Pharmacokinetics of erythromycin after intravenous, intramuscular and oral administration to cats.

The aim of this study was to characterise the pharmacokinetic properties of different formulations of erythromycin in cats. Erythromycin was administered as lactobionate (4 mg/kg intravenously (IV)), base (10mg/kg, intramuscularly (IM)) and ethylsuccinate tablets or suspension (15 mg/kg orally (PO)). After IV administration, the major pharmacokinetic parameters were (mean ± SD): area under the curve (AUC)((0-∞)) 2.61 ± 1.52 microgh/mL; volume of distribution (V(z)) 2.34 ± 1.76L/kg; total body clearance (Cl(t)) 2.1 0 ± 1.37 L/hkg; elimination half-life (t(½)(λ)) 0.75 ± 0.09 h and mean residence time (MRT) 0.88 ± 0.13 h. After IM administration, the principal pharmacokinetic parameters were (mean ± DS): peak concentration (C(max)), 3.54 ± 2.16 microg/mL; time of peak (T(max)), 1.22 ± 0.67 h; t(½)(λ), 1.94 ± 0.21 h and MRT, 3.50 ± 0.82 h. The administration of erythromycin ethylsuccinate (tablets and suspension) did not result in measurable serum concentrations. After IM and IV administrations, erythromycin serum concentrations were above minimum inhibitory concentration (MIC)(90)=0.5 microg/mL for 7 and 1.5h, respectively. However, these results should be interpreted cautiously since tissue erythromycin concentrations have not been measured and can reach much higher concentrations than in blood, which may be associated with enhanced clinical efficacy.

Pharmacokinetics of erythromycin in nonlactating and lactating goats after intravenous and intramuscular administration.

The objectives of this work were to compare the pharmacokinetics of erythromycin administered by the intramuscular (i.m.) and intravenous (i.v.) routes between nonlactating and lactating goats and to determine the passage of the drug from blood into milk. Six nonpregnant, nonlactating and six lactating goats received erythromycin by the i.m. (15 mg/kg) and the i.v. (10 mg/kg) routes of administration. Milk and blood samples were collected at predetermined times. Erythromycin concentrations were determined by microbiological assay. Results are reported as mean +/- SD. Comparison of the pharmacokinetic profiles between nonlactating and lactating animals after i.v. administration indicated that significant differences were found in the mean body clearance (8.38 +/- 1.45 vs. 3.77 +/- 0.83 mL/kg x h respectively), mean residence time (0.96 +/- 0.20 vs. 3.18 +/- 1.32 h respectively), area under curve from 0 to 12 h (AUC(0-12)) (1.22 +/- 0.22 vs. 2.76 +/- 0.58 microg x h/mL respectively) and elimination half-life (1.41 +/- 1.20 vs. 3.32 +/- 1.34 h); however, only AUC(0-12) showed significant differences after the i.m. administration. Passage of erythromycin in milk was high (peak milk concentration/peak serum concentration, 2.06 +/- 0.36 and AUC(0-12milk)/AUC(0-12serum),6.9 +/- 1.05 and 2.37 +/- 0.61 after i.v. and i.m. administrations respectively). We, therefore, conclude that lactation affects erythromycin pharmacokinetics in goats.

Serotipos y susceptibilidad antimicrobiana de Streptococcus agalactiae / Serotypes and antimicrobial susceptibility of Streptococcus agalactiae

Background : Streptococcus agalactiae or group B streptococcus, GBS, is the leading cause of neonatal and maternal infections and an opportunistic pathogen in adults with underlying disease. In the last decade, a dramatic increase in the resistance of this microorganism to erythromycin and clindamycin has been observed. Aim: To determine the serotype distribution and antimicrobial susceptibility of isolates of S agalactiae collected from infections and colonization and to assess the genetic mechanisms of macrolide and clindamycin resistance. Material and methods: A total of 100 GBS isolates were collected between 1998 and 2002, in Santiago, Chile. They were isolated from the amniotic fluid from patients with premature rupture of membranes (7 isolates), blood from neonatal sepsis (10 isolates), neonate colonizations (2 strains), skin and soft tissue infections (7 isolates), urinary tract infections (5 isolates), genital infections (3 isolates), articular fluid (one isolate), and 65 strains were recovered from vaginal colonization55. Results: Serotypes Ia, II and III were the predominant serotypes identified in our study, accounting for 90 (90 percent) of the strains. Five isolates belonged to serotypes Ib (5 percent) and two (2 percent) to serotype V respectively; no strains belonging to serotype IV were found. All strains were susceptible to penicillin G, ampicillin and cefotaxime, and four isolates (4 percent) were resistant to both erythromycin (MIC >64 µg/ml) and clindamycin (MIC >64 µg/ml). The strains had a constitutive macrolide-lincosamide-streptogramin (cMLSB) resistance phenotype and the erm(A) gene was present in the four isolates. Conclusions: Serotypes Ia, II and III were the predominant serotypes in this study. All strains were susceptible to penicillin G, ampicillin and cefotaxime, and four (4 percent) strains were resistant to both erythromycin and clindamycin. The cMLSB resistance phenotype, and the erm(A) gene was detected in resistant strains (Rev MÚd Chile 2004; 132: 549-55).

En coqueluche: ¿es posible? / In pertussis: is it possible?

Existen esquemas alternativos a los recomendados por la Academia Americana de Pediatría para el tratamiento antimicrobiano de la coqueluche. Estudios controlados apoyan la posibilidad de reducir el plazo de tratamiento a 7 días empleando eritromicina. Desde cuidarse en especial la dosficación de eritromicina (para etilsuccinato debe ser de 50 a 60 mg/kg/ día y administrarse siempre inmediatamente después de las comidas). El empleo de nuevos macrólidos requiere mayor base experimental para establecer dosis diaria, duración y eficacia bacteriológica. Es conveniente implementar el cultivo en centros centros centinelas para vigilar la susceptibilidad in vitro de bordetella pertussis y ratificar la eficacia bacteriológica de los esquemas abreviados de terapia específica. Los pasos abreviados de tratamiento de la infección establecida por bordetella pertussis parecen ser extrapolables a los esquemas recomendados para la profilaxis en los contactos

Emergencia de resistencia a macrólidos en streptococcus pyogenes / Emergence of macrolide resistant streptococcus pyogenes strains

Background: Diseases produced by Streptoccocus pyogenes are still a problem in Chile, as in the rest of the world. It exhibits in vitro susceptibility to different antimicrobials, but penicillin continues to be the treatment of choice. Alternative drugs have been developed for allergic patients, such as erythromycin, new macrolides and cephalosporins. Nevertheless, resistant strains are appearing due to the indiscriminate use of macrolides. Aim: To assess present antimicrobial susceptibility of S Pyogenes strains isolated from chilean patients. Material and Methods: The susceptibility to penicillin, macrolides, clindamycin, cephalotin and vancomycin of 153 S Pyogenes strains, obtained from different health centers of the Metropolitan Region and isolated between 1996 and 1998, was assessed using the Kirby-Bauer method. Agar dilution minimal inhibitory concentration was then determined to macrolide resistant strains. Results: All strains were susceptible to penicillin. There was a 7.2 percent cross-resistance to macrolides. Conclusions: These results confirm that S Pyogenes resistance to macrolides has increased considerably in the Metropolitan Region of Chile during the last years

Macrólidos en vías respiratorias altas / Macrolides in upper respiratory tract

Los macrólidos no son el tratamiento de primera línea para amigdalitis estreptocóccica, pero sí una alternativa en caso de alergia a penicilina. Para el tratamiento antimicrobiano de OMA,amoxicilina continúa siendo el fármaco de primera elección. Si el tratamiento fracasa por producción de B lactamasa, los nuevos macrólidos son una alternativa válida. Comparados con las otras alternativas, no presentan ninguna ventaja ni desventajas importantes. La única excepción que pesa a favor puede ser la muy larga vida media de azitromicina, que ofrece la ventaja de un corto curso de tratamiento de tres o cinco días. Respecto al neumococo resistente, falta la información local para saber si los nuevos macrólidos son una alternativa útil, o no. La ventaja muy especial de los macrólidos, su actividad contra Chlamydia sp, Mycoplasma sp,M catarrhalis, legionella sp o Mycobacterium avium, no tiene mayor trascendencia en las infecciones respiratorias altas

Macrólidos en vías respiratorias bajas / Macrolides in lower respiratory tract

Los nuevos macrólidos se han constituido en terapias alternativas seguras para el tratamiento de neumonías leves o moderadas adquiridas en la comunidad y en individuos sin patología asociada. Son los antibióticos de elección frente a neumonías atípicas excepto para la producida por C. psittaci. Las mayores ventajas que aportan los macrólidos son la excelente tolerancia oral, su elevada concentración tisular e intracelular y una vida media prolongada que permite la fácil dosificación y la introducción de terapias acortadas asegurando una mejor adherencia al tratamiento. Las desventajas destacables son sus bajos niveles séricos y el elevado costo actual. Por último, se requiere de un uso racional de estos antibióticos y estudios de sensibilidad para estar alertas a la emergencia de resistencia como ya se ha descrito en otras latitudes, v.g. S. pneumoniae y S. pyogenes resistentes a todos los macrólidos

Haemophilus influenzae type b exoproducts induce chemotaxis and macrolide antibiotic release by human polymorphonuclear leukocytes.

The capacity of phagocytes to concentrate macrolide antibiotics was suggested by previous reports. In this study, we evaluated the capacity of Haemophilus influenzae type b culture supernatants (HICS) to induce polymorphonuclear leukocyte (PMNL) migration and macrolide antibiotic delivery. Using a Boyden multiwell chamber and a chemotaxis assay under agarose combined with a bioassay to measure antibiotic levels in agar, we demonstrated the chemotactic activity of HICS. Preincubation of PMNL with either erythromycin or azithromycin did not affect PMNL chemotaxis. By the agar diffusion test, we established that HICS increased the release of antibiotic from PMNL when compared with spontaneous release. Furthermore, we determined that the antibiotics remain bioactive after release. These results suggest that HICS may have a modulatory effect on transport and delivery of macrolide antibiotics by PMNL at the infection site.

Antibióticos macrolídicos - retorno à vista? / Macrolide antibiotics, a return in sight?

O autor apresenta as perspectivas de progressos, no campo da terapêutica antimicrobiana, representadas pelo aparecimento de novos antibióticos macrolídicos com propriedades que os diferenciam, e muitas vezes os tornam mais atraentes, relativamente aos membros mais antigos da família. Compara esses novos antibióticos com a eritromicina, destacando as diferenças de propriedades farmacocinéticas e de espectro antimicrobiano. Por fim, apresenta as indicaçöes terapêuticas especiais que esses medicamentos poderäo vir a ter

Tetracyclines, macrolides, lincosamides & chloramphenicol.

Macrolides, lincosamides, tetracyclines and chloramphenicol are structurally unrelated antibiotics which share protein synthesis inhibition as their common mechanism of action. Despite their individual differences, they can all be considered broad spectrum antibiotics with practical use for a wide variety of infections. Due to their similarities in function, however, concurrent or sequential administration of these agents must be undertaken with caution in order to prevent antagonism and induction of bacterial resistance. Full understanding of their function and potential interactions are, therefore, important. Indications, interactions, mechanisms of function, side effects and contraindications are fully discussed.

Tetracyclines, macrolides, licosamides & chloramphenicol

Los macrólidos, lincosaminas, tetraciclinas y cloramfenicol son antibióticos no relacionamento estructuralmente que comparten como mecanismo de acción la inhibición de la síntesis de proteínas. A pesar de sus diferencias individuales, se pueden clasificar como agentes de amplio espectro con uso en el manejo de una gran variedad de infecciones. A consecuencia de la similitud entre estos compuestos en cuanto a mecanismos de acción, el uso concurrente o en secuencia de los mismos debe ejercer-se con cautela. Dicha práctica podría resultar en antagonismo entre los agentes o en la inducción de resistencia bacteriana. Es importante, por tanto, entender la función de estos antibióticos y la interacciones potenciales que existen entre ellos. Se discuten las indicaciones, interacciones, mecanismos de acción, efectos adversos y contraindicaciones

Vigilancia de la sensibilidad a antimicrobianos de streptococcus beta-hemolíticos, aislados entre 1982 y 1987 / Antimicrobial sensibility surveillance of betahemolytic streptococcus isolated between 1982 and 1987

El objetivo principal de este trabajo, fue determinar la resistencia o sensibilidad a antimicrobianos de uso habitual, en cepas de Streptococcus beta-hemolíticos grupos A, C y G aisladas de diversas localizaciones, en Santiago, entre los años 1982 y 1987