Infection control knowledge, beliefs and behaviours amongst cystic fibrosis patients with epidemic Pseudomonas aeruginosa

The Adult Cystic Fibrosis Clinic at the Foothills Medical Center, established in 1978, follows and provides all primary and specialty CF care to those with CF residing in Southern Alberta, Canada. Upon enrolment in our clinic, all patients provide prospective consent for the collection, storage and study of sputum and sputum-derived organisms (CHREB E-23087). This established prospectively collected biobank includes all morphologically distinct bacterial isolates from each and every encounter dating back to 1978. Accordingly we have been able to identify infecting pathogens and perform genotyping on P. aeruginosa upon enrolment in the clinic and from the most recently available clinical samples [7].

Prior to 2010 the focus on infection control in the clinic merely involved vigorous adherence to hand and cough hygiene, as well as maintaining a 1 m “protective bubble” between patients. In 2010, these principles were expanded to include mandatory segregation of all patients to private exam rooms (including spirometry) with no possibility for co-mingling, an expansion of the “protective bubble” to 2 m in size, and contact isolation for individuals who had cultured any methicillin resistant Staphylococcus aureus (MRSA) in the prior 2 years. We perform bacterial strain typing by pulse-field gel electrophoresis (PFGE), supplemented with multi-locus sequence typing (MLST) and/or whole genome sequencing (WGS) for any suspected transmission of P. aeruginosa or other respiratory pathogens but have not observed any transmission events during five years of surveillance [15].

Chronic infection with P. aeruginosa was defined as per the Leeds criteria [16]. Infection with another airways pathogen was defined as at least one positive culture in the year prior to assessment, although patients on chronically suppressive M. abscessus therapy that no longer grew this organism were considered positive for the length of their treatment.

Bacterial strain typing was performed using pulsed-field gel electrophoresis following protocols established by our group [7]. For each time point all morphotypes of P. aeruginosa (defined as morphologically distinct populations on MacConkey agar) were assessed. For those patients who were recipients of life saving bilateral lung transplantation, we used sputum culture samples collected immediately prior to their transplant to define their airway infection status (as other groups have established concordance between pre- and post transplant infecting P. aeruginosa which continue to infect the sinuses and periodically the graft) [17]. Strains deemed potentially ePA were those that existed in greater than three individuals from different kindreds, or previously recognized ePA strains. In situations where PFGE determination was questioned, MLST/WGS was used to confirm results.

All patients attending the clinic were approached to complete a survey pertaining to infection control. In particular, past behaviours and risks for acquisition of infection were queried targeting childhood and early adulthood exposure as establishment of ePA infection have been demonstrated to have occurred earlier than age 20 within this cohort [7]. We sought to establish current knowledge and beliefs regarding infection control with respect to: individual pathogens; situations, and interventions in those with ePA relative to those with UNI (chronic stable unique P. aeruginosa) and ENT (the entire cohort who did not have ePA). This survey was completed using a 7-point Likert scale where the following values were used: 1. No risk, 2. Very low risk, 3. Low risk, 4. Neutral, 5. Mild risk, 6. Moderate risk, 7. Extreme risk [18, 19]. Finally, current behaviours and preferences were assessed using a 7-point Likert scale; 1. Strongly disagree, 2. Disagree, 3. Neutral, 4. Neither agree or disagree, 5. Somewhat agree, 6. Agree, 7. Strongly Agree. A complete reference to the survey is available in the appended supplemental material section. While patients were aware of their own lower airways pathogens in principle, they were not aware of whether their particular P. aeruginosa strains were ePA as typing occurred concurrent to the survey. Informed written consent was obtained from each participant. Ethical approval of this study was granted by the Conjoint Health Region Ethics Board (E-24123).

Statistical analysis was performed using Stata version 11.0 (Stata- Corp, TX, USA). Asymmetrically distributed variables were reported as medians with interquartile range (IQR) and compared using the Wilcoxon rank-sum test for pairs or the Kruskal-Wallis test for multiples. Differences in proportions among categorical data were assessed using Fisher’s exact test for pair-wise comparisons and the Chi-square test for multiple groups and reported as odds ratio (OR) with confidence intervals (CI). Significance was based on α < 0.05, and all hypothesis tests were 2-sided.

One hundred and forty-four of 169 active patients (85 %) within the clinic cohort participated in the study. Demographic and infection factors were not different between participants and those few non-participants. Median age of the cohort was 30.2 years (IQR 24.9–40.2) and 79 (55 %) were female. 25 patients (17.3 %) were recipients of saving lung transplantation. Sixty-nine percent of the cohort (99/144) had chronic P. aeruginosa infection as defined by the Leeds criteria. All but two patients with chronic P. aeruginosa underwent bacterial strain typing (98 %). Those two patients were unable to be categorized for the following reasons; one did not produce sputum (PA status determined by cough swab – but these isolates are not available for typing) and one patient transferred to our clinic following transplant and thusly pre-transplant samples were unavailable for assessment. Twenty–one percent (30/142) individuals in the cohort were chronically infected with ePA and 48 % (68/142) were infected with UNI. Of the ePA, 28 patients were infected with PES and two with LES. Patient demographic factors did not significantly differ amongst those with ePA infection relative to those with UNI or ENT (Table 1) with the exception of pancreatic insufficiency ePA 29/30 (97 %) vs non-ePA [93/112 (83 %), RR 1.16, CI 1.04–1.29. Patients with ePA were no more likely to have concurrent infection with other pathogens (Table 1). In fact, patients with ePA were less likely to have concurrent chronic S. aureus infection or non-tuberculous mycobacteria (NTM).

Of patients with ePA, 25/30 acquired infection prior to transition to the adult CF clinic. In those five with ePA super-infections as an adult, these infections were acquired within the first 2 years of transfer and none occurred in the last decade outside of one siblingship where the older of the pair had established infection prior to transfer to the adult clinic (data not shown) [7]. We also assessed how many prior CF clinics patients had attended as infection risk may be clinic dependent. 10 (7 %) had attended only our adult CF clinic, 73 (51.7 %) had attended two clinics (generally the local pediatric CF clinic and the local adult clinic), 38 (26.9 %) had attended three, 13 had attended four (9 %) and seven had attended five or more clinics (5 %). There was no association with number of clinics attended and risk of ePA clinic 0/10 (0 %), two clinics 16/73 (21.9 %), and ≥3 clinics 14/58 (24.1 %), p = 0.30.

Risk factors were assessed for ePA by asking patients about exposures occurring in their childhood or early adulthood. Most notably, patients with ePA were more likely to have attended summer camps (Table 2). Furthermore, patients with ePA were more likely to have directly participated in CF fundraising activities which had social components associated with them although this did not extend to individuals with family members partaking in CF fundraising activities. Having a family member with CF did not increase risk of ePA infection.

Patients with ePA did not significantly differ from those without regarding beliefs around risks and mechanisms of pathogen transmission (Table 3). Both groups recognized the risk of infection acquisition from aerosol, fomite and through health care workers (Table 3). In both groups patients demonstrated an understanding of pathogens with potential transmission potential and demonstrated a heightened concern regarding organisms such as Burkholderia cenocepacia, P. aeruginosa, and methicillin resistant S. aureus (MRSA) relative to other organisms such as S. maltophilia, and Aspergillus spp, and were not different amongst those infected with ePA (data not shown). Patients with ePA were more knowledgeable and concerned with respect to B. cenocepacia (Table 4). Both groups recognized that patients who have undergone transplantation were at increased risk of acquiring infections but participants were ambivalent as to whether those who had received transplant posed a risk for propagating infection.

Whereas patients recognized the risk of infection transmission with failure to comply with mandatory hand hygiene on the part of staff and patients alike, both groups were less concerned about acquisition from the clinic environment (Table 4). Most notably, patients from both groups believed that infection acquisition was much more likely to occur during exposure to a CF patient coughing as opposed to merely talking. Furthermore, neither group was particularly concerned about the role of spirometry in aerosol generation.

We assessed several factors related to patient preference and attitudes. Patients were generally against grouping of individuals in common waiting rooms (ePA 3 (IQR 2–5) vs ENT 3.0 (IQR 1–4), p = 0.69), and preferred segregation in private rooms through their entire clinic visit. Patients generally suggested they were not concerned with acquiring infection in clinic; ePA 5 (IQR 2–6) vs ENT 5 (IQR 2–6), p = 0.93 and did not cite fear of infection as a reason for not attending clinic; ePA 1 (IQR 1–2) vs ENT 1 (IQR 1–2), p = 0.43. Few patients suggested they would prefer to be seen outside of CF clinic altogether, ePA 2 (IQR 1–4) vs ENT 2 (IQR 1–4), p = 0.64. However, socialization with others with CF was seen more commonly in those with ePA(Table 4). When asked if they would continue to socialize outside of CF clinic together patients with ePA were more likely to do so; ePA 5 (IQR 4–6) vs ENT 4 (IQR 2–5), p = 0.03 and UNI 4 (IQR2-6), p = 0.06. The same trend was observed in patients response to interacting on clinic days; ePA 5 (IQR 2–5) vs ENT 3(IQR 2–5), p = 0.05 and UNI 3 (IQR2-5), p = 0.08. Whereas past fundraising activities were observed to associate with ePA, participants did not agree that CF individuals should be excluded from future events; ePA 2 (IQR 1–4) vs non 2 (IQR 1–4), p = 0.5. Patients were ambivalent towards, and many reported being unaware of online social network platforms for those with CF; ePA 4 (IQR 2–5) vs non 4 (IQR2-5), p = 0.93.