RESUMO
BACKGROUND: Gram-positive infections caused by susceptible and resistant strains of Staphylococcus aureus, coagulase-negative staphylococci and enterococci are increasing problems in neonates. Linezolid, a new oxazolidinone, is active against these pathogens and has recently been approved by the Food and Drug Administration for treating Gram-positive infections in pediatric patients. OBJECTIVE: To compare the clinical efficacy and safety of intravenous and oral linezolid with vancomycin (10 to 15 mg/kg every 6 to 24 h) in neonates (age 0 to 90 days). METHODS: Hospitalized infants with known or suspected hospital-acquired pneumonia, complicated skin or skin structure infections, bacteremia or other infections (e.g. pyelonephritis, abdominal abscess) were eligible. Test-of-cure clinical response was evaluated at follow-up. RESULTS: Sixty-three neonates, randomized 2:1 to linezolid (n = 43) or vancomycin (n = 20) were included in the intent-to-treat group. Clinical cure rates at follow-up in the intent-to-treat group were higher, but not significantly different, for linezolid vs. vancomycin (78% vs. 61%; P = 0.196). Corresponding cure rates in clinically evaluable patients were 84% vs. 77% (P = 0.553) for linezolid and vancomycin, respectively. Pathogen eradication rates were as follows in the linezolid and vancomycin groups, respectively: S. aureus (67% vs. 60%; P = 0.850); coagulase-negative staphylococci (88% vs. 100%; P = 0.379); and enterococci (71% vs. 0%; P = 0.168). Results for hematology and chemistry assays were similar between treatment groups. Fewer linezolid-treated neonates had drug-related adverse events than vancomycin-treated neonates (12% vs. 32%; P = 0.058). CONCLUSIONS: Linezolid is well-tolerated and as effective as vancomycin in the treatment of resistant Gram-positive infections in neonates.
Assuntos
Acetamidas/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Oxazolidinonas/farmacologia , Vancomicina/farmacologia , Acetamidas/administração & dosagem , Acetamidas/efeitos adversos , Administração Oral , Antibacterianos/efeitos adversos , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Infusões Intravenosas , Linezolida , Masculino , Oxazolidinonas/administração & dosagem , Oxazolidinonas/efeitos adversos , Resultado do Tratamento , Vancomicina/efeitos adversosRESUMO
BACKGROUND: Nosocomial infections, particularly hospital-acquired pneumonia (HAP) and bacteremia, are an increasing concern in pediatric hospitals and pediatric intensive care units. Gram-positive pathogens are a leading cause of these infections in children. Linezolid is well-tolerated and as effective as vancomycin in the treatment of these infections in adults. OBJECTIVE: To evaluate the clinical effectiveness and safety of iv/oral linezolid and iv vancomycin in children with resistant Gram-positive HAP or bacteremia. METHODS: Hospitalized children <12 years of age were randomized 2:1 to linezolid or vancomycin. Patients received linezolid 10 mg/kg iv every 8 h with the option to change treatment to oral linezolid suspension 10 mg/kg every 8 h or iv vancomycin 10 to 15 mg/kg every 6 to 24 h. Clinical response was evaluated at follow-up. Results from an analysis of patients with HAP or bacteremia are presented. RESULTS: Thirty-nine patients (linezolid, 23; vancomycin, 16) with HAP and 113 patients with bacteremia (linezolid, 81; vancomycin, 32) were included in the intent-to-treat group. Clinical cure rates for clinically evaluable patients with HAP did not differ between treatment groups (linezolid, 90.0% and vancomycin, 100%; P = 0.305). No significant difference was seen in clinical cure rates in the clinically evaluable population between the linezolid and vancomycin groups for patients with catheter-related bacteremia (84.8 and 80.0%, respectively; P = 0.716) or patients with bacteremia of unknown source (79.2 and 69.2%, respectively; P = 0.501). In this subset fewer linezolid-treated patients had drug-related adverse events than did vancomycin-treated patients (19.4% vs. 28.3%; P = 0.230). Similar percentages of patients with laboratory abnormalities, including selected hematologic parameters, were seen in both treatment groups. CONCLUSIONS: Intravenous/oral linezolid was well-tolerated and as effective as vancomycin in treating children with resistant Gram-positive HAP or bacteremia.
Assuntos
Acetamidas/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bacteriemia/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Oxazolidinonas/farmacologia , Pneumonia Bacteriana/tratamento farmacológico , Vancomicina/farmacologia , Acetamidas/administração & dosagem , Acetamidas/efeitos adversos , Administração Oral , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Criança , Pré-Escolar , Resistência Microbiana a Medicamentos , Feminino , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Linezolida , Masculino , Oxazolidinonas/administração & dosagem , Oxazolidinonas/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Gram-positive pathogens are a major cause of complicated skin and skin structure infections (CSSSIs) in children. Many pathogens are developing decreased susceptibility to currently used antibiotics, increasing the need for new therapies. Linezolid is well-tolerated and effective in the treatment of these infections in adults. OBJECTIVE: To evaluate the clinical efficacy and safety of iv/oral linezolid and iv vancomycin in children with Gram-positive CSSSIs. METHODS: Hospitalized children <12 years of age were randomized (2:1 ratio) to receive either linezolid 10 mg/kg iv every 8 h (with the option to change treatment to oral linezolid suspension 10 mg/kg every 8 h) or iv vancomycin 10 to 15 mg/kg every 6 to 24 h (according to age). Clinical response, tolerance and safety were evaluated at follow-up. The results of a subset analysis of patients with CSSSIs are presented here. RESULTS: One hundred twenty intent-to-treat patients (linezolid 80, vancomycin 40) with CSSSI were included in this analysis. Clinical cure rates for clinically evaluable patients with CSSSI did not differ between treatment groups (linezolid, 93.2% vs. vancomycin, 90.0%; P = 0.594). Significantly fewer linezolid-treated patients experienced drug-related adverse events than did vancomycin-treated patients (23% vs. 48%; P = 0.006). The percentages of patients with laboratory abnormalities, including selected hematologic parameters, were generally low and similar between the treatment groups. CONCLUSIONS: Linezolid given iv or orally was well-tolerated and safe. It was as effective as vancomycin in treating children with Gram-positive CSSSIs.
Assuntos
Acetamidas/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Oxazolidinonas/farmacologia , Dermatopatias Bacterianas/tratamento farmacológico , Vancomicina/farmacologia , Acetamidas/administração & dosagem , Acetamidas/efeitos adversos , Administração Oral , Fatores Etários , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Criança , Pré-Escolar , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/patologia , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Linezolida , Masculino , Oxazolidinonas/administração & dosagem , Oxazolidinonas/efeitos adversos , Dermatopatias Bacterianas/microbiologia , Dermatopatias Bacterianas/patologia , Resultado do Tratamento , Vancomicina/administração & dosagem , Vancomicina/efeitos adversosRESUMO
BACKGROUND: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are becoming increasingly prevalent. Linezolid is effective and well-tolerated in the treatment of adults with MRSA infections. OBJECTIVE: To evaluate the clinical efficacy and safety of iv/oral linezolid in children with MRSA infections. METHODS: Data were obtained from two independent clinical trials. In an outpatient trial children (5 to 17 years of age) with uncomplicated skin and skin structure infections (SSSIs) were treated with linezolid or cefadroxil. In an inpatient trial hospitalized children (0 to 11 years of age) with pneumonia, bacteremia or complicated SSSI caused by resistant Gram-positive pathogens were administered iv linezolid with the option to switch to oral suspension (patients >90 days of age) or iv vancomycin. A subset of patients with MRSA infections from the two clinical trials is analyzed herein. RESULTS: In the outpatient trial children with skin infections caused by MRSA were treated with linezolid (15 patients) and cefadroxil (10 patients). In the microbiologically evaluable population, the clinical cure rate was 92.3% in the linezolid group and 85.7% in the cefadroxil group (P = 0.64). The pathogen eradication rate for MRSA was 92.3 and 85.7% in the linezolid and cefadroxil groups, respectively (P = 0.64). There were very few adverse events or drug-related adverse events and no serious adverse events in the outpatient trial. In the inpatient trial 20 children treated with linezolid and 14 treated with vancomycin had infections caused by MRSA. In the microbiologically evaluable population, the clinical cure rate was 94.1% in the linezolid group and 90.0% in the vancomycin group (P = 0.69). Pathogen eradication rates were 88.2 and 90.0% for the linezolid and vancomycin groups, respectively (P = 0.89). Susceptibility patterns of the MRSA isolates showed distinct patterns between the outpatient and inpatient trials. In the inpatient trial fewer patients in the linezolid group had drug-related adverse events than did those in the vancomycin group (20% vs. 43%; P = 0.15). CONCLUSIONS: Intravenous/oral linezolid is effective and well-tolerated in children with MRSA infections.
Assuntos
Acetamidas/farmacologia , Antibacterianos/farmacologia , Cefadroxila/farmacologia , Resistência a Meticilina , Oxazolidinonas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Acetamidas/administração & dosagem , Acetamidas/efeitos adversos , Administração Oral , Adolescente , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Cefadroxila/administração & dosagem , Cefadroxila/efeitos adversos , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Linezolida , Masculino , Pacientes Ambulatoriais , Oxazolidinonas/administração & dosagem , Oxazolidinonas/efeitos adversosRESUMO
BACKGROUND: Linezolid is an effective and well-tolerated antibiotic for the treatment of Gram-positive infections, including hospital and community-acquired pneumonia and complicated and uncomplicated skin and skin structure infections. In adults linezolid treatment for >/=2 weeks has been associated with reversible hematopoietic suppression, primarily thrombocytopenia. OBJECTIVE: To evaluate the occurrence of hematologic effects in children with Gram-positive infections in an open label study of linezolid vs. vancomycin. METHODS: Detailed analyses of hematologic data, including reported hematologic adverse events, complete blood counts, reticulocyte index (RI) and iron studies (serum iron and transferrin saturation), were conducted in both groups at baseline and during and after treatment with the use of an intent-to-treat analysis. RESULTS: Three hundred sixteen patients (median age, 1.65 yr) randomized 2:1 to linezolid (n = 215) or vancomycin (n = 101) were treated. Total treatment durations were similar in the vancomycin group (12.2 +/- 6.4 days; median, 11.0 days) and the linezolid group (11.3 +/- 5.0 days; median, 11.0 days) (P = 0.20). No significant differences were noted in drug-related hematologic events, such as thrombocytopenia (linezolid, 1.9% vs. vancomycin, 0%; P = 0.170), anemia (linezolid, 1.4% vs. vancomycin, 1.0%; P = 0.771) or neutropenia (linezolid, 0% vs. vancomycin, 0%). Hemoglobin values also were similar between treatment groups when assessed by shifts from baseline to lowest recorded value. Frequency of occurrence of any substantially abnormal value for hemoglobin (15.7% vs. 12.4%), platelets (12.9% vs. 13.4%) and neutrophils (5.9% vs. 4.3%) were similar in the linezolid and vancomycin groups. No clinically relevant changes in RI or iron studies were noted between treatment groups, and parallel increases in RI occurred with both linezolid and vancomycin. CONCLUSIONS: No significant differences in hematologic profiles between linezolid and vancomycin occurred in this pediatric population.
Assuntos
Acetamidas/efeitos adversos , Anemia/induzido quimicamente , Antibacterianos/efeitos adversos , Anti-Infecciosos/efeitos adversos , Neutropenia/induzido quimicamente , Oxazolidinonas/efeitos adversos , Trombocitopenia/induzido quimicamente , Vancomicina/efeitos adversos , Acetamidas/administração & dosagem , Acetamidas/farmacologia , Administração Oral , Fatores Etários , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacologia , Criança , Pré-Escolar , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Hemoglobinas/análise , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Linezolida , Masculino , Oxazolidinonas/administração & dosagem , Oxazolidinonas/farmacologia , Vancomicina/administração & dosagem , Vancomicina/farmacologiaRESUMO
BACKGROUND: Linezolid, an oxazolidinone, is effective in the treatment of adults and children with community-acquired and nosocomial pneumonia and uncomplicated and complicated skin and skin structure infections (SSSIs), including infections caused by Gram-positive resistant pathogens. Because of the increasing use of linezolid, it is important to review the common adverse events (AEs) associated with its use in children with the use of data from clinical trials. OBJECTIVE: The safety and tolerability of linezolid in pediatric patients with Gram-positive infections were determined in four pediatric clinical studies. Study I included pediatric patients with community-acquired pneumonia; Study II included otitis media; Study III included SSSIs; and Study IV included complicated SSSIs, nosocomial pneumonia and bacteremia. METHODS: Studies I and II had no comparator arm. Study III was randomized and compared linezolid with cefadroxil. Study IV also was randomized and compared linezolid with vancomycin. Patients <12 years of age received linezolid 10 mg/kg; patients age 12 years and older received 600 mg (intravenous/oral). Dosing frequency (two to three times daily) varied depending on age and clinical diagnosis. The primary safety endpoints were AEs, drug-related AEs, serious AEs and selected laboratory tests. RESULTS: In the 4 studies 958 patients were included in the intent-to-treat analysis. In the linezolid vs. cefadroxil study (Study III), the most common AEs in patients treated with linezolid were diarrhea (7.8%), headache (6.5%) and upper respiratory tract infection (3.7%). In the linezolid vs. vancomycin study (Study IV), the most common AEs in the linezolid group were fever (14.1%), diarrhea (10.8%) and vomiting (9.4%). The most common drug-related AEs for linezolid in all 4 studies were diarrhea, vomiting, loose stools and nausea. None of these common AEs or drug-related AEs occurred more frequently in patients treated with linezolid than in those in the comparator group. CONCLUSIONS: Linezolid was safe and well-tolerated in pediatric patients with community-acquired pneumonia, otitis media, SSSIs and infections caused by Gram-positive resistant pathogens.
Assuntos
Acetamidas/efeitos adversos , Antibacterianos/efeitos adversos , Anti-Infecciosos/efeitos adversos , Cefadroxila/efeitos adversos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Oxazolidinonas/efeitos adversos , Acetamidas/administração & dosagem , Acetamidas/farmacologia , Administração Oral , Adolescente , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacologia , Bacteriemia/tratamento farmacológico , Cefadroxila/administração & dosagem , Cefadroxila/farmacologia , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas , Infecção Hospitalar , Diarreia/induzido quimicamente , Feminino , Cefaleia/induzido quimicamente , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Linezolida , Masculino , Estudos Multicêntricos como Assunto , Otite Média/tratamento farmacológico , Oxazolidinonas/administração & dosagem , Oxazolidinonas/farmacologia , Pneumonia/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias/induzido quimicamente , Dermatopatias Bacterianas/tratamento farmacológicoRESUMO
BACKGROUND: Pediatric infections caused by resistant Gram-positive infections are an increasing concern with limited treatment options. Linezolid, a new oxazolidinone, is active against staphylococci, streptococci and enterococci. OBJECTIVE: To assess clinical efficacy and safety of linezolid vs.vancomycin in antibiotic-resistant Gram-positive infections in children. DESIGN Hospitalized children (birth to 12 years of age) with nosocomial pneumonia, complicated skin/skin structure infections, catheter-related bacteremia, bacteremia of unknown source or other infections caused by Gram-positive bacteria were randomized 2:1 to receive linezolid intravenously followed by oral linezolid or vancomycin and then by an appropriate oral agent. Treatment duration was 10 to 28 days. RESULTS: There were 321 patients enrolled (linezolid 219, vancomycin 102). Clinical cure rates were 79% vs.74% (P = 0.36) and 89% vs.85% (P = 0.31) for linezolid and vancomycin in intent-to-treat and clinically evaluable patients, respectively. Cure rates were similar by age and infection diagnosis. Pathogen eradication rates in microbiologically evaluable patients were high for linezolid and vancomycin, respectively, for methicillin-susceptible S. aureus (95% vs.94%; P = 0.82), methicillin-resistant S. aureus (88% vs.90%; P = 0.89) and methicillin-resistant coagulase-negative staphylococci (85% vs.83%, P = 0.87). In clinically evaluable patients, linezolid-treated patients required significantly fewer days of intravenous therapy compared with vancomycin-treated patients (8.0 +/- 4.8; 10.9 +/- 5.8 days, respectively; P < 0.001). In addition significantly fewer linezolid-treated patients had drug-related adverse events than did vancomycin-treated patients (19% vs.34%, respectively; P = 0.003). Hematologic events were uncommon and similar between treatment groups. CONCLUSIONS: Linezolid was well-tolerated and as effective as vancomycin in treating serious Gram-positive infections in children.
Assuntos
Acetamidas/administração & dosagem , Bacteriemia/tratamento farmacológico , Resistência a Múltiplos Medicamentos , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Oxazolidinonas/administração & dosagem , Vancomicina/administração & dosagem , Bacteriemia/diagnóstico , Criança , Pré-Escolar , Intervalos de Confiança , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Bactérias Gram-Positivas/classificação , Infecções por Bactérias Gram-Positivas/diagnóstico , Humanos , Lactente , Recém-Nascido , América Latina , Linezolida , Masculino , Testes de Sensibilidade Microbiana , Probabilidade , Índice de Gravidade de Doença , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Skin and skin structure infections are common reasons for visits to pediatricians, accounting for up to 18%. Staphylococcus aureus and Streptococcus pyogenes are the most frequently isolated Gram-positive pathogens in uncomplicated skin infections. Increasingly outpatient infections involve antibiotic-resistant Gram-positive pathogens including methicillin-resistant S. aureus. METHODS: This randomized, blinded, comparator-controlled, multinational trial compared the efficacy and safety of linezolid and cefadroxil for treatment of uncomplicated skin/skin structure infections in pediatric patients. Children ages 5 to 11 years were to receive linezolid suspension [10 mg/kg (up to 600 mg)] or cefadroxil suspension [15 mg/kg (up to 500 mg)] every 12 h. Patients ages 12 to 17 years were to receive linezolid tablets (600 mg) or cefadroxil capsules (500 mg) every 12 h. Therapy lasted 10 to 21 consecutive days with a follow-up visit 10 to 21 days posttherapy. RESULTS: Linezolid and cefadroxil were consistently effective treatments across all primary and secondary efficacy assessments. At follow-up cure rates were 88.7% (205 of 231) for linezolid-treated and 86.2% (193 of 224) for cefadroxil-treated intent-to-treat patients; cure rates were 91.0% (201 of 221) for linezolid-treated and 90.0% (189 of 210) for cefadroxil-treated clinically evaluable patients. S. aureus was eradicated in 89.6% (120 of 134) linezolid-treated and 88.8% (111 of 125) cefadroxil-treated microbiologically evaluable patients. Gastrointestinal complaints were the most common adverse events reported, without significant differences between treatment groups, and myelosuppression was not observed in this study. CONCLUSIONS: Linezolid is well-tolerated and as effective as cefadroxil in treating uncomplicated skin infections in pediatric patients. Linezolid effectively treated infections caused by S. aureus, methicillin-resistant S. aureus and S. pyogenes.