Failure of Response to Ampicillin in Hemophilus influenzae Meningitis

Abstract

A 21-month-old Negro boy was referred to the North Carolina Baptist Hospital because he had a febrile illness for three days' duration which had not responded to treatment with penicillin. On admission his temperature was 103 F (39.4 C). He was above the 50th percentile for height and weight. He was lethargic but not critically ill. There were classical clinical manifestations of meningitis. Hemoglobin value was 6.5 gm/100 ml, and the hematocrit reading was 28%. Dietary history, morphology of the peripheral smear, and red blood cell indices indicated an iron deficiency anemia. However, the patient was given a transfusion of packed cells before a serum iron or iron binding capacity was obtained. Hemoglobin electrophoresis was normal. The white blood cell count (WBC) was 9,600/cu mm. The differential count revealed 67% polymorphonuclear leukocytes (PMNs), 27% lymphocytes, and 6% monocytes. Lumbar puncture revealed an opening pressure of 240 mm H-O. The cerebrospinal fluid (CSF) was turbid with 3,000 WBCs per cubic millimeter. Ninety percent of the cells were PMNs. The CSF protein was 154 mg/100 ml and the glucose was 0 mg/100 ml. Smear of the CSF showed gramnegative pleomorphic rods. Hemophilus in¬ fluenzae type was grown from the CSF. Blood and throat culture grew influenzae which was untypable.

Iodometric Detection of Haemophilus influenzae Beta-Lactamase: Rapid Presumptive Test for Ampicillin Resistance

“…Ampicillin is commonly used for therapy of children with systemic disease caused by Haemophilus influenzae. The occasional treatment failures reported earlier were attributed to hostrelated conditions rather than to genetic resistance of the bacteria (1,9,16). However, recent reports have documented the occurrence of clinically significant ampicillin resistance (4-6, 10, 12, 19).…”

“…The marked influence of the method and conditions of in vitro testing on the apparent susceptibility or resistance of H. influenzae to ampicillin has been clearly demonstrated (11). Moreover, it is generally recognized that diffusion tests using ampicillin disks on agar medium may indicate resistance, although the strain actually is susceptible as judged by the MIC of ampicillin in broth (9,11,12,16,18). Many hospital laboratories do not perform susceptibility tests on H. influenzae because of the earlier confidence that type-b isolates are invariably susceptible to ampicillin, and because of technical difficulties encountered in cultivating and testing this nutritionally demanding species (11, 18).…”

Recurrent Bacteremia Following Ampicillin Treatment of Hemophilus Influenzae Meningitis

“…In vitro sensitivity remains virtually complete (9,11). However, eight cases of ampicillin failure in Hemophilus influenzae meningitis have been reported (8,10). Failure has been ascribed to inadequate cerebrospinal fluid levels of ampicillin secondary to inadequate dosage, or improper route of administration in seven of these cases (2,8).…”