key: cord-0735759-p6ilhn65 authors: Imoto, Waki; Yamada, Koichi; Kuwabara, Gaku; Shibata, Wataru; Sakurai, Norihiro; Nonose, Yuka; Okada, Yasuyo; Nakie, Kiyotaka; Fujita, Akiko; Kakeya, Hiroshi title: Impact of coronavirus disease 2019 on infectious disease treatment and infection control at a tertiary hospital in Japan date: 2022-01-26 journal: J Infect Chemother DOI: 10.1016/j.jiac.2022.01.008 sha: d1f39f6bbb35e7107d63777829366e909d20b1f1 doc_id: 735759 cord_uid: p6ilhn65 INTRODUCTION: Coronavirus disease 2019 (COVID-19) has greatly impacted medical care practices. Although the effects on infectious disease treatment and infection control, such as antimicrobial resistance, have been specified, very few reports exist on the specific effects of COVID-19. METHODS: We investigated the effects of COVID-19 on daily medical practices at a tertiary hospital in Japan by comparing the use of hand sanitizers, the detection of bacteria from blood cultures, and the amount dose of antibacterial drugs used for one year before (April 2019 to March 2020, fiscal year 2019.) and after COVID-19 admissions began (April 2020 to March 2021, fiscal year 2020). RESULTS: The use of hand sanitizers increased by 1.4–3 times during the year after COVID-19 admissions began; the incidence of methicillin-susceptible Staphylococcus aureus and all S. aureus detected in blood cultures reduced in all departments. No decrease was observed in the usage of all antibacterial drugs; rather, the usage of all antibacterial drugs tended to increase in all departments. Therefore, no significant change was observed in the detection of drug-resistant bacteria and the trends of antibacterial drug use based on the acceptance of COVID-19 patients. CONCLUSIONS: The prevalence of drug-resistant bacteria and trends of antibacterial drug use remained unchanged despite the increased use of hand sanitizers due to the admission of patients with COVID-19. The world's first case of coronavirus disease 2019 was confirmed in China in December 2019 [1] , and the first case in Japan was reported in January 2020 [2, 3] . Since then, the number of patients with COVID-19 has continued to increase, and the emergency department of our hospital began accepting COVID-19 patients with severe illness in April 2020. Our hospital is equipped to provide advanced medical care, including extracorporeal membrane oxygenation; therefore, the majority of patients have serious illnesses, and only a few patients have mild to moderate illnesses. The COVID-19 pandemic has had a major impact on our daily hospital practices, partly because of the distribution of medical resources and staff to patients with COVID-19. We speculated that it may also have affected antimicrobial resistance (AMR), infectious disease treatment, and infection control. An increased focus on hand hygiene during the COVID-19 pandemic may reduce the development of AMR within healthcare settings. Conversely, increased use of empirical antimicrobial therapy among COVID-19 patients may promote AMR. Several AMR outbreaks have been reported since the start of the COVID-19 pandemic [4, 5] . The COVID-19 pandemic may change doctors' prescribing habits. For example, the use of antimicrobial therapy among patients with respiratory symptoms may increase [4] , and increased AMR may lead to an increase in the prescriptions of broadspectrum antibiotics. Similarly, hospital-wide antibiotic usage may change due to the COVID-19 pandemic because approximately 70% of hospitalized COVID-19 patients receive antibiotics [5] [6] [7] . Healthcare workers may focus on self-protection rather than preventing cross-transmission between patients, and the use of hand sanitizers may increase [5] . In summary, the COVID-19 pandemic may affect behavior regarding infection control, antibiotic prescription, and the detection of AMR. However, there is J o u r n a l P r e -p r o o f limited information on the specific effects of COVID-19, including its effects on AMR, infectious disease treatment, and infection control. Therefore, we conducted a study to describe our hospital's approach to admitting COVID-19 patients and the effect of the COVID-19 pandemic on infectious disease treatment and infection control. This study was conducted at the Osaka City University Hospital, a 965-bed tertiary-care hospital in Osaka, Japan. We considered two periods: the year before the admission of COVID-19 patients began (April 2019 to March 2020, fiscal year 2019), and the year after the admission of COVID-19 patients began (April 2020 to March 2021, fiscal year 2020). We compared the following factors between the emergency department and clinical departments other than the emergency department: number of inpatients, amount of hand sanitizer used, bacteria detected in blood cultures, drug-resistance of Pseudomonas spp., and the amount of antibacterial agents used (expressed as antimicrobial use density [AUD] and days of therapy [DOT] ). All bacteria detected by blood culture were included in the results, and the possibility of contamination could not be excluded. Defined daily doses (DDD), set by the World Health Organization, were used for calculating the AUD. The AUD was calculated as the total antimicrobial use in DDD per 1000 patient-days. The DOT was calculated as the number of antimicrobial therapy days per 1000 patient-days. Due to the instability of the antibacterial drug supply [8] , the AUD and DOT in the fiscal year 2020 were compared to those of fiscal years 2015-2019 combined. J o u r n a l P r e -p r o o f Each patient was included in the study only once during the observation period for each sample. The number of hand sanitizer units used per patient daily was calculated by dividing the total number of hand sanitizer units used in the hospital (or ward) by the total number of inpatients in the hospital (or ward). Because our hospital uses several different types of hand sanitizer, we obtained the total volume of each type of hand sanitizer used (mL) in the hospital (or ward) from the department that manages the purchase of hand sanitizers in our hospital. We calculated the total number of units of hand sanitizer used for each hand sanitizer by dividing the total volume of each sanitizer used (mL) by the recommended single-use amount (mL). The total number of units of hand sanitizer used was calculated by adding the number of units of all the different types of hand sanitizer used. To compare the amount of antibacterial drugs used, the AUD and DOT for each month of each period were calculated and compared between the two periods. All bacterial isolates were identified using colony morphologic analysis and Gram staining. Isolate identification and antimicrobial susceptibility were confirmed using the MicroScan WalkAway-96 SI system (Beckman Coulter, Inc., Brea, CA, USA). Results were interpreted according to the 2018 Clinical and Laboratory Standards Institute guidelines [9] . After screening for drug susceptibility, the presence of extendedspectrum β-lactamase (ESBL)-producing bacteria was confirmed by the disk diffusion method using clavulanate [9] ; in contrast, the presence of AmpC-producing bacteria was confirmed by the disk diffusion method using boronic acid [10] . Carbapenem-resistant Enterobacteriaceae (CRE) were determined according to the standards of the Ministry of Health, Labour, and Welfare of Japan [11] for meropenem (minimum inhibitory J o u r n a l P r e -p r o o f concentration [MIC] of meropenem: ≥2 μg/mL), imipenem (MIC of imipenem: ≥2 μg/mL), and cefmetazole (MIC of cefmetazole: ≥64 μg/mL) susceptibility. Fisher's exact test was used for univariate comparisons of categorical data, and the Mann-Whitney U test was used to compare continuous variables using EZR software (Saitama Medical Center, Jichi Medical University, Saitama, Japan) [12] , which is a modified version of the R commander (version 2.4) that includes statistical functions frequently used in biostatistics. Statistical significance was set at p <0.05. The Ethics Committee of the Osaka City University Graduate School of Medicine approved this study (No. 2021-093) . The need for written informed consent was waived owing to the retrospective nature of the study. The number of inpatients in the fiscal year 2020 was lower than that in the fiscal year 2019 in the emergency department and other departments. While 81 patients with severe COVID-19 were admitted to the emergency department in the fiscal year 2020, the other departments admitted only 18 patients during this period. Nevertheless, it was confirmed that the amount of hand sanitizer used increased in the emergency department, the intensive care unit, and all wards in our hospital, with consumption in the emergency department increasing by approximately three-fold (Table 1) (Table 2) . Further, the changes in susceptibility of Pseudomonas spp. in blood culture, sputum, urine, and skin to antibacterial agents were investigated because there was a rise in the detection of Pseudomonas spp. in blood culture samples obtained from clinical departments other than the emergency department. However, no significant change was observed J o u r n a l P r e -p r o o f potentially affect AMR; thus, it influences infectious disease treatment and control. One of the effects is an increased incidence of infections caused by multidrug-resistant bacteria [5, [13] [14] [15] . This may be due to poor adherence to infection control measures because of staff shortages [13] and improper use of hand sanitizers and personal protective equipment [5, 16] . Moreover, the number of antibacterial agents used in the empiric treatment of patients with COVID-19 and the incidence of infection due to drugresistant bacteria may increase [17] . However, previous reports showed that the COVID-19 pandemic did not affect the incidence of infection due to multidrug-resistant bacteria [5] . This difference in study findings may be attributed to the differences in the nature of the COVID-19 pandemic among countries and the use of infection control measures. The incidence of COVID-19 in Japan has been lower than that of many other countries, with 1,687,422 cases among a total population of over 100 million as of September 24, 2021 [18] . In contrast, the epidemic has been more extensive in North America and Europe, with 43,734,666 cases in the United States of America, 6,994,319 cases in France, 7,664,230 cases in the United Kingdom, 4,660,314 cases in Italy, and 4,203,411 cases in Germany reported as of September 24, 2021 [18] . To the best of our knowledge, this is the first study to investigate the impact of COVID-19 on infection control and infectious disease treatment in Japan. We observed that the use of hand sanitizers increased despite a reduced number of inpatients; however, there were no obvious changes in the detection of drug-resistant bacteria or the amount of antibacterial drugs used. A previous study showed that the COVID-19 pandemic may increase the use of hand sanitizers [4] , and we observed an increase in the use of hand sanitizers in the clinical departments where COVID-19 is directly treated and in those where it is not. This may J o u r n a l P r e -p r o o f be related to the rising awareness regarding infection control when admitting COVID-19 patients. Reportedly, proper hand sanitization reduces the incidence of infection caused by resistant bacteria, such as MRSA and ESBL-producing bacteria [19, 20] . However, we detected no reduction in the incidence of drug-resistant bacterial infections during the study period. This could be because of the relatively short observation period, and there could be a decrease in the incidence of drug-resistant bacterial infection because of increased hand sanitizer use if a longer observation period is considered. However, factors other than the observation period may be involved, such as inappropriate timing and method of hand sanitization. Other studies with an observation period of less than one year found a decreased incidence of MRSA infection due to the appropriate use of hand sanitizers [21, 22] . Therefore, monitoring by the infection control team should focus on increased hand sanitizer use and the method and timing of hand sanitizer use, and appropriate changes should be made to the timing and method of hand sanitizer use by medical staff. The incidence of MSSA bacteremia was similar in the samples obtained from the clinical departments that admitted many COVID-19 patients and in those that did not; therefore, the decreased incidence of MSSA bacteremia may not be an effect of COVID-19. The amount of antibacterial drugs used in the fiscal year 2020 was compared to that in fiscal because the incidence of bacteremia differed between the COVID-19 ward (emergency department) and the other wards; however, the incidence in the emergency department was too low to perform statistical analysis. Studies that have shown an increased incidence of drug-resistant bacterial infections since the onset of the COVID-19 pandemic have been conducted in Germany [13] , the United States of America [14] , and Italy [15] , where the incidence of COVID-19 is several times higher than that in Japan, and, the influence of COVID-19 may, therefore, be more marked. Additionally, our J o u r n a l P r e -p r o o f hospital mainly accepts patients with severe COVID-19, and only a few patients have mild to moderate symptoms. Thus, most of the COVID-19 patients were intubated and received mechanical ventilation, which may have aided in infection control. Our study has several limitations. First, it was a single-center study conducted only in Japan. The COVID-19 situation varies greatly not only between countries but also between different regions within the same country. Furthermore, the process of admission of COVID-19 patients with mild, moderate, or severe disease varies between hospitals. Studies conducted in different hospitals could yield diverse results; therefore, it is necessary to investigate the effect of COVID-19 in different settings. Second, our observation period was relatively short. The relationship between the use of hand sanitizers and detection of resistant bacteria varies according to the observation period, and these findings vary between different reports [19] [20] [21] [22] . Furthermore, the use of antibacterial drugs can change significantly in a single year, depending on the supply. The most significant limitation of this study is that we could not investigate the method and timing of hand sanitizer use. Therefore, this needs to be clarified in a future prospective study. In conclusion, admission of patients with COVID-19 may not affect the detection of drug-resistant bacteria and the use of antimicrobial agents. Nevertheless, increasing the awareness of healthcare staff toward the use of hand sanitizers and sufficient infection control education is needed for the increased use of hand sanitizers to have a positive effect, despite the COVID-19 pandemic. None. A novel coronavirus from patients with pneumonia in China The COVID-19 pandemic in Japan COVID-19 pandemic in Japan COVID-19 and the potential long-term impact on antimicrobial resistance Will coronavirus disease (COVID-19) have an impact on antimicrobial resistance? Bacterial co-infection and secondary infection in patients with COVID-19: A living rapid review and meta-analysis Bacterial and fungal coinfection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing Toward a stable supply of antibacterial agents Performance Standards for antimicrobial Susceptibility Testing; 27th Informational Supplement. M100-S28. 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WHO coronavirus (COVID-19) dashboard Patients' hand washing and reducing hospital-acquired infection methicillin-resistant Staphylococcus aureus (MRSA) infection Performance feedback of hand hygiene, using alcohol gel as the skin decontaminant, reduces the number of inpatients newly affected by MRSA and antibiotic costs Significant reductions in methicillin-resistant Staphylococcus aureus bacteraemia and clinical isolates associated with a multisite, hand hygiene culture-change program and subsequent successful statewide roll-out CRE, carbapenem-resistant Enterobacteriaceae; ESBL, extended spectrum beta-lactamase GNR, gram negative rod; GPC, gram positive cocci GPR, gram positive rod MRCNS, methicillin-resistant coagulase-negative staphylococci; MRSA, methicillin-resistant Staphylococcus aureus MSSA, methicillin-sensitive Staphylococcus aureus We would like to thank Editage (www.editage.jp) for English language editing.