key: cord-0976039-t0vzazs9
authors: Tomczyk, S.; Taylor, A.; Brown, A.; de Kraker, M.; Eckmanns, T.; El-Saed, A.; Alshamrani, M.; Hendriksen, R.; Jacob, M.; Lofmark, S.; Perovic, O.; Shetty, N.; Sievert, D.; Smith, R.; Stelling, J.; Thakur, S.; Tornimbene, B.; Vietor, A. C.; Eremin, S.; Network, WHO AMR Surveillance and Quality Assessment Collaborating Centre
title: Impact of the COVID-19 Pandemic on Antimicrobial Resistance (AMR) Surveillance, Prevention and Control: A Global Survey
date: 2021-03-26
journal: nan
DOI: 10.1101/2021.03.24.21253807
sha: 90d215294f458faa32e2aebca6019e158d0e9f1b
doc_id: 976039
cord_uid: t0vzazs9

Objectives The COVID-19 pandemic has had a substantial impact on health systems. The WHO Antimicrobial Resistance (AMR) Collaborating Centres Network conducted a survey to assess the effects of COVID-19 on AMR surveillance, prevention and control. Methods From October-December 2020, WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) national focal points completed a questionnaire including Likert-scales and open-ended questions. Data were descriptively analysed, income/regional differences were assessed, and free-text questions were thematically analysed. Results Seventy-three countries across income levels participated. During the COVID-19 pandemic, 67% reported limited ability to work with AMR partnerships; decreases in funding were frequently reported by low- and middle-income countries (LMICs; p<0.01). Reduced availability of nursing, medical and public health staff for AMR was reported by 71%, 69% and 64%, respectively, whereas 67% reported stable cleaning staff availability. The majority (58%) reported reduced reagents/consumables, particularly LMICs (p<0.01). Decreased numbers of cultures, elective procedures, chronically ill admissions and outpatients and increased intensive care unit admissions reported could bias AMR data. Reported overall infection prevention and control (IPC) improvement could decrease AMR rates, whereas increases in selected inappropriate IPC practices and antibiotic prescribing could increase rates. Most did not yet have complete data on changing AMR rates due to COVID-19. Conclusions This was the first survey to explore the global impact of COVID-19 on AMR among GLASS countries. Responses revealed universal patterns but also captured country variability. Although focus is understandably on COVID-19, gains in detecting and controlling AMR, a global health priority, cannot afford to be lost.

The coronavirus disease 2019 (COVID-19) pandemic has had a substantial impact on health 73 systems globally, affecting the management of other health threats such as antimicrobial 74 resistance (AMR). The World Health Organization (WHO) declared that AMR is one of the top 75 ten global health threats and, although often more silent than the COVID-19 pandemic, it 76

can have equally devastating consequences. 1 From 2017-2019, the number of countries 77

reporting AMR rates to WHO's Global Antimicrobial Resistance and Use Surveillance System 78 (GLASS) exponentially grew from 729 in 22 countries to more than 64,000 in 66 countries. 2 79

However, the effects of the COVID-19 pandemic threatens the progress made and is thought 80 to be having wide-reaching impacts on AMR surveillance, prevention and control efforts. 81

Experts have highlighted the link between COVID-19 and AMR, indicating that certain 82 changes such as increased antibiotic use could drive an increase in AMR; while other 83 activities such as improved infection prevention and control (IPC) might reduce AMR rates. 3 

A structured questionnaire was developed with expert input from Network members 96

(Supplementary data). The WHO health system building blocks framework was considered to 97 ensure that the impacts of COVID-19 on different health system areas were comprehensively 98 addressed. 8 Accordingly, the questionnaire consisted of compulsory Likert-scale questions 99

to assess the impacts of COVID-19 in ten topic areas (i.e. 2-10 questions per topic area): 100

Funding for AMR activities; Partnerships and oversight for AMR activities; Diagnostics and 101 laboratory testing for AMR; Laboratory supplies and equipment for AMR activities; 102

Availability of staff for AMR activities; AMR data information systems; Patient-case mix; IPC 103 practices; Antibiotic consumption; and AMR rates (Supplementary data). Likert-scale 104 responses included "Large decrease", "Moderate decrease", "No impact", "Moderate 105 increase", "Large increase", and "Do not know." To further explore country experiences, The data collected were descriptively analysed using the statistical programme R (version 120 4.0.3). Completed Likert-scale responses were graphically displayed for each of the ten topic 121 areas. Differences in responses between countries according to WHO regions and World 122

Bank income levels 9 were assessed using the Fisher's exact test and significant differences 123 (p<0.05) were reported. Free-text questions were reviewed to identify specific themes, 124 coded accordingly and considered in relation to the corresponding topic area Likert-scale 125 findings (Supplementary data). If minor typographical errors were corrected in quotations 126 for comprehension, this was indicated with "sic". 127

A total of 73 countries responded to the survey, corresponding to 75% of countries enrolled 130 in GLASS at the time of the survey ( Table 1 ). The regional and income distribution of survey 131 respondents was similar to those in GLASS, including 16% (12/73) low-income, 23% (17/73) 132 lower middle-income, 21% (15/73) upper middle-income and 37% (27/73) high-income 133 countries (Table 1 ). The median number of countries providing a response for each 134 mandatory question was 66 (i.e. incompleteness included selection of "Do not know"). 135 text questions (Table 2) , various countries reported that funding was prioritized for COVID-144 19 over AMR. This ranged from selected low-income countries who reported being 145 dependent on external funding for AMR that was impacted by COVID-19 to high-income 146 countries that reported more indirect effects which reduced resources for AMR activities. In 147 contrast, one middle-income country reported that the COVID-19 pandemic allowed them to 148 secure additional AMR funding, and another was able to purchase resources for overall IPC 149 with COVID-19 funds. since the COVID-19 pandemic. No significant income level or regional differences were seen. 157

In the free-text questions (Table 2 ), a few low-and middle-income countries (LMICs) 158 reported compounding challenges affecting partnerships, such as mobility restrictions and 159 poor internet connections. Selected middle-and high-income countries described 160 opportunities such as the creation of new partnership platforms, possibilities for data 161 exchange, and identified gaps relevant for both COVID-19 and AMR action-planning. 162 susceptibility results (AST), many (48/69; 70%) reported decreases in their ability to provide 168 training for laboratory personnel; 46% (27/59) and 43% (29/68) also reported decreases in 169 the ability to carry out molecular testing and quality management activities, respectively. No 170 significant income level or regional differences were seen. In the free-text questions ( Table  171 2), countries across income levels described influencing factors such as fewer patients 172 visiting hospitals and the need to divert staff, equipment and reagents for COVID-19 testing. 173

In contrast, one low-middle-income country reported that the laboratory network was 174 strengthened in their country and expected this to have a positive impact on the response 175 against AMR. Selected countries across income levels also highlighted the potential for 176 leveraging COVID-19 work for AMR, such as in the area of microbial genomics and rapid 177 testing for co-infections or secondary bacterial infections. 178 179

More than half of responding countries reported decreases in the availability of quality 181 laboratory reagents and consumables for bacteriology and AST (41/71; 58%) and in the 182 ability to service machines and equipment (35/67; 52%) ( Figure 1d ). In contrast, 41% (n=29) 183 and 50% (n=33) of countries reported no impact on reagent/consumable availability and 184 access to advanced technologies, respectively. Decreases in reagent/consumable availability 185 were reported more frequently by low-(11/11) and middle-income (17/31) countries 186 compared to high-income (11/26) countries, respectively (p<0.01). Decreases were also 187 more frequently reported by the African and Eastern Mediterranean regions compared to 188 other regions (p<0.01). In the free-text questions (Table 2) , countries reported broad 189 difficulties receiving supplies due to travel and import restrictions. High-income countries 190 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted March 26, 2021. ; https://doi.org/10.1101/2021.03.24.21253807 doi: medRxiv preprint reported more specific impacts on particular supplies due to COVID-19 testing, such as the 191 availability of molecular diagnostic platforms. 

Most countries who responded reported no impact on clinical (53/67; 79%) or laboratory 210 (56/72; 78%) data information systems for AMR (Figure 1f) . No significant income level or 211 regional differences. In the free-text questions (Table 2) , one low-income country reported 212 decreases in the use of AMR data information systems during the pandemic, whereas one 213 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in Decreases in outpatient visits were reported more frequently by high-(21/24) and middle-222 income (24/30) countries compared to low-income (6/11) countries (p=0.04). In the free-text 223 questions (Table 2) inappropriate IPC practices such as double gowning or gloving and performing hand hygiene 238 over gloved hands. No significant income level or regional differences were seen. In the free-239 text questions (Table 2) respectively. More than half of countries (33/58; 57%) reported no impact on the availability 253 of antibiotics. Increases in total prescribing were reported more frequently by low-(8/10) 254 and middle-income (18/24) countries compared to high-income (7/20) countries (p=0.03). In 255 the free-text questions (Table 2) , countries across income levels highlighted preliminary data 256 suggesting increases in antibiotic use although many were also not yet able to assess. 257

Selected high-income countries specified increases in the use of watch and reserve 258 antibiotics such as azithromycin at health care facilities. One middle-income country 259

reported that antibiotics are being prescribed in almost all cases of COVID-19 regardless of 260 indications and one low-income country reported that more people in the community were 261 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in impacts on selected organisms were reported more frequently by high-and middle-income 273 countries compared to low-income countries (p<0.01). In the free-text questions (Table 2) , 274 many countries across income levels reported that they were not yet able to reliably report 275 on AMR data. Several high-income countries suggested that resistance rates may be higher 276 as a result of more patients being treated in ICUs or long-term care settings. A few LMICs 277 suggested that there may be a reduction in resistance due to fewer patients presenting to 278 the hospital overall. 279 280

In the free-text questions (Table 2) , predictions from countries across income levels on the 282 long-term impacts of the pandemic on AMR were mixed, citing factors that could reduce 283 resistance, such as improved IPC, versus factors that could increase resistance, such as 284 worsening of antimicrobial stewardship practices, increased staff fatigue to detect AMR 285 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The COVID-19 pandemic is having wide-reaching impacts on all aspects of our health 297 systems. These have upended various levels of AMR surveillance, prevention and control. 298

Including a wide range of country settings, this survey gives an important initial picture of 299 the global impacts that COVID-19 has on these AMR aspects. Responses from GLASS national 300 focal points revealed some universal patterns but also captured the variability across 301 countries which, in some cases, could be linked to income level. The reported impacts 302 involved factors that could bias AMR reporting as well as potentially decrease or increase 303 AMR rates. These findings provide a useful framework to inform the ongoing 304 implementation of AMR surveillance and interpretation of data. They also present key 305 country insights on how we might use the COVID-19 response to make continued gains in 306 combatting AMR. 307 308 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in to be taking steps to promote this guidance. Improved IPC awareness and implementation 323 has been shown to improve after large outbreaks, as also seen after the 2014/2016 Ebola 324 outbreak. 14 It is an opportunity that can be utilised to promote sustainable IPC programmes 325 that can more effectively combat emerging threats such as COVID-19 and Ebola as well as 326 AMR transmission. 327 patients received antibiotics, although 3.5% and 8.5% were estimated to have bacterial co-333 infections on presentation and bacterial/fungal co-infections during admission, 334 respectively. 16 Most countries did not yet have complete data on AMR rates. It is still early in the course of 364 the pandemic to reliably report on any changes. Although it will take time to effectively 365 analyse these data, reported factors such as decreases in surveillance capacity could limit 366 the ability to provide data on true AMR changes. It is critical that AMR activities remain a 367 priority for countries and high on the global health agenda to ensure the necessary capacity 368 to detect and respond to emerging threats. Outbreaks and increases in AMR acquisition, 369 such as carbapenemase-producing Enterobacterales, during the COVID-19 pandemic have 370 been reported by hospitals, demonstrating the importance of continuing routine AMR 371 activities and closely monitoring these data. 19, 32-35 372 373 Several survey limitations should be considered. Although these results provide a useful 374 initial global snapshot of the impacts of COVID-19 on AMR, they could also be considered an 375 oversimplification of complex and varying experiences across national and facility levels. 376

Heterogeneity between countries in the robustness of their existing AMR surveillance 377 systems and activities (i.e. capacity, experience, resources) may have affected survey 378

interpretation. If national focal points did not coordinate their responses with other experts 379 or did not have sufficient knowledge of the data or dynamics in their country, the validity 380 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in ways to leverage the COVID-19 response activities to also support routine AMR prevention 391 and control, where possible, and advocate for continued investments in IPC and laboratory 392 strengthening for overall health system preparedness. It is critical to continue to monitor the 393 dynamic situation and update national action plans with lessons learned to include 394 preparedness and mitigation for future emerging threats that may also affect routine AMR 395 work. Countries are encouraged to engage with GLASS and the Network to work collectively 396 towards leveraging opportunities and addressing present challenges to improve AMR 397 surveillance, prevention and control. perpetuity.

preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in

The copyright holder for this this version posted March 26, 2021. ; https://doi.org/10.1101/2021.03.24.21253807 doi: medRxiv preprint

Tackling antimicrobial resistance in the COVID-19 435 pandemic

Multi-drug-resistant infections in the COVID-19 era: a 437 framework for considering the potential impact

Will coronavirus disease (COVID-19) have an impact on antimicrobial

Infection prevention and control in health facilities in 16

Income level Selected illustrative quotations Funding for AMR activities

"Previously, there was a small fund from the WHO country office, but during the COVID-19 pandemic, all funding and activities for AMR stopped till now…During the last 10 months, all focus is on COVID-19 and there is no support for AMR by governments and nongovernmental organizations." Lower-middle "AMR surveillance activities for national and local levels moderately decreased due to the large amount of funding allocated to laboratory services and treatment for covid-19 patients." Upper-middle "There was no funding for AMR surveillance at the national level before the pandemic." High "Indirectly, we may conclude that there is a decrease in AMR support as most microbiologists and epidemiologists were mobilized for COVID diagnostics." Partnerships and oversight for AMR activities

"Due to the mobility restrictions, activities focused on AMR stopped. Sometimes, we try to use distanced calls but no success. Internet connection is very limited in the country, it was difficult to reach each site [sic] ." Lower-middle "The WHO country office had requested a consultant to support our efforts to develop the AMR master plan, but due to the COVID-19 outbreak, all those plans failed [sic] ." "COVID-19 has created platforms for new partnerships and collaborations because of the link in Infection Prevention interventions, e.g. Water and Sanitation and Hygiene (WASH)." Upper-middle "The COVID-19 pandemic crisis and the issuance of some strict measures to confront the Corona epidemic, including the imposition of a complete curfew, led to poor communication with partners." High "More people and organisations have found each other, more possibilities regarding data exchange." Diagnostics and laboratory testing for AMR

"The schedules which had been made to train staff were stalled by the COVID-19 Pandemic. Laboratory turnaround time rose due to less staff levels than usual on the microbiology benches [sic]." Lower-middle "The laboratory network was strengthened in [our country] as part of the COVID-19 response and this will positively impact the AMR surveillance network. The decision makers are now very sensitized to labs issues [sic] ." Upper-middle "Patients avoided visiting hospitals as they were afraid to be in close contact to the healthcare personnel and inpatients. This resulted in a decrease of patient visits and microbiological orders [sic] ." High "Diagnostic pathology activity in microbiology laboratories…has declined when compared with the steep rise in testing work associated with detection of SARS-COV-2." "Whole genome sequencing (WGS) activity on antibiotic resistance strains has decreased because of the availability of WGS machines (reserved for Covid), of molecular reagents and of staff (half team and staff rotation) [sic] ." Laboratory supplies and equipment for AMR activities

"Because there has been a drop in samples being analysed and patients seen facilities, this has caused a reduction in the amount of resources spent on supplies and consumables [sic]." Lower-middle "There was no impact of COVID-19 on laboratory supplies and equipment for AMR activities as there was no functional surveillance during the COVID-19 pandemic." Upper-middle "During Covid-19 lock out, we had many difficulties to import reagents, equipment and some parts in order to repair the equipment [sic]."High "There was some impact on nucleic acid amplification-related work rather than standard culture and antimicrobial susceptibility testing. Assays detecting resistance genes via nucleic acid amplification were in some cases delayed due to the availability of PCR platforms which were in use mostly for SARS-COV-2 RNA detection." Availability of staff responsible for AMR activities

"Human resources has been one of the areas affected due to covid-19 responses, a lot of staff have been pulled to support covid-19 and this leads to no activities and actions done." Lower-middle "In general, most of health staff (doctors, nurses, lab staff, etc.) were called to respond activities of Covid-19 emergency, affecting the availability of these professionals for AMR activities [sic] ." Upper-middle "We had a 2 [moderate impact] in the availability of health professionals in several places and a great increase in the need for professionals during the beginning of the pandemic. Thus, the government supported the hiring of professionals through a specific program that identified non-employed professionals, created a national register of professionals and local demand, and then allocated these professionals where they were most needed." High "Public health colleagues have been under enormous strain throughout 2020 dealing with the ongoing pandemic. In hospitals, particularly those with small teams, the same core group of staff would traditionally deal with AMR response, stewardship and IPC activities and the added demands of COVID-19 disproportionately affects the capacity of those teams to deal with AMR and stewardship. The increased focus on environmental hygiene throughout the pandemic has likely impacted positively on cleaning. Laboratory scientific staffing resources are already very stretched and the added demands of COVID-19 pandemic on staffing has made it even more challenging to recruit [sic] ." AMR data information systems

"The biggest problem is that data are not generated as before and with the special focus on covid, dissemination platforms for data are not available and people are not paying attention to other data sets, but only covid." Lower-middle "We have a National AMR database where AMR data are stored, so no changes were experienced [sic]." Upper-middle "Hospital administration initiated planning to prevent delayed reporting [sic]." High "A laboratory-based surveillance system, originally implemented for AMR surveillance, was adapted to also capture data on SARS-CoV-2 testing and allow for the analysis of co-infections [sic]."

Low "Non-urgent hospital visits and elective surgeries decreased due to the COVID-19 scare…Hospital bed occupancy and intensive care unit admission moderately increased due to COVID-19 positive cases being held for two weeks under observation. On the other end, chronically ill cases were avoiding contact with the COVID-19 situations in the hospitals [sic]." Lower-middle "Reduction or even stopping non-emergency hospital activities (non-urgent and elective surgical procedures) during confinement. Number of ICU beds increased in some hospitals." Upper-middle "We have reorganized health services. Some started to serve only COVID-19...In addition, the understanding at the beginning of the pandemic that you should only k care in case of breathing difficulties generated a low demand for emergency care." High "Preventive measures have been taken to reduce COVID-19 transmission such as the diversion to virtual clinics and phone consultation mainly for outpatients, delivery of medicine to homes, reducing the stay in the hospital and discharging of the patients if the clinical condition is ok, postponing the elective surgeries and working mainly on the emergency procedures and surgeries [sic] ." Infection prevention and control practices

"All people and at every work station were observing hand hygiene, social distancing, alcohol hand rub, and mask wearing which positively controls spread of antimicrobial resistant organisms [sic]." Lower-middle "Our various hospital structures took advantage of this situation to strengthen their IPC activities (particularly awareness, training)." Upper-middle "Several campaigns have been held including WASH awareness campaigns." "Training is not possible due to strict social distancing. Virtual meetings are not practical if the IT system is not well supported [sic]." High "IPC staff was overworked by COVID-19 and IPC training was performed by peers (by peers and IPC link nurses)." "COVID-19 has revealed the need to integrate infection prevention and control across the entire healthcare delivery system. This needed response includes strategies for implementation across all levels of care, use of data for targeted action, tailored tools and strategies for early detection and management, effective ongoing communication and education, strong connection between public health and healthcare, policies for accountability and sustainability, and an ongoing commitment to these improvements."

Low "Due to the fever and other presenting symptoms of COVID-19, patients try to do self-medication and doctors also prescribe antibiotics empirically since the infecting agent was not able to be cultured then." Lower-middle "Consumption of WHO watch and reserve antibiotics increased because in rural facilities where diagnostic tools for COVID-19 are scarce, the use of antibiotics for pneumonia-like symptoms increased and in urban facilities, the use of azithromycin is still frequent [sic]." Upper-middle "For large hospitals, there was no impact. For smaller hospitals, moderate decrease was observed due to decreasing patient numbers [sic] ." High "Preliminary data show slight increase in March/April in watch antibiotics (such as azithromycin/carbapenems) in inpatient settings [sic] ." "We will look at this in more detail, but good data are not yet available." Antimicrobial resistance rates

"Each infection with pathogens avoidable by hygiene for us decreased." Lower-middle "It's too early to comment on impact of increase in use of antimicrobials on AMR during the pandemic, we may have better idea of the impact on AMR trends over the next couple of years." Upper-middle "For large hospitals, there was no impact. For smaller, a moderate decrease was observed due to decreasing patient number [sic] ." High "The national 2020 antibiotic resistance data will be available only next year, so it is too early to assess the impact of COVID-19 on AMR rates. However, the impression is that MDR isolates are more frequent in ICUs caring for COVID patients. Also, decreased sampling in COVID ICUs, due to the lack of personnel may contribute to underestimating the problem of MDR."

"If no concerted work is not done to control the spread of AMR it will be another pandemic to hit the world." Lower-middle "We need to balance AMR and COVID response activities." Upper-middle "We need to harness the potential of virtual and remote working methods, this will allow us to reach a larger audience with regard to training of stewardship committee members and health facility workers in their management and surveillance of AMR." High "We need to support greater resiliency in antibiotic resistance and antibiotic use programs in healthcare and public health. Because, without this resiliency, critical AR work will not happen as new threats emerge." "It is important that pauses in AMR and HCAI surveillance and stewardship activities are short-term and that experienced staff are