Potential pathogenicity of Inquilinus limosus in a pediatric patient with cystic fibrosis.

PRESENTATION: Patient is a 6-year-old male with CF, MRSA colonization, and pancreatic insufficiency that presented with worsening ppFEV1 and systemic symptoms despite multiple interventions. BAL grew NTM, Stenotrophomonas maltophilia, and Inquilinus limosus, a rare organism found in patients with CF. COURSE: I. limosus treatment was deferred. Despite treatment of other pathogens, symptoms worsened. I. limosus was targeted with meropenem, amikacin, and ciprofloxacin along with clindamycin for MRSA colonization. Within weeks, symptoms had resolved with ppFEV1 improvement. DISCUSSION: This case discusses the importance of a rare organism in the CF population. Targeting I. limosus was key to recovery, revealing its potential pathogenicity.

allergic bronchopulmonary aspergillosis

bronchoalveolar lavage

cystic fibrosis

mycobacterium intracellulare

methicillin resistant Staphylococcus aureus

nontuberculous mycobacterium

Pseudomonas aeruginosa

percent predicted forced expiratory volume in one second

Right middle lobe

INTRODUCTION

Inquilinus limosus is an aerobic Gram‐negative rod that has been predominately cultured from patients with cystic fibrosis (CF). It is thought to be a soil bacterium, but little is known about its habitat, reservoir, and transmission.1, 2, 3, 4, 5 This organism is often mis‐identified as Pseudomonas aeruginosa (PA) and is difficult to treat given extensive resistance patterns.

I. limosus’ pathogenicity is poorly understood. Multiple reports identified the organism by culture and 16S rDNA sequencing, yet its relevance remains uncertain given reports ranging from deterioration associated with isolation, to no clinical impact. Here, we describe a pediatric patient with isolation of abundant I. limosus in concert with non‐tuberculous mycobacterium (NTM) and more common pathogens. The patient's symptoms were severe and progressive, only resolving with a treatment regimen optimized against I. limosus.

CASE

The patient is a 6‐year‐old male with CF (N1303 K/2490 + G > A) and pancreatic insufficiency that presented with chest pain and fever. The patient is chronically colonized with methicillin‐resistant Staphylococcus aureus (MRSA), had successfully completed eradication therapy for PA isolated 4 months prior, and grown Haemophilus species, yeast, Exophilala dermatitidis, and Stenotrophomonas maltophilia the year prior to presentation. He initially visited an outside emergency department where he was diagnosed with pneumonia and given intramuscular ceftriaxone followed by oral cephalosporin. Follow up with his pulmonologist prompted a change to trimethroprim‐sulfamethoxazole (TMP‐SMX) given his history of MRSA colonization.

The patient did not improve, presenting 2 days later with fever, cough, chest pain, and a right middle lobe (RML) infiltrate on chest x‐ray. His percent predicted forced expiratory volume in one second (ppFEV1) declined from baseline of 87% to 65%, prompting admission. Bronchoscopy/bronchoalveolar lavage (BAL) was performed. Rare non‐tuberculous mycobacteria (NTM) was isolated for the first time, along with S. maltophilia, and a new gram‐negative rod that was sent to the CDC for identification. This was ultimately identified as I. limosus and was not treated, as its symptomatic role was unclear. The patient's antibiotic regimen was changed to piperacillin‐tazobactam, ceftaroline, and voriconazole to better cover chronic colonization of MRSA and previous pathogens. He was treated for 14 days with a ppFEV1 improvement to 90%, but continued to have symptoms above his baseline.

Two weeks later, the patient had some improvement; however, his fatigue, cough, and weight loss persisted while his ppFEV1 decreased to 83%. There was concern that the treatment for his previous Aspergillus was inadequate, so voriconazole was resumed and he was to return to clinic 2 weeks later.

The patient returned with ongoing fatigue, chest pain, shortness of breath, and decline in his ppFEV1 to 64%, prompting readmission. A chest x‐ray demonstrated a new density in the right lung base with right hilar peribronchial thickening, prompting a chest CT that showed nodular, peripheral consolidations in the lower lobes, and consolidation in the RML. Bronchoscopy was performed, showing rare NTM, abundant I. limosus identified by the state lab, and coronavirus. Due to the presumption that worsening symptoms were primarily due to coronavirus, he was not treated with antibiotics and discharged home. Allergic bronchopulmonary aspergillosis (ABPA) was considered throughout this time, however, his reassuring IgE, eosinophil count, and nonspecific CT scan made diagnosis unlikely.

The patient's fever, headaches, fatigue, and poor appetite continued. One week after discharge, he was started on levofloxacin and inhaled gentamicin to address ongoing symptoms. Within days, symptoms progressed to night sweats, exercise intolerance, increased sputum production, and chest pain, prompting readmission with a ppFEV1 of 66%. In attempts to initiate more aggressive treatment, he was started empirically on moxifloxacin, amikacin, and azithromycin, based on published I. limosus and NTM antibiotic regimens. He continued to worsen with continued night sweats and a decline in ppFEV1 to 60%. Meropenem was added for additional coverage on recommendation by an Infectious Disease consultant. Given that I. limosus had grown in abundance on multiple occasions and NTM growth was rare, it became the focus of treatment and an optimal antibiotic regimen was designed based upon reported literature and identified antimicrobial susceptibilities.1, 6

The patient was placed on meropenem, amikacin, and ciprofloxacin for I. limosus and clindamycin given history of MRSA colonization. After 5 days of this regimen, the patient had a ppFEV1 of 68% and symptomatic improvement. The patient was discharged home on IV amikacin and meropenem, oral ciprofloxacin for I. limosus treatment to complete a total of 4 weeks, and clindamycin for total of 2 weeks. After this course, the patient's fevers, night sweats, and chest pain resolved, and his ppFEV1 rose to 81%. By this time, both cultures of NTM had been identified as Mycobacterium intracellulare (MAC). The patient was subsequently started on azithromycin, ethambutol, and rifampin given patient's course and NTM outcomes at our center. Subsequent spirometry revealed stable ppFEV1 over 80% without isolation of I. limosus or NTM from subsequent throat swabs or sputum.

DISCUSSION

This case demonstrates the challenges of treating CF patients with multifactorial bacterial infections and the potential pathogenicity of I. limosus. This patient had chronic isolation of MRSA from his upper airway and previously had mild exacerbations responding to MRSA treatment, yet did not improve with initial treatment of his usual CF pathogens. The patient repeatedly isolated large amounts of I. limosus from BAL and did not have significant improvement until aggressive treatment targeting this organism was initiated (Figure 1). While his illness began prior to isolation, it is possible I. limosus was contributing earlier given difficulty with identification and published evidence of immune response to Inquilinus prior to culture growth.4 We cannot fully rule out the influence of MRSA or MAC on this patient's course. Notably, he never isolated MRSA from his lower airway during this period and had no first‐line treatment directed toward MAC until after improvement from a prolonged course targeting I. limosus.

Figure 1

Timeline of patient's clinical course over a 6 month period surrounding I. limosus isolation. Box values are ppFEV1. Circled values on timeline are months from index presentation

This case of a young CF patient with multiple sources of infection demonstrates the complexity of CF exacerbations and supports the notion that I. limosus is an emerging pathogen. The patient's clinical course demonstrated the need for antibiotic coverage of I. limosus and reinforces its potential pathogenicity when developing treatment plans.

CONFLICTS OF INTEREST

All authors declare no conflicts of interest.