RESUMO
Seasonal variation of baseline diagnosis (or clinical suspect) of stage I-III colorectal cancer patients has been repeatedly reported as an independent variable influencing overall survival. However, data are conflicting and no information is available about such a rhythm in advanced stage patients. To test whether a circannual rhythm of efficacy outcomes can be detected in this setting, we collected data about response rate (RR), progression-free survival (PFS), and overall survival (OS) to first-line chemotherapy of 1610 newly diagnosed metastatic patients treated at four independent centers. Responses to first-line chemotherapy were available for 1495 patients. A strong circannual rhythm in RR was evident, with the higher proportion of responding patients in the subgroup diagnosed in January (acrophase). At the time of data cutoff, 1322 patients progressed and 986 died, with median PFS and OS of 11 and 25.6 months, respectively. A circannual rhythmicity of the proportion of patients progressing at 6 months and surviving at 1 year was demonstrated, with acrophases located both in winter (February and January, respectively), similar to what reported for RR. Several interpretations about the genesis of this cyclic variation could be claimed: the rhythm in sunlight exposure and, as a consequence, of vitamin D serum levels and folate degradation, the variability in toxic effect intensity of chemotherapy, and the rhythm in the biological behavior of tumor cells. This observation is worth of further investigation both in preclinical and in clinical settings in order to better elucidate the underlying mechanisms.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ritmo Circadiano/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Camptotecina/administração & dosagem , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Resultado do TratamentoAssuntos
Alcaligenes faecalis/isolamento & purificação , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Infecções por Bactérias Gram-Negativas/epidemiologia , Argentina/epidemiologia , Técnicas de Tipagem Bacteriana , Criança , Pré-Escolar , Análise por Conglomerados , Infecção Hospitalar/microbiologia , Impressões Digitais de DNA , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Eletroforese em Gel de Campo Pulsado , Infecções por Bactérias Gram-Negativas/microbiologia , Hospitais , Humanos , Lactente , Recém-Nascido , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Enterobacter spp. es un patógeno intrahospitalario que presenta múltiples mecanismos de resistencia a los antibióticos b-lactámicos. Se caracterizaron fenotípica y genotípicamente las diferentes b-lactamasas presentes en 27 aislamientos consecutivos e ininterrumpidos de Enterobacter spp. (25 Enterobacter cloacae y 2 Enterobacter aerogenes). También se evaluó la habilidad de diferentes métodos fenotípicos para detectar b-lactamasas de espectro extendido (BLEE) en estos microorganismos. En 15/27 aislamientos (63%) se observó resistencia a las cefalosporinas de tercera generación. En 12 de los aislamientos resistentes se detectó un alto nivel de producción de cefalosporinasa cromosómica, siendo 6 de ellos también productores de PER-2. Dicha resistencia en los 3 aislamientos restantes se debió exclusivamente a la presencia de BLEE, PER-2 en 2 de ellos y CTX-M-2 en un caso. Sólo CTX-M-2 se detectó con todas las cefalosporinas probadas en los ensayos de sinergia, utilizando el método de difusión, mientras que cefepima mejoró la detección de PER-2 en 7/8 aislamientos productores de esta BLEE, 4/8 utilizando la prueba de doble disco y 7/8 comparando discos de cefepima con y sin el agregado de ácido clavulánico. El método de dilución empleado solo detectó 1/9 BLEE al comparar las cefalosporinas con y sin el agregado de inhibidor.
Enterobacter spp. are becoming increasingly frequent nosocomial pathogens with multiple resistance mechanism to b-lactam antibiotics. We carried out the phenotypic and genotypic characterization of beta-lactamases in 27 Enterobacter spp. (25 Enterobacter cloacae y 2 Enterobacter aerogenes), as well as the ability of different extended spectrum b-lactamase (ESBL) screening methods. Resistance to third generation cephalosporins was observed in 15/27 (63%) isolates. Twelve resistant isolates produced high level chromosomal encoded AmpC b-lactamase; 6 of them were also producers of PER-2. Resistance to third generation cephalosporins in the remaining 3 isolates was due to the presence of ESBLs, PER-2 in 2 cases, and CTX-M-2 in the other. Only CTX-M-2 production was detected with all tested cephalosporins using difusion synergy tests, while cefepime improved ESBLs detection in 7/8 PER-2 producers, 4/8 in the inhibitor aproximation test and 7/8 with double disk test using cefepime containing disk with and without clavulanic acid. Dilution method, including cephalosporins with and without the inhibitor detected 1/9 ESBLs producers.
Assuntos
Humanos , Resistência às Cefalosporinas , Cefalosporinas/farmacologia , Enterobacter aerogenes/efeitos dos fármacos , Enterobacter cloacae/efeitos dos fármacos , Resistência às Cefalosporinas/genética , Cefalosporinas/classificação , Farmacorresistência Bacteriana Múltipla/genética , Enterobacter aerogenes/enzimologia , Enterobacter aerogenes/genética , Enterobacter cloacae/enzimologia , Enterobacter cloacae/genética , Infecções por Enterobacteriaceae/microbiologia , Genótipo , Ponto Isoelétrico , Testes de Sensibilidade Microbiana , Fenótipo , beta-Lactamases/genéticaRESUMO
Enterobacter spp. are becoming increasingly frequent nosocomial pathogens with multiple resistance mechanism to beta-lactam antibiotics. We carried out the phenotypic and genotypic characterization of beta-lactamases in 27 Enterobacter spp. (25 Enterobacter cloacae y 2 Enterobacter aerogenes), as well as the ability of different extended spectrum-lactamase (ESBL) screening methods. Resistance to third generation cephalosporins was observed in 15/27 (63%) isolates. Twelve resistant isolates produced high level chromosomal encoded AmpC beta-lactamase; 6 of them were also producers of PER-2. Resistance to third generation cephalosporins in the remaining 3 isolates was due to the presence of ESBLs, PER-2 in 2 cases, and CTX-M-2 in the other. Only CTX-M-2 production was detected with all tested cephalosporins using difusion synergy tests, while cefepime improved ESBLs detection in 7/8 PER-2 producers, 4/8 in the inhibitor approximation test and 7/8 with double disk test using cefepime containing disk with and without clavulanic acid. Dilution method, including cephalosporins with and without the inhibitor detected 1/9 ESBLs producers.
Assuntos
Resistência às Cefalosporinas , Cefalosporinas/farmacologia , Enterobacter aerogenes/efeitos dos fármacos , Enterobacter cloacae/efeitos dos fármacos , Resistência às Cefalosporinas/genética , Cefalosporinas/classificação , Farmacorresistência Bacteriana Múltipla/genética , Enterobacter aerogenes/enzimologia , Enterobacter aerogenes/genética , Enterobacter cloacae/enzimologia , Enterobacter cloacae/genética , Infecções por Enterobacteriaceae/microbiologia , Genótipo , Humanos , Ponto Isoelétrico , Testes de Sensibilidade Microbiana , Fenótipo , beta-Lactamases/genéticaRESUMO
Enterobacter spp. are becoming increasingly frequent nosocomial pathogens with multiple resistance mechanism to beta-lactam antibiotics. We carried out the phenotypic and genotypic characterization of beta-lactamases in 27 Enterobacter spp. (25 Enterobacter cloacae y 2 Enterobacter aerogenes), as well as the ability of different extended spectrum-lactamase (ESBL) screening methods. Resistance to third generation cephalosporins was observed in 15/27 (63
) isolates. Twelve resistant isolates produced high level chromosomal encoded AmpC beta-lactamase; 6 of them were also producers of PER-2. Resistance to third generation cephalosporins in the remaining 3 isolates was due to the presence of ESBLs, PER-2 in 2 cases, and CTX-M-2 in the other. Only CTX-M-2 production was detected with all tested cephalosporins using difusion synergy tests, while cefepime improved ESBLs detection in 7/8 PER-2 producers, 4/8 in the inhibitor approximation test and 7/8 with double disk test using cefepime containing disk with and without clavulanic acid. Dilution method, including cephalosporins with and without the inhibitor detected 1/9 ESBLs producers.
