RESUMO
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.
Assuntos
Amoxicilina/farmacologia , Quimioterapia Combinada/farmacologia , Escherichia coli/efeitos dos fármacos , Penicilinas/farmacologia , Sulbactam/farmacologia , Urina/química , Administração Oral , Adulto , Amoxicilina/urina , Resistência Microbiana a Medicamentos , Infecções por Escherichia coli , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Penicilinas/urina , Sulbactam/urina , Infecções Urinárias/tratamento farmacológico , Urina/microbiologiaRESUMO
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)
Assuntos
Humanos , Masculino , Feminino , Adulto , RESEARCH SUPPORT, NON-U.S. GOVT , Amoxicilina/farmacologia , Escherichia coli/efeitos dos fármacos , Penicilinas/farmacologia , Sulbactam/farmacologia , Urina/química , Amoxicilina/urina , Administração Oral , Resistência Microbiana a Medicamentos , Antibacterianos , Infecções por Escherichia coli , Testes de Sensibilidade Microbiana , Penicilinas/urina , Sulbactam/urina , Infecções Urinárias/tratamento farmacológico , Urina/microbiologiaRESUMO
Tandem mass spectrometric analysis of acylcarnitines and amino acids has been applied in newborn screening programmes for the detection of several inborn errors of metabolism. We report a false positive result for isovaleric acidaemia in a newborn screening programme using this method. The newborn screening sample showed a very prominent signal corresponding to the mass of isovalerylcarnitine. Repeat samples (age 6 days) of blood and urine showed similar results. However, urine organic acids were normal. Acylcarnitine analysis in blood, breast milk and urine of the mother also showed a prominent signal of the same mass. Gas chromatography-mass spectrometry of the methyl esters demonstrated that the signal in the patient's urine was due to the presence of pivaloylcarnitine, which is isomeric with isovalerylcarnitine. The patient's mother was receiving an antibiotic containing a derivative of pivalic acid to treat a urinary tract infection. Follow-up samples in the patient and the mother confirmed a decrease in the levels of pivaloylcarnitine, concomitant with the discontinuation of the treatment. We conclude that pivaloylcarnitine can give a false positive result for isovaleric acidaemia in newborns whose mothers are on treatment with pivoxilsulbactam-containing antibiotics.