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PubMed2003

Chronic cases of tuberculosis in Casablanca, Morocco.

OBJECTIVE: To evaluate the prevalence and patterns of drug resistance of Mycobacterium tuberculosis isolates collected from patients with chronic tuberculosis in Casablanca, Morocco. METHODS: Between February 1996 and September 2001, 122 isolates were recovered from 112 different patients. The male to female ratio was 2.4. RESULTS: From February 1996 to May 1997, 77.5% of isolates were multidrug-resistant (MDR-TB), compared to 69.4% from February 1999 to May 2000 and 78.7% from June 2000 to September 2001. The prevalence of MDR-TB is similar from the initial to the last period of this study. Analysis of the 69 bp hypervariable region of the rpoB gene by DNA sequencing on 42 M. tuberculosis isolates (37 resistant, 5 sensitive) showed nine different types of mutations on codons rpoB 513, rpoB 516, rpoB 522, rpoB 523 and rpoB 526. A new point mutation was observed on codon rpoB 523 on one isolate. No mutation was detected on this rpoB region for four resistant isolates. CONCLUSION: The high rate of MDR-TB illustrates a serious problem. The public health authorities have introduced a new regimen protocol consisting of 3 months of kanamycin, ofloxacin, pyrazinamide and ethionamide, followed by 18 months of ofloxacin, pyrazinamide and ethionamide (3KOZEA/18OZEA) for this category of patients, and it is hoped that the additional use of ofloxacin during the intensive phase of treatment will reduce the rate of resistance.

Adult↗
PubMed2003

[Agranulocytosis due to anti-tuberculosis drugs including isoniazid (INH) and rifampicin (RFP)--a report of four cases and review of the literature].

We experienced 4 cases of agranulocytosis due to anti-tuberculosis drugs (rifampicin [RFP], isoniazid [INH], ethambutol [EB], streptomycin [SM] or pyrazinamide [PZA]) among some 6,400 tuberculosis patients who underwent chemotherapy over the past 20 years from 1981 to 2002 in our hospital, and the incidence rate of agranulocytosis was estimated at 0.06%. The 4 cases of agranulocytosis were as follows. CASE 1: A 51-year-old woman with right chest pain and fever was admitted to our hospital on Jan 4, 2001. The white blood cell (WBC) count was 5,200/microliter. The tubercle bacilli were cultured in her sputum. The treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, allopurinol and teprenone was started on Jan 13. Pyrazinamide and allopurinol were stopped because of hyper-uric acidemia on Feb 7. Agranulocytosis and eosinophilia (WBC 1,300 [Neut 1%, Ly 57%, Eos 35%]) developed on Feb 13. All drugs were withdrawn and G-CSF drug nartograstim 100 micrograms was injected subcutaneously for 3 days. The WBC recovered to normal level and she was thereafter treated with INH, EB and Levofloxacin (LVFX) without any further trouble. Agranulocytosis in this case was supposed to be due to RFP. CASE 2: A 66-year-old man who had had nephrotic syndrome and hypothyroidism and has been treated with prednisolone 10 mg/day was admitted to our hospital on Aug 9, 2000 because of miliary tuberculosis. The tubercle bacilli were cultured in his sputum and the treatment with INH 0.3, RFP 0.45, and EB 0.75 g/day were started on Aug 10, but it was withdrawn on Aug 17 because of general skin eruption. After re-starting treatment with EB and INH on Aug 24, RFP was added in small dosage (0.05 g) on Oct 12, but agranulomatosis (WBC 2,300/microliter [Neut 2%]) developed on Nov 21, and all drugs were withdrawn again. The G-CSF drug filgrastim was used once subcutaneously, and WBC recovered immediately. He was thereafter treated with INH, EB, LVFX successfully. Agranulocytosis was supposed to be due to RFP. CASE 3: A 60-year-old woman without symptoms had abnormal chest roentgenograph, and consulted with our hospital on Aug 26, 2002. The broncho-alveolar lavage fluid was smear and culture-negative, but PCR-TB positive, and the case was diagnosed as pulmonary tuberculosis. Treatment with INH 0.3, RFP 0.45, EB 0.75, PZA 1.2 g/day, alloprinol 300 mg and rebamipide 300 mg/day was started on Sept. 5, 2002. Late in September, she complained of appetite loss. The laboratory data on Oct 3 revealed WBC 900/microliter (Neut 1%, Ly 94%), aspartate aminotransferase (AST) 199 IU/l, and alanine aminotransferase (ALT) 253 IU/l, showing agranulocytosis and drug-induced hepatitis. The chemotherapy was immediately withdrawn and she was admitted to our hospital on the next day. Glycyrrhizin derivative (SNMC) 40 ml was injected for 5 days, and WBC recovered, and AST and ALT also became normal. CASE 4: A 60-year-old man was admitted to our hospital on March 11, 1981 because pulmonary tuberculosis had recurred. He had been treated with SM, PAS and INH in 1973 for pulmonary tuberculosis. On admission examination of blood count and blood chemistry were normal. Treatment with RFP, INH and SM was started on March 11. He stopped out from the hospital on April 17, but in a few days he returned back with sore throat, lower lip swelling and gingival bleeding. Blood cell count on April 24 showed pancytopenia with RBC 226, Hb 7.5, WBC 800 (Ly 96%, Eos 4%) and Plt 10,000/microliter. The bone-marrow showed NCC (nuceated cell count) of 5,500, and megakaryocyte 0. Thereafter ground glass appearance shadows were seen on the whole lung field, and he died May 26. Autopsy showed generalized aspergillosis. It was strongly suspected that either of RFP, INH or SM was responsible for his pancytopenia. We collected another 10 cases of agranulocytosis due to anti-tuberculosis drugs in the world wide literature, and found men/women ratio 5/8 (in one case gender was not known), the duration of chemotherapy before appearance of agranulocytosis 1-3 months, no change in the lymphocyte count of the peripheral blood, and the accompanying of another allergic signs such as skin eruption, blood eosinophilia or drug-induced hepatitis in some cases, and these findings suggest that the mechanism of agranulocytosis due to anti-tuberculosis drugs was allergic in nature.

Aged↗
PubMed1992

Hydrazine--a possible cause of isoniazid--induced hepatic necrosis.

Pharmacokinetic parameters of isoniazid, hydrazine (a metabolite of isoniazid), rifampicin and pyrazinamide in a 74-year-old man with pulmonary tuberculosis who died of submassive hepatic necrosis eight days after starting antituberculosis therapy were compared with those of other elderly patients who did not develop hepatotoxicity. Steady-state plasma hydrazine and rifampicin concentrations in this patient exceeded twice the mean +/- 2 SD value for the group of patients without hepatotoxicity, while concentrations for isoniazid and pyrazinamide were comparable. The findings suggest that HYD may have a role in isoniazid-induced hepatic necrosis.

Age Factors↗
PubMed2006

Oral poly(lactide-co-glycolide) nanoparticle based antituberculosis drug delivery: toxicological and chemotherapeutic implications.

The present study reports on the detailed toxicological and chemotherapeutic evaluation of antituberculosis drug loaded nanoparticles in mice. A single oral dose administration of poly(lactide-co-glycolide) (PLG, a synthetic polymer) nanoparticles containing rifampicin+isoniazid+pyrazinamide+ethambutol could maintain drug levels in various tissues for 9-10 days and did not elicit any adverse response even when administered at several fold higher than the recommended therapeutic dose. However, dosing with conventional free drugs at the equivalent higher doses was lethal. Despite multiple oral dosing with the formulation at every 10th day, no toxicity was observed on the completion of subacute (28 days) or chronic (90 days) toxicity studies based on survival, gross pathology, histopathology, blood biochemistry and hematology. In mice harboring a high mycobacterial load (mimicking human tuberculosis), two independent chemotherapeutic regimens, i.e. 5 doses of PLG nanoparticles encapsulating (rifampicin+isoniazid+pyrazinamide+ethambutol) administered 10 days apart, or 2 doses of the 4-drug formulation followed by 3 doses of 2-drug formulation (rifampicin+isoniazid) resulted in undetectable bacilli. Further, the efficacy was comparable to 46 daily doses of oral free drugs. Therefore, the experimental evidence suggests that PLG nanoparticle-based antituberculosis drug delivery system is safe and well suited for prolonged and intermittent oral chemotherapy.

Administration, Oral↗
PubMed2006

[Efficiency of a new standard chemotherapy regimen in the treatment of patients with recurrent pulmonary tuberculosis].

The efficiency of conventional chemotherapy regimens was comparatively studied in 75 patients with recurrent pulmonary tuberculosis. In the patients with recurrent pulmonary tuberculosis, conventional chemotherapy regimen "2b" including isoniazid, rifampicin, pyrazinamide, ethambutol, fluoroquinolone (ofloxacin, ciprofloxacin, and levofloxacin), and canamycin (amikacin) versus conventional chemotherapy regimen "2a" including isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin could cease bacterial isolation after 3-month therapy, as evidenced by sputum microscopy (86.1 and 62.5%, respectively; p < 0.05). Cavity closure was more frequently observed after 6-month chemotherapy using regimen "2b" (76.7 and 48.0%, respectively; p < 0.05). In patients with recurrent pulmonary tuberculosis who isolated Mycobacterium tuberculosis (MBT) resistant to isoniazid and other antituberculous drugs (exclusive of rifampicin), 3-month use of conventional regimen "2b" led to cessation of bacterial isolation (as evidenced by the inoculation test) in 66.7% of cases; but this did not occur with conventional regimen "2a" in any case. Similarly, 3-month use of regimens "2b" and "2a" in patients isolating MBT resistant to rifampicin and other agents (exclusive of isoniazid) resulted in the cessation of bacterial isolation in 80 and 0% of cases, respectively. In multidrug resistance, these parameters were 11.1 and 0%, respectively.

Adolescent↗
PubMed2006

[Risk factors of side effects of antituberculosis drugs].

The aim of this study was to determine the side effects of standard antituberculosis therapy with isoniazid, rifampicin, pyrazinamide and streptomycine in patients treated for tuberculosis. One hundred eighty nine patients with proven tuberculosis, who initially received standard antituberculosis therapy, were retrospectively studied. Begaud and coll's method of side effects drugs imputability elaborated in 1999 was used in our study. Side effects related to therapy were present in 31.7% of the studied population. Gastrointestinal side effect was the most common (13.2%), isoniazid, rifampicin and pyrazinamide were often incriminated. The significant risk factors of hepatotoxicity were female gender (OR : 10.59) and concomitant hepatotoxic drugs (OR 6). Chocleovestibular toxicity was associated significantly with female gender (OR : 8.03) and diabetes mellitus (OR : 6.13). Patients aged above 50, proved to be at risk for pyrazinomide intolerance and females for streptomycine. The study did not reveal any susceptibility to isoniazid and rifadine intolerance.

Adolescent↗
PubMed1990

Dosing regimens in the treatment of tuberculosis.

Specific antituberculosis chemotherapy started in the early 1940s. The development of isoniazid in 1952 enhanced the probability of achieving curative therapy. Introduction of rifampicin in the late 1960s and addition of the sterilizing agent pyrazinamide made it possible to shorten the length of treatment and to give it intermittently so that it could be fully supervised. The important principles to consider in the formulation of adequate therapy for tuberculosis are the different bacterial populations and drug resistance. The antituberculosis drugs vary in their bactericidal action, sterilizing action, ability to prevent the emergence of acquired resistance and suitability for intermittent use. The recommended regimen for newly diagnosed patients is a six month daily regimen of isoniazid and rifampicin, supplemented with pyrazinamide for the first two months. Variants of the standard six month regimen are used when fully supervised intermittent chemotherapy can be organised, when there is a high level of initial resistance or if it is suspected that the patient's strain is resistant to isoniazid. The recommended dosages are appropriate for all forms of tuberculosis and are the same for children and adults.

Antitubercular Agents↗
PubMed1990

[Tuberculosis therapy 1990].

The goal of modern therapy of tuberculosis is the rapid killing of all bacilli with potent and relatively atoxic antituberculous drugs. Currently available first-line drug regimens are highly effective, well tolerated and relatively easily administered. The addition of Pyrazinamide enables the minimum treatment period to be shortened to six months (two months Isoniazid, Rifampin, Pyrazinamide and four months Isoniazid, Rifampicin). This article reviews the available first-line drugs in treatment of tuberculosis, the rationale for the recommended chemotherapeutic regimens, the follow-up of treated patients and special issues related to the treatment of extrapulmonary tuberculosis and tuberculosis in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Bacteriologic basis for the treatment of tuberculosis].

To be fully effective, short-course chemotherapy for tuberculosis should take into account the slow growth rate, high oxygen requirement and high drug-resistant mutant emergence rate of Mycobacterium tuberculosis, as well as the type of the lesions observed and the specific activity of each antituberculous drug. Due to their unique sterilizing activities against bacilli that are not actively metabolizing, rifampicin and pyrazinamide are the key drugs for short-course chemotherapy. To prevent the selection of drug-resistant mutants and the occurrence of therapeutic failures, a combination of isoniazid, rifampicin, pyrazinamide and ethambutol should be given during the first two months of treatment. To kill persisting M. tuberculosis, and thus avoid posttreatment relapses, the isoniazid-rifampicin combination should be prescribed for à further four months.

Antibiotics, Antitubercular↗
PubMed1989

Short course chemotherapy for pulmonary tuberculosis. A randomised controlled trial of a six month versus a nine month oral regimen.

We report on the first trial in the Republic of Ireland to look at chemotherapy for TB. This management trial, carried out in single unit, which treats a third of all TB cases in the Republic of Ireland compared to effectiveness of a three drug/nine month regimen (Rifampicin (R), Isoniazed (R), supplemented with Ethambutol (E) for the first two months = RHE9) with a four drug six months regimen (R, H supplemented with E and Pyrazinamide (Z) for the first two months = RHEZ6). Two hundred and eighty eight patients (288) were entered into the study. A total of 143, (76 were in the RHE9 group and 67 in the RHEZ6 group) completed the trial as planned. At the end of the third month, significantly more patients in the RHEZ6 regimen (98%) were culture negative compared to the RHE9 regimen (88%). All were culture negative at the end of chemotherapy. Drug intolerance was seen in 35 (12%) patients with no significant difference in hepatitis between the two regimens. Toxicity from Pyrazinamide was minimal. One hundred and forty five (145) patients were invalid for analysis for the following reason:- bacteriologically negative TB (41), drug intolerance (35), death (23), non-compliance (19), diagnosis not TB (10), drug resistance (7), extrapulmonary disease (4), consent withdrawn (3), Mycobacteria other than tuberculosis (3). All patients are being followed to monitor relapse rates.

Administration, Oral↗
PubMed1985

Tuberculosis chemotherapy today.

Effective chemotherapy of tuberculosis not only reduces morbidity and mortality, but it is a powerful mechanism to control further spread of infection. Although conventional therapy for 18-24 months is highly effective, a major disadvantage is non-compliance of patients in completing the full course of therapy. With better understanding of bacteriologic action of many antituberculous drugs, the disease can now be cured in six to nine months of bactericidal chemotherapy. Isoniazid and rifampin for nine months, either given daily throughout or initially for one month followed by twice weekly administration for another eight months, is highly effective for cure of the disease. However, this is not recommended for patients in developing countries due to high frequency of initial isoniazid resistance. Bactericidal therapy with four drugs (streptomycin or ethambutol (25 mg/kg), isoniazid, rifampin and pyrazinamide) daily for two months followed by isoniazid and rifampin daily or twice weekly for another four months is very effective. In suspected or proved isoniazid resistance, the therapy has also proven effective. However, therapy may also be changed during the continuation phase to streptomycin, rifampin and pyrazinamide daily or twice weekly for another four to six months. The treatment of extrapulmonary tuberculosis, alone or when associated with other medical disorders, is the same as for pulmonary tuberculosis. There are several short course regimens available for use in developing countries while keeping in consideration the shortage of major drugs and financial constraints. Modern short course chemotherapy has the potential advantage of success in developing countries by increasing the population of patients completing therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitubercular Agents↗
PubMed1994

Tuberculosis susceptibility patterns, predictors of multidrug resistance, and implications for initial therapeutic regimens at a New York City hospital.

BACKGROUND: Multidrug resistance has complicated tuberculosis therapy. We studied antibiotic susceptibilities of Mycobacterium tuberculosis and predictors of multidrug resistance to assist in determining initial drug regimens. METHODS: We conducted a case-control study based on chart review of patients with and without multidrug-resistant tuberculosis, including outpatients and inpatients with culture-proved tuberculosis seen at a large New York, NY, hospital during 1991 and 1992. Patient characteristics studied included serologic findings for human immunodeficiency virus and the presence of the acquired immunodeficiency syndrome. Descriptive analysis considered potential initial drug regimens. A theoretically effective regimen was assumed to contain at least two drugs to which an isolate was susceptible. RESULTS: For 172 patients, 28.5% of isolates were resistant to isoniazid, at least 20.9% to rifampin, 15.7% to ethambutol, 8.1% to pyrazinamide, 18.6% to streptomycin, 9.9% to ethionamide, 8.1% to kanamycin, and none to capreomycin, cycloserine, and ciprofloxacin; 18.6% were resistant to both isoniazid and rifampin. Chart review of 159 patients showed that acquired immunodeficiency syndrome, human immunodeficiency virus seropositivity, female gender, residence in the Bronx, and race were associated with multidrug resistance. The four-drug regimen of isoniazid, rifampin, ethambutol, and pyrazinamide was theoretically effective for 81% to 85% of patients. No subset of patients would have a markedly better theoretical benefit from that regimen. Only five- or six-drug regimens that used the combinations of capreomycin plus ciprofloxacin, capreomycin plus cycloserine, ciprofloxacin plus cycloserine, or all three drugs together theoretically offered significantly higher effectiveness. CONCLUSIONS: Tuberculosis isolates at our hospital have a high frequency of multidrug resistance. Only five- or six-drug regimens are theoretically adequate as initial therapy for our patients.

AIDS-Related Opportunistic Infections↗
PubMed1994

Tuberculosis in liver transplant patients.

Tuberculosis has been increasing especially in urban areas and in immunosuppressed patients; however, the incidence and factors associated with tuberculosis in OLT patients are unknown. Five of 550 patients who underwent OLT at the Mount Sinai Medical Center during a 5-year period were noted to have tuberculosis. The mean age of the patients was 49.2 years; there were 3 males and 2 females and 3 were foreign born. One of 5 had a prior history of tuberculosis. Tuberculin skin tests performed before transplant revealed 1 positive and 2 anergic reactions. The preoperative chest x-ray revealed apical fibrosis in 2 patients and bilateral apical disease with a nodule in 1 patient. Tuberculosis developed from 2 to 57 months after surgery in 4/5 patients. One had miliary lesions of the peritoneum discovered at the time of OLT. One patient had recent contact with a patient with pulmonary tuberculosis. At presentation, fever was present in 4 of 5 patients, pulmonary lesions in 3 patients, meningitis in 2; during hospitalization, 1 had a liver abscess and disseminated intravascular coagulation and peripheral gangrene. Lymphocytosis was noted in the pleural (1), peritoneal (1), and cerebrospinal fluid (1). Acid-fast smears were positive in bronchoalveolar lavage fluid (1), peritoneal isolates (1), and liver biopsy (1). All patients had positive cultures for Mycobacterium tuberculosis. These isolates were all sensitive to isoniazid, streptomycin, rifampin, ethambutol, and pyrazinamide. Four of 5 patients were treated with isoniazid and rifampin, 2 received pyrazinamide, 2, amikacin, 2, ofloxacin, and 2, ethambutol. Three of 5 patients are doing well on antituberculous therapy and 2 expired with tuberculosis as the cause of death. In OLT patients with unexplained fever, tuberculosis including extrapulmonary and disseminated disease should be considered since the mortality rate is very high. Liver transplantation can be performed in the presence of active peritoneal tuberculosis with the use of judicious antituberculous therapy. The role of preventive therapy is controversial, though use in certain high risk patients is suggested.

Adult↗
PubMedDate not supplied

[Infection caused by Mycobacterium tuberculosis with primary resistance to multiple drugs: a case report of a patient with AIDS].

Primary multidrug-resistant Mycobacterium tuberculosis is an important problem in the United States. There is no report in formal literature of this pathogen in Brazilian patients. CASE REPORT--We report a case of ganglionar tuberculosis diagnosed by acid-fast smears in a male, HIV positive patient. Mode of acquisition of HIV was not determined. Treatment was started, and isoniazid, rifampicin and pyrazinamide were prescribed. The patient and his family reported strict adherence to therapy, but no improvement was observed. After 75 days, the patient was admitted in our hospital because of clinical worsening. Clinical features were the presence of large submandibular and axillar lymph nodes, respiratory insufficiency and complains of abdominal pain. He died six days after admission. Culture obtained from the ganglionar aspirate disclosed M. tuberculosis susceptible to ethambutol, but resistant to isoniazid, rifampicin, pyrazinamide, ethionamide and streptomycin. DISCUSSION--Although this was a case of extrapulmonary tuberculosis, there is a concern about multidrug-resistant tuberculosis, that has been poorly evaluated in Brazil. Since high lethality and intrahospital transmission have been reported, we discuss the need of performing culture and antibiogram in suspected cases, and the prevention of the spread of M. tuberculosis to patients and health-care workers through the strict adherence to the isolation practices.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Results of directly observed short-course chemotherapy in 112,842 Chinese patients with smear-positive tuberculosis. China Tuberculosis Control Collaboration.

BACKGROUND: Tuberculosis remains a substantial public health burden in China. The cure rate in treatment programmes has been about 50%. In 1991, a new project based on directly observed short-course chemotherapy was introduced. We report the results of the first 112,842 patients treated. METHODS: Patients with symptoms suggesting tuberculosis are referred by general health services to the tuberculosis county dispensary for physical examination and fluoroscopy. Those with suspicious findings submit three sputum samples for smear examination. Village doctors deliver free, directly observed therapy to all smear-positive patients on an outpatient basis. New cases are treated with streptomycin (750 mg), isoniazid (600 mg), pyrazinamide (2000 mg), and rifampicin (600 mg) every other day for 2 months, followed by 4 months of alternate-day isoniazid plus rifampicin. Previously treated patients receive streptomycin, isoniazid, pyrazinamide, rifampicin, and ethambutol (1250 mg) every other day for 2 months, followed by 6 months of isoniazid, rifampicin, and ethambutol. Patients are re-examined and smears are repeated at 2 months (then 3 months if still positive) and at 5 and 6 months (new cases) or 5 and 8 months (previously treated cases). FINDINGS: Nearly 1.6 million patients with suspected tuberculosis were referred for fluoroscopy between 1991 and 1994. 48% had suspicious findings on fluoroscopy and underwent sputum examination. 104,444 new smear-positive cases and 95,616 previously treated smear-positive cases have been diagnosed. Results of treatment for those enrolled up to the first quarter of 1994 show cure rates of 89.7% among new cases (55,213) and 81.1% among those previously treated (57,629). The failure rate in previously treated cases, an indicator of drug resistance, fell from 17.6% among 437 patients enrolled in 1991 to 6.2% among 7822 patients enrolled in the first quarter of 1994. INTERPRETATION: Our experience shows that high rates of compliance and cure can be achieved on a mass scale and in a short time by means of directly observed short-course chemotherapy and the WHO technical strategy for effective tuberculosis control.

Adult↗
PubMedDate not supplied

Statewide survey of laboratories performing Mycobacterium tuberculosis testing in Minnesota.

Rapid and accurate laboratory detection and identification of Mycobacterium tuberculosis, particularly multidrug-resistant strains, is critical to both public health control measures and patient management. The authors surveyed microbiology laboratories to evaluate whether their methods met national guidelines. As needed, laboratories received individualized recommendations for improvement. The laboratories were resurveyed a year later to assess changes in methods. Current guidelines recommend fluorochrome acid-fast smears, broth cultures, identification by nucleic acid probe or BACTEC-NAP, and BACTEC primary susceptibility panels, which should include pyrazinamide. Of 27 laboratories performing acid-fast smears, 15 used fluorochrome methods. Six of 16 laboratories performing mycobacterial cultures used broth media. Of six laboratories performing species identification, five used nucleic acid probes or BACTEC-NAP. Of five laboratories evaluating drug sensitivity, two used BACTEC and two included pyrazinamide in their protocols. Overall, 24 (89%) laboratories needed improvements; a year later, 16 (67%) of those had altered their methods or made definite plans to do so. Survey results suggest that health departments can facilitate improvements in laboratory testing for pathogens of public health importance.

Data Collection↗
PubMed1996

Isoniazid-induced fever.

A rare case of isoniazid (INH)-induced fever is described. A 27-year-old woman diagnosed with miliary tuberculosis (TB) began to receive combined anti-TB treatment including INH, ethambutol, rifampicin and pyrazinamide on the second day of hospitalization. A spiked fever developed in the afternoon of the seventh hospital day. There was no evidence of a hypersensitivity reaction. All examinations including liver function tests, routine biochemistry tests, serum titer of antinuclear antibody and rheumatoid factor were within normal limits. The blood leukocyte count was also within normal range and no evidence of infection at other sites was found. Following the discontinuance of anti-TB agents, the patient's body temperature gradually returned to normal. When the patient was rechallenged with INH, the high fever recurred. The fever subsided again after the discontinuance of INH, and her recovery followed a smooth course thereafter, on combination therapy with rifampicin, ethambutol and pyrazinamide. This experience demonstrates the potential of INH to cause an isolated fever without other manifestations, which may be misdiagnosed as an infectious process. Though it is very rare, INH-induced fever must be considered when fever develops during anti-TB treatment.

Adult↗
PubMed1998

[Pulmonary tuberculosis with resistance to 4 antitubercular drugs].

A 32-year-old immigrant from Pakistan was admitted to our hospital with cavernous pulmonary tuberculosis. He gave a history of several 1 to 2-months courses of antimycobacterial treatment administered earlier in Pakistan. We initiated combined therapy including isoniazid, rifampin, pyrazinamide, and ethambutol. Subsequently, results of susceptibility testing from M. tuberculosis-complex strains isolated before the onset of treatment documented the presence of resistance against both isoniazid and rifampin which may have been primary or acquired drug resistances. During the course of treatment, two additional resistances to pyrazinamide and ethambutol developed which were probably due to the initial therapy with only two active antimycobacterial agents. The emergence of multidrug-resistant strains of M. tuberculosis complex is a world-wide problem. Our case indicates that multiresistance must be considered in every patient presenting with tuberculosis. If there is a strong suspicion of multidrug-resistant tuberculosis, initial treatment with a combination of 5-6 antimycobacterial agents seems advisable until the results of susceptibility testing become available.

Adult↗