13 May 2020
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COVID-19 represents an unprecedented public health crisis that will bring many novel insights. This worldwide disturbance will probably affect the epidemiology of antimicrobial resistance (AMR) in many different ways that we have not previously considered. Here, I attempt to highlight a few possible effects of the COVID-19 pandemic on AMR and related secondary bacterial infections and report our current experience here at the Geneva University Hospitals, Geneva, Switzerland.
The canton of Geneva experienced the highest incidence of COVID-19 in Switzerland with more than 250 deaths and over 1000 hospitalized COVID-19 patients (in March and April 2020).
Will COVID-19 have an impact on antimicrobial resistance?
Conventional wisdom suggests that COVID-19 will increase AMR worldwide. Indeed, these concerns have been raised in the last three months in magazines, newspaper articles, publications and on the sites of nonprofit organizations, including GARDP. These opinions are based on several factors, which may or may not become true by a large measurable effect on drug-resistant infections. First, many COVID-19 patients receive broad-spectrum antibiotics because of diagnostic uncertainty about possible bacterial pneumonia or nosocomial superinfections. Furthermore, self-medication with antibiotics may increase in some regions of the world. Undoubtedly, this will increase antibiotic selective pressure worldwide, at least for a limited time period. Second, antimicrobial stewardship efforts are massively undermined, as described in a previous Antimicrobial Viewpoint article from Andrew Seaton. Third, past experiences have shown that during massive viral outbreaks healthcare workers (HCWs) cannot respect all basic infection control procedures to protect patients – understandably, their focus shifts towards protecting themselves. This leads for instance to universal gloving practices that increase the risk of nosocomial transmission of drug-resistant infections such those by as MRSA, as was observed during the SARS crisis in Hong Kong almost 20 years ago1. Finally, many AMR control initiatives will be temporarily discontinued or even stopped, due to COVID-19-related public health emergencies and duties. This is what happened with the first global WHO AMR containment strategy, which was launched on 11 September 2001 and went largely unnoticed by the global community and without any major impact for almost a decade due to the disproportional focus on biosecurity issues.
COVID-19 may not necessarily result in increased AMR
Yet will this pessimistic scenario of increasing AMR and related infections become true? Well, I have several doubts and open questions, as outlined below.
- Due to the COVID-19 crisis, fewer chronically ill patients with a long-lasting AMR exposure and carriage history (e.g. oncology patients, diabetic patients, transplant patients) are currently admitted to acute care hospitals. Thus, it is conceivable that we may experience a complete change in the usual multidrug-resistant organism (MDRO) hospital reservoir and carriage status, leading to less nosocomial MDRO colonization pressure and risk of cross-infection.
- No seriously ill patients are currently transferred and repatriated from abroad to their home countries, which are well-known risk factors for hospital outbreaks. Moreover, at least in Western Europe, all COVID-19 patients transferred between countries are routinely screened for MDRO carriage.
- International travel has largely stopped, decreasing the risk of global dissemination of drug-resistant bacteria from highly endemic regions such as South Asia.
- The increasing antibiotic selection pressure may have a rather short-lived effect on the gut and oropharyngeal flora (microbiomes) in selected bacterial species. This may not be easily detectable and may vanish rapidly after the peak of the COVID-19 pandemic and its related irrational misuse and overuse of antibiotic agents2.
- Well-conceived cohort studies with longitudinal sampling may be required to decrease detection bias and document a silent increase in drug-resistant bacteria in the commensal flora (microbiome). However, this effect may not be universal, as I could imagine that the prevalence of certain drug resistances may even decrease and be related to lower use of specific antibiotic classes that are not commonly used for respiratory tract infections (e.g. ciprofloxacin resistance). This was seen during a national restriction in Israel during the anthrax threat in 2001/20023.
- We have observed in many hospitals around the world substantially increased compliance with hand hygiene and other infection control measures, including environmental disinfection and universal chlorhexidine bathing protocols. This may have a positive effect on decreasing the incidence of drug-resistant infections.
- The COVID-19 cohorting units established in most affected regions may help to limit any transmission of drug-resistant bacteria to COVID-19-negative patients hospitalized in the same healthcare facility.
- In contrast to the typical influenza infections and related pneumonias, far fewer COVID-19 patients have had an initial bacterial superinfection at admission due to pneumococci, other streptococci or staphylococci. This observation is starting to be disseminated among clinicians, thereby decreasing possibly antibiotic treatment duration and selection pressure during the anticipated second wave of COVID-19 that may hit the northern hemisphere in 2020.
Many AMR control initiatives will be temporarily discontinued or even stopped, due to COVID-19-related public health emergencies and duties.
COVID-19: Our experience in Geneva
What has our experience in Geneva been so far? The canton of Geneva experienced the highest incidence of COVID-19 in Switzerland with more than 250 deaths and over 1000 hospitalized COVID-19 patients (in March and April 2020), including up to 65 intubated COVID-19 patients in early April. We observed a few nosocomial bacterial and fungal superinfections without large clusters. These were mostly caused by drug-susceptible bacteria. In parallel, based on weekly prevalence surveys for which all patients were screened for asymptomatic carriage of MDROs, a decrease in drug-resistant infections and colonization was observed in the ICU. The next 12 months will show us whether these positive trends will hold true for Geneva and other hospitals, despite increased antibiotic selection pressure during the pandemic period.
Despite these uncertainties, I agree with many colleagues that to prevent drug-resistant infections antibiotic stewardship efforts should not be discontinued and AMR control strategies should be reinforced during the COVID-19 crisis. Most importantly, let’s not forget, as stated in a World Economic Forum (WEF) report in 20134, “while viruses may capture more headlines, arguably the greatest risk of hubris to human health comes in the form of antibiotic-resistant bacteria”.
References:
- Yap FH, Gomersall CD, Fung KS, Ho PL, Ho OM, Lam PK et al. Increase in methicillin-resistant Staphylococcus aureus acquisition rate and change in pathogen pattern associated with an outbreak of severe acute respiratory syndrome. Clin Infect Dis. 2004 Aug 15;39(4):511-6
- Malhotra-Kumar S, Lammens C, Coenen S, Van Herck K, Goossens H. Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet. 2007 Feb 10;369(9560):482-90.
- Gottesman BS, Carmeli Y, Shitrit P, Chowers M. Impact of quinolone restriction on resistance patterns of Escherichia coli isolated from urine by culture in a community setting. Clin Infect Dis. 2009 Sep 15;49(6):869-75.
- World Economic Forum. The Dangers of Hubris on Human Health. 2013.
Stephan Harbarth earned his medical degree in 1993 from Ludwig-Maximilians-University in Munich, Germany, and completed his residency in internal medicine and tropical medicine at Munich University Hospitals. After serving as a clinical fellow in the Infectious Diseases Division in the Department of Internal Medicine at Geneva University Hospitals, Stephan completed his master’s degree in epidemiology at Harvard University, Boston. He is board certified in infectious diseases and was appointed full professor at the University of Geneva in 2018.
Stephan’s work has garnered several awards. His group currently conducts several clinical and epidemiological studies to evaluate key questions related to the control of the acquisition, transmission and infection by multidrug-resistant microorganisms. He participates in several ongoing large-scale EU-funded studies (R-GNOSIS, AIDA, COMBACTE) and coordinated the DRIVE-AB project to address this public health threat.
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