Simple rule boosted yield of molecular tests for enteric pathogens

SAN DIEGO – For adult outpatients with diarrhea, consider limiting molecular testing for enteric pathogens to cases in which patients are immunocompromised or have abdominal pain or fever without vomiting, said Stephen Clark, MD.

“This simple clinical decision rule would reduce testing by 43% while retaining a high sensitivity for clinically relevant infections,” Dr. Clark said at an annual meeting on infectious diseases. In a single-center retrospective cohort study, the decision rule covered 96% of patients with molecular evidence of clinically relevant pathogens.

Several Food and Drug and Administration–approved molecular diagnostic panels for enteric pathogens have become available in the United States during the past 4 years. These panels are fast and sensitive, but costly and not clinically relevant unless they detect a pathogen that merits a change in treatment, such as titrating immunosuppressive drugs or prescribing a course of antimicrobial therapy, said Dr. Clark, a third-year resident at the department of medicine at the University of Virginia in Charlottesville.

Physicians at the University of Virginia often order the FilmArray Gastrointestinal Panel (Biofire Diagnostics) for adult outpatients, especially if they have persistent diarrhea, Dr. Clark said. However, medical records from 452 tested patients showed that only 88 (20%) tested positive for an enteric pathogen and only 4% had an infection clearly meriting antimicrobial therapy. Therefore, the researchers sought predictors of clinically relevant FilmArray results.

Among 376 immunocompetent patients in this cohort, only 12 (3%) had a treatable pathogen detected. None of these 12 patients reported vomiting, while 11 (92%) reported fever or abdominal pain without vomiting, compared with only 47% of immunocompetent patients with no treatable pathogen (P = .002). For immunocompetent patients, the combination of subjective fever or abdominal pain without vomiting was the only demographic or clinical predictor of a clinically relevant positive test result, Dr. Clark said.

Importantly, the FilmArray GI panel showed a much higher clinical yield (about 20%) in immunocompromised patients, who often lacked clinical signs of gastrointestinal infection. “Thinking about this overall, we would recommend testing if patients are either immunocompromised, or if they have abdominal pain or fever in the absence of vomiting,” Dr. Clark said. For this cohort, this decision rule had a sensitivity of 96% (95% confidence interval [CI], 81%-100%) and a negative predictive value of 99% (95% CI, 97%-100%). Specificity was only 45% (95% CI, 41%-51%), but “the aim of this rule was more to help clinicians think about whether it’s possible that there could be a detection, instead of pinpointing what it might be,” Dr. Clark said.

Applying guidelines from the American College of Gastroenterology did not increase testing efficiency, Dr. Clark said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. The researchers are now reviewing another 6 months of medical records to create a validation cohort for the decision rule.

Dr. Clark and his associates reported having no conflicts of interest.

SAN DIEGO – For adult outpatients with diarrhea, consider limiting molecular testing for enteric pathogens to cases in which patients are immunocompromised or have abdominal pain or fever without vomiting, said Stephen Clark, MD.

“This simple clinical decision rule would reduce testing by 43% while retaining a high sensitivity for clinically relevant infections,” Dr. Clark said at an annual meeting on infectious diseases. In a single-center retrospective cohort study, the decision rule covered 96% of patients with molecular evidence of clinically relevant pathogens.

Several Food and Drug and Administration–approved molecular diagnostic panels for enteric pathogens have become available in the United States during the past 4 years. These panels are fast and sensitive, but costly and not clinically relevant unless they detect a pathogen that merits a change in treatment, such as titrating immunosuppressive drugs or prescribing a course of antimicrobial therapy, said Dr. Clark, a third-year resident at the department of medicine at the University of Virginia in Charlottesville.

Physicians at the University of Virginia often order the FilmArray Gastrointestinal Panel (Biofire Diagnostics) for adult outpatients, especially if they have persistent diarrhea, Dr. Clark said. However, medical records from 452 tested patients showed that only 88 (20%) tested positive for an enteric pathogen and only 4% had an infection clearly meriting antimicrobial therapy. Therefore, the researchers sought predictors of clinically relevant FilmArray results.

Among 376 immunocompetent patients in this cohort, only 12 (3%) had a treatable pathogen detected. None of these 12 patients reported vomiting, while 11 (92%) reported fever or abdominal pain without vomiting, compared with only 47% of immunocompetent patients with no treatable pathogen (P = .002). For immunocompetent patients, the combination of subjective fever or abdominal pain without vomiting was the only demographic or clinical predictor of a clinically relevant positive test result, Dr. Clark said.

Importantly, the FilmArray GI panel showed a much higher clinical yield (about 20%) in immunocompromised patients, who often lacked clinical signs of gastrointestinal infection. “Thinking about this overall, we would recommend testing if patients are either immunocompromised, or if they have abdominal pain or fever in the absence of vomiting,” Dr. Clark said. For this cohort, this decision rule had a sensitivity of 96% (95% confidence interval [CI], 81%-100%) and a negative predictive value of 99% (95% CI, 97%-100%). Specificity was only 45% (95% CI, 41%-51%), but “the aim of this rule was more to help clinicians think about whether it’s possible that there could be a detection, instead of pinpointing what it might be,” Dr. Clark said.

Applying guidelines from the American College of Gastroenterology did not increase testing efficiency, Dr. Clark said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. The researchers are now reviewing another 6 months of medical records to create a validation cohort for the decision rule.

Dr. Clark and his associates reported having no conflicts of interest.

SAN DIEGO – For adult outpatients with diarrhea, consider limiting molecular testing for enteric pathogens to cases in which patients are immunocompromised or have abdominal pain or fever without vomiting, said Stephen Clark, MD.

“This simple clinical decision rule would reduce testing by 43% while retaining a high sensitivity for clinically relevant infections,” Dr. Clark said at an annual meeting on infectious diseases. In a single-center retrospective cohort study, the decision rule covered 96% of patients with molecular evidence of clinically relevant pathogens.

Several Food and Drug and Administration–approved molecular diagnostic panels for enteric pathogens have become available in the United States during the past 4 years. These panels are fast and sensitive, but costly and not clinically relevant unless they detect a pathogen that merits a change in treatment, such as titrating immunosuppressive drugs or prescribing a course of antimicrobial therapy, said Dr. Clark, a third-year resident at the department of medicine at the University of Virginia in Charlottesville.

Physicians at the University of Virginia often order the FilmArray Gastrointestinal Panel (Biofire Diagnostics) for adult outpatients, especially if they have persistent diarrhea, Dr. Clark said. However, medical records from 452 tested patients showed that only 88 (20%) tested positive for an enteric pathogen and only 4% had an infection clearly meriting antimicrobial therapy. Therefore, the researchers sought predictors of clinically relevant FilmArray results.

Among 376 immunocompetent patients in this cohort, only 12 (3%) had a treatable pathogen detected. None of these 12 patients reported vomiting, while 11 (92%) reported fever or abdominal pain without vomiting, compared with only 47% of immunocompetent patients with no treatable pathogen (P = .002). For immunocompetent patients, the combination of subjective fever or abdominal pain without vomiting was the only demographic or clinical predictor of a clinically relevant positive test result, Dr. Clark said.

Importantly, the FilmArray GI panel showed a much higher clinical yield (about 20%) in immunocompromised patients, who often lacked clinical signs of gastrointestinal infection. “Thinking about this overall, we would recommend testing if patients are either immunocompromised, or if they have abdominal pain or fever in the absence of vomiting,” Dr. Clark said. For this cohort, this decision rule had a sensitivity of 96% (95% confidence interval [CI], 81%-100%) and a negative predictive value of 99% (95% CI, 97%-100%). Specificity was only 45% (95% CI, 41%-51%), but “the aim of this rule was more to help clinicians think about whether it’s possible that there could be a detection, instead of pinpointing what it might be,” Dr. Clark said.

Applying guidelines from the American College of Gastroenterology did not increase testing efficiency, Dr. Clark said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. The researchers are now reviewing another 6 months of medical records to create a validation cohort for the decision rule.

Dr. Clark and his associates reported having no conflicts of interest.