title: Antibacterial effects on acinetobacter species of commonly employed antineoplastic agents used in the treatment of haematological malignancies: an in vitro laboratory evaluation.
abstract: Although about 75-80% of neutropenic fevers are thought to be caused by infections, a causal organism can be confirmed microbiologically or suspected clinically in only 30-50%, and even fewer of these cases (16%) have a documented bacteraemia. The cause of neutropenic fever in the remaining cases remains elusive. The reasons for this failure may be due to the difficulty in recovering low numbers of organisms, fastidious organisms which fail to grow using conventional culture media, the presence of non-culturable organisms, or the presence of inhibitory substances in specimens. Previously, the authors showed the presence of Acinetobacter in peripheral blood of febrile neutropenic patients with a haematological malignancy, using 16S rDNA polymerase chain reaction (PCR) and sequencing techniques. However, conventional culture was unable to detect these organisms. Hence, it was felt necessary to examine the antibacterial properties of four antineoplastic agents used in the treatment of haematological malignancy, namely bleomycin, cisplatin, doxorubicin and vincristine. A total of 56 wild-type Acinetobacter including seven species (A. calcoaceticus [n=17], A. septicus [n=11], A. baumannii [n=10], A. johnsonii [n=7], A. lwoffii [n=8] A. haemolyticus [n=2] and A. radioresistens [n=1]) were examined for their susceptibility to the four antineoplastic agents at therapeutic concentration. No inhibition was observed, but inhibition was seen at higher concentrations of both bleomycin and doxorubicin. Time to detection of blood culture bottles containing separate antineoplastic agents (i.e., bleomycin and doxorubicin) was compared to that containing saline using a paired t-test. Samples containing doxorubicin at 1 pg/mL were shown to have a mean time to detection of 21.8 h (range: 15.6-31.4 h). Bottles containing saline had a mean time to detection of 22.9 h (range: 18.2-31.3 h). Statistical analysis showed no significant difference (P=0.3361) between time to detection for blood culture bottles containing doxorubicin at achievable plasma concentration and corresponding negative controls. With regard to bleomycin (300 miu/mL), the mean time to detection was 27.29 h (range: 20.2-38.4 h) in the test bottles, with mean time to detection in the saline negative controls of 22.56 h (range: 17.0-30.1 h). Paired t-test gave P=0.000451, hence a significant difference in time to detection for blood cultures containing therapeutic levels of bleomycin. Overall, the antineoplastic agents vincristine, cisplatin or doxorubicin did not have any inhibitory effects on the Acinetobacter organisms examined. At worst, therapeutic concentrations of bleomycin may delay automated detection of an Acinetobacter bacteraemia by a mean time of 5.9 h.
authors.affiliation: Northern Ireland Public Health Laboratory, Department of Bacteriology, Belfast City Hospital.
authors.forename: A J
authors.initials: AJ
authors.lastname: McCarron
authors.forename: C
authors.initials: C
authors.lastname: Armstrong
authors.forename: G
authors.initials: G
authors.lastname: Glynn
authors.forename: B C
authors.initials: BC
authors.lastname: Millar
authors.forename: P J
authors.initials: PJ
authors.lastname: Rooney
authors.forename: C E
authors.initials: CE
authors.lastname: Goldsmith
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: J E
authors.initials: JE
authors.lastname: Moore
mesh_terms: D000150:Acinetobacter / Q000145:classification / Q000187:drug effects*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016470:Bacteremia / Q000175:diagnosis / Q000382:microbiology; D001761:Bleomycin / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D019411:Clinical Laboratory Techniques; D004317:Doxorubicin / Q000494:pharmacology; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008826:Microbial Sensitivity Tests; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D001761:Bleomycin; D014750:Vincristine; D004317:Doxorubicin; D002945:Cisplatin