Hierarchical antibiotic delivery system based on calcium phosphate cement/montmorillonite-gentamicin sulfate with drug release pathways.

Antibiotic-loaded calcium phosphate cement (CPC) has emerged as a promising biomaterial for drug delivery in orthopedics. However, there are problems such as the burst release of antibiotics, low cumulative release ratio, inappropriate release cycle, inferior mechanical strength, and poor anti-collapse properties. In this research, montmorillonite-gentamicin (MMT-GS) was fabricated by solution intercalation method and served as the drug release pathways in CPC to avoid burst release of GS, achieving promoted cumulative release ratios and a release cycle matched the time of inflammatory response. The results indicated that the highest cumulative release ratio and release concentration of GS in CPC/MMT-GS was 94.1 ± 2.8 % and 1183.05 µg/mL, and the release cycle was up to 504 h. In addition, the hierarchical GS delivery system was divided into three stages, and the kinetics followed the Korsmeyer-Peppas model, the zero-order model, and the diffusion-dissolution model, respectively. Meanwhile, the compressive strength of CPC/MMT-GS was up to 51.33 ± 3.62 MPa. Antibacterial results demonstrated that CPC/MMT-GS exhibited excellent in vitro long-lasting antibacterial properties to E. coli and S. aureus. Furthermore, CPC/MMT-GS promoted osteoblast proliferation and exhibited excellent in vivo histocompatibility. Therefore, CPC/MMT-GS has favorable application prospects in the treatment of bone defects with bacterial infections and inflammatory reactions.

Nlmixr2 Versus NONMEM: An Evaluation of Maximum A Posteriori Bayesian Estimates Following External Evaluation of Gentamicin and Tobramycin Population Pharmacokinetic Models.

The objective of this project is to compare the results of the same study carried out on NONMEM and nlmixr2. This analysis consists of evaluating previously published population pharmacokinetic models of gentamicin and tobramycin in our population of interest with sparse concentrations. A literature review was performed to determine the gentamicin and tobramycin models in critically ill adult patients. In parallel, gentamicin and tobramycin dosing data, information on the treatment, the patient, and the bacteria were collected retrospectively in 2 Quebec establishments. The external evaluations were previously performed using NONMEM Version 7.5. Model equations were rewritten with R, and external evaluations were performed using nlmixr2. Predictive performance was assessed based on the estimation of bias and imprecision of the prediction error for maximum a posteriori (MAP) Bayesian PK parameter and observed concentrations. Comparison between nlmixr2 and NONMEM was performed on 4 gentamicin and 3 tobramycin population pharmacokinetic models. Compared to NONMEM, for gentamicin and tobramycin clearance and central volume of distribution, nlmixr2 produced individual pharmacokinetic parameters with bias values ranging from -32.5% to 5.67% and imprecision values ranging from 6.33% to 32.5%. Despite these differences, population bias and imprecision for sparse concentrations were low and ranged from 0% to 5.3% and 0.2% to 6.5%, respectively. The external evaluations performed with both software packages resulted in the same interpretation in terms of population predictive performance for all 7 models. Nlmxir2 showed comparable predictive performance with NONMEM with sparse concentrations that are, at most, sampled twice within a single dose administration (peak and trough).

Predictive Performance of a Gentamicin Pharmacokinetic Model in Term Neonates with Perinatal Asphyxia Undergoing Controlled Therapeutic Hypothermia.

BACKGROUND: Model validation procedures are crucial when population pharmacokinetic (PK) models are used to develop dosing algorithms and to perform model-informed precision dosing. We have previously published a population PK model describing the PK of gentamicin in term neonates with perinatal asphyxia during controlled therapeutic hypothermia (TH), which showed altered gentamicin clearance during the hypothermic phase dependent on gestational age and weight. In this study, the predictive performance and generalizability of this model were assessed using an independent data set of neonates with perinatal asphyxia undergoing controlled TH. METHODS: The external data set contained a subset of neonates included in the prospective observational multicenter PharmaCool Study. Predictive performance was assessed by visually inspecting observed-versus-predicted concentration plots and calculating bias and precision. In addition, simulation-based diagnostics, model refitting, and bootstrap analyses were performed. RESULTS: The external data set included 323 gentamicin concentrations of 39 neonates. Both the model-building and external data set included neonates from multiple centers. The original gentamicin PK model predicted the observed gentamicin concentrations with adequate accuracy and precision during all phases of controlled TH. Model appropriateness was confirmed with prediction-corrected visual predictive checks and normalized prediction distribution error analyses. Model refitting to the merged data set (n = 86 neonates with 935 samples) showed accurate estimation of PK parameters. CONCLUSIONS: The results of this external validation study justify the generalizability of the gentamicin dosing recommendations made in the original study for neonates with perinatal asphyxia undergoing controlled TH (5 mg/kg every 36 or 24 h with gestational age 36-41 and 42 wk, respectively) and its applicability in model-informed precision dosing.

Pharmacokinetics of Locally Applied Antibiotic Prophylaxis for Implant-Based Breast Reconstruction.

Importance: Antibiotic irrigation of breast implants is widely used internationally, but no clinical study has investigated the pharmacokinetics of antibiotic prophylaxis in the breast implant pocket. Objectives: To evaluate how long locally applied gentamicin, cefazolin, and vancomycin concentrations in the implant pocket remain above the minimum inhibitory concentration (MIC) for the most common bacterial infections and to measure systemic uptake. Design, Setting, and Participants: This prospective cohort study was performed at the Department of Plastic Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark, between October 25, 2021, and September 22, 2022, among 40 patients undergoing implant-based breast reconstruction who were part of the ongoing BREAST-AB trial (Prophylactic Treatment of Breast Implants With a Solution of Gentamicin, Vancomycin and Cefazolin Antibiotics for Women Undergoing Breast Reconstructive Surgery: a Randomized Controlled Trial). Patients were randomized to receive locally applied gentamicin, cefazolin, and vancomycin or placebo. Samples were obtained from the surgical breast drain and blood up to 10 days postoperatively. Exposures: The breast implant and the implant pocket were irrigated with 160 µg/mL of gentamicin, 2000 µg/mL of cefazolin, and 2000 µg/mL of vancomycin in a 200-mL saline solution. Main Outcomes and Measures: The primary outcome was the duration of antibiotic concentrations above the MIC breakpoint for Staphylococcus aureus according to the Clinical and Laboratory Standards Institute: gentamicin, 4 µg/mL; cefazolin, 2 µg/mL; and vancomycin, 2 µg/mL. Secondary outcomes included the time above the MIC for Pseudomonas aeruginosa and other relevant bacteria, as well as systemic uptake. Results: The study included 40 patients (median age, 44.6 years [IQR, 38.3-51.4 years]; median body mass index, 23.9 [IQR, 21.7-25.9]) with a median number of 3 drain samples (range, 1-10 drain samples) and 2 blood samples (range, 0-6 blood samples). Vancomycin and cefazolin remained above the MIC for S aureus significantly longer than gentamicin (gentamicin, 0.9 days [95% CI, 0.5-1.2 days] for blood samples vs 6.9 days [95% CI, 2.9 to 10.9 days] for vancomycin [P = .02] vs 3.7 days [95% CI, 2.2-5.2 days] for cefazolin [P = .002]). The gentamicin level remained above the MIC for P aeruginosa for 1.3 days (95% CI, 1.0-1.5 days). Only cefazolin was detectable in blood samples, albeit in very low concentrations (median concentration, 0.04 µg/mL [range, 0.007-0.1 µg/mL]). Conclusions and Relevance: This study suggests that patients treated with triple-antibiotic implant irrigation during breast reconstruction receive adequate prophylaxis for S aureus and other common implant-associated, gram-positive bacteria. However, the protection against P aeruginosa may be inadequate.

Resistencia a gentamicina en infecciones urinarias por E coli en niños / Gentamicin resistant E coli as a cause of urinary tract infections in children

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Parámetros farmacocinéticos de gentamicina en recién nacidos de término: ¿Es necesario monitorizar en forma sistemática sus concentraciones plasmáticas? / Gentamicin pharmacokinetics in term newborn: ¿Is it necessary to systematically monitor plasmatic levels?

Background: Gentamicin is indicated as empiric treatment for neonatal sepsis. Plasmatic levels dosification of gentamicin is a common practice. The relationship between peak plasma concentration (Cmáx) with minimum inhibitory concentration (MIC) (Cmáx/MIC) is the parameter that best predicts treatment efficacy. Aim: To determine pharmacokinetics of gentamicin in term newborn infants. Methods: Term newborn infants receiving gentamicin, without critical illness in which plasmatic levels of gentamicin was performed were included. Elimination clearance (Cl) elimination half-life (t½) and volume of distribution (Vd) were calculated. In each case the value of Cmax/MIC parameter was calculated, considering a MIC value of 1 μg/mL for Escherichia coli. Results: Thirteen newborns were included. The mean PK values were Cl: 0.26 mL/hour, Vd: 0.54 L/kg and t½: 6.8 h. Cmax/MIC was > 8 in 6 newborns. Conclusions: Pharmacokinetic parameters of gentamicin are predictable in term newborn infants. With gentamicin doses normally used Cmax/MIC values reached 8 in 6 newborns. It is necessary to review the usefulness of plasma drug monitoring and gentamicin dosage in this group of newborns.

Introducción: Gentamicina es utilizada como tratamiento empírico en la sepsis neonatal. El monitoreo de su concentración plasmática es una práctica frecuente. La relación entre la concentración plasmática máxima (Cmax) y la concentración inhibitoria mínima (Cmax/ CIM) es el parámetro que mejor predice la eficacia. Objetivo: Determinar los parámetros farmacocinéticos (FC) de gentamicina en recién nacidos (RN) de termino. Material y Métodos: Se incluyeron RN de término, sin enfermedad crítica, en tratamiento con gentamicina (4 mg/kg/24 h) en los que se realizó monitoreo de su concentración plasmática. Se determinaron: clearence de eliminación (Cl), vida media de eliminación (t½) y volumen de distribución (Vd). Se estimó la Cmax/CIM, considerando una CIM de 1 μg/mL para Escherichia coli. Resultados: Participaron 13 RN. La media de Cmax fue 8,19 μg/mL y de Cmin 0,73 μg/mL. La media de los parámetros farmacocinéticos fue: Cl 0,26 mL/h, Vd 0,54 L/kg, t½ 6,8 h. La razón Cmáx/CIM fue ≥ 8 en 6 de los 13 RN. Conclusiones: Los parámetros FC de gentamicina en RN de término, sin enfermedad crítica, son predecibles. La posología habitual no permitió obtener valores de Cmax/CIM > 8 en todos los casos. Es necesario revisar la necesidad de monitorizar su concentración plasmática en forma sistemática y la posología de gentamicina en este grupo de pacientes.

Clinical pharmacology of gentamicin in neonates: regimen, toxicology and pharmacokinetics / Farmacologia clínica da gentamicina em neonatos: modalidades de uso, toxicologia e farmacocinética

Gentamicin is an aminoglycoside antibiotic. It kills bacteria by inhibiting protein synthesis and to some extent by lysing the cell envelope. Gentamicin is frequently the first choice drug because of its reliability, but also because of the long experience with its use. In combination with β-lactam antibiotics it is recommended for the treatment of sepsis or pneumonia and is active against P. aeruginosa, Enterobacter, Klebsiella and Serratia. However, gentamicin is ototoxic and nephrotoxic. The human mitochondrial genetic variant m.1555A > G has been reported to be an important cause of non-syndromic hereditary hearing dysfunction and may cause permanent hearing loss. Even short courses of gentamicin therapy in healty newborn infants can lead to abnormalities of auditory function. It is active against very resistant bacteria at peak concentrations (> 10 mg/l) that are high enough to be potentially toxic. For safe therapeutic efficacy, peak plasma concentrations of gentamicin should range from 4 to 10 mg/l; but trough concentrations, immediately before a new drug administration, must be lower that 2 mg/L to avoid toxic effects. Pharmacokinetic parameters vary considerably in infants. Half-life ranges from 5.4 to 10.0 hours, clearance 0.50 to 1.71 ml/h/kg and distribution volume from 0.4 to 0.7 l/kg. Preterm infants have a longer half-life than full-term infants. Thus, it is mandatory to monitor gentamicin serum concentrations whenever infants are treated for 48 hours or more.

A gentamicina é antibiótico do grupo dos aminoglicosídeos. Destrói bactérias por inibição de síntese proteica e, em certa medida, por lise do envelope celular. A gentamicina é a droga de primeira escolha por causa de sua atividade confiável e em virtude de longa experiência com seu uso. Em combinação com antibióticos β-lactâmicos é recomendada para o tratamento de septicemia ou pneumonia e é ativa contra P. aeruginosa, Enterobacter, Klebsiella e Serratia. No entanto, a gentamicina é ototóxica e nefrotóxica. A variante genética mitocondrial humana m.1555A > G é tida como importante causa de disfunção auditiva hereditária não-sindrômica e pode causar perda permanente da audição. Até mesmo procedimentos terapêuticos de gentamicina de curta duração em recém-nascidos sadios podem levar a anormalidades da função auditiva. É ativa contra algumas espécies de bactérias apenas em concentrações de pico (> 10 mg/l) que são suficientemente altas para produzirem efeitos tóxicos. A gentamicina deve cair a concentrações mínimas menores que 2 mg/l para evitar efeitos tóxicos. Para produzir efeitos terapêuticos, as concentrações plasmáticas máximas de gentamicina deve variar de 4 a 10 mg/l. Os parâmetros farmacocinéticos variam consideravelmente em lactentes. A meia-vida varia entre 5,4-10,0 horas, o "clearance" varia entre 0,50 e 1,71 ml/h/kg e volume de distribuição de 0,4-0,7 l/kg. Em prematuros a meia-vida é mais longa do que a de crianças nascidas a termo. Por esses motivos, sempre que lactentes são tratadas durante 48 horas ou mais, monitorizar as concentrações séricas de gentamicina é essencial.

Effect of Gentamicin on kidney in developing chicks

Gentamicin is one of the most extensively used aminoglycoside antibiotic. The study was planned to study any teratogenic effect of Gentamicin as a result of single dose injection given therapeutically or accidentally. Sixty fertilized eggs of white leghorn species were incubated for 20 days and divided into treated (n=30) and control (n=30) groups. Eggs of treated and control groups were injected with 0.2mg of Gentamicin sulphate and ‘Sterilized water for injection’ respectively on the 4th day of incubation. On the 20th day, the chick embryos were extracted and then dissected to remove the kidneys. No effect of Gentamicin was found on either the mortality of chick embryos or the gross appearance of the newborn chicks and kidney as compared to the control group. The mean weight of both right and left kidneys was found less in treated group, though not statistically significant. On light microscopy, various changes were noticed in both control and treated groups which included glomerular enlargement and hypercellularity, glomerular congestion, mesangial proliferation and cystic dilatation and cloudy swelling of proximal convoluted tubules and infiltration by inflammatory cells and congestion of blood vessels. Statistical analysis revealed that all these changes except glomerular congestion were higher in treated group in comparison to control group, either in both the kidneys or in one-sided kidneys (AU)

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Resistencia antimicrobiana en aislados clínicos de Pseudomonas aeruginosa / Antimicrobial resistance in clinical patterns of Pseudomonas aeruginosa

Pseudomonas aeruginosa es un microorganismo oportunista frecuentemente implicado en infecciones de origen nosocomial que presenta resistencia natural y adquirida a muchos de los antimicrobianos de uso clínico. Se llevo a cabo un estudio de resistencias a antimicrobianos de 3.029 aislamientos de P. aeruginosa de enfermos intra y extrahospitalarios en el periodo 2005-2010. La metodología utilizada fue, el método semiautomatizado WIDER I (Soria Melguizo), para la identificación de las especies y para el estudio de sensibilidades a antimicrobianos. Se consideraron los criterios de sensibilidad y resistencia recomendados por el grupo MENSURA. En nuestro hospital existe un mantenimiento relativo de la sensibilidad antimicrobiana de P. aeruginosa en el periodo 2005-2010, con un aumento de esta en amikacina, gentamicina y cefalosporinas. Existen diferencias de porcentajes de sensibilidades entre las cepas de origen intrahospitalario y extrahospitalario, salvo para fosfomicina y tobramicina. Destacamos la importancia de realizar estudios locales de la sensibilidad y resistencias de P. aeruginosa en cada zona, de forma periódica para poder valorar las diferentes pautas terapéuticas, no siendo posible extrapolar los datos de las diferentes regiones españolas(AU)

Pseudomonas aeruginosa is an opportunistic microorganism that is frequently the cause of nosocomial infections. Multiple mechanisms are involved in its natural and acquired resistance to many of the antimicrobial agents commonly used in clinical practice. We performed an antibiotic resistance study on P. aeruginosa isolated from intrahospitalary and extrahospitalary samples between 2005 and 2010 years. We included in the study a global amount of 3,029 P. aeruginosa isolates from clinical samples received at University Hospital Reina Sofia. Microbiology Service in Córdoba (Spain). Semiautomatic system WIDER I for strains identification and sensibility testing was employed. We considered susceptibility and resistance criteria recommended by MENSURA group. Results of the analysis showed that P. aeruginosa maintanied similar levels of antimicrobial susceptibility during the period 2005-2010, with increased susceptibility to amikacin, gentamicin and cefalosporins. There were also important differences in the degree of susceptibility between intrahospital and extrahospital strains during 2010 year, except for tobramicin and fosfomycin. The intrahospital difference in susceptibility was also evaluated, emphasizing the importance of periodically surveillance of susceptibility and resistance patterns of P. aeruginosa, in each setting in order to evaluate different therapeutic guidelines, because it is not always advisable to extrapolate data from different regions(AU)

Valoración de la resistencia a gentamicina tras su uso diario en curas de catéteres peritoneales / Assessing resistance to gentamicin following its daily use to treat peritoneal catheter infections

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Gentamycin inhibits the growth of Malassezia pachydermatis in culture

AntecedentesMalassezia pachydermatis es una levadura de gran interés tanto en medicina humana como en veterinaria.ObjetivosConocer si la adición de gentamicina a los medios micologicos más comunes era capaz de inhibir el crecimiento de M. pachydermatis.MétodosSe estudiaron 20 cepas de M. pachydermatis en medios micológicos con gentamicina a diferentes concentraciones.ResultadosTodos los aislamientos se inhibieron con altas concentraciones de gentamicina.ConclusionesEl uso de placas con altas concentraciones de gentamicina puede llevar a resultados falsamente negativos en cultivo y a una errónea clasificación de M. pachydermatis como especie lípido-dependiente. Estas observaciones podrían llegar a tener dos aplicaciones hipotéticas: i) en veterinaria, la gentamicina tópica podría ser eficaz en procesos como la dermatitis o la otitis externa, y ii) en humanos, podría ser una terapia (“antibiotic-lock”) para las infecciones por Malassezia relacionadas con el uso de catéteres(AU)

BackgroundMalassezia pachydermatis is a yeast of importance in both veterinary and human medicine.AimsTo know if M. pachydermatis grow on micological media with high concentrations of gentamycin.MethodsTwenty M. pachydermatis strains were streaked on Sabouraud Dextrose Agar plates with different concentrations of gentamycin.ResultsAll isolates were inhibited when high concentrations of gentamycin were added.ConclusionsThe use of plates with high concentrations of gentamycin can lead to some important misdiagnoses: firstly, false-negative cultures, and secondly, an erroneous classification of M. pachydermatis as a lipid-dependent species. Morever, all of this could be useful in two therapeutic fields: i) in animals, topical gentamycin could be an efficacious treatment for a disease such as external otitis in dogs; ii) in humans, we hypothesize that gentamycin could be regarded as a possible therapy (“antibiotic-lock”) for catheter-associated Malassezia spp. infections(AU)

Farmacocinética del metronidazol y la gentamicina en dosis única preoperatoria para profilaxis antibiótica quirúrgica en cirugía colorrectal / The pharmacokinetics of metronidazole and gentamicin in a single preoperative dose as antibiotic prophylaxis in colorectal surgery

Objetivo: Describir, en pacientes sometidos a cirugía colorrectal(CCR), la farmacocinética de una dosis única preoperatoria de metronidazol1.500 mg más gentamicina 240 mg como pauta profiláctica,y estimar su efectividad de acuerdo con parámetros subrogados farmacodinámicosy microbiológicos.Método: Treinta y seis pacientes sometidos a CCR aceptaron su participaciónen el estudio. De cada uno de ellos se tomaron tres muestrasde sangre: Cmáx, 15 min tras finalizar la infusión de la mezcla,CfinIQ al finalizar la cirugía, y Cmín entre las 12 y 24 h posteriores a laadministración. Se determinaron las concentraciones de metronidazoly gentamicina en cada muestra y se estimaron los parámetrosfarmacocinéticos (Vd: volumen de distribución, Cl: aclaramientoplasmático). Para el metronidazol, se consideraron efectivas concentracionessuperiores a 8 mg/ml, y para la gentamicina, Cmáx superioresa 9 mg/ml y cocientes de inhibición superiores a 8.Resultados: Todas las concentraciones de metronidazol, tantoCmáxMTZ como CfinIQMTZ fueron superiores a 8 mg/ml, y todaslas CmáxGEN, superiores a 9 mg/ml. El CIGEN fue de 13,8 ± 3,8, con ningúnvalor individual inferior a 8. Para el metronidazol, se estimó unVd de 0,68 ± 0,2 l/kg y un Cl de 3,15 ± 1,20 l/h, y para la gentamicina,el Vd fue de 0,23 ± 0,06 l/kg, y el Cl, de 4,71 ± 1,95 l/h.Conclusión: En pacientes sometidos a CCR la intervención quirúrgicano modifica significativamente la farmacocinética del metronidazoly la gentamicina respecto a otros grupos de pacientes. La profilaxisen dosis única prequirúrgica permite alcanzar, para ambosantimicrobianos, concentraciones de magnitud suficiente para garantizarsu efectividad clínica

Objective: To describe, in patients undergoing colorectal surgery(CRS), the pharmacokinetics of a single, prophylactic preoperativedose of 1,500 mg of metronidazole plus 240 mg gentamicin and measureits efficacy in accordance with the accepted pharmacodynamicand microbiological parameters.Method: Thirty-six patients undergoing CRS agreed to participate inthe study. Three blood samples were taken from each. Cmax 15 minutesafter finishing the infusion of the mixture, CfinIQ on finishing thesurgery, and Cmin between 12 and 24 hours post-administration. Theconcentrations of metronidazole and gentamicin in each simplewere measured and the pharmacokinetic parameters were estimated(dV- distribution volume , Cl-plasma clearance). For the metronidazole,concentrations in excess of 8 mg/ml were considered effective,and for gentamicin, Cmax in excess of 9 mg/ml and inhibitionquotients above 8.Results: All the concentrations of metronidazole, both CmaxMTZ andCfinIQMTZ were above 8 mg/ml and all the CmaxGEN in excess of9 mg/ml. The CIGEN was 13.8±3.8, with no individual value below 8.For the metronidazole, a dV of 0.68±0.2 l/kg was estimated and a Clof 3.15±1.20 l/h and for the gentamicin, the dV as 0.23±0.06 l/kgand the Cl was 4.71±1.95 l/h.Conclusion: In patients undergoing CRS, surgical intervention didnot significantly modify the pharmacokinetics of metronidazole orgentamicin in comparison with other groups of patients. The prophylaxisusing a single, pre-surgical dose enables the achievement, forboth antimicrobial agents, concentrations of a sufficient size to guarantee clinical efficacy

La profilaxis con gentamicina disminuye la morbi-mortalidad infecciosa bacteriana causada por el catéter venoso central permanente tunelizado / No disponible

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Estudio de cesión de cefalosporinas incluidas en cementos oseos acrílicos / Release assay of cephalosporyns included in acrylic bone cements

El progresivo aumento de la esperanza de vida ha originado un notable incremento de las patologías degenerativas óseas que requieren implatación de prótesis. Estas intervenciones quirúrgicas conllevan en ocasiones serias complicaciones entre las que cabe destacar las infecciones bacterianas. La gentamicina es el agente antimicrobiano de elección incluido en los cementos acrílicos para la prevención de dichas osteomielitis. Sin embargo, debido a la creciente aparición de cepas bacterianas resistentes a la gentamicina, en este trabajo se propone la utilización de terapia local antibacteriana con otros antibióticos del grupo de las cefalosporinas como son la ceftazidima y la cefotaxima: En el presente estudio, se validan los métodos analíticos utilizados para la cuantificación de las cefalosporinas, que se basan en la formación de complejos coloreados tras la reacción de la ceftazidima o cefotaxima con el cloruro de paladio como reactivo y la posterior determinación espectrofotométrica UV-Vis de los mismos a las longitudes de onda de 354 y 280 nm respectivamente. Posteriormente, se ha realizado un estudio de cesión "in vitro"de estos antibióticos tras su inclusión en cementos óseos acrílicos de polimetilmetacrilato (PMMA) (AU)

Resistência a drogas e produçäo de bacteriocinas em linhagens de Escherichia coli e Enterobacter isoladas de indivíduos hospitalizados / Drug resistance and colicin production by Escherichia coli and Enterobacter isolated from hospitalized humans

Escherichia coli e Enterobacter foram isolados de grupos de indivíduos hospitalizados (H), recém-hospitalizados (P), sendo estudados quanto ao perfil de resistência às drogas ampicilina, cefalotina, cloranfenicol, estreptomicina, tetraciclina, gentamicina, canamicina e ao bicloreto de mercúrio, por meio da técnica de diluiçäo em meio sólido, e quanto à produçäo de colicinas. A resistência aos antibióticos betalactâmicos foi maior nas amostras isoladas dos grupos de portadores näo-hospitalizados (P) (modelo ampicilina-cefalosporina), em especial para o gênero Enterobacter. Por outro lado, a freqüencia das amostras colicinogênicas descresceu no grupo H em comparaçäo com amostras colicinogênicas decresceu no grupo H em comparaçäo com as amostras do grupo P. É provável que, em ambientes seletivos pela presença de elevadas concentraçöes de antibióticos, as linhagens portadoras de fenótipos sejam selecionadas e a colicinogênese, deslocada ou substituída, sendo mantida em ambientes näo-seletivos, devido à competitividade as linhagens de uma mesma espécie

Puesta al día en aspectos microbiológicos de enterococos / Update on microbiological topics of enterococci

Clinical microbiology laboratories are faced with the challenge of accurate detection of emerging antibiotic resistance among several important gram positive bacterial pahtogens. For enterococci, vancomycin and ampicillin resistance was significantly more prevalent among E. faecium than among E. faecalis. This finding undescores the importance of identifying enterococcal isolates to species for the sake of more precise surveillance. Enterococci are identified to the genus level with tests like pyrrolidine amilaridase, bile esculin and salt tolerance, but in some instances, species identification is desirable. Initial characterization of the species, as well as the antimicrobial susceptibility testing in enterococci, will be discussed in this report

Parámetros Usados en la Prescripción de Amicacina y Gentamicina en la Unidad Pediátrica de un Hospital de Tercer Nivel / Parameters Used in the Prescription of Amikacin and Gentamicin in the Pediatric Unit of a Third-Level Hospital

Se estudió retrospectiva y descriptivamente un grupo de 105 historias clínicas de pacientes pediátricos hospitalizados y con indicación de administración de un aminoglucósido en la Unidad de Pediatría de la Clínica Henrique De La Vega de la ciudad de Cartagena (Colombia), durante el año de 1994. Se evaluó el número de pacientes que recibieron la dosis ideal del aminoglucósido con base en la edad, peso, talla, función renal (calculada con base en la creatinina sérica) y niveles séricos de aminoglucósidos. Sólo en nueve casos (8.57 por ciento) se determinó la creatinina sérica inicial, de los cuales cinco (4.76 por ciento) tuvieron dosificación adecuada y dos insuficiente (1.91 por ciento). Los 96 restantes recibieron dosis empírica y sólo en 20 casos (19.04 por ciento) se usó el aminoglucásido con intervalo de 24 h. En ningún caso se reportaron niveles séricos del aminoglucósido, ni se utilizó dosis de carga. De los resultados se deduce que en esta clínica no se toma en cuenta la depuración de creatinina para la dosificación del aminoglucósido, como tampoco se controlan los niveles séricos de los mismos, que son indispensables para una buena vigilancia farmacológica

Efectos de la gentamicina y kanamicina a dosis terapéuticas en el desarrollo del oído interno de la ratas / Gentamicin and Kanamicin effects on the development of the internal ear in rat

Los aminoglucósidos son antibióticos de acción bactericida a nivel ribosomal en la subunidad 30s, en donde se inhiben la síntesis proteica y disminuye la fidelidad de la traslación del RNAm. La ototoxicidad es el resultado de la destrucción progresiva de células sensoriales a nivel coclear y vestibular. El objetivo del estudio fue determinar los cambios histopatológicos en el desarrollo del oído interno en embriones de rata al administrarse gentamicina a dosis de 3.5 mg/Kg/día y 7 mg/Kg/día por 21 días y kanamicina a dosis de 7 mg/Kg/día y 15 mg/Kg/día por 21 días. Los productos fueron sacrificados a los 7 y 14 días de gestación e inmediatamente después de termianr el período de gestación. Se observó un detenimiento del desarrollo y crecimiento de las estructuras del oído interno. La gentamicina causó mayores daños a nivel vestibular y la kanamicina a nivel coclear. Los principales cambios cocleares encontrados fueron degeneración de las células externas e internas hacía la porción basal, así como colapso de las rampas vestibular y timpánica. Los principales cambios vestibulares fueron: falta de desarrollo de la cresta ampular, ausencia de células ciliadas e hipodesarrollo de canales semicirculares

Comparison between sprague-dawley and wistar rats as an experimental model of pharmacokinetic alterations induced by spinal cord injury

Two strains of rats, Sprague-Dawley and Wistar, were assayed in order to determine which strain is the more suitable experimental model for the study of pharmacokinetic alterations inuced by spinal cord injury. Animals were submitted to spinal cord contusion at the T8-T9 level by the weight drop method. A single acetaminophen oral dose (100 mg/kg) was administered 24 h after injury and blood samples were drawn for a period of 4 h. Acetaminophen concentration in whole blood was determined by high performance liquid chromatography and pharmacokinetic parameters were estimated. For both strains, Cmax and AUC were significantly lower, whereas tmax remained uchanged, in injured animals compared to sham-injured controls. Circulating acetaminophen concentrations were higher; therefore, pharmacokinetic alterations were more easily discerned, in Sprague-Dawley than in Wistar rats. It is concluded that the Sprague-Dawley strain is a more suitable model for the study of pharmacokinetic alternations induced by spinal cord injury

Cultivo de antimicrobianos en pacientes con sepsis del pie diabético / Cultures and antimicrobial agents used in patients coursing with diabetic foot injuries

Objetivo: Evaluar la repercusión del uso empírico de antimicrobianos y con cultivos, en la morbilidad y estancia hospitlaria en el pie diabético. Diseño: Estudio prolectivo, comparativo y observacional. Sede: División de cirugía general. Centro Médico Nacional, IMSS, en Veracruz, Ver. Sujetos de estudio: De julio de 1993 a marzo de 1994 se estudiaron 63 pacientes con lesiones sépticas del pie por diabetes mellitus tipo 2. Principales mediciones: Comparación de la morbilidad y la estancia hospitalaria con : 1) el tratamiento empírico: monoterapia, doble y triple esquema; 2) la congruencia con el germen cultivado: (subgrupos del A al E) y 3) la respuesta del cirujano a los resultados del cultivo: (subgrupos del 1 al 4). Análisis estadístico: Prueba de chi cuadrada o exacta de Fisher y ANOVA. Resultados: El principal esquema utilizado fue el doble (68 po ciento) y la monoterapia (19 por ciento). No se cubrió el germen aislado (GC) en el 62 por ciento; fue excesivo (GA) en el 31 por ciento; inespecífico (GD) en un caso, y sin pacientes en los grupos B (adecuado) y E(antibiótico redundante). El cirujano no modificó el esquema empírico en dos casos (G1), adicionó en tres (G2), los cambió correctamente en siete (G3) e incorrectamente en uno (G4). La morbilidad y la estancia hospitalaria fueron independientes del uso empírico de uno o más antibióticos y de las modificaciones del cirujano ante el germen aislado (p> 0.05). Conclusiones: La monoterapia de amplio espectro o el régimen combinado presentaron complicaciones y estancia hospitalaria similares. Estas fueron independientes de los cultivos realizados y los ajustes del cirujano al intentar cubrir el germen aislado