Old antibiotics for emerging multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB).

Recently, multidrug-resistant tuberculosis (MDR-TB) has become a therapeutic challenge. In addition to drug resistance, drug adverse events, intravenous delivery, cost and availability of some antibiotics in low-income countries have led to a look back to old drugs, especially those efficient against closely related organisms such as Mycobacterium leprae. Here we review the available drugs that respect the conditions above and could be upgraded to first-line therapy for treating MDR-TB and extensively drug-resistant tuberculosis (XDR-TB).

Rifampicin-induced disseminated intravascular coagulation in pulmonary tuberculosis treatment: A case report and literature review.

RATIONALE: Disseminated intravascular coagulation (DIC) induced by daily rifampicin therapy is rare, especially the patient is absent of malignancy, severe infection, and prior exposure to rifampicin. PATIENT CONCERNS: We report a case of DIC induced by daily rifampicin treatment for pulmonary tuberculosis. A 22-year-old, previously healthy man received an anti-tuberculosis therapy consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide on the daily dose recommended by the World Health Organization tuberculosis guidelines after a diagnosis of pulmonary tuberculosis. Two weeks later, he was transferred to the West China Hospital with nasal hemorrhage for 1 week, hematochezia, hematuria, and petechiae for 5 days. DIAGNOSES: Laboratory data and symptoms on admission indicated DIC. INTERVENTIONS: The anti-tuberculosis drugs were discontinued after admission and he was initiated with targeted treatment for DIC, omeprazole and polyene hosphatidylcholine infusion, as well as nutrition supportive treatment. Five days after admission, ethambutol, moxifloxacin, and amikacin were added to the patient without further active hemorrhage. Eight days after admission, the platelet count had risen gradually. Isoniazid was administered on 24 days after admission, while his liver function tests and platelet counts returned to normal. No recurrence of DIC occurred. The diagnosis of rifampicin-induced DIC was confirmed. OUTCOMES: The patient recovered and left hospital with isoniazid, ethambutol, levofloxacin, and streptomycin after 4 weeks of hospitalization. There was no recurrence of DIC or hemorrhage during the 8 months of follow-up. The literature review revealed that there were 10 other cases of rifampicin-induced DIC. Only 4 cases received rifampicin on a daily basis for pulmonary tuberculosis treatment and the others were on intermittent dosing schedule for pulmonary tuberculosis or leprosy treatment. LESSONS: As a rare adverse effect, DIC induced by rifampicin occurs irregularly and unpredictably, which is reported to be more associated with the intermittent usage of rifampicin, but can occur with rifampicin daily administration. Identification of early symptoms, drug discontinuation, supportive management, and regular monitoring are the key points to correct this adverse effect, which may contribute to severe even fetal results in patients and deserves more attention.

Leprosy and tuberculosis concomitant infection: a poorly understood, age-old relationship.

Historically, archaeological evidence, post-mortem findings and retrospective analysis of leprosy institutions' data demonstrates a high observed incidence of concomitant infection with leprosy and tuberculosis (TB). However, reports of concomitant infection in the modern literature remain scarce, with estimates of annual new case detection rates of concomitant infection at approximately 0.02 cases per 100,000 population. Whilst the mechanism for this apparent decline in concomitant infections remains unclear, further research on this topic has remained relatively neglected. Modelling of the interaction of the two organisms has suggested that the apparent decline in observations of concomitant infection may be due to the protective effects of cross immunity, whilst more recently others have questioned whether it is a more harmful relationship, predisposing towards increased host mortality. We review recent evidence, comparing it to previously held understanding on the epidemiological relationship and our own experience of concomitant infection. From this discussion, we highlight several under-investigated areas, which may lead to improvements in the future delivery of leprosy management and services, as well as enhance understanding in other fields of infection management. These include, a) highlighting the need for greater understanding of host immunogenetics involved in concomitant infection, b) whether prolonged courses of high dose steroids pre-dispose to TB infection? and, c) whether there is a risk of rifampicin resistance developing in leprosy patients treated in the face of undiagnosed TB and other infections? Longitudinal work is still required to characterise these temporal relationships further and add to the current paucity of literature on this subject matter.

Oral drug provocation test to generate a list of safe drugs: experience with 100 patients.

BACKGROUND: Following a drug eruption, patients and their doctors need to know which drugs can be safely administered for subsequent illnesses. Currently available laboratory tests are unable to answer this question in a clinically meaningful manner. AIMS: To describe our use of oral provocation tests to provide a list of safe drugs to patients. METHODS: We studied the records of 100 patients who underwent oral provocation testing in our department between 2003 and 2009. All patients were admitted to hospital and drugs were administered under supervision, one drug per day. A dermatologist evaluated all symptoms and signs that developed following drug intake. RESULTS: Sixty nine women and 31 men underwent provocation testing. There were 96 reactions in 61 patients, of which 44 reactions in 34 patients were judged to be true reactions. All reactions could be controlled, with treatment or spontaneously. A list of safe drugs was provided to the patient along with written instructions to avoid any drug(s) that had produced a reaction. CONCLUSIONS: Oral provocation tests are safe and effective in providing patients with a list of drugs they can take safely. These tests should preferably be undertaken after admitting the patient to hospital.

Severe cutaneous adverse reactions due to isoniazid in a HIV positive patient.

Severe Cutaneous Adverse Reaction (SCAR) represents the spectrum of adverse drug reactions from erythema multiforme, Stevens - Johnson syndrome (SJS) to Toxic Epidermal Necrolysis (TEN). A 55 year old lady presented in a toxic state with peeling of skin, blisters on the body of seven days duration following medications taken for fever and pulmonary tuberculosis. When referred to our institution, she was diagnosed as TEN. Immediately the suspected medications were stopped. The essential investigations were done including the screening for immunosuppression, which was found to be negative. The patient was treated symptomatically with emphasis on skilled nursing care. The patient's skin condition improved gradually but tuberculosis progressively worsened over three months. Thus patient was reinvestigated for seropositivity and was found to be positive. Considering the benefit - risk ratio along with the advice of the pulmonologist, a decision was made to give her a rechallenge test, first for antitubercular drugs and later for antipyretics. The patient developed SJS within two days of starting isoniazid (INH). On withdrawal of INH the patient recovered.

Clinical study of cutaneous drug eruptions in 200 patients.

BACKGROUND: Cutaneous drug reactions are the most common adverse reactions attributed to drugs. Any skin disorder can be imitated, induced or aggravated by drugs. AIMS: The present study was carried out to determine the age, sex incidence and clinical pattern of drug eruptions, to recognize offending drugs (self medication or prescribed), to evaluate mortality and morbidity associated with drugs, to educate the patients, and to avoid self-administration of drugs and re-administration of the offending drugs. METHODS: The diagnosis of cutaneous drug reactions is mainly based on detailed history and correlation between drug intake and the onset of rash. Two hundred patients (112 males and 88 females) presenting with cutaneous drug reactions were studied. RESULTS: Fixed drug eruption was seen in 61 patients; others being urticaria and angioedema, morbilliform rash in 37, pruritus in 25, Stevens Johnson (SJ) syndrome in six, purpura in six, exfoliative dermatitis in five, photosensitivity in five, Toxic Epidermal Necrolysis in two, acneiform eruption in three, and erythema multiforme in two patients. The most frequently affected age group was 41-50 years, followed by the 21-30 and 31-40 years age groups. The youngest patient was one year old and the oldest was 80 years old. The period of development of lesions after the intake of drug(s) varies from 01-45 days. Cotrimoxazole was the offending drug in 26 cases, followed by Ibuprofen in 20 cases. CONCLUSIONS: Fixed drug eruption was the most common drug eruption seen. Cotrimoxazole was the most common cause of drug eruptions.

Cost-effectiveness and total costs of three alternative strategies for the prevention and management of severe skin reactions attributable to thiacetazone in the treatment of Human Immunodeficiency Virus positive patients with tuberculosis in Kenya.

SETTING: Severe skin reactions due to thiacetazone (T) in Human Immunodeficiency Virus (HIV) positive tuberculosis patients have been reported in several publications, one of them from Kenya. However, the abandoning of T may not be feasible in Kenya as this may increase the cost of drugs by about three-fold per regimen. OBJECTIVE: To compare the cost-effectiveness and total cost of three strategies in which T is replaced with ethambutol (E). DESIGN: Three strategies are compared with a baseline strategy in which T is not replaced. The indicator for cost-effectiveness is the cost-per-averted-death attributable to T. RESULTS: Education of patients on the possibility of side-effects and replacement of T with E is the most cost-effective strategy at HIV prevalence rates of 1-90%. Abandonment of T and replacement with E is the most cost-effective at over 90% HIV prevalence. CONCLUSION: In Kenya, education of patients on the possibility of skin reactions should be preferred at low range HIV prevalence rates. Routine HIV testing would be the most attractive strategy in the middle range, and total replacement of T with E is to be preferred in the higher range of HIV prevalence.

PIP: In Kenya, the National Leprosy Tuberculosis Programme (NLTP) used previously reported data from Nairobi to compare the cost-effectiveness and total costs of a hypothetical strategy with three intervention strategies for the prevention and management of severe skin reactions caused by thiacetazone in treating HIV-positive patients with tuberculosis (TB). The hypothetical strategy was continued use of thiacetazone despite adverse skin reactions. The intervention strategies included patient education about possible side effects of anti-TB drugs (discontinue use if skin rash develops, report situation to clinic, replace thiacetazone with ethambutol when other skin diseases have been excluded), abandonment of thiacetazone and replacement with ethambutol, and HIV testing and pre- and post-test counseling. NLTP currently used the education strategy. It assumed a mortality rate of 5%. When the HIV prevalence rate is 1-90%, the education strategy is the most cost-effective strategy. In terms of total costs, the education strategy was also the most inexpensive strategy regardless of the HIV prevalence. At an HIV prevalence rate greater than 65%, the abandonment of thiacetazone strategy was the cheapest strategy. When the assumed mortality rate was 3%, the cost per averted death for the education strategy was reduced from about US$120 to about US$80 and the education strategy became the most cost-effective strategy over the entire range of HIV prevalence. In addition, the cost of HIV testing significantly increased the cost per averted death. Thus, the findings of this study are truly sensitive to different program conditions. Based on these findings, the authors recommended that the education strategy be applied with a range of HIV prevalence of 1-45%, that HIV testing be applied with a range of 46-72%, and that total abandonment be applied with an HIV prevalence greater than 72%.

[Diagnosis, therapy and prognosis of atypical mycobacterial infections--results of a retrospective study]. / Diagnostik, Therapie und Prognose atypischer Mykobakteriosen--Ergebnisse einer retrospektiven Studie.

The most important mycobacteria causing disease in humans are Mycobacterium tuberculosis and Mycobacterium leprae. These germs contrast the so-called atypical mycobacteria. The importance of the atypical mycobacteria was recognized in the fifties. Even if the quantity of atypical mycobacterial disease has increased during the last decades in Germany, it is still a rare disease today, but it is seen in patients with acquired immunodeficiency syndrome more often nowadays. In the period from 1st January 1986 til 31st December 1992 31 HIV-negative patients with a diagnosis of atypical mycobacterial disease have been seen in the department for lung diseases in the Thoraxklinik Heidelberg-Rohrbach. During the same period an atypical mycobacterial disease was diagnosed in 12 out of 413 HIV-positive patients (2.9%) of the AIDS-ambulance of the skin hospital of the University of Heidelberg. Most of the HIV-negative patients showed additional diseases which reduce the immunological resistance. In HIV-positive patients an atypical mycobacteriosis heralds a severe immunodeficiency. Because it is a rare disease and an exact diagnosis is difficult to establish there is a lack of controlled clinical trials and therefore detailed therapeutical guidelines do not exist. A therapeutical approach is also complicated by a lack of effective drugs. With disseminated disease in AIDS-patients, which is mostly caused by Mycobacterium avium-intracellulare, the therapy should be stopped, if there are any severe side-effects. The present results of therapy are still disappointing. In the future the management of atypical mycobacterial disease will be more important, because there is an increasing number of patients with acquired immunodeficiency.