JAC Advance Access published online on December 21, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm481
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Clinical impact of reducing routine susceptibility testing in chronic Pseudomonas aeruginosa infections in cystic fibrosis
1 Adult Cystic Fibrosis Unit, Seacroft Hospital, Leeds LS14 6UH, UK 2 Department of Microbiology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK
* Corresponding author. Tel: +44-113-392-2922; Fax: +44-113-343-5649; E-mail: miles.denton{at}leedsth.nhs.uk
Received 3 September 2007; returned 21 October 2007; revised 13 November 2007; accepted 20 November 2007
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Abstract |
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Background: Susceptibility testing results are not predictive of clinical response to antibiotic therapy in chronic Pseudomonas aeruginosa infections in cystic fibrosis (CF). We assessed the impact of reducing the number of routine susceptibility tests performed on clinical outcome in these cases.
Methods: In June 2006, we introduced a protocol whereby susceptibility tests of P. aeruginosa isolates obtained from respiratory samples of people with CF were limited to those taken at the commencement of antibiotic therapy, when there was evidence of clinical failure or routinely if not tested in the previous 3 months. At all other times, isolates were identified and reported as normal but P. aeruginosa isolates were not subjected to susceptibility testing.
Results: Over a 6 month period, P. aeruginosa was isolated on at least one occasion from 193 patients attending the Adult Cystic Fibrosis Unit. In this period, we reduced the number of routine susceptibility tests by 56% (from a projected 2231 tests on 872 samples to an actual 972 tests on 427 samples). We assessed the response to courses of intravenous antibiotic treatment administered during the 6 month study period in 2006 and for courses administered in the same patients during the same calendar months in 2005. No significant differences in median change of FEV1, FVC, C-reactive protein (CRP), white cell count, weight or duration of intravenous antibiotics were observed. The projected savings of this intervention were 3500
in consumables and 170 h (costed at 6500) of laboratory staff time per annum, a total annual saving of 10 000 (£6500).
Conclusions: For CF units sending regular, routine sputum samples, a reduction in the number of susceptibility tests performed in cases of chronic P. aeruginosa infection can be carried out without impacting on short-term clinical outcomes.
Key Words: respiratory , laboratory , processing , efficiency
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Introduction |
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Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasians, with a frequency of
1 in 2500 live births. It is the result of mutations of a polypeptide, called the cystic fibrosis transmembrane regulator (CFTR), which functions as a chloride channel in epithelial membranes. These confer pathological changes in organs that express CFTR, including the lungs, pancreas, liver and reproductive tract. The most striking changes are seen in the respiratory tract where the defect predisposes to chronic pulmonary infections, most commonly with Pseudomonas aeruginosa. By adulthood, over 80% of people with CF are chronically infected with P. aeruginosa, which is managed by a combination of continuous aerosolized antibiotic therapy (usually colistin or tobramycin) and repeated courses of intravenous antipseudomonal antibiotics.1 Antibiotic susceptibility tests are poorly predictive of clinical outcomes in the management of chronic P. aeruginosa infection in CF, both for aerosolized2 and intravenous therapy.3 Laboratory studies have also revealed that susceptibility tests on P. aeruginosa isolates from chronic infection in CF show wide intra- and inter-laboratory variability4 and are significantly influenced by laboratory conditions.5 Given these findings, we examined the clinical impact of reducing the number of routine susceptibility tests we conducted on isolates of P. aeruginosa obtained from chronic infections in adults with CF.
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Methods |
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Setting
The Microbiology Department of the Leeds Teaching Hospitals NHS Trust provides support for the Regional Adult Cystic Fibrosis Unit, located at Seacroft Hospital in Leeds. The unit provides care for 350 people with CF, almost half of whom have chronic infection with P. aeruginosa.
For adults with CF chronically infected with P. aeruginosa, as defined by the Leeds criteria,6 the standard of care was to attend the outpatient clinic at least once every 8 weeks, and more often if clinical needs dictated. The unit policy at the time was to administer routine intravenous antibiotic therapy every 3–4 months and additional courses as required, e.g. acute exacerbations. All such patients were also offered continuous therapy with aerosolized colistin or tobramycin. Sputum samples would be collected at each clinic visit and at the beginning and end of every course of intravenous antibiotics. This approach is consistent with the UK’s Cystic Fibrosis Trust recommendations that respiratory samples should be obtained every 4–8 weeks.7
Each sputum sample was processed using standard laboratory methods. P. aeruginosa was identified on the basis of colonial appearances, oxidase reaction and growth on cetrimide agar. When required, isolates were further characterized using a commercial biochemical kit (API 20NE, BioMérieux, Marcy l’Étoile, France) or by referral to a reference laboratory for molecular confirmation by species-specific PCR.
Each distinguishable phenotype (variably distinguished on the grounds of alginate production, pigmentation, size, rough or smooth etc.) of P. aeruginosa was tested individually using a disc diffusion method (Stokes’ method). Eight different agents were tested (amikacin, aztreonam, ceftazidime, ciprofloxacin, colistin, meropenem, piperacillin/tazobactam and tobramycin) distributed on two Iso-Sensitest plates (E&O Laboratories, Bonnybridge, UK).
In June 2006, we introduced a protocol whereby susceptibility tests of P. aeruginosa isolates obtained from respiratory samples of people with CF were limited to those taken at the commencement of antibiotic therapy, when there was evidence of clinical failure of therapy or routinely if not tested in the previous 3 months. At all other times, isolates were identified and reported as previously described but P. aeruginosa isolates were not subjected to susceptibility testing. However, each non-tested isolate was kept for a further 7 days after the issue of the final report to allow the clinical team to request testing if clinically required. The impact of the new protocol was evaluated after 6 months.
Clinical evaluation and statistical analysis
Data are presented as median and range for metric variables and proportions (%) for categorical variables. As the data were not normally distributed, non-parametric tests were used. Estimates of the differences between groups were expressed as medians and 95% confidence intervals (95% CIs). The results of the study group variables between 2005 and 2006 were compared using the Mann–Whitney U-test. A P value of <0.05 was considered significant. Statistical analysis was performed using Minitab® version 14.0.
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Results |
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During a 6 month period between June and November 2006, P. aeruginosa was isolated on at least one occasion from 193 patients defined as chronically infected attending the Adult Cystic Fibrosis Unit. In this period, the application of the new protocol reduced the number of susceptibility tests by 56% (from a projected 2231 tests on 872 samples to an actual 972 tests on 427 samples).
Of the 193 patients, 148 had at least one course of intravenous antibiotic treatment during the 6 month study period in 2006 (77.6%). For various reasons (e.g. clinical decision, non-compliance), not all patients classified as ‘chronically infected with P. aeruginosa’ were treated with intravenous antibiotics as per unit protocol. The 148 treated patients had 351 courses of treatment, an average of 2.4 courses per patient. Of the 148 patients that underwent treatment in 2006, 119 of these also received intravenous antibiotics during the same six calendar months in 2005 (80%). These 119 patients had 237 courses of treatment, an average of 2.0 courses per patient (P = 0.437).
We assessed the response to intravenous antibiotic therapy between the study period in 2006 and in the same patients during the same calendar months in 2005 (Table 1). No significant differences in median change of FEV1, FVC, C-reactive protein (CRP), white cell count, weight or duration of intravenous antibiotics were observed. The projected savings of this intervention were 3500 in consumables (media, antibiotic discs and sundries) and 170 h (costed at 6500) of laboratory staff time per annum, a total annual saving of 10 000 (£6500).
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Discussion |
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This study showed that the number of routine susceptibility tests conducted on P. aeruginosa isolates associated with chronic P. aeruginosa infection in CF can be reduced without adversely affecting clinical outcomes of intravenous antibiotic therapy. This is consistent with the findings of clinical2,3 and laboratory studies4,5 indicating poor correlation and poor reproducibility of susceptibility testing results in chronic P. aeruginosa infection in CF. Therefore, the value of such routine testing is questionable. Although we used a non-standardized susceptibility testing method (Stokes’) in our laboratory, reproducibility has been poor even when a standardized approach, such as the BSAC method, has been used.4 More sophisticated susceptibility testing methodologies, such as multiple combination bactericidal antibiotic testing (MCBT), have also failed to correlate with clinical and microbiological outcomes in acute exacerbations of CF caused by P. aeruginosa and other multiresistant pathogens.8
Although this study confirmed the questionable value of susceptibility tests in this setting, we felt that we should not omit them completely. Microbiological doctrine is to perform susceptibility tests on all isolates deemed potentially significant pathogens in order to inform the clinical decision making process. Although those prescribing intravenous antibiotics for chronic P. aeruginosa infection in CF are also influenced by previous clinical responses, current unit policy, the patient’s allergy profile, and toxicity and drug monitoring concerns, they still do use the latest susceptibility results to inform their choices.9 The detection of resistance, particularly multi-resistance, may influence infection control practices and may indicate the possible presence of transmissible strains of P. aeruginosa.10 Particular antibiograms, such as colistin resistance, may also be useful in indicating the possibility that the isolate is actually a member of the Burkholderia cepacia complex, a significant group of pathogens associated with CF.
The reduction in susceptibility testing made a significant contribution to laboratory efficiency, particularly in terms of labour. However, the adoption of such an approach may not be suitable for all laboratories. Those providing support to units with a small number of clinic attendees or units which do not obtain sputum samples at the frequency practised in this study may find the benefits more limited. It is also crucial that there is a robust system in place for identifying those samples to which such a protocol can be applied. Those sending samples must be able to identify individuals chronically infected with P. aeruginosa and give sufficient clinical details on the request form (e.g. commencement of intravenous therapy, clinical deterioration etc.) to allow laboratory staff to correctly apply the protocol. The laboratory must also ensure that it is able to correctly and reliably differentiate between P. aeruginosa and other clinically significant Gram-negative non-fermentative bacteria encountered in sputum samples from people with CF.
While these findings are of interest, this was a small, retrospective, observational study. A larger, prospective study would be needed to assess if these findings are also robust over a longer period of time.
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Funding |
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This study evaluated the impact of reducing the number of susceptibility tests conducted during the provision of our routine clinical service. It received no specific funding.
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None to declare.
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Acknowledgements |
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We would like to thank all the staff in the Adult Cystic Fibrosis Unit and the Microbiology Department of the Leeds Teaching Hospitals NHS Trust whose contributions made this study possible.
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References |
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1 . Doring G, Conway SP, Heijerman HGM, et al. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J (2000) 16:749–67.[Abstract]
2 . LiPuma JJ. Microbiological and immunologic considerations with aerosolized drug delivery. Chest (2001) 120:118S–23S.[CrossRef][Web of Science][Medline]
3 . Smith AL, Fiel SB, Mayer-Hamblett N, et al. Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration: lack of association in cystic fibrosis. Chest (2003) 123:1495–502.[CrossRef][Web of Science][Medline]
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Foweraker JE, Laughton CR, Brown DFJ, et al. Phenotypic variability of Pseudomonas aeruginosa in sputa from patients with acute infective exacerbation of cystic fibrosis and its impact on the validity of antimicrobial susceptibility testing. J Antimicrob Chemother (2005) 55:921–7.
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Hill D, Rose B, Pajkos A, et al. Antibiotic susceptibilities of Pseudomonas aeruginosa isolates derived from patients with cystic fibrosis under aerobic, anaerobic, and biofilm conditions. J Clin Microbiol (2005) 43:5085–90.
6 . Lee TWR, Brownlee KG, Conway SP, et al. Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis. J Cyst Fibros (2003) 2:29–34.[CrossRef][Medline]
7 . Cystic Fibrosis Trust. Antibiotic Treatment for Cystic Fibrosis. Report of the UK Cystic Fibrosis Trust’s Antibiotic Group, April 2000.
8 . Aaron SD, Vandenheem KL, Ferris W, et al. Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial. Lancet (2005) 366:463–71.[CrossRef][Web of Science][Medline]
9 . Taylor RF, Hodson ME. Cystic fibrosis: antibiotic prescribing practices in the United Kingdom and Eire. Respir Med (1993) 87:535–9.[CrossRef][Web of Science][Medline]
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Scott FW, Pitt TL. Identification and characterization of transmissible Pseudomonas aeruginosa strains in cystic fibrosis patients in England and Wales. J Med Microbiol (2004) 53:609–15.
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