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This article reviews the status quo of new antimicrobial agents that have been approved or undergoing phase Ⅱ/Ⅲ clinical trials in last five years at home and abroad, including new β-lactamase inhibitors and their compound preparations, oxazolidinones, tetracyclines, aminoglycosides, glycopeptides, quinolones, new antifungal agents, cyclic lipopeptides and new anti-mycobacterial agents. The antibacterial activities, main mechanisms of drug resistance, and progress of clinical studies of 27 new drugs were introduced to provide a reference for their clinical application.
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Introducción. Staphylococcus aureus resistente a meticilina (SARM) causa infecciones graves de la piel y los tejidos blandos en los hospitales y, en los últimos años, en la comunidad. El tedizolid es una nueva oxazolidinona cuya potencia in vitro ha demostrado ser mayor que la del linezolid frente a este microorganismo. Objetivo. Conocer la actividad antimicrobiana del tedizolid y de algunos antibióticos de comparación en aislamientos de SARM causante de infecciones de piel y tejidos blandos en hospitales de Colombia. Materiales y métodos. Se hizo un estudio multicéntrico prospectivo y descriptivo a lo largo de doce meses en siete hospitales de tercer nivel de Colombia. Se recolectaron aislamientos de SARM de pacientes adultos con infección de piel y tejidos blandos. Se determinó la concentración inhibitoria mínima (CIM) mediante la técnica de ETEST® (bioMérieux) del tedizolid, el linezolid, la vancomicina, la daptomicina, el trimetoprim-sulfametoxazol y la clindamicina. Resultados. Se obtuvieron aislamientos de SARM de 102 pacientes, de los cuales 56 (54,9 %) eran hombres; el promedio de edad fue de 46,8 años. La infección tuvo origen en la comunidad en 77 casos (75,4 %). El tipo de muestra que predominó fue el absceso (69 pacientes: 67,6 %). Todos los aislamientos fueron sensibles a tedizolid, linezolid, daptomicina, trimetoprim-sulfametoxazol y vancomicina. La actividad in vitro del tedizolid fue mayor que la del linezolid. Los intervalos de la CIM del tedizolid oscilaron entre 0,125 µg/ml y 0,5 µg/ml en tanto que los del linezolid fluctuaron entre 1 µg/m y 2 µg/ml. Conclusiones. Las cepas circulantes de SARM en Colombia presentaron una gran sensibilidad al tedizolid, por lo cual sería una alternativa terapéutica para las infecciones de piel y tejidos blandos en nuestro medio.
Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) causes severe skin and soft tissue infections in hospitals and, more recently, in the community. Tedizolid is a new second-generation oxazolidinone derivative having greater in vitro potency than linezolid against this type of microorganism. Objectives: To evaluate the antimicrobial activity of tedizolid and other comparator antibiotics in MRSA isolates causing skin and soft tissue infections in Colombian hospitals. Materials and methods: We conducted a prospective, multi-center descriptive study in seven tertiary-level hospitals in Colombia along a 12-month period. MRSA isolates were collected from adult patients with skin and soft tissue infections. Tedizolid, linezolid, vancomycin, daptomycin, trimethoprimsulfamethoxazole, and clindamycin minimum inhibitory concentration (MIC) was determined by ETEST® (bioMérieux). Results: MRSA isolates were obtained from 102 patients with an average age of 46.8 years of whom 56 (54.9%) were men. Infection was community-acquired in 77 cases (75.4%). Abscess-related samples predominated (69 patients: 67.6%). All isolates were susceptible to tedizolid, linezolid, daptomycin, trimethoprim-sulfamethoxazole, and vancomycin. Tedizolid had greater in vitro activity than linezolid. Tedizolid MIC intervals ranged from 0.125 µg/mL to 0.5 µg/mL while those of linezolid ranged from 1µg/mL to 2µg/mL. Conclusions: MRSA strains circulating in Colombia are highly susceptible to tedizolid and can be considered a therapeutic alternative for hospitals and/or community-acquired skin and soft tissue infections.
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Methicillin-Resistant Staphylococcus aureus , Colombia , Soft Tissue Infections , OxazolidinonesABSTRACT
Objective To investigate the molecular epidemiology and infectious risk factors of linezolid-resistant Enterococci (LRE) isolates in the First Affiliated Hospital of Chongqing Medical University.Methods Thirteen LRE isolates were collected from 2011 to 2013 and confirmed by broth dilution susceptibility testing.The minimum inhibitory concentrations (MIC) of twelve antimicrobial agents were analyzed using Vitek 2 compact.The molecular epidemiology of LRE isolates was determined by multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and the Diversilab.A casecontrol study was conducted for the analysis of risk factors, and Logistic regression was performed to evaluate the independent risk factors.Results All thirteen LRE isolates showed low-level resistance to linezolid, and most of these isolates were resistant to tetracycline, erythromycin and ciprofloxacin.However, they had high sensitivity to penicillin, ampicillin and tigecycline.Sequence type 480 was predominant in the hospital, and three isolates (isolates 3, 4, and 5) from July to September 2013 were found to have the same ST, PFGE pattern and rep-PCR group, indicating the same resistance clone.Admission to intensive care unit (ICU), peripheral vascular disease, males, hypoalbuminaemia, enema and linezolid therapy were identified as significant risk factors for LRE infections.Among these factors, admission to ICU, enema and linezolid therapy were independent risk factors for the acquisition of LRE.Conclusions Thirteen LRE isolates collected in the hospital showed a multidrug-resistant phenotype, and a small-scale prevalence was detected from 2011 to 2013.Therefore, attention should be paid to monitor the LRE in the hospital to decrease the prevalence of LRE infections.
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Las infecciones provocadas por cepas resistentes se hacen cada día más difíciles de tratar con los antibióticos disponibles. Las causadas por Staphylococcus aureus multirresistente han alcanzado niveles sin precedentes y escasean los medicamentos efectivos para combatirla. La resistencia bacteriana es un problema global que disminuye las opciones terapéuticas en infecciones intra y extrahospitalarias y aumenta las posibilidades de fracaso y los costos de los tratamientos. Esta revisión pretende describir los mecanismos de resistencia de las cepas de Staphylococcus aureus y caracterizar las oxazolidinonas (linezolid), como una alternativa para el tratamiento de infecciones por este germen.
Infections caused by resistant strains are becoming more difficult to treat with available antibiotics. Those caused by multidrug-resistant Staphylococcus aureus have reached unprecedented levels and effective drugs to treat them are often scarce. Bacterial resistance is a global problem that decreases therapeutic options in infections of both, hospitalized and non-hospitalized patients. They increase the chances of failure as well as treatment costs. This review is aimed at describing the resistance mechanisms of Staphylococcus aureus strains and at characterizing oxazolidinones (linezolid), as an alternative for the treatment of infections caused by this germ.
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Objective To study the efficacy of linezolid on gram positive bacterial infection in elderly patients and risk factors associated with thrombocytopenia.Methods A retrospective analysis of 50 elderly patients treated with intravenous linezolid for gram-positive bacterial infection from January 2008 to October 2010 was conducted.Clinical data and bacteriological responses were assessed.Efficacy of linezolid on infection and risk factors associated with thrombocytopenia in elderly patients were analyzed.Results The average duration of treatment was (13±2) d,the efficacy rate was 74 ％ and the bacteriological eradication rate was 69 ％ (18/26).Thrombocytopenia occurred in 24 patients during the treatment,and the average platelet count was significantly reduced compared with pretreatment[(146±87) 109/L vs.(239± 114) 109/L,t=3.888,P=0.000)].Thromhocytopenia was associated with the baseline platelet count and the mean time of linezolid treatment.Based on a Logistic regression analysis,the baseline platelet count ＜ 200 × 109/L was identified as the only significant risk factor for linezolid-associated thrombocytopenia in elderly patients (OR =0.244,95％CI:0.068-0.874,P=0.030).The mean platelet count was decreased significantly after 7 days of treatment,and decreased to the lowest value 1-2 days after the end of therapy.Conclusions Linezolid is effective and safe for the elderly with gram-positive bacterial infection,especially hospital acquired methicillin-resistant staphylococcus aureus infection.Linezolid has little effect on liver and renal function in elderly patients,but it can cause thrombocytopenia,which is associated with baseline platelet count and the mean time of linezolid treatment.Platelet counts should be monitored during treatment and measures should be taken to prevent hemorrhagic tendencies.
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Objective To evaluate the hematologic effects of linezolid in advanced aged patients with hospital onset of infection.Methods The clinical characteristics and complete blood routine examination results of 45 elderly patients aged(92.9±5.2)years treated with linezolid over 600 mg of lowest dose everyday for more than 72 hours were retrospectively analyzed.Results Among the 45patients,20 patients(44.4％)had substantially lower platelet,6 patients(13.3％)lower haemoglobin,1 patient(2.2％)lower absolute neutrophil,and the linezolid treatment in 19 patients were discontinued due to hematological system adverse reactions.The significant drop in platelet occurred at(10.2±3.3)days after treatment.The significant drop in hemoglobin occurred at(9.8±3.0)d after treatment.The lowest count of platelet and hemoglobin took place at(13.1±3.9)d and (10.5±3.5)d after treatment,respectively.The drops in platelet and hemoglobin of some patients took place after cease of treatment.Stepwise logistic regression analysis revealed that treatment duration(OR =1.407,P＜0.05)and creatinine clearance rate(OR=0.732,P＜0.05)were the risk factors for thrombocytopenia.Conclusions The elderly patients using linezolid more likely suffer from adverse reactions of hematological system,particularly thrombocytopeniawhich is significantly more common in patients with renal insufficiency and prolongation of treatment time.The blood routine examination should be monitored closely when elderly patients are treated with linezolid.