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.

Betalactámicos con inhibidores de betalactamasas: Amoxicilina-sulbactam / Betalactam antibiotics combined with bectalactamases inhibitors: Amoxicillin-sulbactam

La producción de betalactamasas constituye uno de los principales mecanismos de resistencia bacteriana a los antibióticos betalactámicos. La utilización de inhibidores de betalactamasas en combinación con antibióticos betalactámicos permite la inactivación de determinadas betalactamasas producidas por gérmenes Gram positivos, Gram negativos, anaerobios, y aun por micobacterias. Los inhibidores de betalactamasas representan una alternativa terapéutica mejorada respecto del resto de los betalactámicos al asegurar, en la mayoría de los casos, un mayor espectro antimicrobiano comparado con el de sus análogos. La actividad enzimática de las betalactamasas está dirigida específicamente a la hidrólisis del anillo betalactámico, con producción de un compuesto sin actividad antibacteriana. De acuerdo con su posición genómica dentro de los microorganismos, las betalactamasas pueden ser cromosómicas o plasmídicas. Actualmente existen tres inhibidores de betalactamasas localmente disponibles: ácido clavulánico, sulbactam y tazobactam. De ellos, sólo el sulbactam posee actividad antimicrobiana intrínseca sobre las proteínas ligadoras de penicilina. La experiencia clínica acumulada durante más de 20 años confirma que las combinaciones de betalactámicos-inhibidores de betalactamasas son efectivas en el tratamiento empírico inicial de infecciones respiratorias, intraabdominales, urinarias y ginecológicas, incluidas las de origen polimicrobiano. En el caso particular de amoxicilina-sulbactam, la evidencia citada indica que esta combinación es efectiva para el tratamiento de absceso periamigdalino, otitis media, sinusitis, neumonía extrahospitalaria, exacerbación aguda de enfermedad pulmonar obstructiva crónica (EPOC), infección del tracto urinario e infecciones ginecoobstétricas. Por su espectro y propiedades farmacológicas, la combinación amoxicilina-sulbactam constituye una excelente opción también para el tratamiento de infecciones de piel y partes blandas e infecciones intraabdominales.

Betalactamases production is one of the main bacterial resistance mechanisms to betalactam antibiotics. The use of bectalactamases inhibitors combined with betalactam antibiotics allows the inactivation of certain betalactamases produced by Gram positive, Gram negative and anaerobic organisms, and even by mycobacteria. Betalactamases inhibitors are an improved therapeutic alternative compared with the other betalactam since, in most cases, they cover a wider antimicrobial spectrum than their analogues. Betalactamases enzimatic activity is specifically directed to the betalactam ring hydrolisis, producing a compound without antibacterial activity. According to their genomic position within microorganisms, betalactamases can be either chromosomic or plasmidic. Currently there are three betalactamases inhibitors locally available: clavulanic acid, sulbactam and tazobactam. Of them, only sulbactam has an intrinsic antimicrobial activity against penicillin binding proteins. The clinical experience from over 20 years confirms that the combination of betalactam antibiotics is effective in the empirical initial treatment of respiratory, intraabdominal, urinary tract and gynecologic infections, including those of polymicrobial origin. In the specific case of amoxicillin-sulbactam, experiences have shown the effectiveness of the combination in the treatment of peritonsillar abscess, otitis media, sinusitis, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonar disease (COPD), urinary tract infection and obstetric/ gynecologic infections. The spectrum and pharmacologic properties of this combination makes it also an excellent option for the treatment of skin/soft tissue and intraabdominal infections.

Ontogênese, estresse e dependência de substâncias psicoativas / Ortogenesis, stress and psychoactive substances addiction

O estudo da dependência de substâncias psicoativas apresentou grandes avanços conceituais nas últimas décadas. A evolução dos conceitos foi paralela às evidências científicas que têm revelado os aspectos comportamentais e os mecanismos neurais envolvidos nesse fenômeno. Contudo, um grande desafio que permanece na pesquisa sobre a dependência de substâncias psicoativas é a identificação de quais fatores são responsáveis pela transição do uso controlado para o uso compulsivo. Está demonstrado que muitas variáveis interagem para influenciar a probabilidade de que qualquer indivíduo inicie o uso abusivo de substâncias psicoativas ou se torne dependente. Nos últimos anos, o estresse tem sido destacado como um fator importante na iniciação, manutenção e recaída da utilização de substâncias psicoativas. Neste trabalho analisamos os conceitos e teorias da farmacodependência e as principais evidências comportamentais pré-clínicas que demonstram a relação entre estresse e a vulnerabilidade ao abuso e dependência de psicoestimulantes.

The investigation of the mechanisms of drug abuse and addiction showed great advances in the last decades. New concepts emerged from the scientific evidences on behavioral and neural aspects of this phenomenon. However, the biggest challenge for the future is the identification of which risk factors are implicated in the transition from controlled to compulsive drug use. Stress has been pointed as an important factor related to initiation, maintenance and relapse to drug use. In the present paper we discuss the concepts and theories of drug addiction, and the main behavioral pre-clinical evidences showing the relationship between stress and psychostimulant addiction.

Teicoplanina en el tratamiento de las infecciones osteoarticulares por Staphylococcus meticilino-resistente. Experiencia en adultos / Teicoplanin in the treatment of bone and joint infections due to methicillin resistant staphylococci. Experience in adult patients

We retrospectively evaluated 89 episodes of bone and joint infections due to methicillin-resistant staphylococci: 56 chronic osteomyelitis (CO), 10 septic arthritis (SA) and 23 infections associated to arthroplasties (IAA). We analyzed the efficacy of Teicoplanin (T) in three times a week or daily administration schemes and adequate surgery (AS). Also, we determined cost savings derived from outpatient parenteral antibiotic therapy (OPAT). The overall efficacy of T in CO and both in cases with and without implants, was higher when antibiotic therapy was associated to AS (86 vs. 46, p = 0.001; 100 vs. 33, p = 0.0049 and 76 vs. 50, p = 0.09). All SA were cured. The overall efficacy of T was higher in IAA with implant removal vs. surgical debridement (100 vs. 54, p = 0.045). In all cases, T was similarly effective when administered three times a week vs. daily administration, when associated to AS. The savings derived from OPAT were 897 days/bed and USS 179,400. Adverse effects were few and light (8 episodes, 9). The results obtained are similar to those published in the literature and show that T administered daily or in a three times a week scheme and associated to AS, is effective and safe for the treatment of bone and joint infections. The savings derived from OPAT, mainly related to reduced hospitalization, are significant in these pathologies, which usually require long treatment periods

Características farmacocinéticas y espectro antimicrobiano de la teicoplanina / Pharmacokinetic characteristics and antimicrobial spectrum of teicoplanin

Teicoplanin is a glycopeptide antibiotic with similar spectrum to vancomycin. Its long half-life permits administration in a single daily dose. The adverse effects of teicoplanin are less frequent than those of vancomycin. Rash and local intolerance are the most frequent. Staphylococcus aureus, coagulase-negative staphylococci and Enterococcus sp. are susceptible to teicoplanin. Clinical data have shown teicoplanin to be less nephrotoxic than vancomycin when combined with amino glycosides. Teicoplanin, alone or in combination with additional antibacterial drugs, has proven to be effective in the treatment of several Gram-positive infections, such as sepsis, bone and joint infections, endocarditis and skin and soft tissue infections. Clinical efficacy was obtained in more than 90 of the patients treated. Similar data have been reported in adults, children and elderly patients. Due to its easy administration and dosage, teicoplanin is a treatment of choice for outpatient parenteral therapies

Resistencia del Staphylococcus a la meticilina / [Methicillin resistant Staphylococcus]

The pathogenic potential of Staphylococcus aureus is well known as well as its role both in nosocomial and community-acquired infections. When penicillin was introduced by mid ’40s, S. aureus was almost 94

susceptible to this drug. Widespread resistance to penicillin developed in the ’50s, followed by resistance to semi synthetic penicillins in the ’60s and ’70s. Since then, strains of methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci have spread worldwide. The prevalence of methicillin-resistant S. aureus varies geographically. In our country it reaches nearly 50

. Methicillin resistance in Staphylococci develops due to an additional penicillin binding protein, PBP2a, which is encoded by gene mecA, the responsible of methicillin resistance. Methicillin resistance in Staphylococcus aureus and in coagulase-negative staphylococci represents a serious problem both for the microbiologist and the physician. A special feature of methicillin resistance is its heterogeneous nature with different levels of resistance. Most clinical isolates show a heterogeneous pattern under routine growth conditions. The high prevalence of methicillin-resistant staphylococci compromises the use of semi synthetic penicillins for empiric treatments in many institutions, thus increasing the use of vancomycin. Until 1996, glycopeptides were almost universally active against S. aureus but it was then that the first glycopeptide-intermediate S. aureus (GISA) was described and isolated in Japan, followed by France and USA. The exact mechanism involved has not been elucidated yet, although vancomycin resistance is associated with increased wall synthesis.

Guias para el manejo de las infecciones osteoarticulares por Staphylococcus meticilino-resistente / [Guidelines for the management of bone and joint infections due to methicillin resistant staphylococci]

Bone and joint infections are a group of complicated diseases with high morbidity. Emerging resistant microorganisms and the use of prosthetic devices have increased the difficulty in the medical treatment of patients. The purpose of these guidelines is to offer information on the management of bone and joint infections (post-invasive septic arthritis, chronic osteomyelitis and infected arthroplasty) produced by methicillin resistant staphylococci. They are oriented to physicians dedicated to internal medicine, infectious diseases, trauma and orthopedist surgeons as well as to everybody interested in this issue. The guidelines mainly point to the rational use of diagnostic methods and describe the new treatment modalities. A group of experts analyzed the different strategies for diagnosing and treating bone and joint infections due to methicillin resistant staphylococci and attempted at setting a level of evidence level and the strength of each recommendation.