A trend in prevalence of antimicrobial use and appropriateness of antimicrobial therapy in an acute care hospital from 2018 to 2019: repeated prevalence surveys in Japan
BMC Research Notes volume 12, Article number: 811 (2019)
The supply of cefazolin has been reduced dramatically since March 2019 in Japan. However, no studies have evaluated the effects of cefazolin shortage on the appropriateness of antimicrobial use. Therefore, we compared the appropriateness of inpatient antimicrobial drug use between the two surveys conducted in August 2018 and August 2019 in a Japanese hospital with no supply of cefazolin since the cefazolin shortage.
In the 2019 survey, a total of 275 patients were included, and 256 patients were included in the 2018 survey. The prevalence of antimicrobial drug use did not change from 2018 to 2019 (28.5% versus 28.7%; p = 0.96). The proportion of cefazolin in all antimicrobial drugs used on the survey date significantly decreased from 2018 to 2019 (24.1% versus 0.0%; p < 0.001). The proportion of appropriate antimicrobial use in all antimicrobial therapies tended to be lower in 2019 than in 2018 (41.2% versus 60.6%; p = 0.06), and the proportion of unnecessary use of a broader spectrum of antimicrobial drugs significantly increased from 2018 to 2019 (4.7% versus 37.3%; p = 0.002). The shortage of cefazolin might lead to inappropriate use of other antimicrobial drugs.
Antimicrobial resistance is a major threat to public health. Infection caused by antimicrobial-resistant bacteria is associated with a poor prognosis and a higher cost burden [1, 2]. One strategy to reduce antimicrobial-resistant bacteria is to improve the appropriateness of antimicrobial drug use . In an inpatient setting, the prevalence of antimicrobial drug use is 30–50% [4,5,6,7,8,9,10,11,12,13,14]. However, approximately one-third of their use is considered unnecessary or inappropriate [12, 15,16,17,18,19,20,21].
In Japan, the supply of several antimicrobial drugs, such as ampicillin–sulbactam , has decreased for several reasons since 2018. The supply of cefazolin to Japanese hospitals has also been reduced dramatically because Nichi-Iko Pharmaceutical Co., which covered approximately 60% of the domestic market share of cefazolin in Japan, stopped production of cefazolin due to contaminated ingredients since March 2019 [23,24,25]. Therefore, for the Japanese hospitals that depended only on Nichi-Iko Pharmaceutical Co. for cefazolin, their supply has stopped completely . Given that cefazolin is one of most frequently used parenteral antimicrobial drugs in Japan , no supply of cefazolin can dramatically change inpatient antimicrobial use. Moreover, given that the spectrum activity of cefazolin was the narrowest in the top five consumptive parenteral antimicrobial drugs in Japan , a shortage of cefazolin may cause the excess use of antimicrobial drugs that have unnecessarily broader spectrum activity. However, no studies have been conducted to evaluate the appropriateness of antimicrobial therapy in Japan since March 2019. Therefore, we conducted a point prevalence survey to investigate the appropriateness of antimicrobial therapy in a Japanese hospital with no supply of cefazolin since March 2019 and compared this outcome with those of the survey conducted in August 2018 .
Study design and setting
The National Hospital Organization Tochigi Medical Center is a 350-bed community acute care hospital located in Utsunomiya, Japan. In our hospital, the supply of cefazolin has been suspended completely since March 2019. Since the beginning of 2019, an antibiotic restriction policy for cefazolin has been applied in our hospital. Point prevalence surveys were conducted twice on 6 August 2018 and on 22 August 2019. The results of the former survey were already reported in a previous article . Our hospital had an antimicrobial stewardship team composed of physicians, nurses, pharmacists, and laboratory technicians before the time of these surveys. For each survey, all hospitalized patients at 8:00 A.M. on the survey day were included. No patients were excluded. This study was prospectively registered at the University Hospital Medical Information Network clinical registry (No. UMIN000037720).
Data collection and outcome measures
Data were collected in a manner similar to a previous study . Physicians retrieved information on patient age, sex, and past medical history using electronic medical records. Information on the devices in place was collected by infection control nurses during the morning of the survey day. Regarding antimicrobial drugs, drug prescription data from electronic medical records were used. Based on past studies [4, 14], a patient was considered to receive an antimicrobial drug if the patient was prescribed or planned to be prescribed any antimicrobial drug on the survey date or the calendar day before the survey date. Antimicrobial drugs were classified based on the World Health Organization Anatomical Therapeutic Chemical classification. Drugs used to treat HIV or viral hepatitis and topical antimicrobial drugs were excluded. Like the previous study , the reasons for use of each antimicrobial drug were abstracted from the electronic medical records and classified into the following five categories: treatment of infection, surgical prophylaxis, medical prophylaxis, a noninfection-related reason, or unknown reason.
The primary outcome was the proportion of antimicrobial drugs that were judged to be appropriately used in all antimicrobial therapies. The appropriateness of antimicrobial therapy was assessed by members of the antimicrobial stewardship teams based on the results of microbial tests at the time of the survey, antibiograms of our hospital, and the Infectious Diseases Society of America Practical Guidelines . The following five points were evaluated for the appropriateness of antimicrobial drugs for infection treatment: (1) indication of the antimicrobial therapy, (2) dose or timing of the antimicrobial drug, (3) duration of the antimicrobial drug use, (4) choice of the antimicrobial drug, and (5) spectrum activity of the antimicrobial drug. Antimicrobial drugs used for infection treatment were judged to be appropriate if the use of antimicrobial drugs was appropriate for all five points. The detailed methods to investigate these outcomes were described in a recent article . The secondary outcomes were the proportion of patients who were received antimicrobial drugs and the proportion of cefazolin among all antimicrobial drugs. These outcomes were compared with those of the survey performed in 2018 .
The study population was described by using descriptive statistics. Fisher’s exact test was used to compare the primary and secondary outcome between the 2018 survey  and the 2019 survey. The Stata version 15 (LightStone, Tokyo, Japan) was used for these analyses, and the level of significance was set at 5%.
In the present survey, a total of 275 hospitalized patients were included, while 256 patients were included in the previous survey. In the present survey, the median patient age was 76 years (IQR 65 to 85), 138 (50.2%) were women, and 23 (8.4%) were immunosuppressive drug users (Table 1). The baseline characteristics of the patients in the present survey were similar to those in the previous survey.
In the present survey, a total of 87 antimicrobial drugs were given to 79 patients (Table 2). The prevalence of any antimicrobial drug use was 28.7% (95% confidence interval (CI) 23.4% to 34.1%). The proportion of patients who received any antimicrobial drugs did not change from the previous survey to the present survey (28.5% versus 28.7%; odds ratio (OR) 0.99, 95% CI 0.68 to 1.44). Ceftriaxone accounted for more than one-fourth of all antimicrobial drugs used in the present survey. The proportion of ceftriaxone in all antimicrobial drugs significantly increased from the former survey to the present survey (13.9% versus 28.7%; OR 0.40, 95% CI 0.18 to 0.88). The proportion of cefazolin in all antimicrobial drugs was 0.0%, although cefazolin was most the frequently used antimicrobial drug in the previous survey.
Of the 87 antimicrobial drugs used in the present survey, 51 (58.6%) and 33 (37.9%) were used for treatment and surgical prophylaxis, respectively (see Additional file 1). Of the 51 antimicrobial drugs used for treatment in the present survey, 21 (41.2%) were judged as appropriate antibiotic use (Table 3). The proportion of appropriate antimicrobial drug use in all antimicrobial therapy tended to be lower in the present survey than in the former survey (41.2% versus 60.6%; OR 2.18, 95% CI 0.96 to 5.00). The most common reason for the inappropriateness of antimicrobial therapy was an unnecessary prescription of a broader spectrum of antimicrobial drugs. The proportion of antimicrobial drugs that were judged to be inappropriately used for their spectrum activity significantly increased in the present survey from the previous survey (37.3% versus 4.7%; OR 10.93, 95% CI 2.33 to 51.19).
The present study found that the prevalence of antimicrobial drug use in hospitalized patients did not change from the 2018 survey to the 2019 survey in a Japanese hospital with no supply of cefazolin since its shortage. The prevalence of antimicrobial drug use in the present survey is similar to those of European studies [6, 7, 9, 15] and recent Japanese studies [5, 13, 14] reporting that approximately one-third of hospitalized patients were receiving antimicrobial drugs. However, the proportion of ceftriaxone in all antimicrobial drugs used for hospitalized patients significantly increased from the 2018 survey to the 2019 survey, while cefazolin, which was most frequently used in the 2018 survey , was not used at all in the 2019 survey. In past studies investigating the trend of inpatient antimicrobial use [28,29,30], no studies reported a considerable change in an individual antimicrobial drug within a year similar to our study. A shortage of cefazolin since the beginning of 2019 in Japan is assumed to have increased the use of ceftriaxone as an alternative to cefazolin for hospitalized patients. However, whether the shortage of cefazolin was truly a major cause of the increased use of ceftriaxone is uncertain because causality between the two events cannot be proven by our study design. Further studies to investigate the change in antimicrobial drug use before and after the cefazolin shortage in other Japanese hospitals with or without supply of cefazolin are needed.
The present survey found that approximately three-fifths of antimicrobial therapies were judged to be inappropriate in a Japanese hospital with no supply of cefazolin since the beginning of 2019. Moreover, the appropriateness of inpatient antimicrobial therapy in the present survey tended to be worse than that of the previous survey , although it did not reach statistical significance. Given that unnecessary prescription of a broader spectrum of antimicrobial drugs significantly increased from the previous survey to the present survey, unnecessary prescription of a broader spectrum of antimicrobial drugs is presumed to be a major cause for the decline in the proportion of appropriate antimicrobial therapy from August 2018 to August 2019. The proportion of inappropriate antimicrobial therapy reported in the present survey was higher than that of past point prevalence surveys conducted since 2000 [6, 12, 14, 15, 18, 19, 31]. Given that some past similar studies did not evaluate the appropriateness for the spectrum activity of antimicrobial therapy [6, 12, 15, 18], the difference in methods used to evaluate the appropriateness of antimicrobial therapy might affect our findings. In fact, a recent retrospective study  investigating the appropriateness of antimicrobial therapy for uncomplicated cellulitis also reported that the proportion of inappropriate broad spectrum antimicrobial drug use was high, as in our study.
The cause of the decline in the appropriateness of inpatient antimicrobial therapy in the present study is uncertain. One repeated prevalence survey to evaluate the appropriateness of inpatient antimicrobial drug use also reported a considerable change in the appropriateness of antimicrobial therapy within a year in some surveyed hospitals . Given that cefazolin was the antimicrobial drug used frequently and appropriately for treatment in the 2018 survey  and that cefazolin was not used at all in the 2019 survey, our findings implicate that a shortage of cefazolin since the beginning of 2019 may worsen the appropriateness of inpatient antimicrobial therapy in a Japanese hospital with no supply of cefazolin. Nonetheless, our study did not evaluate the change in the appropriateness of antimicrobial therapy before and after a shortage of cefazolin in Japanese hospitals that were not affected by a cefazolin shortage. Moreover, many confounding factors that could affect outcomes cannot be excluded because our study design was a longitudinal cross-sectional study. Thus, further multicenter studies to investigate the change in appropriateness of antimicrobial therapy before and after a cefazolin shortage in Japanese hospitals with or without supply of cefazolin are needed.
The prevalence of inappropriate antimicrobial therapy was high and tended to increase from August 2018 to August 2019 in a Japanese hospital with no supply of cefazolin since March 2019. The shortage of cefazolin might lead to inappropriate use of other antimicrobial drugs.
First, our study was a single center study. Therefore, our results cannot be generalized to other Japanese hospitals. Second, this was not a randomized controlled design. Moreover, our study had no control groups. Therefore, the association between the shortage of cefazolin and inappropriate use of antimicrobial drugs with a broader spectrum in the present study should be interpreted cautiously.
Availability of data and materials
All data generated or analyzed during this study are included in this published article and its additional file.
Cosgrove SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis. 2006;42(Suppl 2):S82–9.
Lode HM. Clinical impact of antibiotic-resistant gram-positive pathogens. Clin Microbiol Infect. 2009;15:212–7.
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.
Magill SS, Edwards JR, Beldavs ZG, Dumyati G, Janelle SJ, Kainer MA, et al. Prevalence of antimicrobial use in US acute care hospitals, May–September 2011. JAMA. 2014;312:1438–46.
Morioka H, Hirabayashi A, Iguchi M, Tomita Y, Kato D, Sato N, et al. The first point prevalence survey of health care-associated infection and antimicrobial use in a Japanese university hospital: a pilot study. Am J Infect Control. 2016;44:e119–23.
Zarb P, Amadeo B, Muller A, Drapier N, Vankerckhoven V, Davey P, et al. Identification of targets for quality improvement in antimicrobial prescribing: the web-based ESAC point prevalence survey 2009. J Antimicrob Chemother. 2011;66:443–9.
Ansari F, Erntell M, Goossens H, Davey P. The European surveillance of antimicrobial consumption (ESAC) point-prevalence survey of antibacterial use in 20 European hospitals in 2006. Clin Infect Dis. 2009;49:1496–504.
Cai Y, Venkatachalam I, Tee NW, Tan TY, Kurup A, Wong SY, et al. Prevalence of healthcare-associated infections and antimicrobial use among adult inpatients in Singapore acute-care hospitals: results from the first national point prevalence survey. Clin Infect Dis. 2017;64:S61–7.
Robert J, Pean Y, Varon E, Bru JP, Bedos JP, Bertrand X, et al. Point prevalence survey of antibiotic use in French hospitals in 2009. J Antimicrob Chemother. 2012;67:1020–6.
Ren N, Zhou P, Wen X, Li C, Huang X, Guo Y, et al. Point prevalence survey of antimicrobial use in Chinese hospitals in 2012. Am J Infect Control. 2016;44:332–9.
Xie DS, Xiang LL, Li R, Hu Q, Luo QQ, Xiong W. A multicenter point-prevalence survey of antibiotic use in 13 Chinese hospitals. J Infect Public Health. 2015;8:55–61.
Thu TA, Rahman M, Coffin S, Harun-Or-Rashid M, Sakamoto J, Hung NV. Antibiotic use in Vietnamese hospitals: a multicenter point-prevalence study. Am J Infect Control. 2012;40:840–4.
Morioka H, Nagao M, Yoshihara S, Ohge H, Kasahara K, Shigemoto N, et al. The first multi-centre point-prevalence survey in four Japanese university hospitals. J Hosp Infect. 2018;99:325–31.
Komagamine J, Yabuki T, Kobayashi M, Okabe T. Prevalence of antimicrobial use and active healthcare-associated infections in acute care hospitals: a multicentre prevalence survey in Japan. BMJ Open. 2019;9:e027604.
Willemsen I, van der Kooij T, van Benthem B, Wille J, Kluytmans J. Appropriateness of antimicrobial therapy: a multicentre prevalence survey in the Netherlands, 2008–2009. Euro Surveill. 2010;15:19715.
Kunin CM, Tupasi T, Craig WA. Use of antibiotics. A brief exposition of the problem and some tentative solutions. Ann Intern Med. 1973;79:555–60.
Hecker MT, Aron DC, Patel NP, Lehmann MK, Donskey CJ. Unnecessary use of antimicrobials in hospitalized patients: current patterns of misuse with an emphasis on the antianaerobic spectrum of activity. Arch Intern Med. 2003;163:972–8.
Willemsen I, Groenhuijzen A, Bogaers D, Stuurman A, van Keulen P, Kluytmans J. Appropriateness of antimicrobial therapy measured by repeated prevalence surveys. Antimicrob Agents Chemother. 2007;51:864–7.
Cotta MO, Robertson MS, Upjohn LM, Marshall C, Liew D, Buising KL. Using periodic point-prevalence surveys to assess appropriateness of antimicrobial prescribing in Australian private hospitals. Intern Med J. 2014;44:240–6.
Scheckler WE, Bennett JV. Antibiotic usage in seven community hospitals. JAMA. 1970;213:264–7.
Castle M, Wilfert CM, Cate TR, Osterhout S. Antibiotic use at Duke university medical center. JAMA. 1977;237:2819–22.
The Japanese Respiratory Society. Supply of ampicillin-sulbactam [in Japanese]. The Japanese Respiratory Society. https://www.jrs.or.jp/modules/information/index.php?content_id=1213. Accessed 8 Sept 2019.
Kuroda S, Fukuchi K. Hospitals face crisis after supply of key antibiotic halted; 2019. The Asahi Shimbun. http://www.asahi.com/ajw/articles/AJ201904020042.html. Accessed 8 Sept 2019.
Ministry of Health, Labour and Welfare. Decline in cefazolin supply [in Japanese]. Ministry of Health, Labour and Welfare. https://www.mhlw.go.jp/content/10906000/000527494.pdf. Accessed 8 Sept 2019.
Nichi-Iko Pharmaceutical Corporation. Cefazolin sodium details of supply issue. Nichi-Iko Pharmaceutical Corporation. https://www.nichiiko.co.jp/english/press/detail/4657/815/4541_20190513_CEZ_E.pdf. Accessed 8 Sept 2019.
Tsutsui A, Yahara K, Shibayama K. Trends and patterns of national antimicrobial consumption in Japan from 2004 to 2016. J Infect Chemother. 2018;24:414–21.
Infectious Diseases Society of America. IDSA practice guidelines. Infectious Diseases Society of America. https://www.idsociety.org/PracticeGuidelines/?q=&page=4&ref=#/date_na_dt/DESC/0/+/. Accessed 1 Aug 2018.
Baggs J, Fridkin SK, Pollack LA, Srinivasan A, Jernigan JA. Estimating national trends in inpatient antibiotic use among US hospitals from 2006 to 2012. JAMA Intern Med. 2016;176:1639–48.
Skoog G, Struwe J, Cars O, Hanberger H, Odenholt I, Prag M, et al. Repeated nationwide point-prevalence surveys of antimicrobial use in Swedish hospitals: data for actions 2003–2010. Euro Surveill. 2016;21:30264.
Al-Taani GM, Scott M, Farren D, Gilmore F, McCullagh B, Hibberd C, et al. Longitudinal point prevalence survey of antibacterial use in Northern Ireland using the European surveillance of antimicrobial consumption (ESAC) PPS and Global-PPS tool. Epidemiol Infect. 2018;146:985–90.
Ceyhan M, Yildirim I, Ecevit C, Aydogan A, Ornek A, Salman N, et al. Inappropriate antimicrobial use in Turkish pediatric hospitals: a multicenter point prevalence survey. Int J Infect Dis. 2010;14:e55–61.
Walsh TL, Chan L, Konopka CI, Burkitt MJ, Moffa MA, Bremmer DN, et al. Appropriateness of antibiotic management of uncomplicated skin and soft tissue infections in hospitalized adult patients. BMC Infect Dis. 2016;16:721.
We thank Saori Maruyama and Hiromi Murakami for help in collecting information on the devices in place for the surveyed patients.
Ethics approval and consent to participate
This study was approved by the Medical Ethical Committee of the National Hospital Organization Tochigi Medical Center (No. 2019-3). This study was conducted in accordance with the Ethical Guidelines for Epidemiological Research in Japan and was carried out in accordance with the Declaration of Helsinki. The need for individual informed consent was formally waived by the Medical Ethical Committee of the National Hospital Organization Tochigi Medical Center because data were collected without contacting the patients. However, as per Japanese Ethical Guidelines, an opt-out statement was displayed in the waiting room and webpage of the hospitals to inform the study and provide the opportunity to refuse the use of data for the patients.
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Prevalence of antimicrobial drug use according to different specialties according to the survey year. Table S2. The reasons for antimicrobial drug use according to survey year. Table S3. Number and type of antimicrobial drugs given to treat infections according to the survey year. aData are expressed as numbers (percentages). Table S4. Infection sites for which patients received antimicrobial therapy according to the survey year. aAntimicrobial drugs and patients could be given for more than one infection site. bData are expressed as numbers (percentages). Table S5. Appropriateness of the antimicrobial drugs used for treatment according to the location in the hospital, specialty, type of antimicrobial drug, and type of infection. aData are expressed as numbers (percentages). Table S6. Type and duration of antimicrobial drug used for surgical prophylaxis according to the survey year. aData are expressed as numbers (percentages). bA total of 28 and 33 antimicrobial drugs were given to 28 and 32 patients for surgical prophylaxis in August 2018 and 2019, respectively.
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Cite this article
Komagamine, J., Yabuki, T. & Hiraiwa, T. A trend in prevalence of antimicrobial use and appropriateness of antimicrobial therapy in an acute care hospital from 2018 to 2019: repeated prevalence surveys in Japan. BMC Res Notes 12, 811 (2019). https://doi.org/10.1186/s13104-019-4849-0
- Antimicrobial stewardship
- Antimicrobial therapy
- Inpatient antimicrobial use