Trimethoprim: The overlooked component of trimethoprim‐sulfamethoxazole idiosyncratic adverse drug reactions

Goldman, Jennifer L.; Haandel, Leon van

doi:10.1002/pds.4574

“…Likely, the rare and critical nature of this disease contributes to under recognition. To date there is also no clear delineation of whether the trimethoprim or sulfamethoxazole component contributes most to these reactions (4). While TMP-SMX ARDS is a rare ADR, we propose the first cohesive disease definition and only current recommendations for clinical evaluation of TMP-SMX-associated ARDS.…”

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confidence: 99%

Definition and Clinical Evaluation for Trimethoprim-Sulfamethoxazole Severe Acute Respiratory Failure

Miller

¹

,

Khan

²

,

Mino‐Kenudson

³

et al. 2023

Critical Care Medicine

6

4

0

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Objectives: Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition and clinical evaluation for a novel adverse drug reaction (ADR) based on a series of recently identified rare cases of life-threatening ADRs. Design: A retrospective study was conducted. All medical records were evaluated. Available pathology samples were sent to Massachusetts General for clinical consultation. Blood samples from surviving patients were obtained and human leukocyte antigen (HLA) analysis was performed by the Children’s Mercy Hospital Genomic Center and Vanderbilt University Medical Center. Setting: U.S. ICUs, 1996–2021. Patients: Nineteen young patients (10–37) were identified. Patients were previously healthy, with no preexisting pulmonary disease, no other cause for respiratory failure, and no chronic history of smoking/vaping. Interventions: None. Measurements and Main Results: Through our retrospective analysis, we analyzed clinical characteristics associated with TMP-SMX. Pathology samples were reviewed, and HLA analysis was performed on available samples by the study team or as standard of care at treatment hospitals in some cases. In 19 critically ill patients, we identified a pattern of severe respiratory failure requiring ICU admission, mechanical ventilation, and frequent extracorporeal membrane oxygenation use. We describe the first three-part clinical diagnosis and evaluation strategy: 1) Clinical definition: Unexplained severe respiratory failure in a patient receiving greater than or equal to 6 days of TMP-SMX at treatment dose (not prophylaxis). TMP-SMX ARDS is a diagnosis of exclusion. 2) Genetic association: One hundred percent of currently available TMP-SMX respiratory failure patient genomic data, (n = 11) have been carriers of both HLA-B*07:02 and HLA-C*07:02 alleles. HLA allele evaluation could be considered in patients with suspected TMP-SMX respiratory failure. 3) Lung pathology: A unique pulmonary pathologic pattern of lung injury termed diffuse alveolar injury with delayed epithelialization has been observed in these cases. In suspected cases, surgical lung biopsy early in the clinical course could be considered. Conclusions: TMP-SMX is a commonly prescribed antibiotic. However, we find it imperative to share this relatively rare but life-threatening condition with clinicians as the mortality rate approaches 40%.

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“…However, resistance to sulfamethoxazole/trimethoprim among S. maltophilia isolates has been increasingly reported worldwide [10]. Additionally, while sulfamethoxazole/trimethoprim resistance rates generally remain low, hypersensitivity, drug toxicity, and other adverse drug events often preclude the use of this agent, leaving clinicians with even fewer treatment options [11,12]. Previous surveillance of S. maltophilia susceptibility worldwide is generally limited to clinical isolates from hospitalized patients [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…maltophilia isolates has been increasingly reported worldwide [10]. Additionally, while sulfamethoxazole/trimethoprim resistance rates generally remain low, hypersensitivity, drug toxicity, and other adverse drug events often preclude the use of this agent, leaving clinicians with even fewer treatment options [11, 12]. Previous surveillance of S.…”

Section: Introductionmentioning

confidence: 99%

Trends in Stenotrophomonas maltophilia antibiotic resistance rates in the United States Veterans Affairs Health System

Appaneal

¹

,

Lopes

²

,

LaPlante

³

et al. 2022

Journal of Medical Microbiology

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Introduction. Stenotrophomonas maltophilia is an important multidrug-resistant Gram-negative pathogen. While largely a hospital-acquired pathogen, there have been increasing reports of the pathogen in the community. Gap Statement. Trends in S. maltophilia prevalence and resistance rates that include outpatient isolates are unknown. Aim. We described recent trends in prevalence and resistance of S. maltophilia in the national Veterans Affairs (VA) Healthcare system. Methodology. The study identified positive S. maltophilia clinical cultures among VA adult patients from 2010 to 2018 across all VA hospitals, long-term care facilities/units, and outpatient settings. Annual S. maltophilia resistance rates were evaluated. Multidrug resistant (MDR) was defined as resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and minocycline or levofloxacin. Time trends were assessed with regression analyses to estimate annual average percent changes (AAPC) with 95 % confidence intervals using Joinpoint software. Results. Over the 9 year study period, 18 285 S . maltophilia cultures were identified (57 % hospital, 3 % long-term care, 40 % outpatient). The most common source of S. maltophilia cultures were respiratory cultures (34.6 %) followed by urine cultures (30.4 %). In VA hospitals and long-term care facilities, the number of S. maltophilia cultures decreased significantly (by 5.4% and 8.4 % per year respectively). Overall, 3.1 % of isolates were MDR which remained stable over the study period. Resistance to other antibiotics assessed mostly remained stable, except SMX/TMP resistance decreased significantly by 8.5 % (2010, 15 %; 2018, 6 %) per year in VA hospitals. Conclusion. While previous work has recognized S. maltophilia as primarily a nosocomial pathogen, the present study found that 40 % of cultures collected were among outpatients. Between 2010 and 2018, the number of positive S. maltophilia cultures decreased significantly in the national VA Healthcare System. Resistance to SMX/TMP decreased over the study period in VA hospitals and now more closely reflects previously reported resistance rates worldwide (0–10 %). MDR S. maltophilia remained stable and low in the national VA Healthcare System.

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