PubMed Health⌕ Search

Biomedical subjects

R Timperi

Publications and source records attributed to R Timperi.

11 recordsLinked to original sources

rpoB gene mutations in clinical isolates of multidrug-resistant Mycobacterium tuberculosis in northern Lima, Peru.

In many developing countries and outside hospital settings, the characteristics of endemic Mycobacterium tuberculosis strains resistant to multiple drugs remain unknown. In a community-based referral and therapy program in northern Lima, Peru, beginning in 1996, patients found to be failures on standard regimens were referred for drug-susceptibility testing of their isolates, and those found to be infected with M. tuberculosis isolates resistant to at least rifampin were treated with individualized regimens based on their infecting strains. Isolates from 42 of these patients were subjected to DNA sequencing of the rpoB gene region responsible for rifampin resistance. We determined the frequency of types of mutations in the rpoB gene among these Peruvian isolates.

Antibiotics, Antitubercular↗

Drug resistance profiles of Mycobacterium tuberculosis isolates: five years' experience and insight into treatment strategies for MDR-TB in Lima, Peru.

SETTING: Lima, Peru. OBJECTIVE: To describe drug resistance profiles of TB isolates from patients at risk for multidrug-resistant tuberculosis (MDR-TB), and to consider the implications of these findings for treatment. DESIGN: Descriptive study of drug susceptibility testing (DST) results for TB isolates from 1680 patients referred for suspicion of MDR-TB between 1996 and 2001. RESULTS: Of 1680 isolates tested, 1144 (68%) were resistant to at least one anti-tuberculosis drug and 926 (55%) were MDR-TB strains. Of 926 MDR isolates, 50 (5%) were resistant to INH and RMP alone, while 367 (40%) were resistant to at least five first-line drugs. We identified 146 unique drug resistance profiles, the most common of which accounted for 11% of drug-resistant isolates. The annual prevalence of isolates with resistance to at least five first-line drugs rose significantly during the study period, from 29% to 37% (P = 0.00086). CONCLUSIONS: This is a group of patients with TB disease among whom the prevalence of a broad spectrum of often highly drug-resistant strains appears to be increasing over time. A single standardized retreatment regimen may be inadequate to cure most patients. Capacity for drug sensitivity testing is essential for development of multiple standardized retreatment or individualized treatment regimens and epidemiological surveillance for planning.

Drug Resistance, Bacterial↗

Acquisition of drug resistance in multidrug-resistant Mycobacterium tuberculosis during directly observed empiric retreatment with standardized regimens.

The risk of acquiring additional drug resistance in strains of multidrug-resistant tuberculosis (MDR-TB) during failure of empiric standardized retreatment regimens is poorly defined. We sought to estimate this risk by comparing drug susceptibility profiles and RFLP patterns of paired MDR-TB isolates collected from 27 patients before and after retreatment failure. Among 23 patients with paired isolates with concordant RFLP patterns, 19 (83%) had become resistant to at least one additional drug after failed retreatment. In this limited group of MDR-TB patients, acquisition of resistance was common during failure of empiric drug regimens. Further study is needed to confirm these findings.

Adolescent↗

The effectiveness of housing policies in reducing children's lead exposure.

OBJECTIVES: This study evaluated the relation of housing policies to risk of subsequent lead exposure in addresses where lead-poisoned children had lived. METHODS: Addresses where children with lead poisoning lived between May 1992 and April 1993 were selected from lead screening registries in 2 northeastern states differing in their enforcement of lead poisoning prevention statutes. Blood lead levels of subsequently resident children, exterior condition, tax value, age, and census tract characteristics were collected. The odds of elevated blood lead levels in subsequently resident children were calculated with logistic regression. RESULTS: The risk of identifying 1 or more children with blood lead levels of 10 micrograms/dL or greater was 4 times higher in addresses with limited enforcement. Controlling for major confounders had little effect on the estimate. CONCLUSIONS: Enforcement of housing policies interrupts the cycle of repeated lead exposure.

Child, Preschool↗

Recovery of Bordetella holmesii from patients with pertussis-like symptoms: use of pulsed-field gel electrophoresis to characterize circulating strains.

A 4-year retrospective study showing that we isolated Bordetella holmesii, but not Bordetella pertussis, from patients with pertussis-like symptoms was performed. From 1995 through 1998, we isolated B. holmesii from 32 nasopharyngeal specimens that had been submitted from patients suspected of having pertussis. Previously, B. holmesii had been associated mainly with septicemia and was not thought to be associated with respiratory illness. A study was undertaken to describe the characteristics of the B. holmesii isolates recovered and why we were successful in detecting the organism in nasopharyngeal specimens. B. holmesii isolates were characterized for drug sensitivities and for genetic relatedness by pulsed-field gel electrophoresis (PFGE). These isolates, an additional strain of B. holmesii isolated from a blood culture and previously confirmed by the Centers for Disease Control and Prevention, Atlanta, Ga., and 14 other clinical isolates of Bordetella spp., including 4 of B. bronchiseptica, 5 of B. parapertussis, and 5 of B. pertussis, were studied. They were all separately inoculated on three Bordet Gengou (BG) selective media containing either 0.625 microgram of oxacillin per ml, 40 microgram of cephalexin per ml, or 2.5 microgram of methicillin per ml, on BG agar with no antibiotic (control), and on charcoal agar (CA) with and without 40 microgram of cephalexin per ml. We found that cephalexin, the antibiotic commonly incorporated in both CA and BG agar for the recovery of Bordetella spp., is inhibitory to the growth of B. holmesii. In addition, the genotypic analysis of the 32 B. holmesii isolates by PFGE following restriction with XbaI and SpeI identified the dominant strains circulating during the study period.

Bacterial Typing Techniques↗

Using treatment failure under effective directly observed short-course chemotherapy programs to identify patients with multidrug-resistant tuberculosis.

SETTING: Public ambulatory care centers in three districts of northern metropolitan Lima, Peru. OBJECTIVE: To document drug resistance patterns of isolates of Mycobacterium tuberculosis from patients identified as treatment failures under a model tuberculosis (TB) control program based on directly observed, short-course chemotherapy (DOT-SCC). DESIGN: Case series. RESULTS: In a referred, consecutive sample of 173 patients identified as treatment failures on DOT-SCC, 160 (92.5%) had culture-positive TB. Of those 160, 150 (93.8%) had active, pulmonary multidrug-resistant TB (MDR-TB, resistance to at least isoniazid [INH] and rifampicin [RIF]). Sixty of the 150 (40.0%) had isolates resistant to at least INH, RIF, ethambutol (EMB) and pyrazinamide (PZA), the initial first-line empiric treatment regimen used locally. Forty-four (29.3%) had isolates resistant to at least INH, RIF, EMB, PZA and streptomycin (SM), the first retreatment regimen. This series of patients had isolates resistant to a mean of 4.5 of the ten drugs tested. The local profile of multidrug resistance is very different from that obtained from national data from Peru. CONCLUSION: In this setting, treatment failure on DOT-SCC is strongly predictive of active MDR-TB. Because of existing local drug resistance patterns in northern Lima, 89.3% of MDR-TB patients identified as treatment failures will receive ineffective therapy with two or fewer secondary TB drugs if they are given the five-drug empiric retreatment regimen endorsed by the World Health Organization. Further short-course chemotherapy for these patients would only serve to amplify ominous existing drug resistance patterns.

Antitubercular Agents↗

Human exposure to polychlorinated biphenyls in Greater New Bedford, Massachusetts: a prevalence study.

A study was conducted in the community of Greater New Bedford, Massachusetts, from 1984 through 1987 to assess the prevalence of elevated levels of polychlorinated biphenyls (PCBs) in the serum of individuals aged 18 to 64 years who had resided in the area for at least 5 years. Eight hundred and forty subjects were interviewed, examined, and tested in a cross-sectional sample of the towns of Acushnet, Dartmouth, and Fairhaven and the city of New Bedford. Serum PCBs were measured to estimate the extent of human exposure. Because of documented environmental contamination by PCBs in the New Bedford area, and the practice of recreational fishing in the harbor for food, a significant number of persons with elevated serum PCB levels were expected to be identified. Instead, the prevalence of elevated serum PCBs in the sample was found to be typical of "unexposed" urban populations in the United States. Only 1.3% of the subjects had serum PCB levels greater than 30 ppb. The same percentage was observed among males (n = 391) and females (n = 449). The geometric means of PCB levels were 4.3 ppb among males (Range = 0.50-60.9) and 4.2 ppb among females (Range = 0.38-154). We conclude that the prevalence of elevated serum PCBs is low in the population of Greater New Bedford.

Adolescent↗

Isocratic reversed-phase HPLC method to measure pyrimethamine extracted from plasma of infants treated for toxoplasmosis.

An isocratic HPLC method for measuring pyrimethamine extracted from infant plasma is reported. The method is an improvement over previously published methods by requiring lower volumes of plasma (100 microL) and having increased sensitivity to pyrimethamine at 210 nm. The procedure, which entails a basic organic extraction and subsequent HPLC chromatography of the reconstituted extract, can detect 1.4 ng and quantify 4.0 ng of pyrimethamine per 40-microL injection, with two analyses per 100-microL sample. Analytical recovery of pyrimethamine added to plasma at 10, 50, and 125 ng/100 microL averaged 80%, 92%, and 101%, respectively (n = 20). Within- and between-day CVs were less than 7%. Studies of various plasma samples from adults and infants (n = 15) revealed no interference from other plasma peaks with the analyte of interest.

Chromatography, High Pressure Liquid↗

Maternal marijuana use and neonatal outcome: uncertainty posed by self-reports.

To assess the validity of self-reported marijuana use during pregnancy, this study randomly allocated pregnant women into a group who were told their urine would be tested for marijuana, alcohol, and other drugs and another group not so tested. Women told they would be tested reported more marijuana use during pregnancy than did untested women. Moreover, urine assays identified more women who used marijuana during pregnancy than were willing to admit it in the interview even after being told their urine would be tested. No differences in reported drinking or cigarette smoking during pregnancy were found between tested and untested women.

Adult↗