rifampin and Necrosis

Tuberculosis (TB) is a multi-systemic disease instigated by Mycobacterium tuberculosis that can involve any organ. In any child presenting with clinical features involving multiple organ systems, TB forms an important differential. This holds particularly for endemic countries like India. Genitourinary TB (GUTB) comprises up to 27% of all extrapulmonary TB cases. We present an unusual presentation of disseminated TB involving kidneys and presenting as gross hematuria. 12-year-old girl, presented with recurrent episodes of gross hematuria of one-month duration. She received multiple packed cell transfusions for the same. She had chronic malnutrition. USG KUB with renal doppler was normal. Given persistent hematuria, CT urography was done which showed features suggestive of papillary necrosis with cystitis. Tubercular workup showed multiple opacities predominantly involving perihilar regions bilaterally on chest x-ray along with positive Mantoux test. Sputum for AFB was positive for tubercular bacilli. Urine samples were also sent for CBNAAT which showed TB bacilli sensitive to rifampicin. With a diagnosis of disseminated TB, antitubercular therapy (ATT) was started followed by cystoscopic resection of inflamed bladder wall tissue. Bladder mucosal biopsy confirmed caseating granulomas suggestive of tuberculous cystitis. The patient is doing well and symptom-free after completion of ATT.

Topics: Antibiotics, Antitubercular; Blood Transfusion; Child; Cystitis; Female; Hematuria; Humans; Kidney; Mycobacterium tuberculosis; Necrosis; Recurrence; Rifampin; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome; Tuberculosis, Urogenital; Urogenital System

New therapeutic strategies are needed to treat drug resistant tuberculosis (TB) and to improve treatment for drug sensitive TB. Pyrazinamide (PZA) is a critical component of current first-line TB therapy. However, the rise in PZA-resistant TB cases jeopardizes the future utility of PZA. To address this problem, we used the guinea pig model of TB and tested the efficacy of an inhaled dry powder combination, referred to as Pyrazinoic acid/ester Dry Powder (PDP), which is comprised of pyrazinoic acid (POA), the active moiety of PZA, and pyrazinoic acid ester (PAE), which is a PZA analog. Both POA and PAE have the advantage of being able to act on PZA-resistant Mycobacterium tuberculosis. When used in combination with oral rifampicin (R), inhaled PDP had striking effects on tissue pathology. Effects were observed in lungs, the site of delivery, but also in the spleen and liver indicating both local and systemic effects of inhaled PDP. Tissue granulomas that harbor M. tuberculosis in a persistent state are a hallmark of TB and they pose a challenge for therapy. Compared to other treatments, which preferentially cleared non-necrotic granulomas, R+PDP reduced necrotic granulomas more effectively. The increased ability of R+PDP to act on more recalcitrant necrotic granulomas suggests a novel mechanism of action. The results presented in this report reveal the potential for developing therapies involving POA that are optimized to target necrotic as well as non-necrotic granulomas as a means of achieving more complete sterilization of M. tuberculosis bacilli and preventing disease relapse when therapy ends.

Topics: Aerosols; Animals; Antitubercular Agents; Bacterial Load; Disease Models, Animal; Drug Therapy, Combination; Dry Powder Inhalers; Granuloma, Respiratory Tract; Guinea Pigs; Male; Mycobacterium tuberculosis; Necrosis; Pyrazinamide; Respiratory Tract Absorption; Rifampin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

During active TB in humans a spectrum of pulmonary granulomas with central necrosis and hypoxia exists. BALB/c mice, predominantly used in TB drug development, do not reproduce this complex pathology thereby inaccurately predicting clinical outcome. We found that Nos2

Topics: Animals; Antitubercular Agents; Disease Models, Animal; Fibrosis; Foam Cells; Humans; Hypoxia; Isoniazid; Mice; Mice, Knockout; Necrosis; Nitric Oxide Synthase Type II; Rifampin; Treatment Outcome; Tuberculosis, Pulmonary

A small percentage of patients with tuberculosis present with cutaneous findings, which may be difficult to diagnose. We present a patient diagnosed with a rare, non-scarring form of cutaneous tuberculosis (CTB), classically termed as lupus vulgaris erythematoides.

Topics: Adrenal Cortex Hormones; Aged, 80 and over; Anti-Bacterial Agents; Antitubercular Agents; Biopsy; Calcineurin Inhibitors; Dermis; Diagnostic Errors; Drug Therapy, Combination; Eczema; Erythema; Facial Dermatoses; Female; Histiocytosis, Langerhans-Cell; Humans; Immunosuppressive Agents; Isoniazid; Lupus Vulgaris; Mycobacterium tuberculosis; Necrosis; Nose Diseases; Pyrazinamide; Rifampin

Choice of pins, drills, and drilling technique can result in heat generation leading to thermal necrosis of bone. This has been reported frequently in internal as well as in external fixation. This publication is the first report of a patient having osteomyelitis of the proximal tibia due to thermal necrosis following tracker pin placement in computer-navigated total knee arthroplasty.

Topics: Anti-Bacterial Agents; Arthroplasty, Replacement, Knee; Bone Nails; Floxacillin; Hot Temperature; Humans; Knee Joint; Knee Prosthesis; Male; Middle Aged; Necrosis; Osteoarthritis, Knee; Osteomyelitis; Prosthesis-Related Infections; Radiography; Rifampin; Surgery, Computer-Assisted; Tibia; Treatment Outcome

The neglected tropical disease Buruli ulcer (BU) caused by Mycobacterium ulcerans is an infection of the subcutaneous tissue leading to chronic ulcerative skin lesions. Histopathological features are progressive tissue necrosis, extracellular clusters of acid fast bacilli (AFB) and poor inflammatory responses at the site of infection. After the recommended eight weeks standard treatment with rifampicin and streptomycin, a reversal of the local immunosuppression caused by the macrolide toxin mycolactone of M. ulcerans is observed.. We have conducted a detailed histopathological and immunohistochemical analysis of tissue specimens from two patients developing multiple new skin lesions 12 to 409 days after completion of antibiotic treatment. Lesions exhibited characteristic histopathological hallmarks of Buruli ulcer and AFB with degenerated appearance were found in several of them. However, other than in active disease, lesions contained massive leukocyte infiltrates including large B-cell clusters, as typically found in cured lesions.. Our histopathological findings demonstrate that the skin lesions emerging several months after completion of antibiotic treatment were associated with M. ulcerans infection. During antibiotic therapy of Buruli ulcer development of new skin lesions may be caused by immune response-mediated paradoxical reactions. These seem to be triggered by mycobacterial antigens and immunostimulators released from clinically unrecognized bacterial foci. However, in particular the lesions that appeared more than one year after completion of antibiotic treatment may have been associated with new infection foci resolved by immune responses primed by the successful treatment of the initial lesion.

Topics: Antibiotics, Antitubercular; Antigens, CD; Buruli Ulcer; Child; Humans; Immunohistochemistry; Leukocytes; Male; Mycobacterium ulcerans; Necrosis; Neglected Diseases; Rifampin; Skin; Streptomycin; Treatment Outcome

We present a case of community-acquired methicillin-resistant Staphylococcus aureus necrotizing pneumonia, Panton-Valentine leukocidin positive, in a woman at 14 weeks of pregnancy. To our knowledge, this is the first case reporting this critical lung infection occurring during an early phase of pregnancy. This case study alerts physicians to the increasing worldwide spread of these uncommon yet virulent and potentially lethal infections. In our patient, antibiotic therapy with linezolid plus rifampin started at 14 weeks of pregnancy had a successful outcome without inducing toxicity or teratogenesis in the fetus.

Topics: Acetamides; Anti-Bacterial Agents; Bacterial Toxins; Drug Therapy, Combination; Exotoxins; Female; Humans; Leukocidins; Linezolid; Lung; Methicillin-Resistant Staphylococcus aureus; Necrosis; Oxazolidinones; Pneumonia, Staphylococcal; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Radiography; Rifampin; Treatment Outcome; Young Adult

Acetaminophen (APAP) is safe at therapeutic levels but causes hepatotoxicity via N-acetyl-p-benzoquinone imine-induced oxidative stress upon overdose. To determine the effect of human (h) pregnane X receptor (PXR) activation and CYP3A4 induction on APAP-induced hepatotoxicity, mice humanized for PXR and CYP3A4 (TgCYP3A4/hPXR) were treated with APAP and rifampicin. Human PXR activation and CYP3A4 induction enhanced APAP-induced hepatotoxicity as revealed by hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities elevated in serum, and hepatic necrosis after coadministration of rifampicin and APAP, compared with APAP administration alone. In contrast, hPXR mice, wild-type mice, and Pxr-null mice exhibited significantly lower ALT/AST levels compared with TgCYP3A4/hPXR mice after APAP administration. Toxicity was coincident with depletion of hepatic glutathione and increased production of hydrogen peroxide, suggesting increased oxidative stress upon hPXR activation. Moreover, mRNA analysis demonstrated that CYP3A4 and other PXR target genes were significantly induced by rifampicin treatment. Urinary metabolomic analysis indicated that cysteine-APAP and its metabolite S-(5-acetylamino-2-hydroxyphenyl)mercaptopyruvic acid were the major contributors to the toxic phenotype. Quantification of plasma APAP metabolites indicated that the APAP dimer formed coincident with increased oxidative stress. In addition, serum metabolomics revealed reduction of lysophosphatidylcholine in the APAP-treated groups. These findings demonstrated that human PXR is involved in regulation of APAP-induced toxicity through CYP3A4-mediated hepatic metabolism of APAP in the presence of PXR ligands.

Topics: Acetaminophen; Alanine Transaminase; Analgesics, Non-Narcotic; Animals; Anti-Bacterial Agents; Aspartate Aminotransferases; Biomarkers; Biotransformation; Chemical and Drug Induced Liver Injury; Cysteine; Cytochrome P-450 CYP3A; Drug Interactions; Enzyme Induction; Glutathione; Humans; Hydrogen Peroxide; Liver; Liver Diseases; Lysophosphatidylcholines; Male; Metabolomics; Mice; Mice, Knockout; Mice, Transgenic; Necrosis; Oxidative Stress; Pregnane X Receptor; Principal Component Analysis; Receptors, Steroid; Rifampin; RNA, Messenger; Time Factors

Staphylococcus lugdunensis is an infrequent cause of infective endocarditis (IE) and usually involves native valves of the heart. It causes life-threatening events such as rupture of cardiac valve or cerebral or pulmonary embolism due to necrosis on the endocardial tissue involved by the bacteria. Antibiotic therapy without cardiac surgery or delayed cardiac surgery usually follows a fatal course in S. lugdunensis endocarditis. In this report the first case of S. lugdunensis endocarditis from Turkey was presented. A 37-year-old man was admitted to the emergency department with a 2-weeks history of fever chills and accompanying intermittent pain on the left side of the thorax. Other than recurrent folliculitis continuing for 20 years, his history was unremarkable. Echocardiography revealed vegetation on the mitral valve of the patient and vancomycin plus gentamicin were initiated with the diagnosis of IE. All blood cultures (5 sets) taken on admission and within the initial 48 hours of the antibiotic therapy yielded S. lugdunensis. According to the susceptibility test results, the antibiotic therapy was switched to ampicillin-sulbactam plus rifampin. Blood cultures became negative after the third day of therapy, however, cardiac failure was emerged due to rupture of mitral valve and chorda tendiniea on the 12th day of the therapy. Cardiac surgery revealed that mitral valve and surrounding tissue of the valve were evidently necrotic and fragile, anterior leaflet of the mitral valve was covered with vegetation, posterior leaflet and chorda tendiniea were ruptured. Vegetation was removed and the destructed mitral valve was replaced with a mechanical valve. Vegetation culture remained sterile, however, antibiotics were switched to vancomycin plus rifampin due to persistent fever on the 21st day of the therapy (9th day of operation). Fever resolved four days after the antibiotic switch. Antibiotics were stopped on the 9th weeks of admission and the patient was discharged. He had no problem in follow-up controls for one year. In conclusion, proper antibiotic therapy combined with early cardiac surgery seems to be the optimal therapeutic approach in IE caused by S. lugdunensis.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Bacteremia; Chemotherapy, Adjuvant; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Heart Valve Prosthesis Implantation; Humans; Male; Mitral Valve; Necrosis; Rifampin; Staphylococcal Infections; Staphylococcus; Sulbactam; Ultrasonography; Vancomycin

Community-associated strains of methicillin-resistant Staphylococcus aureus (CA-MRSA) have recently emerged as a major cause of serious infections among older children and are now being seen in NICU patients. We present the case of a preterm infant with CA-MRSA necrotizing pneumonia and secondary bacteremia.

Topics: Anti-Bacterial Agents; Antitubercular Agents; Bacteremia; Community-Acquired Infections; Drug Administration Schedule; Gentamicins; Humans; Infant, Newborn; Methicillin Resistance; Necrosis; Pneumonia, Staphylococcal; Rifampin; Staphylococcus aureus; Twins; Vancomycin

This study investigated the hepatoprotective effect of two Indian medicinal plants Tinospora cordifolia (Tc), Phyllanthus emblica (Pe), and their combination, in a rat model of isoniazid, rifampicin and pyrazinamide induced hepatic damage. Hepatic damage was assessed using a composite score assigned to histopathological findings of degeneration, necrosis and fibrosis. The antituberculosis treatment (ATT), when given for 90 days, induced significant degeneration and necrosis (score: 7.5; p < 0.01 vs vehicle) associated with morphological changes. However, no change was found in the serum bilirubin and liver enzymes. Co-administration of silymarin (positive control, 50 mg/kg) with ATT protected against necrosis (score: 1.5; p < 0.001 vs ATT). Tc (100 mg/kg) showed a reduction in liver damage (score: 6.5), which was not statistically significant. On the other hand, Pe (300 mg/kg) prevented the necrotic changes to a significant extent (grade 1.0; p < 0.05; score [corrected] 5.5). Combination of Tc and Pe in their therapeutic doses (1:3) significantly prevented the necrosis (score: 3.5; p < 0.001 vs ATT). Similar effects were seen even when the doses were halved and were comparable to the silymarin group. Thus, this study proves the synergistic protective effects exerted by the combination of Tc and Pe when co-administered with ATT.

Topics: Animals; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Isoniazid; Liver Cirrhosis; Liver Diseases; Male; Necrosis; Phyllanthus emblica; Phytotherapy; Plant Extracts; Pyrazinamide; Rats; Rats, Wistar; Rifampin; Tinospora

We report a case of a four-year-old Angolan boy with the edematous form of Buruli ulcer on the face and scalp, who was treated at a rural hospital in the Bas-Congo Province, Democratic Republic of Congo. Treatment consisted of a series of surgical interventions and antimycobacterial chemotherapy (rifampin and ciprofloxacin) for two months. This case demonstrates the diagnostic and management difficulties of an edematous lesion of BU on the face and suggests an enhancement of healing and limitation of extent of excision by specific antibiotherapy. The outcome in this patient also underscores the importance of prompt referral of suspected cases and training of health professionals in the early diagnosis of BU.

Topics: Angola; Anti-Bacterial Agents; Buruli Ulcer; Child, Preschool; Ciprofloxacin; Edema; Humans; Male; Mycobacterium ulcerans; Necrosis; Rifampin; Treatment Outcome

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 interacts with macrophages and epithelial cells in the alveolar space of the lung, where it is able to invade and replicate in both cell types. M. tuberculosis-associated cytotoxicity to these cells has been well documented, but the mechanisms of host cell death are not well understood. We examined the induction of apoptosis and necrosis of human macrophages (U937) and type II alveolar epithelial cells (A549) by virulent (H37Rv) and attenuated (H37Ra) M. tuberculosis strains. Apoptosis was determined by both enzyme-linked immunosorbent assay (ELISA) and TdT-mediated dUTP nick end labelling (TUNEL) assay, whereas necrosis was evaluated by the release of lactate dehydrogenase (LDH). Both virulent and attenuated M. tuberculosis induced apoptosis in macrophages; however, the attenuated strain resulted in significantly more apoptosis than the virulent strain after 5 days of infection. In contrast, cytotoxicity of alveolar cells was the result of necrosis, but not apoptosis. Although infection with M. tuberculosis strains resulted in apoptosis of 14% of the cells on the monolayer, cell death associated with necrosis was observed in 59% of alveolar epithelial cells after 5 days of infection. Infection with M. tuberculosis suppressed apoptosis of alveolar epithelial cells induced by the kinase inhibitor, staurosporine. Because our findings suggest that M. tuberculosis can modulate the apoptotic response of macrophages and epithelial cells, we carried out an apoptosis pathway-specific cDNA microarray analysis of human macrophages and alveolar epithelial cells. Whereas the inhibitors of apoptosis, bcl-2 and Rb, were upregulated over 2.5-fold in infected (48 h) alveolar epithelial cells, the proapoptotic genes, bad and bax, were downregulated. The opposite was observed when U937 macrophages were infected with M. tuberculosis. Upon infection of alveolar epithelial cells with M. tuberculosis, the generation of apoptosis, as determined by the expression of caspase-1, caspase-3 and caspase-10, was inhibited. Inhibition of replication of intracellular bacteria resulted in an increase in apoptosis in both cell types. Our results showed that the differential induction of apoptosis between macrophages and alveolar epithelial cells represents specific strategies of M. tuberculosis for survival in the host.

Topics: Antibiotics, Antitubercular; Apoptosis; bcl-Associated Death Protein; Carrier Proteins; Cell Line; Enzyme Inhibitors; Epithelial Cells; Gene Expression Regulation; Humans; In Situ Nick-End Labeling; Macrophages; Mycobacterium tuberculosis; Necrosis; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-bcl-2; Pulmonary Alveoli; Rifampin; Staurosporine

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 62-year-old woman with pulmonary tuberculosis was admitted to our hospital. She was completely neurologically free at admission and her CSF was normal. Brain MRI with Gd-DTPA enhancement demonstrated two mass lesions with ring-enhancement in the left temporal lobe and the right frontal lobe. The left temporal lesion had a bright central core with hypointense periphery on T2 weighted image. Extended hyperintense area was observed around this lesions, which represented brain edema. On T1 weighted image, the central core was demonstrated hypointense and its periphery was isointense. After starting antituberculous therapy, MRI revealed paradoxical expansion of left temporal lesion and neurological symptoms worsened temporarily, but, eventually the intracranial lesions diminished in size and disappeared, and the symptoms improved. So we diagnosed her as having intracranial tuberculoma. By long-term following up with MRI, we observed that the central core of the left temporal tuberculoma had changed gradually to hypointense on T2 weighted image and hyperintense on T1 weighted image respectively. We thought that the change of the central core on MRI represented organization of caseated necrosis.

Topics: Antitubercular Agents; Brain; Female; Follow-Up Studies; Humans; Isoniazid; Magnetic Resonance Imaging; Middle Aged; Necrosis; Rifampin; Streptomycin; Time Factors; Tuberculoma, Intracranial

Topics: Disseminated Intravascular Coagulation; Female; Humans; Leprostatic Agents; Leprosy, Lepromatous; Liver; Middle Aged; Necrosis; Rifampin

In the past, Mycobacterium avium complex (MAC) was considered a colonizing microbe in the immunocompetent host. Today it should be considered a potential pathogen. We present a case of MAC necrotizing pneumonia in a 27-year-old man who tested negatively for the human immunodeficiency virus, had no typical granulomas, and responded rapidly to antimicrobial therapy.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Antitubercular Agents; Ciprofloxacin; Clarithromycin; Drug Therapy, Combination; Ethambutol; HIV Seronegativity; Humans; Male; Mycobacterium avium-intracellulare Infection; Necrosis; Pneumonia, Bacterial; Pulmonary Atelectasis; Rifampin

A 58-year-old woman with tuberculosis received antituberculous drugs which included isoniazid, rifampicin, and ethambutol. Nausea and anorexia were initial symptoms while jaundice and abdominal pain were late manifestations. She became comatose and died 7 weeks after therapy. Autopsy revealed submassive necrosis of the liver and active advanced pulmonary tuberculosis. It is, thus, necessary for the physician to be alert for this serious complication in prescribing a combination of these antituberculous drugs.

Topics: Chemical and Drug Induced Liver Injury; Female; Hepatic Encephalopathy; Humans; Isoniazid; Liver; Middle Aged; Necrosis; Rifampin

Topics: Ampicillin; Aortic Rupture; Aortic Valve; Echocardiography; Endocarditis, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Medical Illustration; Middle Aged; Necrosis; Rifampin; Suppuration

Tuberculous aortitis is a rare entity and its association with necrosis and perforation is even more unusual. Our pulmonary medicine service originally evaluated an elderly woman with a right pleural effusion and upper lobe infiltrate thought to be tuberculosis. An abdominal CT scan performed at that time showed extensive periaortic adenopathy. Isoniazid and rifampin were started, but both were stopped by the patient after less than 6 months of therapy. The patient later had night sweats, a left pleural effusion, and a tender abdominal mass thought to be a symptomatic aneurysm. At operation, the aorta was necrotic and had an inflammatory mass and perforation on the left side. Infrarenal aortic ligation and resection were performed to control infection. A previously placed axillofemoral graft obviated the need for concomitant revascularization. The patient was treated postoperatively with isoniazid and rifampin until hyperbilirubinemia developed, which necessitated alternate therapy with ethambutol and streptomycin. The patient died one month after operation of a presumed pulmonary embolus.

Topics: Aged; Aortitis; Combined Modality Therapy; Female; Humans; Isoniazid; Necrosis; Rifampin; Rupture, Spontaneous; Tuberculosis, Cardiovascular

Soluble rifampicin and isoniazid injected rapidly by the intravenous route and streptomycin injected intramuscularly to dogs with disseminated destructive tuberculosis of the lungs provided sterilization of the organs with respect to M. tuberculosis for the period of their use for 2 months. This was confirmed microbiologically. The treatment resulted in resolution of the dissemination foci in the organs and stimulation of immunomorphological and connective tissue reactions in the lungs until the foci cicatrized. The shifts in liver function (bilirubin, ALT and AST) and coagulograms during the treatment were temporary and came to normal by the end of the treatment. The organotropic effect of soluble rifampicin in combination with isoniazid injected rapidly by the intravenous route and streptomycin injected intramuscularly was not observed during the treatment of the dogs with disseminated destructive tuberculosis of the lungs. Rapid intravenous injection of rifampicin in combination with other antimicrobial drugs will provide a significant decrease in the periods of chemotherapy of patients with disseminated destructive tuberculosis of the lungs.

Topics: Animals; Dogs; Drug Evaluation, Preclinical; Drug Therapy, Combination; Guinea Pigs; Injections, Intramuscular; Injections, Intravenous; Isoniazid; Lung; Necrosis; Rifampin; Streptomycin; Time Factors; Tuberculosis, Pulmonary

Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Drug Interactions; Hepatic Encephalopathy; Humans; Isoniazid; Liver; Male; Middle Aged; Necrosis; Rifampin

Topics: Adult; Carbamazepine; Female; Hepatic Encephalopathy; Humans; Isoniazid; Liver; Necrosis; Rifampin

Topics: Animals; Biotransformation; Chemical and Drug Induced Liver Injury; Humans; Isoniazid; Liver; Microsomes, Liver; Necrosis; Rifampin

A case of scleral tuberculosis was successfully treated by combined systemic and local therapy. The importance of biopsy for early diagnosis and initiation of curative treatment is stressed.

Topics: Administration, Topical; Aged; Female; Fluorescein Angiography; Humans; Isoniazid; Necrosis; Radiography; Rifampin; Sclera; Streptomycin; Tuberculosis, Ocular; Wound Healing

Two patients who developed reversible renal failure during intermittent rifampicin therapy are described. Both had febrile reactions to rifampicin. The first was also found to have uraemia associated with swelling of the glomerular endothelial cells. The second developed tubular necrosis unassociated with haemolysis or shock. The pathogenesis of the renal lesion in these two patients, as revealed by light microscopy, immunofluorescence studies and electron microscopy, is discussed.

Topics: Acute Kidney Injury; Adult; Antibodies; Endothelium; Ethambutol; Fever; Fibrin; Humans; Immune Complex Diseases; Ischemia; Kidney Glomerulus; Kidney Tubules; Male; Necrosis; Rifampin; Tuberculosis, Pulmonary; Uremia

Topics: Adolescent; Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Chemical and Drug Induced Liver Injury; Cholestasis; Clinical Enzyme Tests; Drug Therapy, Combination; Ethambutol; Fatty Liver; Female; Humans; Isoniazid; Liver Diseases; Liver Function Tests; Male; Middle Aged; Necrosis; Rifampin; Sulfobromophthalein; Tuberculosis, Pulmonary

Topics: Acute Disease; Bladder Exstrophy; Burns; Carcinoid Tumor; Cholelithiasis; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Emergencies; Esophageal and Gastric Varices; General Surgery; Methods; Necrosis; Pancreatitis; Rifampin; Transportation of Patients; Tuberculosis, Lymph Node; Tuberculosis, Osteoarticular; Vascular Surgical Procedures; Wounds and Injuries

Topics: Anuria; Diagnosis, Differential; Female; Humans; Hypothermia; Jaundice; Kidney Diseases; Liver Diseases; Necrosis; Rifampin; Tuberculosis, Pulmonary