Blasi, Francesco

Downey, Damian G.

Elborn, J. Stuart

Ewing, Judith

Gramegna, Andrea

McCaughan, John

Millar, B. Cherie

Moore, John E.

Queen's University Belfast Research Portal

Increasing burden of antimicrobial resistance in pseudomonasaeruginosa from adult patients with cystic fibrosis (CF) in NorthernIreland: Then and nowGramegna, A., Moore, J. E., McCaughan, J., Millar, B. C., Ewing, J., Elborn, J. S., ... Downey, D. G. (2018).Increasing burden of antimicrobial resistance in pseudomonas aeruginosa from adult patients with cystic fibrosis(CF) in Northern Ireland: Then and now. Ulster Medical Journal, 87(2), 129-130.Published in:Ulster Medical JournalDocument Version:Publisher's PDF, also known as Version of recordQueen's University Belfast - Research Portal:Link to publication record in Queen's University Belfast Research PortalPublisher rightsCopyright 2018 the authors.This is an open access article published under a Creative Commons Attribution-NonCommercial-ShareAlike License(https://creativecommons.org/licenses/by-nc-sa/4.0/), which permits use, distribution and reproduction for non-commercial purposes,provided the author and source are cited and new creations are licensed under the identical terms.General rightsCopyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or othercopyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associatedwith these rights.Take down policyThe Research Portal is Queen's institutional repository that provides access to Queen's research output. Every effort has been made toensure that content in the Research Portal does not infringe any person's rights, or applicable UK laws. If you discover content in theResearch Portal that you believe breaches copyright or violates any law, please contact openaccess@qub.ac.uk.Download date:06. Aug. 2018UMJ is an open access publication of the Ulster Medical Society (http://www.ums.ac.uk).The Ulster Medical Society grants to all users on the basis of a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Licence the right to alter or build upon the work non-commercially, as long as the author is credited and the new creation is licensed under identical terms.Ulster Med J 2018;87(2):129-130LettersINCREASING BURDEN OF ANTIMICROBIAL RESISTANCE IN PSEUDOMONAS AERUGINOSA FROM ADULT PATIENTS WITH CYSTIC FIBROSIS (CF) IN NORTHERN IRELAND: THEN AND NOWEditor,Cystic fibrosis (CF) is characterised by defective mucociliary clearance and chronic airway infection.1  The most commonly isolated pathogen from CF airways is a Gram-negative bacterium, Pseudomonas aeruginosa (PA).2  Chronic PA infection is associated with significant morbidity and mortality in CF patients3 and necessitates multiple antibiotic courses.2 Antimicrobial resistance (AMR) in PA may be driven by the exposure of bacterium to antibiotic, either in the acute setting or during anti-pseudomonal chronic suppressive therapy.  We examined AMR from PA isolates from a single adult CF centre, by comparing antibiotic susceptibility from contemporary isolates with a collection from 13 years ago.Two collections of PA isolates were examined, each consisting of 100 non-duplicated organisms, which had isolated from the sputum of adult CF patients attending the Northern Ireland Adult Cystic Fibrosis Centre, Belfast City Hospital. Collection A was isolated during the period 1996-2001 and Collection B (2015-2016).  Microbiological isolation of PA was performed from freshly expectorated sputum, by employment of selective culture for 24-48h, followed by biochemical confirmation with API20NE identication strips (Biomerieux Ltd, UK). Antibiotic susceptibility was performed on each isolate by standard disk diffusion assay and resulting zone sizes were interpreted against published CLSI criteria.  Eight antibiotics from three classes of antibiotics were examined, including beta-lactams, fluoroquinolone and polymyxin, as detailed in Figure 1.  Antibiotic susceptibility was quantified by employment of a novel marker, Relative Resistance Index [RRI], as recently described.4  Briefly, qualitative “sensitive”, “moderately resistant” and “resistant” data were converted into a quantitative RRI value, through employment of an algorithm.4 An unpaired two-tailed t-test was used for comparison of trends between these two periods and a probability (p) value of less than 5% (p<0.5) was considered statistically significant.  There were no differences in the microbiological isolation methodology nor with the antibiotic susceptibility methodology between these two collection periods.A comparison of RRI scores between the two collection periods is shown (Figure 1).  RRI and AMR increased significantly for ciprofloxacin (p<0.0001)***, aminoglycosides (both amikacin and tobramycin, p<0.0001)*** and meropenem (p<0.0001)*** for PA isolates from 1996-2001 to 2015-2016. There was reduction in AMR during this period with piperacillin/tazobactam and ceftazidime.Overall, this study showed markedly greater resistance in the 2015-2016 PA cohort. Increase in AMR may reflect chronic exposure of PA to several classes of antibiotics used in the management of CF airways infection. Until now, it has been relatively difficult to perform comparative studies on AMR in CF, due to the reliance on generating largely qualitative data (S, I &R) from disk diffusion assay.  However, RRI may help tracking changes in resistance patterns either at a population level or at an individual patient level, either with a single antibiotic agent, several agents within a single class or collectively between antibiotic classes.This approach may be useful in helping to track emergence in AMR epidemiologically, those agents which display the greatest shift in AMR, as well as helping to guide antimicrobial stewardship practices and policies in CF.  FUNDINGAuthor AG was funded by a grant from the Società Italiana di Pneumologia/Italian Respiratory Society (SIP/IRS). The funding Society did not contribute to the content of this manuscript.  The authors have no interests to declare.Andrea Gramegna1,2,3*, John E. Moore1,2,4,5, John McCaughan1,2, B. Cherie Millar1,2,5, Judith Ewing2 , J. Stuart Elborn4,6, Francesco Blasi3 and Damian G. Downey2,41 Department of Bacteriology, Belfast City Hospital, Belfast Health & Social Care Trust, Lisburn Road, BELFAST, BT9 7AD, Northern Ireland, 2 Regional Adult Cystic Fibrosis Centre, Belfast City Hospital, Belfast Health & Social Care Trust, Lisburn Road, BELFAST, BT9 7AD Northern Ireland,3 Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Internal Medicine Department, Respiratory Unit and Regional Adult Cystic Fibrosis Center,IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico,  Milan, Italy4 Centre for Experimental Medicine, Queen’s University Belfast, Northern Ireland,5  School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, Northern Ireland.6 Imperial College and Royal Brompton Hospital, LondonCorrespondence to: Dr. Andrea Gramegna,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Internal Medicine Department, Respiratory Unit and Regional -0.4-0.200.20.40.60.811.2∆ Relative Resistance IndexMore resistantMore sensitiveFigure 1 Change in mean Relative Resistance Index [RRI] over a 13 year period with respect to Pseudomonas aeruginosaisolates (n=200) from the sputum of adult CF patientsAntibiotic Piperacillin/TazobactamCeftazidime Meropenem Aztreonam Tobramycin Amikacin Ciprofloxacin ColistinRRI 1996-2001 1.65 1.68 1.36 1.70 1.14 1.26 1.37 1.02RRI 2015-2016 1.38 1.62 1.77 1.73 1.84 2.30 1.96 1.11p value 0.02* 0.6 <0.0001*** 0.8 <0.0001*** <0.0001*** <0.0001*** 0.056Fig 1. Change in mean Relative Resistance Index [RRI] over a 13 year period with respect to Pseudomonas aeruginosa isolates (n=200) from the sputum of adult CF patients130 The Ulster Medical JournalUMJ is an open access publication of the Ulster Medical Society (http://www.ums.ac.uk).The Ulster Medical Society grants to all users on the basis of a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Licence the right to alter or build upon the work non-commercially, as long as the author is credited and the new creation is licensed under identical terms.Adult Cystic Fibrosis Center, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.gramegna.med@gmail.comREFERENCES1. Fodor AA, KlemER, Gilpin DF et al.  The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilientto antibiotic treatment of exacerbations. PloS one 2012; 7:, e45001.2. Elborn JS. Cystic fibrosis. Lancet. 2016; 388(10059):2519-2531.3. Høiby N. Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis. BMC Med. 2011; 9(32):1-7.4. Ewing J, McCaughan J, Moore JE, Fairley D, Sutherland B, Reid A, Downey D.  Relative resistance index (RRI) - a scoring system for antibiotic resistance in Pseudomonas aeruginosa.  Br J Biomed Sci.2017; 74(4):198-202. 

Increasing burden of antimicrobial resistance in pseudomonas aeruginosa from adult patients with cystic fibrosis (CF) in Northern Ireland: Then and now

A. Gramegna

J.E. Moore

J. Mccaughan

B.C. Millar

J. Ewing

J.S. Elborn

F. Blasi

D.G. Downey

AIR Universita degli studi di Milano

UMJ is an open access publication of the Ulster Medical Society (http://www.ums.ac.uk).
The Ulster Medical Society grants to all users on the basis of a Creative Commons Attribution-NonCommercial-ShareAlike 
4.0 International Licence the right to alter or build upon the work non-commercially, as long as the author is credited 
and the new creation is licensed under identical terms.
Ulster Med J 2018;87(2):129-135
Letters
INCREASING BURDEN OF ANTIMICROBIAL 
RESISTANCE IN PSEUDOMONAS 
AERUGINOSA FROM ADULT PATIENTS WITH 
CYSTIC FIBROSIS (CF) IN NORTHERN IRELAND: 
THEN AND NOW
Editor,
Cystic fibrosis (CF) is characterised by defective mucociliary 
clearance and chronic airway infection.1  The most commonly 
isolated pathogen from CF airways is a Gram-negative 
bacterium, Pseudomonas aeruginosa (PA).2  Chronic 
PA infection is associated with significant morbidity and 
mortality in CF patients3 and necessitates multiple antibiotic 
courses.2 Antimicrobial resistance (AMR) in PA may be 
driven by the exposure of bacterium to antibiotic, either in the 
acute setting or during anti-pseudomonal chronic suppressive 
therapy.  We examined AMR from PA isolates from a single 
adult CF centre, by comparing antibiotic susceptibility from 
contemporary isolates with a collection from 13 years ago.
Two collections of PA isolates were examined, each consisting 
of 100 non-duplicated organisms, which had isolated from 
the sputum of adult CF patients attending the Northern 
Ireland Adult Cystic Fibrosis Centre, Belfast City Hospital. 
Collection A was isolated during the period 1996-2001 
and Collection B (2015-2016).  Microbiological isolation 
of PA was performed from freshly expectorated sputum, 
by employment of selective culture for 24-48h, followed 
by biochemical confirmation with API20NE identication 
strips (Biomerieux Ltd, UK). Antibiotic susceptibility was 
performed on each isolate by standard disk diffusion assay and 
resulting zone sizes were interpreted against published CLSI 
criteria.  Eight antibiotics from three classes of antibiotics 
were examined, including beta-lactams, fluoroquinolone and 
polymyxin, as detailed in Figure 1.  Antibiotic susceptibility 
was quantified by employment of a novel marker, Relative 
Resistance Index [RRI], as recently described.4  Briefly, 
qualitative “sensitive”, “moderately resistant” and “resistant” 
data were converted into a quantitative RRI value, through 
employment of an algorithm.4 An unpaired two-tailed t-test 
was used for comparison of trends between these two periods 
and a probability (p) value of less than 5% (p<0.5) was 
considered statistically significant.  There were no differences 
in the microbiological isolation methodology nor with the 
antibiotic susceptibility methodology between these two 
collection periods.
A comparison of RRI scores between the two collection periods 
is shown (Figure 1).  RRI and AMR increased significantly 
for ciprofloxacin (p<0.0001)***, aminoglycosides (both 
amikacin and tobramycin, p<0.0001)*** and meropenem 
(p<0.0001)*** for PA isolates from 1996-2001 to 2015-
2016. There was reduction in AMR during this period with 
piperacillin/tazobactam and ceftazidime.
Overall, this study showed markedly greater resistance in the 
2015-2016 PA cohort. Increase in AMR may reflect chronic 
exposure of PA to several classes of antibiotics used in the 
management of CF airways infection. Until now, it has been 
relatively difficult to perform comparative studies on AMR 
in CF, due to the reliance on generating largely qualitative 
data (S, I &R) from disk diffusion assay.  However, RRI 
may help tracking changes in resistance patterns either at a 
population level or at an individual patient level, either with 
a single antibiotic agent, several agents within a single class 
or collectively between antibiotic classes.
This approach may be useful in helping to track emergence 
in AMR epidemiologically, those agents which display 
the greatest shift in AMR, as well as helping to guide 
antimicrobial stewardship practices and policies in CF.  
FUNDING
Author AG was funded by a grant from the Società Italiana 
di Pneumologia/Italian Respiratory Society (SIP/IRS). The 
funding Society did not contribute to the content of this 
manuscript.  
The authors have no interests to declare.
Andrea Gramegna1,2,3*, John E. Moore1,2,4,5, John McCaughan1,2, B. Cherie 
Millar1,2,5, Judith Ewing2 , J. Stuart Elborn4,6, Francesco Blasi3 and Damian 
G. Downey2,4
1 Department of Bacteriology, Belfast City Hospital, Belfast Health & 
Social Care Trust, Lisburn Road, BELFAST, BT9 7AD, Northern Ireland, 
2 Regional Adult Cystic Fibrosis Centre, Belfast City Hospital, Belfast 
Health & Social Care Trust, Lisburn Road, BELFAST, BT9 7AD 
Northern Ireland,
3 Department of Pathophysiology and Transplantation, Università degli 
Studi di Milano, Internal Medicine Department, Respiratory Unit and 
Regional Adult Cystic Fibrosis Center,IRCCS Fondazione Cà Granda 
Ospedale Maggiore Policlinico,  Milan, Italy
4 Centre for Experimental Medicine, Queen’s University Belfast, Northern 
Ireland,
5  School of Biomedical Sciences, Ulster University, Cromore Road, 
Coleraine, BT52 1SA, Northern Ireland.
6 Imperial College and Royal Brompton Hospital, London
Correspondence to: Dr. Andrea Gramegna,Department of 
Pathophysiology and Transplantation, Università degli Studi di 
Milano, Internal Medicine Department, Respiratory Unit and Regional 
-0.4
-0.2
0
0.2
0.4
0.6
0.8
1
1.2
∆ 
R
el
at
iv
e 
R
es
is
ta
nc
e 
In
de
x
More resistant
More sensitive
Figure 1 Change in mean Relative Resistance Index [RRI] over a 13 year period with respect to Pseudomonas aeruginosa
isolates (n=200) from the sputum of adult CF patients
Antibiotic Piperacillin/
Tazobactam
Ceftazidime Meropenem Aztreonam Tobramycin Amikacin Ciprofloxacin Colistin
RRI 1996-2001 1.65 1.68 1.36 1.70 1.14 1.26 1.37 1.02
RRI 2015-2016 1.38 1.62 1.77 1.73 1.84 2.30 1.96 1.11
p value 0.02* 0.6 <0.0001*** 0.8 <0.0001*** <0.0001*** <0.0001*** 0.056
Fig 1. Change in mean Relative Resistance Index [RRI] over a 
13 year period with respect to Pseudomonas aeruginosa isolates 
(n=200) from the sputum of adult CF patients
130 The Ulster Medical Journal
UMJ is an open access publication of the Ulster Medical Society (http://www.ums.ac.uk).
The Ulster Medical Society grants to all users on the basis of a Creative Commons Attribution-NonCommercial-ShareAlike 
4.0 International Licence the right to alter or build upon the work non-commercially, as long as the author is credited 
and the new creation is licensed under identical terms.
Adult Cystic Fibrosis Center, IRCCS Fondazione Cà Granda Ospedale 
Maggiore Policlinico, Milan, Italy.
gramegna.med@gmail.com
REFERENCES
1. Fodor AA, KlemER, Gilpin DF et al.  The adult cystic fibrosis airway 
microbiota is stable over time and infection type, and highly resilient 
to antibiotic treatment of exacerbations. PloS one 2012; 7:, e45001.
2. Elborn JS. Cystic fibrosis. Lancet. 2016; 388(10059):2519-2531.
3.   Høiby N. Recent advances in the treatment of Pseudomonas aeruginosa 
infections in cystic fibrosis. BMC Med. 2011; 9(32):1-7.
4.  Ewing J, McCaughan J, Moore JE, Fairley D, Sutherland B, Reid A, 
Downey D.  Relative resistance index (RRI) - a scoring system for 
antibiotic resistance in Pseudomonas aeruginosa.  Br J Biomed Sci. 
2017; 74(4):198-202.
‘DISCHARGE LETTER QUALITY; HOW TO HELP 
BOTH JUNIOR DOCTORS AND GPS?’
Editor,
Discharge letters are an important communication enabling 
the safe transfer of a patient from secondary to primary 
care. Research has shown that many junior doctors feel 
inadequately trained in the process of writing discharge 
letters1. The authors of this work noted a wide variation in 
how long it took junior doctors to complete letters. A survey 
of UK GPs noted that they too are unhappy with the standard 
of letters they receive. They highlight accuracy, clarity and 
timeliness of receiving letters as causes for concern 2. This 
team has completed a quality improvement project aiming 
to reduce time spent writing discharge letters and improve 
their clarity.
METHODS
Baseline data was collected on how long it took 4 junior 
doctors to complete 1 weeks-worth of discharge letters 
working across 4 medical wards of the Ulster Hospital, 
Northern Ireland in January 2017. Two complete Deming 
‘plan-do-study-act’ (PDSA) cycles were then performed. 
In cycle 1 (March 2017) an educational intervention was 
introduced to the 4 junior doctors. This consisted of a 1-hour 
teaching session by medical consultants, with GP input on 
how to write an efficient and effective discharge letter. In 
cycle 2 (August-October 2017), an educational intervention 
was delivered by one of the original junior doctors to all 
incoming junior doctors to Northern Ireland at their regional 
induction day. 
RESULTS
Baseline data showed that the mean time taken to complete 
31 discharge letters was 25.9 minutes, with a range of 58 
minutes (Table 1). After cycle 1, mean time spent completing 
43 discharge letters fell by 43.2% (p<0.001) to 14.7 minutes, 
with a range of 25 minutes. GP and consultant feedback 
indicated that letters written after education had increased 
clarity. After cycle 2, mean time completing 34 letters was 21 
minutes, with a range of 31 minutes. This is a 19% reduction 
relative to baseline (p<0.05). 
DISCUSSION
Over the course of a typical week, the change brought 
about through PDSA cycle 1 could save a junior doctor 2 
hours and 45 minutes. This could free doctors to increase 
exposure to other facets of healthcare provision and training 
opportunities. Despite our findings and evidence showing 
that small group based teaching sessions provided to junior 
doctors can improve the speed of completion and quality of 
discharge letters, many medical schools do not incorporate 
extensive teaching3. Cycle 2, which increases the scale and 
sustainability of our project reduced time spent completing 
discharge letters, but was not as effective as cycle 1.
Discussion with local GPs revealed that they receive large 
volumes of letters and examination results from secondary 
and tertiary care centres each day. This team proposes 
the introduction of educational sessions to junior doctors 
focussing on how to complete efficient and effective discharge 
letters to improve clarity of communication and decrease time 
spent on letter composition.
David Johnston, Owen McMurray, Michael McKee, Michael McConville, 
Niall Leonard
South-Eastern Health and Social Care Trust
REFERENCES
1. Yemm R, Bhattacharya D, Wright D, Poland F. What constitutes a 
high quality discharge summary? A comparison between the views of 
secondary and primary care doctors. Int J Med Educ. 2014;5:125-31.
2. Care Quality Commission. National Study. Managing patients’ medicines 
after discharge from hospital. London: Care Quality Commission; 2009
3. Myers JS, Jaipaul CK, Kogan JR, Krekun S, Bellini LM, Shea JA. Are 
discharge summaries teachable? The effects of a discharge summary 
curriculum on the quality of discharge summaries in an internal medicine 
residency program. Acad Med. 2006;81(10 Suppl):S5-8.
POINT OF DECISION PROMPTS AND 
SIGNPOSTING FOOTPRINTS IMPROVE STAIR 
USE IN A UK CITY CENTRE OFFICE
Editor,
Physical inactivity is a public health priority, with sedentary 
behaviour and lack of physical movement major contributory 
factors to serious illness, including coronary heart disease 
(CHD), stroke, Type 2 diabetes and breast and bowel cancer 
Table 1. 
Time taken to complete discharge letters over a one-week 
period by four junior doctors at baseline and after PDSA 
cycle one and two educational interventions.
Baseline Data PDSA 1 PDSA 2
Mean Time (min) 25.9 14.7 21
Median Time (min) 24 15 21
Range (min) 58 25 31


Increasing burden of antimicrobial resistance in pseudomonas aeruginosa from adult patients with cystic fibrosis (cf) in Northern Ireland : Then and now

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Increasing burden of antimicrobial resistance in pseudomonas aeruginosa from adult patients with cystic fibrosis (CF) in Northern Ireland: Then and now

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