Targeting matrix metalloproteinases with intravenous doxycycline in severe sepsis--A randomised placebo-controlled pilot trial.
Pharmacol Res
; 99: 44-51, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26008138
ABSTRACT
An overwhelming inflammatory process is the hallmark of severe sepsis and septic shock. Matrix metalloproteinases (MMPs)-8 and -9 are released from neutrophils and activated in sepsis to participate in inflammation in several ways. High levels of MMP-8 may associate with increased ICU mortality. The activity of MMP-8 and -9 is regulated by a natural inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1). Moreover, MMPs are chemically inhibited by tetracycline-group antibiotics, such as doxycycline. We therefore aimed to study plasma concentration and MMP inhibition after intravenous doxycycline in critically ill patients with severe sepsis and septic shock in a prospective, randomised, placebo-controlled double-blinded pilot trial. Twenty-four patients with severe sepsis or septic shock were randomised in 3 groups. Group 1 received 200, 100 and 100mg, group 2 100, 50 and 50mg of intravenous doxycycline and group 3 placebo on three consecutive days. We measured doxycycline concentrations from baseline up to day 5. MMPs and TIMP-1 concentrations were measured from baseline up to day 10 of study and we compared their changes over time from baseline to 72 h and from baseline to 120 h. Data from 23 patients were analysed. At 72 h all patients in group 1 showed doxycycline concentrations >1 mg/l, whereas none in group 2 did. No serious adverse effects of the drug were recorded. We observed no differences over time up to 72 or up to 120 h in the concentrations or activities of MMP-8, -9 or TIMP-1 in any of the groups. We found intravenous doxycycline 100, 50 and 50mg to be adequate to achieve a sub-antimicrobial concentration in patients with severe sepsis or septic shock but having no impact on MMP-8, -9 or TIMP-1 concentrations or activities.
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Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Doxiciclina
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Sepsis
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Inhibidores de la Metaloproteinasa de la Matriz
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Antibacterianos
Tipo de estudio:
Clinical_trials
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Pharmacol Res
Asunto de la revista:
FARMACOLOGIA
Año:
2015
Tipo del documento:
Article