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M C Becerra

Publications and source records attributed to M C Becerra.

16 recordsLinked to original sources
PubMed2006

Representative drug susceptibility patterns for guiding design of retreatment regimens for MDR-TB.

BACKGROUND: There is no gold standard on how national tuberculosis programs should design retreatment regimens. Often drug susceptibility testing (DST) is not available for all patients, and representative DST patterns in patient populations are used to guide therapy. OBJECTIVES: To examine DST patterns in different patient populations based on previous treatment and to estimate the number of effective anti-tuberculosis agents in several retreatment regimens. METHODS: We reviewed DST results from patients treated with individualized regimens in Peru between January 1998 and July 2004. We stratified patients into four groups based on previous treatment exposure from Group 1 who had failed only one regimen to Group 4 who had failed three regimens. We compared resistance frequencies across the four groups. In Groups 1 and 3, the number of likely effective agents under six possible retreatment regimen scenarios was estimated. RESULTS: Resistance to second-line drugs was significantly higher in groups with more previous courses of treatment. A few retreatment regimens could be identified that would allow at least 80% of patients to receive at least four likely effective drugs. CONCLUSION: Because it is associated with resistance frequencies, previous treatment exposure can serve to guide the design of non-individualized MDR-TB regimens.

Adult↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

Retreatment management strategies when first-line tuberculosis therapy fails.

SETTING: Public ambulatory centers in northern Lima, Peru. OBJECTIVE: To compare two retreatment strategies in Category I failures. DESIGN: Retrospective cohort study of Category I failures enrolled between February 1997 and October 2001. Strategy A was a nationwide approach, applying a Category II regimen; if that regimen failed, a standardized regimen including second-line drugs was used. Strategy B was a pilot protocol designed to diagnose and treat multidrug-resistant tuberculosis (MDR-TB); this strategy included drug susceptibility testing (DST) and eliminated the Category II regimen. RESULTS: Of 125 patients that Category I failed to cure, 73 entered Strategy A and 52 entered Strategy B. Almost 90% of those with DST results had MDR-TB. Strategy B was three times more likely than Strategy A to cure patients (79% vs. 38%, RR = 2.9, 95% CI 1.7-5.1) and five times more likely to cure patients than the Category II regimen alone (79% vs. 15%, RR 5.2, 95% CI 3.0-9.2). Strategy B also significantly reduced delays to MDR-TB diagnosis and to the initiation of MDR-TB therapy. CONCLUSIONS: Under program conditions, a retreatment strategy based on DST and eliminating the Category II regimen can improve clinical outcomes among Category I treatment failures found to have active, infectious MDR-TB.

Adolescent↗
PubMed2005

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↗
PubMed2004

Identifying early treatment failure on category I therapy for pulmonary tuberculosis in Lima Ciudad, Peru.

SETTING: Ambulatory, public tuberculosis treatment facilities, central Lima, Peru. OBJECTIVE: To identify risk factors for failure on directly observed Category I therapy. DESIGN: Case-control study. All failures of Category I (2HREZ/4H2R2) therapy in 2000 (2.9% of smear-positive TB patients) were included as cases; two controls per case were matched on health center and approximate time of treatment initiation. RESULTS: The study included 38 cases and 76 controls, all new smear-positive, pulmonary TB patients treated with Category I therapy in central Lima in 2000. Neither treatment irregularity nor incidence of adverse events predicted failure in the study group. Mean baseline body mass index was lower in cases than in controls (P = 0.06). Cases gained less weight during therapy (P = 0.01). Smear positivity at 2 months of therapy was strongly associated with failure (OR 11.7; 95%CI 2.4-57.5). No controls had positive smears at or after 3 months of therapy (OR [corrected] 144.9; 95%CI 8.4-2500). Nearly 75% of cases with isolates tested for susceptibility to first-line drugs had multidrug-resistant TB (MDR-TB). CONCLUSION: A large proportion of failures on Category I therapy can be identified early. As three-quarters of patients with susceptibility results have MDR-TB, early referral for culture and drug susceptibility testing is critical for prompt initiation of appropriate therapy and improved outcomes.

Adolescent↗
PubMed2004

Drug resistance trends among previously treated tuberculosis patients in a national registry in Peru, 1994-2001.

SETTING: National mycobacteriology reference laboratory in Peru conducting routine testing of susceptibility to isoniazid, rifampin, ethambutol, pyrazinamide, and streptomycin, in Mycobacterium tuberculosis isolates from previously treated patients. OBJECTIVE: To determine the percentage of isolates resistant to each of five anti-tuberculosis agents and to ascertain in these data the presence of trends of clinical relevance. DESIGN: Retrospective study of a national registry of M. tuberculosis isolates from patients referred for drug susceptibility testing between 1994 and 2001. RESULTS: Among 14,736 isolates tested, 10,837 (73.5%, 95%CI 72.8-74.3) demonstrated anti-tuberculosis resistance, and 8455 (57.4%, 95%CI 56.6-58.2) demonstrated resistance to at least both isoniazid and rifampin, by convention defined as multidrug-resistant tuberculosis (MDR-TB). A significant increasing trend could be discerned for resistance to each of the drugs tested and in isolates classified as MDR-TB (P < 0.001 for trend). Additional clinically relevant trends were found in polyresistance and multidrug resistance percentages. CONCLUSIONS: Data from a national reference laboratory can be used to inform the design of retreatment regimens.

Antitubercular Agents↗
PubMed2003

Contact investigations as a means of detection and timely treatment of persons with infectious multidrug-resistant tuberculosis.

SETTING: Two regions of metropolitan Lima, Peru. OBJECTIVE: To determine the outcomes of two contact investigation strategies used in therapy enrollment cohorts of patients with multidrug-resistant tuberculosis (MDR-TB). DESIGN: From 28 August 1996 to 31 December 1999, 91 index patients received individualized MDR-TB therapy (Group A), and from 1 October 1997 to 31 December 1999, another 101 index patients received a standardized MDR-TB regimen (Group B). We conducted a retrospective chart review and home visits to identify secondary cases among close contacts of both of these groups. Group A secondary cases with MDR-TB received therapy based on the drug susceptibility profile of their infecting strain, while Group B secondary cases received standard short-course therapy. RESULTS: Among 945 close contacts, 72 secondary TB cases (8%) were found. Of 42 who had drug-susceptibility testing, 35 (84%) were MDR-TB, but only seven (17%) had the same drug susceptibility profile as the index case. Cure exceeded 80% in Group A secondary cases, while only half of Group B secondary cases were cured (RR 1.6, 95%CI 1.1-2.2). CONCLUSION: Contact investigation protocols coupled with enrollment in MDR-TB therapy are a useful means of detecting and promptly treating persons with infectious MDR-TB. In settings with endemic MDR strains of Mycobacterium tuberculosis, effective therapy of contacts of MDR-TB patients requires knowledge of drug susceptibility for each contact with active disease.

Adolescent↗
PubMed2002

Oxidative stress induced by ciprofloxacin in Staphylococcus aureus.

Staphylococcus aureus with multiple sensitivity to ciprofloxacin, was investigated to detect alterations in the production of superoxide anion (O(2)(-)), other reactive oxidant species (ROS), and superoxide dismutase (SOD), and to relate them with ciprofloxacin accumulation and sensitivity. Oxidative stress was studied by means of Nitroblue Tetrazolium reaction (NBT) and chemiluminescence (CL); lucigenin was employed to detect O(2)(-), and luminol was used to measure other ROS. Sensitive strains exhibited higher intracellular O(2)(-) increase than resistant ones when incubated with ciprofloxacin. SOD was determined in normal conditions and induction was investigated in the presence of ciprofloxacin. These assays demonstrated that resistant and sensitive strains exported a great amount of SOD and that the induction of SOD intracellular was insufficient to counteract the augment of O(2)(-) in the cytoplasm of sensitive strains. Accumulation of ciprofloxacin, researched by spectrofluorometry, showed high levels of antibiotic in sensitive strains which increased the O(2)(-) causing more oxidative stress than in resistant S. aureus.

Ciprofloxacin↗
PubMed2001

Occurrence of serious adverse effects in patients receiving community-based therapy for multidrug-resistant tuberculosis.

SETTING: A community-based treatment program for multidrug-resistant tuberculosis (MDR-TB) in an urban shantytown of Lima, Peru. OBJECTIVES: To ascertain the occurrence of serious adverse effects associated with therapy for MDR-TB in northern Lima, Peru, where therapy was individualized according to drug-susceptibility testing of patients' infecting strains and delivered through a community-based program. DESIGN: A retrospective record review of 60 patients who had received individualized therapy for MDR-TB between September 1996 and October 1998. RESULTS: Although adverse effects were common, they occurred less frequently than previously reported in the literature and were rarely life-threatening. Effects occurring most frequently in this population included: mild gastritis (100%), dermatological effects (43.3%), peripheral neuropathy (16.7%), depression (18.3%), and anxiety (11.7%). These effects never resulted in the discontinuation of anti-tuberculosis therapy, and only occasionally resulted in the suspension of an agent (11.7%). CONCLUSION: In young patients with little comorbid disease, multidrug, long-course regimens rarely caused life-threatening adverse effects. Common side effects may be managed successfully on an out-patient basis through a community-based treatment program in conjunction with MDR-TB experts, even in resource-poor settings. The very low rate of default in this cohort offers hope that strategies to manage the adverse effects may reduce the incidence of abandonment of therapy and increase rates of cure.

Adolescent↗
PubMed2000

Effect of administering short-course, standardized regimens in individuals infected with drug-resistant Mycobacterium tuberculosis strains.

Presented here are the cases of three siblings with multidrug-resistant tuberculosis who demonstrated increased antituberculous-drug resistance during the periods in which they received standard regimens of directly observed, short-course chemotherapy that were administered before the susceptibility patterns of their Mycobacterium tuberculosis isolates had been checked. More specifically, they acquired resistance to drugs they received as part of ineffective standard treatment and retreatment regimens. Development of antituberculous-drug resistance through inadvertent, inadequate therapy appears to be the most likely explanation for the increased resistance seen in these three patients.

Adolescent↗
PubMed2000

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↗
PubMed2000

Redefining MDR-TB transmission 'hot spots'.

Halting further spread of multidrug-resistant tuberculosis (MDR-TB) requires both new resources and a renewed discussion of priority setting informed by estimates of the existing burden of this disease. The 1997 report of the first phase of the global survey by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) uses the indicator of the proportion of TB cases that are MDR-TB to identify MDR-TB 'hot spots'. We sought to refine the definition of MDR-TB transmission 'hot spots'. For this purpose, we obtained estimates of two additional indicators for regions where data are available: MDR-TB incidence per 100,000 population per year, and expected numbers of new patients with MDR-TB per year. There is generally much agreement in the three indicators considered, and some differences also appear. We conclude that it is useful, when defining indicators of MDR-TB transmission 'hot spots', to include estimates of underlying TB incidence rates and of absolute numbers of MDR-TB cases. Estimating the force of morbidity of MDR-TB in a population is important for comparing this burden across settings with very different underlying TB incidence rates; estimating the absolute number of MDR-TB patients will be critical for planning the delivery of directly observed MDR-TB therapy and the rational procurement of second-line drugs. Through this exercise, we aim to initiate discussion about improved methods of quantifying and comparing current MDR-TB transmission 'hot spots' that require intervention.

Antitubercular Agents↗
PubMedDate not supplied

Comparison of oxidative stress induced by ciprofloxacin and pyoverdin in bacteria and in leukocytes to evaluate toxicity.

Oxidative stress induced by ciprofloxacin and pyoverdin, a leukotoxic pigment, was studied by comparing their effect in bacteria and leukocytes. Chemiluminescence (CL) assays with lucigenin or luminol were adapted to measure the stimuli of superoxide anion (O2 -) and other reactive species of oxygen (ROS) in bacteria. Ciprofloxacin principally induced the production of O2 - in the three species studied: Staphylococcus aureus, Enterococcus faecalis and Escherichia coli. Lucigenin CL assay showed high oxidative stress in S. aureus due to its low superoxide dismutase (SOD) activity, whereas E. coli exhibited important SOD activity, responsible for little production of O2 - in absence or presence of ciprofloxacin. Reduction of nitroblue of tetrazolium (NBT) was applied. This assay indicated that there was higher oxidative stress in S. aureus and E. faecalis than in E. coli. The comparison of oxidative stress generated in bacteria and leukocytes was used to check the selective toxicity of ciprofloxacin in comparison with pyoverdin. Ciprofloxacin did not generate significant stimuli of O2 - in neutrophils, while pyoverdin duplicated the production of O2 -. CL and NBT were useful to study the leukotoxicity of ciprofloxacin. Oxidative stress caused by the antibiotic and the leukotoxic pigment was similar in bacteria.

Animals↗