Chloramphenicol Injection and Voriconazole: Interaction Details

a) A 14-year-old boy with bacterial meningitis and subsequent cerebral aspergillosis showed substantial decreases in voriconazole plasma trough concentrations during concomitant IV chloramphenicol therapy. Upon admission to the pediatric critical care unit for fulminant pneumococcal meningitis and septic shock, the patient showed severe brain edema that required intracranial pressure monitoring and insertion of external ventricular drains in both lateral ventricles. The infection initially resolved, however, the infection relapsed. The patient was diagnosed with sphenoid sinusitis and a sphenoidotomy was performed on days 15 and 21. Following treatment with multiple antibiotics, the patient's condition worsened, with disorientation, vomiting, and fever. A brain abscess in the left frontal lobe was revealed, with signs of ventriculitis. Antibiotic therapy was changed to chloramphenicol (1 g 4 times per day) and ceftriaxone (2 g/day). On the same day, the patient tested positive for aspergillus antigen. Caspofungin (50 mg/day) and voriconazole was initiated for suspected disseminated fungal ventriculitis. Until day 51, the patient showed a stable disease under antimycotic treatment, but cerebral aspergillosis proceeded uncontrolled, and the patient died on day 82. During chloramphenicol and voriconazole treatment, voriconazole plasma concentrations ranged between 2.2 and 3.5 mcg/mL. Ratios between maintenance dose and trough concentration were between 103 and 164 mL/min. Following discontinuation of chloramphenicol, voriconazole plasma concentrations dropped and antifungal doses had to be doubled ¹.