Intereactions between doripenem and clavulanate ­ Application of minimal inhibitory concentration analysis and cytometry flow for bactericidal studies

Background: In view of the current low efficacy of bacterial infection treatment the common trend towards searching for antibiotic systems exhibiting synergistic action is well justified. Among carbapenem analogues a particularly interesting option is provided by combinations of clavulanic acid with meropenem, which have proven to be especially effective. Results: Determination of the minimal inhibitory concentration (MIC) along with the method based on flow cytometry constitutes an important tool in the identification of bacterial sensitivity to active substances. Within this study the inhibitory effect of doripenem, clavulanic acid and the doripenem-clavulanate acid system was analyzed in relation to such bacteria as Salmonella enteritidis, Salmonella typhimurium, Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Clostridium butyricum and Clostridium pasteurianum, Acinetobacter baumannii, Enterobacter aerogenes. The lowest MIC, amounting to 0.03 µg/mL, was observed for the doripenem-clavulanate acid system in the case of E. coli ATCC 25922. In turn, the lowest MIC for doripenem applied alone was recorded for K. pneumoniae ATCC 31488, for which it was 0.1 µg/mL. The strain which proved to be most resistant both to doripenem and the doripenem-clavulanate acid system, was A. baumannii, with MIC of 32 µg/mL (clinical isolate) and 16 µg/mL (reference strain). Cytometric analysis for P. aeruginosa ATCC 27853 and S. aureus ATCC 25923 showed changes in cells following exposure to limiting concentrations of the active substance. Conclusions: Analysis of MIC supplies important information concerning microbial sensitivity to active substances, mainly in terms of limiting concentrations causing mortality or vitality of the tested species, which is essential when selecting appropriate antibiotic therapy.

Comparative in vitro activity of beta-lactam/beta-lactamase inhibitor combinations against gram negative bacteria.

BACKGROUND & OBJECTIVE: Currently, the use of beta-lactamase inhibitors in combination with beta-lactam antibiotics represents an effective measure to combat a specific resistance mechanism of beta-lactamase producing organisms. Knowledge about the susceptibility profile of bacteria to different combination agents available is essential to guide appropriate treatment of severe infections in hospitalized patients. The present study compares the in vitro activity of three commercially available beta-lactam/beta-lactamase inhibitor combinations (piperacillin/tazobactam, cefoperazone/sulbactam, ticarcillin/clavulanic acid) against beta-lactamase producing gram negative bacteria in a tertiary care hospital in north India. METHODS: A total of 9004 consecutively isolated extended spectrum beta-lactamase (ESBL) producing gram negative bacteria isolated from various clinical samples from patients admitted to the All India Institute of Medical Sciences, New Delhi, from September 2003 to August 2004 were included in the study. These isolates were screened for ESBL production by the inhibitor based test recommended by the National Committee for Clinical Laboratory Standards (NCCLS). Antibiotic susceptibility testing was carried out by disc diffusion method as per NCCLS guidelines. RESULTS: Of the 9004 isolates tested, 3232 (35.89%) were sensitive and 568 (6.31%) were resistant to all three combination agents, and rest 5204 (57.80%) were resistant to at least one of the combinations. Susceptibility to piperacillin/tazobactam, cefoperazone/sulbactam, and ticarcillin/clavulanic acid was 81.37, 76.06 and 45.48 per cent respectively. Piperacillin/tazobactam exhibited significantly (P<0.05) greater antimicrobial activity against Pseudomonas spp., Escherichia coli and Klebsiella spp. compared to cefoperazone/sulbactam. INTERPRETATION & CONCLUSION: Overall piperacillin/tazobactam was observed to be the best combination agent followed by cefoperazone/sulbactam in our setting. This difference in activities of these combination agents needs to be evaluated further by ascertaining their efficacy in clinical studies.

Antibióticos en el tratamiento periodontal: revisión bibliográfica / Antibiotics in periodontal treatment: review of the literature

Los antibióticos comparten, junto con otras drogas, determinantes farmacodinámicos y farmacocinéticos y, de igual forma, tienen a su vez determinantes únicos para cada uno de ellos, y de allí que varíen las concentraciones y los intervalos de dosis de ellos. Al estudiar los agentes antimicrobianos, observamos que tienen diferentes mecanismos de acción; por tal motivo, debemos conocer el microorganismo que vamos a atacar, ya que las diversas drogas varían en la forma de producir la muerte o inhibición del crecimiento bacteriano. En este artículo hacemos referencia a una breve reseña de la división de los antibióticos según el efecto que tengan sobre la bacteria, pasando por los parámetros utilizados para caracterizar este comportamiento, y luego, seguimos con una descripción de los antibióticos que se utilizan más frecuentemente como coadyuvantes en el tratamiento periodontal. De ellos sintetizamos sus características más relevantes, su actividad y las indicaciones que tienen en este campo, todo esto con el fin de utilizarlos correctamente en el momento debido

In vitro & in vivo experimental susceptibility of Mycobacterium marinum to augmentin.

The effect of augmentin alone and in combination with various beta-lactam antibiotics was studied against a pathogenic Mycobacterium, M. marinum. The in vitro studies did not reveal any additional advantage over that found with augmentin alone and this antibiotic seemed considerably inhibitory to M. marinum at < 1 microgram/ml concentration. In vivo, the effects of augmentin on experimentally produced lesions in the mouse foot pads (MFPs) showed a significant regression of the lesions, which was compatible with an early disappearance of M. marinum from the MFP, in contrast with those of the untreated, control animals.

Ticarcilina com clavulanato sensibilidade de amostras bacterianas (1994) / Ticarcillin with clavulanic acid bacterial samples susceptibility (1994)

O estudo avalia 414 amostras bacterianas isoladas no Rio de Janeiro (Brasil) testadas para a associaçäo ticarcilina-clavulanato. Observa-se uma sensibilidade global de 67 por cento para Gram-positivos. Entre micoorganismos mais prevalentes na amostragem estudada encontramos 75 por cento de sensibilidade para Pseudomonas aeruginosa, 70,2 por cento em Escherichia coli, 43,3 por cento em Klebsiella pneumoniae e 86,9 por cento em Staphylococcus aureus. Abrem-se expectativas de utilizaçäo da droga em outros grupos microbianos como Acinetobacter calcoaceticus normalmente ditados de estraordinária resistência bacteriana.+

Comparación de dos esquemas de profilaxis antimicrobiana en cirugía de vías biliares: un ensayo clínico controlado por sorteo / Comparison of two schemes of antimicrobial prophylaxis in biliary tracta curgery: a randomized clinicar trial

Objetivo del estudio. Comparar la eficacia en la profilaxis de la amoxicilina/clavulanato y de la combinación cefalotina y clindamicina en cirugía de vesícula y de vías biliares. Diseño. Estudio clínico controlado por sorteo con un evaluador ciego a la maniobra recibida. Lugar. Centro de tercer nivel de atención médica. Pacientes. Se incluyeron 42 pacientes que fueron sometidos a cirugía de vesícula y/o de vías biliares, y se distribuyeron en dos grupos: en el A 22 pacientes (cefalotina y clindamicina) y en el B 20 (amoxicilina/clavulanato). Intervenciones. A los pacientes del grupo A se les administraron por vía intravenosa: tres dosis de cefalotina (2 g al momento de la inducción de la anestesia y dos dosis adicionales de 1 g cada seis horas) y tres dosis de clindamicina de 600 mg (la primera al momento de la inducción anestésica seguido de dos dosis adicionales). A los pacientes del grupo B se les administraron tres dosis de amoxicilina/clavulanato 1000/200 mg IV (la primera durante la inducción de la anestesia y dos dosis subsecuentes con intervalos de seis horas). Mediciones y resultados principales. En el grupo A se presentaron seis infecciones de herida quirúrgica, una de las cuales se acompañó de bacteremia. En el grupo B no se registraron infecciones (Fisher, p<0.01). Se presentó un caso de flebitis en cada grupo Conclusiones. Nuestros resultados indican que la amoxicilina/clavulanato es un esquema útil para profilaxis de cirugía biliar, y más eficaz que la combinación de cefalotina y clindamicina

Inibidores das beta-lactamases e seu uso clínico / Beta-lactamase inhibitors and its clinical use

Os autores fazem uma revisäo bibliográfica sobre as drogas inibidoras das beta-lactamases e abordam sua farmacologia e seu uso clínico atual, baseando-se na combinaçäo dos antimicrobianos e no próprio inibidor da beta-lacatamse. Há muito tempo é conhecido o fato de que germes gram positivos e germes gran negativos säo capazes de produzir enzimas de composiçäo química complexa denominadas beta-lactamases, as quais têm a propriedade de atuar sobre o anel beta-lactamases, beta-lactâmico (componente da estrutura química de alguns antimicrobianos) inativando-o e fazendo com que tais germes se tornem resistentes a estes antimicrobianos (3). Investigaçöes clínicas recentes levaram a descoberta de certas moléculas que podem se ligar de forma irreversível as beta-lactamases e inativá-las, impedindo assim a destruiçäo dos antimicrobianos beta-lactâmicos (3), fazendo com que drogas antigas como ampicilina, amoxacilina e ticarcilina passem a atuar, quando associadas a estas novas substâncias, sobre germes produtores de beta-lactamases, propiciando ao paciente ao mesmo tempo o acesso a uma terapia de custo menor e de menor toxicidade intrínseca. Os agentes inibidores das beta-lactamases têm propriedades, consideravelmente diferentes daquelas das penicilinas e cefalosporinas, assim como säo estruturalmente diferentes destas, tendo baixa atividade intrínseca sobre micoorganismos (4) quando isolados mas que acreditamos de grande valor terapêutico no futuro. Atualmente säo conhecidos dois agentes inibidores das beta-lactamases: o ácido clavulcânico e o sulbactam, os quais passaremos a abordar (5)