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PubMed1995

Appearance of drug-resistant tuberculosis in rural Tennessee.

Drug-resistant tuberculosis (DRTB) is a growing national health concern in both urban populations and rural areas and is exacerbated by the growing epidemic of human immunodeficiency virus (HIV) infection. Between 1989 and 1992, 7 cases of DRTB (5 with multidrug-resistance) were diagnosed in an eight-county region of East Tennessee. During 1990 and 1991 alone, 5 of 100 patients with tuberculosis had drug-resistant strains (5%). All 7 patients with DRTB had 100% resistance to isoniazid; 5 also had resistance to streptomycin, 2 to rifampin, and 1 to pyrazinamide and ethambutol. All patients were white, U.S.-born, and without evidence of HIV infection. Contact investigation revealed that more contacts of patients with DRTB (13 of 74, 18%) were infected than were contacts of patients with drug-sensitive tuberculosis (46 of 290, 16%). Our study demonstrates that DRTB is not confined to geographically distinct areas, but may be a subtle and easily missed diagnosis in presumably low-risk rural populations.

Adult↗

PubMed1996

Spontaneous resolution of a lung mass due to infection with Mycobacterium terrae.

A 61-year-old smoker had a large right lung mass suggestive of bronchogenic carcinoma. Bronchoscopy showed what appeared to be tumor occlusion of a right middle lobe subsegment. Biopsies were nondiagnostic for malignancy. A scheduled percutaneous needle aspiration biopsy 1 week later was canceled because of a significant reduction in size of the lung mass. Acid-fast bacilli were subsequently found in bronchoscopic specimens, and treatment was started with isoniazid, rifampin, pyrazinamide, and ethambutol. The organism was identified as Mycobacterium terrae. In vitro resistance was noted to isoniazid. The early reduction in size of the mass before antimycobacterial therapy suggested that spontaneous regression may be part of the natural history of pulmonary infection with Mycobacterium terrae.

Female↗

PubMed1997

Tuberculosis of the spine. Controversies and a new challenge.

Tuberculosis is a deadly disease affecting many people in the world. The prevalence of spinal tuberculosis is likely to rise as the numbers of those infected with human immunodeficiency virus rises. This presentation summarizes present knowledge of spinal tuberculosis and its management. It describes and updates material the author has previously published on this subject. The scientific basis for the clinical management of spinal tuberculosis has been well established by the British Medical Research Council group and Hong Kong surgeons. It is believed, however, that well-controlled basic and clinical studies are required if the incidence of the three unwanted complications of spinal tuberculosis is to be reduced further. Antituberculosis agents are the mainstay of management, with chemotherapy for 12 months preferred to shorter courses. The standard is a combination of isoniazid, rifampin, and pyrazinamide, with or without ethambutol. Anterior surgery consisting of radical focal debridement without fusion does not prevent vertebral collapse. The major advantage of anterior arthrodesis is the decreased tendency for progression of the deformity. Patients who present late with deformity are candidates for anterior debridement and stabilization with corrective instrumentation. Posterior stabilization with instrumentation has been found to help arrest the disease and to bring about early fusion. Posterior instrumented stabilization to prevent kyphosis in early spinal tuberculosis is indicated, however, only when anterior and posterior elements of the spine are involved, particularly in children. With early detection, institution of chemotherapy, and improved surgical techniques, patients with kyphosis rarely are seen today, particularly in urban centers that have an effective medical system. For these same reasons, patients with spinal tuberculosis who present with paraplegia and no deformity usually respond well to treatment. It is concluded that spinal tuberculosis without unsightly kyphosis and neurologic symptoms is a medical, rather than a surgical, condition. Surgery should be reserved for those patients who have advanced tuberculosis with unacceptable complications such as paraplegia and/or deformity.

Humans↗

PubMed2000

Tuberculosis in orthotopic liver transplant patients: increased toxicity of recommended agents; cure of disseminated infection with nonconventional regimens.

BACKGROUND: Because increased hepatotoxicity was observed with first line antituberculous agents using four drug standard induction therapy in orthotopic liver transplant patients, we evaluated the efficacy and adverse effects of a novel continuation regimen for the treatment of tuberculosis in orthotopic liver transplant patients at a University Hospital in New York City. METHODS: The hospital records of all patients who were referred to Mount Sinai Hospital (n=924) and who underwent orthotopic liver transplant between September 1988 and May 1998 were reviewed. Data were collected from patient records. Nine orthotopic liver transplant patients (0.97%) developed tuberculosis over a 9.5-year period. A total of seven of nine (78%) patients had disseminated tuberculosis including two patients with meningitis. All mycobacterial isolates were sensitive to isoniazid, rifampin, pyrazinamide, and ethambutol. Standard induction therapy with three or four drugs was given for 2 months (mean). Hepatotoxicity related to the standard induction regimen developed in five of six (83.3%) patients. Liver biopsy during induction therapy revealed drug induced hepatitis in five of six (88%) patients and rejection in three of six (50%) patients. Continuation regimens consisted mainly of ethambutol and ofloxacin; mean length of therapy 9 months. RESULTS: Overall mortality was 33.3% (three of nine patients) over a 4.5-year follow-up period. Tuberculosis associated mortality was 22.2%. One patient died before therapy, another died with concomitant bacterial sepsis during induction therapy. Six of seven patients are alive and disease free. One patient died of recurrent hepatitis C and graft failure without evidence of tuberculous infection at death. Another patient retransplanted for chronic rejection, remains disease free at 1 year. The mean follow-up for six patients that completed treatment was 3.75 years (2.5-5.3 years). Six patients are free of tuberculosis. CONCLUSIONS: Our experience reveals that orthotopic liver transplant patients have poor tolerance for conventional therapy due to inherent toxicity of these agents and their concomitant bouts of organ rejection. Our nonconventional therapy yielded remarkably good results in that six patients, all with disseminated disease, were well after mean 3.5 years of follow-up. Consideration should be given to this novel follow-up therapy in patients without cavitary pulmonary disease who develop hepatotoxicity during induction.

Adult↗

PubMed2001

Tuberculous peritonitis--reports of 26 cases, detailing diagnostic and therapeutic problems.

OBJECTIVE: To evaluate the clinical presentation, biochemical (ascites and serum) and laparoscopic findings, and to assess the efficacy of triple antituberculous therapy without rifampicin for 6 months in patients with tuberculous peritonitis. METHODS: Twenty-six tuberculous peritonitis patients (11 male, 15 female) with a mean age of 34.8 +/- 3.4 years (range 14-77) were assessed with regard to diagnostic and therapeutic features. RESULTS: The most common symptoms and signs were abdominal pain (92.3%) and ascites (96.2%), respectively. Tuberculin skin test (TST) was positive in all patients. An abnormal chest radiography suggestive of previous tuberculosis was present in five patients (19.2%), and two patients (7.7%) had extra-peritoneal (cerebral, pericardial) active tuberculous involvement. In 24 of the 25 patients who underwent laparoscopy with directed biopsy, whitish nodules suggested tuberculous peritonitis; 76% of the biopsy specimens revealed caseating, 20% non-caseating granulomatous inflammation, and 4% non-specific findings. The ascitic fluid of one patient (3.8%) was positive for acid-resistant bacilli, and culture was positive in two patients (7.7%). Twenty-four of the patients were treated for 6 months with isoniazid, streptomycin (total dose 40 g) and pyrazinamide (for the first 2 months and then substituted with ethambutol). Eighteen patients also received methyl prednisolone, initially 20 mg/day, for 1 month. The follow-up period was 19 +/- 1.7 months after the end of therapy (range 6-36). Ascites and abdominal pain abated earlier in patients on steroid therapy. All but two of the 24 patients responded to treatment. CONCLUSION: Non-invasive tests such as acid-fast stain and culture of the ascitic fluid are usually insufficient, hence invasive laparoscopy and peritoneal biopsy are necessary for the diagnosis of tuberculous peritonitis if non-invasive tests such as ascites adenosine deaminase activity measurement are not easily available. Triple therapy without rifampicin for 6 months is sufficient to treat tuberculous peritonitis.

Adolescent↗

PubMed2003

Multifocal Pott's disease (tuberculous spondylitis) incidentally detected on Tc-99m MDP bone and Ga-67 citrate scintigraphy in a patient with diabetes.

Pott's disease is an uncommon extrapulmonary form of tuberculosis. Delay in diagnosis and management may cause serious complications. The authors describe Pott's disease incidentally detected on Tc-99m MDP bone and Ga-67 imaging in a patient with diabetes. Tc-99m MDP bone scintigraphy showed intensely increased uptake in the lower cervical spine and lumbosacral regions. Ga-67 scintigraphy revealed intensely increased uptake corresponding to the areas noted on Tc-99m MDP bone scintigraphy. Magnetic resonance imaging showed destructive lesions in the C5-C6 and L5-S1 intervertebral discs with destruction of adjacent end plates. Biopsy of the lumbosacral area was guided by computed tomography, and histologic examination of the bone specimen showed caseation, giant cells, and acid-fast bacilli. Posterior decompression and posterolateral spinal fusion with bone grafts were performed. Antituberculous chemotherapy with isoniazid, rifampicin, pyrazinamide, and ethambutol was started. The patient showed remarkable relief of symptoms during a period of 9 months of therapy. Both Tc-99m MDP bone and Ga-67 imaging can offer the convenience of screening the entire body to detect multiple sites of Pott's disease.

Cervical Vertebrae↗

PubMed1999

Mycobacterium tuberculosis subsp. caprae subsp. nov.: a taxonomic study of a new member of the Mycobacterium tuberculosis complex isolated from goats in Spain.

Isolates from the Mycobacterium tuberculosis complex cultured from caprine pathological tissue samples were biochemically and genetically characterized. The isolates were negative for nitrate reduction and niacin accumulation, they weakly hydrolysed Tween 80, were sensitive to pyrazinamide (50 micrograms ml-1) and were resistant to 1 and 2 micrograms tiophene-2-carboxylic acid hydrazide ml-1 but not to 5 or 10 micrograms tiophene-2-carboxylic acid hydrazide ml-1. Sequencing of the pncA gene revealed a polymorphism characteristic of M. tuberculosis, whereas oxyR, katG and gyrA sequences were characteristic of Mycobacterium bovis. The fingerprinting patterns obtained with IS6110, direct repeats and polymorphic G+C-rich sequence-associated RFLP and direct variable repeat-spacer oligonucelotide typing (spoligotyping) segregated these isolates from the other members of the complex. The results of this testing, together with the repeated association of this micro-organism with goats, suggest that a new member of this taxonomic complex not matching any of the classical species had been identified. This unusual mycobacterium may play a role in the epidemiology of animal and human tuberculosis in Spain. The name Mycobacterium tuberculosis subsp. caprae subsp. nov. is proposed for these isolates. The type strain of Mycobacterium tuberculosis subsp. caprae subsp. nov. is gM-1T (= CIP 105776T).

Amidohydrolases↗

PubMed2003

Elevation of Mycobacterium tuberculosis subsp. caprae Aranaz et al. 1999 to species rank as Mycobacterium caprae comb. nov., sp. nov.

Mycobacterium tuberculosis complex isolates recovered from goats were originally classified as Mycobacterium tuberculosis subsp. caprae; however, this subspecies was recently reclassified as Mycobacterium bovis subsp. caprae. Besides biochemical (sensitivity to pyrazinamide) and epidemiological features, strains of this unusual member of the M. tuberculosis complex show a special combination of pncA, oxyR, katG and gyrA gene polymorphisms. Sequence analysis of the gyrB gene in these strains reveals special nucleotide substitutions not found in other members of the M. tuberculosis complex that can be used to differentiate caprine mycobacterial strains from M. bovis and other members of the M. tuberculosis complex. M. tuberculosis subsp. caprae now appears not to be restricted to Spanish goats, as strains of this organism have been isolated from cattle, wild boar and pigs. Its occurrence has also been reported in France, Austria and Germany. Two studies on the evolution of the M. tuberculosis complex based on the presence/absence of regions of difference have shown that the group of caprine isolates (or its ancestor) is older than M. bovis (or its ancestor). These findings reinforce the original suggestion that the caprine mycobacterial strains are a taxon of the M. tuberculosis complex, independent of M. bovis. Within the current context of the existing nomenclature of the M. tuberculosis complex, it is proposed that M. tuberculosis subsp. caprae be elevated to species status, as Mycobacterium caprae comb. nov., sp. nov.

Animals↗

PubMed2006

Mycobacterium kansasii olecranon bursitis.

A case is reported of a post-traumatic olecranon bursitis caused by Mycobacterium kansasii following an injury sustained in a public swimming pool. It responded to surgical debridement and combined rifampicin, isoniazid, pyrazinamide and ethambutol antimicrobial therapy. A literature search was performed and a treatment regimen for this uncommon condition is suggested.

Antitubercular Agents↗

PubMed1995

Structure-function relations in the inhibition of murine contact hypersensitivity by amiloride.

Topical application of amiloride, a potent inhibitor of the Na+/H+ antiport, inhibits cutaneous inflammation induced by ultraviolet radiation or contact hypersensitivity in mice. Amiloride analogues with greater and lesser inhibition of the Na+/H+ exchange were tested to determine whether anti-inflammatory effects correlate with this activity. Structural analogues of amiloride without significant activity at the Na+/H+ antiport (pyrazine, pyrazinamide, and chloropyrazine) failed to inhibit contact hypersensitivity. N-amidino-3-amino-5-dimethyl amino-6-chloropyrazinecarboxamide (DMA) has a 23-fold greater affinity for the Na+/H+ antiport compared to amiloride, but failed to inhibit contact hypersensitivity in this assay. 3,5-diamino-6-chloropyrazine-amido-guanidine (DCG), which has only 7% of the affinity of amiloride for the antiport, suppressed contact hypersensitivity as well as amiloride. Experiments examining the ability of these agents to diffuse through mouse skin revealed amiloride to be superior to both DCG and DMA, which were approximately equal. DMA, with greater inhibition of the Na+/H+ antiport but lesser ability to inhibit contact hypersensitivity, inhibited protein synthesis and induced cell death more than amiloride or DCG. Amiloride and DCG hold promise as topical anti-inflammatory agents. Their anti-inflammatory properties do not correlate with affinity for the Na+/H+ antiport, ability to penetrate murine skin, or inhibition of protein synthesis.

Amiloride↗

PubMed2006

Rapidly developing giant sized lupus vulgaris on the chest associated with bilateral scrofuloderma on the neck.

Lupus vulgaris and scrofuloderma are the opposite poles of cutaneous tuberculosis. Lupus vulgaris of a giant size and scrofuloderma in the vicinity of this lesion were both present in a 70-year-old female patient. The purified protein derivative of tuberculin (PPD) skin test was strongly positive. In histopathological examination, granulomatous infiltration without caseation necrosis was seen in the dermis. The patient was treated with a four-drug therapy consisting of pyrazinamide (25 mg/kg), isoniazid (5 mg/kg), rifampin (10 mg/kg) and ethambutol (15 mg/kg) daily for 2 months, followed by dual therapy with isoniazid and rifampin for 6 months. Her cutaneous lesions significantly regressed after 4 months, leaving keloid scars.

Aged↗

PubMed1989

Quadruple antimycobacterial chemotherapy in Crohn's disease: results at 9 months of a pilot study in 20 patients.

Twenty patients with active Crohn's disease, the majority refractory to conventional therapy, were treated with rifampicin, ethambutol, isoniazid, and pyrazinamide or clofazamine for 9 months. After this period, 10 were in remission (Crohn's disease activity index less than 150). Of the 10 not in remission, three had been at 6 months, but had relapsed on treatment. Nine of 10 patients on steroids at the beginning were off steroids at 9 months. Six patients came to surgery during the period, five for stricture formation without evidence of florid Crohn's disease outside the strictured segment. Three young patients with severe Crohn's disease facing total colectomy were spared surgery. No serious drug-related side-effects were encountered. The results of this pilot study suggest that controlled trials of antimycobacterial chemotherapy, using four or more of the best agents available, are worthy of assessment in Crohn's disease.

Adolescent↗

PubMed2005

Systematic review: tuberculous peritonitis--presenting features, diagnostic strategies and treatment.

The peritoneum is one of the most common extrapulmonary sites of tuberculous infection. Peritoneal tuberculosis remains a significant problem in parts of the world where tuberculosis is prevalent. Increasing population migration, usage of more potent immunosuppressant therapy and the acquired immunodeficiency syndrome epidemic has contributed to a resurgence of this disease in regions where it had previously been largely controlled. Tuberculous peritonitis frequently complicates patients with underlying end-stage renal or liver disease that further adds to the diagnostic difficulty. The diagnosis of this disease, however, remains a challenge because of its insidious nature, the variability of its presentation and the limitations of available diagnostic tests. A high index of suspicion is needed whenever confronted with unexplained ascites, particularly in high-risk patients. Based on a systematic review of the literature, we recommend: tuberculous peritonitis should be considered in the differential diagnosis of all patients presenting with unexplained lymphocytic ascites and those with a serum-ascites albumin gradient (SAAG) of <11 g/L; culture growth of Mycobacterium of the ascitic fluid or peritoneal biopsy as the gold standard test; further studies to determine the role of polymerase chain reaction, ascitic adenosine deaminase and the BACTEC radiometric system for acceleration of mycobacterial identification as means of improving the diagnostic yield; increasing utilization of ultrasound and computerized tomographic scan for the diagnosis and as a guidance to obtain peritoneal biopsies; low threshold for diagnostic laparoscopy; treatment for 6 months with the first-line antituberculous drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) in uncomplicated cases.

Adolescent↗

PubMed1984

Influence of rifampicin treatment on antipyrine clearance and metabolite formation in patients with tuberculosis.

The influence of an 8-day therapy with rifampicin (600 mg daily) was studied on antipyrine plasma clearance and metabolite formation in seven patients with tuberculosis (age 18-79 years), who were also treated with isoniazid and pyrazinamide. After rifampicin treatment the elimination half-life of antipyrine had decreased in all patients from 12.9 +/- 5.0 to 8.8 +/- 2.0 h (P less than 0.05). Antipyrine clearance had increased from 2.2 +/- 0.9 to 2.9 +/- 0.7 l/h (P less than 0.05), while no change in apparent volume of distribution was observed. The increase in antipyrine clearance was primarily due to a selective increase in the rate of formation of norantipyrine by 80% from 6.9 +/- 3.4 to 12.4 +/- 3.4 ml/min. Rifampicin seems to induce preferentially the cytochrome P-450 (iso-) enzyme(s) involved in the demethylation of antipyrine to norantipyrine. Other pathways of antipyrine metabolism were hardly affected. This provides further evidence for the involvement of different iso-enzymes of the cytochrome P-450 system in antipyrine metabolism in man.

Adolescent↗

PubMed2005

Metastatic tuberculous abscesses in an immunocompetent patient.

The decreased incidence of infectious diseases in developed countries may make their diagnosis difficult. Cutaneous tuberculosis is an example of this fact. A 44-year-old man presented with two painful abscesses on his lower extremities, which developed into chronic ulcers. A cutaneous biopsy revealed necrotizing granulomas in the dermis. Ziehl-Neelsen and periodic acid-Schiff stain were negative. Mantoux test was positive. Tc-99m scintigraphy showed increased uptake in the bone tissue of the left ankle and right tibiae, without direct relation to cutaneous lesions. Chest X-ray showed micronodular, apical, bilateral infiltrates, reduced volume of the right lung, and cavitation of the right superior lobe. Mycobacterium tuberculosis was grown from sputum and skin biopsy samples. Isoniazid, rifampin and pyrazinamide treatment for 2 months, followed by isoniazid and rifampin for 12 months, resulted in complete resolution. The clinical features of cutaneous tuberculosis in our patient were characteristic of tuberculous abscesses. Some uncommon findings, such as the low number of lesions, negative acid-fast resistant stains in cutaneous biopsy samples and his preserved general state of health, may be explained by a higher competence of the immune system than is usual in this clinical subset of disseminated tuberculosis. Cutaneous tuberculosis should be included in the differential diagnosis of cutaneous abscesses in immunocompetent patients.

Adult↗

PubMed2005

How soon does cutaneous tuberculosis respond to treatment? Implications for a therapeutic test of diagnosis.

BACKGROUND: It is difficult to demonstrate Mycobacterium tuberculosis in smears or biopsies and to grow it in culture in cutaneous tuberculosis because most cases are paucibacillary. A therapeutic trial of antitubercular drugs is frequently used to confirm the diagnosis in difficult cases. Information is lacking on the response to antitubercular therapy in cutaneous tuberculosis; consequently there are no clear guidelines on when to expect a response and also when to abandon a therapeutic trial. METHODS: We studied the records of 60 patients treated for cutaneous tuberculosis at our hospital to study the time course of the therapeutic response. All patients were treated with a short-course antitubercular regimen consisting of isoniazid 300 mg daily, rifampicin 450 mg daily, ethambutol 800 mg daily and pyrazinamide 1500 mg daily for 2 months followed by isoniazid and rifampicin in the same doses for 4 months. At follow-up visits, each patient was assessed by a dermatologist who recorded the presence or absence of clinical improvement in the skin lesions. RESULTS: Of the 60 patients seen, eight patients did not follow up after the initial consultation, 48 patients improved with treatment and four patients were classified as treatment failures. The timing of the first visit varied from 3 days to 15 months (median 27.5 days, mean 58.96 +/- 94.50) after initiation of treatment. Twenty-one patients were recorded to have improved within the first month of therapy. Twenty-seven patients who first reported more than 30 days after initiation of treatment were found to have improved. Four patients failed to respond during follow up ranging from 3 to 17 months. CONCLUSION: When a therapeutic trial is undertaken in cutaneous tuberculosis, 6 weeks of therapy with four drugs appears adequate to prove (or disprove) the diagnosis.

Adolescent↗

PubMed2005

Photo-onycholysis due to sparfloxacin.

This paper describes a case of sparfloxacin-induced photodermatitis associated with photo-onycholysis in a 36-year-old man. He was being treated with sparfloxacin, streptomycin, ethambutol and pyrazinamide for pulmonary tuberculosis. He developed an exaggerated sunburn-like rash over the face and the dorsa of hands and feet, and painful onycholysis of finger- and toe-nails. Withdrawal of sparfloxacin resulted in resolution of the skin rash and nail tenderness.

Adult↗

PubMed1995

Acute renal failure after exercise in a child with renal hypouricemia.

We describe a 15 year old boy with renal hypouricemia who developed acute renal failure after a school athletics meeting, accompanied by appendicitis. During acute renal failure, the highest level of uric acid was 5.0 mg/dL, creatinine 7.9 mg/dL and urea nitrogen 58.6 mg/dL. After recovery, the serum uric acid fell to 0.9 mg/dL and the fractional excretion of uric acid (FEuA) exceeded the normal range. The probenecid and pyrazinamide tests showed that the patient had a total defect of uric acid reabsorption. This case suggested that strenuous exercise could be responsible for acute renal failure in patients with renal hypouricemia.

Acute Kidney Injury↗