High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor for adverse reactions in patients with pneumocystis pneumonia and AIDS

Chang, Hui Min; Tsai, Hung Chin; Lee, Susan Shin Jung; Kunin, Calvin M.; Lin, Pei‐Chen; Wann, Shue Ren; Chen, Yao Shen

doi:10.1016/j.jcma.2016.01.007

Cited by 21 publications

(18 citation statements)

References 27 publications

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“…36,37 Chang et al reported that high daily doses of CTX were an independent risk factor for cutaneous and other adverse drug reactions. 38 We did not measure the serum concentrations of CTX, so it is possible that plasma and tissue concentrations of CTX might have influenced the adverse outcomes in our study. However, a previous case-control study by Pirmohamed et al failed to demonstrate an association between genetic polymorphisms in drug metabolizing enzymes with CTX hypersensitivity in patients with HIV.…”

Section: Articlementioning

confidence: 96%

“…A recent case-control study in the Thai population reported an association between CTX-induced SJS/TEN and HLA-B*15:02 (odds ratio (OR) = 3.91; 95% confidence interval (CI): 1.42-10.92; P = 0.0037), HLA-C*06:02 (OR = 11.84; 95% CI: 1.24-566.04; P = 0.0131) and HLA-C*08:01 (OR = 3.53; 95% CI: 1.21-10.40; P = 0.0108). 12 In European patients, the presence of HLA-B* 38 was significantly associated with sulfamethoxazole-related SJS/ TEN, but the different allelic variants of HLA-B*38 did not show significant association with sulfamethoxazole-related SJS/TEN. 13 Additionally, a strong association between SJS/TEN and trimethoprim alone was observed.…”

Section: Genetic Association Of Co-trimoxazole-induced Severe Cutaneomentioning

confidence: 98%

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Genetic Association of Co‐Trimoxazole‐Induced Severe Cutaneous Adverse Reactions Is Phenotype‐Specific: HLA Class I Genotypes and Haplotypes

Sukasem

Pratoomwun

Satapornpong

et al. 2020

Clin Pharma and Therapeutics

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Co-trimoxazole (CTX) causes various forms of severe cutaneous adverse reactions (SCARs). This case-control study was conducted to investigate the involvement between genetic variants of human leukocyte antigen (HLA) and CYP2C9 in CTX-induced SCARs, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in Thai patients. Thirty cases of CTX-induced SCARs were enrolled and compared with 91 CTX-tolerant controls and 150 people from the general Thai population. Cases comprised 18 SJS/TEN and 12 DRESS patients. This study demonstrated that genetic association of CTX-induced SCARs was phenotype-specific. HLA-B*15:02 and HLA-C*08:01 alleles were significantly associated with CTXinduced SJS/TEN, whereas the HLA-B*13:01 allele was significantly associated with CTX-induced DRESS. In addition, a significant higher frequency of HLA-A*11:01-B*15:02 and HLA-B*13:01-C*03:04 haplotypes were detected in the group of CTX-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS cases, respectively. Genetic association of CTX-induced SCARs is phenotype-specific. Interestingly, these association was observed only in HIV-infected patients but not in non-HIV-infected patients.

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Section: Articlementioning

confidence: 96%

Section: Genetic Association Of Co-trimoxazole-induced Severe Cutaneomentioning

confidence: 98%

Genetic Association of Co‐Trimoxazole‐Induced Severe Cutaneous Adverse Reactions Is Phenotype‐Specific: HLA Class I Genotypes and Haplotypes

Sukasem

Pratoomwun

Satapornpong

et al. 2020

Clin Pharma and Therapeutics

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“…According to current guidelines for the prevention and treatment of opportunistic infections in HIV-infected patients, the preferred treatment for PCP is oral or intravenous trimethoprim-sulfamethoxazole (TMP-SMX; TMP, 15 to 20 mg/kg/day; SMX, 75 to 100 mg/kg/day) for 21 days (6). However, clinicians often have to reduce the dose or switch to an alternative treatment due to the occurrence of adverse events (7).…”

mentioning

confidence: 99%

A Four-Center Retrospective Study of the Efficacy and Toxicity of Low-Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Pneumonia in Patients without HIV Infection

Kosaka

Ushiki

Ikuyama

et al. 2017

Antimicrob Agents Chemother

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The dose of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of pneumonia (PCP) in patients without human immunodeficiency virus (HIV) infection has not been verified. The aim of this study was to investigate the efficacy and toxicity of a low-dose TMP-SMX regimen in such patients. A retrospective study was conducted in four hospitals. We reviewed the medical records of patients with PCP but not HIV (non-HIV-PCP) who were treated with TMP-SMX between 2003 and 2016. The patients were divided into conventional-dose (TMP, 15 to 20 mg/kg/day) and low-dose (TMP,<15 mg/kg/day) groups after patients who received high-dose (TMP, >20 mg/kg/day) treatment were excluded. Grouping was done according to a correction dose, which was based on renal function. Eighty-two patients had non-HIV-PCP. The numbers of patients who received high-, conventional-, and low-dose treatments were 5, 36, and 41, respectively. Kaplan-Meier analysis for death associated with PCP showed no statistically significant difference in survival rates between the conventional- and low-dose groups. Ninety-day cause-specific mortality rates were 25.0% and 19.5% in the conventional-dose and low-dose groups ( = 0.76), respectively. Adverse events that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events (version 4.0) (National Cancer Institute, 2010) were 41.7% and 17.1% in the conventional-dose and low-dose groups ( = 0.02), respectively. Moreover, vomiting ( = 0.03) and a decrease in platelet count ( = 0.03) occurred more frequently in the conventional-dose group. Treatment of non-HIV-PCP with low-dose or conventional-dose TMP-SMX produces comparable survival rates; however, the low-dose regimen is better tolerated and associated with fewer adverse effects.

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“…; Chang et al. ; Hernandez et al. ) The risk of sulfonamide HS increases with HIV disease progression, with higher risk seen at lower CD4 + counts.…”

Section: Introductionmentioning

confidence: 99%

Hepatic expression profiles in retroviral infection: relevance to drug hypersensitivity risk

Wong¹,

Johnson

Friedrich

et al. 2017

Pharmacology Res & Perspec

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HIV‐infected patients show a markedly increased risk of delayed hypersensitivity (HS) reactions to potentiated sulfonamide antibiotics (trimethoprim/sulfamethoxazole or TMP/SMX). Some studies have suggested altered SMX biotransformation in HIV infection, but hepatic biotransformation pathways have not been evaluated directly. Systemic lupus erythematosus (SLE) is another chronic inflammatory disease with a higher incidence of sulfonamide HS, but it is unclear whether retroviral infection and SLE share risk factors for drug HS. We hypothesized that retroviral infection would lead to dysregulation of hepatic pathways of SMX biotransformation, as well as pathway alterations in common with SLE that could contribute to drug HS risk. We characterized hepatic expression profiles and enzymatic activities in an SIV‐infected macaque model of retroviral infection, and found no evidence for dysregulation of sulfonamide drug biotransformation pathways. Specifically, NAT1,NAT2,CYP2C8,CYP2C9,CYB5R3,MARC1/2, and glutathione‐related genes (GCLC,GCLM,GSS,GSTM1, and GSTP1) were not differentially expressed in drug naïve SIVmac239‐infected male macaques compared to age‐matched controls, and activities for SMX N‐acetylation and SMX hydroxylamine reduction were not different. However, multiple genes that are reportedly over‐expressed in SLE patients were also up‐regulated in retroviral infection, to include enhanced immunoproteasomal processing and presentation of antigens as well as up‐regulation of gene clusters that may be permissive to autoimmunity. These findings support the hypothesis that pathways downstream from drug biotransformation may be primarily important in drug HS risk in HIV infection.

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High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor for adverse reactions in patients with pneumocystis pneumonia and AIDS

Abstract: We found a high incidence of ADRs among patients with PJP and AIDS treated with TMP/SMX, and most involved the skin and liver. A daily dose of ≥ 16 mg/kg of TMP/SMX and age 34 years were independent risk factors for ADRs.

Cited by 21 publications

References 27 publications

Genetic Association of Co‐Trimoxazole‐Induced Severe Cutaneous Adverse Reactions Is Phenotype‐Specific: HLA Class I Genotypes and Haplotypes

Genetic Association of Co‐Trimoxazole‐Induced Severe Cutaneous Adverse Reactions Is Phenotype‐Specific: HLA Class I Genotypes and Haplotypes

A Four-Center Retrospective Study of the Efficacy and Toxicity of Low-Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Pneumonia in Patients without HIV Infection

Hepatic expression profiles in retroviral infection: relevance to drug hypersensitivity risk

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