Penetrance of nafcillin into human ventricular fluid: correlation with ventricular pleocytosis and glucose levels

Abstract

Fourteen hydrocephalic pediatric patients with suspected shunt infections were studied for penetrance of nafcillin into the ventricular fluid after intravenous administration. In seven patients with bacterial ventriculitis, the concentration of nafcillin in ventricular fluid was 0.8 to 20.4% of the peak concentration in serum. In the remaining seven patients without bacterial ventriculitis, ventricular fluid levels ranged between -0.02 to 4% of peak serum concentrations. Although the degree of pleocytosis correlated poorly with penetrance, ventricular fluid glucose levels correlated inversely with penetrance of nafcillin (r = -0.7275, P < 0.001).The infection rate in hydrocephalic patients with shunts ranges from 6 to 25% (12, 13). Staphylococcus epidermidis and S. aureus account for the majority of such infections. The semisynthetic penicillins represent the drugs of choice for treatment of penicillin-resistant staphylococci. One imnportant factor in evaluating the potential efficacy of a drug for treatment of ventriculitis is its ability to penetrate into the central nervous system and cerebrospinal fluid (CSF). Very low CSF concentrations of methicillin are encountered in meningitis in either experimental animals or humans (1, 9). In contrast, nafcillin levels in the CSF of patients with staphylococcal meningitis are significant, exceeding minimal bactericidal concentrations for the infecting organism (6, 10). Although the data on nafcillin levels in CSF are limited, it seems to be the drug of choice for staphylococcal meningitis (4,8). Kane (6) reported a case of staphylococcal meningitis in which the level of nafcillin in lumbar CSF (58 ,Lg/ml) was markedly different from the level in ventricular fluid (9.8 ug/ml) obtained simultaneously, even though both fluids had the same degree of pleocytosis. This observation suggests that the pharmacokinetics of nafcillin may be different in ventricular fluid than in lumbar CSF.This report describes ventricular fluid nafcillin levels after intravenous administration in a group of hydrocephalic children with and without shunt infection. MATERLALS AND METHODSFourteen hydrocephalic children 3 weeks to 8.5 years of age with suspected ventriculoperitoneal shunt infections were studied. Informed consent was obtained from parents in each instance. In keeping with the standard neurosurgical practice in our institution, the shunt was removed from each patient, and extraventricular drainage was instituted. After placement of the extraventricular drainage catheter, administration of intravenous nafcillin (50 mg/kg every 6 h) was started. Each dose was infused over a 30-to 40-min period. Blood and ventricular fluid samples were obtained at 5 and 30 min and 1, 2, 3, and 6 h after infusion of the fifth or sixth dose of nafcillin. The extraventricular drainage catheter was clamped for 3 to 4 h after completion of the infusion. Ventricular fluid was obtained from the extraventricular drainage catheter as follows: 1.5 ml of ventricular fluid was aspirated and discarded; another 0.5 ...

Pharmacokinetic Evaluation of Cefazolin in the Cerebrospinal Fluid of Critically Ill Patients

“…However, a single nafcillin dose of 40 mg/kg IV in 8 patients resulted in a mean CSF concentration of 0.12 mg/L at 2 hours postdose and a mean CSF concentration of 0.03 mg/L at 4 hours postdose in patients with no meningeal inflammation [ 29 ]. In 7 patients with bacterial ventriculitis, CSF nafcillin was reported as 0.8%–20.4% peak serum concentrations [ 30 ]. Brain tissue concentrations following 2000 mg IV of nafcillin in 13 patients resulted in a mean of 2.7 mcg/g, whereas cefazolin 2000 mg IV resulted a mean of 10.6 mcg/g, suggesting comparable brain penetration of both nafcillin and cefazolin [ 4 ].…”

Staphylococcus aureus meningitis in children: a review of 30 community-acquired cases

“…Nafcillin and oxacillin are four times more potent than methicillin against S. aureus 31 . Studies have indicated that the minimal inhibitory concentrations (MIC) of nafcillin for susceptible S. aureus range from 0,08 to 1,25 µg/ml, with averages of 0,312 to 0,6 µg/ml 32 . Nafcillin enter the CSF reasonably well in patients with severe meningeal inflammation, although great variability exists 19 .…”

Pharmacokinetics and Cerebrospinal Fluid Concentration of Nafcillin in Pediatric Patients Undergoing Cerebrospinal Fluid Shunt Placement

“…No direct comparisons can be made be cause no data are available about the CSF concentrations of nafcillin at the time of insertion. In pediatric patients without meningeal inflammation, the CSF concen tration was reported to be 0.12 pg/ml at 2 h after a 30 min infusion of nafcillin, 40 mg/kg [9], In patients with meningitis, the CSF concentrations of nafcillin ranged from 1.2 to 88 (ig/ml, depending on the dose administered and the time of concentration determination [10,11]. These observations suggest that CSF con centrations of nafcillin achieved in the ab sence of meningeal inflammation would be much lower than those attained in pa tients with meningitis.…”