101 research outputs found

    Potential role for telavancin in bacteremic infections due to gram-positive pathogens: Focus on staphylococcus aureus

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    Staphylococcus aureus bacteremia (SAB) is one of the most common serious bacterial infections and the most frequent invasive infection due to methicillin-resistant S. aureus (MRSA). Treatment is challenging, particularly for MRSA, because of limited treatment options. Telavancin is a bactericidal lipoglycopeptide antibiotic that is active against a range of clinically relevant gram-positive pathogens including MRSA. In experimental animal models of sepsis telavancin was shown to be more effective than vancomycin. In clinically evaluable patients enrolled in a pilot study of uncomplicated SAB, cure rates were 88% for telavancin and 89% for standard therapy. Among patients with infection due to only gram-positive pathogens enrolled in the 2 phase 3 studies of telavancin for treatment of hospital-acquired pneumonia, cure rates for those with bacteremic S. aureus pneumonia were 41% (9/22, telavancin) and 40% (10/25, vancomycin) with identical mortality rates. These data support further evaluation of telavancin in larger, prospective studies of SAB

    Telavancin for the treatment of serious gram-positive infections, including hospital acquired pneumonia

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    Introduction: Hospital-acquired pneumonia is a common infection, associated with substantial mortality. Despite the increasing prevalence of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), approved treatment options for this pathogen are limited. Areas covered: This article reviews the pharmacokinetics, dosing, preclinical studies and clinical efficacy, and safety of telavancin, with a particular focus on results from trials in nosocomial pneumonia. PubMed and Congress websites were searched for relevant articles published between 2003 and 2010. 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    Clinical utility of telavancin for treatment of hospital-acquired pneumonia: focus on non-ventilator-associated pneumonia

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    Ethan Rubinstein,1 Martin E Stryjewski,2 Steven L Barriere31University of Manitoba, Winnipeg, MB, Canada; 2Department of Medicine, Section of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina; 3Theravance, Inc., South San Francisco, CA, USA Background: Hospital-acquired pneumonia (HAP) is the most common health care-associated infection contributing to death. Studies have indicated that there may be differences in the causative pathogens and outcomes of ventilator-associated pneumonia (VAP) and non-ventilator-associated pneumonia (NV-HAP). However, with limited NV-HAP-specific data available, treatment is generally based on data from studies of VAP. The Phase 3 Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia (ATTAIN) studies were two double-blind randomized controlled trials that demonstrated the non-inferiority of telavancin to vancomycin for treatment of Gram-positive HAP. We conducted a post hoc subgroup analysis of patients enrolled in the ATTAIN studies who had NV-HAP. Methods: Data from the two ATTAIN studies were pooled, and patients with NV-HAP were analyzed. The all-treated (AT) population consisted of all randomized patients who received ≥1 dose of study medication, and the clinically evaluable (CE) population consisted of AT patients who were protocol-adherent or who died on or after study day 3, where death was attributable to the HAP episode under study. The primary endpoint was clinical response (cure, failure, or indeterminate) at the follow-up/test of cure visit, conducted 7–14 days after the end of therapy. Results: A total of 1,076 patients (71.6% of overall ATTAIN AT population) had NV-HAP (533 and 543 patients in the telavancin and vancomycin treatment groups, respectively). Clinical cure rates in the CE population were similar for patients with NV-HAP treated with telavancin and vancomycin (83.1% [201/242] and 84.1% [233/277], respectively). In patients with methicillin-resistant Staphylococcus aureus isolated at baseline, cure rates in the CE population were 74.8% (77/103) for telavancin and 79.3% (96/121) for vancomycin. The incidence of adverse events, serious adverse events, and deaths in patients with NV-HAP was similar whether patients received telavancin or vancomycin. Conclusion: This post hoc subgroup analysis of the ATTAIN studies demonstrated similar cure rates for telavancin and vancomycin for treatment of NV-HAP. Keywords: nosocomial pneumonia, Staphylococcus aureus, methicillin-resistant Staphylococcus aureu

    Self‐collected saliva for SARS‐CoV‐2 detection: A prospective study in the emergency room

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    Current diagnostic standards involve severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in nasopharyngeal swabs (NPS), but saliva is an attractive and noninvasive option for diagnosis. The objectives were to determine the performance of saliva in comparison with NPS for detecting SARS-CoV-2 and to compare the optimized home brew reverse-transcription polymerase chain reaction (RT-PCR) with a commercial RT-PCR. Paired NPS and saliva specimens were prospectively collected and tested by RT-PCR from patients presenting at an emergency room with signs and symptoms compatible with coronavirus disease-2019. A total of 348 samples from 174 patients were tested by RT-PCR assays. Among 174 patients with symptoms, 63 (36%) were SARS-CoV-2 positive in NPS using the optimized home-brew PCR. Of these 63 patients, 61 (98%) were also positive in saliva. An additional positive SARS-CoV-2 saliva was detected in a patient with pneumonia. Kappa Cohen´s coefficient agreement between NPS and saliva was 0.96 (95% confidence interval [CI], 0.90?0.99). Median Ct values in NPS versus saliva were 18.88 (interquartile range [IQR], 15.60?23.58; range, 11.97?38.10) versus 26.10 (IQR, 22.75?30.06; range, 13.78?39.22), respectively (p <.0001). The optimized home-brew RT-PCR demonstrated higher analytical and clinical sensitivity compared with the commercial RT-PCR assay. A high sensitivity (98%) and agreement (kappa 0.96) in saliva samples compared to NPS was demonstrated when using an optimized home-brew PCR even when the viral load in saliva was lower than in NPS. This noninvasive sample is easy to collect, requires less consumable and avoids discomfort to patients. Importantly, self-collection of saliva can diminish exposure to healthcare personnel.Fil: Echavarría, Marcela Silvia. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reyes, Noelia Soledad. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Rodriguez, Pamela Elizabeth. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ypas, Martin. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Ricarte, Joaquina Carmen. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodriguez, María P.. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Pérez, Matías Gastón. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Seoane, Alejandro. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Martinez, Alfredo. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Videla, Cristina Mónica. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Stryjewski, Martin E.. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Carballal, Guadalupe. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Staphylococcus Aureus Bacteremia Among Patients with Health Care-associated Fever

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    Background: Although Staphylococcus aureus bacteremia is a common, serious infection, accurately identifying febrile patients with this diagnosis at the time of initial evaluation is difficult. The purpose of this investigation was to define clinical characteristics present at the time of the initial recognition of fever that were associated with the presence of any bloodstream infection and, in particular, with S. aureus bacteremia. Methods: All patients ≥18 years of age with a new episode of health care-associated fever (temperature ≥38°C) and at least one blood culture drawn were eligible for enrollment into this prospective multicenter cohort study. Multivariable analyses were conducted and internally validated scoring systems were developed to categorize the risk of bacteremia. Results: Of 1015 patients enrolled, 181 patients (17.8percent) had clinically significant bacteremia, including 77 patients (7.6percent) with S. aureus bacteremia. Clinical characteristics associated with S. aureus bacteremia were the presence of a hemodialysis graft or shunt (odds ratio [OR] 3.22; 95percent confidence interval [CI], 1.85-5.61), chills (OR 2.38; 95percent CI, 1.43-3.98), and a history of S. aureus infection (OR 2.68; 95percent CI, 1.38-5.20). Peripheral vascular catheters were inversely associated with S. aureus bacteremia (OR 0.42; 95percent CI, 0.26-0.69). Clinical characteristics associated with any bloodstream infection were central venous access, chills, history of S. aureus infection, and hemodialysis access. Conclusions: Among patients with health care-associated fever, the presence of easily recognizable clinical characteristics at the time of obtaining the initial blood cultures can help to identify patients at increased risk for any bloodstream infection, in particular for S. aureus bacteremia. © 2009 Elsevier Inc. All rights reserved.Arvanitidou M, 2005, J HOSP INFECT, V61, P219, DOI 10.1016-j.jhin.2005.03.006; Banerjee SN, 1991, AM J MED S3B, V91, P86; Bates DW, 1997, J INFECT DIS, V176, P1538; BATES DW, 1990, ANN INTERN MED, V113, P495; CLARKE DE, 1991, CHEST, V100, P213, DOI 10.1378-chest.100.1.213; Edmond MB, 1999, CLIN INFECT DIS, V29, P239, DOI 10.1086-520192; Fowler VG, 2003, ARCH INTERN MED, V163, P2066, DOI 10.1001-archinte.163.17.2066; Fowler VG, 2005, CLIN INFECT DIS, V40, P695; Friedman ND, 2002, ANN INTERN MED, V137, P791; Groeneveld ABJ, 2001, CLIN DIAGN LAB IMMUN, V8, P1189, DOI 10.1128-CDLI.8.6.1189-1195.2001; Huang SS, 2003, CLIN INFECT DIS, V36, P281, DOI 10.1086-345955; Jaimes F, 2004, CLIN INFECT DIS, V38, P357, DOI 10.1086-380967; JULANDER I, 1985, SCAND J INFECT DIS, V17, P37, DOI 10.3109-00365548509070418; Kollef MH, 1999, CHEST, V115, P462, DOI 10.1378-chest.115.2.462; LATOS DL, 1977, J DIALYSIS, V1, P399; LEIBOVICI L, 1993, J INTERN MED, V234, P83; Lentino JR, 2000, INFECTION, V28, P355, DOI 10.1007-s150100070005; Lodise TP, 2003, CLIN INFECT DIS, V36, P1418, DOI 10.1086-375057; Lowy FD, 1998, NEW ENGL J MED, V339, P520, DOI 10.1056-NEJM199808203390806; MYLOTTE JM, 1995, INFECT CONT HOSP EP, V16, P203; Mylotte JM, 2000, EUR J CLIN MICROBIOL, V19, P157, DOI 10.1007-s100960050453; MYLOTTE JM, 1987, REV INFECT DIS, V9, P891; Paul M, 2006, CLIN INFECT DIS, V42, P1274, DOI 10.1086-503034; POSES RM, 1991, MED DECIS MAKING, V11, P159, DOI 10.1177-0272989X9101100303; Pujol M, 1996, AM J MED, V100, P509, DOI 10.1016-S0002-9343(96)00014-9; Steyerberg EW, 2001, J CLIN EPIDEMIOL, V54, P774, DOI 10.1016-S0895-4356(01)00341-9; Stryjewski ME, 2007, CLIN INFECT DIS, V44, P190, DOI 10.1086-510386; Tokuda Yasuharu, 2005, Am J Med, V118, P1417; Tokuda Y, 2005, QJM-INT J MED, V98, P813, DOI 10.1093-qjmed-hci120; Van Dissel JT, 1998, LANCET, V352, P374, DOI 10.1016-S0140-6736(05)60475-8; von Eiff C, 2001, NEW ENGL J MED, V344, P11, DOI 10.1056-NEJM200101043440102; Weems JJ, 2006, ANTIMICROB AGENTS CH, V50, P2751, DOI 10.1128-AAC.00096-06; Yehezkelli Y, 1996, J GEN INTERN MED, V11, P98, DOI 10.1007-BF02599585119

    Pharmacotherapy Update: Daptomycin in the Management of Complicated Skin and Soft-tissue Infections

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    Because of the dramatic increase in severe infections caused methicillin-resistant Staphylococcus aureus (MRSA), including skin and skin structure infections (SSSI), and reports of vancomycin failures in the treatment of these infections, agents with better activity against MRSA are clearly needed. Daptomycin, the first cyclic lipopeptide, exerts its concentration dependent bactericidal activity against S. aureus through a calcium dependent formation of channels leading to disruption of the bacterial cell membrane potential. Daptomycin is 90% protein bound, has a half-life of 8–9 h, is eliminated through renal excretion, and has a good penetration into inflammatory skin blisters. This compound was shown to be non-inferior to the comparator in two double-blind randomized phase III studies including patients with complicated SSSI, using a dose of 4 mg/kg/day. In these studies, cure rates in the clinical and microbiology evaluable populations were 83.4% and 84.2% (95% CI, -4 to 5.6), and 84.7% and 85.9% (95% CI, -3.8 to 6.3) for daptomycin and comparator, respectively. Daptomycin also showed efficacy in prospective studies in patients with infective cellulitis or erysipelas, necrotizing soft tissue infection, and infected diabetic foot ulcers. Even though the standard dose of 4 mg/kg/day is considered appropriate for most SSSI, higher doses (e.g. 6 to 10 mg/kg/day) are currently suggested for patients with sepsis, necrotizing infection, prior glycopeptide failure, infections caused by vancomycin intermediate S. aureus (VISA) strains, renal insufficiency, burns, and in intravenous drug users. Overall, daptomycin is considered a well tolerated antibiotic. In clinical trials, drug discontinuation rate has been similar in patients receiving daptomycin compared with those treated with the comparators; however, muscular damage associated with increased serum creatine phopshokinase levels occurs in about 3% and 7% of the patients treated with 4 and 6 mg/kg/day, respectively. This reversible muscle toxicity appears to correlate with the daptomycin trough concentration and time of exposure. </jats:p

    “Breakthrough cases” de COVID-19 y respuesta humoral en personal de salud vacunado con dos do-sis de Sputnik V

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    INTRODUCCIÓN: “Breakthrough cases” se denomina a los casos de COVID-19 luego de 15 días post-segunda dosis de vacuna para SARS-CoV-2. No hay datos respecto al porcentaje de estos casos con la vacuna Sputnik V (SV). El objetivo de este trabajo fue estudiar la respuesta humoral en personal de salud (PS) vacunado con SV y evaluar casos de COVID-19. RESULTADOS: Se realizó un estudio prospectivo, observacional, de cohorte, con aprobación del comité de ética en el Hospital Universitario CEMIC, Marzo-Agosto, 2021. Se enrolaron 126 PS con dos dosis de SV, 67% eran mujeres, mediana de edad: 40 años (rango 21-84), 77% sin previo COVID-19. De los 126, 98% fueron positivo para IgG anti-Spike (COVIDAR) y 11 (9%) desarrollaron COVID-19 leve (casos) post 2da dosis. El 72.7% eran mujeres, mediana de edad 35 años (IQR: 34-64), 45% tenían alguna comorbilidad pero ninguno era inmunocomprometido. La mediana de tiempo entre la 2da dosis y el diagnóstico de COVID-19 fue de 73 días (IQR=32,5-89,5). Fueron IgG positivos el 89% de los casos y 100% de los controles (mediana IgG: 484,56 UI/ml [IQR: 254,9-882,6] y 414 UI/ml [IQR: 99,8-1421.2], respectivamente). Se estudiaron anticuerpos neutra-lizantes a 9 casos positivos y 9 controles apareados por edad y lapso post vacuna. Todos tuvieron anticuerpos neutralizantes contra la cepa salvaje de referencia, siendo 16 la mediana del títuloen ambos grupos (rangos: 4-64 y 4-128, en casos y controles, res-pectivamente). Se secuenciaron muestras de 9/11 casos (6 fueronvariante Gamma y 3 variante Lambda). CONCLUSIONES: Los breakthrough cases por COVID-19 en PS vacunados con SV fueron mayores a los reportados con otras vacunas. Sin embargo, el período de estudio coincidió con la segunda ola de contagios en nuestro país. Todos los casos fueron leves. La mayoría de los casos había desarrollado IgG previo a la infección y todos poseían anticuerpos neutralizantes contra la cepa salvaje. Las variantes de SARS-CoV-2 detectadas fueron Gamma y Lambda.Fil: Echavarría, Marcela Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Reyes, Noelia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Rodriguez, Pamela Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Diaz Balocchi, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Ricarte, Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Ceballos, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Stryjewski, Martin. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; ArgentinaFil: Carballal, Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaXIII Congreso Argentino de VirologíaArgentinaAsociación Argentina de MicrobiologíaSociedad Argentina de Virologí

    Prospective Multicenter Study of Community-Associated Skin and Skin Structure Infections due to Methicillin-Resistant Staphylococcus aureus in Buenos Aires, Argentina

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    Background. Community-associated methicillin-resistant Staphylococcus aureus(CAMRSA) is now the most common cause of skin and skin structure infections (SSSI) in several world regions. In Argentina prospective, multicenter clinical studies have only been conducted in pediatric populations. Objective. Primary: describe the prevalence, clinical and demographic characteristics of adult patients with community acquired SSSI due to MRSA; secondary: molecular evaluation of CA-MRSA strains. Patients with MRSA were compared to those without MRSA. Material and Methods. Prospective, observational, multicenter, epidemiologic study, with molecular analysis, conducted at 19 sites in Argentina (18 in Buenos Aires)between March 2010 and October 2011. Patients were included if they were ≥ 14 years, were diagnosed with SSSI, a culture was obtained, and there had no significant healthcare contact identified. A logistic regression model was used to identify factors associated with CA-MRSA. Pulse field types, SCCmec, and PVL status were also determined. Results. A total of 311 patients were included. CA-MRSA was isolated in 70% (218/311) of patients. Clinical variables independently associated with CA-MRSA were: presence of purulent lesion (OR 3.29; 95%CI 1.67, 6.49) and age <50 years (OR 2.39; 95%CI 1.22, 4.70). The vast majority of CA-MRSA strains causing SSSI carried PVL genes (95%) and were SCCmec type IV. The sequence type CA-MRSA ST30 spa t019 was the predominant clone. Conclusions. CA-MRSA is now the most common cause of SSSI in our adult patients without healthcare contact. ST30, SCCmec IV, PVL+, spa t019 is the predominant clone in Buenos Aires, Argentina.Fil: Lopez Furst, Maria Jose. Sanatorio Municipal Dr. Julio Méndez, Ciudad Autónoma de Buenos Aires; Argentina;Fil: de Vedia, Lautaro. Gobierno de la Ciudad de Buenos Aires. Htal.de Infecciosas F.j. Muñiz; Argentina;Fil: Fernandez, Silvina. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica. Cat.de Microbiologia; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;Fil: Gardella, Noella Mariel. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica. Cat.de Microbiologia; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;Fil: Ganaha, Cristina. Pcia. de Buenos Aires. Hospital Vicente López y Planes, Gral. Rodríguez; Argentina;Fil: Prieto, Sergio. Provincia de Buenos Aires. Hospital Nuestra Señora de Luján; Argentina;Fil: Carbone, Edith. Hospital Aeronautico Central; Argentina;Fil: Lista, Nicolás. Gobierno de la Ciudad de Buenos Aires. Htal.de Infecciosas F.j. Muñiz; Argentina;Fil: Rotryng, Flavio. Universidad Abierta Interamericana; Argentina;Fil: Morera, Graciana I.. Hospital Dr. Jose Cullen; Argentina;Fil: Mollerach, Marta Eugenia. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica. Cat.de Microbiologia; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;Fil: Stryjewski, Martin E.. Centro de Educaciones Medicas E Investig.Clinica "Norberto Quirno"; Argentina
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