Detection, treatment, and prevention of carbapenemase-producing Enterobacteriaceae: recommendations from an International Working Group.

The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) has increased during the past 10 years. Its detection is frequently difficult, because they do not always show a minimum inhibitory concentration (MIC) value for carbapenems in the resistance range. Both broth microdilution and agar dilution methods are more sensitive than disk diffusion method, Etest and automated systems. Studies on antimicrobial treatment are based on a limited number of patients; therefore, the optimal treatment is not well established. Combination therapy with two active drugs appears to be more effective than monotherapy. Combination of a carbapenem with another active agent--preferentially an aminoglycoside or colistin--could lower mortality provided that the MIC is ≤4 mg/l and probably ≤8 mg/l, and is administered in a higher-dose/prolonged-infusion regimen. An aggressive infection control and prevention strategy is recommended, including reinforcement of hand hygiene, using contact precautions and early detection of CPE through use of targeted surveillance.

Resistencia a los antibacterianos en América Latina: consecuencias para la infectología / Antibacterial drug resistance in Latin America: consequences for infectiousdisease control

Antibacterial drug resistance is a particularly significant issue in Latin America. This article explores antimicrobial resistance in three classes of clinically important bacteria: gram-positive bacteria, enterobacteria, and nonfermenting gram-negativebacilli. The gram-positive bacteria frequently responsible for infections in humans are for the most part cocci: staphylococci, streptococci (including pneumococci), and enterococci,in both community and hospital settings. This situation is no different in theRegion of the Americas. Among the gram-positive bacteria, the causative agents of bacteremia are most commonly strains of coagulase-negative Staphylococcus, followed by enterococci. This report explores the resistance of these species to different antimicrobial drugs, resistance mechanisms in community and hospital strains, and new drugs for treating infections caused by these bacteria. In Latin America, antimicrobialresistance in Enterococcus strains is still a minor problem compared to the situation in the United States. The strains of the genus Streptococcus isolated from respiratory infections are still sensitive to penicillin. Furthermore, the resistance of enterobacteriais extremely important in the Region, particularly because of the broad dissemination of CTX-M extended-spectrum beta-lactamases (ESBL), some of which originated in Latin America. This article analyzes the resistance of Streptococcus pneumoniae, betahemolytic streptococci, and viridans group streptococci. Among the nonfermentinggram-negative bacilli, while Pseudomonas aeruginosa strains remain the leading cause of bacteremia, infections caused by strains of Acinetobacter spp. have proliferatedextensively in some areas. With regard to antibiotics, several options are available for treating gram-positive bacterial infections...

La resistencia a los fármacos antibacterianos tiene particular importancia en América Latina. En este artículo se analiza la resistencia a los antimicrobianos de tres clases de bacterias de importancia clínica: bacterias grampositivas, enterobacterias y bacilos gramnegativos no fermentadores.Las bacterias grampositivas que producen infecciones humanas frecuentes son, en su mayoría, cocos: estafilococos, estreptococos (incluidos neumococos) y enterococos, tanto en elmedio comunitario como en el nosocomial. Esta situación no es diferente en la Región de las Américas. Entre las bacterias grampositivas, las que causan bacteriemia con mayor frecuencia corresponden a cepas de estafilococos coagulasa negativos, seguidas de las de enterococos. Eneste informe se analiza la resistencia de estas especies a distintos antimicrobianos, los mecanismosde resistencia para las cepas de origen hospitalario y comunitario y los nuevos medicamentos para tratar las infecciones por estas bacterias. La resistencia a los antimicrobianos delas cepas de Enterococcus en América Latina todavía es un problema menor en relación con la situación en los Estados Unidos de América. Las cepas del género Streptococcus aisladasde infecciones respiratorias aún son sensibles a penicilina. Por otra parte, la resistencia de las enterobacterias es de gran importancia en la Región, particularmente por la gran difusión debetalactamasas de espectro extendido (BLEE) de tipo CTX-M, algunas de las cuales se originaron en América Latina. En el presente artículo se analizan la situación de la resistencia de las cepas de Streptococcus pneumoniae, y de los estreptococos betahemolítico y del grupo viridans. Entre los bacilos gramnegativos no fermentadores, si bien las cepas de Pseudomonasaeruginosa siguen siendo la causa principal de bacteriemias, la proliferación de infecciones por cepas de Acinetobacter spp. tiene en algunas partes gran magnitud...

[Antibacterial drug resistance in Latin America: consequences for infectious disease control]. / Resistencia a los antibacterianos en América Latina: consecuencias para la infectología.

Antibacterial drug resistance is a particularly significant issue in Latin America. This article explores antimicrobial resistance in three classes of clinically important bacteria: gram-positive bacteria, enterobacteria, and nonfermenting gram-negative bacilli. The gram-positive bacteria frequently responsible for infections in humans are for the most part cocci: staphylococci, streptococci (including pneumococci), and enterococci, in both community and hospital settings. This situation is no different in the Region of the Americas. Among the gram-positive bacteria, the causative agents of bacteremia are most commonly strains of coagulase-negative Staphylococcus, followed by enterococci. This report explores the resistance of these species to different antimicrobial drugs, resistance mechanisms in community and hospital strains, and new drugs for treating infections caused by these bacteria. In Latin America, antimicrobial resistance in Enterococcus strains is still a minor problem compared to the situation in the United States. The strains of the genus Streptococcus isolated from respiratory infections are still sensitive to penicillin. Furthermore, the resistance of enterobacteria is extremely important in the Region, particularly because of the broad dissemination of CTX-M extended-spectrum beta-lactamases (ESBL), some of which originated in Latin America. This article analyzes the resistance of Streptococcus pneumoniae, beta-hemolytic streptococci, and viridans group streptococci. Among the nonfermenting gram-negative bacilli, while Pseudomonas aeruginosa strains remain the leading cause of bacteremia, infections caused by strains of Acinetobacter spp. have proliferated extensively in some areas. With regard to antibiotics, several options are available for treating gram-positive bacterial infections. The same cannot be said for infections caused by enterobacteria and nonfermenting gram-negative bacilli, where options for the effective treatment of patients are still insufficient.

Biochemical characterization of PER-2 and genetic environment of blaPER-2.

PER-2 was the first detected and the second most prevalent extended-spectrum beta-lactamase in clinical pathogens isolated in Argentina and was also reported only in other South American countries. Citrobacter freundii 33587 was isolated in 1999 in Buenos Aires and was resistant to all tested beta-lactams except cephamycins and carbapenems. The strain produced both plasmid-borne TEM-1 and PER-2 (pI 5.4), which could be transferred by conjugation. By PCR screening, thermal asymmetric interlaced PCR, and DNA sequencing, we detected an ISPa12/IS1387a insertion sequence upstream of bla(PER-2), previously reported as also being associated with bla(PER-1). The presence of similar structures upstream of bla(PER-1) and bla(PER-2) suggests a common origin and mobilization. Compared to bla(PER-1) genes, an additional putative promoter for bla(PER-2) was found. PER-2 kinetic analysis showed its high hydrolysis efficiencies toward both CTX and CAZ (k(cat)/K(m), 0.76 and 0.43 microM(-1).s(-1), respectively).

Survey of bloodstream infection isolates: SENTRY Antimicrobial Surveillance Program in Buenos Aires, Argentina (1997-2002)

Regional antimicrobial surveillance programs might help to guide empiric antimicrobial therapy. This study reports the antimicrobial susceptibility patterns of 2198 isolates from bloodstream infections in a period of 1997 to 2002. Susceptibility testing was performed by broth microdilution methods. The most frequent organism was Staphylococcus aureus (23.4%) with an oxacillin-resistance rate of 41.8%. Extended Spectrum Beta Lactamases phenotype was presented in 10.0% of Escherichia coli and 49.4% in Klebsiella pneumoniae isolates. Imipenem and meropenem were active against 74.3% and 84.0% of Acinetobacter spp. and Pseudomonas aeruginosa, respectively. Bacterial resistance continues to be a great problem in Argentinean medical centers.

Estudio de un brote debido a aislados de Klebsiella pneumoniae productores de betalactamasas de espectro extendido en un centro asistencial de Rosario - Argentina / An outbreak of extended spectrum beta-lactamase Klebsiella pneumoniae producers in a health care center from Rosario - Argentina

En América Latina (AL) son trascendentes los productores de betalactamasas de espectro extendido (BLEE) en infecciones hospitalarias. Los datos de API y SENTRY revelan una incidencia del 22 a 55. En AL y frecuentemente en el Cono Sur predominan las BLEE de la familia CTX-M contrariamente a EUA y Europa donde prevalecen las derivadas de TEM. Las CTX-M afectan cefotaxima, ceftriaxona y cefepima con más frecuencia que ceftacidima. El tratamiento depende del empleo de carbapenemes con el riesgo de seleccionar resistencia en bacilos gram negativos no fermentadores. El uso de otros betalactámicos particularmente cefepima no es aconsejable por las frecuentes fallas observadas en nuestro medio debido al efecto inóculo por aislados productores de CTX-M-2. Describimos un brote por Klebsiella pneumoniae (Kp) ocurrido entre junio-julio 2004. En el período previo, sólo un paciente presentó una infección debida a Kp productora de BLEE y en el posterior, lo presentaron dos pacientes Se determinó la CIM por microdilución en agar. El fenotipo BLEE se sospechó por ensayo del efecto del clavulanato unido a cefalosporinas de 3ª generación (C3G). Se determinó el punto isoeléctrico (pI) y la detección por PCR del tipo molecular por métodos convencionales. Se comprobaron dos bandas pI 5.4 y 8.2 con ampicilina y ceftriaxona en todas las cepas excepto en dos. Todas las cepas revelaron producción de CTX-M-2 excepto en dos cepas que se identificaron como productoras de SHV-5. Los estudios clonales se correspondieron con los moleculares identificándose dos clones. El brote se resolvió usando dos importantes medidas: 1) lavado de manos y otras medidas de barrera y 2) restringiendo el uso de C3G y ciprofloxacina

Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases.

The prevalence of extended-spectrum beta -lactamase (ESBL) production by Klebsiella pneumonia approaches 50% in some countries, with particularly high rates in eastern Europe and Latin America. No randomized trials have ever been performed on treatment of bacteremia due to ESBL-producing organisms; existing data comes only from retrospective, single-institution studies. In a prospective study of 455 consecutive episodes of Klebsiella pneumoniae bacteremia in 12 hospitals in 7 countries, 85 episodes were due to an ESBL-producing organism. Failure to use an antibiotic active against ESBL-producing K. pneumoniae was associated with extremely high mortality. Use of a carbapenem (primarily imipenem) was associated with a significantly lower 14-day mortality than was use of other antibiotics active in vitro. Multivariate analysis including other predictors of mortality showed that use of a carbapenem during the 5-day period after onset of bacteremia due to an ESBL-producing organism was independently associated with lower mortality. Antibiotic choice is particularly important in seriously ill patients with infections due to ESBL-producing K. pneumoniae.

International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial Infections.

BACKGROUND: Commonly encountered nosocomially acquired gram-negative bacteria, especially Klebsiella pneumoniae, produce extended-spectrum beta-lactamases (ESBLs) as an antibiotic resistance mechanism. OBJECTIVE: To determine whether microbiology laboratories should report the presence of ESBLs and to establish the infection-control implications of ESBL-producing organisms. DESIGN: Prospective observational study. SETTING: 12 hospitals in South Africa, Taiwan, Australia, Argentina, the United States, Belgium, and Turkey. PATIENTS: 440 patients with 455 consecutive episodes of K. pneumoniae bacteremia between 1 January 1996 and 31 December 1997; of these, 253 episodes were nosocomially acquired. MEASUREMENTS: The K. pneumoniae isolates were examined for the presence of ESBLs. Pulsed-field gel electrophoresis was used to analyze the molecular epidemiology of nosocomial bacteremia with ESBL-producing K. pneumoniae. RESULTS: Overall, 30.8% (78 of 253) episodes of nosocomial bacteremia and 43.5% (30 of 69) episodes acquired in intensive care units were due to ESBL-producing organisms. After adjustment for potentially confounding variables, previous administration of beta-lactam antibiotics containing an oxyimino group (cefuroxime, cefotaxime, ceftriaxone, ceftazidime, or aztreonam) was associated with bacteremia due to ESBL-producing strains (risk ratio, 3.9 [95% CI, 1.1 to 13.8]). In 7 of 10 hospitals with more than 1 ESBL-producing isolate, multiple strains with the same genotypic pattern were observed, indicating patient-to-patient spread of the organism. CONCLUSIONS: Production of ESBLs by Klebsiella pneumoniae is a widespread nosocomial problem. Appropriate infection control and antibiotic management strategies are needed to stem the spread of this emerging form of resistance.

CTX-M-12 beta-lactamase in a Klebsiella pneumoniae clinical isolate in Colombia.

We describe the detection of the CTX-M-12 beta-lactamase from a clinical isolate of Klebsiella pneumoniae in Colombia. Screening of nosocomial Klebsiella spp. and Escherichia coli isolates from a network of teaching hospitals revealed the presence of CTX-M enzymes in multiple cities. This is the first description of CTX-M in Colombia.

Argentinean collaborative multicenter study on the in vitro comparative activity of piperacillin-tazobactam against selected bacterial isolates recovered from hospitalized patients.

The in vitro activity of piperacillin-tazobactam and several antibacterial drugs commonly used in Argentinean hospitals for the treatment of severe infections was determined against selected but consecutively isolated strains from clinical specimens recovered from hospitalized patients at 17 different hospitals from 9 Argentinean cities from different geographic areas during the period November 2001-March 2002. Out of 418 Enterobacteriaceae included in the Study 84% were susceptible to piperacillin-tazobactam. ESBLs putative producers were isolated at an extremely high rate since among those isolates obtained from patients with hospital acquired infections 56% of Klebsiella pneumoniae, 32% of Proteus mirabilis and 25% Escherichia coli were phenotypically considered as ESBLs producers Notably P.mirabilis is not considered by for screening for ESBL producers. ESBLs producers were 100% susceptible to imipenem and 70% were susceptible to piperacillin-tazobactam whereas more than 50% were resistant to levofloxacin. The isolates considered as amp C beta lactamase putative producers showed 99% susceptibility to carbapenems while 26.7% were resistant to piperacillin-tazobactam and 38.4% to levofloxacin. Noteworthy only 4% of the Enterobacteriaceae isolates were resistant to amikacin. Piperacillin-tazobactam was the most active agent against Pseudomonas aeruginosa isolates (MIC(90): 128 microg/ml; 78% susceptibility) but showed poor activity against Acinetobacter spp (MIC(90):>256 microg/ml; 21.7% susceptibility). Only 41.7% Acinetobacter spp isolates were susceptible to ampicillin-sulbactam. Piperacillin-tazobactam inhibited 100% of Haemophilus influenzae isolates (MIC(90) < 0.25 microg/ml) but only 16.6% of them were ampicillin resistant. The activity of piperacillin-tazobactam against oxacillin susceptible Staphylococcus aureus or coagulase negative staphylococci was excellent (MIC(90) 2 microg/ml; 100% susceptibility). Out of 150 enterococci 12 isolates (8%) were identified as E.faecium and only three isolates (2%), 2 E.faecium and 1 E.faecalis were vancomycin resistant. All the enterococci isolates were susceptible to linezolid. Piperacillin-tazobactam showed excellent activity (MIC(90) 2 microg/ml; 92% susceptibility). Regarding pneumococci all the isolates showed MICs of 16 microg/ml for piperacillin-tazobactam. Among 34 viridans group streptococci only 67% were penicillin susceptible and 85.2% ceftriaxone susceptible whereas piperacillin-tazobactam was very active (MIC(90) 4 microg/ml).Piperacillin-tazobactam is therefore a very interesting antibacterial drug to be used, preferably in combination (IE: amikacin-vancomycin) for the empiric treatment of severe infections occurring in hospitalized patients in Argentina. Caution must be taken for infections due to ESBL producers considering that the inoculum effect MICs can affect MIC values.

Actividad in vitro de niveles séricos y urinarios de amoxicilina y amoxicilina-sulbactam sobre 820 cepas de escherichia coli aisladas de infecciones urinarias bajas extrahospitalarias: estudio sudamericano / In vitro activity at serum and urinary levels of amoxicillin and amoxicillin-sulbactam against 820 escherichia coli strains isolated from community acquired urinary tract infections: South American collaborative study

Previamente, habíamos demostrado la actividad que poseen amoxicilina-sulbactam y sulbactam solo frente a Escherichia coli en la orina. Realizamos un estudio para determinar la etiología de las infecciones urinarias bajas no complicadas de la comunidad (IUBNCC) en Sudamérica. Participaron 10 laboratorios de 8 países sudamericanos. Cada laboratorio envió al centro coordinador (CEA, Bs. Aires) los resultados de susceptibilidad a amoxicilina y amoxicilina-sulbactam por el método de discos en 100 aislamientos consecutivos obtenidos de pacientes de 3 a 70 años con IUBNCC y además remitieron 20 cepas de E. coli consecutivas consideradas resistentes a amoxicilina por el método de disco. En el CEA se comprobó la CIM de amoxicilina, amoxicilina-sulbactam (2:1) y sulbactam solo; se determinó el título inhibitorio de la orina (TIO) en 12 voluntarios que recibieron una dosis oral de 500:500 mg de amoxicilina-sulbactam. Las orinas se recolectaron a las 0 a 2,2 a 4 y 4 a 6 h luego de la administración de amoxicilina-sulbactam y los TIO se verificaron sobre 5 cepas de E. coli resistentes (R) y 1 cepa sencible (S) a amoxicilina-sulbactam seleccionadas con diferentes CIM, entre las recibidas de cada centro participante; se determinaron las concentraciones de amoxicilina y sulbactam en la orina por un método microbiológico. Resultados: E. coli fue predominante 820/1.000 (82 por ciento); P, mirabilis y K. pneumoniae (4,3 por ciento ambas); S. saprophyticus (4,1 por ciento) y otros (5,3 por ciento). Susceptibilidad por discos en E. coli: 59,4 por ciento R a amoxicilina; 16,9 por ciento intermedias (I) y 23,7 por ciento S y para amoxicilina-sulbactam 28 por ciento R, 19,2 por ciento I y 52,8 por ciento S. Determinación de CIM: se estudiaron 102 E. coli R a amoxicilina-sulbactam, las CIM 90 (µg/ml fueron: amoxicilina > 2.048; amoxicilina-sulbactam: 256/128 y sulbactam solo, 128. TIO: Variaron desde > 1/32 a las 2 h; 1/16-1/4 a las 4 h y 1/4-1/2 a las 6 h para todas cepas estudiadas. Niveles de ATB en orina (µg/mI): amoxicilina y sulbactam respectivamente a las 2 h: 1.414 y 1.904: a las 4 h: 691 y 1.257 y a las 6 h: 462 y 641. Nuestros resultados confirman el predominio de E. coli en IUBNCC en Sudamérica y explican las discrepancias entre las resistencia supuesta por el método de discos y los éxitos clínicos logrados con amoxicilina-sulbactam en IUBNCC

Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns.

We initiated a worldwide collaborative study, including 455 episodes of bacteremia, to elucidate the clinical patterns of Klebsiella pneumoniae. Historically, community-acquired pneumonia has been consistently associated with K. pneumoniae. Only four cases of community-acquired bacteremic K. pneumoniae pneumonia were seen in the 2-year study period in the United States, Argentina, Europe, or Australia; none were in alcoholics. In contrast, 53 cases of bacteremic K. pneumoniae pneumonia were observed in South Africa and Taiwan, where an association with alcoholism persisted (p=0.007). Twenty-five cases of a distinctive syndrome consisting of K. pneumoniae bacteremia in conjunction with community-acquired liver abscess, meningitis, or endophthalmitis were observed. A distinctive form of K. pneumoniae infection, often causing liver abscess, was identified, almost exclusively in Taiwan.

In vitro activity of the new ketolide ABT-773 against community acquired respiratory tract isolates and Viridans Streptococci.

A total of 230 isolates were collected from clinical specimens of patients attending five health centers of the Buenos Aires, Argentina. ABT-773 was compared to erythromycin, azithromycin and clindamycin against bacterial isolates responsible for community-acquired respiratory tract infections and viridans streptococci showing different resistance patterns. Time-kill curves were also performed against selected resistant isolates. All but one of the 105 pneumococcal isolates were susceptible to ABT-773. Among the erythromycin resistant S. pyogenes isolates, all the M type and inducible isolates were susceptible to ABT-773. ABT-773 showed excellent activity against macrolide, azalide, lincosamide (MAL) inducible S. aureus producers but was inactive against constitutive producers. ABT-773 activity against viridans streptococci was also excellent.ABT-773 exerted bactericidal activity against selected isolates of S. pneumoniae, M. catarrhalis and H. influenzae, however, it was only bacteriostatic against methicillin-susceptible S. aureus.

Erradicación de Escherichia coli de la orina vesical por Amoxicilina-sulbactam. Actividad intrínseca del inhibidor / Escherichia coli eradication from the blader urine by amoxicillin-sulbactam. Intrinsic activity of the inhibitor

FUNDAMENTACIÓN. Amoxicilina-sulbactam oral (500/500 mg) inhibe cerca del 90 por ciento de los aislados de Escherichia coli y Proteus mirabilis a las concentraciones urinarias obtenidas. OBJETIVOS. Administrar amoxicilina-sulbactam 875/125 mg y determinar: concentración mínima inhibitoria (CMI) de E. coli y P. mirabilis a sulbactam; poder inhibitorio de la orina (PIO) frentre a E. coli o P. mirabilis resistentes a amoxicilina; concentración urinaria de sulbactam; comprobar si 125 mg de sulbactam solo produce un PIO elevado que avale la acción intrínseca del inhibidor; comparar la acción de amoxicilina-sulbactam con amoxicilina-clavulánico y la de sulbactam con clavulánico. MÉTODOS. Doce voluntarios sanos recibieron de forma cruzada, al azar, amoxicilina-sulbactam 875/125 mg o amoxicilina-clavulánico 875/125 mg, en dosis única. Muestras: basal, 2, 4 y 6 h. Se determinó pH, densidad y PIO. Se sembraron 39 cepas aisladas de orinas: de E. coli 30 hiperproductoras de TEM-1 y 3 de betalactamasa de espectro extendido CTX-M-2; y de P. mirabilis (6) resistentes a ambas combinaciones. Seis voluntarios sanos recibieron 125 mg de sulbactam y se determinó el PIO frente a E. coli con CMI para amoxicilina >2.048 mg/l. RESULTADOS Y DISCUSIÓN. Las CMI 90 de sulbactam o clavulánico con amoxicilina resultaron iguales a las CMI 90 para sulbactam o clavulánico solos, sin diferencias atribuibles a la composición urinaria. La actividad de amoxicilina con inhibidores podría deberse tanto a la inhibición de las betalactamasas, como a la acción intrínseca de los inhibidores. Ambas combinaciones presentan actividad inhibitoria equivalente. Los PIO de 2 horas son francamente elevados y lo siguen siendo a las 6 horas. También las concentraciones de sulbactam exceden, casi hasta las 6 horas, las CMI para sulbactam, resultando así co-responsable de la inhibición de E. coli en orina vesical. Cuestionamos el punto de corte propuesto por National Committee for Clinical Laboratory Standards (NCCLS) para valores "intermedios", que para estos antimicrobianos es 16/8, valor muy por debajo de los alcanzados en orina por los inhibidores. Esto explica las curaciones de infecciones urinarias bajas no complicadas del sexo femenino, con amoxicilina-sulbactam cuando los aislados infectantes fueron considerados como "resistentes" por métodos de difusión (AU)