Since the beginning of 2020, the ongoing coronavirus disease (COVID-19) pandemic has
resulted in the deaths of more than 250,000 patients in the European Union/European
Economic Area (EU/EEA) and the United Kingdom alone [1]. By the end of 2020, as every
year, bacterial infections with antimicrobial resistance (AMR) will have caused the
deaths of more than 30,000 Europeans [2]. AMR is another ongoing pandemic that often
goes unnoticed by a majority of Europeans. Larry Kerr, co-chair of the Transatlantic
Task Force on Antimicrobial Resistance, recently compared the AMR pandemic to a multitude
of small fires that are much less visible than the single massive firestorm that is
the COVID-19 pandemic.
While experts have warned of the link between COVID-19 and AMR [3-8], studies report
conflicting evidence. Several studies—from, in particular, Germany, Italy and the
US—have reported outbreaks or an increase in infections with and/or acquisition of
multidrug-resistant bacteria during the COVID-19 pandemic [9-12]. Further studies
have reported cases of antimicrobial-resistant invasive fungal infections in COVID-19
patients [13,14], and one case of azole-resistant Aspergillus spp. infection in an
immunocompetent COVID-19 patient [15]. However, other studies from France and Spain
did not show an increase in infections with multidrug-resistant bacteria [16,17],
and one Italian study even saw a reduction in Clostridioides difficile infections
in hospitalised patients [18]. In a rapid review, Fattorini et al. found that only
1.3% of 522 COVID-19 patients in intensive care units (ICUs), and apparently no COVID-19
patients in other units, developed a healthcare-associated superinfection with antimicrobial-resistant
bacteria [19].
These different experiences may just be the consequence of previous antibiotic prescribing
and infection prevention and control (IPC) practices that resulted in varying background
AMR prevalence, in particular in healthcare settings, in different countries [8,20].
Still, antibiotic prescribing and IPC practices may change during the COVID-19 pandemic
and AMR could either increase or decrease as a result of these changes [5]. As pointed
out by Nieuwlatt et al. [21], COVID-19 and AMR are parallel and interacting health
emergencies that have similarities and offer opportunities for mutual learning with
regard to their control. But the question remains whether the AMR situation in Europe
and elsewhere will worsen or improve as a consequence of the current COVID-19 pandemic.
We summarised various determinants that may result in either an increase or, inversely,
a decrease in AMR and found them to be balanced (Table). The truth is that the impact
of the COVID-19 pandemic on AMR will only become clear in the coming months and years
as data gradually become available. Changes in AMR will most likely vary depending
on the setting—e.g. ICUs vs other hospital units, hospital vs community settings—and
possibly between countries.
Table
Factors that may influence levels of antimicrobial resistance during the COVID-19
pandemic
Type of factor
Factors that may favour an increase in AMR
Factors that may favour a decrease in AMR
Antibiotic use in hospitals
• About 70% of hospitalised COVID-19 patients receive antibiotics [33,34]• COVID-19
patients often receive empiric broad-spectrum antibiotic therapy [34-36]• 16% of hospitalised
COVID-19 patients develop a secondary bacterial infection [34], which will necessitate
antibiotic therapy• Possible increased use of azithromycin and teicoplanin (because
of the initial absence of clear guidelines for the treatment of COVID-19 patients)
[4,6,8]• Difficulties in accessing advice from experts before prescribing antimicrobial
agents [4]• Antimicrobial stewardship efforts may be undermined because of high workloads
and shifting priorities related to COVID-19 [37,38]• Possible aggravation of existing
shortages of certain narrow-spectrum antimicrobial agents [39,40]
• Bacterial co-infection (estimated on presentation) in only 3.5% (95% CI: 1–7%) of
COVID-19 patients [33]• Bacterial/fungal infection in only 8% of hospitalised COVID-19
patients vs 11% in non-COVID-19 patients [34]; the percentage for COVID-19 patients
may be underestimated because many may have received empiric antimicrobial therapy
[41]• Only 1.3% of COVID-19 patients in ICUs, and apparently no patients in other
units, developed a healthcare-associated superinfection with antimicrobial-resistant
bacteria [19]• Postponed planned surgical interventions result in fewer antibiotic
courses for surgical prophylaxis [42]• Fewer emergency and planned hospital admissions
[43,44], including chronically ill patients (e.g. oncology patients, diabetic patients,
transplant patients), resulting in fewer antibiotic prescriptions
Infection prevention and control in hospitals
• Difficulties for HCWs in adhering to standard IPC precautions because of long shifts
wearing the same PPE [45] and possible shortages of certain equipment [5]• Focus of
HCWs on self-protection (e.g. universal gloving practices) rather than on preventing
cross-transmission between patients• In COVID-19 cohort units and ICUs, sessional
use of PPE, e.g. long-sleeved gowns that prevent effective hand hygiene [46] and gloves
that may not be changed between patients [45]• Overcrowded facilities and possible
staff shortages leading to low HCW-to-patient ratios [5]• Shortages of HCWs with appropriate
IPC training [4]• Longer hospital stays for COVID-19 patients [5]• Traditional IPC
efforts may be temporarily discontinued, including those targeting antibiotic-resistant
bacteria, e.g. decreased frequency of screening for carriage of MDROs and difficulties
in isolating or cohorting MDRO-positive patients [4,47]• Decreased laboratory capacity
to detect AMR carriage, e.g. for processing rapid tests for MDROs, because resources
are focused on SARS-CoV-2 diagnosis [4]
• Isolation of COVID-19 patients with enhanced standard precautions, e.g. increased
hand hygiene and use of PPE, plus universal chlorhexidine bathing protocols for patients
in ICUs [5]• Increased disinfection of the environment [4,5]• COVID-19 patients are
often cohorted in one single unit and cared for by the same group of HCWs [5]• Fewer
emergency and planned hospital admissions [43,44], including chronically ill patients
(e.g. oncology patients, diabetic patients, transplant patients), resulting in lower
colonisation pressure by fewer carriers of MDROs• Fewer transfers from long-term care
facilities may lead to fewer cycles between long-term care facilities and hospitals
[5]• Construction of new COVID-19 facilities without an established reservoir of MDROs
[5]
Antibiotic use in the community
• Likely increased antibiotic use in nursing homes and other long-term care facilities•
Possible increased self-medication with antibiotics in some countries or regions of
the world [48]
• Possible decreased antibiotic consumption because of fewer patient consultations,
e.g. for self-limiting infections that would otherwise have resulted in an antibiotic
prescription [4]• Possible decreased incidence of respiratory tract infections as
a consequence of decreased person-to-person transmission because of lockdowns, resulting
in decreased antibiotic consumption• Possible increased awareness of the difference
between viruses and bacteria, and the fact that there are different types of medicines,
i.e. antivirals and antibiotics, respectively, for different types of infections [8]•
Increased influenza vaccine uptake may decrease the incidence of bacterial superinfections
after influenza
Hygiene practices in the community
• Increased use of sanitisers and other biocidal agents and their release in the environment
[3,6,8,49]
• Increased hand hygiene practices and compliance in the community• Increased physical
distancing and use of face masks• Increased disinfection of the environment
Cross-border spread
• Fewer patient transfers of seriously ill patients between countries, resulting in
less frequent cross-border spread of MDROs• Large decrease in international air travel,
resulting in decreasing risk of global dissemination of antimicrobial-resistant bacteria
and genes from highly endemic regions [8,50]
Public health policy making, including One Health
• Shift in high-level policy making towards viral diseases and preparedness for emerging
viruses• National plans and other initiatives to fight AMR are likely to have been
slowed down, temporarily discontinued or even postponed because of COVID-19 public
health emergencies and duties (similar to the WHO Global Strategy for Containment
of Antimicrobial Resistance, which was launched on 11 September 2001 and went largely
unnoticed by the global community, without any major impact on AMR activities for
almost a decade, because of the disproportional focus on biosecurity issues)• Potential
One Health impact of increased volumes of antibiotics from prescriptions in humans
being released in the environment [3,51]
• Gain in public and political attention for all threats related to communicable diseases,
including already endemic issues such as AMR• Possible decrease in antimicrobial consumption
in animals because of reduction in the size of livestock herds [52], possibly combined
with difficulties in obtaining antibiotics
AMR: antimicrobial resistance; CI: confidence interval; COVID-19: coronavirus disease;
HCW: healthcare worker; ICU: intensive care unit; IPC: infection prevention and control;
MDRO: multidrug-resistant organism; PPE: personal protective equipment; SARS-CoV-2:
severe acute respiratory syndrome coronavirus 2; WHO: World Health Organization.
Keeping the momentum
On the occasion of European Antibiotic Awareness Day (EAAD), the European Centre for
Disease Prevention and Control (ECDC) will publish its annual reports on surveillance
of AMR from the European Antimicrobial Resistance Surveillance Network (EARS-Net)
and on surveillance of antimicrobial consumption in humans from the European Surveillance
of Antimicrobial Consumption Network (ESAC-Net). Data up to 2019 are already available
from the ECDC Surveillance Atlas of Infectious Diseases [20] and the ESAC-Net database
[22]. The World Health Organization (WHO) Regional Office for Europe will also publish
an update of its annual report of the Central Asian and European Surveillance of Antimicrobial
Resistance (CAESAR) [23], including data up to 2019. The European Medicines Agency
(EMA) just published its 10th report on the European Surveillance of Veterinary Antimicrobial
Consumption with data from 2018 [24]. ECDC, EMA and the European Food Safety Authority
are currently working on a third Joint Interagency Antimicrobial Consumption and Resistance
Analysis report, to be published in 2021, which will include a detailed One Health
analysis based on data from 2016 to 2018. At the global level, the latest WHO Global
Antimicrobial Resistance Surveillance System Early Implementation Report 2020 on AMR
has data from 2018 [25].
Unfortunately, more recent data are not yet available from these networks to assess
the impact of COVID-19 on AMR. As of December 2018, only nine EU/EEA countries used
machine-to-machine links for reporting data from clinical laboratory information management
systems to a national database on EU-notifiable diseases and on AMR, respectively
[26]. While the collection and analysis of certain data requires time, we obviously
need to implement systems for AMR surveillance in Europe that can obtain data and
provide results much faster, taking as examples those that have already been implemented
or are being tested in some European countries or projects [26,27].
In addition, specific studies will need to be performed to assess changes in antibiotic
prescribing, IPC practices and their effect on AMR as a consequence of the COVID-19
pandemic. One important point that will require consideration is that the effects
of changes in antibiotic prescribing and IPC practices on AMR is unlikely to be immediate,
and that the necessary delays to observe these effects—as well as the thresholds above
which changes in antibiotic prescribing and IPC result in an effect—will need to be
taken into account when analysing data [28]. We should learn from the COVID-19 pandemic,
with its rapid turnover and use of whole genome sequencing data, and dynamic linkage
of various health databases [8,29]. Surveillance data based on clinical samples in
particular, if focused only on bloodstream infections, may provide a distorted picture
of the effect of COVID-19 on AMR since the effect may only manifest itself in other
clinical sites or even only in the commensal flora. This means that studies based
on existing surveillance data should be complemented by well-designed cohort studies
with serial surveillance swabs, e.g. in ICUs and other high-risk units.
European Antibiotic Awareness Day and World Antimicrobial Awareness Week 2020
On 18 November, we will celebrate the 13th EAAD, in partnership with the World Antimicrobial
Awareness Week, from 18 to 24 November 2020. Much has happened in Europe since the
first EAAD in 2008: repeated awareness campaigns took place, EU and national action
plans were developed in most EU/EEA countries and regulatory actions, policy initiatives
and interventions were enacted at EU and national levels. One example of EU regulatory
action is provided in this issue by Opalska et al., who reviewed all EU post-authorisation
procedures of harmonising product information for antibiotics from 2007 to 2020. The
study found that the majority resulted in a restriction of indications for antibiotics,
which could have contributed to decreasing their consumption and, ultimately, AMR
[30]. The authors are planning further studies on the effect of such regulatory actions
on antimicrobial consumption to inform future policies.
As suggested last year by Peñalva et al., there are signs that the many actions and
initiatives implemented at EU and national levels may start to show their effects
on antimicrobial consumption and AMR trends [31]. Nevertheless, much remains to be
done to prevent and control AMR in Europe. The most recent data from EARS-Net confirm
that AMR is still a serious challenge for the EU/EEA. In particular, the percentages
of Enterococcus faecium from bloodstream infections that are resistant to vancomycin
almost doubled between 2015 and 2019. Resistance to carbapenems—a last-line group
of antibiotics—continues to be a concern, with several countries reporting carbapenem-resistance
proportions above 10% in Klebsiella pneumoniae, and very much higher in Pseudomonas
aeruginosa and Acinetobacter species bloodstream infections [20]. In this issue, a
survey by Lötsch et al. provides further evidence on A. baumannii. Authors found that
seven European countries report an endemic situation, while another nine report regional
or inter-regional spread of specifically carbapenem-resistant A. baumannii, with national
capacities for its surveillance and containment varying depending on the country [32].
For example, only 23 of the 37 participating European countries had a surveillance
system for reporting carbapenem-resistant A. baumannii, 15 had national recommendations
or guidelines for its control and only eight countries had a national plan for its
containment—only one of which was one of the seven endemic countries.
The COVID-19 pandemic reminds us that compliance with IPC measures is critical to
ensure the safety of hospitalised patients. Most IPC measures that are essential for
controlling the spread of SARS-CoV-2 also contribute to reducing the spread of antimicrobial-resistant
bacteria; these, together with antimicrobial stewardship programmes, must be maintained
and strengthened. In the midst of the COVID-19 pandemic, we certainly must not give
up on our efforts to prevent and control AMR and must stay united to preserve the
effectiveness of antimicrobials.