Institutional Control Measures for Tuberculosis in the Era of Multiple Drug Resistance: ACCP/ATS Consensus Conference

Abstract

air changes per hour baeillus CalmetteGueiin Centers for Disease Control and Prevention high-efficiency particulate air isoniazid multidrug resistant National Institute for Occupational Health and Safety Occupational Safety and Health Administration powered air-purifying respirator tuberculosis ultraviolet ultraviolet germicidal irradiation The risk for transmission of Mycobacterium tuberculosis from hospitalized patients to other patients and hospital employees was well established by 1950. Before that time, the risk to hospital employees was debated and indeed minimized, perhaps for fear that acknowledging the risk would frighten young people away from health-care careers.1Sepkowitz K.A. Tuberculosis and the health care worker: a historical perspective.Ann Intern Med. 1994; 120: 71-79Crossref PubMed Scopus (192) Google Scholar Heimbeck,2Heimbeck J. Immunity to tuberculosis.Arch Intern Med. 1928; 41: 336-342Crossref Scopus (23) Google Scholar in 1928, was one of the first to demonstrate that nurses were at high risk of converting the tuberculin skin test and developing clinical tuberculosis (TB); of 220 tuberculin-negative nursing students, 95% had converted by graduation and 22% developed clinical TB. Subsequent reports from large hospitals in Philadelphia, New York, and Boston during the 1930s showed that most nurses working in these institutions converted their tuberculin skin test and were at risk of developing clinical TB at a rate much higher than were workers not involved in the health-care field.3Israel H.L. Hetherington H.W. Ord J.G. A study of tuberculosis among students of nursing.JAMA. 1941; 117: 839-844Crossref Scopus (49) Google Scholar, 4Brahdy L. Immunity and positive tuberculin reaction.Am J Public Health. 1941; 31: 1040-1043Crossref Google Scholar, 5Badger T.L. Ayvazian L.F. Tuberculosis in nurses: clinical observations on its pathogenesis as seen in 15 year follow-up of 745 nurses.Am Rev Tuberc. 1949; 60: 305-331PubMed Google Scholar In 1930, Myers6Myers J.A. The prevention of tuberculosis among nurses.Am J Nurs. 1930; 30: 1361-1372Google Scholar made a series of recommendations for TB control for hospital employees that have relevance today, including tuberculin skin tests and chest radiographs for new employees, isolation of clinical cases, and having a high index of suspicion of TB among all new patients admitted to hospital. Gradually hospitals implemented these and other control measures as their benefits were demonstrated. But as highly effective chemotherapy for TB became the rule and preventive treatment became routine, the incidence of TB in the United States progressively declined, and the risk of TB infection and clinical TB among hospital employees fell sharply. As the risk became less and less, concern about this occupational hazard fell rapidly so that only scattered reports of hospital outbreaks appeared in the 1960s, 1970s, and early 1980s.7Lincoln E.M. Epidemic of tuberculosis.Adv Tuberc Res. 1965; 14: 157-201Google Scholar, 8Alpert M.E. Levison M.E. An epidemic of tuberculosis in medical school.N Engl J Med. 1965; 272: 718-721Crossref PubMed Scopus (15) Google Scholar, 9Ehrenkranz N.J. Kirklighter J.L. Tuberculosis outbreak in a general hospital: evidence for airborne spread of infection.Ann Intern Med. 1972; 77: 377-382Crossref PubMed Scopus (114) Google Scholar, 10Catanzaro A. Nosocomial tuberculosis.Am Rev Respir Dis. 1982; 125: 559-562Crossref PubMed Scopus (191) Google Scholar As has happened with other public health problems, when the incidence of TB decreased, government and private efforts for TB control diminished markedly. In 1944, the Public Health Service Act authorized the establishment of a TB control program for the United States and the Surgeon General established the Tuberculosis Control Division in the Public Health Service. In 1961, the US Congress provided a substantial increase of funds for TB control through project grants; 29 projects were funded in 1962 with a total appropriation of $500,000, and by 1969 the number of projects had increased to 80 funded at a level of approximately $20 million. Funding for TB control by state and local government agencies increased from $1.5 million in 1962 to $40 million in 1969. Support began to be phased down after 1969 and the project grant program ended in 1972. Throughout the 1970s and 1980s, federal funding for TB decreased and special funds for TB control at the federal level were halted altogether for several years in the 1980s. This decrease in funds available for TB control together with the emergence of the HIV epidemic, the large increase in the homeless population, the growing number of elderly Americans, the dramatic increase in the US prison population, and outbreaks of TB caused by multidrug-resistant (MDR) M tuberculosis laid the basis for the reemergence of TB as a major public health problem. A number of alarming hospital outbreaks have been recognized in recent years.11Hutton M.D. Stead W.W. Cauthen G.M. et al.Nosocomial transmission of tuberculosis associated with a draining abscess.J Infect Dis. 1990; 161: 286-295Crossref PubMed Scopus (132) Google Scholar, 12Edlin B.R. Tokars J.I. Grieco M.H. et al.An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome.N Engl J Med. 1992; 326: 1514-1521Crossref PubMed Scopus (742) Google Scholar, 13Pearson M.L. Jereb J.A. Frieden T.R. et al.Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis: a risk to patients and health care workers.Ann Intern Med. 1992; 117: 191-196Crossref PubMed Scopus (487) Google Scholar In one hospital, 21 of 60 employees had a documented tuberculin skin test conversion after exposure to a patient whose condition was not promptly diagnosed after hospital admission; in another hospital, 14 of 45 exposed employees converted.12Edlin B.R. Tokars J.I. Grieco M.H. et al.An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome.N Engl J Med. 1992; 326: 1514-1521Crossref PubMed Scopus (742) Google Scholar The Centers for Disease Control and Prevention (CDC) reported a number of hospital and institutional outbreaks in which TB spread among hospitalized patients and employees, resulting in several deaths due to occupationally acquired MDR M tuberculosis.11Hutton M.D. Stead W.W. Cauthen G.M. et al.Nosocomial transmission of tuberculosis associated with a draining abscess.J Infect Dis. 1990; 161: 286-295Crossref PubMed Scopus (132) Google Scholar, 12Edlin B.R. Tokars J.I. Grieco M.H. et al.An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome.N Engl J Med. 1992; 326: 1514-1521Crossref PubMed Scopus (742) Google Scholar, 13Pearson M.L. Jereb J.A. Frieden T.R. et al.Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis: a risk to patients and health care workers.Ann Intern Med. 1992; 117: 191-196Crossref PubMed Scopus (487) Google Scholar The risk of TB among health-care workers was the subject of a recent review.14Menzies D. Fanning A. Yuan L. et al.Tuberculosis among health care workers.N Engl J Med. 1995; 332: 92-98Crossref PubMed Scopus (325) Google Scholar A recent survey of American medical schools indicated a mean estimated annual conversion rate for students of 1.8%, although schools in areas with more than twice the national incidence rates for TB tended to be overrepresented among the survey respondents.15Fagan M. Poland G.A. Tuberculin skin testing in medical students: a survey of US medical schools.Ann Intern Med. 1994; 120: 930-931Crossref PubMed Scopus (22) Google Scholar The increase in incidence of TB in the United States noted over the past few years is a first in this century. Indeed, TB rates fell progressively throughout the United States beginning in the latter half of 19th century.16Bates J.H. Stead W.W. The history of tuberculosis as a global epidemic.Med Clin North Am. 1993; 77: 1205-1217Crossref PubMed Scopus (105) Google Scholar This increase must be viewed with the realization that for much of the United States, TB remains under control. In 1992, nearly half of all counties in the United States reported having not a single person with TB for that year, and over the past decade, the number of counties having no TB in a given year steadily increased.17Centers for Disease Control and Prevention, Reported tuberculosis in the US, 1993, 1994, Centers for Disease Control and Prevention, Atlanta, 35, OctoberGoogle Scholar The increase in TB has been observed primarily in states with large metropolitan centers, where there is also a substantial minority population together with persons who are foreign bom.18Centers for Disease Control, Management of persons exposed to multi-drug resistant tuberculosis, MMWR, 41, (RR-11), 1992, 61, 71Google Scholar Most persons having MDR TB are from New York, New Jersey, and Florida, but MDR TB has been reported by many other states.19Bloch A.B. Cauthen G.M. Onorato I.M. et al.Nationwide survey of drug-resistant tuberculosis in the United States.JAMA. 1994; 271: 665-671Crossref PubMed Scopus (334) Google Scholar For 1993, only 16 states reported an increase in the number of TB cases and the total number reported for the United States fell by 5.1%, the first decrease since 1988.20Centers for Disease Control, United States, 1993, MMWR, 43, 1994, 361, 366, Expanded tuberculosis surveillance and tuberculosis morbidityGoogle Scholar Today, many hospitals and their employees have been placed under difficult circumstances. They are treating more and more patients who have TB, some of whom harbor MDR strains. Several governmental actions were taken in response. The CDC published guidelines that provide for major changes in hospitals regarding TB control.21Centers for Disease Control, Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities: 1994, MMWR, 43, 1994, 1, 120Google Scholar These guidelines were the subject of considerable controversy within the medical community and among various agencies and interest groups.22Catanzaro A. Preventing nosocmial transmission of tuberculosis [editorial].Lancet. 1995; 345: 204-205Abstract Full Text PDF PubMed Scopus (10) Google Scholar, 23Dunlap N.E. Bailey W.C. Bass Jr, J.B. et al.Occupational exposure to tuberculosis: risk and consequences.Chest. 1994; 106: 658-659Abstract Full Text Full Text PDF Scopus (5) Google Scholar, 24Winters R.E. Guidelines for preventing the transmission of tuberculosis: a better solution?.Clin Infect Dis. 1994; 19: 309-310Crossref PubMed Scopus (21) Google Scholar, 25Jernigan J.A. Adal K.A. Anglim A.M. et al.Mycobacterium tuberculosis transmission rates in a sanitorium: implications for new preventive guidelines.Am J Infect Control. 1994; 22: 329-333Abstract Full Text PDF PubMed Scopus (9) Google Scholar A common criticism has been absence of scientific data on which to base recommendations. A recent retrospective cohort study in a New York City teaching hospital suggests that the implementation of interventions similar to those recommended by the CDC in 1990 resulted in reduced TB transmission to patients and health-care workers.26Maloney S.A. Pearson M.L. Gordon M.T. et al.Efficacy of control measures in preventing nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers.Ann Intern Med. 1995; 122: 90-95Crossref PubMed Scopus (158) Google Scholar,27Centers for Disease Control, Guidelines for preventing the transmission of tuberculosis in health-care settings, with special focus on HIV-related issues, MMWR, 39, 1990, RR, 17Google Scholar Implementation of similar precautions also appeared to have controlled transmission of MDR TB on an HIV ward and among health-care workers at a large Miami hospital.28Wenger P.N. Otten J. Breeden A. et al.Control of nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis among healthcare workers and HIV-infected patients.Lancet. 1995; 345: 235-240Abstract Full Text PDF PubMed Scopus (154) Google Scholar Unfortunately, it is usually not possible to determine by retrospective analysis which of the several interventions enacted were effective and which were ineffective. In October 1993, the Occupational Safety and Health Administration (OSHA) issued a compliance memorandum that establishes an enforcement policy for protecting exposed workers against M tuberculosis. Employers found in violation of the policy mandates have been fined. The current OS HA enforcement policy for TB is based primarily on the 1990 CDC guidelines, but it is expected that OSHA will soon issue an airborne pathogen standard based on the revised 1994 CDC guidelines.21Centers for Disease Control, Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities: 1994, MMWR, 43, 1994, 1, 120Google Scholar The current OSHA enforcement policy and an independent interpretation have been published.29Decker M.D. OSHA enforcement policy for occupational exposure to tuberculosis.Infect Control Hosp Epidemiol. 1993; 14: 689-693Crossref PubMed Google Scholar In response to these important clinical, epidemiologic, and regulatory developments regarding TB, the American College of Chest Physicians and the American Thoracic Society (the medical advisory arm of the American Lung Association) convened a panel of persons having special expertise in TB to review the subject of “Institutional Control Measures for Tuberculosis in the Era of Multiple-Drug Resistance.” The objective of this conference was to review and analyze the risk of TB transmission in health-care facilities today, and the means available for protecting workers, patients, and visitors from the perspective of clinicians who have worked closely with the disease over the years. The following is a report from this group. TB spreads when airborne particles produced by an infectious person are inhaled by a susceptible host. Many details regarding the precise nature of this process have been described. In 1934, Wells30Wells W.F. On air-borne infection: II. Droplets and droplet nuclei.Am J Hyg. 1934; 20: 611-618Google Scholar pointed out that droplets ejected into air evaporate rapidly. The residues of these evaporated droplets are called droplet nuclei. He showed that the death rate of organisms in the transition from droplet to droplet nucleus is very high. Wells et al31Wells W.F. Ratcliffe H.L. Crumb C. On the mechanics of droplet nuclei infection: II. Quantitative experimental air-borne tuberculosis in rabbits.Am J Hyg. 1948; 47: 11-28PubMed Google Scholar demonstrated that the size of the inhaled particle is important. Rabbits inhaling 2 or 3 tubercle bacilli dispersed as single, respirable particles developed more lung lesions than rabbits inhaling 10,000 bacilli dispersed in large aggregates. Study of tissue sections showed that the large clumps of bacilli did not reach the alveolar space, whereas the small particles containing a single bacillus were deposited on the vulnerable alveolar membrane. The large particles, deposited on the mucous blanket of the larger airways, were removed without producing any evidence of infection. Ratcliffe32Ratcliffe H.L. Tuberculosis induced by droplet nuclei infection: pulmonary tuberculosis of predetermined initial intensity in mammals.Am J Hyg. 1952; 55: 36-48PubMed Google Scholar reported a series of animal experiments designed to study airborne transmission of tubercle bacilli in mice, hamsters, guinea pigs, and rabbits. Infections in these animals were induced by inhalation of an infectious aerosol produced by an atomizer that generated particles from an aqueous suspension of tubercle bacilli. From these experiments, it was found that only 0.8% of the organisms remained viable after transfer to the aerosol stage. The killing of 99% of the bacilli as they were put into the airborne state is not explained nor is it known whether this same degree of killing occurs when humans generate droplet nuclei. Ratcliffe and Palladino33Ratcliffe H.L. Palladino V.S. Tuberculosis induced by droplet nuclei infection.J Exp Med. 1953; 97: 61-67Crossref PubMed Scopus (30) Google Scholar showed that in the guinea pig, mouse, and rat, almost all tubercle bacilli inhaled as single organisms reach the alveolar space and produce a tubercle. They also observed that it was most unusual for more than a single organism to be deposited at any one site. From this work, they postulated that TB in man develops in the same manner, ie, by inhalation of a single droplet nucleus containing one or at most a few tubercle bacilli. The details of this work and extensive supporting experimental material were reported by Riley and O'Grady.34Riley R.L. O’Grady F. Airborne infection. Macmillan, New York1961: 26-57Google Scholar To test the droplet nucleus hypothesis Riley et al35Riley R.L. Wells W.F. Mills C.C. et al.Air hygiene in tuberculosis; quantitative studies of infectivity and control in a pilot ward.Am Rev Tuberc. 1957; 75: 420-431PubMed Google Scholar,36Riley R.L. Mills C.C. Nyka W.W. et al.Aerial dissemination of pulmonary tuberculosis: a 2-year study of contagion in a tuberculosis ward.Am J Hyg. 1959; 70: 185-196Google Scholar studied patients with newly diagnosed pulmonary TB who had just been placed on a regimen of chemotherapy and were likely to have tubercle bacilli in their sputum. These patients were placed in hospital rooms with controlled ventilation so that the room air was discharged through an exposure chamber containing guinea pigs located in a penthouse above the ward. Infection rate for the guinea pigs was determined by periodic tuberculin tests. Infectious particles capable of passing through the ventilation ductwork to the exposure chamber above had the aerodynamic characteristics of droplet nuclei. This experiment showed that humans with TB create droplet nuclei containing tubercle bacilli that remain viable and infectious for guinea pigs while suspended in room air. The human respiratory tract emits droplets of different size during quiet breathing, coughing, sneezing, speaking, or singing. Respiratory droplets must obey the physical laws of small particles suspended in air. The largest droplets settle quickly onto surfaces where they aggregate with dust, and are resuspended only briefly when disturbed by air currents produced by open windows or people walking in the room. Considerable energy is required to fragment large dust particles into particles of a respirable size. To our knowledge, there is no evidence of dust-borne TB transmission or infection from contaminated surfaces. The small droplets, which evaporate almost instantly on exiting from the mouth and nose, settle so slowly that air currents normally present in any occupied room keep them airborne indefinitely. Although the size of droplet nuclei generated by infectious patients with TB has not been measured directly, aerodynamic principles governing airborne transport and alveolar deposition dictate that the infectious units of TB must be approximately 1 to 5 pm in diameter. Particles under 1 pm in diameter might not accommodate the organism and are unlikely to settle out in the alveolus, whereas particles larger than 5 pm in diameter are unlikely to remain airborne or reach the alveolus if inhaled. The estimated number of infectious droplet nuclei generated by a patient with TB is highly variable. The great majority of infectious patients have cavitary TB with smear-positive sputum. Patients with laryngeal TB are especially infectious. Some patients have been termed “disseminators” and are usually dangerous sources of infection, but not all patients with smear-positive sputum are disseminators.37Sultan L. Nyka W. Mills C. et al.Tuberculosis disseminators: a study of the variability of aerial infectivity of tuberculosis patinets.Am Rev Respir Dis. 1960; 82: 358-369PubMed Google Scholar Brief exposure to some infectious cases has resulted in high infection rates.10Catanzaro A. Nosocomial tuberculosis.Am Rev Respir Dis. 1982; 125: 559-562Crossref PubMed Scopus (191) Google Scholar,11Hutton M.D. Stead W.W. Cauthen G.M. et al.Nosocomial transmission of tuberculosis associated with a draining abscess.J Infect Dis. 1990; 161: 286-295Crossref PubMed Scopus (132) Google Scholar Investigators have paid little attention to factors that relate to the TB patient as an effective or ineffective producer of droplet nuclei and to the biology of M tuberculosis that determines its stability and long-term viability while suspended in a droplet nucleus. Resistance to TB is expressed in two ways: resistance against acquisition of infection and resistance to the development of disease after infection is established. Although the mechanisms by which uninfected persons resist infection with M tuberculosis are uncertain, the macrophage is believed to play a central role in this process, initially through ingestion of bacilli, then synthesis and release of substances that directly destroy bacilli, and ultimately through production of cytokines that enhance immune defenses. Racial differences in susceptibility to TB infection have been reported. In a provocative report, blacks were approximately twice as likely as whites to develop TB infection after equivalent exposure to a source case, possibly because macrophages from blacks are more permissive for growth of M tuberculosis. 38Stead W.W. Senner J.W. Reddick W.T. et al.Racial differences in susceptibility to infection by Mycobacterium tuberculosis.N Engl J Med. 1990; 322: 422-427Crossref PubMed Scopus (321) Google Scholar,39Crowle A.J. Elkins N. Relative permissiveness of macrophages from black and white people for virulent tubercle bacilli.Infect Immun. 1990; 58: 632-638PubMed Google Scholar This racial difference in susceptibility has been attributed to the prolonged selection pressure brought on whites by the TB epidemic throughout Europe for many generations prior to the first introduction of TB into sub-Saharan Africa.16Bates J.H. Stead W.W. The history of tuberculosis as a global epidemic.Med Clin North Am. 1993; 77: 1205-1217Crossref PubMed Scopus (105) Google Scholar Although the human genes that might regulate resistance to TB have not been identified, several studies in animals indicate that this resistance is expressed in the capacity of the host macrophage to kill phagocytized bacilli. In the mouse, Vidal and coworkers40Vidal S.M. Malo M. Vogan K. et al.Natural resistance to infection with intracellular parasites: isolation of a candidate for BCG.Cell. 1993; 73: 469-485Abstract Full Text PDF PubMed Scopus (966) Google Scholar have designated this gene as the “natural resistance-associated macrophage protein gene of Nramp;” it encodes an integral membrane protein that has macrophage-specific membrane transport function. Additional factors that influence acqusition of TB infection remain undefined, but they are likely to involve genetic and acquired factors that determine the capacity of the alveolar macrophage to effectively eliminate tubercle bacilli. For example, HIV infection results in macrophage dysfunction and this may increase the likelihood of TB infection, although this has not been shown. After TB infection is established, interactions between T lymphocytes and macrophages are pivotal in preventing progression of TB infection to disease. A major factor known to markedly reduce the risk for recently inhaled tubercle bacilli to replicate and progress to cause disease is a prior positive tuberculin reaction. In TB outbreaks in which the prior tuberculin reaction of exposed individuals was known, only 0 to 2% of those previously positive developed TB compared with 9 to 59% of those who converted the skin test.41Stead W.W. Management of health care workers after inadvertent exposure to tuberculosis: a guide for the use of preventive therapy.Ann Intern Med. 1995; 122: 906-912Crossref PubMed Scopus (73) Google Scholar Thus, a positive tuberculin reaction provides substantial protection for employees who work in areas where they are likely to be exposed to infectious patients. Exceptions to this rule include HIV-infected persons and possibly others with impaired host defenses heavily exposed to infection.42Small P.M. Shafer R.W. Hopewell P.C. et al.Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection.N Engl J Med. 1993; 328: 1137-1144Crossref PubMed Scopus (477) Google Scholar,43Nardell E. McInnis B. Thomas B. et al.Exogenous reinfection with tuberculosis in a shelter for the homeless.N Engl J Med. 1986; 315: 1570-1575Crossref PubMed Scopus (193) Google Scholar Numerous risk factors have been reported to increase the risk for development of TB, probably through defects in T-lymphocyte and/or macrophage function. Factors most relevant to those concerned with hospital infection control are chronic renal failure, silicosis, jejunoileal bypass, and immunosuppressive therapy with cytotoxic agents or long-term corticosteroids. Although infection control strategies are designed to protect all health-care workers, patients, and visitors, persons at greater risk should be especially careful to avoid unprotected exposure to infectious TB patients. Other factors such as malnutrition, alcoholism, diabetes mellitus, postsubtotal gastrectomy status, and heavy tobacco smoking have been stated to increase the risk of reactivation TB twofold to fivefold44Rieder H.L. Cauthen G.M. Comstock G.W. et al.Epidemiology of tuberculosis in the United States.Epidemiol Rev. 1989; 11: 79-98Crossref PubMed Scopus (259) Google Scholar Infection with HIV accelerates the progression of TB, but HIV does not fundamentally change the possible results of infection with the tubercle bacillus. The clinical presentation of dually infected persons can be more complicated because (1) nonspecific symptoms such as fever and weight loss may be caused by either disease, (2) the sensitivity of the tuberculin skin test decreases, (3) the typical manifestations of TB such as apical cavitary disease are less commonly seen, and (4) extrapulmonary TB, which is more difficult to diagnose, is more frequent. These factors together cause some cases of TB to go undiagnosed. Despite the widely recognized increased risk of TB, potentially infectious pulmonary TB may not even be suspected against a background of frequent respiratory symptoms and signs in HIV-infected persons. This greatly compromises the application of effective infection control precautions. The infectiousness of the HIV-infected patient who also has pulmonary TB has been studied by several observers. For any given extent of radiographic involvement, the HIV-infected patients in one study had more tubercle bacilli in their sputum than did comparable patients who were HIV seronegative.45Shafer RW, Cauthen GM, Dooley S, et al. Tuberculosis transmission by HIV-associated TB case: proceedings of the Seventh International Conference on AIDS 1991; International AIDS Society and WHO, Florence, Italy; MC3326: 79Google Scholar In most instances, however, skin test conversions have been less frequent among contacts of the HIV-infected persons.45Shafer RW, Cauthen GM, Dooley S, et al. Tuberculosis transmission by HIV-associated TB case: proceedings of the Seventh International Conference on AIDS 1991; International AIDS Society and WHO, Florence, Italy; MC3326: 79Google Scholar,46Mungai M. Nunn P. Nyamwaya J. The effect of HIV-1 on the infectiousness of tuberculosis. Proceedings of the Eighth International Conference on AIDS. 1992Google Scholar The impact of effective chemotherapy on infectiousness among these patients has not been studied fully; however, the time required to sterilize sputum is comparable to that observed before the AIDS era, and quantitative studies of the bacillary response in HIV-infected persons show no delay in the bactericidal effect of chemotherapy.47Brindle R.J. Nunn P.P. Githui W. et al.Quantitative bacillary response to treatment in HIV-associated pulmonary tuberculosis.Am Rev Respir Dis. 1993; 147: 958-961Crossref PubMed Scopus (82) Google Scholar To our knowledge, there are no data regarding this question in HIV-infected persons who harbor MDR organisms, but a reasoned view holds that therapy with ineffective agents will not reduce infectiousness, and chemotherapy with drugs less effective than the “first-line tuberculosis agents” will reduce infectiousness less rapidly. Conclusive data are available demonstrating that coinfection with HIV and M tuberculosis increases the risk for immediate and delayed progression from infection to disease. Studies have shown the risk of progression to disease for coinfected persons is 5 to 10% per year compared with an estimated 5 to 10% lifetime risk for HIV-negative persons.48Selwyn P.A. Hartel D. Lewis V.A. et al.A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection.N Engl J Med. 1989; 320: 545-550Crossref PubMed Scopus (1279) Google Scholar,49Allen S. Batungwanayo J. Kerlikowske K. et al.Two-year incidence of tuberculosis in cohorts of HIV-infected and uninfected Rwandan women.Am Rev Respir Dis. 1992; 146: 1439-1444Crossref PubMed Scopus (106) Google Scholar Although it is not known whether HIV infection will increase the risk for an individual to develop TB infection after inhaling viable tubercle bacilli, defects in macrophage function of HIV-infected persons support a reasonable hypothesis that inhaled tubercle bacilli would be more likely to result in infection.50Kumararante D.S. Pithie A. Bassi F.O.E. et al.Mycobacterial immunity and mycobacterial disease in relation to HIV infection.in: Bird G. Immunology of HIV infection. Kluwer Academic Publishers, Boston1992: 113-154Google Scholar Alth