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PubMed2001

Childhood tuberculosis: treatment strategies and recent advances.

Over the past 20 years, several major studies have shown that 6-month therapy, initially using isoniazid, rifampin and pyrazinamide, is highly effective and extremely safe for the treatment of most forms of childhood tuberculosis. The various drug schedules and frequency of administration will be reviewed. Directly observed therapy is an essential component of a paediatric tuberculosis treatment plan, though using it does not solve all problems with adherence to treatment. As the rates of drug-resistant tuberculosis increase around the world, special aspects of paediatric tuberculosis will have to be considered when designing treatment regimens for children. Finally, the next frontier of antituberculosis therapy may be the manipulation of the host immune system.

AIDS-Related Opportunistic Infections↗
PubMed1998

Genotypic characterization of drug-resistant Mycobacterium tuberculosis isolates from Peru.

SETTING: Twenty-nine epidemiological unrelated and mostly multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains from Peruvian patients. OBJECTIVE: To investigate the molecular genetics of MDR-TB strains recovered in a Latin American country. DESIGN: Antimicrobial agent susceptibility testing, major genetic group designation, IS6110 fingerprinting, spoligotyping, and automated deoxyribonucleic acid sequencing of regions of the katG, rpoB, embB, gyrA, and pncA genes with mutations commonly associated with drug resistance. RESULTS: Nineteen isolates were found to be multidrug-resistant by susceptibility testing. IS6110 typing showed that virtually all isolates were unique and therefore had independently acquired drug resistance. Seventy-nine percent of isoniazid-resistant strains had a Ser315Thr amino acid change in KatG. Ninety-five percent of rifampin-resistant isolates had amino acid replacements in the rifampin-resistance determining region of RpoB. Six of 11 ethambutol-resistant strains had EmbB alterations. Eleven pyrazinamide-resistant strains had distinct mutations in pncA. CONCLUSION: Virtually all organisms evolved drug resistance independently. The types of drug resistance-associated mutations identified were very similar to changes occurring in isolates from other areas of the world. Nucleotide sequence-based strategies for rapid detection of drug resistance-conferring mutants will be applicable to organisms recovered in Peru, and potentially other areas of Latin America.

Amidohydrolases↗
PubMed2002

[Osteomyelitis of the tibial head caused by Mycobacterium haemophilium in a patient with AIDS].

HISTORY AND ADMISSION FINDINGS: A 53-year-old man with known HIV infection and AIDS was admitted because of painful swelling at the right knee for 6 weeks. The cause was thought to be osteomyelitis and surgical treatment was planned. INVESTIGATIONS: No causative pathogen was found at curettage and lavage of an abscess at the right medical head of the tibia, but at a subsequent operative revision acid-fast rods were seen and identified as Mycobacterium haemophilum. TREATMENT AND COURSE: A systemic antibiotic, 1 g levofloxacin daily, had been started at the initial abscess operation. 2 weeks later, because swelling of the right knee had recurred with marked local and systemic signs of infection, a second surgical intervention was performed. Afterwards, in view of the histological finding of acid-fast bacteria suggesting tubercular osteomyelitis, the patient was put on combined treatment with 300 mg/d of isoniazid, 1600 mg/d of ethambutol, 2 g/d of pyrazinamide, and 1 g of streptomycin i.m. every other day. After molecular microbiological identification of M. haemophilum the antibiotic treatment was changed to 1600 mg/d of ethambutol, 300 mg/d of rifabutin and 1 g/d of clarithromycin. The operation wound healed well. CONCLUSION: M. haemophilum infection can be lethal in immunodeficient patients if untreated. Although there is no standard treatment, this rare infectious disease responds relatively well to a modified combined tuberculostatic regimen. Special laboratory techniques to identify the specific causative pathogen are therefore of great importance.

AIDS-Related Opportunistic Infections↗
PubMed2003

Abdominal tuberculosis in children.

UNLABELLED: Abdominal tuberculosis (AT) is a rare cause of intraabdominal infection. Surgical intervention is rarely indicated, other than obtaining a specimen for histopathological diagnosis or for the treatment of complications. METHODS: The medical records of 14 patients who were operated on after the diagnosis of AT between 1983 and 2000 were reviewed retrospectively. RESULTS: Median age was 7 years (6 months to 10 years). The presenting clinical signs and symptoms were as follows: colicky abdominal pain (9), weight loss (8), abdominal mass (6), vomiting (5), and night fever (5). Two patients were operated at another centre and referred to our department with faecal fistula and severe malnutrition. Twelve patients were operated on, while diagnostic laparoscopy was performed in two. In uncomplicated cases, surgical intervention was limited to sampling of peritoneal tissue, lymph node and ascites. The reasons for surgical intervention were intestinal obstruction (9), abdominal mass and ascites (6), psoas abscess (1) and intussusception (1). Adhesive peritonitis and ileal loops were the cause of abdominal mass. Necrosis of the bowel (2) and perforation (1) were detected in three patients. The diagnosis was confirmed either by histopathological or microbiological examination. In eight patients, AT was defined at the intestinal mesentery, in three patients it was localised to the peritoneum and in two patients the disease was diffuse. All patients except one with faecal fistula survived and were treated successfully with antituberculous therapy (isoniasid, rifampicin, streptomycin and pyrazinamide combination). CONCLUSION: The diagnosis of AT is difficult before presentation with complications of intraabdominal infection. Since the response to chemotherapy is usually excellent in patients with suspected AT, aggressive surgery should be avoided and initial surgical intervention should be limited to tissue and/or fluid sampling.

Child↗
PubMed2004

[Pleuritis tuberculosa - therapeutic value of repeated chest tapping].

Tuberculous pleuritis tends to develop fibrosis to a high degree. The use of corticosteroids enhances the absorption of pleural effusions, the residual pleural thickening, however, remains unaffected. Whether repeated chest tapping in patients with persistent effusions in addition to antituberculous therapy favourably influences the outcome is not known. Therefore, patients with tuberculous pleuritis were examined in a prospective, randomized study. After confirmation of the diagnosis patients were randomized in group A with antituberculous treatment (Isoniazid, Rifampicin, Pyrazinamid, and Streptomycin) alone or in group B with additional pleural tapping for four weeks (phase I). In phase II patients in both groups with persistent effusions received oral prednisolone (0,75 mg/kg body weight) tapered over four weeks. The extent of pleural effusions was determined by chest X-ray. Roentgenological changes were evaluated at the end of the observation period. Lung function tests by spirometry were performed after two, four, eight weeks, and at the last follow up visit. At the end of phase I no pleural effusion could be observed roentgenologically in group A in 7 of 16 patients (44 %) and in group B in 10 of 16 patients (63 %) (p = n. s.). At the end of phase II extensive residual thickening was observed in one patient (group B) necessitating pleurectomy six months later. The lung function parameters demonstrated a restrictive pattern, which did not differ significantly at the end of the observation period. After a mean follow-up period of four months none or minimal residual changes could be observed radiologically in the remaining patients. In summary, despite the low number of patients examined, this study shows that in patients with tuberculous pleuritis repeated chest tapping in addition to antituberculous medication does not seem to benefit the patient, as neither the degree of residual pleural thickening nor the restrictive lung function impairment seem to be influenced significantly.

Adult↗
PubMed2005

[Rare cause of right heart failure: two cases].

HISTORY AND ADMISSION FINDINGS: Two asylum seekers (patient A, 30 year old man from Mongolia; patient B, 18 year old woman from the Sudan) were referred to our outpatient clinic because of acute and chronic deterioration of their general condition and shortness of breath. Both patients presented with a clear clinical picture of systemic venous hypertension and moderate pulmonary congestion. Patient B had a paradoxical pulse compatible to cardiac tamponade. INVESTIGATIONS: In patient A, the chest radiogram revealed a markedly enlarged cardiac silhouette and an infiltrate in the upper left lobe of the lung. The echocardiogram confirmed a pericardial effusion causing a cardiac tamponade. A therapeutic and diagnostic pericardiocentesis was performed immediately. In patient B, the chest radiogram revealed a thickened and calcified pericardium and a left-sided pleural effusion. The pleural fluid revealed a lymphocyte-predominant exudate. In both patients the tuberculin skin test was positive. DIAGNOSIS, TREATMENT AND COURSE: In both patients we initiated an antituberculous therapy (four-drug therapy with isoniazid, rifampin, pyrazinamide and ethambutol; in patient A in addition corticosteroids). In patient A the PCR for Mycobacterium tuberculosis complex from pericardial fluid was positive. In patient B we started the antibiotic treatment despite negative microbiological studies because of the high degree of suspicion in a person at high risk. Due to the impaired ventricular filling, patient B required additional pericardectomy. After completion of treatment, both patients have been doing well. CONCLUSION: Despite a clear reduction in the incidence of tuberculous pericarditis in Europe this multifaceted condition should still be of concern in patients at high risk as e. g. immigrants from areas with a high tuberculosis prevalence. Early diagnosis and adequate treatment are required for prevention of severe complications and disabling constrictive pericarditis.

Adolescent↗
PubMed2006

[Gastrointestinal tuberculosis as the main manifestation of systemic tuberculosis].

We describe a rare case of tuberculosis with mainly gastrointestinal problems. The 52-year-aged female patient came to hospital with unclear pain in the lower abdomen and ascites that was refractory to therapy. The computed tomography of the thorax showed right-sided confluating lymphoid nodes, the CT of the abdomen showed ascites and nodular structures near the coecum. Tissue samples were taken from the mucosa of the colon, the inflammatory altered peritoneum, the left bronchus of the upper lobe and the confluating lymphoid nodes in the mediastinum during colonoscopy, diagnostic laparoscopy and bronchoscopy. The samples from the peritoneum showed granulomas with caseating necroses in histological slices. Mycobacterium tuberculosis was detected by PCR in the tissue samples from the lymphoid tissue of the mediastinum. Furthermore, Mycobacterium tuberculosis grew in cultures from samples of the abdominal ascites. The symptoms and pathological findings improved under a therapy comprising isoniazid, rifampicin, ethambutol and pyrazinamid.

Female↗
PubMed1996

Cerebral tuberculosis presenting as complex febrile convulsions.

Complex febrile convulsions were the initial clinical manifestation of miliary tuberculosis in a 4-year-old immigrant girl. The cerebral lesions were visible only after contrast-enhanced cranial computed tomography (CT) while native CT scan as well as cell count and glucose concentration in the cerebrospinal fluid were normal. Mycobacterium tuberculosis was cultured from gastric aspirate and liver biopsy tissue. Treatment with isoniazid and rifampin for 12 months, pyrazinamide for 9 months, and ethambutol for the initial 6 weeks resulted in resolution of the cerebral lesions but a retinal scar after granuloma formation in the right eye caused reduced visus. This case demonstrates the importance of thorough search for tuberculosis even in the absence of overt clinical pulmonary signs especially in high-risk individuals such as immigrants.

Antitubercular Agents↗
PubMed1994

[Primary clinical manifestation of tuberculosis as an incidental finding in the head and neck area].

Between 1988 and 1992 12 patients were seen who had findings leading subsequently to the diagnosis of tuberculosis. The average age was 50 with a range from 22 to 88 years. Women outnumbered the male by 10 to 2 cases. The number of German patients equalled that of foreign patients. Tuberculosis was mainly localised in the cervical lymph nodes in 6 cases. One patient was seen with manifestation in each case at the palate, larynx, nasopharynx, cheek, parotis and middle ear. Diagnosis was made by histology alone six times, by evidence of acid-fast rods once and by both means in 5 cases. Preoperatively a malignant neoplasm was suspected in most patients, and neither CT nor ultrasound revealed a hint to tuberculosis. Tine-test was positive in all patients. Only in 3 patients was there an evidence of acid-fast rods in sputum and gastric juice. None of them suffered from AIDS. They were treated by combination of rifampicin, ethambutol, isoniazid and partially with pyrazinamide. No relapse was observed to date.

Adult↗
PubMed1996

[Miliary tuberculosis and silicosis with predominantly cerebral symptoms].

HISTORY AND CLINICAL FINDINGS: About 10 weeks before admission to hospital a 73-year-old woman developed a fever of up to 40 degrees C for three days. She then had subfebrile temperature for several weeks with some rises to 39 degrees C. She was known to have type II a diabetes mellitus and pulmonary silicosis, having worked in a porcelain and ceramic factory for many years. Before admission her cerebral functions were rapidly deteriorating, especially short-term memory. This was followed by increasing paraplegia of the legs with inability to walk. She finally had urinary and faecal incontinence and swallowing difficulties with tendency to aspiration, which necessitated hospitalisation. INVESTIGATIONS: Both lactate dehydrogenase (339 U/l) and C-reactive protein (112 mg/l) were elevated; the platelet count was low (73000/microliters). Cerebrospinal fluid was unremarkable, as was computed tomography of the skull. But magnetic resonance imaging revealed multiple spotty lesions with low contrast-medium uptake throughout the brain, pointing to a disseminated bacterial or mycotic infection. 3 days later the chest-ray showed small nodular soft shadows in the lungs, and lung functions had decreased. Mycobacteria were found in the urine and liver biopsy showed granulomatous hepatitis, establishing the diagnosis of miliary tuberculosis in the presence of silicosis. TREATMENT AND COURSE: Tuberculostatic treatment was instituted with four drugs (pyrazinamide, ethambutol, isoniazid and streptomycin. After 6 weeks the patient was again able to walk and continent of urine during the day. All cerebral functions gradually improved. CONCLUSION: Miliary tuberculosis should be included in the differential diagnosis of ill-defined feverish disease, especially in the elderly.

Aged↗
PubMed1997

[Costosternal swelling and diffuse bone pain in tubercular osteomyelitis].

HISTORY AND CLINICAL FINDINGS: For about a year a 28-year-old Nigerian had been suffering from diffuse bone pain, intermittent fever, weight loss and weakness. Physical examination was unremarkable except for a swelling at the sternal angle. INVESTIGATIONS: The tuberculin test was clearly positive and tests for inflammatory disease were elevated, but the chest radiograph was normal. Bone scintigraphy demonstrated multiple sites of increased storage in the ribs and vertebral column. Magnetic resonance imaging revealed a large paravertebral abscess, which was needled under computed tomography monitoring. Polymerase chain reaction of the aspirate demonstrated Mycobacterium tuberculosis. TREATMENT AND COURSE: While initial treatment with combined isoniazid, streptomycin, rifampicin and pyrazinamide, the first two drugs had to be discontinued, the microorganism not being sensitive to them, and were replaced by ethambutol and amikacin. The abscess was drained and the vertebral fracture surgically stabilised. There were no neurological abnormalities and the lesions largely healed. CONCLUSION: Even without pulmonary involvement tuberculosis must be included in the differential diagnosis of rheumatic diseases with joint and vertebral column involvement, such as the SAPHO syndrome and other inflammatory bone diseases.

Abscess↗
PubMed1995

[Tuberculous spondylitis--a forgotten differential diagnosis in backache].

A four-year-old boy had been complaining for one year of backache when sitting or bending. Radiological changes in the lumbar spine were at first interpreted as due to an old vertebral fracture. Half a year after the onset of the symptoms his sister was found to have open pulmonary tuberculosis, but a positive Tine test (he had not received BCG vaccination) was without any consequences. He was finally hospitalized five months later because the backache persisted and he now also had impaired movement of the left hip-joint. Physical examination revealed a 10 x 15 cm firm mass in the abdomen. Imaging demonstrated destruction of the 4th and 5th lumbar vertebrae and a large abscess. Acid-fast bacteria were found in gastric juice. Tuberculostatic treatment was started with isoniazid (10 mg/kg), rifampicin (10 mg/kg) and pyrazinamide (30 mg/kg). Two weeks later spondylectomy was performed, the defect being bridged with bone chips from the iliac crest. Four months after the operation, tuberculostatic treatment now being only isoniazid and rifampicin, he was able to partake fully in all activities of his age group.

Anti-Bacterial Agents↗
PubMed1994

[Duodenal tuberculosis. A rare cause of a covered perforation in the duodenal bulb].

Vague upper abdominal pain, weight loss (10 kg) and recurrent bouts of fever had been present for several months in a 77-year-old woman. Abdominal ultrasonography in the region of the head of the pancreas and duodenum had demonstrated several lymphomas, some of them with "air streaking". This finding suggested penetration from the duodenum to neighbouring lymph nodes. Plain film of the abdomen did not show free air, but at gastroscopy a covered perforation into the surrounding lymph nodes was found. At first lymphoma or Crohn's disease were considered in the differential diagnosis. But the finding of acid-fast bacteria in a biopsy from the pelvic crest suggested intestinal tuberculosis with dissemination. This diagnosis was confirmed by the direct demonstration of Mycobacterium tuberculosis in gastric juice. Under tuberculostatic treatment with daily 0.3 g isoniazid, 0.45 g rifampicin, 0.8 ethambutol and 1.5 g pyrazinamide, as well as 50 mg prednisolone to prevent stricture, the size of the tuberculous ulcer had markedly decreased within 2 weeks. Follow-up gastroscopy after 6 months showed almost complete healing without stricture. However rare, gastrointestinal tuberculosis should not be forgotten in the differential diagnosis because it can imitate a large variety of gastrointestinal diseases.

Aged↗
PubMed1994

[Baker's cyst in osteoarticular tuberculosis of the knee joint].

A Baker cyst (synovial cyst) in the right knee-joint was demonstrated by ultrasound in a 70-year-old woman with recurrent knee-joint effusions after minimal trauma to the knee. Radiological examination in two planes showed degenerative changes corresponding to age. Needle puncture of the knee-joint demonstrated numerous neutrophil granulocytes. As the effusion recurred after one week, despite rest and avoidance of weight bearing, arthroscopy with removal of the cyst was indicated. But surprisingly histological examination of synovial tissue revealed epithelioid granulomas and Langerhans giant cells. Culture of fluid obtained on repeat puncture finally grew Mycobacterium tuberculosis. There was no evidence of pulmonary tuberculosis. The knee-joint tuberculosis healed completely without residual damage on antituberculosis treatment, initially 600 mg rifampicin daily, 300 mg isoniazid daily and 2.5 g pyrazinamide daily for 3 months, followed by rifampicin and isoniazid for a further 6 months.

Aged↗
PubMed1994

[Incompatibility of tuberculosis therapy in a patient with AIDS].

A man with advanced HIV infection (CD4 lymphocytes 90/microliter, CD4/CD8 ratio 0.2) was admitted to hospital with fever, cough and weight loss. The radiological and bronchoscopic findings, together with the presence of acid-fast bacilli in the sputum, pointed to open pulmonary tuberculosis caused by Mycobacterium tuberculosis, a diagnosis confirmed by histological examination and culture. Quadruple antibiotic therapy with isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and amikacin was immediately begun and was at first clinically successful. Ten days later, however, a rash appeared; it was ascribed to RMP (anaphylactoid reaction after re-exposure). All the other first-line drugs tried during the ensuing eight months evoked severe adverse reactions (INH: rash and itching; amikacin: hearing impairment and tinnitus; EMB, pyrazinamide, prothionamide, p-aminosalicylic acid: rash and itching). Treatment was nevertheless clinically and microbiologically successful, and the patient insisted upon a 2 1/2 months' rest without therapy. This period was followed by extrapulmonary spread (severe arthritis of the elbow) and recurrence of pulmonary tuberculosis. The tubercle bacilli were sensitive to all the drugs so far employed. Renewed and lasting control of the infection was achieved only by continuous administration of steroids (prednisolone 10 mg twice daily) in conjunction with an unconventional antibiotic regimen consisting of amikacin, protionamide, terizidone, clarithromycin and sparfloxacin for some five months. Because of an episode of cerebral convulsions during treatment of cytomegalovirus retinitis with ganciclovir, the terizidone was discontinued (it was suspected of interacting with ganciclovir). The patient has had no more fits and sputum culture has remained negative for six months.

AIDS-Related Opportunistic Infections↗
PubMed1993

[Mycobacterium genavense infection in AIDS].

Fever, loss of weight, anaemia, hepatosplenomegaly and lymphadenopathy developed in two HIV-infected patients. At first malignant lymphoma with septicaemia was thought to be the cause. In both patients Salmonella enteritidis was isolated by blood culture and found to be sensitive against the antibiotics that were given (5 g azlocillin and 2 g cefotaxime, three times daily each; additionally in case 2, metronidazole, 500 mg three times daily). Because bone-marrow biopsy demonstrated acid-fast rods, antimycobacterial treatment was started (isoniazid 300 mg/d, rifampicin 600 mg/d, ethambutol 1,200 mg/d and pyrazinamide 2 g/d). Despite this the patients died of septic shock. Histological examination revealed massive amounts of acid-fast rods in spleen, liver, gut and bone marrow. Polymerase chain reaction and sequencing identified the structure as that of the recently discovered M. genavense.

AIDS-Related Opportunistic Infections↗
PubMed1993

[Suprasellar space-occupying lesion as initial manifestation of tuberculosis in childhood].

Three days after having sustained a mild trauma to the head a seven-year-old boy developed seizure-like rotatory vertigo. Computed tomography, magnetic resonance imaging and cerebral angiography demonstrated a suprasellar space-occupying lesion. Pulmonary tuberculosis was discovered in subsequent diagnostic work-up. Cerebrospinal fluid examination was unremarkable except for immunological tests (tuberculostearic acid) which pointed to central nervous system (CNS) involvement so that a tuberculoma was suspected. The lesion decreased in size on tuberculostatic treatment (200 mg/d isoniazid, 200 mg/d rifampicin, two times 250 mg/d pyrazinamide). In the next 12 months there merely persisted a mild abnormality of the blood-brain barrier with a little contrast-medium uptake, which regressed in the following 6 months. The differential diagnosis between CNS tuberculosis and brain tumour or pyogenic abscess can be difficult in children if there are no pulmonary signs and/or the cerebrospinal fluid is normal.

Antitubercular Agents↗
PubMed1993

[Pneumonia due to a rare atypical Mycobacterium in AIDS].

A 38-year-old man, HIV-positive for 6 years, developed fever and cough with deterioration in his general state. Chest radiography demonstrated an infiltration in the left upper lobe and computed tomography showed a septated cavity. Three bronchioalveolar lavages over 4 weeks recovered Klebsiella, Candida, Pseudomonas and Staphylococcus in the lavage fluid. Acid-fast rods were not found in any of the microscopic preparations. His clinical condition and the radiological findings deteriorated despite appropriate antibiotic administration. A further cavity occurred in the right upper lobe and the inflammatory infiltrations extended further. Although no acid-fast organism had been demonstrated, tuberculostatic treatment was begun (daily 300 mg isoniazid, 600 mg rifampicin, 900 mg streptomycin, 2 g pyrazinamide). His general condition and the radiological findings rapidly improved. Four weeks after culturing the lavage fluid atypical Mycobacterium xenopi was isolated. This case illustrates the difficulty of diagnosing an atypical mycobacterial infection. It takes time and effort, but it is of great importance because up to 50% of patients with AIDS contract such infection. Early and appropriate treatment will significantly improve quality of life and life expectancy.

AIDS-Related Opportunistic Infections↗