¿Cumplimos el objetivo de farmacocinética y farmacodinamia en pacientes críticos que reciben antibióticos betalactámicos? / Do we meet the goal of pharmacokinetics and pharmacodynamics in critically ill patients receiving beta-lactam antibiotics?

Introducción: Los pacientes críticamente enfermos presentan cambios fisiopatológicos que alteran las concentraciones de antibióticos betalactámicos. El objetivo fue determinar si las dosis de uso habitual en pacientes críticos alcanzan las concentraciones asociadas con mayor actividad y establecer las variables de PK/PD que se asocian con concentraciones subóptimas de antibiótico.Métodos: Estudio prospectivo realizado en una terapia intensiva de adultos en un periodo de 13 meses. Se incluyeron pacientes que recibieron cefazolina, ceftriaxona, ceftazidima o meropenem. Se realizó dosaje de concentración de antibiótico en plasma en el 50% del intervalo de dosis. Se calculó la concentración de antibiótico libre y se comparó con el objetivo 50% fT>CIM y el objetivo 50% fT>CIM x 4 para los microorganismos susceptibles definidos, según criterios del CLSI. Se comparó el grupo de pacientes que cumplió el objetivo 50% fT>CIM x 4 con el que no, en términos de variables de PK/PD.Resultados: Se incluyeron 29 determinaciones y 55 comparaciones. En el 92,7% de los casos se alcanzó el objetivo 50% fT>CIM y en el 61,8% el objetivo 50% fT>CIM x 4. En el peor escenario, es decir considerando el germen susceptible con CIM más alta, solo el 48,3% de los pacientes cumplieron el objetivo 50% fT>CIM x 4. Los pacientes que no llegaron al objetivo 50% fT>CIM x 4 tuvieron mayor RESUMENARTÍCULO ORIGINALaclaramiento renal que los que sí lo hicieron (160 vs 108,5 ml/min/1,73m2, p= 0,01). Conclusiones: un gran porcentaje de pacientes críticos que recibe betalactámicos no alcanza las metas de PK/PD recomendadas en la actualidad

Introduction: critically ill patients have physiopathological changes that upset the concentrations of beta-lactam antibiotics. The aim was to determine if the doses of usual use in critically ill patients reach the concentrations associated with maximal activity and to establish the variables of PK/PD that are associated with suboptimal concentrations of antibiotic. Methods: prospective study conducted in an intensive therapy of adults in a period of 13 months. Patients who received cefazolin, ceftriaxone, ceftazidime or meropenem were included. Dosage of antibiotic concentration in plasma was performed at 50% of the dose interval. The concentration of free antibiotic was calculated and compared with the objective 50% fT>MIC and the objective 50% fT>MIC x 4 for susceptible microorganisms, according to CLSI criteria. The group of patients who met the 50% objective fT>MIC x 4 was compared with the one who did not, in terms of PK/PD variables. Results: 29 determinations and 55 comparisons were included. The objective 50% fT>MIC was reached in 92.7% of the cases and the target 50% fT>MIC x 4 was achieved in 61.8%. In the worst scenario, that is, considering the germ susceptible with MIC higher, only 48.3% of patients met the objective 50% fT>MIC x 4. Patients who did not reach the goal 50% fT>MIC x 4 had greater renal clearance than those who reached the goal (160 vs 108.5 ml/min/1.73m2, p=0.01). Conclusions: a large percentage of critically ill patients receiving beta-lactams do not reach the PK/PD goals recommended nowadays

Interacciones farmacológicas relacionadas con la administración de antibióticos betalactámicos / Drug interactions related to the administration of beta-lactam antibiotics

Los antibióticos betalactámicos son los que más se usan en el tratamientoy profilaxis de las infecciones odontogénicas. Con frecuenciaes necesario prescribir un segundo antibiótico que incremente el efectodel primero. Debido a ello se hizo una revisión de los antibióticos y otros medicamentos que administrados simultáneamente o en forma secuencial con betalactámicos producen efectos deseados (sinergismo, potenciación) o indeseados (antagonismo) o provocan efectos adversos en el organismo.

Beta-lactams are the most commonly used antibiotics in the treatmentand prophylaxis of odontogenic infections. It is often necessary toprescribe a second antibiotic to increase the eff ect of the fi rst. For thisreason, we performed a review of antibiotics and other medicationswhich, when administered simultaneously or sequentially with betalactams,produce desirable (synergism, potentiation) or undesirable(antagonism) eff ects or provoke adverse eff ects in the organism.

Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital

ABSTRACTINTRODUCTION: Monte Carlo simulations have been used for selecting optimal antibiotic regimens for treatment of bacterial infections. The aim of this study was to assess the pharmacokinetic and pharmacodynamic target attainment of intravenous β-lactam regimens commonly used to treat bloodstream infections (BSIs) caused by Gram-negative rod-shaped organisms in a Brazilian teaching hospital.METHODS: In total, 5,000 patients were included in the Monte Carlo simulations of distinct antimicrobial regimens to estimate the likelihood of achieving free drug concentrations above the minimum inhibitory concentration (MIC; fT > MIC) for the requisite periods to clear distinct target organisms. Microbiological data were obtained from blood culture isolates harvested in our hospital from 2008 to 2010.RESULTS: In total, 614 bacterial isolates, including Escherichia coli, Enterobacterspp., Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, were analyzed Piperacillin/tazobactam failed to achieve a cumulative fraction of response (CFR) > 90% for any of the isolates. While standard dosing (short infusion) of β-lactams achieved target attainment for BSIs caused by E. coliand Enterobacterspp., pharmacodynamic target attainment against K. pneumoniaeisolates was only achieved with ceftazidime and meropenem (prolonged infusion). Lastly, only prolonged infusion of high-dose meropenem approached an ideal CFR against P. aeruginosa; however, no antimicrobial regimen achieved an ideal CFR against A. baumannii.CONCLUSIONS:These data reinforce the use of prolonged infusions of high-dose β-lactam antimicrobials as a reasonable strategy for the treatment of BSIs caused by multidrug resistant Gram-negative bacteria in Brazil.

Resistance to B-lactam and tetracycline in Campylobacter spp isolated from broiler slaughterhouses in southern Brazil / Resistência a B-lactâmicos e tetraciclina em Campylobacter spp isolados de matadouros-frigoríficos de aves no sul do Brasil

The study was carried out to screen and analyze the genetic characteristics of antimicrobial resistance in Campylobacter spp. from poultry sources. A total of 141 strains of Campylobacter isolated from samples of broilers of slaughterhouses in southern Brazil was identified by phenotypic and genotypic methods. Campylobacter isolates were evaluated for its antimicrobial susceptibility and the presence of resistance genes. The strains were investigated for antimicrobial susceptibility against two agents (ampicillin and tetracycline) by disk diffusion method. PCR assay was used to confirm the specie and the presence of ampicillin (blaOXA-61), tetracycline tet(O), and the energy-dependent multi-drug efflux pump (cmeB) genes. Campylobacter jejuni was the most ubiquitous; its presence was determined in 140 samples out of 141 (99.3%), whereas Campylobacter coli was found only in one of the contaminated samples (0.70%). The results obtained showed 65% and 35.5% of Campylobacter isolates resistant to β-lactams and tetracyclines, respectively. The cmeB gene responsible for multidrug resistance was detected in 26 isolates out 141 strains (18.5%). Moreover, 36 out of 141 Campylobacter strains (25.6%) were found to be resistant to at least two different antimicrobia resistance markers (β-lactams and tetracyclines)...

O presente estudo foi realizado para examinar e analisar as características genéticas de resistência antimicrobiana de Campylobacter spp. a partir de fontes avícolas. Um total de 141 amostras de Campylobacter isolados em matadouros-frigoríficos de aves do estado do Rio Grande do Sul, Brasil, foi identificado por métodos fenotípicos e genotípicos. Foi analisada a susceptibilidade antimicrobiana e a presença de genes de resistência. As cepas foram testadas para detectar sensibilidade frente a dois antimicrobianos (ampicilina e tetraciclina) pelo método de difusão em disco. A seguir, usando a reação em cadeia da polimerase foi confirmada a espécie e a presença dos genes de resistência à ampicilina (blaOXA-61) e tetraciclina tet(O), assim como a detecção da bomba de efluxo (cmeB). Campylobacter jejuni foi a espécie mais isolada, sua presença foi determinada em 140 amostras (99,3%), e Campylobacter coli foi encontrada em uma única amostra (0,70%). Os resultados obtidos mostraram 65% e 35,5% de Campylobacter isolados resistentes a β-lactâmicos e tetraciclinas, respectivamente. O gene cmeB responsável pela resistência a múltiplos antimicrobianos foi detectado em 26 amostras (18,5%). Neste contexto, 36 das 141 amostras (25,6%) foram consideradas resistentes a dois grupos diferentes de antimicrobianos (β-lactâmicos e tetraciclinas)...

ANTIBIOTIC PROPHYLAXIS IN BARIATRIC SURGERY: a continuous infusion of cefazolin versus ampicillin/sulbactam and ertapenem / Antibioticoprofilaxia em cirurgia bariátrica: infusão contínua de cefazolina versus ampicilina/sulbactam e ertapenem

Background The incidence of surgical site infection in bariatric patients is significant and the current recommendations for antibiotic prophylaxis are sometimes inadequate. Objective The aim of this study was to analyze the effect of three prophylactic antibiotic regimens on the incidence of surgical site infection. Methods A prospective, cross-sectional study was conducted between January 2009 and January 2013 in which 896 Roux-en-Y gastric bypasses were performed to treat obesity. The study compared three groups of patients according to the perioperative antibiotic prophylaxis administered intravenously and beginning at anesthesia induction: Group I consisting of 194 patients treated with two 3-g doses of ampicillin/sulbactam; Group II with 303 patients treated with a single 1-g dose of ertapenem; and Group III with 399 patients treated with a 2-g dose of cefazolin at anesthesia induction followed by a continuous infusion of cefazolin 1g throughout the surgical procedure. The rate of surgical site infection was analyzed, as well as its association with age, sex, preoperative weight, body mass index and comorbidities. Results The rates of surgical site infection were 4.16% in the group treated prophylactically with ampicillin/sulbactam, 1.98% in the ertapenem group and 1.55% in the continuous cefazolin group. Conclusion The prophylactic use of continuous cefazolin in surgeries for morbid obesity shows very promising results. These findings suggest that some prophylactic regimens need to be reconsidered and even substituted by more effective therapies for the prevention of surgical site infections in bariatric patients. .

Contexto A incidência de infecção de sítio cirúrgico em pacientes bariátricos é significativa e as recomendações atuais para a profilaxia antibiótica são por vezes inadequadas. Objetivo O objetivo deste estudo foi analisar o efeito de três esquemas de antibióticos profiláticos sobre a incidência de infecção de sítio cirúrgico. Método Estudo prospectivo, transversal, foi realizado entre janeiro de 2009 e janeiro de 2013, em que 896 derivações gástricas em Y de Roux foram realizadas para tratar a obesidade. O estudo comparou três grupos de pacientes de acordo com a profilaxia antibiótica administrada no perioperatória por via intravenosa, iniciada na indução anestésica: Grupo I constituído de 194 pacientes tratados com duas doses de 3 g de ampicilina/sulbactam; Grupo II com 303 pacientes tratados com uma única dose de 1 g de ertapenem; e Grupo III com 399 pacientes tratados com uma dose de 2 g de cefazolina no momento da indução da anestésica seguida de uma infusão contínua de cefazolina 1 g durante o procedimento cirúrgico. A taxa de infecção de sítio cirúrgico foi analisada, bem como a sua associação com a idade, sexo, peso pré-operatório, o índice de massa corporal e comorbidades. Resultados As taxas de infecção do sítio cirúrgico foram de 4,16% no grupo tratado profilaticamente com ampicilina/sulbactam, 1,98% no grupo de ertapenem e 1,55% no grupo de cefazolina contínua. Conclusão O uso profilático de cefazolina contínua em cirurgias para obesidade mórbida apresenta resultados muito promissores. Estes resultados sugerem que alguns regimes profiláticos precisam ser reconsiderados e até mesmo substituídos por terapias mais eficazes para a prevenção de infecções de sítio cirúrgico em pacientes bariátricos. .

Carbapenem stewardship: positive impact on hospital ecology

INTRODUCTION: Excessive group 2 carbapenem use may result in decreased bacterial susceptibility. OBJECTIVE: We evaluated the impact of a carbapenem stewardship program, restricting imipenem and meropenem use. METHODS: Ertapenem was mandated for ESBL-producing Enterobacteriaceae infections in the absence of non-fermenting Gram-negative bacilli (GNB) from April 2006 to March 2008. Group 2 carbapenems were restricted for use against GNB infections susceptible only to carbapenems and suspected GNB infections in unstable patients. Cumulative susceptibility tests were done for nosocomial pathogens before and after restriction using Clinical and Laboratory Standards Institute (CLSI) guide-lines.Vitek System or conventional identification methods were performed and susceptibility testing done by disk diffusion according to CLSI.Antibiotic consumption (t-test) and susceptibilities (McNemar's test) were determined. RESULTS: The defined daily doses (DDD) of group 2 carbapenems declined from 61.1 to 48.7 DDD/1,000 patient-days two years after ertapenem introduction (p = 0.027). Mean ertapenem consumption after restriction was 31.5 DDD/1,000 patient-days. Following ertapenem introduction no significant susceptibility changes were noticed among Gram-positive cocci. The most prevalent GNB were P. aeruginosa, Klebsiella pneumoniae, and Acinetobacter spp. There was no change in P. aeruginosa susceptibility to carbapenems. Significantly improved P. aeruginosa and K. pneumoniae ciprofloxacin susceptibilities were observed, perhaps due to decreased group 2 carbapenem use. K. pneumoniae susceptibility to trimethoprim-sulfamethoxazole improved. CONCLUSION: Preferential use of ertapenem resulted in reduced group 2 carbapenem use, with a positive impact on P. aeruginosa and K. pneumoniae susceptibility.

Farmacodermia em um cão após administração de antibióticos do grupo betalactâmico: relato de caso / Pharmacodermia in a dog after administration of beta-lactam antibiotics: case report

A severe cutaneous reaction in a female dog after administration of penicillin and cephalexin is described, in which the main signs presented by the patient were fever, lack of appetite, and detachment of epidermis in the dorsal region of body.The established treatment was surgical debridement of the region, topical application of Aloe Vera with sugar, and systemic antibiotic therapy with ciprofloxacin, resulting in the recovery and wound closure in approximately 45 days.

Prevalence of extended spectrum beta-lactamase-producing enterobac-teriaceae by phenotypic and genotypic methods in intensive care units in Tehran, Iran

The occurrence of Extended Spectrum beta-Lactamase [ESBL]-producing Entrobacteriaceae has been steadily increased in recent years, resulting in limitation of therapeutic options. The purpose of this study was to determine prevalence of ESBL-producing Entrobacteriaceae isolated from Intensive Care Units [ICUs] and to investigate their phenotypic and genotypic characteristics. A total of one hundred fifty isolates were collected from urine and urinary catheter, sputum, blood, wound and other clinical samples from patient admitted in ICUs. All isolates were identified by biochemical tests and then were screened for ESBL production by Disk Agar Diffusion [DAD] according to the Clinical and Laboratory Standards Institute [CLSI] guideline. The species that met screening criteria were further tested for the effects of clavulanic acid by confirmatory method. ESBL-positive species were tested for bla[TEM] and bla[SHV] genes by PCR assay. Of total of 150 bacterial isolates, 133 [89.3%] isolates were positive in the resistance to all tested cephalosporin indicators; and 89 [59.3%] isolates were confirmed as ESBL producer. Klebsiella pneumoniae, Escherichia coli and Entrobacter spp. were the most ESBL-producing species. All isolates were sensitive to imipenem. The bla[TEM] [55.5%] was the most common gene detected in ESBL phenotypic-positive isolates using PCR method. The present study shows high prevalence of ESBL-producing Entrobacteriaceae from ICU patients. The increased rate of these species is mainly due to the inadequate and unnecessary antimicrobial therapy. Rational administration of beta-lactams and appropriate infection control policies may reduce prevalence of ESBL-producing bacteria in ICUs

Terapia ambulatoria con cefprozil en niños con neumonía adquirida en la comunidad / Ambulatory therapy with cefprozil in children with pneumonia acquired in the community

Demostrar que el cefprozil es eficaz y seguro en neumonías adquiridas en la comunidad en edad pediátrica en aquellos casos donde no existan evidencias de complicaciones. Se seleccionaron 30 niños de ambos sexos mayores de 6 meses de edad que cumplieron con los criterios de inclusión, con posibilidades de cumplir el tratamiento en forma ambulatoria, suministrándole el cefprozil a dosis de 50 mg/kg/peso/día por vía oral con controles diarios por un lapso de 7 a 10 días, realizándosele evaluación clínica y examen físico detallados, así como pruebas de laboratorio y cultivos. Predominó el sexo masculino (66,6 por ciento). La mayor incidencia por grupo etario fue entre 6 meses y 5 años de edad, con un promedio de 5 años. La fiebre y la tos estuvieron presentes en 15 de los casos (50 por ciento), el hemograma mostró leucocitosis con neutrofilia y positividad de la VSG y PCR en el 50 por ciento de los casos. El hemocultivo fue positivo para Streptococcus pneumoniae (3 = 10 por ciento) y Moraxella catarralis (1 = 3,33 por ciento), siendo negativos en un 86.66 por ciento. El hallazgo radiológico reveló infiltrado intersticial difuso bilateral (22 = 73,33 por ciento) y focos de consolidación (8 = 26,66 por ciento). El fármaco mostró seguridad y eficacia en el 93,33 por ciento de los casos y no se evidenció efectos colaterales. La terapia con cefprozil en NAC en edad pediátrica demostró eficacia terapéutica sin efectos adversos y con beneficios clínicos y económicos tanto para el paciente como para los padres. Asimismo, la terapia con cefprozil en NAC representa una alternativa eficaz en tratamientos ambulatorios por vía oral y disminuye la masificación en hospitalizaciones innecesarias.