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Urinary tract infections in Australian aged care homes: Antibiotic prescribing practices and concordance to national guidelines
ARTICLE IN PRESS American Journal of Infection Control 000 (2019) 1−6
Contents lists available at ScienceDirect
American Journal of Infection Control journal homepage: www.ajicjournal.org
Major Article
Urinary tract infections in Australian aged care homes: Antibiotic prescribing practices and concordance to national guidelines Leslie Dowson MBioethics a,b, Noleen Bennett RN, MPH, PhD a,c,d,*, Kirsty Buising MBBS, MPH, MD a,e,f, Caroline Marshall MBBS, PhD, Grad Dip Clin Epi a,e,f,g, N. Deborah Friedman MBBS, MPH, MD a,h,i, Rhonda L. Stuart MBBS, FRACP, PhD a,j,k, David C.M. Kong PhD a,b,l a
National Centre for Antimicrobial Stewardship at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia c Victorian Healthcare Associated Infection Surveillance System Coordinating Centre at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia d Department of Nursing, Melbourne School of Health Sciences, The University of Melbourne, Victoria, Australia e Victorian Infectious Diseases Service at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia f Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia g Infection Prevention and Surveillance Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia h School of Medicine, Deakin University, Geelong, Victoria, Australia i Department of General Medicine and Department of Infectious Diseases, Barwon Health, Geelong, Victoria, Australia j Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia k Monash Infectious Diseases and Infection Control and Epidemiology, Monash Health, Clayton, Victoria, Australia l Pharmacy Department, Ballarat Health Services, Ballarat, Victoria, Australia b
Key Words: Long-term care Nursing home Antibacterial agents Anti-infective agents Cystitis
Background: Since 2015 the Aged Care National Antimicrobial Prescribing Survey has collected and reported data on antibiotic use in Australian aged care homes (ACHs) as part of the Australian Commission on Safety and Quality in Health Care’s Antimicrobial Use and Resistance in Australia project. The objective of this study was to analyze this data source with regards to prescribing for urinary tract infections (UTIs) to improve the use of antibiotics. Methods: This cross-sectional study analyzed the 2016 and 2017 survey data. Antibiotic prescribing for urinary tract indications was compared with national guideline recommendations. Results: A total of 662 antibiotic prescriptions from 247 ACHs were analyzed. For all prophylactic antibiotics for UTI, 51.8% were prescribed for longer than 6 months, contrary to the guideline recommendation. Most antibiotics prescribed for treatment (71.6%) were for cystitis. Cefalexin was most frequently selected for treatment of cystitis, with 10.4% of these prescriptions being concordant with the recommendations. Prescribing additional daily doses of cefalexin occurred in 63.2% of prescriptions. Conclusions: Antimicrobial stewardship activities targeting UTI prophylaxis for durations longer than 6 months, and excessive daily doses of cefalexin to treat cystitis could yield significant reductions in unnecessary antibiotic consumption among Australian residents of ACHs. Crown Copyright © 2019 Published by Elsevier Inc. on behalf of Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.
*Address correspondence to Noleen Bennett, RN, MPH, PhD, VICNISS Coordinating Centre at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne, Victoria, Australia, 3000. E-mail address: [email protected] (N. Bennett). Funding/support: The Aged Care National Antimicrobial Prescribing Survey is a project collaboration between the National Centre for Antimicrobial Stewardship, the Guidance Group, and the Victorian Healthcare Associated Infection Surveillance System Coordinating Centre. Funding for the Aged Care National Antimicrobial Prescribing Survey is partly provided by the Australian Commission
on Safety and Quality in Health Care under the Antimicrobial Use and Resistance in Australia project. Leslie Dowson receives an Australian Government Research Training Program Scholarship. The National Centre for Antimicrobial Stewardship and its research are funded by the National Health and Medical Research Council of Australia (grant number APP1079625). Conflicts of interest: K.B. is a member of the writing group for the Therapeutic Guidelines: Antibiotic. D.C.M. Kong has sat on advisory boards for Becton Dickinson Pty Ltd and MSD, and received financial/travel support from MSD, all unrelated to this current study.
https://doi.org/10.1016/j.ajic.2019.08.034 0196-6553/Crown Copyright © 2019 Published by Elsevier Inc. on behalf of Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.
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The burden of urinary tract infections (UTIs) in residential aged care homes (ACHs) is significant.1 UTIs are a frequent indication for antibiotic prescribing.2,3 However, using antibiotics for UTIs can also harm ACH residents. Common antibiotic-related adverse events, such as nausea and diarrhea, and serious events, such as allergic reactions, pulmonary, neurological, or liver toxicity, can cause significant morbidity in ACH residents.4-6 Further, antibiotic use in ACHs is of public health concern7 because it increases selective pressure for the development of multidrug-resistant organisms (MDROs).8 MDROs are increasing in prevalence,9 and prior antibiotic use is associated with MDRO carriage in ACH residents.10 ACHs have been identified as reservoirs for MDROs and have the potential to both sustain and drive MDRO epidemics within health care networks.11 In most Australian ACHs, visiting general practitioners are primarily responsible for resident medical care and after-hours locum general practitioner visits are common. Australian ACHs are usually staffed with 1 registered nurse facility manager, and at least 1 registered nurse available for clinical resident care (depending on the size and structure of the ACH). Personal care assistants and enrolled nurses provide direct activities-of-daily-living support to residents. Residents of Australian ACHs typically require assistance with 1 or more activities-of-daily living or health care requirement. Most residents (86%) have at least 1 mental health or behavioral condition, and more than one-half (52%) have been diagnosed with dementia.12 Antimicrobial stewardship (AMS) is an ongoing effort by health care providers to optimize antimicrobial use.13 Recent guidelines for AMS in long-term care facilities, such as ACHs, support designing AMS activities for specific infections such as UTIs,14 but data on realworld prescribing practices are required to design effective AMS activities. Since 2015, the Aged Care National Antimicrobial Prescribing Survey (AC NAPS) has collected and reported data on antibiotic use in Australian ACHs as part of the Australian Commission on Safety and Quality in Health Care’s (ACSQHC’s) Antimicrobial Use and Resistance in Australia project.15 Analyzing these data in a meaningful manner may assist both prescribers and ACH residents. Expert guidance with regards to antibiotic therapy for UTIs in older adults has been updated in recent years as new evidence for optimal prescribing has become available. Since 2003, in Australia, changes include strengthening advice that treating asymptomatic bacteriuria is not recommended (except for people undergoing elective urological procedures and in pregnant women) and halving the recommended days of therapy for cystitis in men.4,16 Little is known about the concordance of antibiotic prescribing with these updates, and adherence to these recommendations could reduce unnecessary antibiotic use in ACHs.17 Many sources of guidance are available to antibiotic prescribers.4,1821 The Therapeutic Guidelines: Antibiotic4 (TG-Antibiotic) is developed for use in Australian clinical settings. Its recommendations are based on expert consensus, using the latest evidence for best practices.4 In environments such as ACHs without specialty infectious diseases clinicians22 and local antibiograms, the TG-Antibiotic guidelines are important because the advice is formulated with consideration of known local resistance data, patient safety, and thresholds for clinical antibiotic failure.4 During this study, the Australian Medicines Handbook Aged Care Companion (AMH)18 (another popular resource for Australian ACH prescribers) recommended antibiotic selections, doses, and frequencies for UTI prophylaxis and cystitis treatment that were concordant with the TG-Antibiotic recommendations, although the AMH’s duration recommendations were less definitive. In Australia, with support from the ACSQHC, the TG-Antibiotic recommendations are utilized to benchmark and identify potentially problematic antibiotic prescribing,23 which can then be addressed through AMS activities. This study was a cross-sectional in-depth interrogation of the 2016 and 2017 AC NAPS data to examine antibiotic prescribing patterns for UTIs in ACHs.
METHODS Data collection As part of the 2016 and 2017 AC NAPS, de-identified point prevalence data were collected from the medical records of ACH residents and entered into the online AC NAPS database by participating ACH nurses, pharmacists, or infection control nurse consultants (ie, surveyors). Numerous strategies were used to recruit ACHs to participate in the survey, including newsletters and direct communications from governmental organizations and professional societies. Participation by the ACHs was mostly voluntary. In 2017, the Victorian State Government mandated their public sector ACHs participate.24 Surveyors were provided with standardized instructions to complete the survey, and they had access to online, e-mail, and telephone support. Data about residents prescribed 1 or more antibiotics were included. Data were collected and entered during the official survey periods, between June 2016 and September 2016 and June 2017 and September 2017, on single days chosen by 339 participating ACHs. The 2015 pilot year data were excluded from this study. Data about antibiotic prescriptions ceased in the month prior to the survey date could be included by surveyors. Data collected included antibiotic selection, start date, dose, frequency, route of administration, and indication. Whether the indication was documented by the prescriber or had been assessed by the surveyor after reviewing the clinical notes of the residents was also recorded. For urinary tract indications, the surveyor could select asymptomatic bacteriuria, cystitis, catheterassociated UTI (CA-UTI), prostatitis, pyelonephritis, or other. The surveyors also indicated if the antibiotic was for prophylaxis against UTIs, if urine specimens were collected and analyzed (microbiologically and/or dipstick), and if the resident had a urinary catheter. Data analysis Data were analyzed using SPSS Statistics software for Windows, version 23 (IBM Corp, Armonk, NY) and Microsoft Excel 2013 for Windows (Microsoft Corporation, Redmond, WA). Frequencies and cross tabulations of antibiotic selections, doses and frequencies were computed from the dataset, and the percentages of concordant and nonconcordant prescriptions calculated after comparison to the TGAntibiotic recommendations that were current at the time of the 2016 and 2017 surveys, as summarized in Box 1. As methenamine hippurate is a urinary antiseptic and not strictly an antibiotic, 82 prescriptions for methenamine hippurate were excluded from the data analysis. Methenamine hippurate is not recommended by the TG-Antibiotic. To avoid oversampling of some ACH practices, for each ACH, data entered on only 1 day (the most recent day) during the official survey periods were analyzed. A sensitivity analysis comparing results between the corrected and uncorrected samples was conducted. Duration of therapy was calculated for current prescriptions from the difference between the prescription start date, and the survey date, where the start date was available. If the start date was not available or if the prescription had ceased, the prescription was excluded from the duration of therapy analysis. Duration was then assessed as less than, equal to, or greater than the TG-Antibiotic recommendation. This method is likely to overestimate concordant prescriptions. For prophylactic antibiotics, durations were assessed as less than, equal to, or greater than 6 months, in accordance with the TG-Antibiotic general recommendation.4 For treatment of cystitis, analysis of the associated microbiology data was undertaken for norfloxacin prescriptions (as the TG-Antibiotic recommends norfloxacin only when resistance to the other
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Box 1. Recommendations* from Therapeutic Guidelines: Antibiotic4 UTI prophylaxis in adults: 1. Trimethoprim 150mg orally at night, or 2. Cefalexin 250mg orally at night For 3-6 months or in some cases for longer periods. Cystitis in women: 1. Trimethoprim 300 mg orally, daily for 3 days; or 2. Cefalexin 500 mg orally, 12-hourly for 5 days; or *3. Amoxicillin + clavulanate 500 + 125 mg orally, 12-hourly for 5 days or *3. Nitrofurantoin 100 mg orally, 12-hourly for 5 days. If resistance to the other drugs are confirmed, then norfloxacin, 400 mg orally, 12-hourly for 3 days. Cystitis in men: 1. Trimethoprim 300 mg orally, daily for 7 days; or 2. Cefalexin 500 mg orally, 12-hourly for 7 days; or *3. Amoxicillin + clavulanate 500 + 125mg orally, 12-hourly for 7 days or *3. Nitrofurantoin 100 mg orally, 12-hourly for 7 days. If resistance to the other drugs are confirmed, then norfloxacin, 400 mg orally, 12-hourly for 7 days. *Numbers indicate preference by ranking, amoxicillin + clavulanate and nitrofurantoin had an equal ranking.
recommended agents is confirmed) and for all nonrecommended antibiotic agents selected by prescribers. An Infectious Diseases Consultant Physician (K.B.) evaluated the individual microbiology results and associated prescription data, and judged whether the antibiotic agents selected were directed by pathogen susceptibilities. This study was approved by Monash University’s Human Research Ethics Office, Project 15016. RESULTS During the study periods, 921 antibiotic prescriptions were attributed to UTIs across 251 Australian ACHs. A total of 259 prescriptions were excluded from the analyses because of ACHs entering data outside the official survey dates or entering data on more than 1 day (Fig 1). Four ACHs only contributed data outside the official survey periods, and 69 ACHs participated on more than 1 day. A total of 662 prescriptions from 247 ACHs were included in the final analyses (Fig 1). The sensitivity analysis comparing results between the corrected sample (662 prescriptions from 247 ACHs) and uncorrected sample (921 prescriptions from 251 ACHs) confirmed the prescribing trends reported in this study. The 247 ACHs contributing UTI prescribing data to these analyses had a mean size of 58.3 beds (range: 10-293) and of the 247 contributing ACHs 95 (38.5%) were from inner regional areas of Australia, 92 (37.2%) were from major cities of Australia, 48 (19.4%) were from outer regional areas of Australia, 9 (3.6%) were from remote areas of Australia, and 3 (1.2%) were from very remote areas of Australia. The majority of the 247 ACHs were government operated (55.1%, 137/247), followed by not-for-profit (36.0%, 89/247) and private incorporated (8.5%, 21/247). Descriptions of the total participating ACHs (including those that did not contribute UTI data) are available elsewhere.3,24 The residents for whom antibiotics were prescribed for UTIs were predominantly women (76.4%, 506/662) and had a mean age of 85 years (range: 49-102). The antibiotic was designated for prophylaxis in 38.4% (254/662) of prescriptions, and for 18.1% (120/662) of
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prescriptions the UTI was not documented by the prescriber, but assessed by the surveyor from other clinical notes as being prescribed for UTI. A total of 18 different antibiotics were prescribed for UTI indications (Table 1). Prophylaxis For prophylaxis against UTIs, 254 prescriptions involving 11 different antibiotics were noted (Table 1). The antibiotic selection, dose, and frequency were concordant with the recommendations in the TG-Antibiotic, and the antibiotic was prescribed for less than 6 months in 16.5% (40/243) of prescriptions (11 prescriptions were removed from the analysis of duration of therapy owing to insufficient information). More than one-half of the prescriptions for prophylactic use (56.3%, 143/254) were for cefalexin, followed by nitrofurantoin (20.1%, 51/ 254), trimethoprim (13.4%, 35/254), trimethoprim-sulfamethoxazole (2.8%, 7/254), and gentamicin (2.0%, 5/254). For the TG-Antibiotic recommended antibiotics, cefalexin and trimethoprim, 57.6% (80/139) and 44.1% (15/34), respectively, were prescribed for longer than 6 months. For all antibiotics prescribed for UTI prophylaxis, 51.8% (126/243) were prescribed for longer than 6 months. Of the 5 total prescriptions for intramuscular prophylactic gentamicin, 3 of these were associated with the manipulation of a catheter, 1 was documented as “prophylaxis for a catheter-associated UTI” and 1 was documented for “prophylaxis of cystitis.” In total, 5 prescriptions (3 for gentamicin, 1 for cephalexin, and 1 for amoxicillin-clavulanate) were associated with the manipulation of a catheter, a practice which is not recommended.4 Treatment In total, 408 prescriptions of antibiotics were for treatment of UTIs. Of these, 382 were analyzed for concordance with the TGAntibiotic (after excluding the indication ‘Other’ [N = 26], which could not be compared with TG-Antibiotic recommendations) (Fig 1). For all treatment indications (cystitis, asymptomatic bacteriuria, CA-UTI, and pyelonephritis), the antibiotic selection, dose, frequency, and duration of treatment was concordant with the recommendations in the TG-Antibiotic in 22.3% (56/251) of prescriptions (131 prescriptions had insufficient data to calculate duration). Dipstick urinalysis was performed in 52.7% (215/408) of treatment prescriptions, and associated microbiological investigations were performed in 47.1% (192/408) of treatment prescriptions. Most of the prescriptions written for treatment of UTIs (71.6%, 292/408) were for cystitis. All antibiotics prescribed for asymptomatic bacteriuria were nonconcordant with the TG-Antibiotic. Further analysis of the antibiotics prescribed for prostatitis (N = 0), pyelonephritis (N = 12), and CA-UTI (N = 44) was not meaningful owing to low numbers of prescriptions. Treatment of cystitis Table 1 shows that 14 different antibiotic agents were prescribed for the treatment of cystitis. The most commonly prescribed was cefalexin (36.3%, 106/292), followed by trimethoprim (35.6%, 104/ 292). Antibiotic selection, dose, frequency, and duration was concordant with recommendations in the TG-Antibiotic for 23.6% (45/191) of prescriptions for cystitis (data were insufficient to calculate duration for 101 prescriptions). Fewer than 27% (26.4%, 28/106) of the prescriptions for cefalexin were concordant with the TG-Antibiotic’s recommendations for frequency of administration (Table 2). In 42.5% (45/106) of the prescriptions for cefalexin, 500 mg per dose was prescribed with 1 additional
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Fig 1. Summary of antibiotic prescriptions for UTIs identified in the 2016 and 2017 AC NAPS. AC NAPS, Aged Care National Antimicrobial Prescribing Survey; ACH, aged care home; UTIs, urinary tract infections.
daily administration (8-hourly, in contrast to the TG-Antibiotic’s recommended 12-hourly administration), and for a further 20.2% (22/ 106) 2 extra daily administrations (6 hourly) of 500 mg per dose
was prescribed. When all recommendations were factored into the analysis (ie, dose, frequency, and duration), only 10.4% (10/96) of the prescriptions for cefalexin for cystitis were concordant with the
Table 1 Frequencies of prescribed antibiotics Category
TG-Antibiotic Guidelines
%
Antibiotic
No.
% of Total prescriptions
Prophylaxis
Recommended
70.1
Not recommended
29.9
143 35 51 7 5 13
56.3 13.4 20.1 2.8 2.0 5.1
Recommended
84.9
Not recommended
15.1
Cefalexin Trimethoprim Nitrofurantoin Trimethoprim-sulfamethoxazole Gentamicin (IM) Others (6) Amoxicillin, Amoxicillin + Clavulanate, Cefalothin, Ciprofloxacin, Doxycycline, Norfloxacin Cefalexin Trimethoprim Amoxicillin + Clavulanate Nitrofurantoin Norfloxacin Amoxicillin Ciprofloxacin Ceftriaxone (IV or IM) Gentamicin (IV or IM) Other (5) Ampicillin, Cefalothin, Clarithromycin, Clindamycin, Trimethoprim-sulfamethoxazole
106 104 24 9 5 17 9 4 3 11
36.3 35.6 8.2 3.1 1.7 5.8 3.1 1.4 1.0 3.8
Cystitis treatment
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Table 2 Concordance for TG-Antibiotic recommended antibiotics: dose, frequency, and duration Concordance with TG-Antibiotic Dose*
Durationy
Frequency*
Dose, frequency, and durationy
Category
Antibiotic
Total
Duration calculation denominator
No.
%
No.
%
No.
%
No.
%
Prophylaxis
Cefalexin Trimethoprim Cefalexin Trimethoprim Amoxicillin + Clavulanate Nitrofurantoin Norfloxacin
143 35 106 104 24
139 34 96 89 23
119 17 91 103 8
83.2 48.6 85.8 99.0 33.3
126 34 28 104 24
88.1 97.1 26.4 100.0 100.0
45 16 47 30 13
31.5 47.0 49.0 33.7 56.5
34 6 10 30 5
24.5 17.6 10.4 33.7 21.7
9 5
8 4
3 3
33.3 60.0
2 2
22.2 40.0
3 1
33.3 20.0
0 0
0.0 0.0
Cystitis treatment
TG-Antibiotic, Therapeutic Guidelines: Antibiotic. *Denominator equals total number of prescriptions. y Denominator equals duration calculation denominator.
recommendations in the TG-Antibiotic (data were insufficient to calculate duration in 10 prescriptions). Less than 34% (30/89) of prescriptions for trimethoprim, for the treatment of cystitis, were concordant with the TG-Antibiotic recommended duration of treatment (ie, 3 days for women, 7 days for men). However, concordance with the TG-Antibiotic’s other recommendations (ie dose and frequency) were both high (99.0% [103/104] and 100.0% [104/104], respectively). Of the 5 prescriptions for norfloxacin, 4 had microbiology results. Microbiology results (ie, pathogen susceptibilities) directed therapy for 2 prescriptions. Microbiology results did not direct therapy for 1 prescription despite being available, and 1 microbiology result could not be analyzed owing to insufficient information. For antibiotic agents which were not recommended by the TGAntibiotic, 26 of 44 prescriptions had associated microbiology results. A total of 14 prescriptions were directed by pathogen susceptibilities. Microbiology results did not direct therapy, despite being available for 9 prescriptions, and 3 prescriptions with associated microbiology results could not be analyzed owing to insufficient information. Where duration of therapy data were available, the mean time between microbiology urine collection and the date of the survey was 7 days (range: 0-21 days). DISCUSSION UTIs in ACHs pose a significant burden to residents, and the associated antibiotic prescribing is important owing to the large numbers of residents affected. Prescribers in ACHs frequently do not prescribe antibiotics in accordance with national guideline recommendations in Australia (ie, TG-Antibiotic). This could be because the prescribers have difficulty with the advice (ie, do not agree or are unable to follow), have sought advice from other or older resources, and/or have developed a habit17 of prescribing without referring to a current reference. The prescribing of antibiotics for UTIs in ACHs warrants further investigation to determine what can be done to assist prescribers in adopting national guideline recommendations. This could include exploring the impact of displaying a summary of the recommendations for staff and prescribers in ACHs. The most common reason where the prescribing of antibiotics for UTI prophylaxis was nonconcordant with the TG-Antibiotic recommendations was that the duration of therapy exceeded 6 months. Although the TG-Antibiotic states in some cases longer durations may be warranted, 51.8% (126/243) of residents receiving prophylaxis against UTIs in the current study had been receiving antibiotics for more than 6 months. This suggests many residents are not reviewed and trialed without antibiotic prophylaxis as often as they should be. Further, the clinical appropriateness of initiating
prophylaxis as compared with the recommended guidelines cannot be assessed by AC NAPS data. Given the prevalence of antibiotic prescribing for prophylaxis of UTI in this study, a future study to assess concordance to the TG: Antibiotic recommendation that prophylaxis for UTI may be considered for frequent symptomatic infections (eg, 2 or more symptomatic UTIs in one 6 month period or 3 or more over a 12 month period) may be worthwhile.4 When antibiotic prophylaxis is considered, the risks, including acquisition of MDROs must be weighed against the symptoms from an occasional UTI. As the clinical situations of residents change, risk-benefit assessments of ongoing antibiotic prophylaxis for UTIs may change. Likewise, whereas trimethoprim for treatment of cystitis in this study was highly concordant with the TG-Antibiotic’s recommendations for dose and frequency, this fell notably when the duration of treatment was considered (Table 2). Advice on duration of trimethoprim treatment for cystitis varies amongst available resources. For example, a commonly used medicines database, MIMS Online19 (as of October 2018) recommends a 7-day duration for treatment without specifying for that women, it can be prescribed for shorter periods as per the TG-Antibiotic. In addition, fewer than 26.4% (28/106) of prescriptions for cefalexin for the treatment of cystitis were concordant with the TG-Antibiotic’s recommendation for administration frequency, and fewer than 11% (10/96) of prescriptions for cefalexin for cystitis treatment were concordant to the combined TG-Antibiotic recommendations (ie, dose, frequency and duration). The specific reasons for the observed common practice of prescribing extra daily doses of cefalexin in ACHs for cystitis remains unknown. Cefalexin is an antibiotic recommended for many other indications including skin and soft tissue infections. As such, prescribers may habitually use recommendations for other indications when prescribing cefalexin for the treatment of cystitis. Alternatively, prescribers may confuse the higher number of doses recommended for pyelonephritis with the number suggested for cystitis, or some may believe extra daily doses are warranted in ACH residents. Access to other resources, use of older guidelines, or engrained habits, are likely to have contributed to nitrofurantoin being the second most commonly prescribed antibiotic for prophylaxis against UTIs. Nitrofurantoin was recommended in the 2006 printed version25 of the TG-Antibiotic for prophylaxis against UTIs, but this was removed prior to the 2010 printed version.26 MIMS Online19 contains information about nitrofurantoin use for UTI prophylaxis. Although uncommon, the use of nitrofurantoin for treatment of cystitis also occurs. Nitrofurantoin is recommended by infectious diseases associations in Britain, Europe, and the United States as first-line treatment for cystitis.20,21 Serious adverse events associated with long-term use of nitrofurantoin have been reported.6 Therefore, it is perplexing that
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nitrofurantoin was more commonly prescribed for prophylaxis than for treatment of cystitis (as longer term use is more likely to confer side effects). Of the prescriptions for antibiotics not recommended by the TGAntibiotic for treatment of cystitis, most (at least 27/44 prescriptions) were not directed by urine culture and pathogen susceptibilities. As a point-prevalence survey, the microbiology results would have been included in the data collection, if they were available on the day the survey was conducted. Thus microbiology results should have been known to the surveyors at the time the residents were receiving nonconcordant therapy in most cases. It raises questions about whether microbiology results are being communicated and responded to promptly and appropriately. The prescribing of quinolones (ciprofloxacin and norfloxacin) in Australian ACHs for UTIs is not widespread. The TG-Antibiotic recommends quinolones only be prescribed when infections are resistant to the other recommended antibiotics or when alternatives are not available.4 Prescribers in Australian ACHs generally appear to be adhering to this recommendation. Restrictions placed on quinolones by the Pharmaceutical Benefits Scheme (PBS) are likely to have contributed to the low use in Australian ACHs. Nonadherence to PBS restrictions has significant cost implications for end users. As these data were gathered and entered by the staff of the participating ACHs, issues regarding inter-rater reliability may exist. This was evident during data cleaning as 15 prescriptions for the IV antibiotic cefazolin from 2 ACHs were amended to cefalexin because of evidence the incorrect antibiotic had been entered. Further, the durations of therapy were calculated from the differences between the therapy start dates and survey dates, therefore, durations that exceeded the TG-Antibiotic recommendations were probably underestimated. Some prescriptions with longer than recommended durations were likely judged as concordant because they were surveyed within the timeframe recommended by the TG-Antibiotic. Means and ranges of the durations of antibiotic prophylaxis could not be calculated because prescriptions of greater than 6 months in duration were entered by surveyors as “>6 months.” Although AC NAPS is the most comprehensive survey of antibiotic prescribing in Australian ACHs, government-operated, inner-regional and major city facilities contributed proportionally more data to the survey than their actual representation in the Australian aged-care sector. CONCLUSIONS AMS activities targeting UTI prophylaxis for durations longer than 6 months and excessive daily doses of cefalexin to treat cystitis could yield significant reductions in unnecessary antibiotic prescribing among Australian ACH residents. References 1. Bennett NJ, Johnson SA, Richards MJ, Smith MA, Worth LJ. Infections in Australian aged-care facilities: evaluating the impact of revised McGeer criteria for surveillance of urinary tract infections. Infect Control Hosp Epidemiol 2016;37:610-2.
2. National Centre for Antimicrobial Stewardship and Australian Commission on Safety and Quality in Health Care (ACSQHC). Antimicrobial prescribing and infections in Australian residential aged care facilities: results of the 2015 Aged Care National Antimicrobial Prescribing Survey pilot. Sydney, NSW (Australia): ACSQHC; 2016. 3. National Centre for Antimicrobial Stewardship and Australian Commission on Safety and Quality in Health Care (ACSQHC). Aged Care National Antimicrobial Prescribing Survey 2016. Sydney (Australia): ACSQHC; 2017. 4. Therapeutic Guidelines Limited. Therapeutic guidelines: antibiotic. Version 15. North Melbourne, VIC (Australia): Therapeutic Guidelines Ltd; 2014. 5. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 2009;7:526-36. 6. Rego LL, Glazer CS, Zimmern PE. Risks of long-term use of nitrofurantoin for urinary tract prophylaxis in the older patient. Urol Sci 2016;27:193-8. 7. Medew J. New superbug cases at St Vincent's hospital and St George's health service in Kew. The age. Melbourne, VIC (Australia): Fairfax Media; 2016. 8. Tenover FC. Mechanisms of antimicrobial resistance in bacteria. Am J Med 2006;119:3-10. 9. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmidmediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 2016;16:161-8. 10. Lim CJ, Cheng AC, Kennon J, Spelman D, Hale D, Melican G, et al. Prevalence of multidrug-resistant organisms and risk factors for carriage in long-term care facilities: a nested case-control study. J Antimicrob Chemother 2014;69:1972-80. 11. van den Dool C, Haenen A, Tjalling L, Wallinga J. The role of nursing homes in the spread of antimicrobial resistance over the healthcare network. Infect Control Hosp Epidemiol 2016;37:761-7. 12. Australian Institute of Health and Welfare. GEN aged care data. Available from: www.gen-agedcaredata.gov.au. Accessed October 14, 2019. 13. Australian Commission on Safety and Quality in Health Care (ACSQHC). Safety and quality improvement guide standard 3: preventing and controlling healthcare associated infections. Sydney (Australia): ACSQHC; 2012. 14. Barlam TF, Cosgrove SE, Abbo LM, Macdougall C, Schuetz AN, Septimus EJ, et al. Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016;62:e51-77. 15. Australian Commission on Safety and Quality in Health Care (ACSQHC). AURA 2017: second Australian report on antimicrobial use and resistance in human health. Sydney (Australia): ACSQHC; 2017. 16. Therapeutic Guidelines Limited. Therapeutic Guidelines: Antibiotic. Version 12. North Melbourne, VIC (Australia): Therapeutic Guidelines Limited; 2003. 17. Daneman N, Gruneir A, Bronskill SE, Newman A, Fischer HD, Rochon PA, et al. Prolonged antibiotic treatment in long-term care role of the prescriber. JAMA Intern Med 2013;173:673-82. 18. Australian Medicines Handbook. AMH aged care companion. 2018. 19. MIMS Australia. MIMS online. 2018. 20. British Society for Antimicrobial Chemotherapy, British Infection Association, Royal College of General Practitioners, Royal College of Nursing. Management and treatment for common infections. Antibiotic guidance for primary care: for consultation and local adaption.2017. 21. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International Clinical Practice Guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e103-20. 22. Stuart RL, Marshall C, Orr E, Bennett N, Athan E, Friedman D, et al. Survey of infection control and antimicrobial stewardship practices in Australian residential aged-care facilities. Intern Med J 2015;45:576-80. 23. Australian Commission on Safety and Quality in Health Care (ACSQHC). Antimicrobial prescribing practice in Australia: results of the 2013 National Antimicrobial Prescribing Survey. Sydney (Australia): ACSQHC; 2014. 24. National Centre for Antimicrobial Stewardship and Australian Commission on Safety and Quality in Health Care (ACSQHC). Antimicrobial prescribing and infections in Australian aged care homes: results of the 2017 Aged Care National Antimicrobial Prescribing Survey. Sydney (Australia): ACSQHC; 2018. 25. Therapeutic Guidelines Limited. Therapeutic Guidelines: antibiotic. Version 13. North Melbourne, VIC (Australia): Therapeutic Guidelines Limited; 2006. 26. Therapeutic Guidelines Limited. Therapeutic Guidelines: antibiotic. Version 14. North Melbourne, VIC (Australia): Therapeutic Guidelines Limited; 2010.
Contents lists available at ScienceDirect
American Journal of Infection Control journal homepage: www.ajicjournal.org
Major Article
Urinary tract infections in Australian aged care homes: Antibiotic prescribing practices and concordance to national guidelines Leslie Dowson MBioethics a,b, Noleen Bennett RN, MPH, PhD a,c,d,*, Kirsty Buising MBBS, MPH, MD a,e,f, Caroline Marshall MBBS, PhD, Grad Dip Clin Epi a,e,f,g, N. Deborah Friedman MBBS, MPH, MD a,h,i, Rhonda L. Stuart MBBS, FRACP, PhD a,j,k, David C.M. Kong PhD a,b,l a
National Centre for Antimicrobial Stewardship at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia c Victorian Healthcare Associated Infection Surveillance System Coordinating Centre at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia d Department of Nursing, Melbourne School of Health Sciences, The University of Melbourne, Victoria, Australia e Victorian Infectious Diseases Service at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia f Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia g Infection Prevention and Surveillance Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia h School of Medicine, Deakin University, Geelong, Victoria, Australia i Department of General Medicine and Department of Infectious Diseases, Barwon Health, Geelong, Victoria, Australia j Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia k Monash Infectious Diseases and Infection Control and Epidemiology, Monash Health, Clayton, Victoria, Australia l Pharmacy Department, Ballarat Health Services, Ballarat, Victoria, Australia b
Key Words: Long-term care Nursing home Antibacterial agents Anti-infective agents Cystitis
Background: Since 2015 the Aged Care National Antimicrobial Prescribing Survey has collected and reported data on antibiotic use in Australian aged care homes (ACHs) as part of the Australian Commission on Safety and Quality in Health Care’s Antimicrobial Use and Resistance in Australia project. The objective of this study was to analyze this data source with regards to prescribing for urinary tract infections (UTIs) to improve the use of antibiotics. Methods: This cross-sectional study analyzed the 2016 and 2017 survey data. Antibiotic prescribing for urinary tract indications was compared with national guideline recommendations. Results: A total of 662 antibiotic prescriptions from 247 ACHs were analyzed. For all prophylactic antibiotics for UTI, 51.8% were prescribed for longer than 6 months, contrary to the guideline recommendation. Most antibiotics prescribed for treatment (71.6%) were for cystitis. Cefalexin was most frequently selected for treatment of cystitis, with 10.4% of these prescriptions being concordant with the recommendations. Prescribing additional daily doses of cefalexin occurred in 63.2% of prescriptions. Conclusions: Antimicrobial stewardship activities targeting UTI prophylaxis for durations longer than 6 months, and excessive daily doses of cefalexin to treat cystitis could yield significant reductions in unnecessary antibiotic consumption among Australian residents of ACHs. Crown Copyright © 2019 Published by Elsevier Inc. on behalf of Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.
*Address correspondence to Noleen Bennett, RN, MPH, PhD, VICNISS Coordinating Centre at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St, Melbourne, Victoria, Australia, 3000. E-mail address: [email protected] (N. Bennett). Funding/support: The Aged Care National Antimicrobial Prescribing Survey is a project collaboration between the National Centre for Antimicrobial Stewardship, the Guidance Group, and the Victorian Healthcare Associated Infection Surveillance System Coordinating Centre. Funding for the Aged Care National Antimicrobial Prescribing Survey is partly provided by the Australian Commission
on Safety and Quality in Health Care under the Antimicrobial Use and Resistance in Australia project. Leslie Dowson receives an Australian Government Research Training Program Scholarship. The National Centre for Antimicrobial Stewardship and its research are funded by the National Health and Medical Research Council of Australia (grant number APP1079625). Conflicts of interest: K.B. is a member of the writing group for the Therapeutic Guidelines: Antibiotic. D.C.M. Kong has sat on advisory boards for Becton Dickinson Pty Ltd and MSD, and received financial/travel support from MSD, all unrelated to this current study.
https://doi.org/10.1016/j.ajic.2019.08.034 0196-6553/Crown Copyright © 2019 Published by Elsevier Inc. on behalf of Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.
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The burden of urinary tract infections (UTIs) in residential aged care homes (ACHs) is significant.1 UTIs are a frequent indication for antibiotic prescribing.2,3 However, using antibiotics for UTIs can also harm ACH residents. Common antibiotic-related adverse events, such as nausea and diarrhea, and serious events, such as allergic reactions, pulmonary, neurological, or liver toxicity, can cause significant morbidity in ACH residents.4-6 Further, antibiotic use in ACHs is of public health concern7 because it increases selective pressure for the development of multidrug-resistant organisms (MDROs).8 MDROs are increasing in prevalence,9 and prior antibiotic use is associated with MDRO carriage in ACH residents.10 ACHs have been identified as reservoirs for MDROs and have the potential to both sustain and drive MDRO epidemics within health care networks.11 In most Australian ACHs, visiting general practitioners are primarily responsible for resident medical care and after-hours locum general practitioner visits are common. Australian ACHs are usually staffed with 1 registered nurse facility manager, and at least 1 registered nurse available for clinical resident care (depending on the size and structure of the ACH). Personal care assistants and enrolled nurses provide direct activities-of-daily-living support to residents. Residents of Australian ACHs typically require assistance with 1 or more activities-of-daily living or health care requirement. Most residents (86%) have at least 1 mental health or behavioral condition, and more than one-half (52%) have been diagnosed with dementia.12 Antimicrobial stewardship (AMS) is an ongoing effort by health care providers to optimize antimicrobial use.13 Recent guidelines for AMS in long-term care facilities, such as ACHs, support designing AMS activities for specific infections such as UTIs,14 but data on realworld prescribing practices are required to design effective AMS activities. Since 2015, the Aged Care National Antimicrobial Prescribing Survey (AC NAPS) has collected and reported data on antibiotic use in Australian ACHs as part of the Australian Commission on Safety and Quality in Health Care’s (ACSQHC’s) Antimicrobial Use and Resistance in Australia project.15 Analyzing these data in a meaningful manner may assist both prescribers and ACH residents. Expert guidance with regards to antibiotic therapy for UTIs in older adults has been updated in recent years as new evidence for optimal prescribing has become available. Since 2003, in Australia, changes include strengthening advice that treating asymptomatic bacteriuria is not recommended (except for people undergoing elective urological procedures and in pregnant women) and halving the recommended days of therapy for cystitis in men.4,16 Little is known about the concordance of antibiotic prescribing with these updates, and adherence to these recommendations could reduce unnecessary antibiotic use in ACHs.17 Many sources of guidance are available to antibiotic prescribers.4,1821 The Therapeutic Guidelines: Antibiotic4 (TG-Antibiotic) is developed for use in Australian clinical settings. Its recommendations are based on expert consensus, using the latest evidence for best practices.4 In environments such as ACHs without specialty infectious diseases clinicians22 and local antibiograms, the TG-Antibiotic guidelines are important because the advice is formulated with consideration of known local resistance data, patient safety, and thresholds for clinical antibiotic failure.4 During this study, the Australian Medicines Handbook Aged Care Companion (AMH)18 (another popular resource for Australian ACH prescribers) recommended antibiotic selections, doses, and frequencies for UTI prophylaxis and cystitis treatment that were concordant with the TG-Antibiotic recommendations, although the AMH’s duration recommendations were less definitive. In Australia, with support from the ACSQHC, the TG-Antibiotic recommendations are utilized to benchmark and identify potentially problematic antibiotic prescribing,23 which can then be addressed through AMS activities. This study was a cross-sectional in-depth interrogation of the 2016 and 2017 AC NAPS data to examine antibiotic prescribing patterns for UTIs in ACHs.
METHODS Data collection As part of the 2016 and 2017 AC NAPS, de-identified point prevalence data were collected from the medical records of ACH residents and entered into the online AC NAPS database by participating ACH nurses, pharmacists, or infection control nurse consultants (ie, surveyors). Numerous strategies were used to recruit ACHs to participate in the survey, including newsletters and direct communications from governmental organizations and professional societies. Participation by the ACHs was mostly voluntary. In 2017, the Victorian State Government mandated their public sector ACHs participate.24 Surveyors were provided with standardized instructions to complete the survey, and they had access to online, e-mail, and telephone support. Data about residents prescribed 1 or more antibiotics were included. Data were collected and entered during the official survey periods, between June 2016 and September 2016 and June 2017 and September 2017, on single days chosen by 339 participating ACHs. The 2015 pilot year data were excluded from this study. Data about antibiotic prescriptions ceased in the month prior to the survey date could be included by surveyors. Data collected included antibiotic selection, start date, dose, frequency, route of administration, and indication. Whether the indication was documented by the prescriber or had been assessed by the surveyor after reviewing the clinical notes of the residents was also recorded. For urinary tract indications, the surveyor could select asymptomatic bacteriuria, cystitis, catheterassociated UTI (CA-UTI), prostatitis, pyelonephritis, or other. The surveyors also indicated if the antibiotic was for prophylaxis against UTIs, if urine specimens were collected and analyzed (microbiologically and/or dipstick), and if the resident had a urinary catheter. Data analysis Data were analyzed using SPSS Statistics software for Windows, version 23 (IBM Corp, Armonk, NY) and Microsoft Excel 2013 for Windows (Microsoft Corporation, Redmond, WA). Frequencies and cross tabulations of antibiotic selections, doses and frequencies were computed from the dataset, and the percentages of concordant and nonconcordant prescriptions calculated after comparison to the TGAntibiotic recommendations that were current at the time of the 2016 and 2017 surveys, as summarized in Box 1. As methenamine hippurate is a urinary antiseptic and not strictly an antibiotic, 82 prescriptions for methenamine hippurate were excluded from the data analysis. Methenamine hippurate is not recommended by the TG-Antibiotic. To avoid oversampling of some ACH practices, for each ACH, data entered on only 1 day (the most recent day) during the official survey periods were analyzed. A sensitivity analysis comparing results between the corrected and uncorrected samples was conducted. Duration of therapy was calculated for current prescriptions from the difference between the prescription start date, and the survey date, where the start date was available. If the start date was not available or if the prescription had ceased, the prescription was excluded from the duration of therapy analysis. Duration was then assessed as less than, equal to, or greater than the TG-Antibiotic recommendation. This method is likely to overestimate concordant prescriptions. For prophylactic antibiotics, durations were assessed as less than, equal to, or greater than 6 months, in accordance with the TG-Antibiotic general recommendation.4 For treatment of cystitis, analysis of the associated microbiology data was undertaken for norfloxacin prescriptions (as the TG-Antibiotic recommends norfloxacin only when resistance to the other
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Box 1. Recommendations* from Therapeutic Guidelines: Antibiotic4 UTI prophylaxis in adults: 1. Trimethoprim 150mg orally at night, or 2. Cefalexin 250mg orally at night For 3-6 months or in some cases for longer periods. Cystitis in women: 1. Trimethoprim 300 mg orally, daily for 3 days; or 2. Cefalexin 500 mg orally, 12-hourly for 5 days; or *3. Amoxicillin + clavulanate 500 + 125 mg orally, 12-hourly for 5 days or *3. Nitrofurantoin 100 mg orally, 12-hourly for 5 days. If resistance to the other drugs are confirmed, then norfloxacin, 400 mg orally, 12-hourly for 3 days. Cystitis in men: 1. Trimethoprim 300 mg orally, daily for 7 days; or 2. Cefalexin 500 mg orally, 12-hourly for 7 days; or *3. Amoxicillin + clavulanate 500 + 125mg orally, 12-hourly for 7 days or *3. Nitrofurantoin 100 mg orally, 12-hourly for 7 days. If resistance to the other drugs are confirmed, then norfloxacin, 400 mg orally, 12-hourly for 7 days. *Numbers indicate preference by ranking, amoxicillin + clavulanate and nitrofurantoin had an equal ranking.
recommended agents is confirmed) and for all nonrecommended antibiotic agents selected by prescribers. An Infectious Diseases Consultant Physician (K.B.) evaluated the individual microbiology results and associated prescription data, and judged whether the antibiotic agents selected were directed by pathogen susceptibilities. This study was approved by Monash University’s Human Research Ethics Office, Project 15016. RESULTS During the study periods, 921 antibiotic prescriptions were attributed to UTIs across 251 Australian ACHs. A total of 259 prescriptions were excluded from the analyses because of ACHs entering data outside the official survey dates or entering data on more than 1 day (Fig 1). Four ACHs only contributed data outside the official survey periods, and 69 ACHs participated on more than 1 day. A total of 662 prescriptions from 247 ACHs were included in the final analyses (Fig 1). The sensitivity analysis comparing results between the corrected sample (662 prescriptions from 247 ACHs) and uncorrected sample (921 prescriptions from 251 ACHs) confirmed the prescribing trends reported in this study. The 247 ACHs contributing UTI prescribing data to these analyses had a mean size of 58.3 beds (range: 10-293) and of the 247 contributing ACHs 95 (38.5%) were from inner regional areas of Australia, 92 (37.2%) were from major cities of Australia, 48 (19.4%) were from outer regional areas of Australia, 9 (3.6%) were from remote areas of Australia, and 3 (1.2%) were from very remote areas of Australia. The majority of the 247 ACHs were government operated (55.1%, 137/247), followed by not-for-profit (36.0%, 89/247) and private incorporated (8.5%, 21/247). Descriptions of the total participating ACHs (including those that did not contribute UTI data) are available elsewhere.3,24 The residents for whom antibiotics were prescribed for UTIs were predominantly women (76.4%, 506/662) and had a mean age of 85 years (range: 49-102). The antibiotic was designated for prophylaxis in 38.4% (254/662) of prescriptions, and for 18.1% (120/662) of
3
prescriptions the UTI was not documented by the prescriber, but assessed by the surveyor from other clinical notes as being prescribed for UTI. A total of 18 different antibiotics were prescribed for UTI indications (Table 1). Prophylaxis For prophylaxis against UTIs, 254 prescriptions involving 11 different antibiotics were noted (Table 1). The antibiotic selection, dose, and frequency were concordant with the recommendations in the TG-Antibiotic, and the antibiotic was prescribed for less than 6 months in 16.5% (40/243) of prescriptions (11 prescriptions were removed from the analysis of duration of therapy owing to insufficient information). More than one-half of the prescriptions for prophylactic use (56.3%, 143/254) were for cefalexin, followed by nitrofurantoin (20.1%, 51/ 254), trimethoprim (13.4%, 35/254), trimethoprim-sulfamethoxazole (2.8%, 7/254), and gentamicin (2.0%, 5/254). For the TG-Antibiotic recommended antibiotics, cefalexin and trimethoprim, 57.6% (80/139) and 44.1% (15/34), respectively, were prescribed for longer than 6 months. For all antibiotics prescribed for UTI prophylaxis, 51.8% (126/243) were prescribed for longer than 6 months. Of the 5 total prescriptions for intramuscular prophylactic gentamicin, 3 of these were associated with the manipulation of a catheter, 1 was documented as “prophylaxis for a catheter-associated UTI” and 1 was documented for “prophylaxis of cystitis.” In total, 5 prescriptions (3 for gentamicin, 1 for cephalexin, and 1 for amoxicillin-clavulanate) were associated with the manipulation of a catheter, a practice which is not recommended.4 Treatment In total, 408 prescriptions of antibiotics were for treatment of UTIs. Of these, 382 were analyzed for concordance with the TGAntibiotic (after excluding the indication ‘Other’ [N = 26], which could not be compared with TG-Antibiotic recommendations) (Fig 1). For all treatment indications (cystitis, asymptomatic bacteriuria, CA-UTI, and pyelonephritis), the antibiotic selection, dose, frequency, and duration of treatment was concordant with the recommendations in the TG-Antibiotic in 22.3% (56/251) of prescriptions (131 prescriptions had insufficient data to calculate duration). Dipstick urinalysis was performed in 52.7% (215/408) of treatment prescriptions, and associated microbiological investigations were performed in 47.1% (192/408) of treatment prescriptions. Most of the prescriptions written for treatment of UTIs (71.6%, 292/408) were for cystitis. All antibiotics prescribed for asymptomatic bacteriuria were nonconcordant with the TG-Antibiotic. Further analysis of the antibiotics prescribed for prostatitis (N = 0), pyelonephritis (N = 12), and CA-UTI (N = 44) was not meaningful owing to low numbers of prescriptions. Treatment of cystitis Table 1 shows that 14 different antibiotic agents were prescribed for the treatment of cystitis. The most commonly prescribed was cefalexin (36.3%, 106/292), followed by trimethoprim (35.6%, 104/ 292). Antibiotic selection, dose, frequency, and duration was concordant with recommendations in the TG-Antibiotic for 23.6% (45/191) of prescriptions for cystitis (data were insufficient to calculate duration for 101 prescriptions). Fewer than 27% (26.4%, 28/106) of the prescriptions for cefalexin were concordant with the TG-Antibiotic’s recommendations for frequency of administration (Table 2). In 42.5% (45/106) of the prescriptions for cefalexin, 500 mg per dose was prescribed with 1 additional
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4
Fig 1. Summary of antibiotic prescriptions for UTIs identified in the 2016 and 2017 AC NAPS. AC NAPS, Aged Care National Antimicrobial Prescribing Survey; ACH, aged care home; UTIs, urinary tract infections.
daily administration (8-hourly, in contrast to the TG-Antibiotic’s recommended 12-hourly administration), and for a further 20.2% (22/ 106) 2 extra daily administrations (6 hourly) of 500 mg per dose
was prescribed. When all recommendations were factored into the analysis (ie, dose, frequency, and duration), only 10.4% (10/96) of the prescriptions for cefalexin for cystitis were concordant with the
Table 1 Frequencies of prescribed antibiotics Category
TG-Antibiotic Guidelines
%
Antibiotic
No.
% of Total prescriptions
Prophylaxis
Recommended
70.1
Not recommended
29.9
143 35 51 7 5 13
56.3 13.4 20.1 2.8 2.0 5.1
Recommended
84.9
Not recommended
15.1
Cefalexin Trimethoprim Nitrofurantoin Trimethoprim-sulfamethoxazole Gentamicin (IM) Others (6) Amoxicillin, Amoxicillin + Clavulanate, Cefalothin, Ciprofloxacin, Doxycycline, Norfloxacin Cefalexin Trimethoprim Amoxicillin + Clavulanate Nitrofurantoin Norfloxacin Amoxicillin Ciprofloxacin Ceftriaxone (IV or IM) Gentamicin (IV or IM) Other (5) Ampicillin, Cefalothin, Clarithromycin, Clindamycin, Trimethoprim-sulfamethoxazole
106 104 24 9 5 17 9 4 3 11
36.3 35.6 8.2 3.1 1.7 5.8 3.1 1.4 1.0 3.8
Cystitis treatment
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Table 2 Concordance for TG-Antibiotic recommended antibiotics: dose, frequency, and duration Concordance with TG-Antibiotic Dose*
Durationy
Frequency*
Dose, frequency, and durationy
Category
Antibiotic
Total
Duration calculation denominator
No.
%
No.
%
No.
%
No.
%
Prophylaxis
Cefalexin Trimethoprim Cefalexin Trimethoprim Amoxicillin + Clavulanate Nitrofurantoin Norfloxacin
143 35 106 104 24
139 34 96 89 23
119 17 91 103 8
83.2 48.6 85.8 99.0 33.3
126 34 28 104 24
88.1 97.1 26.4 100.0 100.0
45 16 47 30 13
31.5 47.0 49.0 33.7 56.5
34 6 10 30 5
24.5 17.6 10.4 33.7 21.7
9 5
8 4
3 3
33.3 60.0
2 2
22.2 40.0
3 1
33.3 20.0
0 0
0.0 0.0
Cystitis treatment
TG-Antibiotic, Therapeutic Guidelines: Antibiotic. *Denominator equals total number of prescriptions. y Denominator equals duration calculation denominator.
recommendations in the TG-Antibiotic (data were insufficient to calculate duration in 10 prescriptions). Less than 34% (30/89) of prescriptions for trimethoprim, for the treatment of cystitis, were concordant with the TG-Antibiotic recommended duration of treatment (ie, 3 days for women, 7 days for men). However, concordance with the TG-Antibiotic’s other recommendations (ie dose and frequency) were both high (99.0% [103/104] and 100.0% [104/104], respectively). Of the 5 prescriptions for norfloxacin, 4 had microbiology results. Microbiology results (ie, pathogen susceptibilities) directed therapy for 2 prescriptions. Microbiology results did not direct therapy for 1 prescription despite being available, and 1 microbiology result could not be analyzed owing to insufficient information. For antibiotic agents which were not recommended by the TGAntibiotic, 26 of 44 prescriptions had associated microbiology results. A total of 14 prescriptions were directed by pathogen susceptibilities. Microbiology results did not direct therapy, despite being available for 9 prescriptions, and 3 prescriptions with associated microbiology results could not be analyzed owing to insufficient information. Where duration of therapy data were available, the mean time between microbiology urine collection and the date of the survey was 7 days (range: 0-21 days). DISCUSSION UTIs in ACHs pose a significant burden to residents, and the associated antibiotic prescribing is important owing to the large numbers of residents affected. Prescribers in ACHs frequently do not prescribe antibiotics in accordance with national guideline recommendations in Australia (ie, TG-Antibiotic). This could be because the prescribers have difficulty with the advice (ie, do not agree or are unable to follow), have sought advice from other or older resources, and/or have developed a habit17 of prescribing without referring to a current reference. The prescribing of antibiotics for UTIs in ACHs warrants further investigation to determine what can be done to assist prescribers in adopting national guideline recommendations. This could include exploring the impact of displaying a summary of the recommendations for staff and prescribers in ACHs. The most common reason where the prescribing of antibiotics for UTI prophylaxis was nonconcordant with the TG-Antibiotic recommendations was that the duration of therapy exceeded 6 months. Although the TG-Antibiotic states in some cases longer durations may be warranted, 51.8% (126/243) of residents receiving prophylaxis against UTIs in the current study had been receiving antibiotics for more than 6 months. This suggests many residents are not reviewed and trialed without antibiotic prophylaxis as often as they should be. Further, the clinical appropriateness of initiating
prophylaxis as compared with the recommended guidelines cannot be assessed by AC NAPS data. Given the prevalence of antibiotic prescribing for prophylaxis of UTI in this study, a future study to assess concordance to the TG: Antibiotic recommendation that prophylaxis for UTI may be considered for frequent symptomatic infections (eg, 2 or more symptomatic UTIs in one 6 month period or 3 or more over a 12 month period) may be worthwhile.4 When antibiotic prophylaxis is considered, the risks, including acquisition of MDROs must be weighed against the symptoms from an occasional UTI. As the clinical situations of residents change, risk-benefit assessments of ongoing antibiotic prophylaxis for UTIs may change. Likewise, whereas trimethoprim for treatment of cystitis in this study was highly concordant with the TG-Antibiotic’s recommendations for dose and frequency, this fell notably when the duration of treatment was considered (Table 2). Advice on duration of trimethoprim treatment for cystitis varies amongst available resources. For example, a commonly used medicines database, MIMS Online19 (as of October 2018) recommends a 7-day duration for treatment without specifying for that women, it can be prescribed for shorter periods as per the TG-Antibiotic. In addition, fewer than 26.4% (28/106) of prescriptions for cefalexin for the treatment of cystitis were concordant with the TG-Antibiotic’s recommendation for administration frequency, and fewer than 11% (10/96) of prescriptions for cefalexin for cystitis treatment were concordant to the combined TG-Antibiotic recommendations (ie, dose, frequency and duration). The specific reasons for the observed common practice of prescribing extra daily doses of cefalexin in ACHs for cystitis remains unknown. Cefalexin is an antibiotic recommended for many other indications including skin and soft tissue infections. As such, prescribers may habitually use recommendations for other indications when prescribing cefalexin for the treatment of cystitis. Alternatively, prescribers may confuse the higher number of doses recommended for pyelonephritis with the number suggested for cystitis, or some may believe extra daily doses are warranted in ACH residents. Access to other resources, use of older guidelines, or engrained habits, are likely to have contributed to nitrofurantoin being the second most commonly prescribed antibiotic for prophylaxis against UTIs. Nitrofurantoin was recommended in the 2006 printed version25 of the TG-Antibiotic for prophylaxis against UTIs, but this was removed prior to the 2010 printed version.26 MIMS Online19 contains information about nitrofurantoin use for UTI prophylaxis. Although uncommon, the use of nitrofurantoin for treatment of cystitis also occurs. Nitrofurantoin is recommended by infectious diseases associations in Britain, Europe, and the United States as first-line treatment for cystitis.20,21 Serious adverse events associated with long-term use of nitrofurantoin have been reported.6 Therefore, it is perplexing that
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nitrofurantoin was more commonly prescribed for prophylaxis than for treatment of cystitis (as longer term use is more likely to confer side effects). Of the prescriptions for antibiotics not recommended by the TGAntibiotic for treatment of cystitis, most (at least 27/44 prescriptions) were not directed by urine culture and pathogen susceptibilities. As a point-prevalence survey, the microbiology results would have been included in the data collection, if they were available on the day the survey was conducted. Thus microbiology results should have been known to the surveyors at the time the residents were receiving nonconcordant therapy in most cases. It raises questions about whether microbiology results are being communicated and responded to promptly and appropriately. The prescribing of quinolones (ciprofloxacin and norfloxacin) in Australian ACHs for UTIs is not widespread. The TG-Antibiotic recommends quinolones only be prescribed when infections are resistant to the other recommended antibiotics or when alternatives are not available.4 Prescribers in Australian ACHs generally appear to be adhering to this recommendation. Restrictions placed on quinolones by the Pharmaceutical Benefits Scheme (PBS) are likely to have contributed to the low use in Australian ACHs. Nonadherence to PBS restrictions has significant cost implications for end users. As these data were gathered and entered by the staff of the participating ACHs, issues regarding inter-rater reliability may exist. This was evident during data cleaning as 15 prescriptions for the IV antibiotic cefazolin from 2 ACHs were amended to cefalexin because of evidence the incorrect antibiotic had been entered. Further, the durations of therapy were calculated from the differences between the therapy start dates and survey dates, therefore, durations that exceeded the TG-Antibiotic recommendations were probably underestimated. Some prescriptions with longer than recommended durations were likely judged as concordant because they were surveyed within the timeframe recommended by the TG-Antibiotic. Means and ranges of the durations of antibiotic prophylaxis could not be calculated because prescriptions of greater than 6 months in duration were entered by surveyors as “>6 months.” Although AC NAPS is the most comprehensive survey of antibiotic prescribing in Australian ACHs, government-operated, inner-regional and major city facilities contributed proportionally more data to the survey than their actual representation in the Australian aged-care sector. CONCLUSIONS AMS activities targeting UTI prophylaxis for durations longer than 6 months and excessive daily doses of cefalexin to treat cystitis could yield significant reductions in unnecessary antibiotic prescribing among Australian ACH residents. References 1. Bennett NJ, Johnson SA, Richards MJ, Smith MA, Worth LJ. Infections in Australian aged-care facilities: evaluating the impact of revised McGeer criteria for surveillance of urinary tract infections. Infect Control Hosp Epidemiol 2016;37:610-2.
2. National Centre for Antimicrobial Stewardship and Australian Commission on Safety and Quality in Health Care (ACSQHC). Antimicrobial prescribing and infections in Australian residential aged care facilities: results of the 2015 Aged Care National Antimicrobial Prescribing Survey pilot. Sydney, NSW (Australia): ACSQHC; 2016. 3. National Centre for Antimicrobial Stewardship and Australian Commission on Safety and Quality in Health Care (ACSQHC). Aged Care National Antimicrobial Prescribing Survey 2016. Sydney (Australia): ACSQHC; 2017. 4. Therapeutic Guidelines Limited. Therapeutic guidelines: antibiotic. Version 15. North Melbourne, VIC (Australia): Therapeutic Guidelines Ltd; 2014. 5. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 2009;7:526-36. 6. Rego LL, Glazer CS, Zimmern PE. Risks of long-term use of nitrofurantoin for urinary tract prophylaxis in the older patient. Urol Sci 2016;27:193-8. 7. Medew J. New superbug cases at St Vincent's hospital and St George's health service in Kew. The age. Melbourne, VIC (Australia): Fairfax Media; 2016. 8. Tenover FC. Mechanisms of antimicrobial resistance in bacteria. Am J Med 2006;119:3-10. 9. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmidmediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 2016;16:161-8. 10. Lim CJ, Cheng AC, Kennon J, Spelman D, Hale D, Melican G, et al. Prevalence of multidrug-resistant organisms and risk factors for carriage in long-term care facilities: a nested case-control study. J Antimicrob Chemother 2014;69:1972-80. 11. van den Dool C, Haenen A, Tjalling L, Wallinga J. The role of nursing homes in the spread of antimicrobial resistance over the healthcare network. Infect Control Hosp Epidemiol 2016;37:761-7. 12. Australian Institute of Health and Welfare. GEN aged care data. Available from: www.gen-agedcaredata.gov.au. Accessed October 14, 2019. 13. Australian Commission on Safety and Quality in Health Care (ACSQHC). Safety and quality improvement guide standard 3: preventing and controlling healthcare associated infections. Sydney (Australia): ACSQHC; 2012. 14. Barlam TF, Cosgrove SE, Abbo LM, Macdougall C, Schuetz AN, Septimus EJ, et al. Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016;62:e51-77. 15. Australian Commission on Safety and Quality in Health Care (ACSQHC). AURA 2017: second Australian report on antimicrobial use and resistance in human health. Sydney (Australia): ACSQHC; 2017. 16. Therapeutic Guidelines Limited. Therapeutic Guidelines: Antibiotic. Version 12. North Melbourne, VIC (Australia): Therapeutic Guidelines Limited; 2003. 17. Daneman N, Gruneir A, Bronskill SE, Newman A, Fischer HD, Rochon PA, et al. Prolonged antibiotic treatment in long-term care role of the prescriber. JAMA Intern Med 2013;173:673-82. 18. Australian Medicines Handbook. AMH aged care companion. 2018. 19. MIMS Australia. MIMS online. 2018. 20. British Society for Antimicrobial Chemotherapy, British Infection Association, Royal College of General Practitioners, Royal College of Nursing. Management and treatment for common infections. Antibiotic guidance for primary care: for consultation and local adaption.2017. 21. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International Clinical Practice Guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e103-20. 22. Stuart RL, Marshall C, Orr E, Bennett N, Athan E, Friedman D, et al. Survey of infection control and antimicrobial stewardship practices in Australian residential aged-care facilities. Intern Med J 2015;45:576-80. 23. Australian Commission on Safety and Quality in Health Care (ACSQHC). Antimicrobial prescribing practice in Australia: results of the 2013 National Antimicrobial Prescribing Survey. Sydney (Australia): ACSQHC; 2014. 24. National Centre for Antimicrobial Stewardship and Australian Commission on Safety and Quality in Health Care (ACSQHC). Antimicrobial prescribing and infections in Australian aged care homes: results of the 2017 Aged Care National Antimicrobial Prescribing Survey. Sydney (Australia): ACSQHC; 2018. 25. Therapeutic Guidelines Limited. Therapeutic Guidelines: antibiotic. Version 13. North Melbourne, VIC (Australia): Therapeutic Guidelines Limited; 2006. 26. Therapeutic Guidelines Limited. Therapeutic Guidelines: antibiotic. Version 14. North Melbourne, VIC (Australia): Therapeutic Guidelines Limited; 2010.