No Evidence for Ceftobiprole-Induced Immune Hemolytic Anemia in Three Phase 3 Clinical Trials

Figures & data

Figure 1 A proposed unifying model of drug-induced immune hemolytic anemias based on the hapten theory of antibody production. Reproduced with permission from Branch DR. Drug-induced immune haemolytic anaemias. ISBT Sci Ser. 2018;14(1):49-52.© 2018 International Society of Blood Transfusion.⁶

Table 1 Outcome of Direct Antiglobulin Testing in Phase 3 Clinical Trials of Ceftobiprole

Clinical Trial	Number of Patients with Positive DAT Results (n/N)
BPR-PIP-002	Ceftobiprole		IV SOC cephalosporin^a ± vancomycin
	Baseline	TOC^b	Baseline	TOC
	9/72	14/75	1/30	1/39
TARGET	Ceftobiprole		Vancomycin ± aztreonam
	Baseline	EOT	Baseline	EOT^c
	0/289	0/291	0/280	0/305
ERADICATE	Treatment (ceftobiprole or daptomycin ± aztreonam)^d
	Baseline	EOT	Post-treatment Day 70
	1/187	1/163	0/127

Notes: ^aCeftriaxone (baseline: n=28, TOC: n=37) and ceftazidime (baseline: n=2, TOC: n=2). ^b1 patient had a DAT at an unscheduled visit at treatment day 9. ^c1 patient had a DAT at an unscheduled visit 12 days after EOT. ^dResults cannot be allocated by treatment, as the trial is ongoing and blinded.

Abbreviations: DAT, direct antiglobulin test; n, number of patients with positive DAT results; N, number of DATs performed; IV, intravenous; SOC, standard of care; TOC, test of cure; EOT, end of treatment.

Table 2 Breakdown of Positive Direct Antiglobulin Test Results in BPR-PIP-002 Trial by Visit

DAT Results at Baseline and TOC		Ceftobiprole Number of Patients with Tests Performed: N=72 at Baseline; N=75 at TOC Visit^a	IV SOC Cephalosporin ± Vancomycin Number of Patients with Tests Performed: Ceftriaxone: 28 at Baseline; 37 at TOC Ceftazidime: 2 at Baseline; 2 at TOC
Baseline	TOC^a	Number of Patients with Positive DAT Results
Negative	Positive	5	0
Not performed	Positive	4	1^b
Positive	Positive	5^a	0
Positive	Negative	1	1^b
Positive	Not performed	3	0

Notes: ^a1 patient had a DAT at an unscheduled visit at treatment day 9. ^bBoth patients with a positive DAT result in the SOC cephalosporin treatment group received ceftriaxone.

Abbreviations: DAT, direct antiglobulin test; TOC, test of cure; N, number of tests performed; IV, intravenous; SOC, standard of care.

Branch DR. Drug-induced immune haemolytic anaemias. ISBT Sci Ser. 2019;14(1):49–52. doi:10.1111/voxs.12469

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