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Biomedical subjects

L W Riley

Publications and source records attributed to L W Riley.

At least 55 records · Page 3Linked to original sources

Retreatment tuberculosis cases. Factors associated with drug resistance and adverse outcomes.

STUDY OBJECTIVE: Risk factors associated with treatment failure and multidrug-resistant tuberculosis (MDR-TB) were examined among HIV-seronegative patients who were previously treated for tuberculosis (TB). DESIGN: Prospective, cohort study of patients referred to the study hospital for retreatment of TB between March 1986 and March 1990. PATIENTS: The patients belonged to three groups, according to outcomes following their previous treatment: 37 patients who abandoned treatment or suffered relapse after completion of therapy (group A), 91 patients who failed to respond to the first-line drug regimen (group B), and 78 patients who failed to respond to the second-line drug regimen (group C). RESULTS: Patients with Mycobacterium tuberculosis strains resistant to rifampin and isoniazid were found in 2 (6%) in group A, 29 (33%) in group B, and 49 (65%) in group C. Cure was achieved in 77% in group A, 54% in group B, and 36% in group C. Death occurred in none of the patients in group A, 8% in group B, and 24% in group C. In a multivariate logistic regression analysis, unfavorable response (failure to sterilize sputum culture, death, and abandonment) was significantly associated with infection with a multidrug-resistant M tuberculosis strain (p = 0.0002), cavitary disease (p = 0.0029), or irregular use of medications (p < 0.0001). CONCLUSIONS: These observations show that a previous treatment outcome and current clinical and epidemiologic histories can be used to predict the development of MDR-TB and adverse outcomes in patients undergoing retreatment for TB. Such information may be useful for identifying appropriate patient candidates for programs such as directly observed therapy.

Adult↗

Risk factors and outcome of human immunodeficiency virus-infected patients with sporadic multidrug-resistant tuberculosis in New York City.

SETTING: An 880 bed university teaching hospital in New York City. OBJECTIVE: To assess risk factors and outcome for sporadic cases of multidrug-resistant tuberculosis (MDR-TB) in persons with human immunodeficiency virus (HIV) infection. DESIGN: In a retrospective cohort analysis, 13 HIV-positive patients with MDR-TB (cases) diagnosed between January 1991 and December 1993 were compared to 31 HIV-infected patients with susceptible or single drug-resistant tuberculosis (controls) diagnosed during the same time period to assess for differences in risk factors and outcome. RESULTS: Risk factors for MDR-TB included homosexual contact as a risk for HIV transmission, prior antiretroviral therapy and Pneumocystis carinii prophylaxis. Fatality rates were 62% for MDR-TB patients and 26% for controls (P < 0.04). The median survival time was 5.8 months for cases and 9.8 months for controls. Risk factors associated with death included multidrug-resistance and CD4-lymphocyte counts below 200. CONCLUSION: Sporadic MDR-TB infection in HIV-infected patients is associated with increased morbidity and mortality compared to infection with susceptible or single-drug-resistant TB. The median survival for HIV-infected patients with MDR-TB in this study is, however, two to three times longer than previously reported in MDR-TB outbreaks.

AIDS-Related Opportunistic Infections↗

Tuberculosis among foreign-born persons in New York City, 1992-1994: implications for tuberculosis control.

OBJECTIVE: To study the pattern of transmission of tuberculosis (TB) among foreign-born persons living in New York City. DESIGN: A retrospective multicenter study comparing 158 foreign-born patients to 231 US-born patients diagnosed with TB between 1992 and 1994. The patients were stratified according to their Mycobacterium tuberculosis isolate DNA fingerprint patterns. RESULTS: Nineteen (16%) of 122 isolates from foreign-born TB patients and 75 (42%) of 180 isolates from US-born TB patients had DNA fingerprint patterns (cluster patterns) indicative of recent exogenous transmission (P < 0.001). All cluster pattern strains from foreign-born cases were identical to those found among US-born patients. The likelihood of infection with a cluster pattern strain among foreign-born persons increased with duration of residence in the US, and was significantly associated with being homeless (P < 0.05), or having multidrug-resistant TB (P = 0.00072). CONCLUSION: Although most (84%) cases of TB among foreign-born persons in New York City appear to result from reactivation of infections they acquired abroad, the ones who acquire new infections become infected with strains that are already circulating among the US-born TB patients in New York City, and they have risk factors similar to those faced by US-born tuberculosis patients.

Adult↗

Tuberculosis and HIV infection among female inmates in São Paulo, Brazil: a prospective cohort study.

Prison populations are at increased risk of both human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections, but among female inmates information on such risks remains scarce, especially in developing countries. Between October 1992 and November 1993, 350 women incarcerated at a prison in São Paulo, Brazil, were prospectively evaluated for HIV and M. tuberculosis infection and disease. Among them, 87 (25%) were HIV seropositive, and 20 (5.7%) had tuberculosis (TB). During the incarceration period, the purified protein derivative test conversion rate was 29% for HIV-positive and 32% for HIV-negative women. However, the incidence of TB was 9.9 per 100 person-years for HIV-positive and 0.7 per 100 person-years of incarceration for HIV-negative women (p < 0.0001). A multivariate analysis indicated that HIV infection (p < 0.0001) and incarceration time < 12 months (p < 0.05) were each associated with TB. These findings indicate that new transmissions of M. tuberculosis infection are common among female inmates and that HIV-infected women are more likely to acquire active disease during the first 12 months of incarceration. Because of their role in childbearing and care female inmates are an important potential source of transmission of M. tuberculosis, and new strategies to control the spread of TB in prisons need to be developed.

Adolescent↗

Risk factors associated with vancomycin-resistant Enterococcus faecium infection or colonization in 145 matched case patients and control patients.

Risk factors and mortality associated with vancomycin-resistant Enterococcus faecium (VREF) infection or colonization were examined at a tertiary care hospital by comparing 145 patients who had VREF isolates (cases) to 145 patients with vancomycin-susceptible Enterococcus faecium (VSEF) isolates (controls). The number of deaths per 100 person-days of hospitalization after diagnosis did not differ significantly between VREF patients (1.2) and VSEF patients (0.8). Multivariate analyses found that the duration of hospitalization ( > or = 7 days), intrahospital transfer between floors, use of antimicrobials (i.e., vancomycin and third-generation cephalosporins), and duration of vancomycin use ( > or = 7 days) was independently associated with VREF infection or colonization. This study, which has a large sample size, confirms some earlier observations regarding risks for VREF infection or colonization and identifies factors that may be potentially exploited to develop interventional strategies for the control of this emerging nosocomial problem.

Adolescent↗

Association of penicillin-resistant pneumococci with residence in a pediatric chronic care facility.

Risk factors for the acquisition of penicillin-resistant pneumococci (PRP) were analyzed at a university hospital in New York City. Patients with PRP and control patients with penicillin-sensitive pneumococcal infections were compared. In 1994, 24 (21%) of 113 patients with Streptococcus pneumoniae infections had PRP; 13 PRP isolates were from children and 11 from adults. Only white race (P < .05) and residence in a pediatric chronic care facility (P < .05) were significantly associated with penicillin resistance. An investigation at one chronic care facility revealed that 33% of children (17/52) had PRP colonization. Fourteen of the 17 PRP isolates were also resistant to ceftriaxone. Prior antibiotic use and specifically beta-lactam use were associated with penicillin resistance. All typeable PRP isolates were multidrug-resistant serotype 23. Pediatric residents in chronic care facilities may be an important reservoir of PRP and may serve as a source of PRP transmission when they are transferred to acute care hospitals.

Adolescent↗

Transmission of tuberculosis to close contacts of patients with multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDRTB) has emerged as a major public health problem worldwide. To determine the incidence and risk factors associated with tuberculosis among contacts of MDRTB index cases, we studied human immunodeficiency virus-seronegative close contacts of 64 culture-confirmed MDRTB patients in Rio de Janeiro, Brazil. Between March 1988 and July 1992, tuberculosis developed in 17 (7.8%) of 218 previously healthy close contacts of 64 MDRTB index cases (1.6 cases per 1,000-person-months of contact). Among strains of Mycobacterium tuberculosis isolated from 13 contacts of 12 index cases, six (46%) had susceptibility patterns identical to those of their index cases, four (31%) had different patterns of resistance, and three (23%) were susceptible to all drugs. Tuberculosis developed more frequently in male contacts (p < 0.05), persons > or = 15 yr of age (p < 0.05), nonwhites (p < 0.001), and persons not previously vaccinated with bacillus Calmette-Guerin (BCG) (p < 0.05). The association of BCG vaccination with decreased risk of disease was significant even when this variable was controlled (by Cox's regression analysis) for age, sex, race, purified protein derivative (PPD) status, and isoniazid prophylaxis. BCG vaccination appears to offer protection against tuberculosis during prolonged exposures to persons with MDRTB, which identifies a novel and specific indication of BCG use.

Adolescent↗

The transcontinental transmission of tuberculosis: A molecular epidemiological assessment.

Many tuberculosis control activities are based on principles learned from studies of tuberculosis transmission. To date, these have largely been limited to outbreak investigations in confined geographical regions. In this report conventional and computerized DNA fingerprint- based approaches were integrated to demonstrate that the most widely prevalent strain of Mycobacterium tuberculosis from New York City was cultured from only 1 of 755 patients in San Francisco, Calif, who was a traveling salesman. Large-scale molecular epidemiologic studies may provide a better understanding of the dynamics of tuberculosis transmission between geographic regions and suggest rational measures to interrupt such transmission.

Adult↗

High sensitivity of Mycobacterium species to the bactericidal activity by polylysine.

Bactericidal effects of polylysine on different bacterial species were measured. Marked differences in sensitivity were observed. Based on the concentration of polylysine required to reduce cell viability by 50%, Mycobacterium smegmatis and Mycobacterium tuberculosis were found to be the most sensitive and Escherichia coli the most resistant. In addition, two Gram-positive organisms, Staphylococcus epidermidis and Streptococcus salivarius exhibited significant differences in sensitivity which suggests that the relationship between sensitivity towards polylysine and bacterial cell type is not necessarily a function of the overall cell envelope structure. The high sensitivity of mycobacteria suggests the possible use of polylysine, or a conjugate of polylysine and another agent in anti-mycobacterial drug design.

Anti-Bacterial Agents↗

Determinants of cell entry and intracellular survival of Mycobacterium tuberculosis.

The ability of Mycobacterium tuberculosis to sustain a chronic infection and cause disease in a subset of those infected depends on its products--virulence factors--that enable the organism to enter and survive indefinitely inside mononuclear phagocytic cells by subverting cellular antimicrobial mechanisms. Characterizing these factors is essential to understanding the pathogenesis of M. tuberculosis.

Adult↗

Catalase expression, katG, and MIC of isoniazid for Mycobacterium tuberculosis isolates from São Paulo, Brazil.

The MIC of isoniazid, peroxidase-catalase expression, and the presence of the katG gene for 102 Mycobacterium tuberculosis isolates from patients in São Paulo were compared. Fifty-three isoniazid-resistant and 49 isoniazid-sensitive isolates were analyzed by polymerase chain reaction (PCR) for the presence of katG sequences. All isoniazid-sensitive and 43 (81%) isoniazid-resistant isolates expressed catalase (P = .001). None of isoniazid-sensitive and 4 (7%) of 53 isoniazid-resistant isolates lacked katG sequences. Among 6 isolates with MICs > 50 micrograms/mL, 5 (83%) did not express catalase and 2 lacked katG sequences; only 1 had complete gene deletion shown by Southern blot analysis. These findings indicate a correlation between loss of catalase and isoniazid resistance among highly resistant isolates, but these isolates were a small proportion of resistant clinical M. tuberculosis isolates from São Paulo.

Bacterial Proteins↗

Differentiation of pathogenic Escherichia coli strains in Brazilian children by PCR.

A PCR technique to differentiate pathogenic enteric Escherichia coli strains in a field setting was evaluated. Among 76 children with acute diarrhea, this technique identified 12 children (16%) with enterotoxigenic E. coli, 6 (8%) with enteropathogenic E. coli, and 1 (1%) with enteroinvasive E. coli infection. Compared with the conventional assays, the PCR method proved to be simpler, more rapid, and inexpensive and therefore suitable for application in a developing-country field setting.

Bacteriological Techniques↗

Identification of enteropathogenic Escherichia coli by PCR-based detection of the bundle-forming pilus gene.

A rapid and simple method of detecting enteropathogenic Escherichia coli (EPEC) was developed. The procedure is based on amplifying by the PCR method a 326-bp region of the bundle-forming pilus gene of EPEC. The oligonucleotide DNA primers used in this procedure did not amplify DNA of any other bacterial enteropathogens tested. The procedure was 100% specific for EPEC strains that exhibit a characteristic pattern of attachment (localized adherence) to HeLa cells.

Bacteriological Techniques↗

Double-repetitive-element PCR method for subtyping Mycobacterium tuberculosis clinical isolates.

We describe a rapid method for subtyping Mycobacterium tuberculosis based on PCR amplification of segments located between two distinct DNA repetitive elements. This method, double-repetitive-element PCR, classified 46 clinical isolates as having 25 distinct patterns; the conventional restriction fragment length polymorphism analysis classified the same isolates as having 23 distinct patterns. The double-repetitive-element PCR is a rapid subtyping method that has a discriminating power similar to that of the restriction fragment length polymorphism method.

Bacterial Typing Techniques↗

Transmission of multidrug-resistant tuberculosis in a large urban setting.

Multidrug resistance has become an increasingly important problem in the control and prevention of tuberculosis in large urban centers. Although several small outbreaks of multidrug-resistant (MDR) tuberculosis in New York City have been reported, the increase in the number of cases is not fully explained by these recognized outbreaks, and the modes of transmission have not been clearly delineated. Transmission patterns of MDR tuberculosis in New York City, therefore, were studied by stratifying Mycobacterium tuberculosis isolates from 167 newly diagnosed tuberculosis patients according to their DNA restriction fragment length polymorphisms (RFLP). Forty-three (34%) of 127 drug-susceptible isolates and 19 (79%) of 24 multidrug-resistant isolates had RFLP patterns representing possible recent exogenous infection (primary tuberculosis). Patients who had such isolates were more likely to be seropositive for human immunodeficiency virus (58%; p < 0.05), non-Hispanic black (56%; p < 0.005), U.S.-born (57%; p < 0.001), and have MDR tuberculosis (79%; p < 0.0005). In a logistic regression model, primary tuberculosis remained significantly associated with MDR tuberculosis and black race. In contrast to previous reports, in New York City recent exogenous transmission accounts for most new cases of multidrug-resistant tuberculosis.

Adult↗

Restriction fragment length polymorphism analysis of clinical isolates of Mycobacterium haemophilum.

Mycobacterium haemophilum is an emerging opportunistic pathogen, and since 1989, infections caused by this organism have been identified more frequently in the New York City area than in any other region of the United States. A DNA fingerprinting method, based on restriction fragment length polymorphisms (RFLPs) was developed. A genomic library of M. haemophilum isolate 1A was constructed; screening the library yielded a recombinant strain that incorporated a genetic element present in multiple copies in the M. haemophilum genome. This clone was used to produce a probe for RFLP analyses of PvuII digests of genomic DNA. We used this probe to determine the RFLP patterns of 43 clinical isolates of M. haemophilum from 28 patients. A total of six distinct patterns were observed. Two patterns, designated types 1 and 2, accounted for 91% of the infections in patients from the New York City area. Two isolates from Arizona had identical patterns but were distinct from those of New York isolates, and an isolate from Israel, the type strain, had another distinct pattern (type 6). The type 6 pattern was also seen in a recent isolate from Norway. All of the type 1 isolates and 60% of the type 2 isolates were recovered from patients with AIDS in the New York City area. This molecular subtyping method should provide a useful tool for epidemiological studies and may help identify the associated risk factors, vehicles, and possible reservoirs of this newly emerging pathogen.

AIDS-Related Opportunistic Infections↗

Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells.

Mycobacterium tuberculosis infects one-third of the world's human population. This widespread infection depends on the organism's ability to escape host defenses by gaining entry and surviving inside the macrophage. DNA sequences of M. tuberculosis have been cloned; these confer on a nonpathogenic Escherichia coli strain an ability to invade HeLa cells, augment macrophage phagocytosis, and survive for at least 24 hours inside the human macrophage. This capacity to gain entry into mammalian cells and survive inside the macrophage was localized to two distinct loci on the cloned M. tuberculosis DNA fragment.

Bacterial Proteins↗

Drug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDRTB) is an iatrogenic disease that is emerging as a major infectious disease problem throughout the world. The AIDS pandemic, increased incidence of tuberculosis in populations with easy access to antituberculosis medications, the deterioration of the public health infrastructure, and inadequate training of health care providers in the epidemiology of tuberculosis are some of the factors contributing to the increased incidence of MDRTB. Mortality from MDRTB exceeds 80% in persons infected with human immunodeficiency virus (HIV) but is also high in patients free of HIV. The management of MDRTB is complicated by the lack of methods for rapid detection of resistant strains of Mycobacterium tuberculosis. The risk of infection among close contacts of patients with MDRTB, the probability of the development of active MDRTB after infection, and the likelihood of cure of MDRTB need to be determined quantitatively. Attributable risk estimates for factors associated with MDRTB should be calculated for each community as part of the strategies to prevent MDRTB. Issues regarding chemoprophylaxis in newly infected contacts of MDRTB cases remain unanswered. Basic research on the mechanisms of action of existing antituberculosis drugs may contribute to an understanding of the mechanism of resistance in M. tuberculosis. There is an urgent need to expand the scope of epidemiological, clinical, and laboratory research to address these problems.

Drug Resistance, Microbial↗