Resistencia a antibióticos de última línea en cocos Gram positivos: la era posterior a la vancomicina / Resistance to "last resort" antibiotics in Gram-positive cocci: The post-vancomycin era

En los últimos años se han desarrollado nuevas alternativas para el tratamiento de infecciones por patógenos Gram positivos multirresistentes, entre los cuales Staphylococcus aureus resistente a la meticilina (SARM) y los enterococos resistentes a la vancomicina (ERV) se consideran un verdadero reto terapéutico, y aunque el uso de la vancomicina en infecciones graves causadas por SARM ha generado serias dudas en los últimos años, continúa siendo escasa la información clínica de respaldo al uso de agentes terapéuticos que la superen en eficacia. El linezolid, la daptomicina y la tigeciclina son agentes que tienen actividad contra los cocos Gram positivos y que fueron aprobados e introducidos en la terapia clínica en la década pasada. Además, se han probado o están en las fases finales de desarrollo otros agentes como las cefalosporinas de última generación (ceftarolina y ceftobiprol). El propósito de esta revisión fue describir las nuevas alternativas terapéuticas, particularmente en la era posterior a la vancomicina, y repasar las características químicas más relevantes de los compuestos y su espectro de actividad, haciendo énfasis en sus mecanismos de acción y resistencia.

New therapeutic alternatives have been developed in the last years for the treatment of multidrug-resistant Gram-positive infections. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are considered a therapeutic challenge due to failures and lack of reliable antimicrobial options. Despite concerns related to the use of vancomycin in the treatment of severe MRSA infections in specific clinical scenarios, there is a paucity of solid clinical evidence that support the use of alternative agents (when compared to vancomycin). Linezolid, daptomycin and tigecycline are antibiotics approved in the last decade and newer cephalosporins (such as ceftaroline and ceftobiprole) and novel glycopeptides (dalvavancin, telavancin and oritavancin) have reached clinical approval or are in the late stages of clinical development. This review focuses on discussing these newer antibiotics used in the "post-vancomycin" era with emphasis on relevant chemical characteristics, spectrum of antimicrobial activity, mechanisms of action and resistance, as well as their clinical utility.

Resistencia a carbapenemes en aislamientos de pseudomonas aeruginosa: un ejemplo de interacción entre distintos mecanismos / Carbapenem resistance in pseudomonas aeruginosa isolates: an example of interaction between different mechanisms

Objetivo. Identificar la proteína de membrana externa ausente en los aislamientos resistentes y determinar tanto las causas de su ausencia en la membrana, como la presencia de otros mecanismos de resistencia a carbapenemes en aislamientos clínicos de Pseudomonas aeruginosa. Métodos. Se estudió un brote de 20 aislamientos de P. aeruginosa previamente caracterizados como productores de la metalobetalactamasa IMP-13. Estos aislamientos presentaron igual expresión de la enzima IMP-13, pero solo cinco de ellos fueron resistentes acarbapenemes. En esos cinco aislamientos resistentes se confirmó la ausencia de una proteína de membrana externa. Se secuenciaron oprD y ampC; se identificaron las proteínas de membrana externa por desorción/ionización láser asistida por matriz/espectometría de masa tiempo de vuelo (MALDI-TOF); se determinó el nivel de expresión de OprD, de AmpC y de los sistemas de eflujo tipo Mex, por reacción en cadena de polimerasa en tiempo real, y por último, se determinó la contribución del déficit de OprD a la resistencia a carbapenemes. Resultados. La proteína de la membrana externa ausente en el grupo R (resistentes a ambos carbapenemes) fue identificada como OprD-TS, pero no se observaron variaciones en suexpresión. El gen oprD presentó mutaciones en los cinco aislamientos resistentes. Se observó la misma producción de la enzima tipo AmpC PDC-5 y del sistema de eflujo Mex AB-OprM entre los aislamientos sensibles y resistentes a carbapenemes. Se analizó cómo la presencia conjunta de IMP-13 y el déficit de OprD contribuyen al aumento de la resistencia.Conclusiones. Distintos mecanismos contribuyen a la resistencia de aislamientos productores de IMP-13 a carbapenemes. La posibilidad de no detectar estos aislamientos productores de IMP-13 representa un riesgo latente de selección de mutantes con mecanismos de resistencia que se suman para aumentar la resistencia a carbapenemes.

Objective. To identify the outer membrane protein absent in the resistant isolates and to determine both the causes of its absence in the membrane and the presence of othermechanisms of carbapenem resistance in clinical isolates of Pseudomonas aeruginosa. Methods. Twenty isolates from an outbreak of P. aeruginosa previously characterized as metallo-beta-lactamase IMP-13 producers were studied. All the isolates exhibitedequal expression of the IMP-13 enzyme, but only five of them were carbapenemresistant. It was found that the five resistant isolates lacked a outer membrane protein. The oprD and ampC genes were sequenced; the outer membrane proteins were identifiedusing matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry; the OprD and AmpC expressions, as well as the Mex efflux system, were assessed by real-time polymerase chain reaction; and finally, the contribution of reduced OprD to carbapenem resistance was determined. Results. The absent outer membrane protein in group R was identified as OprD-TS; however, no variations in its expression were observed. The oprD gene presentedmutations in the five resistant isolates. The production of AmpC PDC-5-type enzyme and the MexAB-OprM efflux system was the same in both carbapenem-sensitive and‑resistant isolates. The contribution of the combined presence of IMP-13 and reducedOprD to increased resistance was examined. Conclusions. Different mechanisms contribute to carbapenem resistance in IMP-13-producing isolates. The possibility that these IMP-13-producing isolates could go undetected poses a latent risk when selecting mutants with added resistancemechanisms in order to enhance carbapenem resistance.

Criterios de ensayo, interpretación e informe de las pruebas de sensibilidad a los antibióticos en los bacilos gram negativos no fermentadores de importancia clínica: recomendaciones de la Subcomisión de Antimicrobianos de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas, Asociación Argentina de Microbiología / Antimicrobial susceptibility testing in clinically relevant non-fermenting gram-negative bacilli: recommendations from the Antimicrobial Agents Subcommittee of the Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas, Asociación Argentina de Microbiología

En este documento se dan a conocer una serie de recomendaciones para el ensayo, la lectura, la interpretación y el informe de las pruebas de sensibilidad a los antimicrobianos para los bacilos gram negativos no fermentadores (BGNNF) que se aíslan en humanos. Se adoptaron como base las recomendaciones internacionales, las de la Subcomisión de Antimicrobianos de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas y las de un grupo de expertos invitados. Se incluye, además, la nomenclatura actualizada de los BGNNF y la descripción de algunas de sus características individuales, de sus resistencias naturales o habituales a los antimicrobianos de uso clínico y de los mecanismos responsables de tales resistencias. También se indican los agentes antimicrobianos que se deberían ensayar frente a las distintas especies, con la especificación de cuáles deberían ser informados, y su ubicación estratégica en las placas de cultivo para poder detectar los mecanismos de resistencia más frecuentes y relevantes. Por último, se detallan los métodos de detección y de confirmación fenotípica de la presencia de b-lactamasas emergentes en Argentina, como las carbapenemasas clases A y B.

This document contains the recommendations for antimicrobial susceptibility testing of the clinically relevant non-fermenting gram-negative bacilli (NFGNB), adopted after conforming those from international committees to the experience of the Antimicrobial Agents Subcommittee members and invited experts. This document includes an update on NFGNB classification and description, as well as some specific descriptions regarding natural or frequent antimicrobial resistance and a brief account of associated resistance mechanisms. These recommendations not only suggest the antimicrobial drugs to be evaluated in each case, but also provide an optimization of the disk diffusion layout and a selection of results to be reported. Finally, this document also includes a summary of the different methodological approaches that may be used for detection and confirmation of emerging b-lactamases, such as class A and B carbapenemases.

Bombas de expulsión multidrogas en Acinetobacter baumannii y resistencia a antimicrobianos / Multi-drug efflux pumps and antibiotic resistance in Acinetobacter baumannii

Los sistemas multidrogas bacterianos contribuyen al desarrollo del fenotipo de multi-resistencia presentado por cepas de Acinetobacter baumannü, patógeno intrahospi-talario, que durante los últimos años ha incrementado su importancia por la creciente resistencia a carbapenémicos. El fenotipo de multi-resistencia está otorgado por la combinación de varios mecanismos de resistencia entre los cuales se encuentran estos sistemas de bombas de expulsión. El sistema multidroga AdeABC se ha detectado en muchas de estas cepas multi-resistentes de A. baumannü y, se ha relacionado con resistencia a diversos grupos de antimicrobianos, incluidos tigeciclina y meropenem. La inhibición de dichos sistemas multidrogas permitiría aumentar la eficacia de la terapia antimicrobiana. La siguiente revisión se enfoca en las bombas de expulsión multidrogas presentes en A. baumannü, con particular énfasis en el sistema AdeABC.

Bacterial multi-drugs systems contribute to the development of multi-resistance patterns of Acinetobacter baumannii, a nosocomial pathogen of increasing importance due to its emerging resistance to carbapenems. The multi-resistance phenomena is generated by a combination of mechanisms, one of which the efflux pump system. Many of these multiresistant isolates of A. baumannii harbor genes for the AdeABC multi-drug efflux system, related with resistance to various groups of antibacterial agents, including tygecicline and meropenem. Inhibition of these systems would allow to increase the efficacy of this antimicrobial. This review focuses on the multi-drug efflux pump system oí A. baumanni with special emphasis in the AdeABC system.

Changing profile of prostatic abscess

PURPOSE: To compare the clinical presentation of prostatic abscess and treatment outcome in two different time frames with regards to etiologies, co-morbid factors and the impact of multidrug resistant organism. MATERIALS AND METHODS: We retrospectively assessed the charts of 48 patients with the diagnosis of prostatic abscess from 1991 to 2005. The period was divided arbitrarily into two different time frames; phase I (1991-1997) and phase II (1998-2005). Factors analyzed included presenting features, predisposing factors, imaging, bacteriological and antibiotic susceptibility profile, treatment and its outcome. RESULTS: The mean patient age in phase I (n = 18) and phase II (n = 30) were 59.22 ± 11.02 yrs and 49.14 ± 15.67 respectively (p = 0.013). Diabetes mellitus was most common predisposing factor in both phases. Eleven patients in phase II had no co-morbid factor, of which nine were in the younger age group (22 - 44 years). Of these eleven patients, five presented with pyrexia of unknown origin and had no lower urinary tract symptoms LUTS Two patients with HIV had tuberculous prostatic abscess along with cryptococcal abscess in one in phase II. Two patients had melioidotic prostatic abscess in phase II. The organisms cultured were predominantly susceptible to first line antibiotics in phase I whereas second or third line in phase II. CONCLUSION: The incidence of prostatic abscess is increasing in younger patients without co-morbid factors. The bacteriological profile remained generally unchanged, but recently multi drug resistant organisms have emerged. A worrying trend of HIV infection with tuberculous prostatic abscess and other rare organism is also emerging.

Drug-resistant tuberculosis among prisoners of three prisons in Bangkok and the vicinity.

The purpose of this study was to determine the prevalence of drug-resistant tuberculosis and some factors associated with drug resistance among prisoners of three prisons in Bangkok and the vicinity. Susceptibility testing to four first-line antituberculous drugs was performed on 165 M. tuberculosis strains isolated from prisoners of three prisons including Klongprem Central (KC) prison, Bangkwang Central (BC) prison and the Correctional Institution (CI) for Male Drug Addicts. Of 165 smear positive tuberculosis (TB) cases with drugs susceptibility results, resistance to one or more drugs was 49.7 per cent. Resistance to one, two, three, and four drugs was 20.0, 13.3, 4.2 and 12.1 per cent, respectively. Multidrug resistant tuberculosis (MDR-TB) was 18.8 per cent. Patients classified as primary and acquired drug resistant were 6.7 and 50.0 per cent. The primary drug resistance to one or more drugs among prisoners at KC, BC and CI were 42.5, 36.4 and 53.9 per cent, respectively and MDR-TB were 8.2, 3.0, and 7.7 per cent, respectively. Of several factors analyzed in the present study, only a history of previous TB treatment was significantly associated with drug resistance (p < 0.05). In conclusion, the results indicate the high prevalence of drug-resistant tuberculosis and the seriousness of the TB problem in prisons. The public health sector and prison authorities should work in close collaboration and co-ordination to continue improving TB case detection. Directly Observed Treatment Short course (DOTS) is highly recommended. Moreover, discharged prisoners with tuberculosis should be appropriately referred to hospitals or TB control centers.