Failure of cefamandole in treatment of meningitis due to Haemophilus influenzae type b

Abstract

The in vitro activity of cefamandole was determined against 58 isolates of Haemophilus influenzae type b; 47 were beta-lactamase-negative (ampicillin-susceptible), and 11 produced beta-lactamase (ampicillin-resistant). Ampicillin-susceptible strains were susceptible to cefamandole with a median minimal bactericidal concentration (MBC) of 0.4 microgram/ml. Ampicillin-resistant strains had a median MBC of 0.8 microgram/ml. Prior studies have documented these concentrations of cefamandole in cerebrospinal fluid in the presence of inflamed meninges. Three children with meningitis due to H. influenzae type b were treated with cefamandole (200 mg/kg per day), including one child with disease due to an ampicillin-resistant strain. All patients showed clinical improvement during therapy. However, sterility of the cerebrospinal fluid was never achieved in two patients during 72--96 hr of therapy with cefamandole. The third patient relapsed with a recurrence of positive cultures during the seventh day of cefamandole therapy. Therefore, cefamandole does not appear to be a useful agent for treatment of meningitis due to H. influenzae type b irrespective of in vitro susceptibility or evidence of penetration into the cerebrospinal fluid.