The resistance mechanisms of b-lactam antimicrobials in clinical isolates of Acinetobacter baumannii

BACKGROUND: Despite increasing importance of Acinetobacter baumannii in nosocomial infections and rapid development of multi-antimicrobial resistance in this strain, the resistance mechanisms of beta-lactam antimicrobials in A. baumannii were not clearly defined. In order to observe the resistance mechanisms against beta-lactams and carbapenem, we characterized the production of beta-lactamases and outermembrane protein (OMP) profiles for the 44 clinical isolates of A. baumannii. METHODS: The MICs of antimicrobials were determined by agar dilution test. The secondary beta-lactamases were characterized by isoelectric focusing, polymerase chain reactions and nucleotide sequencing, and the production of chromosomal beta-lactamases was quantitated by spectrophotometric method. For two strains with an elevated MIC of carbapenem, outermembrane protein (OMP) profile was analyzed by ultracentrifugation of the sonicated bacteral cells and SDS-PAGE. RESULTS AND CONCLUSION: Twenty two or 4 of 44 strains produced TEM-1-like beta-lactamase or PER-1 extended-spectrum beta-lactamase, respectively. However, when we analyzed the MICs of several beta-lactams with the beta-lactamase production, the resistance level of beta-lactam was mainly determined by the production of chromosomal beta-lactamase, not by the secondary beta-lactamases in the clinical isolates of A. baumannii. In two strains with an elevated MIC of imipenem, a decrease or loss of about 35 kDa and 22 kDa proteins in OMP was observed, which suggested that the change of OMP played a role in carbapenem resistance.

Propiedades microbiológicas, clasificación y relación estructuras-actividad de cefalosporinas e importancia de las cefalosporinas de cuarta generación / Microbiological properties, classification and structure-activity relationships of cephalosporins and the importance of fourth generation cephalosporins

Las cefalosporinas son uno de los grupos de mayor importancia dentro de los ß-lactámicos. Existen diversas clasificaciones de esta moléculas, siendo la más utilizada aquella que agrupa a estos compuesto de acuerdo a propiedades estructurales, microbiológicas y desarrollo histórico: primera a cuarta generación. Las cefalosporinas de tercera generación han sido ampliamente utilizadas, pero la emergencia de resistencia bacteriana fundamentalmente derivada de la producción de ß-lactamasas tanto cromosomales como plasmidiales, ha limitado el uso de estos compuestos. Las cefalosporinas de cuarta generación se caracterizan por la presencia de un nitrógeno cuaternario en C, además de mantener el grupo metoxi-imino aminotiazolil en C. Presentan una elevada penetración intracelular a través de la membrana externa de bacilos Gram negativos y tienen una baja afinidad por enzimas que degradan cefalosporinas de tercera generación. Cefepime, una cefalosporina de cuarta generación, demostró una mayor actividad inhibitoria sobre cepas chilenas de Klebsiella pneumoniae y Escherichia coli productoras de ß- lactamasa de espectro extendido, que cefotaxima y ceftazidima

Susceptibility of clinical isolates of Bacteroides fragilis group strains to cefoxitin, cefoperazone and ticarcillin/clavulanate

A total of 40 strains of the B. fragilis group was isolated from clinical specimens in two hospital centers in Fortaleza from 1993 to 1997. The most frequently isolated species was Bacteroides fragilis (19 strains) and most isolates came from intra-abdominal and wound infections. The susceptibility profile was traced for cefoxitin, cefoperazone and ticarcillin-clavulanate by using the agar dilution reference method. All isolates were susceptible to ticarcillin-clavulanate (128/2mug/ml). Resistance rates of 15 and 70 percent were detected to cefoxitin (64mug/ml) and cefoperazone (64mug/ml), respectively. Such regional results permit a better orientation in choosing this group of antibiotics for prophylaxis and therapy especially in relation to cefoxitin, which is frequently used in the hospital centers studied.

Evaluation of the in vitro activity of two fourth-generation cephalosporins against bacterial samples isolated from patients in several Brazilian Hospitals

Cefpirome and cefepime are two fourth-generation cephalosporins recently introduced in Brazil. They have a very similar range of in vitro antimicrobial activity, but some differences have been noticed. The goal of this study was to compare the in vitro activity of cefpirome and cefepime against bacterial samples isolated in Brazilian hospitals. We studied 931 samples taken from hospitalized patients between April and June, 1998. The minimum inhibitory concentration (MIC) was determined by the Etest method. The potency of cefpirome was similar to that of cefepime, except against enterococci and coagulase-negative staphylococci, where cefpirome proved 2-fold more potent. The MICs90 for cefepime were inferior to cefpirome in response to Klebsiella pneumoniae (MICs90, 24 and 96µg/mL, respectively), Pseudomonas aeruginosa (MICs90, 48 and 128µg/mL, respectively), and other Gram-negative organisms (MICs90, 64 and 256µg/mL, respectively). Despite the fact that cefpirome presented a slightly broader range of action against Gram-positive bacteria(90 percent sensitive vs. 78 percent sensitive to cefepime), and that cefepime presented an equally broad range against Gram-negative bacteria (74 percent sensitive vs. 65 percent sensitive to cefpirome), these differences were not considered clinically significant because the sensitivity differed in MIC by less than 2 dilutions. Only 16 (1.7 percent) of the 931 samples tested showed a significant difference in sensitivity. This study suggests that, except for Acinetobacter sp. and P. aeruginosa, laboratories may routinely test only cefpirome and apply the same category result to cefepime. Since category discrepancies are very rare and cefpirome is slightly less active than cefepime against Enterobacteriaceae, isolates susceptible to cefepime will certanly also be susceptible to cefpirome. To optimize the treatment of severely infected patients, especially where species such as Acinetobacter sp and P. aeruginosa are involved, we recommend that both cephalosporins be tested by using the same susceptibility test method to determine the MIC.

Vigilancia de susceptibilidad de cocáceas grampositivas a betalactámicos, glicopéptidos y otros antimicrobianos / Surveillance of gram positive cocci susceptibility to betalactamics, glycopeptides and other antimicrobials

Background: During the last decade, there has been a progressive increase in the resistance of gram (+) cocci to betalactamics and other antimicrobials. Therefore, vancomycin and teicoplanin have incorporated as alternative antimicrobial drugs. Aim: To assess the susceptibility of gram (+) cocci to different antimicrobials including vancomycin and teicoplanin. Material and methods: We studied 447 strains of gram (+) cocci coming from ambulatory and hospitalized patients. These included 308 enterococcus sp strains, 99 staphycoccus aureus strains and 40 coagulase negative staphylococci strains. Enterococci susceptibility was measured using minimal inhibitory concentrations in agar and that of staphylococci, through diffusion. Susceptibility to vancomycin and teicoplanin was measured using minimal inhibitory concentrations in all strains. Results: Enterococcus faecalis was 100 percent susceptible to ampicillin, penicillin, vancomycin and teicoplanin, 23 percent susceptible to tetracyclin and 47 percent to chloramphenicol. Susceptibility of E faecium was 61 percent to penicillin, 49 percent to chloramphenicol, 41 percent to tetracyclin, 100 percent to vancomycin and teicoplanin. Of 19 enterococcus spp strains, 90 percent were susceptible to ampicillin, 80 percent to penicillin, 55 percent to chloramphenicol and 45 percent to tetracyclin. Only one E casseiflavus strain had a low level resistance to vancomycin and was susceptible to teicoplanin. No staphylococcus aureus strain was resistant to vancomycin or teicoplanin. Conclusions: A permanent surveillance of gram (+) cocci antimicrobial susceptibility is required to update therapeutic schemes

Multirresistencia antimicrobiana en cepas de shigella sp en una comuna semi rural del área norte de Santiago / Antimicrobial multiresistance of shigella sp strains in a semi rural community of north Santiago

Appropriate antimicrobial therapy shortens the duration of Shigellosis and significantly reduces the risk of transmission. Shigella strains resistant to common antimicrobials have increased during the past years, determining the need for a periodic surveillance, to guide effective therapy. Aim: To report the results of a surveillance program in a rural community near Santiago (Colina), for Shigella infections. Material and methods: Between 1995 and 1997, stool samples from 3,534 episodes of diarrhoea, that occurred in Colina, were obtained. Two hundred twenty six Shigella strains were isolated and studied for susceptibility to ampicilin (AM), amoxicillin/clavulanic acid (AMC), cotrimoxazole (STX), chloramphenicol (CAF), tetracycline (TET), furazolidine (FU), ciprofloxacine (CIPR), nalidixic acid (AC NAL), gentamycin (GENT) and cefotaxime (CFTX). Results: Shigella flexnerii represented 134 of 226 Shigella strains isolated. All strains were susceptible to CIPR, AC NAL, GENT and CFTX. Yearly variation of resistance patterns to other antimicrobials were observed for these strains. Resistance to AM varied from 56 to 76 percent, to AMC from 25 to 56 percent, to STX from 21 to 47 percent, to CAF from 36 to 39 percent, to TET from 44 to 78 percent and to FU from 9 to 18 percent. Overall resistance was higher during 1997. All 85 strains of S sonnei were susceptible to CIPR, AC NAL and CFTX. Resistance throughout the years varied from 56 to 88 percent for AM, from 0 to 28 percent for AMC, from 44 to 53 percent for STX, from 11 to 40 percent for CAF, from 11 to 42 percent for TET and from 5 to 11 percent for FU. Overall resistance was also higher during 1997, except for AM and STX. Seven S boydii strains were isolated, only during 1995. All seven were resistant to AM and TET and none were resistant to FU, CIPR, AC NAL and CFTX. One strain was resistant to AMC, STX and CAF. Conclusions: Antimicrobial resistance patterns of Shigella sp isolated in Colina have increased from 1995 to 1997, specially for commonly used antimicrobials. Resistance remains low for furazolidine and all strains remain susceptible to quinolones

Actualidad y perspectivas de la farmacología de drogas antibacterianas / Update and perspectives of the pharmacology of antibacterial drugs

Se hizo una revisión de los grupos y fármacos antimicrobianos que con mayor éxito se utilizan para tratar infecciones bacterianas provocadas por los microorganismos más resistentes y preocupantes. Se adicionaron los que por los resultados obtenidos en las fases iniciales de investigación tienen mayores perspectivas de ser introducidos en la práctica clínica con el fin de controlar y resolver infecciones bacterianas de dificil manejo

Atividade antimicrobiana in vitro da cefpiroma em comparaçäo com outros beta-lactâmicos de amplo espectro contra 804 amostras clínicas de nove hospitais brasileiros / Antimicrobial activity of cefpirome compared to other broad-spectrum beta-lactam drugs against 804 clinical isolates from 9 Brazilian hospitals

Objetivo. Avaliar a atividade in vitro da cefalosporina de quarta geraçao, cefpiroma em comparaçao com ceftazidima, ceftriaxona, cefotaxima e imipenem em um estudo multicêntrico envolvendo nove hospitais de seis cidades em quatro estados. Material e Métodos. Foram estudadas 804 amostras clínicas isoladas em pacientes internados em unidades de terapia intensiva ou unidades de oncohematologia. As amostras foram coletadas no período de junho a novembro de 1995, isto é, antes da cefpiroma estar disponível comercialmente no Brasil, e testadas através do método de microdiluiçao em placas conforme descrito pelo National Committee for Clinical Laboratory Standards (NCCLS). Todas as amostras resistentes à cefpiroma foram retestadas utilizando-se o E-test. Resultados. Contra as amostras de enterobactérias (n=344), a cefpiroma apresentou atividade de 2 a 32 vezes superior àquela apresentada pelas cefalosporinas de terceira geraçao (CTGs) e semelhnate àquela apresentada pelo imipenem. As porcentagens de enterobactérias sensíveis foram: 88 por cento para a cefpiroma, 69 por cento para as CTGs e 96 por cento para o imipenem. O espectro de açao da cefpiroma foi maior ou igual ao do imipenem contras as espécies Citrobacter freundii, E. aerogenes, Morganella morganii e Serratia marcescens. Contra Acinetobacter sp. (n=77), a cefpiroma foi ligeiramente mais ativa que a ceftazidima, porém as porcentagens de resistência foram muito altas para esses compostos (84 por cento e 88 por cento respectivamente). As atividades da cefpiroma, ceftazidima e imipenem foram semelhantes contra Pseudomonas aeruginosa (n=128), com MIC50/porcentagem de sensibilidade de 8/59 por cento, 8/62 por cento e 4/62 por cento respectivamente. Contra bactérias aeróbias gram-positivas, a cefpiroma foi de 4 a 16 vezes mais ativa que as CTGs. Contra S. epidermidis e outras espécies de estafilococos coagulase-negativos a cefpiroma foi ligeiramente superior ao imipenem, porém, contra as outras espécies de bactérias gram-positivas avaliadas, o imipenem apresentou atividade um pouco superior. Conclusao: Os resultados desse estudo sugerem que, no Brasil, a cefpiroma apresenta espectro de açao superior ao das CTGs contra bactérias gram-negativas (Enterobacteriaceae e nao fermentadares) e gram-positivas e semelhante ao do imipenem contra algumas espécies de enterobactérias e contra P. aeruginosa.

Antibacterianos de acción sistémica, parte I: antibióticos betalactámicos / Systemic antibacterial drugs, part I: other groups of antibiotics

Se presenta una revisión bibliográfica sobre los antibacterianos de acción sistémica, de los cuales en esta primera parte se desarrolla la de los antibióticos betalactámicos, así como algunos conceptos básicos y los diferentes tipos de clasificación de los antibióticos en general. Se abordan los derivados penicilánicos y cafalosporánicos más conocidos internacionalmente

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

Agentes antituberculosos. Nuevas alternativas farmacológicas / Antituberculous drugs. New alternatives

La principal indicación de los fármacos antituberculosos de segunda línea es la presencia de tuberculosis resistente a drogas primarias. Comparados con los antituberculosos de primera línea, estos fármacos tienen una menor actividad antimicrobiana, más efectos colaterales, algunos son más caros y varios regímenes en los que se incluyen estas drogas son administradas por un mayor tiempo. Los principales fármacos son: ácido paraaminosalicílico (PAS), tiacetazona, clofazimina, etionamida, cicloserina, capreomicina, amikacina y kanamicina. Sus mecanismos de acción y de resistencia, así como su absorción, eliminación y efectos colaterales son diferentes para cada droga. Para el PAS y la tiacetazona los efectos colaterales más importantes son a nivel gastrointestinal; la clofazimina puede producir hiperpigmentación de la piel; la ciloserina puede originar síntomas neurológicos; los aminoglucósidos y la capreomicina generalmente causan trastornos vestibulococleares. Las contraindicaciones y las dosis de cada fármaco, de acuerdo a las posibles enfermedades concomitantes, son quizás de los aspectos a considerar más importantes cuando estas drogas son administradas

Penicillin-binding proteins of pathogenic Yersinia species

As PBPs de Yersinia pestis, Y. enterocolitica e Y. pseudotuberculosis crescidas a 28ºC ou a 37ºC foram detectadas após marcaçäo com [3H]-benzilpenicilina e fluorografia dos géis de poliacrilamida. Cada amostra apresentou um perfil único de PBPs composto por 3 a 6 proteínas com peso molecular variando entre 120.000 e 43.000. Incubaçäo a 37ºC resultou em mudanças significativas nos perfis de PBPs das 3 espécies estudadas. As possíveis implicaçöes destes resultados na açäo dos antibióticos ß-lactâmicos e na fisiologia destas bactérias

Antibióticos (II): betalactámicos, B. cefalosporinas o cefemes / Antibiotics (II): betalactamics, B. cephalosporins or cefemes

Las cefalosporinas o cefemes son antibióticos betalactámicos que tienen un núcleo constituído por el ácido 7-amino-cefalosporánico. Las hay de primera, segunda y tercera generación. Las de primera, tienen un espectro parecido al de las aminopenicilinas. Las de tercera, son más resistentes a las cefalosporinasas; se administran por vía parenteral y en su espectro de acción se incluyen las enterobacterias refractarias a las aminopenicilinas y a las cefalosporinas de primera generación. La cefixima es la única cefalosporina de tercera generación de administración oral

Antibióticos I: betalactámicos: penicilinas o penames / Antibiotics I: betalactamics: penicillins or penames

Entre los 53 años transcurridos desde la introducción de la penicilina al campo de la terapéutica, se ha modificado substancialmente la patología infecciosa; han aparecido cepas microbianas resistentes a algunos antibióticos y se han descubierto nuevos antimicrobianos de espectros más amplios; de efectos más potentes y de mejor tolerancia. Uno de los grupo de antibióticos de mayor utilidad es el de las penicilinas o penames que tienen todas un núcleo 6 aminopenicilánico común y que forman parte de los betalactámicos. En esta revisión se presentan esquemáticamente los espectros de acción, las principales indicaciones clínicas y las dosis habituales de los diversos tipos de penicilinas disponibles

Comparative evaluation of in vitro activity of different combinations of new B-lactam antimicrobial agents and amikacin against pseudomonas aeruginosa using the checkerboard titration technique

In vitro activities of antibiotic combinations containing amikacin and either piperacillin, aztreonam, ceftazidime, imipenem, or cefsulodin were evaluated by the checkerboard broth dilution method in 96-well microtiter plates. A total of 100 strains of Ps. Aeruginosa were tested. All drugs were tested in serial dilutions ranging from 250 to 3.9 mug/ml against standardized inoculum of 108 cells/ml of the bacterial suspension. Results showed that newer beta-lactams with antipseudomonal activity [as cefsulodin, piperacillin and aztreonam] in combination with amikacin are effective combination regimens against clinical isolates of Ps. aeruginosa and may be useful for empirical management of patients with serious Ps. Aeruginosa infection

Ensaio comparativo milticêntrico do aztreonam no tratamento de infecçöes Gram-negativas em pacientes comprometidos sob tratamento intensivo / A multicenter comparative trial of aztreonam in the treatment of Gram-negative infections in compromised intensive-care patients

Um ensaio comparativo multicêntrico foi realizado em 4 hospitais universitários para avaliar a eficácia do aztreonam, um novo antibiótico monobactâmico. Todos os pacientes incluídos no estudo haviam sido admitidos à unidade de tratamento intensivo hospitalar com distúrbios subjacentes severos. No total, foram documentadas 167 infecçöes em 157 pacientes (78 pneumonias, 26 infecçöes do trato urinário, 23 peritonites e 40 septicemias). O estudo foi realizado em duas fases. Na fase 1, 49 pacientes que receberam aztreonam foram comparados a 26 que receberam amicacina. Ambas as drogas foram administradas como cobertura única contra bacilos Gram-negativos. Na fase 2, 48 pacientes tratados com aztreonam foram comparados a 34 que receberam uma combinaçäo sinérgica de amicacina e um beta-lactâmico de amplo espectro. Os resultados sugerem que o aztreonam pode ser adotado como monoterapia no tratamento de infecçöes Gram-negativas sistêmicas, com uma eficácia comparável à do tratamento antimicrobiano convencional. O aztreonam provavelmente é mais eficaz que a amicacina no tratamento de infecçöes do trato respiratório e pelo menos täo eficaz quanto à combinaçäo de beta-lactâmicos e aminoglicosídeos. Pode-se estabelecer uma dose-padräo adequada de 3-4 g/dia de aztreonam em pacientes comprometidos, devendo ser combinada a uma cobertura Gram-positiva quando o tratamento for prescrito empiricamente

El uso de antibióticos en el embarazo: parte I / The use of antibiotics during pregnancy: part I

El empleo de antibióticos durante el embarazo guarda riesgos particulares, siendo los efectos nocivos que pueden resultar del uso de éstos fármacos en la gestación: teratogenicidad, efectos sobre la madre, efectos sobre el curso del embarazo y efectos sobre el feto o el recién nacido. Se ha estimado que la gran mayoría de los antibióticos atraviesan la placenta en grado variable, algunos de ellos son seguros para utilizarse durante el embarazo mientras que algunos otros están completamente contraindicados. Las infecciones severas en la embarazada conllevan un riesgo alto de morbi-mortalidad tanto materna como fetal, sobrepasando en muchos casos el riesgo de los efectos nocivos de los antibióticos, es por ello que en ésta situación las pacientes deben recibir tratamiento antimicrobiano independientemente de los efectos adversos descritos o teóricos, debiendose seleccionar el antibiótico con mayor actividad antimicrobiana y menor riesgo tanto para la madre como para el feto.

Effect of subminimal inhibitory concentrations of clindamycin, streptomycin, chloramphenicol, erythromycin and clavulanic acid on the penicillinase production of Staphylococcus aureus, Bacillus cereus and Pseudomonas fluorescens

The influence of subminimal inhibitory concentrations of clindamycin, streptomycin, chloramphenicol, erythromycin and clavulanic acid on the penicillinase production of Staphylococ-cus aureus, Bacillus cereus and Pseudomonas fluorescens were tested. Results revealed that the penicillinase activity can be inhibited by subminimal inhibitory concentrations of these antibiotics. The maximal inhibitory effect was generally induced by concentrations ranging from 1/2 to 1/32 the minimal inhibitory concentrations of clmdamycin and clavulanic acid. Results also revealed that the clindamycin or clavulanic acid produced synergy when combined with penicillin G [Na] against three strains tested in vitro