DECREASED MORTALITY WITH GENTAMICIN + AMPICILLIN IN TREATMENT OF NEUTROPENIC MICE WITH GROUP B STREPTOCOCCAL (GBS) INFECTION

Abstract

Pencillin G or ampicillin (amp) is recommended for GBS infection although recurrence and relapse are seen in some penicillin treated infants. As previously reported, GBS are resistant to gentamicin (gen) alone, but gen accelerates killing of GBS by amp in vitro and in normal weanling mice. Additionally, survival of GBS-infected mice was greater with amp + gen than with amp. Because of the poor outcome in neutropenic infants with GBS infection, we have studied the effect of amp and gen in weanling mice made neutropenic (granulocytes < 1000/mm3) with cyclophosphamide and infected IP with 107 CFU of GBS strains la or lc. One hour after infection, 3 doses of amp (peak serum level 18 mcg/ml) or amp + gen (peak level 5 mcg/ml) were given at 4 h intervals. Mortality was significantly less in mice given amp + gen (12/62 - 19%) than in mice given only amp 40/60 = 67%). To determine if simultaneous treatment was protective, a single dose of amp (peak level 30 mcg/ml) or amp + gen (peak level 8 mcg/ml) was given at the time of infection. Mortality was again significantly less in mice given amp + gen than in those given amp alone for strain la (37/60 = 62% vs 49/54 = 91%) and for strain lc (5/20 = 25%. vs 15/20 = 75%). Since amp + gen was more effective than amp both in treatment and protection against lethal mouse infection, the combination may be of value for GBS infection in neutropenic infants.