Vancomycin Hypersensitivity: It Is Not Always What It Seems

Vancomycin was first isolated in 1957 from the bacteria Amycolatopsis orientalis jungles of Borneo. Its name is derived word “vanquish.” It a bactericidal tricyclic glycopeptide active against gram-positive aerobic cocci and bacilli through inhibition cell wall synthesis. In addition to being first-line therapy for methicillin-resistant Staphylococcus infections, it used as second-line antimicrobial patients labeled allergic beta-lactam antimicrobials. also anaerobes including Clostridium difficile. With vancomycin resistance limited only handful strains, one most antimicrobials United States. Hypersensitivity reactions (HSRs) were reported early 1962. Most immediate HSRs do not appear be IgE-mediated. Only 10% HSR case reports suggest possible IgE-mediated mechanism based on convincing clinical presentation, positive skin testing (ST) result, breakthrough symptoms despite premedication or during desensitization.1Minhas J.S. Wickner P.G. Long A.A. Banerji A. Blumenthal K.G. Immune-mediated vancomycin: systematic review analysis.Ann Allergy Asthma Immunol. 2016; 116: 544-553Abstract Full Text PDF PubMed Scopus (46) Google Scholar This may an overestimation because (severe) red man syndrome (RMS) can clinically difficult distinguish anaphylaxis. IgE-independent mast basophil degranulation, causing RMS, occurs up 47% treated with vancomycin.2Wallace M.R. Mascola J.R. Oldfield E.C. Red syndrome: incidence, etiology prophylaxis.J Infect Dis. 1991; 164: 1180-1185Crossref (121) RMS mediated MAS-related G-protein–coupled receptor X2 does require prior sensitizing exposure.3Azimi E. Reddy V.B. Lerner E.A. Brief communication: MRGPRX2, atopic dermatitis syndrome.Itch (Phila). 2017; 2: e5Crossref Among pediatric patients, age 2 years more, previous doses greater than equal 10 mg/kg, concentrations 5 mg/mL have been identified risk factors developing RMS.4Myers A.L. Gaedigk Dai H. James L.P. Jones B.L. Neville K.A. Defining children adults.Pediatr Dis J. 2012; 31: 464-468Crossref (31) The characteristics indistinguishable, uncertainty remains whether serum tryptase ST act differentiators.5Wazny L.D. Daghigh B. Desensitization protocols hypersensitivity.Ann Pharmacother. 2001; 35: 1458-1464Crossref (67) Establishing underlying important management options differ. Unlike IgE-dependent HSRs, readministered following precautions slower infusion rates. desensitization should considered if there are no alternatives careful risk-benefit assessment. Successful intravenous protocols, both rapid slow, published.5Wazny associated mild such pruritus; slow usually after failed attempts. Oral inhaled routes described. contraindicated severe cutaneous adverse (SCARs) (Figure 1). Although vancomycin-induced nonimmediate occur less frequently, account two-thirds antibiotic-associated drug rash eosinophilia systemic (DRESS).6Lam B.D. Miller M.M. Sutton A.V. Peng D.M. Crew A.B. DRESS: retrospective chart 32 cases Los Angeles, California.J Am Acad Dermatol. 77: 973-975Abstract (12) Other include maculopapular rash, linear IgA bullous dermatosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, frequently acute generalized exanthematous pustulosis. Owing structural similarities antimicrobials, cross-reactivity possible. However, immunologic has demonstrated, suspected cross-reactivity, delayed, limited.7De Luca J.F. Holmes N.E. Trubiano J.A. Adverse other antibiotics.Curr Opin Clin 2020; 20: 352-361Crossref (9) between teicoplanin unlikely activate X2.3Azimi current issue, Alvarez-Arango et al8Alvarez-Arango S. Yerneni Tang O. Zhou L. Mancini C.M. Blackley S.V. al.Vancomycin hypersensitivity documented electronic health records.J Immunol Pract. 2021; 9: 906-912Abstract (7) explore prevalence allergy labeling challenges identifying, characterizing, documenting HSRs. large cross-sectional study across US care systems explored records over 2-year period. Of 4,490,618 0.3% (n = 14,426) had allergy/hypersensitivity label 18,761 During same period, more labels added (mean, 253 ± 12) removed (mean 12 2) per quarter. 42% determined likely 20% basis signs documented. Common reaction descriptions included (or words/variations synonymous, n 1909), hives 1759), itching 1651), flushing 1106), anaphylaxis 708). commonest description 3710) followed by DRESS 82) 41). constituted 60% (82 136) all SCARs. 3% 536) offered suggestive intolerances side effects. A further 34% 6440) could categorized lack provided. flushing, hives, itching, count. authors did acknowledge possibility these 10,051 experienced RMS. highlights limitation: dermatology workup confirm refute presence true hypersensitivity. Therefore, provides data but confirmed Similarly, phenotyping conducted authors, only, validated specialist workup. Attempts phenotype undermined information regarding timing. For example, without details assumed rashes compared rashes. Reaction timings form critical part history taking, which misdiagnosis incorrect determination occur. Vancomycin-induced DRESS, although rare, accounts significant proportion antibiotic-induced literature SCARs al.6Lam Scholar,8Alvarez-Arango Notably, 82.6% (19 23) RegiSCAR-defined carried HLA-A∗32:01, 0% matched vancomycin-tolerant controls.9Konvinse K.C. Pavlos R. I. Shaffer Bejan C.A. al.HLA-A∗32:01 strongly symptoms.J 2019; 144: 183-190Abstract (65) If this association larger diverse cohorts, allele offer potential means diagnosing preventing potentially life-threatening SCAR. observed Data cohort referred allergist dermatologist provided insight into infrequent removal labeling. ambiguity surrounding tryptase, provocation (DPT) criterion standard differentiating risks, DPT often performed when results levels raised. Tolerance and/or rates confirms permits future use Where diagnosis clearly, clinicians assume mechanism, lead unnecessary avoidance. Such avoidance implications delays treatment, suboptimal therapy, worse outcomes, increased costs.10Charneski Deshpande G. Smith S.W. Impact medical record outcomes hospitalized patients.Pharmacotherapy. 2011; 742-747Crossref (106) conclusion, illustrate faced partly due difficulty phenotypes. At present, apart high costly DPT, tests allow readministration. addition, allergenic determinants identified. Further research focused epitope mapping role HLA-A∗32:01 might help develop reliable vitro capable confirming identifying mechanism. Reactions Documented Electronic Health RecordsThe Journal Clinical Immunology: PracticeVol. 9Issue 2PreviewVancomycin, common hospitals, cause reactions, (HSRs). Yet, little known about records. Full-Text