Correctly processing respiratory samples is critical to treating people with cystic fibrosis (CF), but the microbiology landscape continues to evolve as advances are made in both the clinical care of people with CF and clinical microbiology technologies. To help provide high-quality care to these patients, an international panel of experts in CF, infectious diseases and clinical microbiology laboratories issued guidance for clinical laboratories in processing respiratory samples.
“We hope that this document facilitates ongoing communication between the cystic fibrosis care teams and clinical microbiology laboratories by giving them an expanded vocabulary for doing so,” said Lisa Saiman, MD, MPH, the lead author of the guidance and a professor of pediatrics at Columbia University Irving Medical Center and New York-Presbyterian Morgan Stanley Children’s Hospital, in New York City.
Cystic fibrosis affects the cells that produce mucus, sweat and digestive juices. This leads to the thick, sticky mucus where bacteria can grow and establish chronic infections. While the new CF transmembrane conductance regulator (CFTR) modulator therapies may be associated with reductions of certain bacteria, antibiotics are often needed.
“There is a predictable cascade of organisms that occur in people with cystic fibrosis, and Pseudomonas aeruginosa and Staphylococcus aureus are the most common pathogens,” Dr. Saiman said. “When you sample the respiratory tract, you are looking for the organism(s) that are causing pulmonary exacerbations. If the patient becomes symptomatic, those are the organisms that you treat.”
Less common bacteria that are detected in people with CF include Haemophilus influenzae, Burkholderia cepacia complex, Stenotrophomonas maltophilia, Inquilinus, Achromobacter, Ralstonia and Pandoraea. The last guidance was published in 2006, but many advances have been made since then, including the FDA’s approval of the first CFTR modulator in 2012. In addition, an increased understanding of CF’s microbiology has increased, as well as advances in processing respiratory tract samples for detection and identification of potential pathogens.
“Traditional microbiology was really developed to identify one pathogen and manage it accordingly,” said Jonathan Schmitz, PhD, MD, an assistant professor of pathology, microbiology and immunology at the Vanderbilt Institute for Infection, Immunology, and Inflammation, in Nashville, Tenn. “What we’re realizing now is that there is a community of organisms where their interaction with each other, the environment and the host ultimately determines health, disease and cystic fibrosis symptoms.”
To develop the guideline, the Cystic Fibrosis Foundation (CFF) assembled a multidisciplinary team of experts across North America, Europe and Australia. In addition to reviewing the available literature, the co-authors modified an annual survey in 2,021 of 287 CFF accredited care centers in the United States to assess current methods used by their clinical microbiology laboratories. The questions included: “Do you record whether the sample is sputum, oropharyngeal swab or a bronchoalveolar lavage?” and “Does your laboratory contact the clinical team for new detection of CF pathogens?”
The guidance makes 14 overarching key recommendations for processing respiratory samples. Specifically, it states that antimicrobial susceptibility testing is not recommended for every routine culture but can be helpful in selected circumstances. Indications for susceptibility testing should be developed by the clinical microbiology laboratory and care teams. Furthermore, it recommends that identification of bacteria from CF samples to the genus level by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is excellent, but the databases do not include all species known to infect individuals with CF. Clinical microbiology laboratories using this technology should communicate these limitations to the care teams.
The guidance also notes that homogenizing sputum, or phlegm, to enhance uniform sampling may improve the recovery of microorganisms present in low concentrations. This is routinely performed in many laboratories, but there is not enough evidence for a consensus recommendation in this area. On the flip side, it recommends against routinely performing Gram stain smears because they do not yield clinically relevant information. Dr. Schmitz said there has been “a great deal of suspicion on the lack of utility of doing routine quality screens based upon Gram stain of these specimens.
“It is not anecdotal anymore. Dedicated studies have been done, and it is codified here, but the fact it is reinforcing what a lot of clinicians have suspected for a long time is very nice to see,” said Dr. Schmitz, who is also a member of the Infectious Disease Special Edition editorial advisory board.
The guidance also notes most testing is conducted in laboratories in CFF-accredited centers that specialize in CF, but increasingly more respiratory samples are being processed in commercial labs. In addition, the growth of telemedicine and at-home collection of respiratory samples, compounded by the COVID-19 pandemic, have reduced collection of samples from people with CF.
“At Columbia, I can just walk over to my clinical microbiology lab where I know everybody by first name and have their email addresses and cellphone numbers. When samples are sent to a commercial laboratory, the care teams do not have that same relationship,” Dr. Saiman said.
Dr. Saiman and colleagues wrote the guidance to reflect current care paradigms for people with CF and acknowledge that recommendations will evolve as research expands the evidence base for laboratory practices.
Dr. Saiman receives grant funding from and is a consultant to the CFF. Dr. Schmitz reported no relevant financial disclosures.
This article is from the October 2024 print issue.