RESUMEN
BACKGROUND: Botulism is a rare, life-threatening paralytic illness. Botulism Antitoxin Heptavalent (A,B,C,D,E,F,G)-(Equine) (BAT) manufactured by Emergent BioSolutions Canada Inc is an equine-derived heptavalent botulinum antitoxin product indicated for the treatment of symptomatic botulism following documented or suspected exposure to botulinum neurotoxin serotypes A-G in adults and pediatric patients. BAT product was US-licensed in 2013. METHODS: In the United States, from October 2014 through July 2017, safety and clinical outcomes data were collected under a registry for patients treated with BAT product. RESULTS: Registry patients had a median age of 51 years (range, 32 days to 92 years). Among 162 patients, 7 (4.3%) experienced BAT product-related serious adverse events, including 1 (0.6%) report each of pneumonia, pneumonia aspiration, ventricular tachycardia, upper gastrointestinal hemorrhage, anaphylactic reaction, acute kidney injury, and acute myocardial infarction. Thirty-one (19.1%) patients had 41 BAT product-related adverse events. Six (3.7%) deaths were reported in the registry. All deaths were attributed to the underlying illness and were assessed as unlikely related to BAT product. Among 113 (69.8%) patients with a final diagnosis of botulism, those treated early (≤2 days) spent fewer days in the hospital (5 vs 15.5 days), in the intensive care unit (ICU) (4 vs 12 days), and on mechanical ventilation (6 vs 14.5 days) than those treated late (>2 days), respectively. CONCLUSIONS: BAT product was well tolerated in patients. Treatment with BAT product at ≤2 days of symptom onset was associated with shorter hospital and ICU stays, and shorter duration and need for mechanical ventilation, showing clinical benefit associated with early treatment.
Asunto(s)
Toxinas Botulínicas , Botulismo , Adulto , Animales , Antitoxina Botulínica/uso terapéutico , Botulismo/diagnóstico , Botulismo/tratamiento farmacológico , Canadá , Niño , Caballos , Humanos , Factores de Tiempo , Estados UnidosRESUMEN
OBJECTIVES: To evaluate the efficacy and safety of tigecycline in patients with selected serious infections caused by resistant Gram-negative bacteria, or failures who had received prior antimicrobial therapy or were unable to tolerate other appropriate antimicrobials. Secondary objectives included an evaluation of the microbiological efficacy of tigecycline and in vitro activity of tigecycline for resistant Gram-negative bacteria. METHODS: This open-label, Phase 3, non-comparative, multicentre study assessed the efficacy and safety of intravenous tigecycline (100 mg initially, then 50 mg 12 hourly for 7-28 days) in hospitalized patients with serious infections including complicated intra-abdominal infection; complicated skin and skin structure infection (cSSSI); community-acquired pneumonia (CAP); hospital-acquired pneumonia, including ventilator-associated pneumonia; or bacteraemia, including catheter-related bacteraemia. All patients had infections due to resistant Gram-negative organisms, including extended-spectrum beta-lactamase-producing strains, or had failed on prior therapy or could not receive (allergy or intolerance) one or more agents from three classes of commonly used antibiotics. The primary efficacy endpoint was clinical response in the microbiologically evaluable (ME) population at test of cure (TOC). Safety data included vital signs, laboratory tests and adverse events (AEs). RESULTS: In the ME population at TOC, the clinical cure rate was 72.2% [95% confidence interval (CI): 54.8-85.8], and the microbiological eradication rate was 66.7% (95% CI: 13.7-78.8). The most commonly isolated resistant Gram-negative pathogens were Acinetobacter baumannii (47%), Escherichia coli (25%), Klebsiella pneumoniae (16.7%) and Enterobacter spp. (11.0%); the most commonly diagnosed serious infection was cSSSI (67%). The most common treatment-emergent AEs were nausea (29.5%), diarrhoea (16%) and vomiting (16%), which were mild or moderate in severity. CONCLUSIONS: In this non-comparative study, tigecycline appeared safe and efficacious in patients with difficult-to-treat serious infections caused by resistant Gram-negative organisms.
Asunto(s)
Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Enterobacter/efectos de los fármacos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Klebsiella pneumoniae/efectos de los fármacos , Minociclina/análogos & derivados , Infecciones por Acinetobacter/microbiología , Adulto , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Infecciones por Enterobacteriaceae/microbiología , Femenino , Hospitalización , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Minociclina/administración & dosificación , Minociclina/efectos adversos , Minociclina/farmacología , Minociclina/uso terapéutico , Tigeciclina , Resultado del TratamientoRESUMEN
AIMS: Real-world evidence on the safety profile and costs associated with immune thrombocytopenic purpura (ITP) treatment in adults is lacking. This study quantifies and compares adverse event (AE) crude rates and costs associated with ITP treatments as found in claims data. MATERIALS AND METHODS: A retrospective claims-based analysis was conducted using IMS Pharmetrics Plus database. Included patients were ≥18 years old, with a diagnosis of ITP (2007-2012); an ITP-related claim for anti-D, intravenous immunoglobulin (IVIG), rituximab, romiplostim, or eltrombopag; and 1-year continuous enrollment (3-years for rituximab) during follow-up. AEs and event costs were identified during active treatment, defined from the first claim of each drug to a pre-defined treatment gap or end of study period. Descriptive statistics were reported with Wilcoxon rank-sum significance tests. RESULTS: A total of 2,518 patients were identified (mean age = 50.8 (±16.3 years); 55.8% male). Of all patients, 22.8% experienced any AE. Significantly fewer anti-D patients had any AE (13.8% vs IVIG: 21.1%, rituximab: 29.4%, romiplostim: 28.1%, eltrombopag: 22.4%). Nausea/vomiting and arthralgia/musculoskeletal pain were most common across treatments, and hemolytic events did not differ significantly across treatments. Most costly AEs were urinary tract infection, aseptic meningitis, and fever ($5000+/case); headache, nasal congestion, and hemolytic event were $4,000-5,000/case. Cost per AE did not differ by treatment. LIMITATIONS AND CONCLUSIONS: Although lower than trial-based AE rates, claims for ITP treatment-related AEs are common, with higher numbers for rituximab and lower numbers for anti-D. This disparity suggests a possible differential cost burden overall that future analysis should explore.
Asunto(s)
Factores Inmunológicos/efectos adversos , Factores Inmunológicos/economía , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adulto , Anciano , Benzoatos/efectos adversos , Benzoatos/economía , Femenino , Humanos , Hidrazinas/efectos adversos , Hidrazinas/economía , Inmunoglobulinas Intravenosas/efectos adversos , Inmunoglobulinas Intravenosas/economía , Factores Inmunológicos/uso terapéutico , Revisión de Utilización de Seguros , Masculino , Persona de Mediana Edad , Pirazoles/efectos adversos , Pirazoles/economía , Receptores Fc , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/economía , Estudios Retrospectivos , Globulina Inmune rho(D)/efectos adversos , Globulina Inmune rho(D)/economía , Rituximab/efectos adversos , Rituximab/economía , Trombopoyetina/efectos adversos , Trombopoyetina/economíaRESUMEN
Given increasing resistance, therapeutic options to treat MRSA soft tissue infections should be evaluated. This pooled analysis evaluated data from subjects enrolled in 6 tigecycline clinical trials with documented MRSA complicated skin and skin structure infections or diabetic foot infections (DFIs). Baseline characteristics were compared between subjects with and without molecularly classified community-acquired (CA) MRSA, specifically staphylococcal cassette chromosome mec (SCCmec) IV. Clinical response was compared by CA-MRSA designation and treatment group. A total of 378 subjects with MRSA soft tissue infections were identified, including 79 with DFI. A total of 249 (65.9%) were molecularly classified as CA-MRSA. Clinical response rates for MRSA soft tissue infection were similar between tigecycline and vancomycin (treatment difference, 1.0%; 95% confidence interval: -9.3, 12.0) as well as by infection type, SCCmec, and Panton-Valentine leukocidin (PVL) status. Tigecycline demonstrated comparable efficacy for treatment of MRSA soft tissue infections regardless of infection type, SCCmec, or PVL status.
Asunto(s)
Antibacterianos/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Minociclina/análogos & derivados , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/epidemiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/epidemiología , Adulto , Anciano , Ensayos Clínicos como Asunto , Pie Diabético/tratamiento farmacológico , Pie Diabético/epidemiología , Pie Diabético/microbiología , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Persona de Mediana Edad , Minociclina/uso terapéutico , Tipificación Molecular , Infecciones de los Tejidos Blandos/microbiología , Infecciones Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/epidemiología , Infecciones Cutáneas Estafilocócicas/microbiología , Tigeciclina , Resultado del TratamientoRESUMEN
This report summarizes data from the Study for Monitoring Antimicrobial Resistance Trends 2005-2010 to identify trends in susceptibility from intra-abdominal infections in North America. Escherichia coli and Klebsiella pneumoniae were the most frequently isolated pathogens. Extended-spectrum beta-lactamase rates (%) in 2005/2010 for E. coli and K. pneumoniae were 1.7/7.3 and 3.2/13.1, respectively. Ertapenem, imipenem, amikacin, and cefoxitin showed stable susceptibility.
Asunto(s)
Infecciones por Escherichia coli/microbiología , Escherichia coli/efectos de los fármacos , Infecciones Intraabdominales/microbiología , Resistencia betalactámica , Antibacterianos/farmacología , Canadá , Monitoreo Epidemiológico , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/epidemiología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Humanos , Infecciones Intraabdominales/epidemiología , Pruebas de Sensibilidad Microbiana , Quinolonas/farmacología , Estados Unidos , beta-Lactamas/farmacologíaRESUMEN
BACKGROUND: This randomized, open-label, multi-center trial compared tigecycline (TGC), a broad-spectrum glycylcycline, with ceftriaxone-metronidazole (CTX/MET) for the treatment of complicated intra-abdominal infections (cIAI). METHODS: Eligible subjects were randomized to receive TGC 100 mg followed by 50 mg q 12 h or CTX 2 g qd plus MET 1-2 g daily for 4-14 days. Subjects were stratified by Acute Physiology and Chronic Health Evaluation (APACHE) II score ≤10 or >10 and could not receive oral therapy. The primary endpoint was clinical response in the clinically evaluable (CE) population at the test of cure (TOC) assessment 8-44 days after the last drug dose. RESULTS: Clinical responses in the CE population were 81.8% (162/198) vs. 79.4% (150/189) for TGC and CTX/MET, respectively; a weighted estimate of the difference of 1.6 (95% confidence interval [CI] -6.4, 9.6). In the microbiologically evaluable (ME) population, microbiological eradication rates were 82.4% (98/119) for TGC vs. 79.6% (86/108) for CTX/MET: a difference of 2.7 (95% CI -7.9, 13.3). Common adverse events were nausea (21.6% TGC vs. 21.3% CTX/MET) and vomiting (17.7% TGC vs. 13.2% CTX/MET). Discontinuation rates because of adverse events were 7.8% for TGC and 6.4% for CTX/MET. CONCLUSIONS: Tigecycline was effective in the treatment of cIAI and was non-inferior to CTX/MET for the treatment of cIAI in hospitalized adults. Clinical Trials Identifier: NCT00230971.
Asunto(s)
Antibacterianos/administración & dosificación , Ceftriaxona/administración & dosificación , Infecciones Intraabdominales/tratamiento farmacológico , Metronidazol/uso terapéutico , Minociclina/análogos & derivados , Adulto , Anciano , Antibacterianos/efectos adversos , Ceftriaxona/efectos adversos , Drenaje/efectos adversos , Drenaje/métodos , Quimioterapia Combinada , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Minociclina/administración & dosificación , Minociclina/efectos adversos , Tigeciclina , Resultado del TratamientoRESUMEN
During 2004-2009, 20004 isolates of Staphylococcus aureus were collected from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Of these isolates, 8249 (41.2%) were meticillin-resistant S. aureus (MRSA) and 11755 (58.8%) were meticillin-susceptible S. aureus (MSSA). A total of 4.0%, 5.3% and 3.0% of all S. aureus, MRSA and MSSA isolates, respectively, exhibited vancomycin minimum inhibitory concentrations (MICs) ≥ 2 µg/mL. Whilst no vancomycin-resistant S. aureus were encountered in this study and the majority of these isolates remained susceptible to vancomycin at the Clinical and Laboratory Standards (CLSI) breakpoint of 2 µg/mL, the total number of isolates with MICs creeping up to 2 µg/mL and above increased in all S. aureus from 4.0% in 2004 to 7.7% in 2009 (P < 0.001). Moreover, in MRSA this phenotype increased from 5.6% in 2004 to 11.1% in 2009 (P < 0.001). The increase was also notable for MSSA, which rose from 2.6% in 2004 to 5.6% in 2009 (P < 0.001). Of the 12 antibiotics tested, linezolid, minocycline, tigecycline and vancomycin were the most active agents by susceptibility against all S. aureus, all MRSA and all MSSA isolates. Against MRSA isolates with vancomycin MICs ≥ 2 µg/mL, susceptibility to vancomycin decreased from 100% in 2004 to 95.77% in 2009 (P > 0.05). Similarly, in MSSA isolates susceptibility to vancomycin decreased from 100% in 2004 to 91.07% in 2009 (P > 0.05). These data suggest that although the number of isolates of S. aureus with reduced susceptibility to vancomycin has increased significantly from 2004 to 2009, this upward creep of MICs has not yet impacted significantly on the overall susceptibility of vancomycin against either MRSA or MSSA.