PMID- 37449964
OWN - NLM
STAT- MEDLINE
DCOM- 20240116
LR  - 20240327
IS  - 1530-0293 (Electronic)
IS  - 0090-3493 (Print)
IS  - 0090-3493 (Linking)
VI  - 51
IP  - 12
DP  - 2023 Dec 1
TI  - Definition and Clinical Evaluation for Trimethoprim-Sulfamethoxazole Severe Acute 
      Respiratory Failure.
PG  - e264-e268
LID - 10.1097/CCM.0000000000006002 [doi]
AB  - 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%.
CI  - Copyright (c) 2023 by the Society of Critical Care Medicine and Wolters Kluwer 
      Health, Inc. All Rights Reserved.
FAU - Miller, Jenna
AU  - Miller J
AD  - Department of Pediatrics, Children's Mercy Hospital, University of 
      Missouri-Kansas City, Kansas City, MO.
FAU - Khan, Hason
AU  - Khan H
AD  - Department of Pediatrics, Children's Mercy Hospital, University of 
      Missouri-Kansas City, Kansas City, MO.
AD  - Kansas City University of Medicine and Biosciences, Kansas City, MO.
FAU - Mino-Kenudson, Mari
AU  - Mino-Kenudson M
AD  - Department of Pathology, Massachusetts General Hospital and Harvard Medical 
      School, Boston, MA.
FAU - Taylor, Martin
AU  - Taylor M
AD  - Department of Pathology, Massachusetts General Hospital and Harvard Medical 
      School, Boston, MA.
FAU - Shih, Angela
AU  - Shih A
AD  - Department of Pathology, Massachusetts General Hospital and Harvard Medical 
      School, Boston, MA.
FAU - Goldman, Jennifer
AU  - Goldman J
AD  - Department of Pediatrics, Children's Mercy Hospital, University of 
      Missouri-Kansas City, Kansas City, MO.
LA  - eng
GR  - R01 GM129783/GM/NIGMS NIH HHS/United States
GR  - T32 CA009216/CA/NCI NIH HHS/United States
GR  - T32CA009216/GF/NIH HHS/United States
GR  - R01GM129783/GF/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230714
PL  - United States
TA  - Crit Care Med
JT  - Critical care medicine
JID - 0355501
RN  - 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination)
RN  - 0 (Anti-Bacterial Agents)
SB  - IM
MH  - Child
MH  - Humans
MH  - Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects
MH  - Retrospective Studies
MH  - Anti-Bacterial Agents/adverse effects
MH  - *Respiratory Distress Syndrome/drug therapy
MH  - *Respiratory Insufficiency/chemically induced/drug therapy
PMC - PMC10787807
MID - NIHMS1939672
COIS- Dr. Miller's institution received funding from the National Institutes of Health 
      (NIH) (T32CA009216 and R01GM129783); received funding from Ocugen. Drs. Taylor 
      and Goldman received support for article research from the NIH. Dr. Mino-Kenudson 
      received funding from AstraZeneca, Sanofi, Innate, Janssen Oncology, and 
      Elsevier. Dr. Goldman institution received funding from the National Institute of 
      General Medical Sciences (R01GM129783). The remaining authors have disclosed that 
      they do not have any potential conflicts of interest.
EDAT- 2023/07/14 13:08
MHDA- 2024/01/16 06:41
PMCR- 2024/02/16
CRDT- 2023/07/14 10:33
PHST- 2024/01/16 06:41 [medline]
PHST- 2023/07/14 13:08 [pubmed]
PHST- 2023/07/14 10:33 [entrez]
PHST- 2024/02/16 00:00 [pmc-release]
AID - 00003246-202312000-00030 [pii]
AID - 10.1097/CCM.0000000000006002 [doi]
PST - ppublish
SO  - Crit Care Med. 2023 Dec 1;51(12):e264-e268. doi: 10.1097/CCM.0000000000006002. 
      Epub 2023 Jul 14.