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Maya J.J.,International Center for Medical Research and Training | Ruiz S.J.,International Center for Medical Research and Training | Blanco V.M.,International Center for Medical Research and Training | Gotuzzo E.,Hospital Nacional Cayetano Heredia | And 5 more authors.
Expert Review of Anti-Infective Therapy

Enterobacteriaceae and non fermenting Gram-negative bacilli have become a threat to public health, in part due to their resistance to multiple antibiotic classes, which ultimately have led to an increase in morbidity and mortality. β-lactams are currently the mainstay for combating infections caused by these microorganisms, and β-lactamases are the major mechanism of resistance to this class of antibiotics. Within the β-lactamases, carbapenemases pose one of the gravest threats, as they compromise one of our most potent lines of defense, the carbapenems. Carbapenemases are being continuously identified worldwide; and in Latin America, numerous members of these enzymes have been reported. In this region, the high incidence of reports implies that carbapenemases have become a menace and that they are an issue that must be carefully studied and analyzed. © 2013 Informa UK Ltd. Source

Guarino A.,University of Naples Federico II | Dupont C.,University of Paris Descartes | Gorelov A.V.,University College Dublin | Gottrand F.,Center Hospitalier University | And 5 more authors.
Expert Opinion on Pharmacotherapy

Introduction: Acute diarrhea remains a major problem in children and is associated with substantial morbidity, mortality and costs. While vaccination against rotavirus could reduce the burden of the disease, the persistent impact of intestinal infections requires effective treatment in adjunct to oral rehydration solutions, to reduce the severity and duration of diarrhea. Several therapeutic options have been proposed for acute diarrhea, but proof of efficacy is available for few of them, including zinc, diosmectite, selected probiotics and racecadotril. However, at present there is no universal drug, and therapeutic efficacy has only been shown for selected drugs in selected settings, such as: outpatients/inpatients, developed/developing countries and viral/bacterial etiology. Areas covered: This narrative review reports the opinions of experts from different countries of the world who have discussed strategies to improve the management of diarrhea. Expert opinion: More data are needed to optimize the management of diarrhea and highlight the research priorities at a global level; such priorities include improved recommendations on oral rehydration solution composition, and the reevaluation of therapeutic options in the light of new trials. Therapeutic strategies need to be assessed in different settings, and pharmacoeconomic analyses based on country-specific data are needed. Transfer to clinical practice should result from the implementation of guidelines tailored at a local level, with an eye on costs. Source

Gotuzzo E.,Hospital Nacional Cayetano Heredia | Markowitz M.,Rockefeller University | Ratanasuwan W.,Siriraj Hospital | Smith G.,Canadian Immunodeficiency Research Collaborative | And 7 more authors.
Journal of Acquired Immune Deficiency Syndromes

Raltegravir as initial HIV therapy was examined in a double-blind study; 160 patients were randomized to raltegravir (400 mg bid after dose-ranging), 38 to efavirenz, both with tenofovir/lamivudine. At week 240, HIV-RNA remained <50 copies per milliliter in 68.8% (raltegravir) versus 63.2% (efavirenz), and CD4 increases were 302 versus 276 cells per microliter, respectively. Early HIV-RNA decline predicted later CD4 increases in both groups. Raltegravir resistance was observed in 3 of 10 raltegravir recipients with virologic failure. Few drug-related adverse events were reported after week 48. Raltegravir had minimal effect on laboratory values, including lipids. Raltegravir with tenofovir/lamivudine showed durable efficacy and good tolerability over 5 years. © 2012 Lippincott Williams & Wilkins. Source

Soto A.,Hospital Nacional Hipolito Unanue | Solari L.,Institute of Tropical Medicine | Diaz J.,Hospital Nacional Cayetano Heredia | Mantilla A.,Hospital Nacional Hipolito Unanue | And 2 more authors.

Background: Clinical suspects of pulmonary tuberculosis in which the sputum smears are negative for acid fast bacilli represent a diagnostic challenge in resource constrained settings. Our objective was to validate an existing clinical-radiographic score that assessed the probability of smear-negative pulmonary tuberculosis (SNPT) in high incidence settings in PER. Methodology/Principal Findings: We included in two referral hospitals in Lima patients with clinical suspicion of pulmonary tuberculosis and two or more negative sputum smears. Using a published but not externally validated score, patients were classified as having low, intermediate or high probability of pulmonary tuberculosis. The reference standard for the diagnosis of tuberculosis was a positive sputum culture in at least one of 2 liquid (MGIT or Middlebrook 7H9) and 1 solid (Ogawa) media. Prevalence of tuberculosis was calculated in each of the three probability groups. 684 patients were included. 184 (27.8%) had a diagnosis of pulmonary tuberculosis. The score did not perform well in patients with a previous history of pulmonary tuberculosis. In patients without, the prevalence of tuberculosis was 5.1%, 31.7% and 72% in the low, intermediate and high probability group respectively. The area under de ROC curve was 0.76 (95% CI 0.72-0.80) and scores ≥6 had a positive LR of 10.9. Conclusions/Significance: In smear negative suspects without previous history of tuberculosis, the clinical-radiographic score can be used as a tool to assess the probability of pulmonary tuberculosis and to guide the decision to initiate or defer treatment or to requesting additional tests. © 2011 Soto et al. Source

Lalezari J.P,Quest Clinical Research | Latiff G.H.,Maxwell Center | Brinson C.,Central Texas Clinical Research | Echevarria J.,Hospital Nacional Cayetano Heredia | And 12 more authors.
The Lancet HIV

Background: BMS-663068 is an oral prodrug of BMS-626529, an attachment inhibitor that binds to HIV-1 gp120, blocking viral attachment to host CD4 cells. AI438011 is an ongoing trial investigating the effi cacy, safety, and dose- response of BMS-663068 in treatment-experienced, HIV-1-infected patients. Herein we present the results of the primary analysis. Methods: AI438011 is a phase 2b, randomised, active-controlled trial, at 53 hospitals and outpatient clinics across ten countries in North and South America, Europe, and Africa. Individuals with an HIV-1 RNA viral load of at least 1000 copies per mL and a BMS-626529 half-maximum inhibitory concentration lower than 100 nmol/L were randomly assigned (1:1:1:1:1) to receive either BMS-663068 at 400 mg twice daily, 800 mg twice daily, 600 mg once daily, or 1200 mg once daily or ritonavir-boosted atazanavir (300 mg of atazanavir and 100 mg of ritonavir once daily), each with 400 mg of raltegravir twice daily and 300 mg of tenofovir disoproxil fumarate once daily as a backbone. The sponsor, participants, and investigators were masked for BMS-663068 dose but not for allocation. Primary endpoints were the proportion of patients with an HIV-1 RNA viral load less than 50 copies per mL (response rate) at week 24 and the frequency of serious adverse events and adverse events leading to discontinuation, up to the week 24 analysis. The primary analyses included all patients who received at least one dose of study drug (modifi ed intention-to-treat population). This study is registered at ClinicalTrials.gov, NCT01384734. Findings: Between July 26, 2011, and July 16, 2012, 581 participants were assessed for eligibility. Of these, 254 patients were randomly assigned to receive either BMS-663068 (n=52 for the 400 mg twice daily group, n=50 for the 800 mg twice daily group, n=51 for the 600 mg once daily group, and n=50 for the 1200 mg once daily group) or ritonavir-boosted atazanavir (n=51). 200 patients received at least one dose of BMS-663068, and 51 patients received at least one dose of ritonavirboosted atazanavir. At week 24, 40 (80%) of 50 patients in the BMS-663068 400 mg twice daily group, 34 (69%) of 49 patients in the 800 mg twice daily group, 39 (76%) of 51 patients in the 600 mg once daily group, and 36 (72%) of 50 patients in the 1200 mg once daily group had an HIV-1 RNA viral load less than 50 copies per mL, compared with 38 (75%) of 51 patients in the ritonavir-boosted atazanavir group. Serious adverse events were noted in 13 (7%) of 200 patients in the BMS-663068 groups and fi ve (10%) of the 51 patients in the ritonavir-boosted atazanavir group. Four (2%) of the 200 patients in the BMS-663068 groups and two (4%) of the 51 patients in the ritonavir-boosted atazanavir group discontinued because of adverse events. No serious adverse events or adverse events leading to discontinuation were BMS-663068-related. Grade 2-4 adverse events related to study drug(s) occurred in 17 (9%) of 200 patients across the BMS-663068 groups and 14 (27%) of 51 patients in the ritonavir-boosted atazanavir group. For the BMS-663068 groups these events were mostly single instances with no dose relation and for the ritonavir-boosted atazanavir group these were mostly gastrointestinal or hepatobiliary disorders associated with hyperbilirubinaemia. Interpretation: In a comparison with ritonavir-boosted atazanavir, effi cacy and safety of BMS-663068 up to the week 24 analysis support continued development of BMS-663068, which is being assessed in a phase 3 trial in heavily treatment-experienced individuals. Source

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