Eficacia del alprazolam en comprimidos sublinguales para el tratamiento de los trastornos de pánico en la fase aguda / Efficacy of alprazolam sublingual tablets in the treatment of the acute phase of panic disorders

Introducción. El trastorno de pánico afecta del 2 al 5% de la población general. En Argentina habría un millón de afectados con una tasa de comorbilidad psiquiátrica del 91%. Objetivo. Comparar parámetros de eficacia entre comprimidos convencionales (CC) y sublinguales (CS) de alprazolam en el tratamiento de la fase aguda de los trastornos de pánico con o sin agorafobia. Metodología. Estudio comparativo, multicéntrico (6 centros), doble ciego, aleatorizado. Se trataron 190 pacientes con (n=117) y sin (n=73) agorafobia, con CC o CS durante 12 semanas y se evaluaron con: Impresión Clínica Global (CGI), Escala de Ansiedad de Hamilton, Escala de Experiencia Sexual de Arizona (ASEX), Impresión General del Paciente (PGI), Índice de Bienestar Psicológico y General (PGWBI), Escala de Severidad del Trastorno de Pánico (PDSS) y por la cantidad de ataques de pánico, su duración, intensidad y ansiedad anticipatoria. Resultados. Ambos tratamientos lograron una mejoría clínica estadísticamente significativa en todas las mediciones. El ASEX no presentó cambios durante el estudio. La dosis promedio de alprazolam durante las 12 semanas fue de 1,36 ± 0,70 mg/día (1,39 ± 0,77 CC y 1,33 ± 0,64 CS). Con CS los ataques de pánico fueron más breves (p < 0,05) así como menor la duración (p=0,16) e intensidad de la ansiedad anticipatoria (p=0,14). El tratamiento fue bien tolerado sin diferencias entre los dos grupos. Conclusiones. El alprazolam demostró eficacia, seguridad y buena tolerabilidad en el tratamiento de la fase aguda de los trastornos de pánico. Los comprimidos sublinguales mostraron algunas ventajas comparativas (AU)

Background. Panic disorder affects 2-5% of the general population. In Argentina, one million people would be affected with a 91% rate of psychiatric comorbidity. Aim. To compare efficacy parameters between sublingual (ALP-SL) and conventional (ALP-CT) tablets of alprazolam in the treatment of acute phase of panic disorder with and without agoraphobia. Subjects and Methods. A comparative, multicenter (6 sites), double blind, randomized study was carried out. A total of 190 outpatients with (n=117) and without (n=73) agoraphobia were treated with ALP-SL or ALP-CT for 12 weeks. Outcome was assessed with the Clinical Global Impressions (CGI-S/CGI-I), Hamilton Rating Scale for Anxiety (HAM-A), Arizona Sexual Experiences Scale (ASEX),Patient Global Impression (PGI), Psychological General Well-Being Index (PGWBI), Panic Disorder Severity Scale (PDSS) also by the number of panic attacks and extension and intensity of panic attacks and anticipatory anxiety. Results. Both treatments resulted in statistically significant clinical improvement in all measures. ASEX presented no changes during the study. The average dose of alprazolam for 12 weeks was 1.36 ± 0.70 mg/day (1.39± 0.77 ALP-CT and 1.33 ± 0.64 ALP-SL). With ALP-SL, panic attacks were shorter (p < 0.05) with shorter extension (p=0.16) and intensity of anticipatory anxiety(p=0.14). The treatment was well tolerated, there being no differences between both groups. Conclusions. Alprazolam has been demonstrated to have efficacy, safety and good tolerability in the treatment of the acute phase of panic disorder, the sublingual tablets showing some comparative advantages (AU)

Efficacy of alprazolam sublingual tablets in the treatment of the acute phase of panic disorders.

BACKGROUND: Panic disorder affects 2-5% of the general population. In Argentina, one million people would be affected with a 91% rate of psychiatric comorbidity. AIM; To compare efficacy parameters between sublingual (ALP-SL) and conventional (ALP-CT) tablets of alprazolam in the treatment of acute phase of panic disorder with and without agoraphobia. SUBJECTS AND METHODS: A comparative, multicenter (6 sites), double blind, randomized study was carried out. A total of 190 outpatients with (n=117) and without (n=73) agoraphobia were treated with ALP-SL or ALP-CT for 12 weeks. Outcome was assessed with the Clinical Global Impressions (CGI-S/CGI-I), Hamilton Rating Scale for Anxiety (HAM-A), Arizona Sexual Experiences Scale (ASEX), Patient Global Impression (PGI), Psychological General Well-Being Index (PGWBI), Panic Disorder Severity Scale (PDSS) also by the number of panic attacks and extension and intensity of panic attacks and anticipatory anxiety. RESULTS. Both treatments resulted in statistically significant clinical improvement in all measures. ASEX presented no changes during the study. The average dose of alprazolam for 12 weeks was 1.36 ± 0.70 mg/day (1.39 ± 0.77 ALP-CT and 1.33 ± 0.64 ALP-SL). With ALP-SL, panic attacks were shorter (p < 0.05) with shorter extension (p=0.16) and intensity of anticipatory anxiety (p=0.14). The treatment was well tolerated, there being no differences between both groups. CONCLUSIONS: Alprazolam has been demonstrated to have efficacy, safety and good tolerability in the treatment of the acute phase of panic disorder, the sublingual tablets showing some comparative advantages.

Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model

Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/ß-lactamase inhibitor combination currently available in 29 countries and may be a suitable option for treating infections caused by Acinetobacter spp. Thus, we sought to search the optimal dosing strategy for this formulation through an ex vivo pharmacodynamic human model against Acinetobacter baumanniii. Four volunteers were randomized to receive alternatively a single dose AMX-SUL infused both either over 30 min or 3h at the following ratios (g/g): 1/0.5; 1/1, and 0/2. Time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h sera after dose against a clinical isolate of A. baumannii (sulbactam MIC, 4µg/mL). Bactericidal activity (i.e. a mean decrease >3 log10 CFU/mL in the viable cell counts from the initial inoculum) was displayed by the 0.5- and the 2-h sera after dose for all formulations. The 4-h sera proved inhibitory with the AMX-SUL 1g/1g formulation, albeit a trend to regrowth was observed after 24-h incubation. With the AMX-SUL 0g/2g dose, the 4-h sera proved almost bactericidal activity (i.e. a mean decrease of 2.4 log10 CFU/mL in the viable cell counts from the initial inoculum), whereas the 6-h sera was inhibitory, with a trend to regrowth after 24-h incubation. When infused over 3h, AMX-SUL 1g/0.5g and 1g/1g, bactericidal activity was displayed by the 0.5-, 2- and the 4-h sera after dose and the 6-h sera proved inhibitory with the AMX-SUL 1g/1g formulation. The present study, albeit preliminary, might give a rationale for the dosing strategy to treat infections caused by A. baumannii with sulbactam, either alone or combined with amoxicillin. A 2-g sulbactam dose seems to be optimal to be infused over 30 min with a 6-h dosing interval. When infused over 3h, AMX-SUL 1g/1g given every 6h or 8h seems a suitable dosing schedule.

[Acid suppression capacity of omeprazole, sodium bicarbonate and alginic acid in an oral powder combination]. / Capacidad acidosupresora de omeprazol, bicarbonato de sodio y alginato de sodio en polvo para suspensión oral.

BACKGROUND: The combination of omeprazole, sodium bicarbonate and alginic acid protects omeprazole from acid degradation and enhances the speed of action of the proton pump inhibitors. AIM: To assess acid suppression capacity and speed of action of an oral powder combination (omeprazole 20 mg, sodium bicarbonate 1680 mg and alginic acid 250.08 mg) in healthy subjects, using gastric 24 h pHmetry. SUBJECTS AND METHODS: Gastric 24 h pHmetry was performed in 13 healthy subjects on days 0 and 6. During the first pHmetry, 7 subjects received the combination 2 h before the end of the procedure. The second study was performed after the subjects had been administered the medication for the six previous days. The measurements were: a) time with pH < 4, b) time to reach maximum pH value, and c) pH peak after first drug administration. RESULTS: The percentage of time with pH < 4 was 72.02 +/- 20.18 in the first study and 34.05 +/- 20.50 in the second (p < 0.01). Maximum pH obtained after first drug administration was 6.98 +/- 1.66 and the time to reach the pH peak was 18.34 +/- 9.84 minutes. CONCLUSION: This oral powder combination induces significant, fast and intensive gastric acid suppression. Unlike delayed-release proton pump inhibitors, this product provides a faster but equally sustained control of gastric acidity.

Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model.

Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/ss-lactamase inhibitor combination currently available in 29 countries and may be a suitable option for treating infections caused by Acinetobacter spp. Thus, we sought to search the optimal dosing strategy for this formulation through an ex vivo pharmacodynamic human model against Acinetobacter baumanniii. Four volunteers were randomized to receive alternatively a single dose AMX-SUL infused both either over 30 min or 3h at the following ratios (g/g): 1/0.5; 1/1, and 0/2. Time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h sera after dose against a clinical isolate of A. baumannii (sulbactam MIC, 4microg/mL). Bactericidal activity (i.e. a mean decrease >3 log10 CFU/mL in the viable cell counts from the initial inoculum) was displayed by the 0.5- and the 2-h sera after dose for all formulations. The 4-h sera proved inhibitory with the AMX-SUL 1g/1g formulation, albeit a trend to regrowth was observed after 24-h incubation. With the AMX-SUL 0g/2g dose, the 4-h sera proved almost bactericidal activity (i.e. a mean decrease of 2.4 log10 CFU/mL in the viable cell counts from the initial inoculum), whereas the 6-h sera was inhibitory, with a trend to regrowth after 24-h incubation. When infused over 3h, AMX-SUL 1g/0.5g and 1g/1g, bactericidal activity was displayed by the 0.5-, 2- and the 4-h sera after dose and the 6-h sera proved inhibitory with the AMX-SUL 1g/1g formulation. The present study, albeit preliminary, might give a rationale for the dosing strategy to treat infections caused by A. baumannii with sulbactam, either alone or combined with amoxicillin. A 2-g sulbactam dose seems to be optimal to be infused over 30 min with a 6-h dosing interval. When infused over 3h, AMX-SUL 1g/1g given every 6h or 8h seems a suitable dosing schedule.

Amoxicillin-sulbactam versus amoxicillin-clavulanic acid for the treatment of non-recurrent-acute otitis media in Argentinean children.

Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi) are the leading bacterial cause of acute otitis media (AOM), having the nasopharynx (NP) as their reservoir. In October 2001 we began a prospective, multicenter, randomized, evaluator blind study, comparing the efficacy of amoxicillin-sulbactam (Ax/S) and amoxicillin-clavulanic acid (Ax/C) for the treatment of non-recurrent AOM (nr-AOM). Both antimicrobial susceptibility (AS) to Ax/S and Ax/C from Sp and Hi carried by study children (aged 6-48 months with nr-AOM) and, clinical outcome after treatment with high dose of either Ax/C (7:1) or Ax/S (4:1) (amoxicillin dose: 80 mg/(kg day), b.i.d. for 10 days) were assessed. Nasal cultures (NCs) were taken at Day 0. Follow-up NCs, were done only for Sp carriers. On final analysis 247/289 pts (85.5%) were fully evaluable (120 Ax/S and 127 Ax/C). NP carriage rate of Hi and Sp at Day 0 was 32.2% (93/289 pts) and 28.7% (83/289 pts), respectively. Persistent Sp carriage was detected only in 2 pts. Hi betalactamase positive rate was 13% (12/93). MICs for Ax/S and Ax/C were identical when tested against Sp and Hi isolates (range < or = 0.016-1.0 and < or = 0.016-0.25 mg/L, respectively). Clinical efficacy at Days 12-14 and 28-42 were 98.3% (115/117) and 94.2% (97/103) for Ax/S; and 98.3% (115/117) and 95.1% (98/103) for Ax/C, respectively (pNS). We conclude, that Sp and Hi isolated from NCs of nr-AOM pts were highly sensitive to both drugs and correlated with high clinical efficacy rate.

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.

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

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 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.

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)