Prospective evaluation of nontuberculous mycobacteria disease in cystic fibrosis: The design of the PREDICT study.

BACKGROUND: Nontuberculous mycobacteria (NTM) are an important cause of airway infections in people with cystic fibrosis (pwCF). Isolation of NTM from respiratory specimens of pwCF do not mandate treatment in the absence of clinical and radiologic features of NTM pulmonary disease (NTM-PD), as some pwCF clear the infection without treatment and others do not appear to progress to NTM-PD despite persistent infection. An evidence-based protocol to standardize diagnosis of NTM-PD is needed to systematically identify pwCF who may benefit from treatment. METHODS: In this multicenter observational study, eligible pwCF who are 6 years of age and older and who have had a recent positive NTM culture are systematically evaluated for NTM-PD. Participants are identified based on positive NTM culture results obtained during routine clinical care and following enrollment are evaluated for NTM-PD and CF-related comorbidities. Participants are followed in PREDICT until they meet NTM-PD diagnostic criteria and are ready to initiate NTM treatment, or until study termination. Active participants who have not met these criteria are re-consented every 5 years to enable long-term participation. RESULTS: The primary endpoint will summarize the proportion of participants who meet the NTM-PD diagnosis definition. The time from enrollment to NTM-PD diagnosis will be derived from Kaplan-Meier estimates. CONCLUSION: A prospective protocol to identify NTM-PD in pwCF will test if this standardized approach defines a cohort with signs and symptoms associated with NTM-PD, to assist with clinical decision making and to build a framework for future therapeutic trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02073409.

Late Diagnosis in the Era of Universal Newborn Screening Negatively Affects Short- and Long-Term Growth and Health Outcomes in Infants with Cystic Fibrosis.

Newborn screening for cystic fibrosis was fully implemented in the US by 2010, but delays in timeliness of evaluation for infants with positive newborn screening tests persist. Through evaluation of national patient registry data, we determined that late initiation of cystic fibrosis care is associated with poorer long-term nutritional outcomes.

Deficient Complement Opsonization Impairs Mycobacterium avium Killing by Neutrophils in Cystic Fibrosis.

Nontuberculous mycobacteria (NTM), including Mycobacterium avium, are clinically important pathogens in cystic fibrosis (CF). The innate immune response to M. avium remains incompletely understood. We evaluated the role of complement opsonization in neutrophil-mediated killing of M. avium. Killing assays were performed using neutrophils from healthy donors (HDs) and persons with CF (pwCF). Clinical isolates of M. avium were opsonized with plasma from HDs or pwCF, which was intact or heat-treated to inactivate complement. HD neutrophils had killing activity against M. avium opsonized with intact HD plasma and killing was significantly reduced when M. avium was opsonized with heat-inactivated HD plasma. When opsonized with HD plasma, CF neutrophils had killing activity against M. avium that was not different than HD neutrophils. When opsonized with intact plasma from pwCF, HD neutrophil killing of M. avium was significantly reduced. Opsonization of M. avium with C3-depleted serum or IgM-depleted plasma resulted in significantly reduced killing. Plasma C3 levels were elevated in pwCF with NTM infection compared to pwCF without NTM infection. These studies demonstrate that human neutrophils efficiently kill M. avium when opsonized in the presence of plasma factors from HD that include C3 and IgM. Killing efficiency is significantly lower when the bacteria are opsonized with plasma from pwCF. This indicates a novel role for opsonization in neutrophil killing of M. avium and a deficiency in complement opsonization as a mechanism of impaired M. avium killing in CF. IMPORTANCE Mycobacterium avium is a member of a group of bacterial species termed nontuberculous mycobacteria (NTM) that cause lung disease in certain populations, including persons with cystic fibrosis (CF). NTM infections are challenging to diagnose and can be even more difficult to treat. This study investigated how the immune system responds to M. avium infection in CF. We found that neutrophils, the most abundant immune cell in the lungs in CF, can effectively kill M. avium in individuals both with and without CF. Another component of the immune response called the complement system is also required for this process. Levels of complement proteins are altered in persons with CF who have a history of NTM compared to those without a history of NTM infection. These results add to our understanding of how the immune system responds to M. avium, which can help pave the way toward better diagnostic and treatment strategies.

Culture independent markers of nontuberculous mycobacterial (NTM) lung infection and disease in the cystic fibrosis airway.

Nontuberculous mycobacteria (NTM) are opportunistic pathogens that affect a relatively small but significant portion of the people with cystic fibrosis (CF), and may cause increased morbidity and mortality in this population. Cultures from the airway are the only test currently in clinical use for detecting NTM. Culture techniques used in clinical laboratories are insensitive and poorly suited for population screening or to follow progression of disease or treatment response. The lack of sensitive and quantitative markers of NTM in the airway impedes patient care and clinical trial design, and has limited our understanding of patterns of acquisition, latency and pathogenesis of disease. Culture-independent markers of NTM infection have the potential to overcome many of the limitations of standard NTM cultures, especially the very slow growth, inability to quantitate bacterial burden, and low sensitivity due to required decontamination procedures. A range of markers have been identified in sputum, saliva, breath, blood, urine, as well as radiographic studies. Proposed markers to detect presence of NTM or transition to NTM disease include bacterial cell wall products and DNA, as well as markers of host immune response such as immunoglobulins and the gene expression of circulating leukocytes. In all cases the sensitivity of culture-independent markers is greater than standard cultures; however, most do not discriminate between various NTM species. Thus, each marker may be best suited for a specific clinical application, or combined with other markers and traditional cultures to improve diagnosis and monitoring of treatment response.

Disparities in first evaluation of infants with cystic fibrosis since implementation of newborn screening.

OBJECTIVE: We evaluated whether implementation of cystic fibrosis (CF) newborn screening (NBS) leads to equitable timeliness of initial evaluation. We compared age at first event (AFE, age at sweat test, encounter and/or care episode) between infants categorized as Black/African American, American Indian/ Native Alaskan, Asian, and/or Hispanic and/or other (Group 1) to White and not Hispanic infants (Group 2). METHODS: This retrospective cohort study from the Cystic Fibrosis Foundation Patient Registry (CFFPR) included infants born 2010-2018. Race and ethnicity categories followed US Census definitions. The primary outcome was AFE; the secondary outcome was weight for age (WFA) z-score averaged 12 to < 24 months. We compared distributions by Wilcoxon rank-sum test and proportions by Chi-square or Fisher's exact tests. A nested cohort study used a linear mixed effects model of variables that affect WFA, chosen a priori, to evaluate associations with 1-year WFA z-score. RESULTS: Among 6354 infants, 21% were in Group 1. Group 1 median AFE was 31 days (IQR 19, 49) and Group 2 was 22 days (IQR 14,36) (p< .001). Median WFA z-score at 1-2 years was lower in Group 1. In 3017 infants with complete data on variables of interest, AFE, Black race, CFTR variant class I-III, prematurity and public insurance were associated with lower 1-year WFA z-score. CONCLUSIONS: Differences in AFE for infants with CF from historically marginalized groups may exacerbate long standing health disparities. We speculate that inequitable identification of CFTR gene variants and/or bias may influence timeliness of evaluation after an out-of-range NBS.

Nontuberculous Mycobacterial Infections in Cystic Fibrosis.

Nontuberculous mycobacteria (NTM) are important pathogens, with a longitudinal prevalence of up to 20% within the cystic fibrosis (CF) population. Diagnosis of NTM pulmonary disease in people with CF (pwCF) is challenging, as a majority have NTM infection that is transient or indolent, without evidence of clinical consequence. In addition, the radiographic and clinical manifestations of chronic coinfections with typical CF pathogens can overlap those of NTM, making diagnosis difficult. Comprehensive care of pwCF must be optimized to assess the true clinical impact of NTM and to improve response to treatment. Treatment requires prolonged, multidrug therapy that varies depending on NTM species, resistance pattern, and extent of disease. With a widespread use of highly effective modulator therapy (HEMT), clinical signs and symptoms of NTM disease may be less apparent, and sensitivity of sputum cultures further reduced. The development of a disease-specific approach to the diagnosis and treatment of NTM infection in pwCF is a research priority, as a lifelong strategy is needed for this high-risk population.

Newborn Screening for Cystic Fibrosis: A Qualitative Study of Successes and Challenges from Universal Screening in the United States.

Cystic fibrosis (CF) newborn screening (NBS) was universally adopted in 2009 in the United States. Variations in NBS practices between states may impact the timing of diagnosis and intervention. Quantitative metrics can provide insight into NBS programs (NBSP), but the nuances cannot be elucidated without additional feedback from programs. This study was designed to determine facilitators and barriers to timely diagnosis and intervention following NBS for CF. The median age at the first CF event for infants with CF within each state was used to define early and late states (n = 15 per group); multiple CF centers were invited in states with more than two CF centers. Thirty states were eligible, and 61 NBSP and CF centers were invited to participate in structured interviews to determine facilitators and barriers. Once saturation of themes was reached, no other interviews were conducted. Forty-five interviews were conducted (n = 16 early CF center, n = 12 late CF center, n = 11 early NBSP, and n = 6 late NBSP). Most interviewees reported good communication between CF centers and NBSP. Communication between primary care providers (PCPs) and families was identified as a challenge, leading to delays in referral and subsequent diagnosis. The misperception of low clinical risk in infants from racial and ethnic minority groups was a barrier to early diagnostic evaluation for all groups. NBSP and CF centers have strong relationships. Early diagnosis may be facilitated through more engagement with PCPs. Quality improvement initiatives should focus on continuing strong partnerships between CF centers and NBS programs, improving education, communication strategies, and partnerships with PCPs, and improving CF NBS timeliness and accuracy.

Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection.

Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject's bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments. M. abscessus isolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics. The anti-phage neutralizing antibody titers to one phage increased with time but did not prevent clinical improvement throughout the course of treatment. The subject received lung transplantation on day 379, and systematic culturing of the explanted lung did not detect M. abscessus. This study describes the course and associated markers of a successful phage treatment of M. abscessus in advanced lung disease.

Clinical characteristics of people with cystic fibrosis and frequent fungal infection.

BACKGROUND: Individuals with cystic fibrosis (CF) and fungal airway infection may present with fungal bronchitis, allergic bronchopulmonary aspergillosis (ABPA) or may appear unaffected despite fungal detection. We sought to characterize people with CF with frequent detection of fungi from airway samples and determine clinical outcomes. METHODS: This retrospective study included individuals with CF with ≥4 lower airway cultures over a 2-year baseline period and ≥2 years of follow-up. We defined two groups: ≤1 positive fungus culture (rare) or ≥2 positive cultures during baseline (frequent). Clinical characteristics and outcomes were determined. RESULTS: Between 2004 and 2016, 294 individuals met inclusion with 62% classified as rare and 38% as frequent fungi during baseline. Median follow-up was 6 years (range: 2-9 years). Aspergillus fumigatus was the most common fungal species detected. Individuals with frequent fungi were older (13.7 vs. 11.7 years, p = .02) and more likely to have Stenotrophomonas maltophilia (35% vs. 17%, p < .001) at baseline, but did not differ in lung function or ABPA diagnosis. During follow-up, those with frequent fungi were more likely to have chronic Pseudomonas aeruginosa and S. maltophilia. Individuals with ABPA and frequent fungi had the highest rates of co-infection and co-morbidities, and a trend towards more rapid lung function decline. DISCUSSION: Fungal infection in CF was associated with frequent P. aeruginosa and S. maltophilia co-infection even in those without ABPA. Individuals with frequent fungi and ABPA had worse outcomes, highlighting the potential contribution of fungi to CF pulmonary disease.

ATS Core Curriculum 2021. Pediatric Pulmonary Medicine: Pulmonary Infections.

The following is a concise review of the Pediatric Pulmonary Medicine Core reviewing pediatric pulmonary infections, diagnostic assays, and imaging techniques presented at the 2021 American Thoracic Society Core Curriculum. Molecular methods have revolutionized microbiology. We highlight the need to collect appropriate samples for detection of specific pathogens or for panels and understand the limitations of the assays. Considerable progress has been made in imaging modalities for detecting pediatric pulmonary infections. Specifically, lung ultrasound and lung magnetic resonance imaging are promising radiation-free diagnostic tools, with results comparable with their radiation-exposing counterparts, for the evaluation and management of pulmonary infections. Clinicians caring for children with pulmonary disease should ensure that patients at risk for nontuberculous mycobacteria disease are identified and receive appropriate nontuberculous mycobacteria screening, monitoring, and treatment. Children with coronavirus disease (COVID-19) typically present with mild symptoms, but some may develop severe disease. Treatment is mainly supportive care, and most patients make a full recovery. Anticipatory guidance and appropriate counseling from pediatricians on social distancing and diagnostic testing remain vital to curbing the pandemic. The pediatric immunocompromised patient is at risk for invasive and opportunistic pulmonary infections. Prompt recognition of predisposing risk factors, combined with knowledge of clinical characteristics of microbial pathogens, can assist in the diagnosis and treatment of specific bacterial, viral, or fungal diseases.

Population Genomics and Inference of Mycobacterium avium Complex Clusters in Cystic Fibrosis Care Centers, United States.

Mycobacterium avium complex (MAC) species constitute most mycobacteria infections in persons with cystic fibrosis (CF) in the United States, but little is known about their genomic diversity or transmission. During 2016-2020, we performed whole-genome sequencing on 364 MAC isolates from 186 persons with CF from 42 cystic fibrosis care centers (CFCCs) across 23 states. We compared isolate genomes to identify instances of shared strains between persons with CF. Among persons with multiple isolates sequenced, 15/56 (27%) had >1 MAC strain type. Genomic comparisons revealed 18 clusters of highly similar isolates; 8 of these clusters had patients who shared CFCCs, which included 27/186 (15%) persons with CF. We provide genomic evidence of highly similar MAC strains shared among patients at the same CFCCs. Polyclonal infections and high genetic similarity between MAC isolates are consistent with multiple modes of acquisition for persons with CF to acquire MAC infections.

Improving outcomes for Colorado's IRT-IRT-DNA cystic fibrosis newborn screening algorithm by implementing floating cutoffs.

The Colorado Newborn Screening Program (CO-NBS) screens for cystic fibrosis (CF) by measuring immunoreactive trypsinogen (IRT) from two screens coupled with DNA analysis (IRT/IRT/DNA). The Colorado CF Care Center identified 8 missed CF cases among 358,187 infants screened by the CO-NSP since 2016. Retrospective analysis of CO-NSP IRT data shows that a 96th percentile floating IRT cutoff with a 50 ng/mL fixed cutoff on the first screen, and second screen 50 ng/mL fixed cutoff would have identified 7 of the 8 missed cases. These efforts demonstrate the importance of continuous quality improvement in order to increase sensitivity and reduce missed cases.

Outcomes of infants born during the first 9 years of CF newborn screening in the United States: A retrospective Cystic Fibrosis Foundation Patient Registry cohort study.

INTRODUCTION: Newborn screening (NBS) for cystic fibrosis (CF) was implemented in all US states and DC by 2010. This hypothesis-generating study was designed to form the basis of additional analyses and to plan quality improvement initiatives. The aims were to describe the outcomes of infants with CF born during the first 9 years of universal NBS. METHODS: We included participants in the CF Foundation Patient Registry born 2010-2018 with age of recorded CF diagnosis 0-365 days old. We compared the age of center-reported diagnosis, age at first CF event (defined as earliest sweat test, clinic visit, or hospitalization), demographics, and outcomes between three cohorts born between 2010-2012, 2013-2015, and 2016-2018. RESULTS: In 6354 infants, the median age at first CF event decreased from the first to the third cohort. Weight-for-age (WFA) was < 10th percentile in about 40% of infants at the first CF Center visit. Median WFA z-score at 1-2 years was more than 0 but height-for-age (HFA) z-score was less than 0 through age 5-6 years. The second cohort had a higher HFA z-score than the first cohort at age 5-6 years. Pseudomonas aeruginosa infection was less common in later cohorts. About 1/3 of infants were hospitalized in the first year of life with no changes over time. CONCLUSION: Over 9 years of CF NBS, median age at first CF event decreased. CF NBS had positive health impacts, but early life nutritional deficits and a high rate of infant hospitalizations persist.

Safety and effectiveness of a risk-stratified venous thromboembolism prophylaxis algorithm in young people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis (CF) have an increased risk of thrombosis due to acquired thrombophilia secondary to chronic systemic inflammation and central venous catheter use for treatment of pulmonary infections. The objective of this study is to determine the safety and effectiveness of a risk-stratified, venous thromboembolism (VTE) prophylaxis intervention. METHODS: This single-center, IRB-approved, retrospective study assessed patients with CF admitted to our institution for treatment of a pulmonary exacerbation from 2017 to 2019. Data and outcomes were manually extracted from the electronic medical record and internal CF clinical database. Subject characteristics, calculated VTE risk, prophylaxis interventions prescribed, VTE incidence, and adverse events were captured. RESULTS: A total of 135 CF patients had 354 admissions for pulmonary exacerbations in the time frame of the study. The majority of admissions (88.7%) were classified as moderate or high risk for VTE using the algorithm. Overall, VTE prophylaxis intervention determined by the algorithm was initiated in 36.2% of admissions. During the study period, no VTE events occurred. Four minor bleeding adverse effects were reported in patients receiving VTE chemical prophylaxis with enoxaparin (4.2%). CONCLUSIONS: This study provides the first reported outcomes following implementation of a risk-stratified VTE prophylaxis algorithm in hospitalized young people with CF. In this population at increased risk, use of risk-stratified prophylaxis was safe and effective in preventing VTE. Additional work to improve and maintain adherence to the algorithm and VTE prophylaxis interventions at our institution is planned and similar care should be considered at other pediatric CF care centers.

Pharmacokinetics of oral antimycobacterials and dosing guidance for Mycobacterium avium complex treatment in cystic fibrosis.

BACKGROUND: Treatment failure of Mycobacterium avium complex (MAC) pulmonary disease occurs in about 30% of people with cystic fibrosis (CF) and may be a result of abnormal drug concentrations. METHODS: Prospective, cross-over, single-dose PK study of 20 pancreatic insufficient individuals with CF and 10 healthy controls (HC). CF subjects received simultaneous doses of oral azithromycin, ethambutol, and rifampin in the fasting state and with food and pancreatic enzymes, separated by two weeks. HC received fasting doses only. A non-compartmental model was used to estimate PK parameters of drugs and metabolites. RESULTS: Azithromycin maximum concentration (Cmax ) was higher and rifampin Cmax was lower in fasting CF subjects compared to HC, while other PK measures, including those for ethambutol, were similar. Addition of food and enzymes did not improve the Cmax of the antimycobacterial drugs. Nineteen of 20 CF subjects had one or more abnormal Cmax z-scores in either the fasting or fed state (or both), when compared to HC. CONCLUSION: PK profiles of azithromycin and ethambutol were similar between CF and HC, except azithromycin Cmax was slightly higher in people with CF after a single dose. Rifampin PK parameters were altered in persons with CF. Addition of food and enzymes in CF subjects did not improve PK parameters. Standard dosing guidelines should be used as a starting point for people with CF initiating MAC therapy and therapeutic drug monitoring should be routinely performed to prevent the possibility of treatment failure due to abnormal drug concentrations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02372383 Prior abstract publication: 1. Martiniano S, Wagner B, Brennan L, Wempe M, Anderson P, Nick J, Sagel S. Pharmacokinetics of oral MAC antibiotics in cystic fibrosis. Am J Resp Crit Care Med A4842-A4842, 2017. 2. Martiniano SL, Wagner BD, Brennan L, Wempe MF, Anderson PL, Nick JA, Sagel SD. Pharmacokinetics of oral MAC antibiotics in cystic fibrosis. J Cyst Fibros 16: S52-53, 2017.

Population Genomics of Mycobacterium abscessus from U.S. Cystic Fibrosis Care Centers.

Rationale:Mycobacterium abscessus is a significant threat to individuals with cystic fibrosis (CF) because of innate drug resistance and potential transmission between patients. Recent studies described global dominant circulating clones of M. abscessus, but detailed genomic surveys have not yet been described for the United States. Objectives: We examined the genetic diversity of respiratory M. abscessus isolates from U.S. patients with CF and evaluated the potential for transmission events within CF Care Centers. Methods: Whole-genome sequencing was performed on 558 M. abscessus isolates from 266 patients with CF attending 48 CF Care Centers in 28 U.S. states as part of a nationwide surveillance program. U.S. isolates were also compared with 64 isolate genomes from 13 previous studies to evaluate the prevalence of recently described dominant circulating clones. Results: More than half of study patients with CF and M. abscessus had isolates within four dominant clones; two clones of M. abscessus subspecies (subsp.) abscessus (MAB) and two clones of M. abscessus subsp. massiliense (MMAS). Acquired drug resistance mutations for aminoglycosides and macrolides were rare in the isolate population, and they were not significantly enriched in dominant clones compared with unclustered isolates. For a subset of 55 patients, there was no relationship between dominant clones and diagnosis of active lung disease (P = 1.0). Twenty-nine clusters of genetically similar MAB isolates and eight clusters of genetically similar MMAS isolates were identified. Overall, 28 of 204 (14%) patients with MAB and 15 of 64 (23%) patients with MMAS had genetically isolates similar to those of at least one other patient at the same CF Care Center. Genetically similar isolates were also found between 60 of 204 (29%) patients with MAB and 19 of 64 (30%) patients with MMAS from different geographic locations. Conclusions: Our study reveals the predominant genotypes of M. abscessus and frequency of shared strains between patients in U.S. CF Care Centers. Integrated epidemiological and environmental studies would help to explain the widespread presence of dominant clones in the United States, including the potential for broad distribution in the environment. Single site studies using systematic, evidence-based approaches will be needed to establish the contributions of health care-associated transmission versus shared environmental exposures.

Detection of bacterial pathogens using home oropharyngeal swab collection in children with cystic fibrosis.

BACKGROUND: Collection of respiratory cultures for airway microbiology surveillance is an essential component of routine clinical care in cystic fibrosis (CF). The COVID-19 global pandemic has necessitated increased use of telehealth, but one limitation of telehealth is the inability to collect respiratory specimens. We initiated a protocol for at-home collection of oropharyngeal (OP) swabs from children with CF. METHODS: Home respiratory specimen collection was offered during telehealth encounters. Home OP swab kits were sent to participating families via mail with instructions for collection and return. Specimens were returned by overnight shipping or dropped off at a hospital lab for processing and culture. We evaluated demographic data and compared culture results from the home-collected specimen to the most recent specimen collected in clinic. We also tracked the frequency of newly identified Pseudomonas aeruginosa. RESULTS: Home OP swab kits were sent to families of 33 children with CF (range 1.5-19 years). OP swab kits were successfully returned from 19 children (range 1.5-19 years). One or more CF pathogens grew from 79% of the specimens. For four individuals, the home collected specimen demonstrated the new growth of P. aeruginosa. CONCLUSIONS: Home collection of OP swabs for bacterial culture is feasible in children with CF across a range of ages. Most home-collected specimens demonstrated growth of one or more CF pathogens and results were similar to recent in-clinic specimens, suggesting acceptable sample collection technique. Anti-pseudomonal therapy was initiated for four children based on the growth of P. aeruginosa from the home respiratory specimen.

Clinical characteristics and outcomes associated with Inquilinus infection in cystic fibrosis.

BACKGROUND: Molecular diagnostics have led to the identification of a broad range of bacterial species in cystic fibrosis (CF) including Inquilinus. The clinical significance of Inquilinus in CF has not been thoroughly characterized. METHODS: Retrospective, case-control study of persons with CF from two CF centers with at least one respiratory culture positive for Inquilinus spp. compared with age-matched CF controls with chronic Pseudomonas aeruginosa. Percent predicted forced expiratory volume in one second (ppFEV1) and body mass index percentile (BMI) were modeled from time of first positive culture up to 5 years later. Rates of pulmonary exacerbations were compared. Inquilinus isolates were genotyped to evaluate strain diversity. RESULTS: Seventeen patients with Inquilinus infection were identified with a mean age of 13 years at first positive culture. Most cases had multiple cultures positive for Inquilinus. ppFEV1 was not different between cases versus controls (80.2% vs 81.6%, p = 0.97 at baseline, 67.5% vs. 73.3%, p = 0.82 at 5 years). Patients were undernourished and BMI percentiles did not differ between groups (30.7% vs 43.4%, p = 0.32 at baseline, 37.9% vs. 37.6%, p = 0.98 at 5 years). There was no difference in the pulmonary exacerbation rate (3.0/year vs 2.5/year, p = 0.34). Genotyping showed diverse genetic strains between patients. CONCLUSIONS: Inquilinus can present in childhood and is often associated with chronic infection in CF. Lung function and nutrition status at time of detection, lung function decline, and pulmonary exacerbation rates in Inquilinus cases were similar to those with chronic P. aeruginosa, a well-established CF pathogen.