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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
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| Series: | Brazilian Journal of Infectious Diseases |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702009000500006&lng=en&tlng=en |
| _version_ | 1830486769479450624 |
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| author | Carlos Bantar Liliana Fernández Canigia María Alejandra Berger Jorge L Soutric Héctor J Arenoso |
| author_facet | Carlos Bantar Liliana Fernández Canigia María Alejandra Berger Jorge L Soutric Héctor J Arenoso |
| author_sort | Carlos Bantar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T18:50:04Z |
| format | Article |
| id | doaj.art-1fe1fc58106f458f98e000b9b02aa67a |
| institution | Directory Open Access Journal |
| issn | 1678-4391 |
| language | English |
| last_indexed | 2024-12-21T18:50:04Z |
| publisher | Elsevier |
| record_format | Article |
| series | Brazilian Journal of Infectious Diseases |
| spelling | doaj.art-1fe1fc58106f458f98e000b9b02aa67a2022-12-21T18:53:47ZengElsevierBrazilian Journal of Infectious Diseases1678-439113534835210.1590/S1413-86702009000500006S1413-86702009000500006Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo modelCarlos Bantar0Liliana Fernández Canigia1María Alejandra Berger2Jorge L Soutric3Héctor J Arenoso4Laboratorio Domingo I NanniHospital AlemánHospital AlemánLaboratorios Bagó S.A.Laboratorios Bagó S.A.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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702009000500006&lng=en&tlng=enAmoxicillin-sulbactamAcinetobacter |
| spellingShingle | Carlos Bantar Liliana Fernández Canigia María Alejandra Berger Jorge L Soutric Héctor J Arenoso Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model Brazilian Journal of Infectious Diseases Amoxicillin-sulbactam Acinetobacter |
| title | Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model |
| title_full | Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model |
| title_fullStr | Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model |
| title_full_unstemmed | Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model |
| title_short | Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model |
| title_sort | pharmacodynamic assessment of amoxicillin sulbactam against acinetobacter baumannii searching the optimal dose and infusion time through a human ex vivo model |
| topic | Amoxicillin-sulbactam Acinetobacter |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702009000500006&lng=en&tlng=en |
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