Peripheral blood eosinophilia and hypersensitivity reactions among patients receiving outpatient parenteral antibiotics

Abstract

Background While drug-induced peripheral eosinophilia complicates antimicrobial therapy, little is known about its frequency and implications. Objective We aimed to determine the frequency and predictors of antibiotic-induced eosinophilia and subsequent hypersensitivity reactions (HSRs). Methods We evaluated a prospective cohort of former inpatients receiving intravenous antibiotic therapy as outpatients with at least one differential blood count. We used multivariate Cox proportional hazards models, with time-varying antibiotic treatment indicators, to assess the impact of demographic data and antibiotic exposures on eosinophilia and subsequent HSR, including documented rash, renal injury, and liver injury. Possible Drug Rash Eosinophilia and Systemic Symptoms (DRESS) syndrome cases were identified and manually validated. Results Of 824 patients (60% male, median age 60 years, median therapy duration 41 days), 210 (25%) developed eosinophilia with median peak absolute eosinophil count of 726/mL [IQR: 594–990/mL]. Use of vancomycin, penicillin, rifampin, and linezolid were associated with a higher hazard of developing eosinophilia. There was subsequent HSR in 64/210 (30%) patients with eosinophilia, including rash (N=32), renal injury (N=31), and liver injury (N=13). Patients with eosinophilia were significantly more likely to develop rash (HR = 4.16 [2.54, 6.83]; p<0.0001) and renal injury (HR = 2.13 [1.36, 3.33]; p=0.0009), but not liver injury (HR = 1.75 [0.92, 3.33]; p=0.09). Possible DRESS syndrome occurred in 7/824 (0.8%) patients; 4 (57%) were on vancomycin. Conclusions Drug-induced eosinophilia is common with parenteral antibiotics. While most patients with eosinophilia do not develop an HSR, eosinophilia increases the hazard rate of developing rash and renal injury. DRESS syndrome was more common than previously described.

Adverse Drug Reactions Associated with Ceftaroline Use: A 2-Center Retrospective Cohort

“…While our findings may be partially explained by a patient population who is medically complex with prolonged antibiotic exposures, this is an area that warrants careful future study to understand if the drug has a different propensity to cause ADRs/HSRs than other cephalosporin class antibiotics, or if the observed differences are due to patients factors (i.e., confounding by indication). 9,25,26 Indeed, in the one report that included patients similar to ours (i.e., comorbid patients, long duration of therapy, off-label indications), among 12 inpatients treated with ceftaroline, 9 patients (75%) discontinued ceftaroline because of an ADR. 22 Reported ADRs similarly included cutaneous and hematologic findings.…”

“…12–15 To date, there are few reported cases where a patient with prior beta-lactam allergy received ceftaroline, 2026 and these used empiric desensitizations. Our cohort included 22 patients who received ceftaroline without empiric desensitization, and only one associated HSR (rash in patient 14).…”

“…This is not surprising given the low likelihood that a patient reporting a beta-lactam allergy is truly allergic, 29 and the low likelihood of cross reactivity between penicillins and cephalosporins. 26,30 Except in cases in which the cephalosporin allergy is to a cephalosporin which shares similar side chains (e.g. ceftobiprole medocaril) or in cases where there is a history of a severe delayed reaction such as SJS/TEN or DRESS syndrome that warrants additional caution, 26,30 patients with penicillin or cephalosporin allergy should largely be able to tolerate ceftaroline.…”

“…26,30 Except in cases in which the cephalosporin allergy is to a cephalosporin which shares similar side chains (e.g. ceftobiprole medocaril) or in cases where there is a history of a severe delayed reaction such as SJS/TEN or DRESS syndrome that warrants additional caution, 26,30 patients with penicillin or cephalosporin allergy should largely be able to tolerate ceftaroline. The 22 patients with prior beta-lactam allergy given ceftaroline without desensitization included four patients whose allergy history was suggestive of a severe IgE-mediated HSR.…”

Eosinophilic Disorders: Extrinsic and Intrinsic Immune Response, New Diagnostic Perspectives, and Therapeutic Alternatives

“…However, for the doctor, concern may arise in cases of impending hypersensitivity reaction (HSR). Severe HSRs associated with peripheral blood may include specific reactions of organs (heart, kidney, liver, Eosinophilic Disorders: Extrinsic and Intrinsic Immune Response, New Diagnostic Perspectives… DOI: http://dx.doi.org /10.5772/intechopen.89229 lungs, joints, central nervous system, and skin) and adverse skin reactions (SCAR) where SJS, TEN, and DRESS are included [32,33]. Hypersensitivity reactions require that the individual has been previously sensitized or exposed at least once to the antigens in question.…”