Penicillin Allergy

Penicillin is the most common drug "allergy" noted at hospital admission, although it is often inaccurate. We sought to determine total hospital days, antibiotic exposures, and the prevalence rates of Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) in patients with and without penicillin "allergy" at hospital admission. We performed a retrospective, matched cohort study of subjects admitted to Kaiser Foundation hospitals in Southern California during 2010 through 2012. It was possible to match 51,582 (99.6% of all possible cases) unique hospitalized subjects with penicillin "allergy" to 2 unique discharge diagnosis category-matched, sex-matched, age-matched, and date of admission-matched control subjects each. Cases with penicillin "allergy" averaged 0.59 (9.9%; 95% CI, 0.47-0.71) more total hospital days during 20.1 ± 10.5 months of follow-up compared with control subjects. Cases were treated with significantly more fluoroquinolones, clindamycin, and vancomycin (P < .0001) for each antibiotic compared with control subjects. Cases had 23.4% (95% CI, 15.6% to 31.7%) more C difficile, 14.1% (95% CI, 7.1% to 21.6%) more MRSA, and 30.1% (95% CI, 12.5% to 50.4%) more VRE infections than expected compared with control subjects. A penicillin "allergy" history, although often inaccurate, is not a benign finding at hospital admission. Subjects with a penicillin "allergy" history spend significantly more time in the hospital. Subjects with a penicillin "allergy" history are exposed to significantly more antibiotics previously associated with C difficile and VRE. Drug "allergies" in general, but most those notably to penicillin, are associated with increased hospital use and increased C difficile, MRSA, and VRE prevalence. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

β-Lactam antibiotics are among the safest and most effective antibiotics. Many patients report allergies to these drugs that limit their use, resulting in the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance and adverse events.

Drug-induced liver injury (DILI), especially from antimicrobial agents, is an important cause of serious liver disease. Amoxicillin-clavulanate (AC) is a leading cause of idiosyncratic DILI, but little is understood about genetic susceptibility to this adverse reaction. We performed a genome-wide association study using 822,927 single nucleotide polymorphism (SNP) markers from 201 White European and US cases of DILI following AC administration (AC-DILI) and 532 population controls, matched for genetic background. AC-DILI was associated with many loci in the major histocompatibility complex. The strongest effect was with an HLA class II SNP (rs9274407, P=4.8×10(-14)), which correlated with rs3135388, a tag SNP of HLA-DRB1*1501-DQB1*0602 that was previously associated with AC-DILI. Conditioned on rs3135388, rs9274407 is still significant (P=1.1×10(-4)). An independent association was observed in the class I region (rs2523822, P=1.8×10(-10)), related to HLA-A*0201. The most significant class I and II SNPs showed statistical interaction (P=.0015). High-resolution HLA genotyping (177 cases and 219 controls) confirmed associations of HLA-A*0201 (P=2×10(-6)) and HLA-DQB1*0602 (P=5×10(-10)) and their interaction (P=.005). Additional, population-dependent effects were observed in HLA alleles with nominal significance. In an analysis of autoimmune-related genes, rs2476601 in the gene PTPN22 was associated (P=1.3×10(-4)). Class I and II HLA genotypes affect susceptibility to AC-DILI, indicating the importance of the adaptive immune response in pathogenesis. The HLA genotypes identified will be useful in studies of the pathogenesis of AC-DILI but have limited utility as predictive or diagnostic biomarkers because of the low positive predictive values. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.