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1.
Klin Lab Diagn ; 67(5): 315-320, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35613352

RESUMO

Stenotrophomonas maltophilia is a common opportunistic microorganism and an important respiratory pathogen in cystic fibrosis (CF). The aim of this study was to determine antimicrobial resistance phenotypes, sequence-types (ST) and genetic determinants of antibiotic resistance in S. maltophilia strains recovered from CF patients in Russia. S. maltophilia isolates recovered from 170 CF patients were analyzed. Minimum inhibitory concentrations of antibacterial agents were determined using Sensititre Gram Negative GNX2F plates and the results were interpreted according to Clinical and Laboratory Standards Institute (CLSI) criteria. Whole-genome sequencing (WGS) was performed on MGISEQ-2000 platform. SPAdes software, Galaxy, ResFinder, Integrall and PubMLST were used for analysis of WGS data. S. maltophilia strains were identified from 24/170 (14%) CF patients. In total, 25 isolates were detected, two strains were isolated from the same patient. The isolates belonged to 17 different STs, including 5 new STs; ST4 was the most prevalent ST. Resistance to ceftazidime was observed in 60% of strains, to ticarcillin-clavulanate - in 32%, to levofloxacin - in 24%, to trimethoprim/sulfamethoxazole - in 12% of strains. All isolates were susceptible to minocycline. All ST4 isolates were resistant or intermediate to ceftazidime and ticarcillin-clavulanate. In two isolates, the sul1 gene was detected. In one isolate, sul1 was part of a class 1 integron. The detected integron also contained the blaGES-7 and aac(6')-Ib-cr genes. The ST4 sequence-type was the most prevalent ST among S. maltophilia strains recovered from CF patients in Russia. Antibiotic resistance genes, including sul1, blaGES-7, aac(6')-Ib-cr, were detected in single strains.


Assuntos
Fibrose Cística , Infecções por Bactérias Gram-Negativas , Stenotrophomonas maltophilia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftazidima/farmacologia , Ácido Clavulânico , Fibrose Cística/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Stenotrophomonas maltophilia/genética , Ticarcilina
2.
Biochimie ; 197: 1-8, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35093453

RESUMO

Infectious diseases account for 25% of the causes of death worldwide and this rate is expected to increase due to antibiotic resistance. Among the bacteria associated with healthcare infections, Staphylococcus aureus is a prevalent pathogen and about 50% of the isolates are found to be methicillin-resistant. Here we describe the identification of ticarcillin as a weak binder of the S. aureus UDP-N-acetylglucosamine 2-epimerase. After a docking screening, ticarcillin was identified as a ligand in using the recently proposed isothermal analysis of differential scanning fluorimetry data. Finally, an equilibrium MD simulation confirmed the docking binding mode as a stable pose, with large contributions to the binding energy coming from interactions between Arg206 and Arg207 and the carboxylate groups in ticarcillin.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Staphylococcus aureus , Antibacterianos/farmacologia , Carboidratos Epimerases/metabolismo , Staphylococcus aureus/metabolismo , Ticarcilina , beta-Lactamas
3.
Cochrane Database Syst Rev ; 5: CD013836, 2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33998665

RESUMO

BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis. OBJECTIVES: To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis. SEARCH METHODS: We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up. MAIN RESULTS: We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors. AUTHORS' CONCLUSIONS: Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.


ANTECEDENTES: La sepsis neonatal es una causa importante de morbilidad y mortalidad. Es la tercera causa de mortalidad neonatal a nivel mundial y constituye el 13% de la mortalidad neonatal total. A pesar de la elevada carga de la sepsis neonatal, la evidencia de alta calidad en el diagnóstico y el tratamiento es escasa. Debido a las dificultades de diagnóstico de la sepsis y a la relativa inmunosupresión del neonato, muchos reciben antibióticos por sospecha de sepsis. Los antibióticos se han convertido en el tratamiento más utilizado en las unidades de cuidados intensivos neonatales, y los estudios observacionales realizados en países de ingresos altos indican que entre el 83% y el 94% de los neonatos tratados con antibióticos por sospecha de sepsis tienen hemocultivos negativos. La última revisión Cochrane se actualizó en 2005. Se necesita una revisión sistemática actualizada que evalúe los efectos de los diferentes regímenes de antibióticos para la sepsis neonatal de inicio tardío. OBJETIVOS: Evaluar los efectos beneficiosos y perjudiciales de diferentes regímenes antibióticos para la sepsis neonatal de inicio tardío. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en las siguientes bases de datos electrónicas: CENTRAL (2021, número 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED y Conference Proceedings Citation Index ­ Science el 12 de marzo de 2021. También se buscaron ensayos controlados aleatorizados (ECA) y cuasialeatorizados en las bases de datos de ensayos clínicos y en las listas de referencias de artículos identificados. CRITERIOS DE SELECCIÓN: Se incluyeron ECA que compararon diferentes regímenes de antibióticos para la sepsis neonatal de inicio tardío. Se incluyeron participantes mayores de 72 horas de vida en el momento de la asignación al azar, con sospecha o diagnóstico de sepsis neonatal, meningitis, osteomielitis, endocarditis o enterocolitis necrosante. Se excluyeron los ensayos que evaluaron el tratamiento de las infecciones micóticas. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron los estudios para inclusión, extrajeron los datos y evaluaron el riesgo de sesgo. Se utilizó el método GRADE para evaluar la certeza de la evidencia. El desenlace principal fue la mortalidad por todas las causas, y los desenlaces secundarios fueron: eventos adversos graves, asistencia respiratoria, apoyo circulatorio, nefrotoxicidad, deterioro del desarrollo neurológico, enterocolitis necrosante y ototoxicidad. El punto temporal principal de interés fue el seguimiento máximo. RESULTADOS PRINCIPALES: Se incluyeron cinco ECA (580 participantes). Todos los ensayos tuvieron alto riesgo de sesgo y evidencia de certeza muy baja. Los cinco ensayos incluidos evaluaron cinco comparaciones diferentes de antibióticos. No se realizó un metanálisis debido a la falta de datos relevantes. De los cinco ensayos incluidos, un ensayo comparó cefazolina más amikacina con vancomicina más amikacina; un ensayo comparó ticarcilina más ácido clavulánico con flucloxacilina más gentamicina; un ensayo comparó cloxacilina más amikacina con cefotaxima más gentamicina; un ensayo comparó meropenem con atención estándar (ampicilina más gentamicina o cefotaxima más gentamicina); y un ensayo comparó vancomicina más gentamicina con vancomicina más aztreonam. Ninguna de las cinco comparaciones encontró evidencia de una diferencia al evaluar la mortalidad por todas las causas, los eventos adversos graves, el apoyo circulatorio, la nefrotoxicidad, el deterioro del desarrollo neurológico o la enterocolitis necrosante; sin embargo, ninguno de los ensayos se acercó a un tamaño de información que pudiera contribuir significativamente a la evidencia de los beneficios y los riesgos comparativos de cualquier régimen antibiótico en particular. Ninguno de los ensayos evaluó la asistencia respiratoria o la ototoxicidad. Los efectos beneficiosos y perjudiciales de los diferentes regímenes de antibióticos aún no están claros debido a la falta de ensayos con un poder estadístico adecuado y al alto riesgo de errores sistemáticos. CONCLUSIONES DE LOS AUTORES: La evidencia actual no es suficiente para apoyar que un régimen de antibióticos sea superior a otro. Se justifica la realización de ECA con bajo riesgo de sesgo que evalúen diferentes regímenes antibióticos en la sepsis neonatal de inicio tardío.


Assuntos
Antibacterianos/uso terapêutico , Sepse Neonatal/tratamento farmacológico , Amicacina/efeitos adversos , Amicacina/uso terapêutico , Ampicilina/efeitos adversos , Ampicilina/uso terapêutico , Antibacterianos/efeitos adversos , Aztreonam/efeitos adversos , Aztreonam/uso terapêutico , Viés , Cefazolina/efeitos adversos , Cefazolina/uso terapêutico , Ácido Clavulânico/efeitos adversos , Ácido Clavulânico/uso terapêutico , Quimioterapia Combinada , Floxacilina/efeitos adversos , Floxacilina/uso terapêutico , Gentamicinas/efeitos adversos , Gentamicinas/uso terapêutico , Humanos , Recém-Nascido , Ensaios Clínicos Controlados Aleatórios como Assunto , Ticarcilina/efeitos adversos , Ticarcilina/uso terapêutico , Vancomicina/efeitos adversos , Vancomicina/uso terapêutico
4.
Diagn Microbiol Infect Dis ; 100(2): 115343, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33652305

RESUMO

Minimal inhibitory concentrations (MICs) of ticarcillin/clavulanic acid (TLc), ceftolozane/tazobactam (C/T), and aztreonam (AT) were determined for 6 SPM-1-producing Pseudomonas aeruginosa (PSA) using Etest® strips and the synergistic effect of such antimicrobials against was evaluated by gradient diffusion strip crossing (GDSC) test. The fraction inhibitory concentration indexes (FICI) were calculated and showed a synergistic (n = 3) and additive (n = 2) effects of TLc + AT against SPM-1 producers, while TLc + C/T combination caused no effect. Average MIC reduction of TLc and AT by GDSC was 3-fold and 2-fold dilutions, respectively. Thus, TLc + AT might be a candidate as a combination therapy to treat SPM-1-producing PSA infections.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , beta-Lactamases/metabolismo , Aztreonam/administração & dosagem , Aztreonam/farmacologia , Cefalosporinas/farmacologia , Ácidos Clavulânicos/administração & dosagem , Ácidos Clavulânicos/farmacologia , Sinergismo Farmacológico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Tazobactam/farmacologia , Ticarcilina/administração & dosagem , Ticarcilina/farmacologia , beta-Lactamases/genética
5.
J Int Med Res ; 48(12): 300060520967822, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33356736

RESUMO

OBJECTIVE: To establish a specific and rapid ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method for measuring ticarcillin and clavulanate levels in rat plasma. METHODS: A Waters ACQUITY BEH C18 column (50 mm × 2.1 mm, 1.7 µm) and SCIEX QTRAP® LC-MS/MS System were used. Analyses were conducted to optimize the chromatographic and MS conditions, and the pharmacokinetic parameters of ticarcillin and clavulanate were assessed. RESULTS: Linear relationships were observed in the ranges of 10 to 10,000 ng/mL for ticarcillin R (r2 = 0.9967) 30 to 10,000 ng/mL for ticarcillin S (r2 = 0.9961), and 30 to 10,000 ng/mL for clavulanate (r2 = 0.9981). The average extraction recoveries of all compounds ranged from 86.9% to 96.4%. The pharmacokinetic parameters of the ticarcillin R and S isomers in rats were distinctive. The ticarcillin R and S isomers and clavulanate were rapidly absorbed in vivo. Ticarcillin S and clavulanate had similar elimination rates, whereas that of ticarcillin R was slower. CONCLUSION: A UPLC-ESI-MS/MS method was developed and validated for the determination of ticarcillin and clavulanate in rat plasma.


Assuntos
Espectrometria de Massas em Tandem , Ticarcilina , Administração Oral , Animais , Cromatografia Líquida , Ácido Clavulânico , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
6.
Int J Antimicrob Agents ; 56(3): 106058, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32590056

RESUMO

OBJECTIVES: To describe the adsorption of ticarcillin and piperacillin on to polyethersulfone (PES) membranes using the recirculation function on an ex-vivo renal replacement circuit. METHODS: Low (4-8 mg) or high (35-45 mg) doses of ticarcillin and low (4-8 mg) or high (70-80 mg) doses of piperacillin were added to 1 L of human blood-crystalloid mixture and circulated around an ex-vivo modified continuous renal replacement therapy machine at three different blood flow settings (150, 300 and 450 mL/min). Plasma samples were collected from the pre-filter port of the haemodiafilter circuit at consecutive timepoints for a total duration of 4 h. Plasma samples were measured using a validated ultra high performance liquid chromatography-tandem mass spectrometry method. RESULTS: Eighty-one samples including both drugs were collected from 18 experimental runs. Overall, the percentage of piperacillin adsorption for the low and high doses ranged from 21.3% to 27.1% and from 11.5% to 23%, and the percentage of ticarcillin adsorption for the low and high doses ranged from 4.2% to 14.3% and from 3.7% to 15.1%, respectively. The low dose of piperacillin consistently yielded more than 20% adsorption of dose for all blood flow rates. This decreased with high blood flow rates when the high dose of piperacillin was used. Ticarcillin generally displayed ≤5% adsorption, with the exceptions being the high dose at 150 mL/min and the low dose at 300 mL/min, which displayed ~15% adsorption. CONCLUSIONS: Adsorption of both drugs tended to be higher at the lowest blood flow rates and lowest doses. This is likely due to saturation of parts of the filter that have a chemical attraction to both piperacillin and ticarcillin. At low doses at all three blood flow rates, piperacillin demonstrated >20% adsorption, whereas ticarcillin tended to have low rates (up to ~≤15%) of adsorption on to PES membrane filters.


Assuntos
Antibacterianos/farmacocinética , Hemodiafiltração/métodos , Piperacilina/farmacocinética , Polímeros/metabolismo , Sulfonas/metabolismo , Ticarcilina/farmacocinética , Adsorção , Antibacterianos/farmacologia , Velocidade do Fluxo Sanguíneo/fisiologia , Humanos , Membranas Artificiais , Piperacilina/farmacologia , Terapia de Substituição Renal/métodos , Ticarcilina/farmacologia
7.
Medicine (Baltimore) ; 99(8): e19250, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080131

RESUMO

Stenotrophomonas maltophilia (S. maltophilia) is an important nosocomial bacterial pathogen. However, the clinical features of children with S. maltophilia infection, the predisposing factors, and the antibiotic susceptibility of the bacteria have not been fully evaluated.In this study, the data of children with S. maltophilia infection from the West China Second University Hospital of Sichuan University (Chengdu, China) between July 2010 and October 2017 were collected and analyzed. The clinical features of enrolled children, the predisposing factors, and the antibiotic susceptibility were reported.In total, infection of S. maltophilia was identified in 128 patients. Most of these patients were under 1 year old (67.2%) and were mainly diagnosed as pneumonia (69%). A large proportion had underlying diseases (45.3%), received immunosuppressive therapy (53.1%), had undergone invasive operations (41.4%), had a history of carbapenem antibiotics use within 7 days before culture acquisition (54.7%), history of intensive care unit (ICU) hospitalization within previous 30 days (34.4%), and other risk factors. In particular, invasive operation (95% confidence interval [CI]: 1.125-14.324, P = .032), especially mechanical ventilation (95% CI: 1.277-20.469, P = .021), and ICU admission (95% CI: 1.743-22.956, P = .005) were independent risk factors for the children to develop severe S. maltophilia infection. As for antibiotic susceptibility, trimethoprim sulfamethoxazole (TMP-SMX), piperacillin tazobactam, ticarcillin clavulanate, and ceftazidime exhibited strong antibacterial activities against S. maltophilia, the susceptibility rates were 97.5%, 86.7%, 92.9%, and 81.5%, respectively.We report the clinical features of children with S. maltophilia infection, the predisposing factors and the antibiotic susceptibility. TMP-SMX can continue to be the first choice for the treatment of S. maltophilia infection. Piperacillin tazobactam, ticarcillin clavulanate, and the third generation cephalosporins can be used as alternative drugs.


Assuntos
Infecções por Bactérias Gram-Negativas/epidemiologia , Stenotrophomonas maltophilia , Distribuição por Idade , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Ceftazidima/uso terapêutico , Pré-Escolar , China/epidemiologia , Ácidos Clavulânicos/uso terapêutico , Comorbidade , Feminino , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Humanos , Imunossupressores/uso terapêutico , Lactente , Unidades de Terapia Intensiva Pediátrica , Tempo de Internação/estatística & dados numéricos , Masculino , Combinação Piperacilina e Tazobactam/uso terapêutico , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Ticarcilina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
8.
Med Mal Infect ; 50(3): 305-307, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32014291

RESUMO

OBJECTIVE: To compare the minimum inhibitory concentrations (MIC) of the ceftazidime-avibactam (CZA) combination versus ceftazidime alone (TZ) for Stenotrophomonas maltophilia. PATIENTS AND METHODS: MIC comparison was performed by E-tests. We assumed that CZA was more effective in vitro than TZ alone when CZA led to a category change from "Resistant" with TZ alone to "Susceptible" or "Intermediate" with CZA, or if the MIC of CZA was at least 4-fold lower than the MIC of TZ for TZ-susceptible isolates. RESULTS: For the 54 clinical isolates included in the study, CZA showed better results in terms of the proportion of susceptible isolates (66.7% vs. 38.9%, P<0.01), MIC50 (2µg/mL vs. 12µg/mL, P<0.05), and MIC distribution. According to our definition, CZA was also more effective in vitro than TZ alone for 50% of the isolates. CONCLUSION: Using CZA for empirical treatments in severe or polymicrobial infections with S. maltophilia seems appropriate.


Assuntos
Compostos Azabicíclicos/farmacologia , Ceftazidima/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Stenotrophomonas maltophilia/efeitos dos fármacos , Ácidos Clavulânicos/farmacologia , Fibrose Cística/complicações , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana , Estudos Multicêntricos como Assunto , Ticarcilina/farmacologia
9.
Vet Microbiol ; 241: 108553, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31928700

RESUMO

The objectives of this work were to evaluate ß-lactamase-mediated ß-lactam resistance in Campylobacter coli and Campylobacter jejuni isolates obtained from broiler chickens, expression of the blaOXA-61 gene in relation to ß-lactamase production, and the possible association between blaOXA-61 gene expression and the action of inhibitors when combined with ß-lactams. All strains were tested by disk diffusion and nitrocefin methods to assess antibiotic susceptibility and ß-lactamase production, respectively. PCR and qPCR amplification were performed to evaluate qualitative and quantitative blaOXA-61 expression. Campylobacter spp. showed a high level of resistance to the most of antimicrobials tested. C. coli strains were ampicillin resistant and blaOXA-61 positive, and 59 out of 60 isolates were positive in the nitrocefin test. Twenty C. jejuni isolates were positive for blaOXA-61 and the nitrocefin test, although two isolates were ampicillin sensitive. Amoxicillin/clavulanic acid and ticarcillin/clavulanic acid do not seem to be active against C. coli, as 73.3 %, and 88.3 % of isolates were resistant to amoxicillin/clavulanic acid and ticarcillin/clavulanic acid, respectively. C. jejuni was not susceptible to amoxicillin/clavulanic acid, with 90 % of the strains showing resistance, whereas ticarcillin associated with clavulanic acid was significantly more efficient than ticarcillin alone (P < 0.01), with 90 % of the strains found to be susceptible. An association between blaOXA-61 expression and amoxicillin/clavulanic acid and ticarcillin/clavulanic acid resistance (P = 0.0001) was seen in C. coli, as well as in C. jejuni for ampicillin/sulbactam (P = 0.0001). Our results suggest that the clavulanic acid only shows an inhibitory effect on C. jejuni when combined with ticarcillin and that the inhibitors action is lower if the blaOXA-61 gene is highly expressed.


Assuntos
Antibacterianos/farmacologia , Campylobacter coli/efeitos dos fármacos , Campylobacter jejuni/efeitos dos fármacos , Resistência beta-Lactâmica , Inibidores de beta-Lactamases/farmacologia , Algoritmos , Resistência a Ampicilina , Animais , Campylobacter coli/genética , Campylobacter coli/isolamento & purificação , Campylobacter jejuni/genética , Campylobacter jejuni/isolamento & purificação , Galinhas , Ácidos Clavulânicos/farmacologia , Cloaca/microbiologia , Expressão Gênica , RNA Bacteriano/química , RNA Bacteriano/isolamento & purificação , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Ticarcilina/farmacologia , beta-Lactamases/genética , beta-Lactamases/metabolismo
10.
Surg Infect (Larchmt) ; 21(3): 284-292, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31770083

RESUMO

Background: Empirical antibiotherapy (EA) should target all bacteria in post-operative peritonitis (PP). Nevertheless, recent studies failed to prove a link between adequacy of EA and prognosis of PP. We sought to confirm this loss of association between adequate EA and prognosis and to analyze the evolution of patients' characteristics and antimicrobial strategies. Methods: This is was retrospective study. Patients with a positive fungal culture were excluded. The cohort was divided into two time periods. Data of survivors and non-survivors were compared within each time period. Differences between the two periods were assessed. A multivariable analysis searched for parameters associated with a higher hospital mortality rate. Results: Two hundred fifty-one patients were included, with 92 patients in the first period (P1) and 152 patients in the second period (P2). Inadequate EA was associated with a worse outcome only in P1. The multivariable analysis in the whole cohort showed that inadequate EA was associated with a higher mortality rate. When the differences noticed between the two periods were entered in the model (presence of resistant gram-positive cocci and EA comprising glycopeptides), inadequate EA was no longer associated with worse outcome. In P1, the most severe patients had more resistant bacteria, hence, had a higher rate of inadequate EA. This artifact disappeared in P2, during which broader antibiotherapies with triple EA were more often prescribed for the most severe patients. Conclusion: This study showed that the link between inadequate EA and outcome of patients with PP was at least partly artifactual in older studies.


Assuntos
Antibacterianos/uso terapêutico , Procedimentos Cirúrgicos do Sistema Digestório , Mortalidade Hospitalar , Peritonite/tratamento farmacológico , Infecção da Ferida Cirúrgica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoglicosídeos/uso terapêutico , Fístula Anastomótica , Líquido Ascítico/microbiologia , Ácidos Clavulânicos/uso terapêutico , Estudos de Coortes , Técnicas de Cultura , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana Múltipla , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Imipenem/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Peritonite/microbiologia , Combinação Piperacilina e Tazobactam/uso terapêutico , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/microbiologia , Ticarcilina/uso terapêutico , Resultado do Tratamento , Vancomicina/uso terapêutico
11.
Artigo em Inglês | MEDLINE | ID: mdl-31685462

RESUMO

The prevalence of multidrug-resistant Pseudomonas aeruginosa has led to the reexamination of older "forgotten" drugs, such as temocillin, for their ability to combat resistant microbes. Temocillin is the 6-α-methoxy analogue of ticarcillin, a carboxypenicillin with well-characterized antipseudomonal properties. The α-methoxy modification confers resistance to serine ß-lactamases, yet temocillin is ineffective against P. aeruginosa growth. The origins of temocillin's inferior antibacterial properties against P. aeruginosa have remained relatively unexplored. Here, we analyze the reaction kinetics, protein stability, and binding conformations of temocillin and ticarcillin with penicillin-binding protein 3 (PBP3), an essential PBP in P. aeruginosa We show that the 6-α-methoxy group perturbs the stability of the PBP3 acyl-enzyme, which manifests in an elevated off-rate constant (k off) in biochemical assays comparing temocillin with ticarcillin. Complex crystal structures with PBP3 reveal similar binding modes of the two drugs but with important differences. Most notably, the 6-α-methoxy group disrupts a high-quality hydrogen bond with a conserved residue important for ligand binding while also being inserted into a crowded active site, possibly destabilizing the active site and enabling water molecule from bulk solvent to access and cleave the acyl-enzyme bond. This hypothesis is supported by the observation that the acyl-enzyme complex of temocillin has reduced thermal stability compared with ticarcillin. Furthermore, we explore temocillin's mechanism of ß-lactamase inhibition with a high-resolution complex structure of CTX-M-14 class A serine ß-lactamase. The results suggest that the α-methoxy group prevents hydrolysis by locking the compound into an unexpected conformation that impedes access of the catalytic water to the acyl-enzyme adduct.


Assuntos
Penicilinas/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Ticarcilina/farmacologia , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas/genética , Proteínas de Ligação às Penicilinas/metabolismo , Pseudomonas aeruginosa/genética , beta-Lactamases/genética , beta-Lactamas/metabolismo
12.
Int J Antimicrob Agents ; 54(3): 351-355, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279852

RESUMO

The aim of this study was to describe the population pharmacokinetics of ticarcillin during extended daily diafiltration (EDDf) in critically ill patients with acute kidney injury. Blood samples were collected from critically ill patients prescribed ticarcillin during one to two dosing intervals during which EDDf was performed. Plasma samples were measured using a validated ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Concentration-time data were analysed using a population pharmacokinetics approach with Pmetrics®. A total of 53 blood samples were collected from six critically ill patients (three male). The mean ± standard deviation patient age, weight and body mass index (BMI) was 43 ± 22 years, 88 ± 14 kg and 31 ± 5 kg/m2, respectively. A two-compartment linear model adequately described the data. Median population pharmacokinetic parameter estimates were as follows: clearance in the presence of EDDf (CLEDDf), 6.41 L/h; clearance of EDDf (CLnon-EDDf), 4.97 L/h; volume of distribution of the central compartment (Vc), 56.46 L; intercompartmental clearance from the central to peripheral compartment (kCP), 13.54 L/h; and intercompartmental clearance from the peripheral to central compartment (kPC), 21.93 L/h. This is the first population pharmacokinetic model of ticarcillin in patients receiving EDDf. Large pharmacokinetic variability was found, supporting further investigation of the pharmacokinetics of less-studied ß-lactam antibiotics in prolonged intermittent renal replacement therapy.


Assuntos
Injúria Renal Aguda/terapia , Antibacterianos/farmacocinética , Estado Terminal , Hemofiltração/métodos , Ticarcilina/farmacocinética , Adulto , Idoso , Antibacterianos/administração & dosagem , Cromatografia Líquida , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Plasma/química , Ticarcilina/administração & dosagem , Adulto Jovem
13.
Thorax ; 74(8): 740-748, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31203197

RESUMO

BACKGROUND: While Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown. AIM: To determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years. METHODS: Cross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years. RESULTS: Cross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32-3.79) years and 3.69 (1.68-4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event. CONCLUSION: In young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.


Assuntos
Antibacterianos/uso terapêutico , Fibrose Cística/complicações , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa , Aspergilose Pulmonar/epidemiologia , Antibacterianos/administração & dosagem , Lavagem Broncoalveolar , Ceftazidima/uso terapêutico , Pré-Escolar , Ciprofloxacina/uso terapêutico , Ácidos Clavulânicos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Prevalência , Aspergilose Pulmonar/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Fatores de Risco , Ticarcilina/uso terapêutico , Tobramicina/uso terapêutico
14.
Int J Antimicrob Agents ; 54(2): 261-264, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30904466

RESUMO

There are very limited data on ticarcillin-clavulanate elimination by haemofiltration. We measured in vitro ticarcillin-clavulanate adsorption to polyacrylonitrile (PAN) filters and the sieving coefficient using a well-described bench model of haemofiltration. The dose of ticarcillin-clavulanate was 60/2 mg or 180/3 mg, and 0 or 12 g albumin was added to the 1 L of circulating blood-crystalloid mixture to produce four different experimental conditions. The experiment was repeated four times under each condition. Median (interquartile range [IQR] ) ticarcillin adsorption varied from 28 (27-30) mg to 85 (78-90) mg. Adsorption was increased when the dose of ticarcillin was higher (P<0.001), but was not affected by the addition of albumin. Median (IQR) adsorption of clavulanate ranged from 0.67 (0.55-0.75) mg to 1.8 (0.33-3.5) mg and was neither dose dependent (P = 0.505) nor significantly affected by the addition of albumin. Median (IQR) ticarcillin sieving coefficient ranged from 0.73 (0.67-0.75) to 0.99 (0.97-1.03). It was significantly higher with a higher dose of ticarcillin (P = 0.021) and without addition of albumin (P = 0.015). Median (IQR) clavulanate sieving coefficient ranged from 1.03 (1.00-2.24) to 2.0 (1.98-2.47). Clavulanate sieving coefficient was not significantly affected by dose or the addition of albumin. These data indicate that significant adsorption of both ticarcillin and clavulanate occurs in vitro; however, this requires confirmation by clinical pharmacokinetic studies. The sieving coefficient data may help guide appropriate dosing of critically ill patients receiving haemofiltration until more extensive clinical pharmacokinetic data are available.


Assuntos
Adsorção , Antibacterianos/farmacocinética , Hemofiltração/métodos , Inibidores de beta-Lactamases/farmacocinética , Resinas Acrílicas/química , Antibacterianos/sangue , Ácidos Clavulânicos/sangue , Ácidos Clavulânicos/farmacocinética , Humanos , Técnicas In Vitro , Ticarcilina/sangue , Ticarcilina/farmacocinética , Inibidores de beta-Lactamases/sangue
15.
Br J Clin Pharmacol ; 85(5): 1021-1027, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30710387

RESUMO

Ticarcillin-clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin-clavulanate dosing are lacking. We enrolled 15 premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin-clavulanate. The infants had a median (range) postnatal age (PNA) of 18 days (6-44 days) and gestational age of 25 weeks (23-28 weeks). Clearance was lower in infants with a PNA <14 days (0.050 L/kg/h [range 0.043-0.075]) compared with a PNA ≥14-45 days (0.078 L/kg/h [0.047-0.100]), consistent with maturation of renal function. Dosing simulations determined that ticarcillin 75 mg/kg q12h (PNA <14 days) or q8h (PNA ≥ 14-45 days) achieved the target exposure for organisms with a minimum inhibitory concentration ≤16 µ/mL in >90% of simulated infants. For highly resistant organisms (minimum inhibitory concentration 32 µg/mL), increased dosing frequency or extended infusion are necessary.


Assuntos
Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus/efeitos dos fármacos , Inibidores de beta-Lactamases/farmacocinética , Ácidos Clavulânicos/administração & dosagem , Ácidos Clavulânicos/farmacocinética , Simulação por Computador , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Modelos Biológicos , Estudos Prospectivos , Infecções Estafilocócicas/microbiologia , Staphylococcus/fisiologia , Ticarcilina/administração & dosagem , Ticarcilina/farmacocinética , Inibidores de beta-Lactamases/administração & dosagem
16.
Artigo em Inglês | MEDLINE | ID: mdl-30718248

RESUMO

Burkholderia spp. are opportunistic human pathogens that infect persons with cystic fibrosis and the immunocompromised. Burkholderia spp. express class A and C ß-lactamases, which are transcriptionally regulated by PenRA through linkage to cell wall metabolism and ß-lactam exposure. The potency of temocillin, a 6-methoxy-ß-lactam, was tested against a panel of multidrug-resistant (MDR) Burkholderia spp. In addition, the mechanistic basis of temocillin activity was assessed and compared to that of ticarcillin. Susceptibility testing with temocillin and ticarcillin was conducted, as was biochemical analysis of the PenA1 class A ß-lactamase and AmpC1 class C ß-lactamase. Molecular dynamics simulations (MDS) were performed using PenA1 with temocillin and ticarcillin. The majority (86.7%) of 150 MDR Burkholderia strains were susceptible to temocillin, while only 4% of the strains were susceptible to ticarcillin. Neither temocillin nor ticarcillin induced bla expression. Ticarcillin was hydrolyzed by PenA1 (k cat/Km = 1.7 ± 0.2 µM-1 s-1), while temocillin was slow to form a favorable complex (apparent Ki [Ki app] = ∼2 mM). Ticarcillin and temocillin were both potent inhibitors of AmpC1, with Ki app values of 4.9 ± 1.0 µM and 4.3 ± 0.4 µM, respectively. MDS of PenA revealed that ticarcillin is in an advantageous position for acylation and deacylation. Conversely, with temocillin, active-site residues K73 and S130 are rotated and the catalytic water molecule is displaced, thereby slowing acylation and allowing the 6-methoxy of temocillin to block deacylation. Temocillin is a ß-lactam with potent activity against Burkholderia spp., as it does not induce bla expression and is poorly hydrolyzed by endogenous ß-lactamases.


Assuntos
Antibacterianos/farmacologia , Burkholderia/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Penicilinas/farmacologia , beta-Lactamas/farmacologia , Burkholderia/metabolismo , Humanos , Testes de Sensibilidade Microbiana/métodos , Ticarcilina/farmacologia , Estados Unidos , beta-Lactamases/metabolismo
17.
PLoS One ; 13(12): e0208468, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30521623

RESUMO

Conjugation is a type of horizontal gene transfer (HGT) that serves as the primary mechanism responsible for accelerating the spread of antibiotic resistance genes in Gram-negative bacteria. The present study aimed to elucidate the mechanisms underlying the conjugation-mediated gene transfer from the extensively drug-resistant Acinetobacter baumannii (XDR-AB) and New Delhi Metallo-beta-lactamase-1-producing Acinetobacter baumannii (NDM-AB) to environmental isolates of Acinetobacter spp. Conjugation experiments demonstrated that resistance to ticarcillin and kanamycin could be transferred from four donors to two sodium azide-resistant A. baumannii strains, namely, NU013R and NU015R. No transconjugants were detected on Mueller-Hinton Agar (MHA) plates containing tetracycline. Plasmids obtained from donors as well as successful transconjugants were characterized by PCR-based replicon typing and S1-nuclease pulsed-field gel electrophoresis (S1-PFGE). Detection of antibiotic resistance genes and integrase genes (int) was performed using PCR. Results revealed that the donor AB364 strain can transfer the blaOXA-23 and blaPER-1 genes to both recipients in association with int1. A 240-kb plasmid was successfully transferred from the donor AB364 to recipients. In addition, the aphA6 and blaPER-1 genes were co-transferred with the int1 gene from the donor strains AB352 and AB405. The transfer of a 220-kb plasmid from the donors to recipient was detected. The GR6 plasmid containing the kanamycin resistance gene (aphA6) was successfully transferred from the donor strain AB140 to both recipient strains. However, the blaNDM-1 and tet(B) genes were not detected in all transconjugants. Our study is the first to demonstrate successful in vitro conjugation, which indicated that XDR-AB contained combination mechanisms of the co-transfer of antimicrobial resistance elements with integron cassettes or with the plasmid group GR6. Thus, conjugation could be responsible for the emergence of new types of antibiotic-resistant strains.


Assuntos
Acinetobacter baumannii/genética , Farmacorresistência Bacteriana Múltipla , Integrons , Plasmídeos/genética , Acinetobacter baumannii/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Conjugação Genética , Canamicina/farmacologia , Testes de Sensibilidade Microbiana , Viabilidade Microbiana , Azida Sódica/farmacologia , Tetraciclina/farmacologia , Ticarcilina/farmacologia
18.
Cochrane Database Syst Rev ; 10: CD008319, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376155

RESUMO

BACKGROUND: Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. This is an update of a previously published review. OBJECTIVES: To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work and improves their long-term survival. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 03 October 2018.We searched ClinicalTrials.gov, the Australia and New Zealand Clinical Trials Registry and WHO ICTRP for relevant trials. Date of last search: 09 October 2018. SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. They assessed the quality of the evidence using the GRADE criteria. Authors of the included trials were contacted for more information. MAIN RESULTS: Four trials with 167 participants are included in the review. Two trials (77 participants) compared inhaled antibiotics alone to intravenous antibiotics alone and two trials (90 participants) compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone. Trials were heterogenous in design and two were only available in abstract form. Risk of bias was difficult to assess in most trials, but for all trials we judged there to be a high risk from lack of blinding and an unclear risk with regards to randomisation. Results were not fully reported and only limited data were available for analysis.Inhaled antibiotics alone versus intravenous antibiotics aloneOnly one trial (n = 18) reported a perceived improvement in lifestyle (quality of life) in both groups (very low-quality of evidence). Neither trial reported on time off work or school. Both trials measured lung function, but there was no difference reported between treatment groups (very low-quality evidence). With regards to our secondary outcomes, one trial (n = 18) reported no difference in the need for additional antibiotics and the second trial (n = 59) reported on the time to next exacerbation. In neither case was a difference between treatments identified (both very low-quality evidence). The single trial (n = 18) measuring adverse events and sputum microbiology did not observe any in either treatment group for either outcome (very low-quality evidence).Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics aloneNeither trial reported on quality of life or time off work or school. Both trials measured lung function, but found no difference between groups in forced expiratory volume in one second (one trial, n = 28, very low-quality evidence) or vital capacity (one trial, n = 62). Neither trial reported on the need for additional antibiotics or the time to the next exacerbation; however, one trial (n = 28) reported on hospital admissions and found no difference between groups. Both trials reported no difference between groups in adverse events (very low-quality evidence) and one trial (n = 62) reported no difference in the emergence of antibiotic-resistant organisms (very low-quality evidence). AUTHORS' CONCLUSIONS: There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.


Assuntos
Antibacterianos/administração & dosagem , Fibrose Cística/complicações , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Administração por Inalação , Amicacina/administração & dosagem , Carbenicilina/administração & dosagem , Ceftazidima/administração & dosagem , Fibrose Cística/microbiologia , Progressão da Doença , Volume Expiratório Forçado , Humanos , Injeções Intravenosas , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Ticarcilina/administração & dosagem , Tobramicina/administração & dosagem
19.
Artigo em Inglês | MEDLINE | ID: mdl-30150476

RESUMO

Inducible expression of L1 and L2 ß-lactamases is the principal mechanism responsible for ß-lactam resistance in Stenotrophomonas maltophilia Ticarcillin-clavulanate (TIM) is one of the few effective ß-lactams for S. maltophilia treatment. Clavulanate (CA) is a ß-lactamase inhibitor that specifically targets class A, C, and D ß-lactamases. In view of the presence of class B L1 ß-lactamase, it is of interest to elucidate why TIM is valid for S. maltophilia treatment. The L1-L2 allelic variation and TIM susceptibilities of 22 clinical isolates were established. Based on L1 and L2 protein sequences and TIM susceptibility, three L1-based phylogenetic clusters (L1-A, L1-B, and L1-C) and three L2-based phylogenetic clusters (L2-A, L2-B1, and L2-B2) were classified. The contribution of each L1- and L2-based phylogenetic cluster to ticarcillin (TIC) and TIM susceptibility was investigated. All the L1s and L2s tested contributed to TIC resistance. The L1s tested were inert to CA; nevertheless, the sensitivities of L2s to CA were widely different. In addition, the genetic organizations upstream of the L1 gene varied greatly in these isolates. At least three different L1 promoter structures (K279a type, D457 type, and none) were found among the 22 isolates assayed. The differences in the L1 promoter structure had a great impact on TIC-induced L1 ß-lactamase activities. Collectively, the L1 promoter activity in response to TIC challenge and L2 susceptibility to CA are critical factors determining TIM susceptibility in S. maltophilia.


Assuntos
Ácido Clavulânico/farmacologia , Variação Genética/genética , Regiões Promotoras Genéticas/genética , Stenotrophomonas maltophilia/genética , Ticarcilina/farmacologia , beta-Lactamases/genética , Alelos , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Humanos , Testes de Sensibilidade Microbiana/métodos , Filogenia , Stenotrophomonas maltophilia/efeitos dos fármacos , beta-Lactamas/farmacologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-29775394

RESUMO

This study was performed to investigate the mineralization of ticarcillin in the artificially prepared aqueous solution presenting ticarcillin contaminated waters, which constitute a serious problem for human health. 81.99% of total organic carbon removal, 79.65% of chemical oxygen demand removal, and 94.35% of ticarcillin removal were achieved by using eco-friendly, time-saving, powerful and easy-applying, subcritical water oxidation method in the presence of a safe-to-use oxidizing agent, hydrogen peroxide. Central composite design, which belongs to the response surface methodology, was applied to design the degradation experiments, to optimize the methods, to evaluate the effects of the system variables, namely, temperature, hydrogen peroxide concentration, and treatment time, on the responses. In addition, theoretical equations were proposed in each removal processes. ANOVA tests were utilized to evaluate the reliability of the performed models. F values of 245.79, 88.74, and 48.22 were found for total organic carbon removal, chemical oxygen demand removal, and ticarcillin removal, respectively. Moreover, artificial neural network modeling was applied to estimate the response in each case and its prediction and optimizing performance was statistically examined and compared to the performance of central composite design.


Assuntos
Simulação por Computador , Ticarcilina/metabolismo , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodos , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/farmacologia , Redes Neurais de Computação , Oxirredução , Reprodutibilidade dos Testes , Temperatura , Ticarcilina/isolamento & purificação , Fatores de Tempo , Poluentes Químicos da Água/isolamento & purificação
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