Vancomycin-induced Drug Research Articles

A Rare Case of Vancomycin-Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome, Eosinophilic Pneumonitis, and Steroid-Resistant Acute Interstitial Nephritis Requiring Additional Immunosuppression: A Case Report

A Rare Case of Vancomycin-Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome, Eosinophilic Pneumonitis, and Steroid-Resistant Acute Interstitial Nephritis Requiring Additional Immunosuppression: A Case Report

Associations of HLA-A and HLA-B with vancomycin-induced drug reaction with eosinophilia and systemic symptoms in the Han-Chinese population.

Vancomycin is a commonly used antibiotic; however, it can cause life-threatening severe cutaneous adverse reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS). A previous study has reported a strong association between HLA-A*32:01 and vancomycin-induced DRESS in European ethnicity. Herein, we aim to investigate the genetic predisposition of vancomycin-induced DRESS in the Han-Chinese population. In this study, we enrolled a total of 26 patients with vancomycin-induced DRESS, 1,616 general population controls, and 51 subjects tolerant to vancomycin. In vitro granulysin-based lymphocyte activation tests (LAT) were conducted among 6 vancomycin-induced DRESS patients who were concomitantly receiving other medicines. HLA-A and HLA-B genotypes were determined by sequencing-based typing. Our results found that vancomycin-induced DRESS was associated with HLA-A*32:01 [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 1.7-35.8; p-value = 0.035], HLA-B*07:05 (OR = 32.3, 95% CI = 2.8-367.7; p-value = 0.047), HLA-B*40:06 (OR = 4.7, 95% CI = 1.3-16.1; p-value = 0.036) and HLA-B*67:01 (OR = 44.8, 95% CI = 7.2-280.4; p-value = 0.002) when comparing the vancomycin-induced DRESS patients with the general population controls. LAT results showed that granulysin significantly increased in the vancomycin-induced DRESS patients upon vancomycin stimulation (4.7 ± 3.7 fold increased), but not upon other co-medicines. This study identified that, in addition to HLA-A*32:01, HLA-B*07:05, HLA-B*40:06, and HLA-B*67:01 were also genetic markers for vancomycin-induced DRESS in the Han-Chinese population. Associations of ethnic variances in HLA with vancomycin-DRESS were observed.

Deciphering Adverse Drug Reactions: In Vitro Priming and Characterization of Vancomycin-Specific T Cells From Healthy Donors Expressing HLA-A*32:01.

Drug rash with eosinophilia with systemic symptoms (DRESS) is a serious adverse event associated with use of the glycopeptide antibiotic vancomycin. Vancomycin-induced drug rash with eosinophilia with systemic symptoms is associated with the expression of human leukocyte antigen (HLA)-A*32:01, suggesting that the drug interacts with this HLA to activate CD8+ T cells. The purpose of this study was to utilize peripheral blood mononuclear cell from healthy donors to: (1) investigate whether expression of HLA-A*32:01 is critical for the priming naïve of T cells with vancomycin and (2) generate T-cell clones (TCC) to determine whether vancomycin exclusively activates CD8+ T cells and to define cellular phenotype, pathways of drug presentation and cross-reactivity. Dendritic cells were cultured with naïve T cells and vancomycin for 2 weeks. On day 14, cells were restimulated with vancomycin and T-cell proliferation was assessed by [3H]-thymidine incorporation. Vancomycin-specific TCC were generated by serial dilution and repetitive mitogen stimulation. Naïve T cells from HLA-A*02:01 positive and negative donors were activated with vancomycin; however the strength of the induced response was significantly stronger in donors expressing HLA-A*32:01. Vancomycin-responsive CD4+ and CD8+ TCC from HLA-A*32:01+ donors expressed high levels of CXCR3 and CCR4, and secreted IFN‐γ, IL-13, and cytolytic molecules. Activation of CD8+ TCC was HLA class I-restricted and dependent on a direct vancomycin HLA binding interaction with no requirement for processing. Several TCC displayed cross-reactivity with teicoplanin and daptomycin. To conclude, this study provides evidence that vancomycin primes naïve T cells from healthy donors expressing HLA-A*32:01 through a direct pharmacological binding interaction. Cross-reactivity of CD8+ TCC with teicoplanin provides an explanation for the teicoplanin reactions observed in vancomycin hypersensitive patients.

Acute kidney injury in vancomycin-induced drug reaction with eosinophilia and systemic symptoms: A case-control study

Acute kidney injury in vancomycin-induced drug reaction with eosinophilia and systemic symptoms: A case-control study

Vancomycin-induced drug rash with eosinophilia and systemic symptoms (DRESS)

A 52-year-old previously healthy man presented to the emergency department with pruritic rash, angioedema and fever of 39.3°C that started the day previously. Four weeks ago, he was treated for...

A case of vancomycin-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome with failure to respond to cyclosporine treatment

Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare delayed drug reaction that often occurs 2-6 weeks after initiation of therapy and may develop into a life-threatening systemic reaction. Besides immediate discontinuation of the suspected inciting drug, initiation of high dose systemic corticosteroids has long been the mainstay of treatment for severe cases. Nevertheless, significant drawbacks associated with systemic corticosteroid therapy, such as the requirement of a long tapering period post resolution and extensive adverse side effects profile, have motivated clinicians to seek alternative treatment options. Over the past decade, an undisputed increasing number of favorable case reports has highlighted cyclosporine as an emerging, safe, and effective alternative despite inconsistent dosing regimens reported. Herein, we report a severe case of vancomycin-induced DRESS syndrome in which the patient failed initial intervention with cyclosporine and needed rescue with methylprednisolone. To the best of our knowledge, this constitutes the first unsuccessful report of cyclosporine treatment for DRESS syndrome.

A Rapid Allele-Specific Assay for HLA-A*32:01 to Identify Patients at Risk for Vancomycin-Induced Drug Reaction with Eosinophilia and Systemic Symptoms

Human leukocyte antigen (HLA) alleles have been implicated as risk factors for immune-mediated adverse drug reactions. The authors recently reported a strong association between HLA-A*32:01 and vancomycin-induced drug reaction with eosinophilia and systemic symptoms. Identification of individuals with the risk allele before or shortly after the initiation of vancomycin therapy is of great clinical importance to prevent morbidity and mortality, and improve drug safety and antibiotic treatment options. A prerequisite to the success of pharmacogenetic screening tests is the development of simple, robust, cost-effective single HLA allele test that can be implemented in routine diagnostic laboratories. In this study, the authors developed a simple, real-time allele-specific PCR for typing the HLA-A*32:01 allele. Four-hundred and fifty-eight DNA samples including 30 HLA-A*32:01-positive samples were typed by allele-specific PCR. Compared with American Society for Histocompatibility and Immunogenetics-accredited, sequence-based, high-resolution, full-allelic HLA typing, this assay demonstrates 100% accuracy, 100% sensitivity (95% CI, 88.43% to 100%), and 100% specificity (95% CI, 99.14% to 100%). The lowest limit of detection of this assay using PowerUp SYBR Green is 10 ng of template DNA. The assay demonstrates a sensitivity and specificity to differentiate the HLA-A*32:01 allele from closely related non-HLA-A*32 alleles and may be used in clinical settings to identify individuals with the risk allele before or during the course of vancomycin therapy.

Vancomycin-Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Masquerading as Elusive Sepsis

We present a unique case of vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome masquerading as elusive endocarditis. A 37-year-old female actively using intravenous drugs presented with worsening right upper extremity pain, fever, and chills. Workup revealed methicillin-resistant staphylococcus aureus (MRSA) bacteremia and multiple right-sided septic pulmonary emboli. Echocardiogram was negative for vegetation. Vancomycin was initiated for bacteremia management suspected secondary to right upper extremity abscesses. However, despite resolution of abscesses, fevers persisted, raising suspicion for endocarditis not detected by echocardiogram. On hospital day 25, the patient began showing signs of DRESS syndrome, ultimately manifesting as transaminitis, eosinophilia, and a diffuse, maculopapular rash. Vancomycin was switched to Linezolid and she improved on high dose steroids. The persistent fevers throughout this hospital course were thought to be an elusive endocarditis before DRESS syndrome fully manifested. Although Vancomycin-induced DRESS is uncommon, this case highlights the importance of identifying early signs of significant adverse effects.

HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms

Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs. We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS. Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele. Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P=1×10-8) and 6.3% of the BioVU population (n=54,249, P=2×10-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4weeks. HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.

Vancomycin-Induced Drug Rash With Eosinophilia and Systemic Symptoms

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced hypersensitivity reaction associated with 10% mortality rate with an incidence ranging from 1/1,000 to 1/10,000 drug exposures. Symptoms include fever, rash, eosinophilia and multi-organ failure. DRESS has been most commonly reported with anticonvulsants, allopurinol, sulfonamides and less commonly with vancomycin. This is a case of a 34-year-old female with history of osteomyelitis being treated with vancomycin in a rehabilitation facility. After 3 weeks on vancomycin, patient started to have fever and generalized rash and was still continued on vancomycin. One week thereafter, patient was noted to be hypoxic and tachycardic, and initially admitted and treated as severe sepsis. Initial laboratory studies were remarkable for WBC 21.6 × 10 3 /?L, eosinophils 2.2 × 10 3 /?L, creatinine 1.51 mg/dL, AST 710 unit/L, ALT 659 unit/L and lactic acid 2.8 mg/dL. CMV and HHV-6 were detected in serum. Chest CT showed ground glass opacities and lymphadenopathies. Liver ultrasound showed mild hepatosplenomegaly. Patient continued to be on broad spectrum antibiotics and showed no improvement. Due to worsening liver function tests and kidney injury, all antibiotics were withdrawn, after which she showed significant improvement of symptoms. During her 4 weeks of prolonged clinical course she had one relapse of symptoms with fever, rash and leukocytosis. Eventually, patient slowly recovered with supportive treatment. DRESS syndrome usually has a delayed onset with known relapse of symptoms throughout its clinical course. Addition of new drugs and herpesvirus reactivation have both been shown to cause relapse of symptoms. The mainstay of treatment remains to be withdrawal of drug and treatment with steroids. This case demonstrates DRESS syndrome secondary to vancomycin exposure with relapse of symptoms most likely associated with addition of new drugs, herpes viral reactivation and absence of steroid therapy. Vancomycin, as a commonly used drug especially with increasing MRSA, warrants increased awareness of its association with DRESS for prompt early recognition of symptoms and withdrawal of offending drug. J Med Cases. 2015;6(5):201-204 doi: http://dx.doi.org/10.14740/jmc2103w

Vancomycin-Induced Drug Rash With Eosinophilia and Systemic Symptoms

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced hypersensitivity reaction associated with 10% mortality rate with an incidence ranging from 1/1,000 to 1/10,000 drug exposures. Symptoms include fever, rash, eosinophilia and multi-organ failure. DRESS has been most commonly reported with anticonvulsants, allopurinol, sulfonamides and less commonly with vancomycin. This is a case of a 34-year-old female with history of osteomyelitis being treated with vancomycin in a rehabilitation facility. After 3 weeks on vancomycin, patient started to have fever and generalized rash and was still continued on vancomycin. One week thereafter, patient was noted to be hypoxic and tachycardic, and initially admitted and treated as severe sepsis. Initial laboratory studies were remarkable for WBC 21.6 × 10 3 /μL, eosinophils 2.2 × 10 3 /μL, creatinine 1.51 mg/dL, AST 710 unit/L, ALT 659 unit/L and lactic acid 2.8 mg/dL. CMV and HHV-6 were detected in serum. Chest CT showed ground glass opacities and lymphadenopathies. Liver ultrasound showed mild hepatosplenomegaly. Patient continued to be on broad spectrum antibiotics and showed no improvement. Due to worsening liver function tests and kidney injury, all antibiotics were withdrawn, after which she showed significant improvement of symptoms. During her 4 weeks of prolonged clinical course she had one relapse of symptoms with fever, rash and leukocytosis. Eventually, patient slowly recovered with supportive treatment. DRESS syndrome usually has a delayed onset with known relapse of symptoms throughout its clinical course. Addition of new drugs and herpesvirus reactivation have both been shown to cause relapse of symptoms. The mainstay of treatment remains to be withdrawal of drug and treatment with steroids. This case demonstrates DRESS syndrome secondary to vancomycin exposure with relapse of symptoms most likely associated with addition of new drugs, herpes viral reactivation and absence of steroid therapy. Vancomycin, as a commonly used drug especially with increasing MRSA, warrants increased awareness of its association with DRESS for prompt early recognition of symptoms and withdrawal of offending drug. J Med Cases. 2015;6(5):201-204 doi: https://doi.org/10.14740/jmc2103w

Drug rash, eosinophilia, and systemic symptoms syndrome: Two pediatric cases demonstrating the range of severity in presentation—A case of vancomycin-induced drug hypersensitivity mimicking toxic shock syndrome and a milder case induced by minocycline

Drug rash, eosinophilia, and systemic symptoms syndrome is a type of drug hypersensitivity reaction characterized by the clinical triad of skin eruption, fever, and internal organ involvement. Drug rash, eosinophilia, and systemic symptoms syndrome has rarely been reported in association with vancomycin or in the pediatric population. There have only been four pediatric case reports of drug rash, eosinophilia, and systemic symptoms syndrome and three cases of drug rash, eosinophilia, and systemic symptoms syndrome involving vancomycin published in the English literature to date. We describe two pediatric cases of drug rash, eosinophilia, and systemic symptoms syndrome to illustrate the range in severity of presentation. The first case illustrates drug rash, eosinophilia, and systemic symptoms syndrome associated with vancomycin exposure in a 14-yr-old boy with Duchenne muscular dystrophy after posterior spinal fusion, whose clinical presentation was indistinguishable from toxic shock syndrome. The second case illustrates a milder and more typical presentation of drug rash, eosinophilia, and systemic symptoms syndrome in a 14-yr-old boy being treated with minocycline for acne. We also present a review of the literature relevant to this syndrome. : Drug rash, eosinophilia, and systemic symptoms syndrome is relatively unknown among general pediatricians and pediatric intensivists and may potentially become more common with the increasing use of long-term medications in the pediatric population. Our cases demonstrate the importance of an awareness of drug rash, eosinophilia, and systemic symptoms syndrome among general pediatricians and pediatric intensivists because drug rash, eosinophilia, and systemic symptoms syndrome may present in any range of severity, from indolent illness to frank and refractory shock.

Severe vancomycin-induced drug rash with eosinophilia and systemic symptoms syndrome imitating septic shock

Severe vancomycin-induced drug rash with eosinophilia and systemic symptoms syndrome imitating septic shock

A case of vancomycin-induced drug hypersensitivity syndrome

반코마이신 투여 후에 발생하는 약물 과민성 증후군은 아주 드물게 보고되고 있다. 저자들은 11세 여자 환아에서 감염성 심내막염에 대한 치료로 반코마이신을 투여한 후 18일째부터 발열, 반구진성 발진이 관찰되어, 반코마이신 투여 중단 및 코르티코스테로이드를 투여한 지 24시간 이내에 임상 증상의 호전을 보인 약물 과민성 증후군 1예를 경험하였다. 본 증례의 환아에서는 발열, 반구진성 발진, 간염, 급성 신부전 등이 약물 과민성 증후군의 증상으로 관찰되었다.