rifampin and Granuloma

Combinations of rifampin and clindamycin or rifampin, metronidazole, and moxifloxcin have been reported as effective treatments for hidradenitis suppurativa (HS) Hurley Stage 1 and Hurley Stage 2.  Clinical trials suggest that for stage 1 and mild stage 2 HS, clindamycin 300 mg twice daily and rifampin 300 mg twice daily for 10 weeks can substantially abate HS in ~80% of cases and remit HS in ~50% of cases.  Another study notes use of rifampin-moxifloxacin-metronidazole given for 6 weeks, dosed as rifampin (10 mg/kg once daily), moxifloxacin (400 mg daily), and metronidazole (500 mg thrice daily) with the metronidazole stopped at week 6.   Rifampin and moxifloxacin were continued if the HS improved and side effects did not occur.  Using this triple antibiotic regimen remission occurred in 100% Hurley Stage 1, 80% Hurly Stage 2, and 16.7 % of Hurley Stage 3 HS.   The author typically gives HS clindamycin 300 mg and rifampin 300 mg, each twice daily, for 10 weeks and assesses if remission has occurred.  If the patient has not achieved remission the author continues the regimen as long as the patient's clinical status continues to improve without side effects.  The reasons why rifampin is so effective against HS have not been fully defined and might involve rifampin's (1) antibacterial effects (2) effects on bacterial biofilms (3) anti-inflammatory effects (4) effects against granulomas (5) and immunomodulatory effects on neutrophils.  It is notable that rifampin, although not first line, is an effective treatment for Clostridium difficile, a pathogen that arises during treatment with clindamycin.  Thus, rifampin enhances safety when rifampin and clindamycin are combined for the treatment of HS.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Biofilms; Clindamycin; Corynebacterium Infections; Drug Therapy, Combination; Granuloma; Hidradenitis Suppurativa; Humans; Immunologic Factors; Neutrophils; Rifampin; Staphylococcal Infections; Streptococcal Infections

We report two new cases of hepatic brucelloma in addition to the 22 previously reported cases in the literature. Our analysis of these cases reveals certain characteristics. Hepatic brucelloma is a rare localization that follows previously undetected acute brucellosis. Brucelloma is a result of caseification of a granulomatous reaction induced by persistent Brucella in macrophages. Clinical manifestations can mimic malignant liver tumors or pyogenic, amebic liver abscess. Diagnosis is based on the association of characteristic imaging features (central calcification and peripheral necrotic areas), positive serology and hepatic granulomas. Brucella is rarely isolated in the blood or liver. Awareness of this clinical variant can prevent unnecessary laparotomy. Treatment should begin with rifampicine (900 mg per day) and doxycyclin (200 mg per day) for 3 months. If medical treatment is unsuccessful, percutaneous or surgical drainage should be performed. A cure should be achieved in all cases.

Topics: Anti-Bacterial Agents; Brucellosis; Diagnosis, Differential; Doxycycline; Granuloma; Humans; Liver Diseases; Macrophages; Male; Middle Aged; Rifampin

Ocular tuberculosis can manifest in a wide variety of clinical presentations. The prevalence is higher in endemic areas as a cause of granulomatous uveitis. While posterior segment manifestations are well known, anterior segment granulomas alone are relatively rare. We report two cases of unilateral iris granulomata in two young patients who presented with decreased vision and redness and were found to have well-circumscribed iris granulomas. Both underwent systemic evaluation and had a negative Mantoux test. Biopsy pathology of the lesions revealed granulomatous inflammation but were negative for PCR, staining, and culture for TB. One patient turned out to have multiple pulmonary lesions. The ocular condition initially worsened with steroid therapy alone and improved and resolved completely after starting a 9 months course of anti-tubercular therapy (ATT).

Topics: Adult; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Granuloma; Humans; Iris Diseases; Isoniazid; Male; Microscopy, Acoustic; Pyrazinamide; Rifampin; Tuberculin Test; Tuberculosis, Ocular

Tuberculosis (TB) causes a global burden with its high rates of infection and death, especially the irrepressible threats of latent infection and drug resistance. Therefore, it is important to construct efficient theranostics for the prevention and control of TB. Herein, we created a targeted theranostic strategy for TB with a rifampicin-loaded aggregation-induced emission (AIE) carrier and performed testing in laboratory animals. The AIE carrier was constructed to localize in the granulomas and emit fluorescent signals at the early stage of infection, enabling the early diagnosis of TB. Subsequently, reactive oxygen species (ROS) were generated to eradicate infection, and the loaded rifampicin (RIF) was released for the synergistic treatment of persistent bacteria. Furthermore, targeted TB therapy was performed with the light-controlled release of ROS and accurate delivery of RIF, which realizes an anti-infection effect, providing an especially important treatment for drug-resistant TB. Thus, targeted theranostics for TB in laboratory animals possess the potential to become granulomas-tracking and anti-infection strategies for the diagnosis and treatment of TB.

Topics: Animals; Granuloma; Mycobacterium tuberculosis; Precision Medicine; Rifampin; Tuberculosis

Up to 1.3 million children from the former Soviet Union (fSU) and Eastern Europe have been placed in institutional care worldwide. With the hope of ensuring the child's health in the immediate post-adoption period, these children are known to receive many injections of vaccines, vitamins, and medications, many unnecessary and often administered with unsafe technique. This practice can lead to formation of suppurative granulomas in these children. Though rare, dermatologists should be aware of these conditions in adoptees from Eastern Europe.

Topics: Abscess; Child, Adopted; Clarithromycin; Europe, Eastern; Female; Granuloma; Humans; Infant; Injections, Intramuscular; Rifampin; Risk Assessment; Russia; Skin Diseases; USSR

Topics: Adolescent; Adult; Antitubercular Agents; Choroid Diseases; Drug Combinations; Ethambutol; Female; Granuloma; Humans; Immunocompetence; Isoniazid; Magnetic Resonance Imaging; Male; Pyrazinamide; Rifampin; Tomography, X-Ray Computed; Tuberculosis, Ocular; Tuberculosis, Pulmonary; Ultrasonography

Topics: Administration, Intravesical; Aged; Balanitis; BCG Vaccine; Drug Therapy, Combination; Granuloma; Humans; Isoniazid; Lymphadenitis; Male; Rifampin

Drug resistant tuberculosis is increasing world-wide. Resistance against isoniazid (INH), rifampicin (RIF), or both (multi-drug resistant TB, MDR-TB) is of particular concern, since INH and RIF form part of the standard regimen for TB disease. While it is known that suboptimal treatment can lead to resistance, it remains unclear how host immune responses and antibiotic dynamics within granulomas (sites of infection) affect emergence and selection of drug-resistant bacteria. We take a systems pharmacology approach to explore resistance dynamics within granulomas. We integrate spatio-temporal host immunity, INH and RIF dynamics, and bacterial dynamics (including fitness costs and compensatory mutations) in a computational framework. We simulate resistance emergence in the absence of treatment, as well as resistance selection during INH and/or RIF treatment. There are four main findings. First, in the absence of treatment, the percentage of granulomas containing resistant bacteria mirrors the non-monotonic bacterial dynamics within granulomas. Second, drug-resistant bacteria are less frequently found in non-replicating states in caseum, compared to drug-sensitive bacteria. Third, due to a steeper dose response curve and faster plasma clearance of INH compared to RIF, INH-resistant bacteria have a stronger influence on treatment outcomes than RIF-resistant bacteria. Finally, under combination therapy with INH and RIF, few MDR bacteria are able to significantly affect treatment outcomes. Overall, our approach allows drug-specific prediction of drug resistance emergence and selection in the complex granuloma context. Since our predictions are based on pre-clinical data, our approach can be implemented relatively early in the treatment development process, thereby enabling pro-active rather than reactive responses to emerging drug resistance for new drugs. Furthermore, this quantitative and drug-specific approach can help identify drug-specific properties that influence resistance and use this information to design treatment regimens that minimize resistance selection and expand the useful life-span of new antibiotics.

Topics: Antitubercular Agents; Computer Simulation; Drug Resistance, Bacterial; Drug Resistance, Multiple; Granuloma; Isoniazid; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant

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Topics: Adult; Anti-Bacterial Agents; Antitubercular Agents; Clarithromycin; Diagnosis, Differential; Ethambutol; Granuloma; Humans; Immunocompromised Host; Male; Mycobacterium avium Complex; Polymerase Chain Reaction; Rifampin; Spleen; Splenic Diseases

Topics: Axilla; BCG Vaccine; Consanguinity; Diagnosis, Differential; Granuloma; Humans; Infant; Isoniazid; Lymphadenitis; Male; Receptors, Interleukin-12; Rifampin

Topics: Adult; Antibiotics, Antitubercular; Automation, Laboratory; Bacterial Proteins; Biopsy; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Endometrium; Female; Granuloma; Hospitals, University; Humans; India; Infertility, Female; Molecular Typing; Mycobacterium tuberculosis; Real-Time Polymerase Chain Reaction; Rifampin; Sensitivity and Specificity; Tuberculosis, Female Genital; Young Adult

While active tuberculosis (TB) is a treatable disease, many complex factors prevent its global elimination. Part of the difficulty in developing optimal therapies is the large design space of antibiotic doses, regimens and combinations. Computational models that capture the spatial and temporal dynamics of antibiotics at the site of infection can aid in reducing the design space of costly and time-consuming animal pre-clinical and human clinical trials. The site of infection in TB is the granuloma, a collection of immune cells and bacteria that form in the lung, and new data suggest that penetration of drugs throughout granulomas is problematic. Here we integrate our computational model of granuloma formation and function with models for plasma pharmacokinetics, lung tissue pharmacokinetics and pharmacodynamics for two first line anti-TB antibiotics. The integrated model is calibrated to animal data. We make four predictions. First, antibiotics are frequently below effective concentrations inside granulomas, leading to bacterial growth between doses and contributing to the long treatment periods required for TB. Second, antibiotic concentration gradients form within granulomas, with lower concentrations toward their centers. Third, during antibiotic treatment, bacterial subpopulations are similar for INH and RIF treatment: mostly intracellular with extracellular bacteria located in areas non-permissive for replication (hypoxic areas), presenting a slowly increasing target population over time. Finally, we find that on an individual granuloma basis, pre-treatment infection severity (including bacterial burden, host cell activation and host cell death) is predictive of treatment outcome.

Topics: Animals; Anti-Bacterial Agents; Antitubercular Agents; Calibration; Computer Simulation; Disease Models, Animal; Dose-Response Relationship, Drug; Granuloma; Humans; Immunity; Isoniazid; Mice; Models, Biological; Mycobacterium tuberculosis; Primates; Rifampin; Time Factors; Treatment Outcome; Tuberculosis

Improvement in tuberculosis treatment regimens requires selection of antibiotics and dosing schedules from a large design space of possibilities. Incomplete knowledge of antibiotic and host immune dynamics in tuberculosis granulomas impacts clinical trial design and success, and variations among clinical trials hamper side-by-side comparison of regimens. Our objective is to systematically evaluate the efficacy of isoniazid and rifampin regimens, and identify modifications to these antibiotics that improve treatment outcomes.. We pair a spatio-temporal computational model of host immunity with pharmacokinetic and pharmacodynamic data on isoniazid and rifampin. The model is calibrated to plasma pharmacokinetic and granuloma bacterial load data from non-human primate models of tuberculosis and to tissue and granuloma measurements of isoniazid and rifampin in rabbit granulomas. We predict the efficacy of regimens containing different doses and frequencies of isoniazid and rifampin. We predict impacts of pharmacokinetic/pharmacodynamic modifications on antibiotic efficacy. We demonstrate that suboptimal antibiotic concentrations within granulomas lead to poor performance of intermittent regimens compared to daily regimens. Improvements from dose and frequency changes are limited by inherent antibiotic properties, and we propose that changes in intracellular accumulation ratios and antimicrobial activity would lead to the most significant improvements in treatment outcomes. Results suggest that an increased risk of drug resistance in fully intermittent as compared to daily regimens arises from higher bacterial population levels early during treatment.. Our systems pharmacology approach complements efforts to accelerate tuberculosis therapeutic development.

Topics: Animals; Antitubercular Agents; Computer Simulation; Drug Resistance, Bacterial; Granuloma; Isoniazid; Mycobacterium tuberculosis; Rifampin; Treatment Outcome; Tuberculosis

Nanoparticles (NPs) enclosing antibiotics have provided promising therapy against Mycobacterium tuberculosis (Mtb) in different mammalian models. However, the NPs were not visualized in any of these animal studies. Here, we introduce the transparent zebrafish embryo as a system for noninvasive, simultaneous imaging of fluorescent NPs and the fish tuberculosis (TB) agent Mycobacterium marinum (Mm). The study was facilitated by the use of transgenic lines of macrophages, neutrophils, and endothelial cells expressing fluorescent markers readily visible in the live vertebrate. Intravenous injection of Mm led to phagocytosis by blood macrophages. These remained within the vasculature until 3 days postinfection where they started to extravasate and form aggregates of infected cells. Correlative light/electron microscopy revealed that these granuloma-like structures had significant access to the vasculature. Injection of NPs induced rapid uptake by both infected and uninfected macrophages, the latter being actively recruited to the site of infection, thereby providing an efficient targeting into granulomas. Rifampicin-loaded NPs significantly improved embryo survival and lowered bacterial load, as shown by quantitative fluorescence analysis. Our results argue that zebrafish embryos offer a powerful system for monitoring NPs in vivo and rationalize why NP therapy was so effective against Mtb in earlier studies; bacteria and NPs share the same cellular niche.

Topics: Animals; Anti-Bacterial Agents; Biological Transport; Coumarins; Drug Carriers; Embryo, Nonmammalian; Granuloma; Lactic Acid; Macrophages; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Nanoparticles; Optical Imaging; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rhodamines; Rifampin; Thiazoles; Tuberculosis; Zebrafish

Topics: Adult; Clofazimine; Dapsone; Drug Therapy, Combination; Granuloma; Guinea; Histiocytes; Humans; Leprostatic Agents; Leprosy, Lepromatous; Male; Morocco; Rifampin; Staining and Labeling

Gastric tuberculosis is an uncommon manifestation of extra-pulmonary tuberculosis infection. The clinical signs of this type of infection are nonspecific and misleading. Clinically gastric tuberculosis resembles peptic ulcer disease or malignancy. We report a case of gastric tuberculosis, which was treated as acid peptic disease, in an Iranian immunocompetent adult with no pulmonary tuberculosis, who received surgery for gastric cancer. Diagnosis was based on PCR despite the detection of negative acid-fast bacilli in the histopathologic specimen. We recommend PCR for Mycobacterium tuberculosis to be done when granuloma or caseation is detected on biopsy in patients who are suspected of having gastric malignancy or acid peptic diseases.

Topics: Adult; Antitubercular Agents; Diagnostic Errors; Gastrectomy; Gastric Mucosa; Granuloma; Humans; Male; Mycobacterium tuberculosis; Rifampin; Stomach Neoplasms; Tuberculosis

Tuberculosis (TB) is responsible for death of nearly two million people in the world annually. Upon infection, Mycobacterium tuberculosis (Mtb) causes formation of granuloma where the pathogen goes into dormant state and can live for decades before resuscitation to develop active disease when the immune system of the host is weakened and/or suppressed. In an attempt to better understand host-pathogen interactions, several groups have been developing in vitro models of human tuberculosis granuloma. However, to date, an in vitro granuloma model in which Mtb goes into dormancy and can subsequently resuscitate under conditions that mimic weakening of the immune system has not been reported. We describe the development of a biomimetic in vitro model of human tuberculosis granuloma using human primary leukocytes, in which the Mtb exhibited characteristics of dormant mycobacteria as demonstrated by (1) loss of acid-fastness, (2) accumulation of lipid bodies (3) development of rifampicin-tolerance and (4) gene expression changes. Further, when these micro granulomas were treated with immunosuppressant anti-tumor necrosis factor-alpha monoclonal antibodies (anti-TNFα mAbs), resuscitation of Mtb was observed as has been found in humans. In this human in vitro granuloma model triacylglycerol synthase 1deletion mutant (Δtgs1) with impaired ability to accumulate triacylglycerides (TG), but not the complemented mutant, could not go into dormancy. Deletion mutant of lipY, with compromised ability to mobilize the stored TG, but not the complemented mutant, was unable to come out of dormancy upon treatment with anti-TNFα mAbs. In conclusion, we have developed an in vitro human tuberculosis granuloma model that largely exhibits functional features of dormancy and resuscitation observed in human tuberculosis.

Topics: Antibiotics, Antitubercular; Antibodies, Neutralizing; Bacterial Proteins; Drug Resistance, Bacterial; Gene Deletion; Gene Expression; Granuloma; Host-Pathogen Interactions; Humans; Latent Tuberculosis; Lipase; Models, Biological; Mutation; Mycobacterium tuberculosis; Rifampin; Triglycerides; Tumor Necrosis Factor-alpha

Standard antituberculosis (anti-TB) therapy requires the use of multiple drugs for a minimum of 6 months, with variable outcomes that are influenced by a number of microbiological, pathological, and clinical factors. This is despite the availability of antibiotics that have good activity against Mycobacterium tuberculosis in vitro and favorable pharmacokinetic profiles in plasma. However, little is known about the distribution of widely used antituberculous agents in the pulmonary lesions where the pathogen resides. The rabbit model of TB infection was used to explore the hypothesis that standard drugs have various abilities to penetrate lung tissue and lesions and that adequate drug levels are not consistently reached at the site of infection. Using noncompartmental and population pharmacokinetic approaches, we modeled the rate and extent of distribution of isoniazid, rifampin, pyrazinamide, and moxifloxacin in rabbit lung and lesions. Moxifloxacin reproducibly showed favorable partitioning into lung and granulomas, while the exposure of isoniazid, rifampin, and pyrazinamide in lesions was markedly lower than in plasma. The extent of penetration in lung and lesions followed different trends for each drug. All four agents distributed rapidly from plasma to tissue with equilibration half-lives of less than 1 min to an hour. The models adequately described the plasma concentrations and reasonably captured actual lesion concentrations. Though further refinement is needed to accurately predict the behavior of these drugs in human subjects, our results enable the integration of lesion-specific pharmacokinetic-pharmacodynamic (PK-PD) indices in clinical trial simulations and in in vitro PK-PD studies with M. tuberculosis.

Topics: Animals; Antitubercular Agents; Aza Compounds; Biological Availability; Disease Models, Animal; Drug Administration Schedule; Female; Fluoroquinolones; Granuloma; Humans; Isoniazid; Lung; Moxifloxacin; Mycobacterium tuberculosis; Pyrazinamide; Quinolines; Rabbits; Rifampin; Tissue Extracts; Tuberculosis, Pulmonary

Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against Mycobacterium tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease.

Topics: Animals; BCG Vaccine; Combined Modality Therapy; Female; Granuloma; Guinea Pigs; Isoniazid; Lung; Mycobacterium tuberculosis; Pyrazinamide; Rifampin; Tuberculosis

With a host of new antitubercular chemotherapeutics in development, methods to assess the activity of these agents beyond mouse efficacy are needed to prioritize combinations for clinical trials. Lesions in Mycobacterium tuberculosis-infected rabbits are hypoxic, with histopathologic features that closely resemble those of human tuberculous lesions. Using [(18)F]2-fluoro-deoxy-d-glucose ([(18)F]FDG) positron emission tomography-computed tomography (PET-CT) imaging, we studied the dynamics of tuberculosis infection in rabbits, revealing an initial inflammatory response followed by a consolidative chronic disease. Five weeks after infection, as much as 23% of total lung volume was abnormal, but this was contained and to some extent reversed naturally by 9 weeks. During development of this chronic state, individual lesions in the same animal had very different fates, ranging from complete resolution to significant progression. Lesions that remained through the initial stage showed an increase in volume and tissue density over time by CT. Initiation of chemotherapy using either isoniazid (INH) or rifampin (RIF) during chronic infection reduced bacterial load with quantitative changes in [(18)F]FDG uptake, lesion density and total lesion volume measured by CT. The [(18)F]FDG PET uptake in lesions was significantly reduced with as little as 1 week of treatment, while the volume and density of lesions changed more slowly. The results from this study suggest that rabbits may be a useful surrogate species for evaluating novel chemotherapies and understanding changes in both PET and CT scans in human clinical trials.

Topics: Animals; Antitubercular Agents; Bacterial Load; Disease Models, Animal; Fluorodeoxyglucose F18; Granuloma; Isoniazid; Lung; Multimodal Imaging; Mycobacterium tuberculosis; Positron-Emission Tomography; Rabbits; Radiopharmaceuticals; Random Allocation; Rifampin; Tomography, X-Ray Computed; Tuberculosis, Pulmonary

Topics: Administration, Oral; Adult; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Granuloma; Humans; Isoniazid; Male; Prednisolone; Pyrazinamide; Retinal Vasculitis; Rifampin; Tuberculosis, Ocular; Visual Acuity; Vitreous Hemorrhage

Paragonimiasis is a food-borne zoonosis caused by a trematode of the genus Paragonimus(1,2). Infestation is rare in Spain, but the influx of people from endemic areas should make us keep this condition in the differential diagnosis of our patients(2,5). We report the case a patient from Ecuador and resident in Spain for 7 years with active pulmonary tuberculosis on arrival in Spain and later diagnosed with of pulmonary paragonimiasis due to persistent haemoptysis. The diagnosis was established by surgical lung specimen showing granulomas containing parasite eggs and the macroscopic view of the fluke within a lung cavity. Initial tuberculosis treatment and current treatment with praziquantel controlled both conditions.

Topics: Adult; Animals; Anthelmintics; Antitubercular Agents; Caulobacteraceae; Delayed Diagnosis; Ecuador; Ethambutol; Food Parasitology; Gram-Negative Bacterial Infections; Granuloma; Hemoptysis; Humans; Isoniazid; Lung Diseases, Parasitic; Male; Paragonimiasis; Pneumonia, Bacterial; Praziquantel; Pyrazinamide; Radiography; Rifampin; Spain; Tuberculosis, Pulmonary

Tuberculosis (TB) remains the "great pretender." We report the case of a 10-year-old female, who presented with a mass in the left chest that was suspected initially to be a tumor. This was later confirmed to be tuberculous in nature, with dissemination to the liver. A large granuloma eventually replaced the left lung, leaving her with "tuberculous destroyed lung" (TDL), an extremely rare, life-threatening sequela of the disease. We review the pathophysiology, radiologic findings, and management options, which includes pneumonectomy, for this seldom seen but preventable condition.

Topics: Antitubercular Agents; Child; Drug Therapy, Combination; Ethambutol; Female; Granuloma; Humans; Isoniazid; Lung; Lung Neoplasms; Mycobacterium tuberculosis; Pyrazinamide; Radiography; Rifampin; Treatment Outcome; Tuberculosis, Hepatic; Tuberculosis, Pulmonary

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

A case of Mycobacterium Marinum infection of the nasal cavity is described. A 57 years old man was being on Infliximab for 2 years for severe psoriasis presented with five months history of epistaxis, nasal blockage and snoring. Local examination revealed bilateral nasal mass. The diagnosis of mycobacterial infection was suspected based upon the histopathological finding of granuloma in the biopsy specimen, and later confirmed by Mycobacterial culture. The patient was treated with 3 months therapy of Ethambutol and Rifampicin with good clinical response.The clinical presentation of the case is discussed with a review of the literature about current guidelines for prophylaxis and other preventive strategy for infection among patients receiving TNF antagonists.

Topics: Anti-Inflammatory Agents; Antibodies, Monoclonal; Antitubercular Agents; Ethambutol; Granuloma; Humans; Infliximab; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Rifampin; Treatment Outcome

Infection with Mycobacterium ulcerans involves a devastating skin disease called Buruli ulcer (BU). Currently, dual therapy with rifampicin and streptomycin (R/S) for 8 weeks as well as surgery are the standard treatments.. To elucidate the processes taking place in BU lesions in the course of chemotherapy we performed an in-depth histological analysis of lesions after 4 weeks of R/S treatment and compared results with findings in untreated lesions and lesions treated for 8 weeks.. Tissue specimens were collected from patients who had no treatment and from patients after 4 and 8 weeks of R/S treatment. The main features evaluated were local immune responses, histopathological alterations and bacterial distribution.. After 4 weeks of R/S treatment we observed a large proportion of mycobacteria inside macrophages, occasionally forming globus-like aggregations. While distinct bands of inflammatory leucocytes surrounded the necrotic core in an ulcer and early granuloma formation was apparent in the healthy-appearing margins, acute cellular infiltration covering the whole lesion had developed in a nodular lesion. In contrast, ulcerative lesions after 8 weeks of chemotherapy showed intra- and extracellular bacterial debris as well as the presence of extensive chronic infiltrates forming huge granulomas.. R/S treatment of BU results in a rapid onset of local cellular immune responses associated with phagocytosis of the extracellular M. ulcerans. This may be related to declining levels of the macrolide toxin mycolactone in the tissue, thus leading to an enhanced chemotherapy-induced clearance of the infection.

Topics: Adolescent; Anti-Bacterial Agents; Buruli Ulcer; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Child; Drug Therapy, Combination; Female; Granuloma; Humans; Macrophages; Male; Middle Aged; Phagocytosis; Rifampin; Streptomycin; Treatment Outcome

A 22-year-old woman presented with recurrent non-ulcerating skin nodules overlying the great saphenous vein on the anteromedial lower legs. Histology showed a granulomatous phlebitis, and polymerase chain reaction performed on lesional skin detected DNA specific for Mycobacterium tuberculosis. The lesions resolved with anti-tuberculous therapy. This case may be a further example of nodular granulomatous phlebitis, a phlebitic tuberculid.

Topics: Adult; Antitubercular Agents; Diagnosis, Differential; Female; Granuloma; Humans; Isoniazid; Mycobacterium tuberculosis; Panniculitis; Phlebitis; Rifampin; Treatment Outcome; Tuberculosis, Cutaneous

Mathematical models for the population dynamics of de novo resistant Mycobacterium tuberculosis within individuals are studied. The models address the use of one or two antimicrobial drugs for treating latent tuberculosis (TB). They consider the effect of varying individual immune response strength on the dynamics for the appearance of resistant bacteria. From the analysis of the models, equilibria and local stabilities are determined. For assessing temporal dynamics and global stability for sensitive and drug-resistant bacteria, numerical simulations are used. Results indicate that for a low bacteria load that is characteristic of latent TB and for small reduction in an immune response, the use of a single drug is capable of curing the infection before the appearance of drug resistance. However, for severe immune deficiency, the use of two drugs will provide a larger time period before the emergence of resistance. Therefore, in this case, two-drugs treatment will be more efficient in controlling the infection.

Topics: Algorithms; Anti-Bacterial Agents; Computer Simulation; Drug Resistance, Microbial; Drug Therapy, Combination; Granuloma; Humans; Isoniazid; Models, Biological; Mycobacterium tuberculosis; Rifampin; Tuberculosis, Pulmonary

Etanercept is a tumor necrosis factor (TNF) inhibitor that has been licensed in the United States for the treatment of adult and juvenile rheumatoid arthritis as well as psoriatic arthritis. Reactivation of tuberculosis is a complication of its use. We report the first case of tuberculous uveitis due to etanercept.. We performed a clinical chart review.. A 58-year-old Caucasian woman was referred to our hospital for chronic unilateral granulomatous panuveitis of the right eye (RE). She was on etanercept and methotrexate for rheumatoid arthritis. Since the patient was immunosuppressed with etanercept and since the uveitis was granulomatous we considered tuberculosis as a possible etiology. An aqueous humor tap was performed and sent for polymerase chain reaction analyses of Herpes simplex, Herpes zoster, and Mycobacterium tuberculosis (MT). This last test was positive. Another aqueous humor sample was taken and sent for microscopic examination of sputum for acid-fast bacilli and culture, both of which were positive for MT. A diagnosis of tuberculous uveitis was established; the patient was treated with rifampin, isoniazid pyrazinamide, and ethambutol and etanercept was stopped. Four months later there were no cells in the anterior chamber and the vitreous was clear.. To our knowledge this is the first reported case of tuberculous uveitis following treatment with etanercept. This etiology has to be considered in patients taking this drug who present with intraocular inflammation.

Topics: Antirheumatic Agents; Antitubercular Agents; Aqueous Humor; Arthritis, Rheumatoid; Drug Therapy, Combination; Etanercept; Female; Granuloma; Humans; Immunoglobulin G; Isoniazid; Middle Aged; Mycobacterium tuberculosis; Panuveitis; Pyrazinamide; Receptors, Tumor Necrosis Factor; Retrospective Studies; Rifampin; Tuberculosis, Ocular

The lengthy chemotherapy of tuberculosis reflects the ability of a small subpopulation of Mycobacterium tuberculosis bacteria to persist in infected individuals. To date, the exact location of these persisting bacteria is not known. Lung lesions in guinea pigs infected with M. tuberculosis have striking similarities, such as necrosis, mineralization, and hypoxia, to natural infections in humans. Guinea pigs develop necrotic primary lesions after aerosol infection that differ in their morphology compared to secondary lesions resulting from hematogenous dissemination. In infected guinea pigs conventional therapy for tuberculosis during 6 weeks reduced the bacterial load by 1.7 logs in the lungs and, although this completely reversed lung inflammation associated with secondary lesions, the primary granulomas remained largely unaffected. Treatment of animals with the experimental drug R207910 (TMC207) for 6 weeks was highly effective with almost complete eradication of the bacteria throughout both the primary and the secondary lesions. Most importantly, the few remnants of acid-fast bacilli remaining after R207910 treatment were to be found extracellular, in a microenvironment of residual primary lesion necrosis with incomplete dystrophic calcification. This zone of the primary granuloma is hypoxic and is morphologically similar to what has been described for human lung lesions. These results show that this acellular rim may, therefore, be a primary location of persisting bacilli withstanding drug treatment.

Topics: Animals; Antibiotics, Antitubercular; Antitubercular Agents; Colony Count, Microbial; Diarylquinolines; Female; Granuloma; Guinea Pigs; Hypoxia; Isoniazid; Lung; Mycobacterium tuberculosis; Nitroimidazoles; Pyrazinamide; Quinolines; Radiation-Sensitizing Agents; Rifampin; Spleen; Tuberculosis

Topics: Diagnosis, Differential; Drug Therapy, Combination; Granuloma; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Ofloxacin; Rifampin; Skin Diseases

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

Nontuberculous mycobacteria (NTM) are increasingly recognized as important pulmonary pathogens. Mycobacterium avium intracellulare complex (MAC) causes most lung infections due to NTM. Patients with preexisting lung disease or immunodeficiency are at greatest risk for developing MAC infection. The majority of MAC pulmonary cases, however, occur in immunocompetent elderly women in association with nodular infiltrates and bronchiectasis. More recently, pulmonary disease has also been described in immunocompetent patients after exposure to MAC-contaminated hot tubs. We describe a case of aggressive MAC lung disease in a young immunocompetent female patient without preexisting lung disease whose clinical and pathologic characteristics do not fit into any of these categories and may represent a unique manifestation of MAC lung disease.

Topics: Adult; Amikacin; Biopsy; Clarithromycin; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Female; Granuloma; Humans; Lung; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Necrosis; Pneumonia, Bacterial; Prednisone; Rifampin; Sputum; Tomography, X-Ray Computed

Mycobacterium tuberculosis residing within pulmonary granulomas and cavities represents an important reservoir of persistent organisms during human latent tuberculosis infection. We present a novel in vivo model of tuberculosis involving the encapsulation of bacilli in semidiffusible hollow fibers that are implanted subcutaneously into mice. Granulomatous lesions develop around these hollow fibers, and in this microenvironment, the organisms demonstrate an altered physiologic state characterized by stationary-state colony-forming unit counts and decreased metabolic activity. Moreover, these organisms show an antimicrobial susceptibility pattern similar to persistent bacilli in current models of tuberculosis chemotherapy in that they are more susceptible to the sterilizing drug, rifampin, than to the bactericidal drug isoniazid. We used this model of extracellular persistence within host granulomas to study both gene expression patterns and mutant survival patterns. Our results demonstrate induction of dosR (Rv3133c) and 20 other members of the DosR regulon believed to mediate the transition into dormancy, and that rel(Mtb) is required for Mycobacterium tuberculosis survival during extracellular persistence within host granulomas. Interestingly, the dormancy phenotype of extracellular M. tuberculosis within host granulomas appears to be immune mediated and interferon-gamma dependent.

Topics: Animals; Cell Survival; Disease Models, Animal; Female; Gene Expression Regulation, Bacterial; Granuloma; Isoniazid; Mice; Mice, Hairless; Mice, Inbred BALB C; Mutation; Mycobacterium tuberculosis; Oligonucleotide Array Sequence Analysis; Phenotype; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; Time Factors; Up-Regulation

Topics: Antibiotics, Antitubercular; Biopsy; Cat-Scratch Disease; Fever; Granuloma; Humans; Infant; Male; Rifampin; Spleen; Splenomegaly

Leprosy is an infectious disease of prevalence still high in endemic areas in Brazil. The neurological presentation depends on the involved nerve and is usually associated with skin lesions and the formation of multiple abscesses. We present a case of isolated tuberculoid leprosy, discuss the occurrence, the differential diagnosis and the treatment of this rare presentation and reaffirm the importance of considering leprosy in the differential diagnosis of patients with polyneuropathy or nerve enlargement with no skin lesions.

Topics: Adult; Antibiotics, Antitubercular; Brazil; Dapsone; Forearm; Granuloma; Humans; Leprostatic Agents; Leprosy, Tuberculoid; Male; Peripheral Nervous System Diseases; Rifampin; Treatment Outcome

TNF-deficient mice are highly susceptible to Mycobacterium tuberculosis H37Rv infection. Here we asked whether TNF is required for postinfectious immunity in aerosol-infected mice. Chemotherapy for 4 wk commencing 2 wk postinfection reduced CFU to undetectable levels. While wild-type mice had a slight rise in CFU, but controlled infection upon cessation of chemotherapy, TNF-deficient mice developed reactivation of infection with high bacterial loads in lungs, spleen, and liver, which was fatal within 13-18 wk. The increased susceptibility of TNF-deficient mice was accompanied by diminished recruitment and activation of T cells and macrophages into the lung, with defective granuloma formation and reduced inducible NO synthase expression. Reduced chemokine production in the lung might explain suboptimal recruitment and activation of T cells and uncontrolled infection. Therefore, despite a massive reduction of the mycobacterial load by chemotherapy, TNF-deficient mice were unable to compensate and mount a protective immune response. In conclusion, endogenous TNF is critical to maintain latent tuberculosis infection, and in its absence no specific immunity is generated.

Topics: Animals; Cell Migration Inhibition; Chemokines; Down-Regulation; Granuloma; Isoniazid; Lymphocyte Activation; Lymphocyte Subsets; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium tuberculosis; Necrosis; Pneumonia, Bacterial; Recurrence; Rifampin; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha

A 36-year-old man with treated hairy cell leukemia developed a skin infection due to Mycobacterium marinum. A spectrum of atypical cutaneous mycobacteriosis presentations with immunosuppression can be found. The recognition of the disease needs cutaneous biopsies for histopathology and its identification by specific laboratory methods to adapt treatment.

Topics: Adult; Biopsy; Clarithromycin; Drug Therapy, Combination; Granuloma; Humans; Leukemia, Hairy Cell; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium marinum; Rifampin; Skin Diseases, Bacterial

Topics: Anti-Infective Agents; Drug Therapy, Combination; Granuloma; Humans; Leprostatic Agents; Leprosy; Minocycline; Ofloxacin; Rifampin; Tetracycline

Although there have been reports of Brucella granuloma or abscess in the literature, they were all localized extradurally except one, and most patients underwent surgery.. A 40-year-old female presented with urinary and fecal incontinence and a two-month history of progressive weakness of the right leg and numbness of the left leg. Four months previously, she had been diagnosed with systemic brucellosis with a period of radiculomeningoencephalitis; she was treated successfully with rifampicin, doxycycline, trimethoprim/sulfamethoxazole (TMP/SMZ), and streptomycin, and was discharged symptom-free on rifampicin and doxycycline. Neurological examination revealed spastic paraparesis, globally hyperactive deep tendon reflexes (DTRs) and sensory level at T6. Magnetic resonance imaging (MRI) of the spinal cord revealed a 10 x 30 mm intradural-intramedullary mass lesion at the T5 level with surrounding edema that enhanced with contrast. The cerebrospinal fluid (CSF) was xanthochromic with lymphocytic pleocytosis and elevated levels of albumin, immunoglobulins, and antibody titers for Brucella. The medications were modified to rifampicin 1200 mg, doxycycline 400 mg, and TMP/SMZ 480/2400 mg daily, and methylprednisolone 100 mg in decremental doses (for 6 weeks). After 2 months, the patient was almost symptom-free and her medication doses were decreased. After 5 months, the mass lesion resolved almost completely. The treatment was discontinued after 2 years.. The case is presented because of its uniqueness. In cases of Brucella granuloma, the authors recommend a trial of medical treatment with adequate dosages for a reasonable length of time before considering surgical intervention.

Topics: Adult; Brucellosis; Dose-Response Relationship, Drug; Doxycycline; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Granuloma; Humans; Magnetic Resonance Imaging; Methylprednisolone; Neurologic Examination; Rifampin; Spinal Cord; Spinal Cord Diseases; Thoracic Vertebrae; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Histopathological activity was assessed in the skin tissue of 13 skin-smear negative, borderline tuberculoid leprosy patients after administration of a single dose of ROM (rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg) therapy. Biopsies taken just before therapy showed Mycobacterium leprae to be present in eight cases. After 6 months, only three showed granulomatous lesions and others showed only resolving or inactive lesions. Acid-fast bacilli (AFB) persisted in the nerves of three cases. At the end of 12 months, granulomas persisted in 2 out of 13 (15%) patients. No bacilli, however, were detected in any of them at the end of 12 months. This study demonstrated that 12 months after a single dose of ROM granuloma cleared in 85% of the patients and AFB were absent in all of them.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Granuloma; Humans; Leprosy, Lepromatous; Male; Minocycline; Ofloxacin; Rifampin; Skin

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Dapsone; Drug Monitoring; Granuloma; Histiocytes; Humans; Leprostatic Agents; Leprosy, Borderline; Leprosy, Tuberculoid; Lymphocytes; Male; Minocycline; Ofloxacin; Recurrence; Rifampin

The purpose of this case report was to present a rare case of optic disk tubercle. The optic disk edema resolved on antituberculous therapy with recovery of vision. We concluded that visual loss from an optic disk tubercle can be the presenting sign of tuberculosis.

Topics: Adult; Anti-Bacterial Agents; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Fluorescein Angiography; Fundus Oculi; Granuloma; Humans; Isoniazid; Male; Optic Disk; Papilledema; Rifampin; Tuberculosis, Ocular; Vision Disorders

Tuberculosis of the liver is common in patients with acquired immunodeficiency syndrome (AIDS). Tuberculous liver granulomas in such patients are usually atypical. The liver granulomas may be even totally absent, but liver tissue usually reveals numerous acid-fast bacilli. Focal tuberculosis of the liver is a less common form of liver tuberculous infection. We present a 33-year old white homosexual man infected with the human immunodeficiency virus. He had three tumour-like lesions in the left liver lobe, which were subsequently diagnosed as focal hepatic tuberculosis with local hemorrhage. This unusual presentation of liver tuberculosis indicates the necessity of an aggressive diagnostic approach for the evaluation of focal liver lesions in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Ethambutol; Granuloma; Histocytochemistry; Homosexuality, Male; Humans; Isoniazid; Liver; Male; Mycobacterium; Pyrazinamide; Rifampin; Tuberculosis

The length of treatment advocated for leprosy has been very long and arbitrary. During the past few years, attempts have been made to reduce the length of treatment required. World Health Organization (WHO) has recommended six months therapy for paucibacillary leprosy. The present study was undertaken to see the extent of histological changes that occur with this therapy. Thirty four untreated tuberculoid (TT/BT) leprosy patients were biopsied initially and after completion of fixed course of this treatment. Clinically, 50 percent of the patients showed regression of disease activity at the end of six months. Morphology of the lesions was studied, in clinically active and inactive cases on completion of therapy. It was found that after six month's therapy, histology of the lesions was similar, whether the case was active or not. After the prescribed treatment, biopsy showed marked reduction in the extent of granuloma, along with significant increase in lymphocytes and a increase in epithelioid cells in these granulomas.

Topics: Dapsone; Drug Combinations; Epithelium; Granuloma; Humans; Leprosy, Tuberculoid; Lymphocytes; Prospective Studies; Rifampin; Skin; Time Factors

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

We tested the ability of teicoplanin alone and in combination with rifampicin or gentamicin to cure experimental endocarditis and granuloma pouch infections in rats caused by Streptococcus faecalis, Str. sanguis, methicillin-sensitive and -resistant Staphylococcus aureus. Vancomycin and ampicillin were also tested. Teicoplanin was more active than vancomycin and ampicillin. Combinations of teicoplanin with rifampicin or gentamicin were significantly more effective than single drug therapy. These results suggest that teicoplanin could be an interesting alternative to vancomycin in the treatment of serious streptococcal and staphylococcal infections in man.

Topics: Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Glycopeptides; Granuloma; Male; Methicillin; Penicillin Resistance; Rats; Rats, Inbred F344; Rifampin; Skin Diseases, Infectious; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Teicoplanin; Vancomycin

Topics: Adult; Female; Granuloma; Humans; Isoniazid; Pharyngeal Diseases; Rifampin; Tuberculosis

Four cases of chronic granulomatous skin infections (two due to Sporothrix schenckii and two to Mycobacterium marinum) were treated primarily by the intermittent application of local hyperthermia. This treatment was initiated either because of intolerance to conventional iodide therapy for sporotrichosis or as interim therapy while awaiting diagnosis of the mycobacterial infections. The response indicated that the application of heat is a useful adjunct to the therapy of these infections. Our experience, and that of others, suggests that in some cases heat alone may be curative.

Topics: Adult; Aged; Chronic Disease; Ethambutol; Female; Granuloma; Hot Temperature; Humans; Iodides; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Rifampin; Skin Diseases, Infectious; Sporotrichosis

A patient with oesophageal stenosis caused by Histoplasma granulomas is reported. He was treated with an initial combined course of intravenous amphotericin B and oral rifampicin. Complications included adrenal insufficiency, operative perforation of the oesophagus, amphotericin nephrotoxicity and tuberculosis. The histoplasmosis has not recurred for over 3 years.

Topics: Aged; Amphotericin B; Drug Therapy, Combination; Esophageal Stenosis; Granuloma; Histoplasmosis; Humans; Male; Rifampin

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 the course fo evaluating the effect of different drugs on the morphology of Mycobacterium leprae (Edwards, Draper & Draper, 1972) and on the phagocytic cells containing these organisms (Edwards, 1973), an unusual feature was observed in the dermal connective tissue of skin biopsies obtained from some of the patients. Variable amounts of an extracellular, cross-striated osmiophilic material were present in the dermis. The purpose of this communication is to describe the banded substance observed in the extracellular space of the lepromatous skin and to compare it briefly with similar substances and structures reported to occur elsewhere.

Topics: Animals; Collagen; Connective Tissue; Dapsone; Extracellular Space; Granuloma; Humans; Leprosy; Microscopy, Electron; Mycobacterium leprae; Rifampin; Skin; Staining and Labeling; Streptomycin

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

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

Topics: Animals; Brain; Dogs; Exudates and Transudates; Female; Granuloma; Intestinal Mucosa; Kidney; Liver; Lung; Male; Mice; Muscles; Rats; Rifampin