Baraf H.S.B.,2730 University Blvd West |
Becker M.A.,University of Chicago |
Gutierrez-Urena S.R.,Hospital Civil de 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. Source
Morfin-Otero R.,Hospital Civil de 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. Source
Villasenor-Sierra A.,Instituto Mexicano del Seguro Social |
Katahira E.,Veterans Affairs Medical Center |
Jaramillo-Valdivia A.N.,Instituto Mexicano del Seguro Social |
Barajas-Garcia M.D.L.A.,Instituto Mexicano del Seguro Social |
And 8 more authors.
International Journal of Infectious Diseases | Year: 2012
Objective: To compare the prevalence, phenotypes, and genes responsible for erythromycin resistance among Streptococcus pyogenes isolates from Mexico and the USA. Methods: Eighty-nine invasive and 378 non-invasive isolates from Mexico, plus 148 invasive, 21 non-invasive, and five unclassified isolates from the USA were studied. Susceptibilities to penicillin, erythromycin, clindamycin, ceftriaxone, and vancomycin were evaluated according to Clinical and Laboratory Standards Institute (CLSI) standards. Phenotypes of erythromycin resistance were identified by triple disk test, and screening for mefA, ermTR, and ermB genes was carried out by PCR. Results: All isolates were susceptible to penicillin, ceftriaxone, and vancomycin. Erythromycin resistance was found in 4.9% of Mexican strains and 5.2% of USA strains. Phenotypes in Mexican strains were 95% M and 5% cMLS; in strains from the USA, phenotypes were 33.3% iMLS, 33.3% iMLS-D, and 33.3% M. Erythromycin resistance genes in strains from Mexico were mefA (95%) and ermB (5%); USA strains harbored ermTR (56%), mefA (33%), and none (11%). In Mexico, all erythromycin-resistant strains were non-invasive, whereas 89% of strains from the USA were invasive. Conclusions: Erythromycin resistance continues to exist at low levels in both Mexico and the USA, although the genetic mechanisms responsible differ between the two nations. These genetic differences may be related to the invasive character of the S. pyogenes isolated. © 2011 International Society for Infectious Diseases. Source
Chung S.,St Josephs Hospital And Medical Center |
Ceja H.,Hospital Civil de 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. Source
Borbon-Esquer E.M.,Instituto Mexicano del Seguro Social IMSS |
Villasenor-Sierra A.,Instituto Mexicano del Seguro Social IMSS |
Martinez-Lopez E.,Hospital Civil de 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. Source