A Comparative Analysis Between Antibiotic- and Nonantibiotic-Associated Delayed Cutaneous Adverse Drug Reactions.
The difference in clinical presentation, causality assessments, and outcomes of patients with delayed antibiotic-associated cutaneous adverse drug reactions (AA-cADR) and nonantibiotic-associated (NA)-cADR is ill defined.



We examined the etiology of AA-cADR, with regard to the type of antibiotic exposure, allergy labeling, and patient outcomes, in comparison with NA-cADR.



A retrospective observational inpatient cohort study of cADR was performed from January 2004 to August 2014. Patients were divided into AA-cADR and NA-cADR groups for analysis. cADR was defined as erythema multiforme, fixed drug eruption, acute generalized erythematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), drug-associated linear IgA disease, Stevens-Johnson syndrome, and toxic epidermal necrolysis.



Of the 84 patients with cADR, 48% were AA-cADR. Male sex (60% vs 32%, P = .004), median length of stay (14.5 vs 11 days, P = .05), median Charlson comorbidity index (3 vs 1, P = .03), and inpatient mortality (20% vs 5%, P = .04) were higher in AA-cADR compared with NA-cADR. The median drug latency was lower in AA-cADR (6 vs 20 days, P = .001). Sulfonamide antibiotics and glycopeptides were implicated in 20% of AA-cADR. DRESS was more frequently reported in AA-cADR. After cADR diagnosis, further antibiotic therapy was administered in 64% of patients, higher in AA-cADR (75%, 30 of 40) compared with NA-cADR (55%, 24 of 44) (P = .06). Fluoroquinolones (53% vs 21%, P = .02), glycopeptides (vancomycin and teicoplanin; 70% vs 38%, P = .05), and carbapenems (33% vs 13%, P = .11) were used more commonly in AA-cADR.



Antibiotics were the cause of cADR requiring hospital admission in 48% of episodes, and were associated with longer length of stay, higher age-adjusted Charlson comorbidity index, shorter drug latency, and mortality. In AA-cADR, glycopeptide and sulfonamide antibiotic exposure predominated.
Department of Infectious Diseases, Alfred Health & Monash University, Melbourne, Victoria, Australia; Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia; Department of Infectious Diseases, Peter MacCallum Cancer Centre, Victoria, Australia; Department of Medicine, University of Melbourne, Parkville, Victoria, Australia. Electronic address: j.trubiano@alfred.org.au.
Jason A
JA
Trubiano
Department of Infectious Diseases, Alfred Health & Monash University, Melbourne, Victoria, Australia; Department of General Medicine, Alfred Health, Melbourne, Victoria, Australia.
Ar Kar
AK
Aung
Department of Infectious Diseases, Alfred Health & Monash University, Melbourne, Victoria, Australia.
Mary
M
Nguyen
Department of Infectious Diseases, Alfred Health & Monash University, Melbourne, Victoria, Australia.
Sasha R
SR
Fehily
Department of Pharmacy, Alfred Health & Monash University, Melbourne, Victoria, Australia.
Linda
L
Graudins
Burns Unit, Alfred Health, Melbourne, Victoria, Australia.
Heather
H
Cleland
Department of Infectious Diseases, Alfred Health & Monash University, Melbourne, Victoria, Australia.
Alex
A
Padiglione
Department of Infectious Diseases, Alfred Health & Monash University, Melbourne, Victoria, Australia.
Anton Y
AY
Peleg
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology*; D004348:Drug Labeling; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged
D000900:Anti-Bacterial Agents
Allergy; Drug reactions; Steven-Johnson syndrome; Toxic epidermal necrolysis