Évolution expérimentale aux limites de l'extinction : Le cas de Pseudomonas fluorescens soumise au stress. Les stress environnementaux : ces perturbations d'origine biotiques ou abiotiques des conditions de vie qui ont un impact sur les populations par l'altération des capacités de reproduction et/ou de survie des organismes, peuvent parfois mener une espèce à l'extinction si celle-ci n'est pas en mesure de s'adapter suffisamment rapidement. Avec l'augmentation de l'impact des activités humaines, le taux d'extinction des espèces est aujourd'hui estimé être de plusieurs ordres de grandeur au dessus du taux d'extinction basal. Il est donc important de comprendre les facteurs écologiques et évolutifs, à l'échelle de l'espèce comme de la communauté, qui déterminent la survie ou l'extinction d'une espèce soumise à un stress sévère.Au cours de cette thèse, nous utiliserons les outils de l'évolution expérimentale avec la bactérie Pseudomonas fluorescens soumise à un stress antibiotique, ainsi que des outils théoriques, pour étudier les facteurs déterminants les conditions d'un sauvetage évolutif : événement d'évolution rapide d'une population en situation d'effondrement démographique sous l'effet d'un stress létal. Nous étudierons aussi le rôle d'un stress plus modérés : une carence en ressource, sur deux aspects de la structure des communautés liés à la stabilité de ces dernières face aux perturbations environnementales : La topologie d'un réseau trophique bactérie-phage, ainsi que la distribution des tailles de populations, décrite par la loi de Taylor, pour des populations bactériennes en mono-culture ou en compétition sur un gradient de ressource. Nos travaux ont permis de mieux comprendre le sauvetage évolutif, en montrant notamment le rôle déterminant de la taille des populations et de leur diversité génétique initiale dans la capacité d'adaptation à un stress létal. Mais aussi en proposant une meilleure description des dynamiques de populations typiques de cette situation. Nous avons aussi montré la capacité d'une limitation des ressources à altérer la structure des réseaux trophiques et ainsi leur stabilité face aux perturbations. / Experimental Evolution at the Edge of Extinction, The Case of Pseudomonas fluorescens in Stressful Environments.Environmental stresses : the biotic or abiotic perturbations of life conditions which have an impact on populations through impaired organism's ability to survive and/or reproduce, can sometimes result in species extinction if rapid evolutionary adaptation doesn't occur. With the increasing impact of human activities, the rate of species extinction is now estimated to be several orders of magnitudes above the background rate. It is therefore crucial to understand the ecological and evolutionary factors, at species and community levels, which determine the survival or extinction of species exposed to severe stresses. All along this thesis, we will use experimental evolution tools with the bacterium Pseudomonas fluorescens exposed to antibiotic stress, as well as theoretical tools, to study the factors driving evolutionary rescue : the rapid evolutionary adaptation occurring in populations experiencing demographic collapse under a lethal stress. Then we will study how a moderate stress (low resource availability) drives different aspects of communities structure related to their stability against environmental perturbations : The topology of a bacteria-bacteriophage trophic network, and the distribution of population sizes along a resource gradient, described by Taylor's law, for bacterial populations either in mono-culture or in competition. Our results led to a better understanding of evolutionary rescues. In particular, we show the crucial role of initial population size and genetic diversity in the ability to evolve adaptation to an initially lethal stress. And we refined the description of populations dynamics in such cases. We show also how resource limitation can disturb trophic network structure, resulting in a lower stability against environmental perturbations.

Šio darbo tikslas – nustatyti skirtingų laktobacilų antagonistines savybes ir atsparumą antibiotikams. Darbo tikslo įgyvendinimui iškelti sekantys uždaviniai: Išgryninti jogurtuose esančias laktobacilas – Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus. Ištirti laktobacilų Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus, Lactobacillus plantarum ir Lactobacillus fermentum antagonistines savybes Salmonella enteritidis, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli ir Proteus mirabilis bakterijoms. Ištirti laktobacilų Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus, Lactobacillus plantarum ir Lactobacillus fermentum atsparumą antibiotikams. Palyginti Lactobacillus plantarum ir Lactobacillus fermentum antagonistines savybes prieš liofilizaciją ir po liofilizacijos praėjus 10 metų. Tirtos pienarūgščių mikroorganizmų Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus, Lactobacillus plantarum ir Lactobacillus fermentum antagonistinis aktyvumas Salmonella enteritidis, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli ir Proteus mirabilis bakterijų atžvilgiu, bei atsparumas antibiotikams. Atlikus tyrimus nustatyta, kad Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus, Lactobacillus plantarum ir Lactobacillus fermentum kultūros pasižymi antagonistiniu aktyvumu Salmonella enteritidis, Staphylococcus aureus... [toliau žr. visą tekstą] / The aim of this work is to identify antagonistic characteristics of different lactobacillus as well as notify the resistance to antibiotics. In order for this work to succeed, the following tasks were adressed: Purification the following lactobacillus in yogurts – Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus. Examination the antagonistic characteristic of Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus, Lactobacillus plantarum and Lactobacillus fermentum for bacteria Salmonella enteritidis, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Proteus mirabilis. Examination of resistance to antibiotics of Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus, Lactobacillus plantarum and Lactobacillus fermentum. Comparison in antagonistic characteristics of Lactobacillus plantarum and Lactobacillus fermentum before lyophilization and after 10 years of lyophilization. The characteristics of the following lactic microorganisms have been examined: antagonistic activeness of Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus rhamnosus, Lactobacillus plantarum and Lactobacillus fermentum in terms of resistance to antibiotics in Salmonella enteritidis, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Proteus mirabilis bacteria. Performed examinations revealed that: Lactobacillus acidophillus, Lactobacillus bulgaricus, Lactobacillus rhamnosus... [to full text]

Made available in DSpace on 2014-06-11T19:31:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-12-16Bitstream added on 2014-06-13T20:01:47Z : No. of bitstreams: 1 masson_gcih_dr_jabo.pdf: 739097 bytes, checksum: 2fef2cb4d684c81bde182928eafa28f3 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / S. aureus é responsabilizado por diversos problemas clínicos em suinocultura e em humanos. Estudos epidemiológicos comprovam o potencial deste microrganismo em adquirir resistência a antibióticos. Atualmente estirpes resistentes a meticilina (MRSA), responsabilizados por casos de infecções nosocomiais, são as mais estudadas uma vez que o MRSA encontra-se disseminado em ambientes extra-hospitalares e frenquentemente tem sido isolado de vários animais domésticos inclusive suínos. O objetivo desde trabalho foi determinar a presença de S. aureus em granjas de suínos, identificar a ocorrência dos genes mecA, icaA e icaD e o perfil de resistência a antimicrobianos. Ao todo foram colhidas 458 amostras de cinco granjas e dois frigoríficos. As amostras foram semeadas em ágar Braid - Parker e ágar sangue seguido de provas bioquímicas. As amostras sugestivas, foram submetidas a PCR para confirmação de espécie, detecção do gene coa, mecA para avaliar a resistência a meticilina além dos genes de virulência icaA e icaD que expressam capacidade para formação de biofilmes. Na sequência, realizou-se o antibiograma para a avaliação de 11 antimicrobianos. Ao todo foram identificados 81 (79%) S. aureus isolados de todas as granjas e frigoríficos incluindo, três amostras isoladas de funcionários das granjas. Nenhuma amostra foi positiva para o gene mecA. Em relação aos genes icaA e icaD, observou predomínio do gene icaD e que 41% das amostras foram positivas para os dois genes. O antibiograma demonstrou grande resistência às penicilinas e tetraciclinas, além de grande quantidade de S aureus multirresistentes / Staphylococcus aureus are involved in a wide range of clinical problems to swine industry as son in humans. Epidemiological researchs prove his potential to acquire resistantence to antibiotics. Nowadays, methicillin-resistant S. aureus (MRSA) are responsabilized for nosocomial infections and many studies are done because MRSA are spread to extra hospitalar enrivonment and frequentely isolated from domestic animals including pigs. The aim of this study was to determine the presence o S. aureus at swine farms and identify the mecA, icaA and icaD genes and the resistant proflife to antibiotics. Overal, 458 swabs were taked from five pigeris and two slautherhouses. All the samples were placed on Braid – Parker and blood agar follow by biochemical analyses. The suspect colonies were submitted to PCR to confirm the S. aureus species, by the detection of the coa gene, mecA to avaible meticillin-resistant as son to the virulence gens icaA and icaD that can determine slime production. Antibiogram were done to evaluate the response to 11 antibiotics. All pigeris and slautherhouse were positive and 81 (79%) samples were S. aureus positive including three isolates from pigs employeers. The mecA gene was not detected. The icaD gene was most frequent and 41% were positive to both genes. The antibiogram show a lot of samples penicillin and tetraciclin resistant. Most of the samples were multirestant

Orientador: Luiz Fernando de Oliveira e Silva Carvalho / Banca: Everlon Cid Rigobelo / Banca: Aníbal de Sant'Anna Moretti / Banca: Luiz Carlos Marques / Banca: Mario Roberto Hatayde / Resumo: S. aureus é responsabilizado por diversos problemas clínicos em suinocultura e em humanos. Estudos epidemiológicos comprovam o potencial deste microrganismo em adquirir resistência a antibióticos. Atualmente estirpes resistentes a meticilina (MRSA), responsabilizados por casos de infecções nosocomiais, são as mais estudadas uma vez que o MRSA encontra-se disseminado em ambientes extra-hospitalares e frenquentemente tem sido isolado de vários animais domésticos inclusive suínos. O objetivo desde trabalho foi determinar a presença de S. aureus em granjas de suínos, identificar a ocorrência dos genes mecA, icaA e icaD e o perfil de resistência a antimicrobianos. Ao todo foram colhidas 458 amostras de cinco granjas e dois frigoríficos. As amostras foram semeadas em ágar Braid - Parker e ágar sangue seguido de provas bioquímicas. As amostras sugestivas, foram submetidas a PCR para confirmação de espécie, detecção do gene coa, mecA para avaliar a resistência a meticilina além dos genes de virulência icaA e icaD que expressam capacidade para formação de biofilmes. Na sequência, realizou-se o antibiograma para a avaliação de 11 antimicrobianos. Ao todo foram identificados 81 (79%) S. aureus isolados de todas as granjas e frigoríficos incluindo, três amostras isoladas de funcionários das granjas. Nenhuma amostra foi positiva para o gene mecA. Em relação aos genes icaA e icaD, observou predomínio do gene icaD e que 41% das amostras foram positivas para os dois genes. O antibiograma demonstrou grande resistência às penicilinas e tetraciclinas, além de grande quantidade de S aureus multirresistentes / Abstract: Staphylococcus aureus are involved in a wide range of clinical problems to swine industry as son in humans. Epidemiological researchs prove his potential to acquire resistantence to antibiotics. Nowadays, methicillin-resistant S. aureus (MRSA) are responsabilized for nosocomial infections and many studies are done because MRSA are spread to extra hospitalar enrivonment and frequentely isolated from domestic animals including pigs. The aim of this study was to determine the presence o S. aureus at swine farms and identify the mecA, icaA and icaD genes and the resistant proflife to antibiotics. Overal, 458 swabs were taked from five pigeris and two slautherhouses. All the samples were placed on Braid - Parker and blood agar follow by biochemical analyses. The suspect colonies were submitted to PCR to confirm the S. aureus species, by the detection of the coa gene, mecA to avaible meticillin-resistant as son to the virulence gens icaA and icaD that can determine slime production. Antibiogram were done to evaluate the response to 11 antibiotics. All pigeris and slautherhouse were positive and 81 (79%) samples were S. aureus positive including three isolates from pigs employeers. The mecA gene was not detected. The icaD gene was most frequent and 41% were positive to both genes. The antibiogram show a lot of samples penicillin and tetraciclin resistant. Most of the samples were multirestant / Doutor

La propagation de bactéries à Gram négatif multirésistantes aux antibiotiques représente un problème de santé publique majeur urgent à résoudre car le risque d’un retour à l’ère pré-antibiotique est réel. Parmi les modes de résistance existant, la production de métallo-B-lactamases (MBLs) responsables de l’inactivation des B-lactamines, la famille d’antibiotiques la plus utilisée, représente un challenge thérapeutique.Les travaux décrits dans ce manuscrit concernent la synthèse, la caractérisation et l’évaluation biologique de composés construits autour d’un cœur 2,4-dihydro-3H-1,2,4-triazole-3-thione substitués en deux positions. En se basant sur des études de criblage in silico et des études cristallographiques ayant permis d’identifier ce noyau comme un bon candidat dans le développement d’inhibiteurs de MBLs, la synthèse de différentes séries d’analogues a été entreprise afin d’identifier de nouveaux inhibiteurs pouvant potentiellement atteindre les tests cliniques.Dans un premier temps, une série de composés 4-amino-1,2,4-triazole-3-thione substitués en position 5 a été préparée en suivant des voies de synthèse classiques. Différentes séries ont ensuite été développées en introduisant une diversité structurale et fonctionnelle en position 4. Ces composés ont ensuite été testés sur des enzymes représentatives des 3 sous-classes de MBLs et les plus intéressants ont été évalués sur bactéries résistantes recombinantes.Afin de réaliser une évaluation rapide des produits synthétisés au sein du laboratoire, une méthode de criblage à moyen débit en plaque 96 puits sur cinq MBLs représentatives a été mise au point et validée grâce à l’appui de nos collaborateurs spécialistes des MBLs. / The spread of multiresistant Gram negative bacteria is a growing threat to public health and the risk of return to the pre-antibiotic era is real. Among existing resistance modes, the production of metallo-B-lactamases (MBLs) responsible of the inactivation of B-lactams, the most used family of antibiotics, represents a therapeutical challenge.This manuscript describes the synthesis, characterization and biological evaluation of compounds built on a 2,4-dihydro-3H-1,2,4-triazole-3-thione scaffold substituted on two positions. Based on previous in silico screening and crystallographic studies, which identified this structure as a good candidate for MBLs inhibition, several series have been developed to found new inhibitors that could potentially be amenable to clinical development.First, 1,2,4-triazole-3-thione compounds substituted at position 5 have been prepared following classical pathways. Then, several series have been developed where the structural and functional diversity was introduced at position 4. Compounds have been tested on representative MBLs of the three sub-classes and the most interesting ones on recombinant resistant bacteria.To perform a rapid screening of compounds in the laboratory, a method of medium throughput screening inhibition tests on five MBLs performed in 96-wells plate has also been developed and validated during this study with the help of our collaborators specialists of MBLs

The main topic of this diploma thesis is ARE (resistance) proteins from the ABC-F family of the second class of ABC proteins. ARE proteins confer resistance to antibiotics that bind to a large ribosomal subunit and therefore inhibit proteosynthesis. One of the ARE proteins is the Lmr (C) protein, which is part of the linkomycin biosynthesis cluster of Streptomyces lincolnensis, and according to new results, Lmr (C) does not have to be just resistant protein but may have also regulatory function. We decided to study Sco0636, the closest homologue to Lmr (C) in Streptomyces coelicolor, which is a model organism in the study of secondary metabolism. Thanks to the production of color pigments, it is possible to monitor the effect of ARE proteins on secondary metabolism directly on the plates. I prepared the deletion mutant and the strain with constitutive expression of sco0636, and observed the effect on the phenotype. I followed the production of a blue asset and set a minimum inhibitory concentration to selected antibiotics, which bind to the ribosome. I have found that Sco0636 gives high resistance to tiamulin and so it has been named TiaA. The deletion of gene sco0636 accelerated production of actinorodine, and constitutive expression of this gene slowed down production. Keywords: ABC proteins,...

The main topic of this diploma thesis is ARE (resistance) proteins from the ABC-F family of the second class of ABC proteins. ARE proteins confer resistance to antibiotics that bind to a large ribosomal subunit and therefore inhibit proteosynthesis. One of the ARE proteins is the Lmr (C) protein, which is part of the linkomycin biosynthesis cluster of Streptomyces lincolnensis, and according to new results, Lmr (C) does not have to be just resistant protein but may have also regulatory function. We decided to study Sco0636, the closest homologue to Lmr (C) in Streptomyces coelicolor, which is a model organism in the study of secondary metabolism. Thanks to the production of color pigments, it is possible to monitor the effect of ARE proteins on secondary metabolism directly on the plates. I prepared the deletion mutant and the strain with constitutive expression of sco0636, and observed the effect on the phenotype. I followed the production of a blue asset and set a minimum inhibitory concentration to selected antibiotics, which bind to the ribosome. I have found that Sco0636 gives high resistance to tiamulin and so it has been named TiaA. The deletion of gene sco0636 accelerated production of actinorodine, and constitutive expression of this gene slowed down production. Keywords: ABC proteins,...

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Submitted by admin tede (tede@pucgoias.edu.br) on 2017-03-07T13:16:26Z No. of bitstreams: 1 CHRISTIANO PATRÍCIO PÓVOA.pdf: 970820 bytes, checksum: 80130d52367b620a227e0d91d34abb17 (MD5) / Made available in DSpace on 2017-03-07T13:16:26Z (GMT). No. of bitstreams: 1 CHRISTIANO PATRÍCIO PÓVOA.pdf: 970820 bytes, checksum: 80130d52367b620a227e0d91d34abb17 (MD5) Previous issue date: 2016-09-08 / The urinary tract infections (UTI) are one of the most common types of infection, both community as nosocomial, the ITU is caused by bacteria are more common in men and in. The study was descriti-vo retrospective and prospective type, from 2011 to 2016 were analyzed from 3388 antibiograms of ITU of Community origin in the elderly. The age of patients ranged from 60 to 100 years, with a mean age of 73 years, and 77.28% occurred in women and 22.72% in men. The microranalyzed organisms were Escherichia coli (75.65%) with 80.72% by Women's res and 19.28% in men, followed by Klebsiella pneumoniae (16.59%) with 66.73% infection 33.27% in women and in men. Proteus spp. It was respon-sible for 5.70% cases, with 70.47% occurred in women and 29.53% in ho-mens. Enterobacter spp. It was the causative organism of UTI in 2.07%; 45.71% women and 54.29% in men. The highest prevalence of resistance to E. coli were to sulfonamide (40.54%), Ciprofloxacin (35.04%), Nalidixic acid (34.92%), Cephalosporins 1st Generation (31,45%), Norfloxacin (24 , 50%), Penicillin (23.68%) and 3rd generation cephalosporins (12.29%), an increase in the evolution of resistance to cephalosporins 2nd generation (p = 0.0074). For K. pneumoniae, the major resistance prevalence occurs to ram for Norfloxacin (16.73%), cephalosporins 3rd Generation (20.46%), Aci-of Nalidixic (26.87%), Cephalosporins 1st Generation (29 , 00%), Penicillin (33.99%), sulfonamide (35.05%), Nitrofurantoin (37.90%), Gemifloxacin (46.09%) and ofloxacin (46.09%) with increased resistance evolution Carbapenems for (p = 0.0271) and Cephalosporins 1st generation (p = 0.0496). Proteus spp., The major resistance prevalences were to Gati-floxacina (12.95%), Norfloxacin (12.95%), penicillins (14.51%), cephalosporins on the 2nd Generation (21.24%) , sulfonamide (36.27%), Cephalosporins 1st Ge-feed (38.86%), Gemifloxacin (46.11%), ofloxacin (46.11%), nitrofurantoin (76.68%), Nalidixic acid (81 , 87%) and levofloxacin (81.87%). For Enterobac-have spp., The major resistance prevalences were compared to Cefalospo-mandarins of 4th Generation (15.71%), Gatifloxacin (21.43%), Norfloxacin (21.43%), Ciprofloxacin (28.57 %), Moxifloxacin (28.57%), Nitrofurantoin (31.43%), 3rd generation cephalosporins (32.86%), sulfonamide (38.57%), Gemifloxacin (42.86%), ofloxacin (42, 86%) 1st generation cephalosporins (44.29%), nalidixic acid (77.14%), Levofloxacin (77.14%) and Penicillins (97.14%) with au-ment in the evolution of resistance to cephalosporins 2nd Generation (p = 0.0057). For empiric treatment of complicated UTI due to the found resistance to the antimicrobials of choice, the aminoglycosides, Carbapenems and monobactam can be used until they are met, the causative agents of infection and susceptibility to tested Antimicro-bianos and should be replaced by re-duced antimicrobial spectrum, but with high power. / As infecções no trato urinário (ITU) correspondem a um dos tipos mais comuns de infecção, tanto comunitária quanto nosocomial, sendo as ITU causadas por bactérias são mais comuns, tanto em homens quanto em. O estudo foi descritivo tipo retrospectivo e prospectivo, no período de 2011 a 2016. Foram analisados 3388 antibiogramas de ITU de origem comunitária em idosos. A faixa etária dos pacientes variou de 60 até 100 anos, com média de idade de 73 anos, sendo que 77,28% ocorreram em mulheres e 22,72% em homens. Os microrganismos analisados foram Escherichia coli (75,65%), com 80,72% em mulheres e 19,28% em homens, seguido por Klebsiella pneumoniae, (16,59%), com 66,73% infecções em mulheres e 33,27% em homens. Proteus spp. foi responsável por 5,70% casos, com 70,47% ocorreram em mulheres e 29,53% em homens. Enterobacter spp. foi o organismo causador de ITU em 2,07%; 45,71% em mulheres e 54,29% em homens. As maiores prevalências de resistência para E. coli foram para Sulfonamida (40,54%), Ciprofloxacina (35,04%), Ácido Nalidíxico (34,92%), Cefalosporinas de 1ª Geração (31,45%), Norfloxacina (24,50%), Penicilinas (23,68%) e Cefalosporinas de 3ª Geração (12,29%), com aumento na evolução da resistência para Cefalosporinas de 2ª Geração (p = 0,0074). Para K. pneumoniae, as maiores prevalências de resistência ocorreram para Norfloxacina (16,73%), Cefalosporinas de 3ª Geração (20,46%), Ácido Nalidíxico (26,87%), Cefalosporinas de 1ª Geração (29,00%), Penicilinas (33,99%), Sulfonamida (35,05%), Nitrofurantoína (37,90%), Gemifloxacina (46,09%) e Ofloxacina (46,09%) com aumento na evolução da resistência para Carbapenêmicos (p = 0,0271) e Cefalosporinas de 1ª Geração (p = 0,0496). Para Proteus spp., as maiores prevalências de resistência foram para Gatifloxacina (12,95%), Norfloxacina (12,95%), Penicilinas (14,51%), Cefalosporinas de 2ª Geração (21,24%), Sulfonamida (36,27%), Cefalosporinas da 1ª Geração (38,86%), Gemifloxacina (46,11%), Ofloxacina (46,11%), Nitrofurantoína (76,68%), Ácido Nalidíxico (81,87%) e Levofloxacina (81,87%). Para Enterobacter spp., as maiores prevalências de resistência foram em relação à Cefalosporinas de 4ª Geração (15,71%), Gatifloxacina (21,43%), Norfloxacina (21,43%), Ciprofloxacina (28,57%), Moxifloxacina (28,57%), Nitrofurantoína (31,43%), Cefalosporinas de 3ª Geração (32,86%), Sulfonamida (38,57%), Gemifloxacina (42,86%), Ofloxacina (42,86%), Cefalosporinas de 1ª Geração (44,29%), Ácido Nalidíxico (77,14%), Levofloxacina (77,14%) e Penicilinas (97,14%), com aumento na evolução da resistência para Cefalosporinas de 2ª Geração (p = 0,0057). Para o tratamento empírico das ITU complicadas, devido à resistência encontrada para os antimicrobianos de primeira escolha, podem ser usados os Aminoglicosídeos, Carbapenêmicos e Monobactama, até que sejam conhecidos os agentes causadores das infecções e a susceptibilidade aos antimicrobianos testados, devendo ser substituídos por antimicrobiano de espectro reduzido, porém com potência elevada.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal