Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent outbreaks of multi-drug-resistant tuberculosis (MDR-TB) have resulted in significant morbidity and mortality in patients with AIDS. The poor outcomes are attributable to delayed diagnoses, slow reporting of antimycobacterial susceptibility results, inadequate treatment regimens and profound immunosuppression. There are no prospective clinical trials which have evaluated the optimal treatment of MDR-TB. A retrospective study has shown that in immunocompetent patients with secondary MDR-TB, only 56% responded to prolonged courses of multiple drug regimens, and 22% died of TB. In patients with AIDS, even fewer patients respond, with median survivals of 2-4 months. In general, better responses have been associated with in vitro susceptibility of patients' isolates. If possible, patients with MDR-TB should receive at least three drugs to which their isolates are susceptible for at least 24 months; these regimens are likely to include ethambutol, pyrazinamide, a quinolone, and an aminoglycoside. Selected patients benefit from surgical intervention combined with aggressive chemotherapy. MDR-TB is best prevented by directly observed therapy of patients with susceptible organisms and rigorous infection control practices in areas of high incidence of MDR-TB. Effective treatment regimens for MDR-TB await the development of novel compounds which have better in vitro activity against MDR-TB than currently available drugs.
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PMID:Treatment of multidrug-resistant tuberculosis. 756 Sep 68

Tuberculosis, a major killer in developing countries, is on the rise again in industrialized nations. AIDS, increased use of immunosuppression and the emergence of multiple drug-resistant Mycobacterium tuberculosis (MDR-TB) have further enhanced its significance. TB is projected to cause 3.5 million deaths per year by 2000. Also, other types of mycobacteria are being incriminated in human infections with increasing frequency. Thus, the enhanced risk of nosocomial and iatrogenic spread of mycobacteria is forcing a review of infection control in general and claims of mycobactericidal activity of disinfectants in particular. Mycobacteria are more resistant to disinfection than enveloped viruses and other types of vegetative bacteria, but a proper comparison with non-enveloped viruses requires more data. Flaws in currently used protocols for mycobacterial activity are: (i) a lack of proper quantitation; (ii) unrealistically long contact times at higher than ambient temperatures; (iii) absence of a suitable organic load; (iv) ineffective neutralizers; (v) unsuitable surrogates for M. tuberculosis; (vi) improper recovery media; and (vii) inappropriate types of carriers. Furthermore, we have recently found a product meant for 14 day reuse to become non-mycobactericidal after only a week under actual use in an endoscopy unit. These considerations make the available data on product efficacy unreliable, especially in view of the increasing threat from MDR-TB. Recent findings suggest that the use of Mycobacterium terrae as a surrogate, better recovery media, flat surfaces as carriers, elimination of neutralizers, proper removal of cell clumps and a required > or = 4 log10 reduction in the number of colony forming units of the test bacterium after disinfectant treatment should make mycobacteridal tests more precise and reliable, thus making product registration and selection easier. There is also an urgent need to develop standardized protocols to determine the mycobactericidal activity of disinfectants under conditions of reuse.
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PMID:Mycobactericidal testing of disinfectants: an update. 756 Sep 75

Tuberculosis (TB) has remained a major infectious disease in the world. With the AIDS epidemic, the emergence of TB as a cause of severe and life-threatening infection has become a common-place occurrence in many countries. In the USA, the increase of new cases of TB average at the rate of 20% each year. Of great alarm is the findings of multidrug-resistant TB (MDR-TB) with outbreaks in hospitals throughout the world, as well as in other institutions. No health care worker is immune from exposure to TB. TB control requires education of health care workers, a program of ongoing screening, isolation of patients early in the course of their disease, and administration of multiple anti-TB drug to cover and treat MDR-TB. Newer diagnostic methods are needed as well as more active and less toxic drug therapies. Controlled clinical trials are required to determine optimum therapy.
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PMID:Re-emergence of tuberculosis. 774 2

Outbreaks of multidrug-resistant Mycobacterium tuberculosis (multidrug-resistant tuberculosis; MDR-TB) have recently been reported in hospitals in the United States. Rapid spread of these bacilli and a high mortality among immunocompromised patients, i.e. HIV-infected individuals and AIDS patients, were observed. Factors that play a role in these outbreaks and the prevention of MDR-TB are discussed in this article. Awareness of a possible M. tuberculosis infection and the early introduction of measures to reduce the spread of these micro-organisms are steps that can prevent a nosocomial outbreak. The use of more rapid methods for culturing mycobacteria and determining their sensitivity to antimicrobial drugs can accelerate the diagnostic process and the recognition of multiresistance. In view of the poor results of treatment of MDR-TB, prevention should be the first requirement.
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PMID:Prevention of nosocomial spread of multidrug-resistant tubercle bacilli. 805 47

The management of MDR-TB requires that the clinician become familiar with the "second-line" antimycobacterial agents. These drugs are generally less potent and frequently more toxic than isoniazid and rifampin. Because they are less active, innovative dosing schedules may allow us to take advantage of the few strengths that they possess. This approach will require further research into the dose-response relationships for each agent. Based on our current knowledge of these drugs, practical guidelines for their use have been described. These guidelines include the gradual escalation of the oral doses of PAS, cycloserine, and ethionamide over several days, and the intravenous administration of streptomycin and capreomycin. Both ciprofloxacin and ofloxacin may be used for the treatment of MDR-TB, but data from clinical trials are currently lacking. Finally, because patients with AIDS appear to develop antimycobacterial drug malabsorption over the course of their HIV infection, therapeutic drug monitoring can be used to verify drug absorption in the individual patient. This approach may improve therapy for that patient and prevent the selection of additional drug resistance.
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PMID:Pharmacology of the antimycobacterial drugs. 823 10

We recently observed a striking increase in multidrug-resistant tuberculosis (MDR-TB) among patients admitted to the Chest Service at Bellevue Hospital Center in New York. We reviewed the laboratory susceptibility test results of 4,681 tuberculosis (TB) cases over the past 20 years, Combined resistance to isoniazid and rifampin increased from 2.5 percent in 1971 to 16 percent in 1991 with higher rates noted for individual drugs. We reviewed the medical records of 100 patients with drug-resistant TB, finding that these individuals were predominantly less than 40 years of age, minority, male, jobless, undomiciled, with a high percentage of drug abuse and human immunodeficiency virus infection. We conclude that the epidemics of AIDS and TB are complicated by a third epidemic of MDR-TB. This third epidemic requires urgent attention to achieve more rapid diagnosis, to develop new therapeutic regimens, and to address the social and hospital environment ot care for these individuals.
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PMID:The third epidemic--multidrug-resistant tuberculosis. 827 81

Mycobacterium avium-intracellulare complex (MAC) is a ubiquitous environmental microorganism whose pathogenicity ranges from innocuous colonization to disease, in immunocompetent as well as immunocompromised individuals. We sought to determine the clinical significance of MAC in sputum cultures of patients with pulmonary tuberculosis (TB). A retrospective analysis between January 1994 and March 1995 at Bellevue Hospital Center revealed both Mycobacterium tuberculosis and MAC in 35 patients (11% of all patients with TB). Of 27 patients reviewed, 52% were HIV-1 infected (median CD4 + 25 cells per microliter). Radiographic manifestations in patients with TB and MAC were similar to those seen in patients with TB alone. Both mycobacteria were cultured primarily from respiratory sources. M tuberculosis was usually cultured first or concurrent with MAC, and in nearly all cases, both species were recovered within 2 months of each other. Most patients improved clinically, bacteriologically, and radiographically with standard antituberculous therapy, except those with advanced AIDS, multidrug-resistant TB (MDR-TB), or disseminated MAC. We conclude that recovery of MAC in sputum is common in patients with pulmonary TB, regardless of HIV-1 infection, MDR-TB, or other clinical, bacteriologic, or radiographic attributes. MAC cultivation in most of these patients likely represents transient colonization, and in most cases is not clinically significant.
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PMID:The significance of Mycobacterium avium complex cultivation in the sputum of patients with pulmonary tuberculosis. 899 8

The available data suggest that selected patients with tuberculosis and MAC fail to respond to therapy because they malabsorb their medications. In particular, patients with AIDS and known gastrointestinal diseases have problems absorbing these drugs. In addition, because MDR-TB and MAC are so difficult to treat, TDM with the antimycobacterial drugs offers the clinician a chance to ensure that the patient achieves serum concentrations above the MIC of the pathogen. TDM has become the standard of practice at the National Jewish Center for Immunology and Respiratory Medicine. By combining specific and sensitive assays, carefully collected samples, and clinical expertise, we are able to control and optimize antimycobacterial drug therapy. We continue to refine our approach with ongoing pharmacokinetic and pharmacodynamic research, including the development of population pharmacokinetic models. We hope that these efforts will provide insight into the nature of current therapeutic problems. We also hope they will help us improve the clinical outcomes of our patients.
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PMID:Using therapeutic drug monitoring to dose the antimycobacterial drugs. 909 12

A major form of multidrug resistance, which represents a serious obstacle to the success of chemotherapy, is caused by the over-expression of MDR-1 gene encoded P-glycoprotein. The present investigation was aimed to determine whether AZT, a cytostatic agent that interferes with the human immunodeficiency virus replication, is able to induce MDR-1 expression in tumor cells. After a short term exposure of human lymphoblastoid cells to AZT MDR-1 P-glycoprotein was found in the treated cells. This ATP-dependent drug-efflux pump interferred with cytotoxic efficacy of anticancer drugs such as vinblastine. This phenomenon should be carefully considered during anti-viral and anti-tumoral combined chemotherapies in AIDS patients.
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PMID:Induction of the multidrug-transporter P-glycoprotein by 3'-azido-3'-deoxythymidine (AZT) treatment in tumor cell lines. 914 57

Megestrol acetate is a synthetic analog of progesterone. In general, megestrol acetate exerts its progesterone-like hormonal effect by binding to the progesterone receptor. It has been recognized that megestrol acetate can increase weight and improve some aspects of quality of life in cancer patients and in patients with the acquired immunodeficiency syndrome. This effect occurs in patients with or without concurrent chemotherapy or radiotherapy, through an as yet unknown mechanism. Recently, megestrol acetate has been shown to reverse, at least partially, multidrug resistance to doxorubicin and/or vincristine in cancer cell lines. This potentially beneficial effect has not yet been studied in clinical trials. This biological activity is thought to be mediated through the unique binding of megestrol acetate to p-glycoprotein. At least in vitro megestrol acetate can also enhance the cytotoxic effect of these two chemotherapeutic agents in some MDR-nonexpressing cell lines. These findings suggest that megestrol acetate deserves further preclinical and clinical studies to evaluate its potential role of enhancing cytotoxicity of chemotherapy and improving the quality of life of cancer patients.
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PMID:Megestrol acetate as a biomodulator. 962 85


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