Immune-mediated reactions to vancomycin: A systematic case review and analysis

Abstract

Background: Vancomycin is a broad-spectrum antibiotic whose use may be limited by adverse drug reactions (ADRs). Although vancomycin toxic effects are known, there are limited data on vancomycin hypersensitivity reactions (HSRs).

Objective: To understand the most commonly reported vancomycin HSRs through systematic case review.

Methods: We performed a literature search for English-language case reports and series from 1982 through 2015 (last search July 31, 2015) on Ovid MEDLINE and PubMed. The search included the subject heading vancomycin with the subheading adverse effects and separate text searches for vancomycin with a list of specified HSRs. References of identified articles were reviewed to find additional articles. Clinical data were collected and summarized.

Results: Of 201 identified articles, 84 were screened and 57 fully assessed; these 57 articles contained 71 vancomycin HSR cases that were included in analysis. Vancomycin HSRs were immediate (anaphylaxis, n = 7) and nonimmediate (n = 64). Nonimmediate HSRs included linear IgA bullous dermatosis (LABD, n = 34), drug rash eosinophilia and systemic symptoms (DRESS) syndrome (n = 16), acute interstitial nephritis (AIN, n = 8), and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN, n = 6). Median times of vancomycin therapy before HSR onset was 7 days (interquartile range [IQR], 4-10 days) for LABD, 9 days (IQR, 9-22 days) for SJS/TEN, 21 days (IQR, 17-28 days) for DRESS syndrome, and 26 days (IQR, 7-29 days) for AIN. Overall, 11 patients (16%) died, and 4 (6%) had deaths attributed to the HSR.

Conclusion: Vancomycin causes a variety of HSRs; the most commonly identified were nonimmediate HSRs, with LABD being most frequent. We observed a high frequency of HSR mortality. Further data are needed to understand the frequency and severity of vancomycin HSRs.

Figure 1

Flow chart of methodology for studies chosen for the review Legend. Of 201 identified publications; 84 were screened and 58 met inclusion criteria. The 58 articles included 71 HSR cases.

Figure 2

Cases of Immune-Mediated Hypersensitivity Reactions to Vancomycin Legend. HSRs were immediate (n=7) and non-immediate (n=64). Non-immediate hypersensitivity reactions included LABD ( n=34), DRESS syndrome (n=16), acute interstitial nephritis (n=8), and SJS/ TEN (n=6).

Figure 3

Immune-mediated Hypersensitivity Reactions to Vancomycin. (a) Timing of Hypersensitivity Reactions (b) Observed fatalities by Hypersensitivity Reaction Legend: (A) Median time to onset of hypersensitivity reactions varied by type. (B) Overall 11 (16%) of patients with vancomycin HSRs died, with 4(6%) of deaths attributed to HSR.

Figure 3

Immune-mediated Hypersensitivity Reactions to Vancomycin. (a) Timing of Hypersensitivity Reactions (b) Observed fatalities by Hypersensitivity Reaction Legend: (A) Median time to onset of hypersensitivity reactions varied by type. (B) Overall 11 (16%) of patients with vancomycin HSRs died, with 4(6%) of deaths attributed to HSR.