Sundy J.S.,Duke University |
Baraf H.S.B.,Center for Rheumatology and Bone Research |
Yood R.A.,Fallon Clinic |
Edwards N.L.,University of Florida |
And 12 more authors.
JAMA - Journal of the American Medical Association | Year: 2011
Context: Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control Disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need. Objective: To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. Design, Setting, and Patients: Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. Intervention: Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). Main Outcome Measure: Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. Results: In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebotreated patients reached the primary end point (0/23; 95% CI, 0%-15%; P=.001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). Conclusion: Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. Trial Registration clinicaltrials.gov Identifier: NCT00325195. ©2011 American Medical Association. All rights reserved.
Zajdenverg R.,Federal University of Rio de Janeiro |
Badal-Faesen S.,University of Witwatersrand |
Andrade-Villanueva J.,Hospital Civil Of Guadalajara |
Gathe J.,Therapeutic Concepts |
Mingrone H.,Muniz Hospital
Journal of Acquired Immune Deficiency Syndromes | Year: 2010
OBJECTIVES: To compare the safety and antiviral activity of once (QD) or twice (BID) daily lopinavir/ritonavir (LPV/r) in combination with investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in treatment-experienced subjects. METHODS: Subjects failing treatment with HIV-1 RNA > 1000 copies per milliliter received LPV/r tablets 800/200 mg QD (n = 300) or 400/100 mg BID (n = 299) with investigator-chosen nucleoside/nucleotide reverse transcriptase inhibitors. Efficacy was determined by the intent-to-treat time to loss of virologic response (ITT-TLOVR) algorithm. Safety, tolerability, adherence, impact of baseline protease mutations on virologic response, and emergence of resistance on therapy were assessed. RESULTS: Demographics were comparable across groups. By intent-to-treat time to loss of virologic response, 166 QD subjects (55.3%) and 155 BID subjects (51.8%) were responders at week 48 (P = 0.413), with similar mean increases in CD4 T-cell count. QD subjects demonstrated better adherence than BID subjects. The occurrence of treatment-related moderate/severe adverse events was comparable for all events except nausea, which was reported more frequently among BID-treated subjects. Emergence of new protease resistance mutations on treatment was similarly infrequent in both groups. CONCLUSION: LPV/r dosed QD resulted in increased treatment adherence and was as efficacious as BID LPV/r while providing similar safety, tolerability, and limited resistance evolution. © 2010 Lippincott Williams & Wilkins.
PubMed | Bayer AG, Cognigen Corporation, National University of Rosario, Bayer Yakuhin and 2 more.
Type: Clinical Trial, Phase III | Journal: The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases | Year: 2016
Acute bacterial skin and skin structure infections are caused mainly by Gram-positive bacteria which are often treated with intravenous vancomycin, daptomycin, or linezolid, with potential step down to oral linezolid for outpatients. Tedizolid phosphate 200mg once daily treatment for six days demonstrated non-inferior efficacy, with a favourable safety profile, compared with linezolid 600mg twice daily treatment for 10 days in the Phase 3 ESTABLISH-1 and -2 trials. The objective of the current post-hoc analysis of the integrated dataset of ESTABLISH-1 and -2 was to evaluate the efficacy and safety of tedizolid (N=182) vs linezolid (N=171) in patients of Latino origin enrolled into these trials. The baseline demographic characteristics of Latino patients were similar between the two treatment groups. Tedizolid demonstrated comparable efficacy to linezolid at 48-72h in the intent-to-treat population (tedizolid: 80.2% vs linezolid: 81.9%). Sustained clinical success rates were comparable between tedizolid- and linezolid-treated Latino patients at end-of-therapy (tedizolid: 86.8% vs linezolid: 88.9%). Tedizolid phosphate treatment was well tolerated by Latino patients in the safety population with lower abnormal platelet counts at end-of-therapy (tedizolid: 3.4% vs linezolid: 11.3%, p=0.0120) and lower incidence of gastrointestinal adverse events (tedizolid: 16.5% vs linezolid: 23.5%). Population pharmacokinetic analysis suggested that estimated tedizolid exposure measures in Latino patients vs non-Latino patients were similar. These findings demonstrate that tedizolid phosphate 200mg, once daily treatment for six days was efficacious and well tolerated by patients of Latino origin, without warranting dose adjustment.
Baraf H.S.B.,2730 University Blvd West |
Becker M.A.,University of Chicago |
Gutierrez-Urena S.R.,Hospital Civil Of Guadalajara |
Treadwell E.L.,East Carolina University |
And 5 more authors.
Arthritis Research and Therapy | Year: 2013
Introduction: Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.Methods: Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.Results: Among 212 patients randomized in the RCTs, 155 (73%) had ≥1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).Both overall tophus CR and TT-CRs increased with treatment duration in the OLE, reaching 70% (39/56) of patients and 55% (132/238) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE. At that time point, more tophi had resolved in responders (102/145 or 70% of tophi) than nonresponders (30/93; 32%).Conclusions: Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy. Trial registrations: NCT00325195, NCT01356498. © 2013 Baraf et al.; licensee BioMed Central Ltd.
Morfin-Otero R.,Hospital Civil Of Guadalajara |
Clinical Therapeutics | Year: 2012
Background: The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) began in 2004 to monitor global antimicrobial susceptibility to tigecycline and a range of comparator antimicrobials among gram-positive and gram-negative organisms. Objective: The aim of this study was to report changes in MIC for tigecycline and other antimicrobial agents among 10,149 . Acinetobacter baumannii isolates collected globally between 2004 and 2009. Methods: MICs of 10,149 isolates were determined locally using Clinical Laboratory and Standards Institute (CLSI) methodologies. Antimicrobial susceptibility was ascertained according to CLSI interpretive criteria (no interpretive criteria have been approved for tigecycline against . Acinetobacter spp). Results: Increases in resistance were noted for most antimicrobial agents in all regions. Significant (P < 0.05) increases in percentage resistance were reported for all antimicrobial agents globally. The smallest changes in cumulative geometric mean MICs were reported for tigecycline (0.2 mg/L) and cefepime (3.5 mg/L). MIC 90s were at the top of their testing ranges for most agents against both multidrug-resistant (MDR) and non-MDR isolates; only tigecycline showed little change in MIC 90 between MDR (2 mg/L) and non-MDR (1 mg/L) isolates. Resistance was higher among isolates from the intensive care unit (ICU) compared with non-ICU isolates. Conclusion: These findings suggest that resistance is increasing among clinical isolates of . A baumannii globally. Although resistance to tigecycline has been reported in the treatment of infections caused by . A baumannii, it retains in vitro activity against this pathogen. © 2012 Elsevier HS Journals, Inc.
Chung S.,St Josephs Hospital and Medical Center |
Ceja H.,Hospital Civil Of Guadalajara |
Gawlowicz J.,State Hospital |
Avakyan G.,Moscow State University |
And 3 more authors.
Epilepsy Research | Year: 2012
This double-blind, randomised, multicentre, conversion to monotherapy, historical control study (N01280; NCT00419094) evaluated the efficacy, safety and tolerability of levetiracetam extended release (LEV XR) 2000. mg/day once daily for the treatment of patients with partial-onset seizures compared with a historical control. Patients aged 12-75 years with 2-40 partial-onset seizures per 4 weeks, taking 1-2 antiepileptic drugs (AEDs) and receiving a stable dosage for ≥4 weeks prior to screening were randomised in a 3:1 ratio to LEV XR 2000 or 1000. mg/day. The study comprised baseline (8 weeks), LEV XR up-titration (2 weeks), baseline AED tapering (6 weeks), LEV XR monotherapy (10 weeks), and entry into open-label follow-up study or down-titration (1 week). The primary efficacy variable was the cumulative exit rate at Day 112 due to predefined exit criteria compared with the historical control. Of the 171 patients randomised to LEV XR 2000. mg/day and 57 randomised to 1000. mg/day, 141 (82.5%) and 50 (87.7%) completed the study. The cumulative exit rate for patients on LEV XR 2000. mg/day (0.375 [95% CI 0.297, 0.453]) was significantly lower than historical control (0.653). Both LEV doses were well tolerated. The most common adverse events during the treatment period were somnolence (21.9%), headache (19.7%) and convulsion (14.9%). © 2012 Elsevier B.V.
Borbon-Esquer E.M.,Instituto Mexicano Del Seguro Social IMSS |
Villasenor-Sierra A.,Instituto Mexicano Del Seguro Social IMSS |
Martinez-Lopez E.,Hospital Civil Of Guadalajara |
Jauregui-Lomeli J.J.,Autonomous University of Guadalajara |
And 2 more authors.
Scandinavian Journal of Infectious Diseases | Year: 2014
Background: The aim of this study was to determine the prevalence, SCCmec types, presence of the Panton-Valentine leukocidin (PVL) gene, and susceptibility to antibiotics of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from hospitalized children. Methods: From August 2009 to September 2011, 291 S. aureus strains were isolated from normally sterile body sites, of which 190 (65%) were MRSA. One hundred and two of the MRSA strains were genetically evaluated. SCCmec genotypes were identified by M-PCR and the PVL gene (pvl) by end-point PCR. Resistance to erythromycin, rifampicin, clindamycin, and trimethoprim-sulfamethoxazole (SXT) was assessed by Kirby-Bauer disk diffusion method in accordance with the Clinical and Laboratory Standards Institute guidelines of 2012. Results: Of the 102 strains evaluated, 97 (95%) were SCCmec type II, 5 (5%) were SCCmec type IVa, and all (100%) were pvl-negative. Resistance to erythromycin, clindamycin, rifampicin, and SXT was 97%, 95%, 0%, and 0%, respectively. Conclusions: The prevalence of hospital-acquired MRSA was high. SCCmec type II was predominant and the pvl gene appeared not to play any role in the virulence of the MRSA strains from hospitalized children. © 2014 Informa Healthcare.
Gallant J.E.,Southwest Center |
Koenig E.,Institute Dominicano Of Estudios Virologicos |
Andrade-Villanueva J.F.,Hospital Civil Of Guadalajara |
Chetchotisakd P.,Khon Kaen University |
And 9 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2015
Background: Cobicistat (COBI) is a pharmacoenhancer with no antiretroviral activity. Methods: International, randomized double-blind active-controlled trial to evaluate the efficacy and safety of COBI vs ritonavir (RTV) as a pharmacoenhancer of atazanavir in combination with emtricitabine/tenofovir disoproxil fumarate in HIV treatment-naive patients followed through week 144. Results: At Week 144, virologic suppression was achieved in 72% (COBI) and 74% (RTV) of patients. Adverse events leading to study drug discontinuation occurred in 11% of patients in each group. Median changes in serum creatinine (mg/dL) were +0.13 (COBI) and +0.07 (RTV) and were unchanged from week 48. Conclusions: Once-daily COBI is a safe and effective pharmacoenhancer of the protease inhibitor atazanavir. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study
Molina J.-M.,Paris West University Nanterre La Défense |
Molina J.-M.,University Paris Diderot |
Andrade-Villanueva J.,Hospital Civil Of Guadalajara |
Echevarria J.,Hospital Nacional Cayetano Heredia |
And 11 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2010
Background: Once-daily atazanavir/ritonavir demonstrated similar antiviral efficacy to twice-daily lopinavir/ritonavir over 48 weeks, with less gastrointestinal disturbance and a better lipid profile, in treatment-naive patients. Methods: International, multicenter, open-label, 96-week noninferiority randomized trial of atazanavir/ritonavir 300/100 mg once daily vs lopinavir/ritonavir 400/100 mg twice daily, each in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily, in antiretroviral-naive, HIV-1-infected patients. The primary end point was the proportion of patients with HIV RNA <50 copies/mL at 48 weeks. Results through 96 weeks are reported. Results: Of 883 patients enrolled, 440 were randomized to atazanavir/ritonavir and 443 to lopinavir/ritonavir. At week 96, more patients receiving atazanavir/ritonavir achieved HIV RNA <50 copies/mL (74% vs 68%, P < 0.05) in the intent-to-treat analysis. On both regimens, 7% of subjects were virologic failures by 96 weeks. Bilirubin-associated disorders were greater in patients taking atazanavir/ritonavir. Treatment-related gastrointestinal adverse events were greater in patients taking lopinavir/ritonavir. Mean changes from baseline in fasting total cholesterol, non-high-density lipoprotein cholesterol, and triglycerides at week 96 were significantly higher with lopinavir/ritonavir (P < 0.0001). Conclusions: Noninferiority of atazanavir/ritonavir to lopinavir/ritonavir was confirmed at 96 weeks. Atazanavir/ritonavir had a better lipid profile and fewer gastrointestinal adverse events than lopinavir/ritonavir. Copyright © 2010 by Lippincott Williams & Wilkins.
PubMed | Hospital Civil Of Guadalajara, Autonomous University of Nuevo León and University of Guadalajara
Type: Journal Article | Journal: The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases | Year: 2016
Clostridium difficile infections caused by the NAP1/B1/027 strain are more severe, difficult to treat, and frequently associated with relapses.A case-control study was designed to examine a C. difficile infection (CDI) outbreak over a 12-month period in a Mexican hospital. The diagnosis of toxigenic CDI was confirmed by real-time polymerase chain reaction, PCR (Cepheid Xpert C. difficile/Epi).During the study period, 288 adult patients were evaluated and 79 (27.4%) patients had confirmed CDI (PCR positive). C. difficile strain NAP1/B1/027 was identified in 31 (39%) of the patients with confirmed CDI (240 controls were included). Significant risk factors for CDI included any underlying disease (p<0.001), prior hospitalization (p<0.001), and antibiotic (p<0.050) or steroid (p<0.001) use. Laboratory abnormalities included leukocytosis (p<0.001) and low serum albumin levels (p<0.002). Attributable mortality was 5%. Relapses occurred in 10% of patients. Risk factors for C. difficile NAP1/B1/027 strain infections included prior use of quinolones (p<0.03). Risk factors for CDI caused by non-027 strains included chronic cardiac disease (p<0.05), chronic renal disease (p<0.009), and elevated serum creatinine levels (p<0.003). Deaths and relapses were most frequent in the 027 group (10% and 19%, respectively).C. difficile NAP1/BI/027 strain and non-027 strains are established pathogens in our hospital. Accordingly, surveillance of C. difficile infections is now part of our nosocomial prevention program.