Pharmacokinetic model for tobramycin in acinetobacter meningitis.
OBJECTIVE
To report a case of acinetobacter meningitis treated with a once-daily intravenous dose of tobramycin and to propose a pharmacokinetic model for the drug disposition.


METHODS
A 28-year-old man with chronic hydrocephalus was admitted with a diagnosis of intracranial hypertension. Acinetobacter spp. was detected in the cerebrospinal fluid (CSF); it was sensitive to tobramycin, ampicillin/sulbactam, and colistin. Based on the culture report, multiple daily-dose therapy with tobramycin was started. As the infectious symptoms remained, once-daily therapy was recommended; the optimal dose was calculated with nonlinear regression by least-squares analysis and a Bayesian method, using plasma and CSF samples. The infection was resolved, tobramycin therapy was discontinued, and the patient was discharged from the intensive care unit.


CONCLUSIONS
We use once-daily intravenous tobramycin therapy because, although the intrathecal administration of drugs is generally well tolerated, the presence of preservatives may be a source of central nervous system adverse effects. Pharmacokinetic parameters were calculated with plasma and CSF concentration values obtained during the first once-daily dose by using a compartment-effect model which allows fitting of simultaneous plasma and CSF concentrations. The prediction level was determined by the estimation of drug concentrations during the fourth once-daily dose. CSF concentrations of drug were enough to eradicate the clinical signs of infection.


CONCLUSIONS
Therapy using once-daily intravenous administration of tobramycin may be an adequate alternative for acinetobacter infections in neurosurgical patients when an intrathecal route is initially not recommended. The development of a compartment-effect model can be useful to predict drug concentrations.
Chicano-Piá
Pedro V
PV
Department of Pharmacy, La Fe University Hospital, 21 Campanar Av., 46009 Valencia, Spain.
Cercós-Lletí
Ana-Cristina
AC
Romá-Sánchez
Eva
E
D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002557:Cerebrospinal Fluid Shunts / Q000009:adverse effects*; D006801:Humans; D006849:Hydrocephalus / Q000150:complications; D007275:Injections, Intravenous; D008297:Male; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D008954:Models, Biological; D014031:Tobramycin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D014031:Tobramycin