key: cord-0970636-74b3h7e7 authors: Lai, Chih-Cheng; Chen, Shey-Ying; Ko, Wen-Chien; Hsueh, Po-Ren title: Increased antimicrobial resistance during the COVID-19 pandemic date: 2021-03-19 journal: Int J Antimicrob Agents DOI: 10.1016/j.ijantimicag.2021.106324 sha: b6276cbfe7446c046937ffdc6dc55d2854ddcfe7 doc_id: 970636 cord_uid: 74b3h7e7 In addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection itself, an increase in the incidence of antimicrobial resistance poses collateral damage to the current status of the coronavirus disease 2019 (COVID-19) pandemic. There has been a rapid increase in multidrug resistant organisms (MDROs), including extended-spectrum β-lactamases-producing Klebsiella pneumoniae, carbapenem-resistant New Delhi metallo-β-lactamase-producing Enterobacterales, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, pan-echinocandin-resistant Candida glabrata, and multi-triazole-resistant Aspergillus fumigatus. The cause is multifactorial and particularly related to high rates of antimicrobial agent utilization in COVID-19 patients with a relatively low rate of co- or secondary infection. Appropriate prescription and optimized use of antimicrobials according to the principles of antimicrobial stewardship program, quality diagnosis, and aggressive infection control measures may help prevent the occurrence of MDROs during this pandemic. Since the first case of coronavirus disease 2019 , initially named 2019 novel coronavirus (2019-nCoV) pneumonia, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan, China, the disease has affected more than 32.7 million people, with over one million fatalities worldwide [1, 2] . To combat this global health crisis, every health authority developed and implemented numerous infection control and prevention measures including maskwearing, practicing good hand hygiene, social distancing, avoiding crowded areas, active identification and quarantine of close contacts, and rapid set-up of shelter hospital and lock down strategies [3] [4] [5] [6] [7] . These aggressive management measures in response to COVID-19 brought additional benefits in terms of reducing other infections. Many studies have reported decreased incidence of several infectious respiratory diseases, such as seasonal influenza, invasive pneumococcal disease, and tuberculosis during the COVID- 19 pandemic as compared to that in the same period in previous years [8] [9] [10] [11] . However, we cannot neglect the increased incidence of antimicrobial resistance, which may be attributed to the excess use of antimicrobial agents during the COVID-19 pandemic [12] . 5 Several recent reports [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] have described an increase in multidrug resistant organisms (MDROs) during the COVID-19 pandemic. A retrospective study [13] found that the incidence of carbapenem-resistant Enterobacterales (CRE) colonization increased from 6 [14] . Another retrospective study [15] [20] . In New Delhi, India, candidemia affected 15 critical COVID-19 patients during April-July 2020 and multidrug-resistant C. auris accounted for 10 cases and six deaths [21] . Mohamed et al [22] reported on an Irish patient with severe COVID-19 pneumonia, which was complicated by a fatal coinfection with a multi-triazole resistant strain of Aspergillus fumigatus. In light of the COVID-19 pandemic, it has been reported that the necessity for the use of antimicrobial agents has increased compared to previous years. In an early report of 99 cases in China, more than 70% of patients with COVID-19 had received antibiotic treatment, approximately 15% of whom received antifungal agents [24] . Another study including 138 hospitalized patients showed that moxifloxacin, ceftriaxone, and azithromycin were prescribed in 89 (64.4%), 34 (24.6%), and 25 (18.1%) patients, respectively [25] . A large-scale study showed that 58% of 1,099 patients received intravenous antibiotics [26] , whereas a smaller Brazilian cohort (84.7% of 72) of hospitalized patients had received intravenous antibiotic therapy [27] . Additionally, a recent review showed that 72% (1,450/2,010) of hospitalized COVID-19 patients received antibiotics [28] . Overall, more than half of COVID-19 patients may receive an intravenous antibiotic, and this number can be higher in 7 patients with severe diseases. Patients withCOVID-19 could be vulnerable to other infections due to multiple comorbidities in patients with severe COVID-19, prolonged hospitalization, and SARS-CoV-2 associated immune dysfunction [29, 30] . However, the prevalence of co-infection among COVID-19 patients is considerably lower due to the frequency of antibiotic use for patients with SARS-CoV-2 infection. In the UK, a retrospective study involving 836 patients with SARS-CoV-2 infection showed 3.2% patients (n = 27) to have confirmed bacterial infection within the first 5 days after admission, the incidence of which rose to 6.1% (n = 55) for the duration of admission [16] . Li et al [14] showed that 6 [15, 28, [31] [32] [33] [34] . However, the majority of MDROs developed in patients with severe or critical COVID-19 and the incidence of co-or secondary infection may increase, resulting in prolonged hospitalization [16, 18, 20, 25, 28, 31] . The increase in the incidence of antimicrobial resistance was reported in sites with a high burden of severe or critical COVID-19 cases [14] [15] [16] [17] [18] [19] Figure 1 species notably decreased during these periods (Figure 2A) . These findings were partly consistent with those of other studies [9, 11] . However, the number of isolates of S. aureus, Enterococcus species, E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii complex remained stable ( Figure 2B) The greatest barrier to appropriate use of antimicrobial agents is that clinicians cannot definitively diagnose a co-pathogen with a SARS-CoV-2 infection, or easily identify the precise co-pathogen in a severe COVID-19 patient (Table 1) [44] . Among patients with severe COVID-19, an elevated level of procalcitonin was common, and could be associated with adverse outcomes [44] [45] [46] . However, previous meta-analysis of 32 randomized controlled trials shows that the use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with acute respiratory tract infection could result in a lower risks of death, antibiotic utilization, and antibiotic-associated adverse events [47, 48] . Therefore, the use of procalcitonin in the context of antibiotic stewardship may be applied when caring for severe COVID-19 patients. Based on the experience of influenza patients, procalcitonin has a high sensitivity, particularly in ICU patients. However, it has a low specificity for identifying secondary bacterial infections and may not be sufficient as a stand-alone marker for discontinuing antibiotics [49, 50] . Thus far, there is little associated research regarding the use of procalcitonin in COVID-19 patients [48, 51] . Further study is warranted to define the role of procalcitonin as a co-treatment in COVID-19 patients. The emergence of antimicrobial resistance is an unforeseen and unavoidable 13 consequence of the COVID-19 pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus COVID-19): The epidemic and the challenges Containing SARS-CoV-2 in hospitals facing finite PPE, limited testing, and physical space variability: Navigating resource constrained enhanced traffic control bundling How to prevent outbreak of a hospital-affiliated dementia day-care facility in the pandemic COVID-19 infection in Taiwan COVID-19 in long-term care facilities: An upcoming threat that cannot be ignored Active case finding with case management: the key to tackling the COVID-19 pandemic Fangcang shelter hospitals: a novel concept for responding to public health emergencies Seasonal influenza activity during the 15 SARS-CoV-2 outbreak in Japan Decline in invasive pneumococcal disease during COVID-19 pandemic in Taiwan The COVID-19 pandemic and tuberculosis in Taiwan The outcome and implications of public precautionary measures in Taiwan-declining respiratory disease cases in the COVID-19 pandemic Could the COVID-19 pandemic aggravate antimicrobial resistance? COVID-19, and infection control: spread of carbapenem-resistant Klebsiella pneumoniae colonization in ICU COVID-19 patients. What did not work? Etiology and antimicrobial resistance of secondary bacterial infections in patients hospitalized with COVID-19 in Wuhan, China: a retrospective analysis Bacterial and viral co-infections in patients with severe SARS-CoV-2 pneumonia admitted to a French ICU Evaluation of bacterial co-infections of the respiratory tract in COVID-19 patients admitted to ICU Secondary bacterial infections in critical ill patients with coronavirus disease 2019 Emerging co-pathogens: New Delhi Metallo-beta-lactamase producing Enterobacteriaceae infections in New York City COVID-19 patients Enterobacteriaceae outbreak: another dark side of COVID-19 Pan-echinocandin-resistant Candida glabrata bloodstream infection complicating COVID-19: A fatal case report Multidrug-resistant Candida auris infections in critically ill coronavirus disease patients Multi-triazole-resistant Aspergillus fumigatus and SARS-CoV-2 coinfection: A lethal combination Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting Epidemiological and clinical characteristics of 99 cases of China: a descriptive study Clinical characteristics of 138 hospitalizedpatients with 2019 novel coronavirus-infected pneumonia in Wuhan, China Clinical characteristics of coronavirus disease 2019 in China Epidemiologic and clinical features of patients with COVID-19 in Brazil Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing SARS-CoV-2-induced immunodysregulation and the need for higher clinical suspicion for co-infection and secondary infection in COVID-19 patients Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths Co-infections among patients with COVID-19: The need for combination therapy with non-anti-SARS-CoV-2 agents? COVID-19 associated with pulmonary aspergillosis: A 18 literature review Case Report: Multidrug-resistant tuberculosis and COVID-19 coinfection in Port-au-Prince, Haiti Cavitary pulmonary tuberculosis with COVID-19 coinfection How to keep COVID-19 at bay: a Taiwan perspective Antibiotic prescribing for children in primary care and adherence to treatment guidelines Quality assessment in general practice: diagnosis and antibiotic treatment of acute respiratory tract infections Actual versus 'ideal' antibiotic prescribing for common conditions in English primary care Continued high rates of antibiotic prescribing to adults with respiratory tract infection: survey of 568 UK general practices Tackling antimicrobial resistance in the COVID-19 pandemic In vitro diagnostics of coronavirus disease 2019: Technologies and application The Impact of the COVID-19 Pandemic on healthcare acquired infections with multidrug resistant organisms Nurses' and midwives' cleaning knowledge, attitudes and practices: An Australian study Procalcitonin and secondary bacterial infections in COVID-19: association with disease severity and outcomes Characteristics, laboratories, and prognosis of severe COVID-19 in the Tokyo metropolitan area: A retrospective case series Association between procalcitonin levels and duration of mechanical ventilation in COVID-19 patients Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a metaanalysis Can procalcitonin tests aid in identifying bacterial infections associated with 20 influenza pneumonia? A systematic review and meta-analysis Procalcitonin for diagnosis of bacterial pneumonia in critically ill patients during 2009 H1N1 influenza pandemic: a prospective cohort study, systematic review and individual patient data meta-analysis Biomarkers and outcomes of COVID-19 hospitalisations: systematic review and metaanalysis Ethical approval: Not required.