Ticarcillin-Induced Neutropenia Corroborated by in vitro CFU-C Toxicity

Abstract

A patient developed a drug rash and neutropenia while receiving tobramy-cin, ticarcillin and flucloxacillin intravenously for osteomyelitis. Incorporation of these antibiotics into in vitro cultures of bone marrow granulocyte macrophage precursors (CFU-C) showed no inhibition of the patient’s marrow or normal marrow by tobramy-cin. The patient’s marrow was more sensitive to ticarcillin than were control cultures, and all cultures incorporating flucloxacillin failed to show growth of CFU-C. Drugs of the penicillin group appear to be responsible for the patient’s neutropenia.

Stem cells in myelotoxicity

“…CFU-GM clonogenic assays were initially utilized in toxicology to confirm the origin in drug-induced agranulocytosis (Ascencao et al, 1984;Barrett et al, 1976;Boogaerts et al, 1984;Irvine et al, 1983;Kelton et al, 1979;Lind et al, 1973;Young and Vincent, 1980). The development of predictive in vitro hematotoxicity assays using CFU-GM was developed further.…”

Prospective in vitro testing for drug-induced neutropenia in a patient requiring anti-malarial prophylaxis: confirmation of findings on exposure of patient to drug

“…Bone marrow culture for the formation of CFU-G was carried out as described previously (Irvine et al 1983). Stock solutions of chloroquine sulphate (Nivoquine, May & Baker, Dagenham, Essex), proguanil hydrochloride and cycloguanil (ICI, Macclesfield, Cheshire) were prepared by dilution in HEPES-buffered TC199 (Gibco-Europe, Paisley, Scotland).…”

“…The in vitro system for the growth of granulocyte progenitors (colony-forming units-granulocyte; CFU-G) has been used to demonstrate sensitivity of patients suffering from neutropenia or agranulocytosis due to anti-malarial drugs (Lind, Levi & Vincent 1973;Sutherland et al 1977;Ellis, Steed & Addison 1987) or other agents (Barrett et al 1976;Irvine et al 1983). In a limited number of cases, such in vitro testing has been used as a basis for formulating a further drug policy as opposed to simple avoidance of the demonstrated aetiological agent (Ellis et al 1987).…”

Alternative testing systems for evaluating noncarcinogenic, hematologic toxicity.

“…Bone Marrow Stroma In contrast to the proliferation and expansion of tissue mass by hematopoietic cells, the primary function of the stroma is the nurture and support of developing blood cells (52,(65)(66)(67). However, there is a stromal colony-forming unit called CFUfibroblastoid (CFU-f), which produces a colony composed of adherent cells exhibiting morphologic features of fibroblasts, adipocytes, and other stromal elements (65,68 (106,(117)(118)(119)(120)(121)(122)(123)(124) (78,81,83,84,106,(125)(126)(127)(128)(129)(130)(131)(132)(133)(134)(135)(136) (131,132,146,147).…”