PCR Testing Finds Infections in Lung Transplant Recipients

Mucor PCR testing of bronchoalveolar lavage (BAL) fluid showed high specificity in identifying invasive pulmonary mucormycosis (IPM) in lung transplant recipients, especially when used in conjunction with imaging, based on data from approximately 800 individuals. Previous research has shown that Mucor PCR testing of BAL fluid can speed diagnosis of IPM in lung transplant patients, but the diagnostic effectiveness remains unclear, wrote Shoaib Ahmad, MD, a postdoctoral research fellow at St. Joseph’s Hospital and Medical Center in Phoenix, and colleagues wrote in a study presented at the annual meeting of the International Society for Heart and Lung Transplantation . Ahmad and colleagues reviewed a total of 3588 BAL Mucor PCR results collected from 743 adult patients between January 1, 2020, and December 31, 2024. The researchers used Fisher’s exact test to identify IPM within 6 months of a positive PCR result. A total of 50 samples (1.4%) were positive and identified in 41 lung transplant recipients with a median age of 67 years; 71% were men. Not all patients with positive samples developed IPM. A total of 16 (32%) of the 50 positive samples corresponded to 10 lung transplant recipients with IPM. All 10 lung transplant recipients with positive PCR results who developed IPM had abnormal chest CT scans; nine patients had Mucor detected via for-cause bronchoscopy, and one patient had Mucor detected via surveillance bronchoscopy. In addition, five lung transplant recipients with negative PCR results went on to develop IPM, all of whom had normal chest CT scans. The positive predictive value (PPV) of the Mucor PCR testing was 32.0%, the negative predictive value was 99.9%, with sensitivity and specificity of 76.2% and 99.0%, respectively. The median time from lung transplant to an IPM diagnosis was 495 days. Approximately two thirds (64%) of the 50 positive Mucor PCR samples corresponded with abnormal chest CT scans, which improved the PPV of the PCR (50% vs 32.0%). The PPV of a positive PCR also improved with a for-cause bronchoscopy vs surveillance bronchoscopy (57.7% vs 4%), or with both CT and bronchoscopy (68.2%). “The main takeaway is that Mucor PCR performs best when there is already a reason to suspect invasive mucormycosis; the test adds value, but it shouldn’t be interpreted in isolation,” said co-author Sofya Tokman, MD, ISHLTF, associate medical director of lung transplantation at Norton Thoracic Institute, St. Joseph’s Hospital and Medical Center. No patients with a positive PCR and normal imaging developed IPM. The findings were limited by several factors including the retrospective design. However, the results suggest a possible role for Mucor PCR as an element of an infection work-up, the researchers concluded. “As we adopt more molecular diagnostics in transplant medicine, we need to be thoughtful about how we use them, especially if the treatment is potentially toxic,” said co-author Christine Pham, PharmD, BCTXP, a transplant clinical pharmacy specialist at the Department of Pharmacy Services, St. Joseph’s Hospital and Medical Center. “Finding microbial DNA is important, but it’s only one piece of the diagnostic puzzle,” Pham noted.

Addressing Uncertainty

The current study is important because IPM in lung transplant patients, while uncommon, has significant consequences for graft survival and mortality, said Jacqueline Burnell, MD, associate professor of clinical medicine at the Lewis Katz School of Medicine at Temple University in Philadelphia, and a specialist in infections in transplant and immunocompromised patients. Diagnosis of IPM has multiple levels of uncertainty, given clinical overlap with other syndromes, and lower culture yield compared to other invasive fungal infections, said Burnell, who was not involved in the new study. “Molecular testing is thought to enhance diagnosis, but when applied to every BAL sample, clinicians often face major dilemmas as to whether positive testing represents true invasive disease, early infection, or colonization,” she said. “The very high negative predictive value was not surprising because IPM is relatively rare, and a negative test in a low-prevalence population will naturally have a high negative predictive value,” said Burnell. The finding that abnormal CT and for-cause bronchoscopy increased PPV also was not unexpected, she said. “Molecular detection is more meaningful when pretest probability is high; however, of particular interest, none of the patients with a positive PCR and normal imaging developed IPM, while all patients who developed IPM despite negative PCR had abnormal chest imaging,” Burnell noted. Burnell agreed with the researchers’ message not to interpret BAL Mucor PCR in isolation. “The best application of PCR was found in patients with abnormal chest imaging, when respiratory sampling was done for diagnostic purposes rather than surveillance with positive predictive value approaching 68%,” she said. “This highlights the need for interpretation of PCR in the clinical context of the patient, as the positive predictive value of PCR in patients without changes on chest imaging was 0%,” she added. The findings were subject to the typical limitations of a retrospective single-center study, and generalizability may be limited by local bronchoscopy practices, mold epidemiology and antifungal prophylaxis said Burnell. In addition, low numbers of true IPM cases limit precision regarding sensitivity, PPV, and subgroup comparisons, and larger collaborative studies are needed to collect more data, she said. The study received no outside funding. The researchers had no financial conflicts to disclose. Burnell had no financial conflicts to disclose.