Frequency and antibiotic susceptibility patterns of urinary pathogens in male outpatients in Argentina.

INTRODUCTION: Knowledge of the etiology and antimicrobial susceptibility patterns of uropathogens is important for determining the best treatment option. This study aimed to determine the distribution and antibiotic susceptibility patterns of bacterial strains isolated from adult male outpatients. METHODOLOGY: Between November 2012 and April 2013, 3,105 community urine samples were analyzed from adult male patients who attended the Laboratorio Hidalgo, Buenos Aires, Argentina. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disc diffusion method. Isolates resistant to third generation cephalosporin were tested for extended-spectrum beta-lactamase (ESBL) production using the double-disk synergy test. RESULTS: Of the 3,105 urine samples analyzed, 791 (25.5%) had significant bacteriuria. The frequency of positive urine cultures increased significantly with patient age. Escherichia coli was isolated most frequently (47.3%), followed by Enterococcus faecalis (13.6%), and Klebsiella pneumoniae (11.9%). Gram-negative organisms represented 78.8% of urinary pathogens. The highest activities against Gram-negative bacteria were found with imipenem (99.0%), amikacin (98.1%), ertapenem (94.2%), fosfomycin (90.7%), and piperacillin-tazobactam (90.1%). The frequencies of ESBLs among E. coli, K. pneumoniae, and P. mirabilis were 15.2 %, 22.3%, and 8%, respectively. Fosfomycin, piperacillin-tazobactam, and nitrofurantoin were most effective against Gram-positive organisms. CONCLUSIONS: Fosfomycin may be an excellent option for cystitis treatment in patients without risk factors, whereas piperacillin-tazobactam is preferred for the treatment of parenchymatous UTIs, complicated UTIs, and UTIs associated with risk factors. To ensure the optimal selection of antibiotics, physicians should have access to up-to-date information about the local prevalence of antimicrobial resistance.

Rápida adquisición de resistencia in vitro al ertapenem en Escherichia coli productora de betalactamasa de espectro extendido / In vitro emergence of ertapenem resistance in Escherichia coli producing extended-spectrum beta-lactamase

Introducción. Las infecciones por Escherichia coli productoras de BLEE son cada vez mas frecuentes en la comunidad. Ertapenem (ERT) presenta muy buena actividad frente a estas cepas y es una excelente indicación en infecciones severas en etapa de manejo ambulatorio. El objetivo de este trabajo fue determinar la frecuencia de selección de mutantes resistentes a carbapenemas en una colección de aislamientos clínicos de E. coli productoras de BLEE. Material y métodos. Se buscaron mutantes resistentes en uno y dos pasos a ERT, imipenem (IMI) y meropenem (MER) por inoculación de 109 ufc/ml en placas de agar Mueller Hinton conteniendo las carbapenemas a diferentes concentraciones. La concentración inhibitoria mínima (CMI) en las cepas originales y mutantes se determinó con el método epsilometrico Etest. Resultados. No se pudieron seleccionar mutantes resistentes con IMI y MER. Al utilizar ERT se obtuvieron mutantes resistentes en 13 de 57 aislamientos clínicos (22,8 %). Todos los mutantes resistentes fueron resistentes a ERT con CMI ≥ 1 mg/L pero mantuvieron sensibilidad a IMI y MER. Se obtuvieron 6 MR segundo paso con ERT las cuales presentaron resistencia de alto nivel a ERT (CMI ≥ 8 mg/L). Se observó resistencia cruzada a MER en 3 de ellas y en 1 a IMI. Los cuatro mutantes resistentes de segundo paso obtenidos con MER fueron resistentes a ERT y MER y en 2 de ellas se observó resistencia cruzada a IMI. Conclusiones. La selección de mutantes resistentes a ERT es frecuente en cepas de E. coli productoras de BLEE. Para obtener mutantes resistentes a MER e IMI es necesario un segundo paso de selección. El uso de ERT en infecciones con inóculo alto, focos no drenados y con cepas productoras de BLEE debería ser vigilado para reducir el riesgo de selección de resistencia (AU)

Introduction. The occurrence of community-associated infections due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. These organisms are frequently resistant to many of the antimicrobial agents but remain susceptible to carbapenems. We investigated the in vitro emergence of carbapenem resistance in a collection of clinical isolates of ESBL -producing E. coli Material and methods. First and second-step resistant mutants were obtained from E. coli with ESBL. Aliquots of 50μl containing > 109 CFU were applied to Mueller-Hinton plates containing meropenem, imipenem or ertapenem. MICs for native strains and mutants were determined using the epsilometric test (E-test). Results. Resistant mutants were not selected with imipenem or meropenem. E. coli growth was observed on ertapenem (0.5 mg/L)-containing plates in 13 of 57 clinical isolates (22.8 %).The ertapenem MIC for these first-step mutants were ≥ 1 mg/L, remaining susceptible to imipenem and meropenem. The first-step mutants were used as native strains. Six second-step resistant mutants were selected with ertapenem. All were fully resistant (CMI ≥ 8 mg/L) to ertapenem, three were resistant to meropenem and one to imipenem. Four second-step resistant mutants were selected with meropenem. All were resistant to ertapenem, meropenem, and two of them were resistant to imipenem. Conclusions. Stable resistant mutants were easy to select with ertapenem among ESBL-producing E. coli. Two steps were necessary to select resistant mutants to meropenem or imipenem. The use of ertapenem in high-inoculum infections or in undrained focus of infection should be monitored to reduce the risk on selection of resistance (AU)

Comparación del crecimiento y de la pérdida de viabilidad de Streptococcus pneumoniae en botellas FAN aeróbicas y BACTEC aeróbicas Plus / Comparison of growth and loss of viability of Streptococcus pneumoniaein FAN aerobic or BACTEC Plus aerobic culture bottles

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Urine inhibitory titers against resistant Escherichia coli isolates after oral amoxicillin-sulbactam.

UNLABELLED: It has been previously shown that following the oral administration of amoxicillin-sulbactam (AXS) the urinary activity against Escherichia coli (Ec) is due to beta-lactamase inhibition (i.e. TEM-1) as well as to the intrinsic activity of sulbactam (SB). Similarly, it has been previously demonstrated in volunteers that a single oral dose of AXS 500/500 mg allows high urine inhibitory titers (UITs) against resistant Ec isolates. In this in vitro and ex vivo study we assessed the urinary activity of a new AXS proportion: 875/125 mg. Urine was collected from 12 volunteers at 0-2; 2-4; 4-6 h after a single oral dose of AXS 875/125 mg. Previous studies had shown that pooled urine from 12 volunteers did not differ significantly in the UIT as compared to the mean individual values. Urine pools for each period were prepared. Each pool was tested for UIT against 60 Ec isolates received from 10 different laboratories in South American countries: 10 susceptible (S) to AXS; 10 intermediate (I) and 40 resistant (R); the latter ranging 32/16-256/128 mg/l. Amoxicillin (AX) and SB urine concentrations were determined in all the samples. UIT ranged from 1/4 to > 1/32 for S and I strains and from 1/1 to 1/4 for R strains. For one strain (AXS, MIC 256/128 mg/l) the UIT titer was 1/1 at 2 and 4 h but it was not inhibited at 6 h. AX mean levels ranged from 1872 (2 h) to 522 mg/l (6 h) while SB ranged from 1075 (2 h) to 334 (6 h) mg/l. It is noteworthy that 59/60 strains were inhibited by 128 mg/l SB alone. IN CONCLUSION: The AXS 875/125 proportion has a remarkable in vitro and ex vivo activity against Ec urinary isolates.

Urine inhibitory titers against resistant Escherichia coli isolates after oral amoxicillin-sulbactam.

It has been previously shown that following the oral administration of amoxicillin-sulbactam (AXS) the urinary activity against Escherichia coli (Ec) is due to beta-lactamase inhibition (i.e. TEM-1) as well as to the intrinsic activity of sulbactam (SB). Similarly, it has been previously demonstrated in volunteers that a single oral dose of AXS 500/500 mg allows high urine inhibitory titers (UITs) against resistant Ec isolates. In this in vitro and ex vivo study we assessed the urinary activity of a new AXS proportion: 875/125 mg. Urine was collected from 12 volunteers at 0-2; 2-4; 4-6 h after a single oral dose of AXS 875/125 mg. Previous studies had shown that pooled urine from 12 volunteers did not differ significantly in the UIT as compared to the mean individual values. Urine pools for each period were prepared. Each pool was tested for UIT against 60 Ec isolates received from 10 different laboratories in South American countries: 10 susceptible (S) to AXS; 10 intermediate (I) and 40 resistant (R); the latter ranging 32/16-256/128 mg/l. Amoxicillin (AX) and SB urine concentrations were determined in all the samples. UIT ranged from 1/4 to > 1/32 for S and I strains and from 1/1 to 1/4 for R strains. For one strain (AXS, MIC 256/128 mg/l) the UIT titer was 1/1 at 2 and 4 h but it was not inhibited at 6 h. AX mean levels ranged from 1872 (2 h) to 522 mg/l (6 h) while SB ranged from 1075 (2 h) to 334 (6 h) mg/l. It is noteworthy that 59/60 strains were inhibited by 128 mg/l SB alone. In CONCLUSION: The AXS 875/125 proportion has a remarkable in vitro and ex vivo activity against Ec urinary isolates.

Urine inhibitory titers against resistant Escherichi Coli isolates after oral amoxicillin-sulbactam

It has been previously shown that following the oral administration of amoxicillin-sulbactam (AXS) theurinary activity against Escherichia coli (Ec) is due to beta-lactamase inhibition (i.e.TEM-1) as well asto the intrinsic activity of sulbactam (SB). Similarly, it has been previously demonstrated in volunteers that a single oral dose of AXS 500/500 mg allows high urine inhibitory titers (UITs) against resistant Ec isolates. In this in vitro and ex vivo study we assessed the urinary activity of a new AXS proportion: 875/125 mg. Urine was collected from 12 volunteers at 0-2; 2-4; 4-6 h after a single oral dose of AXS 875/125mg. Previous studies had shown that pooled urine from 12 volunteers did not differ significantly in the UIT as compared to the mean individual values. Urine pools for each period were prepared. Each pool was tested for UIT against 60 Ec isolates received from 10 different laboratories in South American countries: 10 susceptible (S) to AXS; 10 intermediate (I) and 40 resistant (R); the latter ranging 32/16-256/128 mg/l. Amoxicillin (AX) and SB urine concentrations were determined in all the samples. UIT ranged from 1/4 to >1/32 for S and I strains and from 1/1 to 1/4 for R strains. For one strain (AXS, MIC 256/128mg/l) the UIT titer was 1/1 at 2 and 4 h but it was not inhibited at 6 h. AX mean levels ranged from 1872 (2 h) to 522 mg/l (6 h) while SB ranged from 1075 (2 h) to 334 (6 h) mg/l. It is noteworthy that 59/60 strains were inhibited by 128 mg/l SB alone. In conclusion: the AXS 875/125 proportion has a remarkable in vitro and ex vivo activity against Ec urinary isolates.(AU)

Urine inhibitory titers against resistant Escherichi Coli isolates after oral amoxicillin-sulbactam

It has been previously shown that following the oral administration of amoxicillin-sulbactam (AXS) theurinary activity against Escherichia coli (Ec) is due to beta-lactamase inhibition (i.e.TEM-1) as well asto the intrinsic activity of sulbactam (SB). Similarly, it has been previously demonstrated in volunteers that a single oral dose of AXS 500/500 mg allows high urine inhibitory titers (UITs) against resistant Ec isolates. In this in vitro and ex vivo study we assessed the urinary activity of a new AXS proportion: 875/125 mg. Urine was collected from 12 volunteers at 0-2; 2-4; 4-6 h after a single oral dose of AXS 875/125mg. Previous studies had shown that pooled urine from 12 volunteers did not differ significantly in the UIT as compared to the mean individual values. Urine pools for each period were prepared. Each pool was tested for UIT against 60 Ec isolates received from 10 different laboratories in South American countries: 10 susceptible (S) to AXS; 10 intermediate (I) and 40 resistant (R); the latter ranging 32/16-256/128 mg/l. Amoxicillin (AX) and SB urine concentrations were determined in all the samples. UIT ranged from 1/4 to >1/32 for S and I strains and from 1/1 to 1/4 for R strains. For one strain (AXS, MIC 256/128mg/l) the UIT titer was 1/1 at 2 and 4 h but it was not inhibited at 6 h. AX mean levels ranged from 1872 (2 h) to 522 mg/l (6 h) while SB ranged from 1075 (2 h) to 334 (6 h) mg/l. It is noteworthy that 59/60 strains were inhibited by 128 mg/l SB alone. In conclusion: the AXS 875/125 proportion has a remarkable in vitro and ex vivo activity against Ec urinary isolates.

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

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)