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Antimicrobial use in Hungarian long-term care facilities: High proportion of quinolone antibacterials
Archives of Gerontology and Geriatrics 59 (2014) 190–193
Contents lists available at ScienceDirect
Archives of Gerontology and Geriatrics journal homepage: www.elsevier.com/locate/archger
Antimicrobial use in Hungarian long-term care facilities: High proportion of quinolone antibacterials Rita Szabo´ *, Karolina Bo¨ro¨cz 1 National Centre for Epidemiology, Department of Hospital Epidemiology, Albert Flo´ria´n u´t 2-6, H-1097 Budapest, Hungary
A R T I C L E I N F O
A B S T R A C T
Article history: Received 2 January 2014 Received in revised form 25 February 2014 Accepted 28 February 2014 Available online 13 March 2014
The aim of this survey was to estimate the burden of antimicrobial use and to describe the determinants for antimicrobial use in Hungarian long-term care facilities (LTCFs) in order to increase the attention given to the proper prescription for this vulnerable population. A one-day point-prevalence study was undertaken between April and May 2013. Data on resident treated with an antibacterial, antimycotic or tuberculostatic for systemic use were collected prospectively on a single day in each participating LTCF with over 50 beds. Descriptive statistics were used to present the data. 91 LTCFs with 11,823 residents participated in this survey. 156 residents (1.3%) were given antimicrobials. 96.8% of antimicrobials were mostly prescribed for therapy included urinary tract infections (40.3%), respiratory tract infections (38.4%) and skin and soft tissue infections (13.2%). The most common therapeutic antimicrobials (97.5%) belonged to the ATC J01 class of ‘antibacterials for systemic use’. The most important J01 subclasses were J01M quinolone antibacterials (32.7%), J01C beta-lactam antibacterials (25.2%), J01D other beta-lactam antibacterials (11.3%) and J01F macrolides, lincosamides and streptogramins (11.3%). Antimicrobials were mostly prescribed empirically whereas 3.8% was microbiologically documented treatments. 3.2% of all prescribed antimicrobials were prescribed for the prophylaxis of urinary tract infections (60%) and ear, nose, mouth infections (40%). Our results emphasize the need of a national recommendation for good practice in LTCFs in order to avoid inappropriate antimicrobial therapy leading to spread of multidrug resistant pathogens. In addition, continuing education of prescribers on antimicrobial treatment is essential. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Point-prevalence survey Antimicrobial use Elderly residents Long-term care facilities
1. Introduction Elderly residents of long-term care facilities (LTCFs) are at high risk for acquirement of infections due to their increased susceptibility (e.g. immonusenesence, functional disability, chronic diseases, the use of invasive devices) and institutional factors (e.g. close proximity, low priority of infection prevention and control measures). Because of infections, residents are frequently treated with antimicrobial agents, which are leading to the emergence of antimicrobial resistant pathogens (e.g. methicillinresistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp.) (Bronzwaer et al., 2002; Van Buul et al., 2012). Several studies have been published with regard to excess use of antimicrobials and resistance in LTCFs, nevertheless there is only
* Corresponding author. Tel.: +36 061 476 1106. E-mail addresses: [email protected], [email protected] (R. Szabo´). 1 Tel.: +36 061 476 1106. http://dx.doi.org/10.1016/j.archger.2014.02.011 0167-4943/ß 2014 Elsevier Ireland Ltd. All rights reserved.
a limited knowledge about the prescription of antibacterial agents in European LTCFs. Therefore, the European Centre for Disease Prevention and Control (ECDC) implemented the methodology of two EU-funded projects, the ‘Improving Patient Safety in Europe’ survey on the status of infection control and surveillance programs in LTCFs (IPSE, 2006–2008) and the ‘European Surveillance of Antimicrobial Consumption – Nursing Homes subproject’ survey on antimicrobial use in nursing homes (ESAC-NH, 2008–2010) and funded the HALT project (Healthcare Associated Infections in LTCFs) in 2008. The purposes of HALT project were to get crosscountry comparable data on infections, antimicrobial use and infection control practices in European LTCFs. After a pilot survey in 2009, the European-wide point prevalence survey was performed in 2010, including 25 countries with 722 LTCFs (including 42 Hungarian LTCFs) (Suetens, 2012). In 2013, a repeated survey (HALT-2) was set up including 19 countries with 1.182 LTCFs. This article presents the Hungarian results of the HALT-2 survey, focusing on antimicrobial use in participating LTCFs.
R. Szabo´, K. Bo¨ro¨cz / Archives of Gerontology and Geriatrics 59 (2014) 190–193
2. Materials and methods The HALT-2 survey was conducted between April and May 2013. In Hungary, all registered LTCFs (e.g. general nursing care, residential care, psychiatric care) with 50 beds and over (in total, 420 LTCFs; 24% of all Hungarian LTCFs) were invited to participate voluntary and anonym in this survey. Participating LTCFs were asked to choose one single day during the survey period to collect all necessary data prospectively. Within the participating LTCF, a resident was considered eligible for the survey if (1) she/he lived permanently in the LTCF, (2) had resided there for at least one day and (3) was present at 8 AM on the day of the survey. According to the protocol, data were collected at LTCF and resident level (for the latter, including infection and antimicrobial use data if any) on standardized data collection forms (paper-based questionnaires). The LTCF questionnaire collected data on structural and functional characteristics of LTCF (e.g. demographics, predisposing factors of all eligible residents as denominator data, infection control practices). For each eligible resident who showed a sign/symptom of an infection and/or treated with an antibacterial agent on the day of the survey, a resident questionnaire was completed. In respect of antimicrobial use, the Anatomical Therapeutic Chemical (ATC) classification system of the World Health Organization Collaborating Centre for Drug Statistics Methodology was used to classify the substances used. Data on all oral, rectal, intramuscular, intravenous or by inhalation administered treatments with antibacterials (ATC class J01), antimycotics (J02) and tuberculostatics (J04) for systemic use were collected. Antivirals for systemic use, antimicrobials for topical use and antiseptics were not included. This form also included questions on resident demographics included demographic data, antimicrobial name, administration route, type of treatment (prophylactic or therapeutic), indication for antimicrobial use (the site of diagnosis for treatment intention of an infection), place and person of prescription, isolated microorganisms and selected antimicrobial resistance data (oxacillin-sensitive/resistant Staphylococcus aureus, glycopeptides-sensitive/resistant Enterococcus species, 3rd generation cephalosporin and carbapenem-sensitive/resistant Enterobacteriaceae, carbapenem-sensitive/resistant Pseudomonas aeruginosa, carbapenem-sensitive/resistant Acinetobacter baumannii). Because of it was important that surveyors record all necessary data perfectly on resident questionnaire to allow prevalence to be precisely estimated, training of LTCF staff was considered a priority throughout the preparation of the survey. Prior to the survey period, six, one-day national training courses were given by the national coordinating center (National Center for Epidemiology, NCE) to familiarize LTCD surveyors with the methodology and the data collection. Standardized training curriculum and material was provided in English by the ECDC. Completed questionnaires were sent to the NCE by each LTCF. After data cleaning, these data were inputted into a software program. An electronic copy of data from each LTCF was emailed securely to the ECDC EU-wide database without residentidentifying data. All LTCF were sent a national and an institutional summary report generated by the software program. The objectives of this study also were to assess the validity of collected data collected by LTCFs. Thus, a data validation study was performed in one LTCF with over 100 beds per country. A trained external surveyor (NCE staff) had to visit the randomly selected LTCF on the same day as the point prevalence survey and conduct a parallel blinded data collection. The survey did not entail any direct contact with the residents therefore ethical approval was not important. Confidentiality of
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data was assured by the use of a unique study number for each participating LTCFs and eligible residents allotted by the national coordinating center. 3. Results A total of 91 LTCFs with 11 823 eligible residents participated in the survey. During the survey period, 156 residents (mean prevalence: 1.3%; range: 0–6.4%) were receiving one or more antimicrobial agents on the day of the survey. Among residents receiving antimicrobial, 61.6% were female and 25.8% were over 85 years. The most frequent risk factors were the impaired mobility (63.5%), followed by incontinence (61.6%) and disorientation (35.8%). Antimicrobials were mostly used for therapeutic purposes (96.8%). The most frequent indication for antimicrobial use was the treatment of urinary tract infections (40.3%), respiratory tract infections (38.4%) and skin and soft tissue infections (13.2%). The most common therapeutic antimicrobial agent (97.5%) belonged to the ATC J01 class of ‘antibacterials for systemic use’. The most important J01 subclasses were J01M quinolone antibacterials (32.7%), J01C beta-lactam antibacterials (25.2%), J01D other betalactam antibacterials (11.3%) and J01F macrolides, lincosamides and streptogramins (11.3%). The most often empirically prescribed antibacterials for urinary tract infections were quinolone antibacterials (64%), followed by sulfonamides and trimethoprim (15.6%) and beta-lactam antibacterials (7.8%). The most commonly prescribed empirically treatments for respiratory tract infections were beta-lactam antibacterials (40.9%), followed by other beta-lactam antibacterials (21.3%) and macrolides, lincosamides and streptogramins (14.8%). The most common antibacterials prescribed for therapy of skin and soft tissue infections were beta-lactam antibacterials (47.4%), followed by macrolides, lincosamides and streptogramins (26.3%) and tetracyclines (10.5%). The distribution of antimicrobial agents for infections is presented in Table 1. Therapeutic antimicrobials were mostly prescribed empirically whereas 3.8% was microbiologically documented treatments. 3 positive microbiology results were available for gastrointestinal infection (Clostridium difficile), 2 for urinary tract infection (Enterobacter cloacae, Escherichia coli) and one for other infection (S. aureus). During the survey, no resistant strains were found. A total of 3.2% of all prescribed antimicrobial agents was used for the prevention of urinary tract infections (60%) and ear, nose, mouth infections (40%). Elements of antimicrobial policy (e.g. availability of an antimicrobial committee, regular training on appropriate antimicrobial prescribing, restrictive list of antimicrobials, local data on antimicrobial resistant pathogens, written therapeutic guidelines) were available in 82 LTCFs (90.2%). 4. Discussion In the last decade, several European and overseas countries set up programs to increase awareness for the problem of infections and antimicrobial use in their LTCFs. The aim of the HALT-2 project was to collect comparable data on infections and use of antimicrobial agents among elderly residents in European LTCFs. In Hungary, the collected national data allowed for the estimation of the prevalence of antimicrobial use in participating LTCFs. The prevalence of antimicrobial use among participating LTCFs was lower (1.3%) compared with results from other European and overseas surveys (6–15%), that is the overuse of antimicrobials is not common in participating LTCFs (Blix, Bergman, & Schjott, 2010; Cotter, Donlon, Roche, Byrne, & Fitzpatrick, 2012; Eikelenboom-Boskamp et al., 2011; Pakyz & Dwyer, 2010).
R. Szabo´, K. Bo¨ro¨cz / Archives of Gerontology and Geriatrics 59 (2014) 190–193
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Table 1 Distribution of antimicrobial agents for therapeutic purposes by type of infections among residents in Hungarian long-term care facilities, April–May 2013. Class of antimicrobial
Total of infections (n, %)
UTIa (n)
RTIb (n)
SSTc (n)
GId (n)
EENe (n)
BSIf (n)
Unexplained fever (n)
Other (n)
Tetracyclines (J01A) Amphenicols (J01B) Beta-lactam antibacterials, penicillins (J01C) Other beta-lactam antibacterials (J01D) Sulfonamides and trimethoprim (J01E) Macrolides, lincosamides and streptogramins (J01F) Aminoglycoside antimicrobials (J01G) Quinolone antibacterials (J01M) Combinations of antimicrobials (J01R) Other antimicrobials (J01X) Antifungals (D01 and J02)
8 – 40 18 12 18
(5.1%)
– – 5 3 10 2
6 – 25 13 1 9
2 – 9 1 – 5
– – – – – –
– – 1 1 – 1
– – – – – –
– – – – – –
– – – – 1 1
3 52 – 3 2
(1.9%) (33.3%)
1 41 – 2 –
1 6 – – –
1 1 – – 2
– 1 – 1
– – – – –
– – – – –
– 2 – – –
– 1 – – –
a b c d e f
(25.6%) (11.5%) (7.7%) (11.5%)
(1.9%) (1.3%)
Urinary tract infection. Respiratory tract infection. Skin and soft tissue infection. Gastrointestinal infection. Eye, ear, nose and mouth infection. Bloodstream infection.
Urinary tract infection is the most frequently reported indication for antimicrobial prescribing (40.3%). Several studies have reported similar results, accounting for 32–66% of the antimicrobial prescriptions in LTCFs. However, it was noted that all episodes of urinary tract infections led to routine prescribing of antimicrobials without further diagnostic investigation to confirm bacterial etiology (Blix et al., 2010; Petterson, Vernby, Moltstad, & Lundborg, 2008). Similar to several overseas studies, quinolones (32.7%) were the most commonly prescribed antimicrobial agents for infections in Hungarian LTCFs (Kyne et al., 1999; Loeb et al., 2003; Maslow, Lautenbach, Glaze, Bilker, & Johnson, 2004; McClean, Hughes, Tunney, Goossens, & Jans, 2011; Pakyz & Dwyer, 2010; Petterson et al., 2008; Viray et al., 2005). Based on literature, antibiotic exposure, especially use of clindamycin, quinolones and cephalosporines, is an important risk factor for C. difficile infections (Deshpandel et al., 2013; Marwick et al., 2013; Wilcox et al., 2008). Moreover, excessive use of quinolones has been associated with the emergence of C. difficile ribotype 027 in healthcare settings, including LTCFs (Deshpandel et al., 2013). In addition, several studies have reported that more than 50% of isolates recovered from LTCF residents are resistant to quinolone antibacterials (Maslow et al., 2004; Viray et al., 2005). Among eligible residents receiving antibacterial agent for treatment of an infection (96.8%), only 3.8% of prescriptions were based microbiologically results which can result inappropriate, unvalidated antimicrobial prescriptions. In comparison with the results from Norwegian and Dutch surveys (5.8% and 6.6%), our culture sampling rate was low, probably due to the fact that microbiological diagnostic tests were not commonly requested by the physicians in the elderly care in Hungary (Andersen & Rasch, 2000; Eikelenboom-Boskamp et al., 2011; Eriksen, Iversen, & Aavitsland, 2004). Our survey had some limitations. Firstly, the representativeness of the survey sample was less than optimal because LTCFs participated on a voluntary basis (convenient sample). Different types of LTCFs exist across Europe and one definition cannot capture the whole concept of long-term care service. Moreover, not all countries were able to provide exact national numbers of LTCFs. Thus, representativeness was not required. Secondary, the number of residents who received antibacterial agents was too small to generate reliable national estimate. The low prevalence of antibacterial use is unlikely to reflect the true prevalence in Hungarian LTCFs, but is probably due to underreporting as a
consequence of limited microbiological diagnostic tests requested by the physicians working in the LTCFs. Therefore, these data must be interpreted with caution. However, these limitations may be improved in future surveys by increasing the number of participating LTCFs and enhanced training of LTCF staff. Despite the limitations, the HALT-2 project was the largest point-prevalence survey performed to date which was a great opportunity to collected valuable information of antimicrobial use in Hungarian LTCFs. In addition, this project took an important step in improving surveillance skills in LTCFs. This skill is beneficial for LTCF staff in arming themselves against the threat of antimicrobial resistance. Moreover, this survey should also raise awareness for intensifying antimicrobial resistance. 5. Conclusions Our results highlight the requirement for antimicrobial stewardship programs, treatment algorithms and the presence of a multidisciplinary antibiotic committee specifically for LTCFs (Fleming, Browne, & Byrne, 2013; Forsetlund et al., 2009; Nicolle, 2014). Our survey identified an important area for targeted improvement of antimicrobial use including: reducing the use of quinolone antibacterials in order to prevent the spread of C. difficile and other antimicrobial resistant pathogens among residents of LTCFs. Moreover, comprehensive interventions, including continuing training sessions (diagnosis, management, prevention and in particular treatment of urinary tract infection) in small groups and regular feedback about prescribing patterns for prescribers are needed in order to elaborate recommendations for good practice for institutionalized elders and change prescribing behavior which leading to appropriate antimicrobial therapy (Fleming et al., 2013; Forsetlund et al., 2009; Ivers et al., 2012). For additional research, we consider it necessary to also take in consideration other factors (e.g. knowledge, attitude and perception of prescribers) in order to explore which efforts help to prevent inappropriate antimicrobial use. Furthermore, other detailed information on the cost of antimicrobial use is needed to prepare the national policies. Authors’ contributions All authors generated the datasets, participated in the statistical analysis and contributed to the manuscript. All authors read and agreed with the final manuscript.
R. Szabo´, K. Bo¨ro¨cz / Archives of Gerontology and Geriatrics 59 (2014) 190–193
Funding The HALT project was funded and supported by European Centre for Disease Prevention and Control (ECDC): ECDC/2011/023. Conflict of interest statement The authors declare no conflicts of interest. Acknowledgements The authors thank all participating LTCFs and their surveyors who attended the training sessions and complete the questionnaires. We also thank our colleagues (Andrea Kurcz MD, A´gnes Hajdu MD, Ida Prantner MD, Andrasne´ Szo˝ nyi, Istva´n Veress and Emı´lia Su¨veges) their professional support. Without whom this survey would not have been possible. References Andersen, B. M., & Rasch, M. (2000). Hospital-acquired infections in Norwegian longterm care institutions. A three-year survey of hospital-acquired infections and antibiotic treatment in nursing/residential homes, including 4500 residents in Oslo. Journal of Hospital Infection, 46, 288–296. Blix, H. S., Bergman, J., & Schjott, J. (2010). How are antibacterials used in nursing homes? Results from a point-prevalence prescription study in 44 Norwegian nursing homes. Pharmacoepidemiology and Drug Safety, 19(10), 1025–1030. Bronzwaer, S. L., Cars, O., Buchholz, U., Mo¨lstad, S., Goettsch, W., Veldhuijzen, I. K., et al. (2002). A European study on the relationship between antimicrobial use and antimicrobial resistance. Emerging Infectious Diseases, 8, 278–282. Cotter, M., Donlon, S., Roche, F., Byrne, H., & Fitzpatrick, F. (2012). Healthcare-associated infection in Irish long-term care facilities: Results from the First National Prevalence Study. Journal of Hospital Infection, 80, 212–216. Deshpandel, A., Pasupuleti, V., Thota, P., Pant, C., Rolston, D. D., Sferra, T. J., et al. (2013). Community-associated Clostridium difficile infection and antibiotics: A meta-analysis. Journal of Antimicrobial Chemotherapy http://dx.doi.org/10.1093/jac/dkt129. European Centre for Disease Prevention and Control (ECDC). (2009–2010). The HALT project. How to perform a successful HALT Point Prevalence Survey (PPS)? HALT_PPS2 Stockholm: ECDC. Available from: http://halt.wiv-isp.be/manual/Study%20documents%20PPS2/Forms/AllItems.aspx. Eikelenboom-Boskamp, A., Cox-Claessens, J. H., Boom-Poels, P. G., Drabbe, M. I., Koopmans, R. T., Voss, A., et al. (2011). Three-year prevalence of healthcare-associated infections in Dutch nursing homes. Journal of Hospital Infection, 78, 59–62. Eriksen, H. M., Iversen, B. G., & Aavitsland, P. (2004). Prevalence of nosocomial infections and use of antibiotics in long-term care facilities in Norway, 2002 and 2003. Journal of Hospital Infection, 57, 316–320.
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Fleming, A., Browne, J., & Byrne, S. (2013). The effect of interventions to reduce potentially inappropriate antibiotic prescribing in long-term care facilities: A systematic review of randomised controlled trials. Drugs and Aging, 30, 401–408. Forsetlund, L., Bjordal, A., Rashidian, A., Jamtvedt, G., O’Brien, M. A., Wolf, F., et al. (2009). Continuing education meetings and workshops: Effects on professional practice and health care outcomes. Cochrane Database Systematic Reviews (Online), 2, CD003030. Ivers, N., Jamtvedt, G., Flottorp, S., Young, J. M., Odgaard-Jensen, J., French, S. D., et al. (2012). Audit and feedback: Effects on professional practice and healthcare outcomes. Cochrane Database Systematic Reviews (Online), 6, CD000259. Kyne, L., Merry, C., O’Connell, B., Kelly, A., Keane, C., O’Neill, D., et al. (1999). Factors associated with prolonged symptom and severe diseases due to Clostridium difficile. Age and Ageing, 28(2), 107–113. Loeb, M. B., Craven, S., McGeer, A. J., Simor, A. E., Bradley, S. F., Low, D. E., et al. (2003). Risk factors for resistance to antimicrobial agents among nursing homes residents. American Journal of Epidemiology, 157, 40–47. Marwick, C. A., Yu, N., Lockhart, M. C., McGuigan, C. C., Wiuff, C., Davey, P. G., et al. (2013). Community-associated Clostridium difficile infection among older people in Tayside, Scotland, is associated with antibiotic exposure and care home residence: Cohort study with nested case–control. Journal of Antimicrobial Chemotherapy http://dx.doi.org/10.1093/jac/dkt257. Maslow, J. N., Lautenbach, E., Glaze, T., Bilker, W., & Johnson, J. R. (2004). Colonization with extraintestinal pathogenic Escherichia coli among nursing home residents and its relationship to fluoroquinolone resistance. Infection Control of Hospital Epidemiology, 48(9), 3618–3620. McClean, P., Hughes, C., Tunney, M., Goossens, H., & Jans, B. European Surveillance of Antimicrobial Consumption (ESAC) Nursing Home Project Group. (2011). Antimicrobial prescribing in European nursing homes. Journal of Antimicrobial Chemotherapy, 66, 1609–1616. Nicolle, L. E. (2014). Antimicrobial stewardship in long term care facilities: What is effective? Antimicrobial Resistance and Infection Control, 3, 6. Pakyz, A. L., & Dwyer, L. L. (2010). Prevalence of antimicrobial use among united states nursing home residents: Results from a National Survey. Infection Control of Hospital Epidemiology, 31(6), 661–662. Petterson, E., Vernby, A., Moltstad, S., & Lundborg, C. S. (2008). Infections and antibiotic prescribing in Swedish nursing homes: A cross-sectional study. Scandinavian Journal of Infectious Diseases, 40, 393–398. Suetens, C. (2012). Healthcare-associated infections in European long-term care facilities: How big is the challenge? Eurosurveillance17(35). pii=20259. Van Buul, L. W., Van der Steen, J. T., Veenhuizen, R. B., Achterberg, W. P., Schellevis, F. G., Essink, R. T., et al. (2012). Antibiotic use and resistance in long term care facilities. Journal of American Medical Directors Association13(6). 568.e1-568.e13. Viray, M., Linkin, D., Maslow, J. N., Stieritz, D. D., Carson, L. S., Bilker, W. B., et al. (2005). Longitudinal trends in antimicrobial susceptibilities across long-term care facilities: Emergence of fluoroquinolone resistance. Infection Control of Hospital Epidemiology, 26(1), 56–62. WHO Collaborating Centre for Drug Statistics Methodology. (2013). Guidelines for ATC classification and DDD assignment. Oslo, 2012. Available from: http:// www.whocc.no/atc_ddd_index. Wilcox, M. H., Mooney, L., Bendall, R., Settle, C. D., Fawley, W. N., et al. (2008). A case– control study of community-associated Clostridium difficile infection. Journal of Antimicrobial Chemotherapy, 62, 388–396.
Contents lists available at ScienceDirect
Archives of Gerontology and Geriatrics journal homepage: www.elsevier.com/locate/archger
Antimicrobial use in Hungarian long-term care facilities: High proportion of quinolone antibacterials Rita Szabo´ *, Karolina Bo¨ro¨cz 1 National Centre for Epidemiology, Department of Hospital Epidemiology, Albert Flo´ria´n u´t 2-6, H-1097 Budapest, Hungary
A R T I C L E I N F O
A B S T R A C T
Article history: Received 2 January 2014 Received in revised form 25 February 2014 Accepted 28 February 2014 Available online 13 March 2014
The aim of this survey was to estimate the burden of antimicrobial use and to describe the determinants for antimicrobial use in Hungarian long-term care facilities (LTCFs) in order to increase the attention given to the proper prescription for this vulnerable population. A one-day point-prevalence study was undertaken between April and May 2013. Data on resident treated with an antibacterial, antimycotic or tuberculostatic for systemic use were collected prospectively on a single day in each participating LTCF with over 50 beds. Descriptive statistics were used to present the data. 91 LTCFs with 11,823 residents participated in this survey. 156 residents (1.3%) were given antimicrobials. 96.8% of antimicrobials were mostly prescribed for therapy included urinary tract infections (40.3%), respiratory tract infections (38.4%) and skin and soft tissue infections (13.2%). The most common therapeutic antimicrobials (97.5%) belonged to the ATC J01 class of ‘antibacterials for systemic use’. The most important J01 subclasses were J01M quinolone antibacterials (32.7%), J01C beta-lactam antibacterials (25.2%), J01D other beta-lactam antibacterials (11.3%) and J01F macrolides, lincosamides and streptogramins (11.3%). Antimicrobials were mostly prescribed empirically whereas 3.8% was microbiologically documented treatments. 3.2% of all prescribed antimicrobials were prescribed for the prophylaxis of urinary tract infections (60%) and ear, nose, mouth infections (40%). Our results emphasize the need of a national recommendation for good practice in LTCFs in order to avoid inappropriate antimicrobial therapy leading to spread of multidrug resistant pathogens. In addition, continuing education of prescribers on antimicrobial treatment is essential. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Point-prevalence survey Antimicrobial use Elderly residents Long-term care facilities
1. Introduction Elderly residents of long-term care facilities (LTCFs) are at high risk for acquirement of infections due to their increased susceptibility (e.g. immonusenesence, functional disability, chronic diseases, the use of invasive devices) and institutional factors (e.g. close proximity, low priority of infection prevention and control measures). Because of infections, residents are frequently treated with antimicrobial agents, which are leading to the emergence of antimicrobial resistant pathogens (e.g. methicillinresistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp.) (Bronzwaer et al., 2002; Van Buul et al., 2012). Several studies have been published with regard to excess use of antimicrobials and resistance in LTCFs, nevertheless there is only
* Corresponding author. Tel.: +36 061 476 1106. E-mail addresses: [email protected], [email protected] (R. Szabo´). 1 Tel.: +36 061 476 1106. http://dx.doi.org/10.1016/j.archger.2014.02.011 0167-4943/ß 2014 Elsevier Ireland Ltd. All rights reserved.
a limited knowledge about the prescription of antibacterial agents in European LTCFs. Therefore, the European Centre for Disease Prevention and Control (ECDC) implemented the methodology of two EU-funded projects, the ‘Improving Patient Safety in Europe’ survey on the status of infection control and surveillance programs in LTCFs (IPSE, 2006–2008) and the ‘European Surveillance of Antimicrobial Consumption – Nursing Homes subproject’ survey on antimicrobial use in nursing homes (ESAC-NH, 2008–2010) and funded the HALT project (Healthcare Associated Infections in LTCFs) in 2008. The purposes of HALT project were to get crosscountry comparable data on infections, antimicrobial use and infection control practices in European LTCFs. After a pilot survey in 2009, the European-wide point prevalence survey was performed in 2010, including 25 countries with 722 LTCFs (including 42 Hungarian LTCFs) (Suetens, 2012). In 2013, a repeated survey (HALT-2) was set up including 19 countries with 1.182 LTCFs. This article presents the Hungarian results of the HALT-2 survey, focusing on antimicrobial use in participating LTCFs.
R. Szabo´, K. Bo¨ro¨cz / Archives of Gerontology and Geriatrics 59 (2014) 190–193
2. Materials and methods The HALT-2 survey was conducted between April and May 2013. In Hungary, all registered LTCFs (e.g. general nursing care, residential care, psychiatric care) with 50 beds and over (in total, 420 LTCFs; 24% of all Hungarian LTCFs) were invited to participate voluntary and anonym in this survey. Participating LTCFs were asked to choose one single day during the survey period to collect all necessary data prospectively. Within the participating LTCF, a resident was considered eligible for the survey if (1) she/he lived permanently in the LTCF, (2) had resided there for at least one day and (3) was present at 8 AM on the day of the survey. According to the protocol, data were collected at LTCF and resident level (for the latter, including infection and antimicrobial use data if any) on standardized data collection forms (paper-based questionnaires). The LTCF questionnaire collected data on structural and functional characteristics of LTCF (e.g. demographics, predisposing factors of all eligible residents as denominator data, infection control practices). For each eligible resident who showed a sign/symptom of an infection and/or treated with an antibacterial agent on the day of the survey, a resident questionnaire was completed. In respect of antimicrobial use, the Anatomical Therapeutic Chemical (ATC) classification system of the World Health Organization Collaborating Centre for Drug Statistics Methodology was used to classify the substances used. Data on all oral, rectal, intramuscular, intravenous or by inhalation administered treatments with antibacterials (ATC class J01), antimycotics (J02) and tuberculostatics (J04) for systemic use were collected. Antivirals for systemic use, antimicrobials for topical use and antiseptics were not included. This form also included questions on resident demographics included demographic data, antimicrobial name, administration route, type of treatment (prophylactic or therapeutic), indication for antimicrobial use (the site of diagnosis for treatment intention of an infection), place and person of prescription, isolated microorganisms and selected antimicrobial resistance data (oxacillin-sensitive/resistant Staphylococcus aureus, glycopeptides-sensitive/resistant Enterococcus species, 3rd generation cephalosporin and carbapenem-sensitive/resistant Enterobacteriaceae, carbapenem-sensitive/resistant Pseudomonas aeruginosa, carbapenem-sensitive/resistant Acinetobacter baumannii). Because of it was important that surveyors record all necessary data perfectly on resident questionnaire to allow prevalence to be precisely estimated, training of LTCF staff was considered a priority throughout the preparation of the survey. Prior to the survey period, six, one-day national training courses were given by the national coordinating center (National Center for Epidemiology, NCE) to familiarize LTCD surveyors with the methodology and the data collection. Standardized training curriculum and material was provided in English by the ECDC. Completed questionnaires were sent to the NCE by each LTCF. After data cleaning, these data were inputted into a software program. An electronic copy of data from each LTCF was emailed securely to the ECDC EU-wide database without residentidentifying data. All LTCF were sent a national and an institutional summary report generated by the software program. The objectives of this study also were to assess the validity of collected data collected by LTCFs. Thus, a data validation study was performed in one LTCF with over 100 beds per country. A trained external surveyor (NCE staff) had to visit the randomly selected LTCF on the same day as the point prevalence survey and conduct a parallel blinded data collection. The survey did not entail any direct contact with the residents therefore ethical approval was not important. Confidentiality of
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data was assured by the use of a unique study number for each participating LTCFs and eligible residents allotted by the national coordinating center. 3. Results A total of 91 LTCFs with 11 823 eligible residents participated in the survey. During the survey period, 156 residents (mean prevalence: 1.3%; range: 0–6.4%) were receiving one or more antimicrobial agents on the day of the survey. Among residents receiving antimicrobial, 61.6% were female and 25.8% were over 85 years. The most frequent risk factors were the impaired mobility (63.5%), followed by incontinence (61.6%) and disorientation (35.8%). Antimicrobials were mostly used for therapeutic purposes (96.8%). The most frequent indication for antimicrobial use was the treatment of urinary tract infections (40.3%), respiratory tract infections (38.4%) and skin and soft tissue infections (13.2%). The most common therapeutic antimicrobial agent (97.5%) belonged to the ATC J01 class of ‘antibacterials for systemic use’. The most important J01 subclasses were J01M quinolone antibacterials (32.7%), J01C beta-lactam antibacterials (25.2%), J01D other betalactam antibacterials (11.3%) and J01F macrolides, lincosamides and streptogramins (11.3%). The most often empirically prescribed antibacterials for urinary tract infections were quinolone antibacterials (64%), followed by sulfonamides and trimethoprim (15.6%) and beta-lactam antibacterials (7.8%). The most commonly prescribed empirically treatments for respiratory tract infections were beta-lactam antibacterials (40.9%), followed by other beta-lactam antibacterials (21.3%) and macrolides, lincosamides and streptogramins (14.8%). The most common antibacterials prescribed for therapy of skin and soft tissue infections were beta-lactam antibacterials (47.4%), followed by macrolides, lincosamides and streptogramins (26.3%) and tetracyclines (10.5%). The distribution of antimicrobial agents for infections is presented in Table 1. Therapeutic antimicrobials were mostly prescribed empirically whereas 3.8% was microbiologically documented treatments. 3 positive microbiology results were available for gastrointestinal infection (Clostridium difficile), 2 for urinary tract infection (Enterobacter cloacae, Escherichia coli) and one for other infection (S. aureus). During the survey, no resistant strains were found. A total of 3.2% of all prescribed antimicrobial agents was used for the prevention of urinary tract infections (60%) and ear, nose, mouth infections (40%). Elements of antimicrobial policy (e.g. availability of an antimicrobial committee, regular training on appropriate antimicrobial prescribing, restrictive list of antimicrobials, local data on antimicrobial resistant pathogens, written therapeutic guidelines) were available in 82 LTCFs (90.2%). 4. Discussion In the last decade, several European and overseas countries set up programs to increase awareness for the problem of infections and antimicrobial use in their LTCFs. The aim of the HALT-2 project was to collect comparable data on infections and use of antimicrobial agents among elderly residents in European LTCFs. In Hungary, the collected national data allowed for the estimation of the prevalence of antimicrobial use in participating LTCFs. The prevalence of antimicrobial use among participating LTCFs was lower (1.3%) compared with results from other European and overseas surveys (6–15%), that is the overuse of antimicrobials is not common in participating LTCFs (Blix, Bergman, & Schjott, 2010; Cotter, Donlon, Roche, Byrne, & Fitzpatrick, 2012; Eikelenboom-Boskamp et al., 2011; Pakyz & Dwyer, 2010).
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Table 1 Distribution of antimicrobial agents for therapeutic purposes by type of infections among residents in Hungarian long-term care facilities, April–May 2013. Class of antimicrobial
Total of infections (n, %)
UTIa (n)
RTIb (n)
SSTc (n)
GId (n)
EENe (n)
BSIf (n)
Unexplained fever (n)
Other (n)
Tetracyclines (J01A) Amphenicols (J01B) Beta-lactam antibacterials, penicillins (J01C) Other beta-lactam antibacterials (J01D) Sulfonamides and trimethoprim (J01E) Macrolides, lincosamides and streptogramins (J01F) Aminoglycoside antimicrobials (J01G) Quinolone antibacterials (J01M) Combinations of antimicrobials (J01R) Other antimicrobials (J01X) Antifungals (D01 and J02)
8 – 40 18 12 18
(5.1%)
– – 5 3 10 2
6 – 25 13 1 9
2 – 9 1 – 5
– – – – – –
– – 1 1 – 1
– – – – – –
– – – – – –
– – – – 1 1
3 52 – 3 2
(1.9%) (33.3%)
1 41 – 2 –
1 6 – – –
1 1 – – 2
– 1 – 1
– – – – –
– – – – –
– 2 – – –
– 1 – – –
a b c d e f
(25.6%) (11.5%) (7.7%) (11.5%)
(1.9%) (1.3%)
Urinary tract infection. Respiratory tract infection. Skin and soft tissue infection. Gastrointestinal infection. Eye, ear, nose and mouth infection. Bloodstream infection.
Urinary tract infection is the most frequently reported indication for antimicrobial prescribing (40.3%). Several studies have reported similar results, accounting for 32–66% of the antimicrobial prescriptions in LTCFs. However, it was noted that all episodes of urinary tract infections led to routine prescribing of antimicrobials without further diagnostic investigation to confirm bacterial etiology (Blix et al., 2010; Petterson, Vernby, Moltstad, & Lundborg, 2008). Similar to several overseas studies, quinolones (32.7%) were the most commonly prescribed antimicrobial agents for infections in Hungarian LTCFs (Kyne et al., 1999; Loeb et al., 2003; Maslow, Lautenbach, Glaze, Bilker, & Johnson, 2004; McClean, Hughes, Tunney, Goossens, & Jans, 2011; Pakyz & Dwyer, 2010; Petterson et al., 2008; Viray et al., 2005). Based on literature, antibiotic exposure, especially use of clindamycin, quinolones and cephalosporines, is an important risk factor for C. difficile infections (Deshpandel et al., 2013; Marwick et al., 2013; Wilcox et al., 2008). Moreover, excessive use of quinolones has been associated with the emergence of C. difficile ribotype 027 in healthcare settings, including LTCFs (Deshpandel et al., 2013). In addition, several studies have reported that more than 50% of isolates recovered from LTCF residents are resistant to quinolone antibacterials (Maslow et al., 2004; Viray et al., 2005). Among eligible residents receiving antibacterial agent for treatment of an infection (96.8%), only 3.8% of prescriptions were based microbiologically results which can result inappropriate, unvalidated antimicrobial prescriptions. In comparison with the results from Norwegian and Dutch surveys (5.8% and 6.6%), our culture sampling rate was low, probably due to the fact that microbiological diagnostic tests were not commonly requested by the physicians in the elderly care in Hungary (Andersen & Rasch, 2000; Eikelenboom-Boskamp et al., 2011; Eriksen, Iversen, & Aavitsland, 2004). Our survey had some limitations. Firstly, the representativeness of the survey sample was less than optimal because LTCFs participated on a voluntary basis (convenient sample). Different types of LTCFs exist across Europe and one definition cannot capture the whole concept of long-term care service. Moreover, not all countries were able to provide exact national numbers of LTCFs. Thus, representativeness was not required. Secondary, the number of residents who received antibacterial agents was too small to generate reliable national estimate. The low prevalence of antibacterial use is unlikely to reflect the true prevalence in Hungarian LTCFs, but is probably due to underreporting as a
consequence of limited microbiological diagnostic tests requested by the physicians working in the LTCFs. Therefore, these data must be interpreted with caution. However, these limitations may be improved in future surveys by increasing the number of participating LTCFs and enhanced training of LTCF staff. Despite the limitations, the HALT-2 project was the largest point-prevalence survey performed to date which was a great opportunity to collected valuable information of antimicrobial use in Hungarian LTCFs. In addition, this project took an important step in improving surveillance skills in LTCFs. This skill is beneficial for LTCF staff in arming themselves against the threat of antimicrobial resistance. Moreover, this survey should also raise awareness for intensifying antimicrobial resistance. 5. Conclusions Our results highlight the requirement for antimicrobial stewardship programs, treatment algorithms and the presence of a multidisciplinary antibiotic committee specifically for LTCFs (Fleming, Browne, & Byrne, 2013; Forsetlund et al., 2009; Nicolle, 2014). Our survey identified an important area for targeted improvement of antimicrobial use including: reducing the use of quinolone antibacterials in order to prevent the spread of C. difficile and other antimicrobial resistant pathogens among residents of LTCFs. Moreover, comprehensive interventions, including continuing training sessions (diagnosis, management, prevention and in particular treatment of urinary tract infection) in small groups and regular feedback about prescribing patterns for prescribers are needed in order to elaborate recommendations for good practice for institutionalized elders and change prescribing behavior which leading to appropriate antimicrobial therapy (Fleming et al., 2013; Forsetlund et al., 2009; Ivers et al., 2012). For additional research, we consider it necessary to also take in consideration other factors (e.g. knowledge, attitude and perception of prescribers) in order to explore which efforts help to prevent inappropriate antimicrobial use. Furthermore, other detailed information on the cost of antimicrobial use is needed to prepare the national policies. Authors’ contributions All authors generated the datasets, participated in the statistical analysis and contributed to the manuscript. All authors read and agreed with the final manuscript.
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Funding The HALT project was funded and supported by European Centre for Disease Prevention and Control (ECDC): ECDC/2011/023. Conflict of interest statement The authors declare no conflicts of interest. Acknowledgements The authors thank all participating LTCFs and their surveyors who attended the training sessions and complete the questionnaires. We also thank our colleagues (Andrea Kurcz MD, A´gnes Hajdu MD, Ida Prantner MD, Andrasne´ Szo˝ nyi, Istva´n Veress and Emı´lia Su¨veges) their professional support. Without whom this survey would not have been possible. References Andersen, B. M., & Rasch, M. (2000). Hospital-acquired infections in Norwegian longterm care institutions. A three-year survey of hospital-acquired infections and antibiotic treatment in nursing/residential homes, including 4500 residents in Oslo. Journal of Hospital Infection, 46, 288–296. Blix, H. S., Bergman, J., & Schjott, J. (2010). How are antibacterials used in nursing homes? Results from a point-prevalence prescription study in 44 Norwegian nursing homes. Pharmacoepidemiology and Drug Safety, 19(10), 1025–1030. Bronzwaer, S. L., Cars, O., Buchholz, U., Mo¨lstad, S., Goettsch, W., Veldhuijzen, I. K., et al. (2002). A European study on the relationship between antimicrobial use and antimicrobial resistance. Emerging Infectious Diseases, 8, 278–282. Cotter, M., Donlon, S., Roche, F., Byrne, H., & Fitzpatrick, F. (2012). Healthcare-associated infection in Irish long-term care facilities: Results from the First National Prevalence Study. Journal of Hospital Infection, 80, 212–216. Deshpandel, A., Pasupuleti, V., Thota, P., Pant, C., Rolston, D. D., Sferra, T. J., et al. (2013). Community-associated Clostridium difficile infection and antibiotics: A meta-analysis. Journal of Antimicrobial Chemotherapy http://dx.doi.org/10.1093/jac/dkt129. European Centre for Disease Prevention and Control (ECDC). (2009–2010). The HALT project. How to perform a successful HALT Point Prevalence Survey (PPS)? HALT_PPS2 Stockholm: ECDC. Available from: http://halt.wiv-isp.be/manual/Study%20documents%20PPS2/Forms/AllItems.aspx. Eikelenboom-Boskamp, A., Cox-Claessens, J. H., Boom-Poels, P. G., Drabbe, M. I., Koopmans, R. T., Voss, A., et al. (2011). Three-year prevalence of healthcare-associated infections in Dutch nursing homes. Journal of Hospital Infection, 78, 59–62. Eriksen, H. M., Iversen, B. G., & Aavitsland, P. (2004). Prevalence of nosocomial infections and use of antibiotics in long-term care facilities in Norway, 2002 and 2003. Journal of Hospital Infection, 57, 316–320.
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