Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
J. bras. econ. saúde (Impr.) ; 14(Suplemento 2)20220800.
Article in Portuguese | LILACS, ECOS | ID: biblio-1412727

ABSTRACT

Objetivo: Comparar custos da terapia endovenosa exclusiva com linezolida com os custos da terapia iniciada por via endovenosa com transição para via oral após 72 horas, como estratégia de intervenção em programas de gestão de antimicrobianos. Métodos: Avaliação econômica de custo-minimização comparando custos diretos da terapia endovenosa exclusiva com linezolida com a terapia endovenosa seguida de transição para via oral em cenário simulado, sob a perspectiva do Sistema Único de Saúde (SUS), com árvore de decisão como modelo para tomada de decisão. Resultados: A alternativa englobando a transição de via mostrou-se a mais econômica em todos os cenários analisados. Para 28 dias de tratamento com linezolida, houve redução de 22% nos custos, considerando o paciente internado. Ao considerar alta após o sexto dia de tratamento, a redução de custos variou de 26%, com financiamento pelo SUS do restante do tratamento, a 84%, com financiamento do tratamento pós-alta pelo paciente. Conclusão: Conclui-se que a transição de via de linezolida é uma importante estratégia nos programas de gerenciamento de antimicrobianos, capaz de gerar economia significativa para a instituição. As avaliações econômicas de custo-minimização, nesse contexto, são uma importante ferramenta para demonstrar o aspecto econômico com potencial para sensibilizar gestores e tomadores de decisão.


Objective: To compare the direct costs of linezolid intravenous therapy with the costs of intravenous therapy switching to oral therapy after 72 hours as an intervention strategy in antimicrobial stewardship programs. Methods: Economic evaluation cost-minimization comparing direct costs of exclusive linezolid intravenous therapy with intravenous therapy for 72 hours and after switching to oral therapy in a simulated scenario, from the perspective of the National Health Service, with a decision tree as a decision modeling. Results: The alternative encompassing the therapy transition proved to be the most economical in all analyzed scenarios. For 28 days of treatment with linezolid, there was a 22% reduction in costs, considering the hospitalized patient. When considering discharge after the sixth day of treatment, the cost reduction ranged from 26%, with funding from the National Health Service for the rest of the treatment, to 84%, with funding for the post-discharge treatment by the patient. Conclusion: It was concluded that the linezolid therapy transition is an important strategy in antimicrobial management programs, capable of generating significant savings for the institution. In this context, economic cost-minimization assessments are an important tool to demonstrate the economic aspect with the potential to raise awareness among managers and decision-makers.


Subject(s)
Drug Administration Routes , Economics, Pharmaceutical , Costs and Cost Analysis , Linezolid , Antimicrobial Stewardship
2.
J. bras. econ. saúde (Impr.) ; 14(Suplemento 2)20220800.
Article in English | ECOS, LILACS | ID: biblio-1412751

ABSTRACT

Objective: This study aimed to compare the occurrence of acute kidney injury (AKI) in pediatric patients who used vancomycin (VAN) or linezolid (LNZ) to treat Gram-positive coccus (GPC) infections and to assess which treatment (VAN or LNZ) is the most cost-effective considering a pediatric hospital perspective. Methods: A retrospective cohort was performed to evaluate the occurrence of nephrotoxicity in pediatric patients without previous AKI, with GPC infections that used LNZ, or VAN monitored by serum VAN levels. Initially, descriptive analysis and Fisher and chisquare test were performed for this comparison. Then, a cost-effectiveness analysis was conducted through a decision tree model. The outcomes of interest were the rate of AKI related to the drug and the rate of admission to the intensive care unit (ICU) and cure. Results: In patients without previous acute kidney injury (AKI), 20% developed nephrotoxicity associated with VAN versus 9.6% in the LNZ group (p = 0.241). As there was no difference in nephrotoxicity between VAN andlinezolid (LNZ), vancomycin (VAN) monitored by serum VAN levels can optimize and rationalize the treatment. The nephrotoxicity risk criterion should not guide the prescription for LNZ. Furthermore, the average global cost of treatment with VAN was approximately R$ 43,000, while for LNZ, it was R$ 71,000. Conclusion: VAN was considered dominant (lower cost and greater effectiveness) over LNZ for treating patients with GPC infection.


Objetivo: Este estudo objetivou comparar a ocorrência de lesão renal aguda (LRA) em pacientes pediátricos que usaram vancomicina (VAN) ou linezolida (LNZ) para tratar infecções por cocos Gram-positivos (CGP) e avaliar qual tratamento (VAN ou LNZ) é o mais custo-efetivo considerando a perspectiva de um hospital pediátrico. Métodos: Foi realizada uma coorte retrospectiva para avaliar a ocorrência de nefrotoxicidade em pacientes pediátricos sem LRA prévia, com infecções por CGP que utilizaram LNZ ou VAN, combinada com vancocinemia. Para essa comparação, inicialmente foram realizados análise descritiva e testes de Fisher e qui-quadrado. Em seguida, foi realizada uma análise de custo-efetividade por meio de um modelo de árvore de decisão. Os desfechos de interesse foram a taxa de LRA relacionada ao medicamento e a taxa de internação em unidade de terapia intensiva e cura. Resultados: Nos pacientes sem LRA prévia, 20% deles desenvolveram nefrotoxicidade associada à VAN versus 9,6% no grupo LNZ (p = 0,241). Como não houve diferença na nefrotoxicidade entre VAN e LNZ, a VAN combinada com a vancocinemia pode otimizar e racionalizar o tratamento, e a prescrição de LNZ não deve ser guiada pelo critério de risco de nefrotoxicidade. Além disso, o custo médio global do tratamento com VAN foi de aproximadamente R$ 43.000, enquanto para LNZ foi de R$ 71.000. Conclusão: Assim, a VAN foi considerada dominante (menor custo e maior eficácia) sobre a LNZ para o tratamento de pacientes com infecção por CGP.


Subject(s)
Pediatrics , Vancomycin , Cost-Effectiveness Analysis , Renal Insufficiency , Linezolid
3.
Arch. argent. pediatr ; 115(5): 470-475, oct. 2017. ilus, tab
Article in English, Spanish | LILACS, BINACIS | ID: biblio-887373

ABSTRACT

Introducción. La linezolida puede causar efectos adversos, como trombocitopenia, que, según lo observado, se relacionan con la administración de linezolida durante más de 2 semanas. Se ha realizado una cantidad limitada de estudios sobre la seguridad y el momento de aparición de los efectos adversos relacionados con la linezolida en los niños. El objetivo de este estudio fue evaluar la incidencia de los efectos adversos asociados con la linezolida, especialmente en relación con el momento de su aparición. Población y métodos. Se incluyeron a todos los niños (< 18 años de edad) que recibieron tratamiento con linezolida durante > 3 días. Se evaluaron los efectos adversos atribuidos a la linezolida y el momento de aparición de los efectos secundarios. Resultados. En total, se incluyeron 179 niños. La mediana de edad de los pacientes fue 4 años (entre 6 días y 17 años). Durante el tratamiento con linezolida, 36 (20,1%) pacientes tuvieron efectos adversos. El efecto adverso más frecuente fue la trombocitopenia, detectada en 26 (14,5%) pacientes. Los demás efectos adversos fueron: elevación de las enzimas hepáticas en 4 pacientes, leucopenia y anemia en 2 pacientes, disfunción renal en 1 y reacciones cutáneas graves en 3 pacientes. Los efectos adversos se detectaron dentro de una mediana de 7,5 días de tratamiento (intervalo: de 4 a 18 días). Entre los 36 pacientes, 26 (72,2%) presentaron un efecto adverso en los primeros 10 días de tratamiento. Conclusiones. Se detectaron efectos adversos transitorios en el 20,1% de los pacientes durante el tratamiento con linezolida. Estos efectos adversos podrían detectarse antes de los 10 días de tratamiento. La linezolida debe recetarse de manera segura a los niños siempre que se vigilen los efectos adversos, en especial el recuento de trombocitos y el nivel de enzimas hepáticas.


Introduction: Linezolid may cause adverse effects such as thrombocytopenia, which were found to be dependent on receiving linezolid for longer than 2 weeks. There are limited studies concerning the safety and timing of linezolid-related adverse effects in children. Objective of this study was to evaluate the incidence of adverse effects associated with linezolid, with especially focusing on the time of occurrence. Population and Methods: All children (<18 years of age) who received >3 days of linezolid therapy were included in this study. Adverse effects attributed to linezolid and time of occurrence of side effects was evaluated. Results: A total of 179 children were enrolled to the study. The patients' median age was 4 years (6 days to 17 years). During linezolid treatment, 36 (20.1%) patients experienced adverse effects. The most common adverse effect was thrombocytopenia that was detected in 26 patients (14.5%). Other adverse effects were as following; elevated liver enzymes in 4 patients, leucopenia and anemia in 2 patients, renal function impairment in one patient, and serious skin reactions in 3 patients. Adverse effects were detected within median 7.5 days of therapy (ranging from 4 to 18 days). Among 36 patients, 26 (72.2%) patients had adverse effect on the first 10 days of therapy. Conclusions: Transient adverse effects were detected in 20.1% of the patients during linezolid therapy. These adverse effects may be detected earlier than ten days of treatment. Linezolid should be prescribed safely in children with monitoring adverse effects especially platelet count and level of liver enzymes.


Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Linezolid/adverse effects , Anti-Bacterial Agents/adverse effects , Time Factors , Retrospective Studies
4.
Iatreia ; 30(1): 5-20, ene. 2017. graf, tab
Article in Spanish | LILACS | ID: biblio-834661

ABSTRACT

Introducción: Para el tratamiento de las infecciones por Enterococcus resistente a vancomicina (ERV) se emplean fármacos de segunda línea como daptomicina y linezolid. Objetivo: hacer una revisión sistemática para evaluar el tratamiento de la bacteriemia por ERV, con daptomicina o linezolid. Metodología: búsqueda electrónica en las bases de datos de Pubmed, Embase, Scopus, ScienceDirect, CENTRAL, Lilacs y Google Académico, para identificar estudios anteriores a julio de 2015 que hayan comparado los tratamientos con daptomicina o linezolid de pacientes infectados por ERV. Resultados: se incluyeron 15 estudios de 1307 registros. No hubo diferencias entre daptomicina y linezolid con respecto a la mortalidad a 30 días. Con la daptomicina se logró más tempranamente el control microbiológico (OR: 0,64; IC95 %: 0,45-0,92). No hubo diferencias entre los dos antibióticos en cuanto a la mejoría clínica, la necesidad de admisión a la UCI o la aparición de efectos adversos como trombocitopenia, neutropenia e insuficiencia renal. Conclusiones: no encontramos diferencias entre daptomicina y linezolid en cuanto a la mortalidad de pacientes infectados por ERV, aunque con la daptomicina se logró una cura microbiológica más rápida.


Introduction: Second-line drugs such as linezolid and daptomycin are used for treatment of vancomycin-resistant Enterococcus (VRE) infections. Objective: A systematic review to evaluate treatment of VRE bacteremia with linezolid versus daptomycin. Methods: A search was done in the databases of Pubmed, Embase, Scopus, ScienceDirect, CENTRAL, Lilacs and Google Scholar to identify studies comparing treatment with daptomycin or linezolid of patients infected by VRE up to July 2015. Result: Only 15 studies were included of a total of 1.307 records. There were no differences between daptomycin and linezolid with respect to mortality at 30 days. Microbiological cure was better with daptomycin (OR: 0.64; 95 % CI: 0.45-0.92), whereas there was no difference between the two antibiotics with respect to clinical cure, need to ICU admission, and the occurrence of adverse effects such as thrombocytopenia, neutropenia and renal failure. Conclusions: No significant differences were observed between daptomycin and linezolid in reference to mortality of patients infected with VRE, although daptomycin treatment produced a faster microbiological cure.


Introdução: Para o tratamento das infecções por Enterococcusresistente a vancomicina (ERV) se empregam fármacos de segunda linha como daptomicina e linezolida. Objetivo: fazer uma revisão sistemática para avaliar o tratamento da bacteriemia por ERV, com daptomicina o linezolida. Metodologia: busca eletrônica nas bases de dados de Pubmed, Embase, Scopus, ScienceDirect, CENTRAL, Lilacs e Google Acadêmico, para identificar estudos anteriores a julho de 2015 que foram comparados os tratamentos com daptomicina ou linezolida de pacientes infectados por ERV. Resultados: se incluíram 15 estudos de 1.307 registros. Não houve diferenças entre daptomicina e linezolida com respeito à mortalidade a 30 dias. Com a daptomicina se conseguiu mais precoce o controle microbiológico (OR: 0,64; IC95 %: 0,45-0,92). Não houve diferenças entre os dois antibióticos em quanto à melhoria clínica, a necessidade de admissão à UTI ou a aparição de efeitos adversos como trombocitopenia, neutropenia e insuficiência renal. Conclusões: não encontramos diferenças entre daptomicina e linezolida em quanto à mortalidade de pacientes infectados por ERV, embora com a daptomicina se conseguiu uma cura microbiológica mais rápida.


Subject(s)
Humans , Adult , Anti-Bacterial Agents , Bacteremia , Daptomycin , Enterococcus , Vancomycin , Infections
5.
Infectio ; 20(4): 269-271, jul.-dic. 2016. graf
Article in Spanish | LILACS, COLNAL | ID: biblio-953972

ABSTRACT

Se presenta un caso de osteitis del pubis por Staphylococcus aureus, en un varón de 30 años y tratado exitosamente con linezolid y levofloxacina.


We describe a case o infectious osteitis pubis in one male patient of 30 years. The patient had favorable clinical course after treament with linezolid and levofloxacin.


Subject(s)
Humans , Male , Adult , Osteitis , Pubic Bone , Staphylococcus aureus , Levofloxacin , Linezolid
6.
Rev. ciênc. farm. básica apl ; 36(4): 531-538, 01/10/2015.
Article in English | LILACS | ID: biblio-2594

ABSTRACT

Due to the paucity of cost-minimization studies about linezolid, the aim of this study was to estimate the cost differential between intravenous and oral administration. A retrospective cohort study and costminimization analysis was conducted between August 2009 and August 2013 in a public hospital in southern Brazil. Inpatient records were evaluated for 152 patients who received linezolid intravenously or orally. Over two-thirds of the patients (103, 67.8%) received the antibiotic by the intravenous route only (IV group), and the remainder received the antibiotic both routes sequentially (mixed group). In the IV group, 33 patients (31.7%) were eligible to receive the antibiotic orally. The total cost per patient (mean) after changing from intravenous to oral administration was significantly lower than the real cost paid per patient (mean) (p<0.001). The cost savings associated with switching to oral linezolid administration would be US$14,328.32 over four years. Pharmacoeconomic analyses of linezolid therapy can inform hospitals' decisions about the rational use of therapeutics and economic resources.


Devido à escassez de estudos de custo-minimização a cerca da linezolida, o objetivo deste estudo foi estimar a diferença de custo entre a administração intravenosa e oral desse antibiótico. Um estudo de coorte retrospectiva e uma análise de custo-minimização foram realizados entre agosto de 2009 e agosto de 2013, em um hospital público do sul do Brasil. Foram avaliados os prontuários médicos de 152 pacientes que receberam linezolida por via intravenosa e / ou oralmente. Mais de dois terços dos pacientes (103, 67.8%) receberam o medicamento exclusivamente por via intravenosa (grupo IV), e o restante (grupo misto) recebeu o antibacteriano por via intravenosa e por via oral sequencialmente. No grupo IV, 33 pacientes (31.7%) eram elegíveis para receber o antibiótico por via oral. O custo médio total por paciente após a troca hipotética da via de administração intravenosa para oral foi significativamente mais baixo do que o custo médio real pago por cada tratamento com linezolida (p <0.001). A economia de custos associados com a mudança para a administração oral de linezolida seria de US $ 14,328.32 ao longo de quatro anos. A análise farmacoeconômica da terapia com linezolida pode orientar as decisões dos hospitais quanto ao uso racional de terapêuticas e de recursos econômicos.


Subject(s)
Humans , Administration, Intravenous , Costs and Cost Analysis , Economics, Pharmaceutical , Linezolid/administration & dosage , Administration, Oral
7.
J. bras. econ. saúde (Impr.) ; 7(2)maio-ago. 2015.
Article in Portuguese | LILACS | ID: lil-756208

ABSTRACT

A tendência mundial pelo sistema de home care é uma estratégia de desospitalização. A assistência domiciliar favorece a redução dos custos operacionais dos serviços, na medida em que proporciona a diminuição do tempo médio de permanência nas instituições de internação, redução do número de reinternações, diminuição de complicações infecciosas sucedidas de hospitalizações prolongadas e aumento da adesão do paciente ao tratamento. A mudança da terapia endovenosa para a via oral permite a alta hospitalar precoce do paciente. A linezolida (Zyvox®) é um agente antibacteriano da classe das oxazolidinonas, indicado para o tratamento de infecções de pele e partes moles (IPPMs) e pneumonia adquirida em ambiente hospitalar ou comunitário. Devido à sua apresentaçãooral, pode ser uma opção para uso em home care para o tratamento de pacientes com infecções por cocos gram positivos resistentes aos beta-lactâmicos. As evidências disponíveis sobre o processo da desospitalização que avaliam o impacto clínico e econômico da linezolida mostram menortempo de hospitalização e alta precoce, além de menor custo total de tratamento, quando comparada a outras opções de tratamento. A linezolida mostra uma característica única no tratamento de infecções por Staphylococcus aureus resistentes à meticilina (MRSA), que é sua biodisponibilidade clinicamente semelhante entre as formas parenteral e oral, que possibilita a mudança da via de administração assim que o quadro clínico seja propício. Dessa forma, constata-se que a principal razão para a obtenção da economia é a possibilidade de oferecer um tratamento oral em regime domiciliar, realizado, até o momento, somente com a linezolida.


The global tendency of home care system is an early hospital discharge strategy. Home care assistance promotes a reduction in operating services costs, as it minimizes the mean of length hospital stay, reduces hospital readmissions, decreases infectious complications due to prolonged hospital stays and increases patient adherence to treatment. The switch therapy, from intravenous to oral allows an early hospital discharge. Linezolid (Zyvox®) is an antibacterial agent from the oxazolidinone class, indicated for the treatment of complicated skin and soft-tissue infection (cSSTI) and nosocomial or community-acquired pneumonia. Due to its oral administration, it may be an option for home care in the treatment of patients infected with beta-lactam-resistant Gram-positive cocci. The availableevidences about early hospital discharge that evaluate clinical and economic impacts of linezolid present shorter length of hospital stay and early discharge, as well as lower total cost of treatment, when compared to other treatment options. Linezolid shows an exclusive characteristic in infectionswith methicillin-resistant Staphylococcus aureus (MRSA) treatment, which is its bioavailability that is clinically similar between parenteral and oral administration, thereby allowing changes in the administration route as soon as the clinical presentation be adequate. Accordingly, it is observed that themain reason to economize is the possibility to offer an oral treatment in domiciliary care, performed, until now, only with linezolid.


Subject(s)
Humans , Administration, Oral , Anti-Bacterial Agents , Bacterial Infections , Cost Savings , Home Nursing
8.
São Paulo; s.n; 2012. xi,82 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: lil-691546

ABSTRACT

Linezolida foi o primeiro fármaco da classe das oxazolidinonas a ser aprovado para o uso clínico. Esta nova oxazolidinona inibe a síntese protéica impedindo a formação do complexo de iniciação formado pelo mRNA, tRNA f-Met e a subunidade 50S do ribossomo bacteriano. Embora a resistência à linezolida possa ser mediada pelo produto do gene cfr ou por mutações nas proteínas ribossômicas L3, L4 e L22, o mecanismo de resistência mais comum envolve mutações no domínio V do gene rRNA 23S. Entre março de 2008 a dezembro de 2011, 38 cepas de estafilococos coagulase-negativos (SCNs) resistentes à linezolida (20 S. epidermidis, 14 S. haemolyticus, 3 S. hominis e 1 S. warneri) isoladas de hemoculturas e pontas de cateter de pacientes internados em dois hospitais terciários do Estado de São Paulo foram incluídas neste estudo para a determinação dos mecanismos de resistência e análise da estabilidade do fenótipo resistente. As cepas de SCNs apresentaram altos níveis de resistência à linezolida (CIMs de 16-128 µg/ml) e foram multi-resistentes, permanecendo sensíveis à vancomicina e teicoplanina. A mutação G2576T foi identificada no domínio V do gene rRNA 23S em todas as cepas de SCNs, exceto em uma cepa de S. haemolyticus. O gene cfr e mutações nas proteínas L4 e L22 não foram detectados. Em relação à proteína L3, todas as cepas de S. epidermidis do hospital A, incluindo a cepa controle sensível à linezolida, apresentaram a substituição Leu101Val, sugerindo que essa mutação seja um marcador clonal dessa população sem envolvimento com a resistência à linezolida. A única cepa proveniente do hospital B (S. epidermidis) foi selvagem para essa proteína ribossômica. Somente uma cepa de S. haemoyticus teve uma mutação no gene rplC, resultando na alteração Val154Leu. Em S. hominis, a mutação Phe147Ile foi identificada em uma cepa, enquanto a associação de Gly139Arg e Met156Thr foi observada nas outras duas cepas dessa espécie. A identificação dessas mutações na proteína L3 de...


Linezolid was the first agent of the oxazolidinone class to be introduced clinically. This oxazolidinone inhibits protein biosynthesis by preventing the formation of the initiation complex that consists of the mRNA, the f-Met tRNA and the 50S subunit of the ribosome. Although linezolid resistance has been mediated by the cfr-encoded product or by ribosomal proteins (L3, L4 and L22), the most common mechanism of resistance involves mutations in the central loop of domain V of the 23S rRNA gene. From March 2008 to December 2011, 38 coagulase-negative staphylococci (CNS) strains (20 S. epidermidis, 14 S. haemolyticus, 3 S. hominis e 1 S. warneri) exhibiting resistance to linezolid were isolated from blood and catheter cultures from patients in two tertiary care hospitals in the State of São Paulo and were included in this study for the ascertainment of the resistance mechanisms to this antimicrobial agent and for the analysis of the stability of this resistance. The strains exhibited high-level resistance to linezolid (MICs 16-128 µg/ml) and all were multidrug resistant, remaining susceptible to vancomycin and teicoplanin. The G2576T mutation in domain V region of 23S rRNA was identified in all isolates, except in a linezolid-resistant S. haemolyticus strain. The cfr gene and mutations in ribosomal proteins L4 and L22 were not detected. Regarding L3 protein analysis, all S. epidermidis strains of hospital A, including the linezolid-susceptible control strain, showed the L3 Leu101Val mutation, suggesting that this alteration is probably not involved in linezolid resistance. The one strain from hospital B (S. epidermidis) was wild-type for this ribosomal protein. Only one S. haemolyticus strain had a mutation in the L3 protein, Val154Leu. Two S. hominis strains showed Gly139Arg/Met156Thr mutations whereas one strain had Phe147Ile in L3 protein. The identification of these mutations in L3 protein of the linezolid-resistant S. haemolyticus and S. hominis strains...


Subject(s)
Anti-Bacterial Agents/analysis , Coagulase/analysis , Molecular Mechanisms of Pharmacological Action , Molecular Structure , Oxazolidinones , Phenotype
9.
São Paulo; s.n; s.n; 2012. 82 p. ilus, tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-882921

ABSTRACT

Linezolid was the first agent of the oxazolidinone class to be introduced clinically. This oxazolidinone inhibits protein biosynthesis by preventing the formation of the initiation complex that consists of the mRNA, the f-Met tRNA and the 50S subunit of the ribosome. Although linezolid resistance has been mediated by the cfr-encoded product or by ribosomal proteins (L3, L4 and L22), the most common mechanism of resistance involves mutations in the central loop of domain V of the 23S rRNA gene. From March 2008 to December 2011, 38 coagulase-negative staphylococci (CNS) strains (20 S. epidermidis, 14 S. haemolyticus, 3 S. hominis e 1 S. warneri) exhibiting resistance to linezolid were isolated from blood and catheter cultures from patients in two tertiary care hospitals in the State of São Paulo and were included in this study for the ascertainment of the resistance mechanisms to this antimicrobial agent and for the analysis of the stability of this resistance. The strains exhibited high-level resistance to linezolid (MICs 16-128 µg/ml) and all were multidrug resistant, remaining susceptible to vancomycin and teicoplanin. The G2576T mutation in domain V region of 23S rRNA was identified in all isolates, except in a linezolid-resistant S. haemolyticus strain. The cfr gene and mutations in ribosomal proteins L4 and L22 were not detected. Regarding L3 protein analysis, all S. epidermidis strains of hospital A, including the linezolid-susceptible control strain, showed the L3 Leu101Val mutation, suggesting that this alteration is probably not involved in linezolid resistance. The one strain from hospital B (S. epidermidis) was wild-type for this ribosomal protein. Only one S. haemolyticus strain had a mutation in the L3 protein, Val154Leu. Two S. hominis strains showed Gly139Arg/Met156Thr mutations whereas one strain had Phe147Ile in L3 protein. The identification of these mutations in L3 protein of the linezolid-resistant S. haemolyticus and S. hominis strains strengthens the role of these sites in the acquisition of linezolid resistance in Staphylococcus spp. However, the presence of G2576T in the 23S rRNA gene makes difficult to determine exactly the role of L3 mutations in conferring elevated linezolid MIC values showed by these clinical strains. In the absence of antibiotic pressure, after 130 passages, linezolid resistance was stable in the clinical strains of this study, which did not have all copies of the 23S rRNA gene mutated, according to the restriction of the domain V fragment with NheI enzyme. Sequencing of the individual copies of the 23S rRNA gene in the serially passaged strains showed G2576T in all amplified copies by PCR: 4/4 and 5/5 in S. epidermidis and 3/3 in S. haemolyticus strains (MIC of 16-32 µg/ml). The stability of the mutant rRNA copy was also observed in the linezolid-susceptible S. epidermidis strain (MIC of 4 µg/ml). After the passages in antibiotic-free medium, the linezolid MIC of this strain fell to 1 µg/ml and the G2576T mutation persisted in one 23S rRNA gene copy. The clonal relatedness of the strains was determined by PFGE and revealed a clonal dissemination of different CNS species. Regarding MLST analysis, all S. epidermidis strains belonged to the sequence type ST2 (CC2). Most likely, the increased selective pressure has contributed to the selection of endemic linezolid-resistant CNS clones showing the G2576T mutation that have been disseminated in the institution A since 2008. Differently, the restricted use of linezolid in the institution B could explain the occurrence of a single resistant strain since 2005


Subject(s)
Phenotype , Drug Resistance, Microbial , Linezolid/adverse effects , Microbial Sensitivity Tests/instrumentation , Disk Diffusion Antimicrobial Tests/methods
SELECTION OF CITATIONS
SEARCH DETAIL