RESUMO
We measured ceftriaxone pharmacokinetics in patients' plasma and cerebrospinal fluid (CSF) and assessed the influence of biometric, demographic, genetic (ABCB1, ABCC2, ABCB11, ABCG2, and SLCO1A2 polymorphisms) and pathological features. Adult patients with signs and symptoms of central nervous system infections, receiving intravenous ceftriaxone, were enrolled. Ceftriaxone plasma and CSF concentrations were measured by high-precision liquid chromatographic methods; allelic discrimination was performed by real-time polymerase chain reaction. Forty-three patients were included: median ceftriaxone maximal concentration was 15,713 ng/mL in plasma and 3512 ng/mL in CSF with a CSF-to-plasma ratio of 0.3. ABCC2 1249 rs2273697 (P = .027) and ABCG2 1194+928 rs13120400 (P = .015) variants were significantly associated with CSF concentrations and CSF-to-plasma ratios. At linear regression analysis, CSF-to-serum albumin ratio was an independent predictor of ceftriaxone CSF concentrations (P = .001; also in those with intact blood-brain barrier: P = .031) and CSF-to-plasma ratio (P = .001; also in those with blood-brain barrier impairment: P = .040). We here report the role of transporters' genetic variants as well as of blood-brain barrier permeability in predicting ceftriaxone exposure in the central nervous system.
Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Ceftriaxona/sangue , Ceftriaxona/líquido cefalorraquidiano , Meningites Bacterianas/tratamento farmacológico , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Antibacterianos/sangue , Antibacterianos/líquido cefalorraquidiano , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Ceftriaxona/farmacocinética , Ceftriaxona/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência MúltiplaRESUMO
Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy decreases the progression risk of non-muscle-invasive bladder cancer, but potentially yields a broad spectrum of side effects. We report the case of a 73-year-old man affected by miliary pulmonary BCG infection, whose microbiological diagnosis was probably hindered by empiric fluoroquinolones, focusing on imaging and clinical work-up.