutol; Female; Fingers; Hand; Humans; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Osteomyelitis; Rifampin; Skin Diseases, Infectious; Skin Ulcer; Synovitis; Tuberculosis

Topics: Antitubercular Agents; Drug Therapy, Combination; Humans; Leprosy; Mycobacterium Infections; Rifampin; Time Factors; Tuberculosis

Topics: Drug Therapy, Combination; Ethambutol; Humans; Microbial Sensitivity Tests; Mycobacterium Infections; Rifampin; Sulfamethoxazole; Trimethoprim

Topics: Aged; Diagnosis, Differential; Ethambutol; Female; Humans; Lymphoma, Non-Hodgkin; Mycobacterium; Mycobacterium Infections; Rifampin; Skin Diseases, Infectious

Topics: Animals; Body Weight; Coal; Dust; Guinea Pigs; Lung; Lung Diseases; Macrophages; Mycobacterium; Mycobacterium Infections; Organ Size; Pneumoconiosis; Pulmonary Fibrosis; Radiography; Rifampin; Silicon Dioxide; Tracheal Diseases

Topics: Administration, Oral; Carrier State; Drug Interactions; Drug Resistance, Microbial; Drug Synergism; Female; Humans; Male; Mycobacterium Infections; Neisseria meningitidis; Pregnancy; Rifampin; Tuberculosis

Topics: Adult; Aged; Costs and Cost Analysis; Drug Resistance, Microbial; Ethambutol; Female; Follow-Up Studies; Humans; Isoniazid; Male; Middle Aged; Mycobacterium Infections; Rifampin; Sputum; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Rifampin; Sputum

Topics: Humans; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Rifampin; Skin Diseases, Infectious

Topics: Aniline Compounds; Animals; Dapsone; Disease Models, Animal; Drug Combinations; Ethionamide; Humans; Isoniazid; Leprosy; Mice; Models, Biological; Mycobacterium Infections; Phenazines; Pyrazines; Rabbits; Rifampin; Sulfonamides; Trimethoprim

Topics: Animals; Drug Combinations; Foot; Hindlimb; Male; Mice; Mycobacterium Infections; Phenazines; Pyrimethamine; Pyrimidines; Rifampin; Skin Ulcer; Sulfonamides

Topics: Adolescent; Agglutination Tests; Biopsy; Ethambutol; Humans; Male; Mycobacterium; Mycobacterium Infections; Rifampin; Skin Diseases, Infectious

Topics: Biopsy; Bronchoscopy; Child, Preschool; Diagnosis, Differential; Ethionamide; Female; Humans; Lung Diseases; Mycobacterium; Mycobacterium Infections; Rifampin; Tuberculosis, Pulmonary

Topics: Adult; Animals; Biopsy; Fishes; Granuloma; Humans; Male; Mycobacterium; Mycobacterium Infections; Rifampin; Skin; Skin Diseases, Infectious; Swimming Pools

Topics: Administration, Oral; Animals; Dapsone; Demeclocycline; Ethionamide; Female; Isoniazid; Mice; Mice, Inbred Strains; Mycobacterium Infections; Phenylthiourea; Pyrazines; Rifampin; Sulfonamides

Topics: Aged; Animals; Arm; Cycloserine; Fishes; Hand; Humans; Male; Mycobacterium Infections; Rifampin; Skin Diseases, Infectious

Atypical mycobacteria (209 strains) were examined for susceptibility to rifampin by the proportion method by using Middlebrook 7H-10 agar. All strains of Mycobacterium kansasii and tap-water scotochromogens were inhibited by 0.25 to 1 mug of the drug per ml. Seventy-six per cent of M. scrofulaceum and 61% of M. intracellulare strains were susceptible to 4 mug/ml or less; 5% of the former and 8% of the latter were resistant to 16 mug/ml. All strains of M. gastri and M. triviale and most strains of M. terrae were sensitive to 1 to 4 mug/ml. Two strains of M. borstelense were both inhibited by 8 mug/ml. Nearly all strains of M. fortuitum were resistant to the drug. The results of this study suggest that rifampin may be a valuable agent for the treatment of many atypical mycobacterial infections.

Topics: Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Rifampin; Species Specificity

Topics: Animals; Drug Resistance, Microbial; Drug Synergism; Ethionamide; Female; Heart; Isoniazid; Kidney; Mice; Mice, Inbred Strains; Mycobacterium Infections; Rifampin; Streptomycin

Topics: Antitubercular Agents; Child, Preschool; Humans; Male; Mycobacterium bovis; Mycobacterium Infections; Rifampin; Tuberculosis, Lymph Node

Topics: Animals; Drug Combinations; Drug Resistance, Microbial; Ethambutol; Ethionamide; Isoniazid; Mice; Mycobacterium Infections; Phenylthiourea; Rifampin; Streptomycin; Time Factors; Tuberculosis

Topics: Adult; Diagnosis, Differential; Humans; Lung Diseases; Male; Mycobacterium; Mycobacterium Infections; Rifampin; Tuberculosis, Pulmonary

Topics: Animals; Anterior Chamber; Mycobacterium Infections; Mycobacterium tuberculosis; Rabbits; Rifampin; Tuberculosis, Ocular