Natural disasters often result in the mass evacuation of people to shelters. Postdisaster disease trends may differ from one disaster to another, but many involve communicable diseases.[2–6] Antibiotics had been frequently prescribed in these settings. Studies had evaluated the appropriateness of antibiotic use in regular settings,[7–9] but ones for healthcare in postdisaster settings have not been evaluated.
The Tohoku area in Japan was hit by a massive earthquake with a magnitude of 9.0 and a subsequent tsunami on March 11, 2011, which resulted in more than 15,000 deaths (the Great East Earthquake). The earthquake also led to mass evacuation with many people staying in shelters. To evaluate the appropriateness of antibiotic use there, we reviewed clinical data on the medical services provided at these shelters.
2.1 Setting and patients
We extracted clinical data from database at Department of Health Crisis Management, National Institute of Public Health. The database was produced based on data from clinical charts used to provide care at 98 shelters or their accessory aid stations at Ishinomaki City, Miyagi, Japan. Ishinomaki was one of the most damaged areas following the Great East Japan Earthquake, mostly due to the massive tsunami. More than 50,000 people were evacuated to shelters following the tsunami, and more than 3800 people died or went missing. Japanese Red Cross Ishinomaki Hospital was the only designated disaster hospital in the Ishinomaki Medical Zone, and it was undamaged by the earthquake. The Ishinomaki Zone Joint Relief Team coordinated medical support from all over Japan, and medical workers provided care to people in shelters, typically rotating weekly. Many shelters and their aid stations lacked lifelines such as electricity, water, or sewerage systems, and medical care was provided without laboratory tests or imaging studies. Those who needed referral were transferred to Japanese Red Cross Ishinomaki Hospital, but transfer was difficult due to destroyed roads and lack of vehicles. The study was approved by the ethic committees both at Kobe University Graduate School of Medicine and Japanese Red Cross Ishinomaki Hospital.
2.2 Estimating appropriate antibiotic use
We included patients who were prescribed oral antibiotics at each clinic. The use of intravenous, intramuscular, or topical antibiotics were excluded from the analyses. We collected age, sex, diagnosis, and prescriptions from the database, and evaluated the appropriateness of antibiotic use.
For the definition of appropriateness, we applied and adapted the criteria developed by Fleming-Dutra et al, which were based on clinical guidelines for appropriate antibiotics prescription by age group in the outpatient setting. For example, antibiotic therapy was not recommended for upper respiratory infections (URI) for both adults and children in this criteria.[13–15] We judged the criteria were useful and applicable in the postdisaster setting in Japan.
For acute gastroenteritis, which was the 2nd most common infectious disease after URI in a precedent study but no recommendation was made by Fleming-Dutra et al, we applied and adapted the Japanese Association for Infectious Diseases (JAID) and Japanese Society of Chemotherapy (JSC) guideline as the reference, which recommended no antibiotic therapy for mild acute gastroenteritis in children, but recommended clarithromycin, amoxicillin, fosfomycin, or norfloxacin for suspected Campylobacter infections. Although meta-analysis on antibiotic treatment for Campylobacter infection showed only limited effects, we allowed this antibiotic use for this condition, considering the significant damage to quality of life at shelters. We also accepted other fluoroquinolones such as levofloxacin as an alternative to norfloxacin being mindful of the possible lack of stock at each clinic. For muscloskeletal traumatic injuries, we applied Lane et al as a reference for recommendation, but allowed other antibiotics such as amoxicillin/clavulanate or even the use of fluoroquiolones for the same reason above. For skin and soft tissue infections (SSTI) such as cellulitis, we used the latest Infectious Diseases Society of America guideline.
We categorized the use of antibiotics to appropriate, acceptable, or inappropriate. Acceptable antibiotic use was defined as the use of an antibiotic which was not necessarily ideal, but which can be used as an alternative to the first choice, particularly in disaster situations. For example, the use of fluoroquinolones for SSTI cannot be recommended routinely due to their broad spectrum nature, but may be acceptable in circumstances where no other antibiotics were available. We restricted the recommended antibiotics to those approved in Japan. We considered oral 3rd-generation cephalosporins not appropriate for use in most circumstances, due to poor bioavailability, their broad spectrum, and the existence of better alternatives. Likewise, we did not include fosfomycin in our recommendation since the fosfomycin calcium which is available in Japan has much worse bioavailability than the fosfomycin tromethamine available abroad. For other miscellaneous infections, we used our expert recommendations as the basis for the appropriateness of the use of antibiotics. On the other hand, we allowed the use of cefaclor for the treatment of SSTI since it is usually regarded as “first-generation cephalosporin” in Japan, instead of 2nd-generation in other countries. Cefaclor has reasonable bioavailability, and we judged that it can be used as an alternative to cephalexin for the management of SSTIs. If there is an ambiguity between appropriate/acceptable and inappropriate, 2 infectious diseases specialists discussed the issue to resolve the issue (KI and TF). These recommendations were summarized in Table 1.
2.3 Statistical analyses
Statistical analyses were performed using STATA 14.1 (STATA Corp). Ninety-five percent confidence intervals (CIs) were calculated for estimates.
From March to July, 2011, a total of 23,704 clinic visits occurred at 98 shelters with 7934 residents. Oral antibiotics were prescribed 2253 times. The median age of the patients who were given antibiotics was 48.5 years old (range 0–97), and 43.7% were male.
Of 2253 antibiotic prescriptions, 156, 153, and 1944 were judged to be appropriate, acceptable, and inappropriate, respectively (Table 2). This means that only 6.9% of antibiotic prescriptions were appropriate (95% CI 5.9%–8.1%), 6.8% were acceptable (95% CI 5.8%–7.9%), and the remaining 86.3% were inappropriate (95% CI 84.8%–87.7%).
The most prescribed antibiotic was clarithromycin (646 times, 28.7%), followed by cefcapene pivoxil (644 times, 28.6%), levofloxacin (380, 16.9%), cefdinir (194, 8.6%), and cefditren pivoxil (98, 4.4%). For each antibiotic, most prescriptions were judged to be inappropriate (Table 3).
The most frequent diagnosis for which antibiotics were prescribed was URI (1,040 visits, 46.2%), followed by acute bronchitis (369, 16.4%), pharyngitis (298, 13.2%), traumatic injuries (194, 8.6%), acute gastroenteritis (136, 6.0%), urinary tract infections (123, 5.5%), and allergic rhinitis (5.1%) (Table 4). Again, antibiotics were used inappropriately in most diagnoses except for urinary tract infection and pneumonia, with inappropriate antibiotic use of 17.5% and 25.9%, respectively.
4 Discussion and conclusions
Our analyses describe the appropriateness of antibiotics used at clinics in Ishinomaki city after the Great East Japan Earthquake. We found most antibiotics were used inappropriately, and the most of them were given for diagnoses such as URI, for which no antibiotics are recommended. For other diagnoses where antibiotic use is recommended or justified, we found many cases of the misuse of antibiotics.
Fleming-Dutra et al estimated the prevalence of inappropriate antibiotic prescriptions among ambulatory care visits in the United States, and found that 153 out of 506 annual antibiotic prescriptions per 1000 population were not appropriate (30.2%). Although there are studies investigating the amount of antibiotic consumption in Japan, few studies have investigated their appropriateness. Our findings, even though criteria for appropriateness are slightly different, were much worse than those in the United States.
According to Muraki et al, although, the rate of defined daily doses per 1000 inhabitants per day for penicillin was much smaller in Japan than in European countries, oral 3rd-generation cephalosporins, oral macrolides, and oral fluoroquinolones were consumed at high rates in Japan. Our study findings are consistent with them, and we found that not only these broad spectrum antibiotics were used frequently, but also they were used inappropriately.
The overuse of 3rd-generation cephalosporins poses significant risk to society. Oral 3rd-generation cephalosporins generally have poor bioavailability, yet can kill Enterobacteriaceae in the intestine unnecessarily, which can lead to an increase in antibiotic resistant organisms and Clostridium difficile infection.[22,37,38]
In our study, the use of macrolides was accepted for the treatment of pharyngitis and acute gastroenteritis. Macrolides are recommended for acute bacterial pharyngitis when penicillin cannot be used due to allergy. Also, the use of macrolides were judged to be acceptable in treating selected cases of Campylobacter infection. Despite this allowance, most macrolides prescribed in our study were inappropriate. Inappropriateness might be even worse than our estimate, since most cases of pharyngitis are caused by viral infection, and many can be treated with penicillins even if caused by bacteria. Additionally, most diarrheal illnesses are not caused by Campylobacter. However, given the circumstances where few diagnostic tests were available, we had to accept the potential overtreatment with macrolides to a certain extent. Despite this allowance, macrolides, particularly clarithromycin, were overused and misused according to our findings.
The overuse of macrolides in Japan has resulted in an increase in macrolide resistant organisms, such as Mycoplasma pneumoniae, Streptococcus pneumoniae, and Streptococcus pyogenes.[39,40] In addition, the use of macrolides is associated with significant side effects such as cardiovascular death. Clarithromycin is known to increase the risk of rhabdomyolysis when coadministered with statins. Even though macrolides can be useful in certain infections, they should never be used unnecessarily, particular in postdisaster settings, where one may not be able to treat the complications of medication use promptly.
We are not trying to make an assertion that the health care workers that provided care after the Great East Japan Earthquake were incompetent or ignorant. We simply sought the appropriateness of antibiotic prescriptions. The inappropriateness could come from number of factors, such as the lack of antibiotic stock at each clinic, the need to deliver hope to devastated people at shelters, or the lack of diagnostic tools to name a few. Some volunteer doctors might be specialists of different areas and might not be used to prescribe antibiotics at such settings (We have no data on demographics of specialties of volunteer doctors during this period). In Japan, not every physicians received training on primary care, not to mention the field of “disaster medicine.” We were able to reveal “what happened” after the earthquake, but were not able to reveal “why” this happened. In-depth investigations such as qualitative studies might reveal the root cause of antibiotic misuse.
We investigated the cases where antibiotics were used, but we did not investigate the cases where antibiotics were not used. For example, 2739 diagnoses of URI were made during the study period, and antibiotics were prescribed in 1040, suggesting URI were appropriately managed in more than half the cases (62.0%). This is similar to antibiotic prescription rate for URI at nondisaster setting according to a cross-sectional study in Japan (60%). Further studies are needed to evaluate to what extent inappropriate antibiotic use is due to unusual environment after disasters, or due to inappropriate antibiotic use in daily practice.
There are several limitations inherent in our study. First, since we extracted data for the diagnoses and the names of the antibiotics used, we might be missing important contextual information on each practice. There might have been justifiable reasons to prescribe antibiotics in individual cases, for which we judged them inappropriate. On the other hand, since we were not able to obtain detailed information about patients, there might have been more antibiotic misuse than we identified, such as contraindications due to underlying health problems, interactions with other medications, or the presence of known allergies. Second, our criteria of appropriate, acceptable, or inappropriate antibiotic use might be seen as too austere. However, we applied precedent studies on appropriate antibiotic use and current clinical guidelines. We were also mindful of the extreme environment after disasters, allowing rather broad spectrum antibiotics for certain infections, such as fluoroquinolones for SSTIs. We are afraid that we might have been underestimating the proportion of inappropriate antibiotic use, but we do not consider that we overestimated it.
In conclusion, we found a significant number of inappropriate antibiotic use at clinics held after the Great East Japan Earthquake. Japan suffered another large scale earthquake in the Kumamoto area in 2016, and we will definitely experience other disasters with health care needs.
We believe that even refugees after disasters do have the right to receive appropriate medications, such as antibiotics for their health and environment. Further improvement in the use of antibiotics in such circumstances should be undertaken.
The authors thank Dr Seiichi Kobayashi for invaluable comments and discussion. The authors also thank Dr Daniel Mosby for editing the manuscript to eliminate grammatical or spelling errors.
. Klein KR, Nagel NE. Mass medical evacuation: Hurricane Katrina and nursing experiences at the New Orleans airport. Disaster Manag Response 2007;5:56–61.
. Nufer KE, Wilson-Ramirez G, Shah MB, et al. Analysis of patients treated during four Disaster Medical Assistance Team deployments. J Emerg Med 2006;30:183–7.
. Ligon BL. Infectious diseases that pose specific challenges after natural disasters: a review. Semin Pediatr Infect Dis 2006;17:36–45.
. Guha-Sapir D, van Panhuis WG. Health impact of the 2004 Andaman Nicobar earthquake and tsunami in Indonesia. Prehosp Disaster Med 2009;24:493–9.
. Kouadio IK, Aljunid S, Kamigaki T, et al. Infectious diseases following natural disasters: prevention and control measures. Expert Rev Anti Infect Ther 2012;10:95–104.
. Salazar MA, Pesigan A, Law R, et al. Post-disaster health impact of natural hazards in the Philippines in 2013. Glob Health Action 2016;9:31320.
. Gonzales R, Malone DC, Maselli JH, et al. Excessive antibiotic use for acute respiratory infections in the United States. Clin Infect Dis 2001;33:757–62.
. Kronman MP, Zhou C, Mangione-Smith R. Bacterial prevalence and antimicrobial prescribing trends for acute respiratory tract infections. Pediatrics 2014;134:e956–65.
. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. PRevalence of inappropriate antibiotic prescriptions
among us ambulatory care visits, 2010–2011. JAMA 2016;315:1864–73.
. Nakahama S, Ichikawa M. Mortality in the 2011 Tsunami in Japan. J Epidemiol 2013;23:70–3.
. Ishii T. Medical response to the Great East Japan Earthquake
in Ishinomaki City. Western Pac Surveill Response J 2011;2:e1–1.
. Hersh AL, Jackson MA, Hicks LA, et al. Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics. Pediatrics 2013;132:1146–54.
. Dowell SF, Schwartz B, Phillips WR. Appropriate use of antibiotics for URIs in children: Part II. Cough, pharyngitis and the common cold. The Pediatric URI Consensus Team. Am Fam Physician 1998;58:1335–42, 1345.
. Snow V, Mottur-Pilson C, Gonzales R, et al. Principles of appropriate antibiotic use for treatment of nonspecific upper respiratory tract infections in adults. Ann Intern Med 2001;134:487–9.
. Kawano T, Hasegawa K, Watase H, et al. Infectious disease frequency among evacuees at shelters after the great eastern Japan earthquake and tsunami: a retrospective study. Disaster Med Public Health Prep 2014;8:58–64.
. Ohnishi K, Ainoda Y, Imamura A, et al. [The JAID/JSC Guidelines to Clinical Management of Infectious Diseases (Intestinal infection)]. Kansenshogaku Zasshi 2016;90:31–65. (in Japanese).
. Ternhag A, Asikainen T, Giesecke J, et al. A meta-analysis on the effects of antibiotic treatment on duration of symptoms caused by infection with Campylobacter species. Clin Infect Dis 2007;44:696–700.
. Lane JC, Mabvuure NT, Hindocha S, et al. Current concepts of prophylactic antibiotics in trauma: a review. Open Orthop J 2012;6:511–7.
. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;ciu296.
. Sastry S, Doi Y. Fosfomycin: resurgence of an old companion. J Infect Chemother 2016;22:273–80.
. James NC, Donn KH, Collins JJ, et al. Pharmacokinetics of cefuroxime axetil and cefaclor: relationship of concentrations in serum to MICs for common respiratory pathogens. Antimicrob Agents Chemother 1991;35:1860–3.
. Snow V, Mottur-Pilson C, Gonzales R, et al. Principles of appropriate antibiotic use for treatment of acute bronchitis in adults. Ann Intern Med 2001;134:518–20.
. Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest 2006;129(1 Suppl):1S–23S.
. Fiore A, Fry A, Shay D, et al. Antiviral agents for the treatment and chemoprophylaxis of influenza – recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60:1–24.
. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis 2012;55:e86–102.
. National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007;120(5 Suppl):S94–138.
. Bradley JS, Byington CL, Shah SS, et al. Executive summary: the management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis 2011;53:617–30.
. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(Suppl 2):S27–72.
. Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media. Pediatrics 2013;131:e964–99.
. Wald ER, Applegate KE, Bordley C, et al. Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years. Pediatrics 2013;132:e262–80.
. Chow AW, Benninger MS, Brook I, et al. IDSA Clinical Practice Guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis 2012;54:e72–112.
. Roberts KB. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and ManagementUrinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 2011;128:595–610.
. Gupta K, Hooton TM, Naber KG, 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.
. Muraki Y, Yagi T, Tsuji Y, et al. Japanese antimicrobial consumption surveillance: first report on oral and parenteral antimicrobial consumption in Japan (2009–2013). J Glob Antimicrob Resist 2016;7:19–23.
. Rafii F, Sutherland JB, Cerniglia CE. Effects of treatment with antimicrobial agents on the human colonic microflora. Ther Clin Risk Manag 2008;4:1343–58.
. Owens RC, Donskey CJ, Gaynes RP, et al. Antimicrobial-associated risk factors for Clostridium difficile
infection. Clin Infect Dis 2008;46(Suppl 1):S19–31.
. Kawai Y, Miyashita N, Kubo M, et al. Nationwide surveillance of macrolide-resistant mycoplasma pneumoniae infection in pediatric patients. Antimicrob Agents Chemother 2013;57:4046–9.
. Cheng Y-J, Nie X-Y, Chen X-M, et al. The role of macrolide antibiotics in increasing cardiovascular risk. J Am Coll Cardiol 2015;66:2173–84.
. Patel AM, Shariff S, Bailey DG, et al. Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med 2013;158:869–76.
. Zhang Z, Zhan X, Zhou H, et al. Antibiotic prescribing of village doctors for children under 15 years with upper respiratory tract infections in rural China. Medicine (Baltimore) 2016;95:e3803.
. Higashi T, Fukuhara S. Antibiotic prescriptions
for upper respiratory tract infection in Japan. Intern Med 2009;48:1369–75.