Article Type : Case Report
Authors : Tanios JM, Ots B and Kumar P
Keywords : Escherichia coli; Cavitating lung lesion; Gram-negative cavitation; Thick-walled cavitating lesions
In July of 2020, a 79-year-old woman with a background of
bronchiectasis was referred to the Mackay Base Hospital respiratory department
for assessment of her productive cough that had progressively worsened over six
months. Radiological evaluation of the thorax revealed diffuse thick-walled
cavitating lesions bilaterally, greater than 4mm in size, and surrounded by
homogenous consolidation. Following extensive investigations with no conclusive
diagnosis, our patient underwent a bronchoscopy. Samples from the patient’s
bronchial wall and lingula were obtained via bronchoalveolar lavage and
revealed growth of gram-negative anaerobic Escherichia coli (E. coli) – a
facultative bacterium more commonly found manifesting the gastrointestinal and
urological tracts. In this article, we report a rare case of E. Coli colonising
the respiratory tract with diffuse thick-walled cavities despite antibiotic
therapy.
A wide variety of
diseases manifest as cavitating lung lesions, including pathological processes
unrelated to the respiratory system. The cause of cavitation can be classified
as infectious and non-infectious. Infectious pathogens include bacteria (ie. Klebsiella
pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae,
Staphylococcus aureus, Nocardia, and Burkholderia Pseudomallei);
tubercular and non-tubercular mycobacterium; endemic fungi (cryptococcus);
and parasites. Non-infectious processes include malignancy, vasculitis, and
rheumatological origins [1,2].
E. coli is a gram-negative bacillus that forms part of the normal commensal
intestinal flora. The strain that inherently inhabits the gastrointestinal
system lacks virulence here. Infection occurs when E.coli translocates
to extraintestinal locations via aspiration or hematogenous dissemination; or
when pathogenic strains (ie.ETEC and EHEC/STEC) are ingested; or through
environmental transmission in health-care settings [3]. Despite it being a major
cause of urinary, intestinal and perineal infections, E. coli rarely
colonises the respiratory tract and only a few cases have been previously
reported [4,5].
The patient was a 79-year-old female with a
background of bronchiectasis who had been seen previously in our respiratory
clinic for surveillance of a lung nodule in the right upper lobe. She was
discharged from the clinic in 2015 following two years of stable radiological
findings. In 2020 the patient was referred to the clinic again for increased
cough and sputum production over six months. She denied dyspnoea, haemoptysis,
chest pain, or constitutional symptoms. She was a former smoker with a
45-pack-year history and had no environmental or tuberculosis exposures. Her
medical history consisted of bronchiectasis of the right middle lobe and
chronic kidney disease secondary to hypertension. Of particular importance, her
general practitioner reported that she had a urinary tract infection in 2018
with physical signs of systemic involvement and a urine culture positive for E.
coli. Her medications included telmisartan, prolia injections, and panadol
osteo. Physical examination revealed a frail and underweight (39kg) woman who
was mildly tachypnoeic at 22 breaths per minute. She was talking in full
sentences with no accessory muscle use and maintaining oxygen saturations of
98% on room air. Auscultation of her heart and lungs was unremarkable.
Formal lung functions testing revealed an
obstructive picture (FEV1/FVC ratio of 63.31%) with evidence of small airway
disease (MFEF 39%), gas trapping (RV 132.9%), and impaired volume corrected gas
diffusion (KCO 72.6%) consistent with her background of bronchiectasis.
Chest imaging in April 2013 using high-resolution computed tomography (HRCT) revealed multiple centrilobular nodules with a spiculated lesion in the right upper lobe, along with bronchiectatic changes and tree in bud inflammation. The spiculated right upper lobe lesion was monitored over a 2-year period. In April 2013 (Figure 1) it measured 10 x 7mm and in October 2014 (Figure 2) the size remained unchanged. Consequently, our patient was discharged from the clinic. She was referred again in July 2020 due to worsening respiratory symptoms. Imaging of the thorax at that time revealed a cavitating lesion in the right upper lobe measuring 1.8 x 1.4cm (Figure 3). This was the previously solid nodule that had remained stable over two years of interval CT scanning.
Figure 1: HRCT chest axial (April 2013) showing original nodular density in right upper lobe inferiorly. Measuring 10 x 7mm.
Figure 2: HRCT chest axial (October 2014) showing RUL lesion measuring 10mm in maximal diameter. Stable interval changes for 2 years and patient discharged from clinic.
Figure 3: HRCT chest axial (July 2020) showing progression of RUL nodule to thick-walled cavitating lesion with margins of 18 x 14mm.
Figure 4: HRCT chest axial (February 2021) with further growth of lesion – 18 x 8.1mm – despite antibiotic therapy.
The patient was commenced on antimicrobial therapy
sensitive to E. Coli in December 2020. A repeat CT scan of the chest two
months later (February 2021) showed progressive growth of the lesion despite
antibiotic therapy – measuring 18 x 8.1mm (Figure 4). We reference the
cavitating lesion in the right upper lobe since it was the first lesion
detected on imaging in April 2013 as well as being the largest in size.
However, consistent imaging showed the emergence of multiple other cavitating
lesions scattered bilaterally, as shown in (Figures 5 and 6).
Bronchoalveolar washings (collected in November 2020) from the left main bronchi, left lower lobe, right middle lobe and right upper lobe all revealed growth of E. coli. The washings yielded cloudy mucoid fluid that was moderately blood-stained. All the E. coli isolates were resistant to ampicillin, gentamycin, and tobramycin, with sensitivity to amoxycillin/clavulanic acid, cefazolin, trimethoprim/sulfamethoxazole, and meropenem. Mycobacterial cultures, malignant cells, and viral respiratory panels returned negative. There was no evidence of bacteraemia in blood and her QuantiFERON-TB Gold was negative. A urine culture was not performed. Full blood count showed a leucocytosis with elevated neutrophils, eosinophils, and monocytes. Following consultation with the infectious disease specialist it was recommended that we also obtain serology for melioidosis and cryptococcal antigen, both of which returned negative.
Figure 5: HRCT chest axial (July 2020) showing an
additional bilobular lesion in the posterior segment of the right upper lobe
measuring 2.1 x 0.9cm.
Figure 6: HRCT chest axial (February 2021) shows multiple lesions scattered bilaterally with varying degrees of cavitation.
The patient was provided a script for amoxicillin
and clavulanic acid for two weeks, however only completed ten days in total.
She was reviewed in clinic two months after treatment. Follow-up HRCT displayed
progressive changes with evidence of additional cavitating lesions that had
increased in wall thickness. Enlarged mediastinal lymph nodes were also noted.
Repeat bronchoalveolar washings (collected in May 2021) yielded identical
results and the patient reported no improvement in her symptoms. A second trial
of amoxicillin and clavulanic acid was trialled to curb further growth of the
cavities and attempt to eradicate E. Coli from her lower respiratory
tract. This has proved unsuccessful to date and the next phase of treatment
step will involve admitting the patient to hospital and trialling a course of
intravenous antibiotics. It should be noted that the intensity of antibiotic
treatment in this patient was limited by her renal function, age, and low body
weight.
Schneer et al conducted a prospective cohort study
over seven years to measure the incidence of E. coli isolated from
respiratory secretions in 177 712 patients hospitalised or reviewed in
outpatient departments between 2009 and 2016. For every 10,000 secretions
screened, only 4.5 returned positive cultures for E. coli. The Tillotson
et al. study researching pneumonia and its causative organisms found that among
1882 subjects, E. Coli was responsible for a mere 0.7% of cases [4-7].
In the majority of patients returning positive cultures there was a
degree of immunosuppression or associated comorbidity including diabetes
mellitus, chronic alcoholism, malignancy, cirrhosis, or a chronic respiratory
disease [8,9]. These studies emphasise the infrequency of E. coli
as an aetiological factor in pulmonary infections.
E. coli
may localise to the respiratory tract via hematogenous dissemination from a
primary infection in the urogenital or intra-abdominal compartments, or via
aspiration of oropharyngeal secretions [10]. Our patient initially
suffered from a urinary tract infection confirmed with urine culture growing E.
Coli. It is suspected that E. Coli disseminated from the bladder and
deposited in the patient’s damaged lung tissue secondary to longstanding
bronchiectasis. The bladder has three main defence mechanisms including the
uroepithelium which acts as a physical barrier, Tamm-Horsfall proteins which
prevent bacterial colonization, and urine flow to promote continuous pathogen
clearance [11]. Haematogenous dissemination occurs when E. coli
adheres to receptors in the bladder epithelium, subsequently colonizing and
invading the mucosal surface. Upon invasion of the uroepithelium, E. coli releases
toxins and proteases enabling it to overcome host defences and cross the
tubular epithelial barrier, thus resulting in bacteraemia [12]. The degree of
bacteraemia depends on host factors such as the urine flow rate, immune status,
and ammonium concentration [13]. In our patient with bronchiectatic changes, it
is possible that E. Coli harboured the scarred lung tissue causing the
pulmonary cavities however further research into this pathophysiology is
required.
Radiologically, cavitating
lesions with a wall thickness greater than or equal to 4mm are classified as
thick-walled cavities. They may be focal, multifocal, or diffusely spread on
chest imaging [1]. Differentials considered in the work-up for this patient
included more common causes of lung cavitation such as fungal or atypical
mycobacterium fostered by underlying bronchiectasis, metastatic disease
secondary to a squamous carcinoma or lymphoma, pulmonary Koch’s, pulmonary
lymphangioleiomyomatosis, and pulmonary Langerhans cell histiocytosis [12]. This
patient’s diffuse cavitation pattern is similar to the presentation of
pulmonary Koch’s of mycobacterium tuberculosis. Additionally, the progression
from nodule to cavitation associated with centrilobular nodules in a ‘tree in
bud’ pattern is typical of non-tubercular mycobacteria (NTMB). As such, an atypical
mycobacterium was at the forefront of our differentials prior to the return of
negative acid-fast bacilli and QuantiFERON-TB results [1]. There
is inconclusive evidence as to whether E. coli has a pathogenic role in
causing damage to lung parenchyma or conversely, if E. coli has
propensity to inhabit diseased lung [8]. Nonetheless, we believe this patient’s
background of bronchiectasis was a significant contributing factor to E.
coli migrating to the susceptible lung parenchyma and causing diffuse cavitation
[13-15].
The solitary nodule in our patient’s right upper
lobe was stable over two years (2011-2013) as monitored radiologically. Five
years later (2018) she represented with evidence of numerous nodules which were
scattered bilaterally and with many showing some degree of thick-walled
cavitation. Urine cultures in 2018 returned positive for E. coli growth
and the patient was symptomatic with signs of bacteraemia, although this was
not confirmed through formal blood cultures. Therefore, we postulate that the
seeding of E. coli in the lungs was due to a long term undiagnosed
urinary tract infection since 2011 with E. Coli as the infecting
organism harbouring the bladder and undergoing hematogenous dissemination
causing bacteraemia [9].
It is hypothesised
that our patient’s history of bronchiectasis was a major influence for E.
Coli’s residence in the lower respiratory tract. Bronchiectasis is a
condition caused by ongoing airway inflammation as a result of infection,
autoimmune disease, drugs or a pathogenic insult [16].
Continuous inflammation results in scarring of smooth muscle and cartilage soft
tissue producing airways which are thickened and dilated [17]. For a diagnosis
of bronchiectasis, chest radiography is required with HRCT as the gold standard
imaging modality. The advantages of HRCT here is that it is a non-invasive
technique which can provide signs suggesting bronchiectasis such as a tree in
bud pattern as is the case in our patient. The tree in bud appearance is caused
from a build-up of mucous debris along with simultaneous gas trapping [18]. Cystic
bronchiectasis was a differential we excluded early due to no change in the
lesion’s air volume as interpreted across different CT slices [15]. We
concluded that our patient’s lesions were indeed cavitations which was a rare
situation [19]. We also considered pneumatoceles which are lesions also
developing post infection and appearing on chest imaging approximately 5-7 days
after the initial infection [20]. Interestingly, chronic pneumatocele formation
is typically associated with Buckley-Job Syndrome which is a condition
predisposing a patient to multiple pathogens such as E. Coli. However,
our patient’s lesions had a wall thickness greater than 4mm thus excluding
pneumatoceles. Furthermore, our research showed that the incidence of E.
Coli causing pneumatoceles is incredibly rare with only a single published
case on the phenomenon [21].
In
summary, this case describes an atypical cause of cavitating pulmonary nodules.
Although there are a multitude of diseases that present in this manner,
persistent infection with E. coli is an etiology rarely observed.
Therefore, despite the numerous cultures that returned positive for E. coli,
ambivalence around the true causative pathogen remains. As proposed by our
infectious disease consultant, it is possible that the robust growth of
gram-negative bacteria has prevented detection of other underlying pathogens.
Further research and case reports are required to understand the
pathophysiology of this chronic infection and its implications on pre-existing
pulmonary conditions.