QIAGEN

Sonia N. Rao

The Coronavirus Disease 2019 (COVID-19) pandemic has presented an unprecedented challenge to public health and has had a significant impact on healthcare resource utilization. A newfound concern presenting extreme challenges to Antimicrobial Stewardship Programs (ASP) is the high rates of prescribed antibiotics to patients with either confirmed or suspected COVID-19 which potentially further contributes to antimicrobial resistance (AMR). Even prior to the pandemic, there were 2.8 million antibiotic-resistant infections that accounted for 35,000 deaths from AMR and an excess of $20 billion in health-care expenditure within the United States alone1.

“The COVID-19 pandemic has highlighted the indisputable need for accurate, reliable, and time-sensitive diagnostics”

As many patients with COVID-19 present with overlapping clinical and radiological findings of respiratory illness that are consistent with a range of respiratory pathogens, including bacteria, it is no surprise that healthcare providers begin empiric antimicrobial therapy per standard of care. However, limited and variable data exist on rates of bacterial infection associated with COVID-192,3. A systematic analysis by Langford et al. demonstrated that the overall proportion of COVID-19 cases with bacterial co-infection was 6.9% (95% CI; 4.3-9.5%), of which 3.5% were co-infections on presentation, 14.3% were secondary infections post-COVID-19, and higher rates of co-infection were seen in critically ill patients (8.1%, 95% CI; 2.3-13.8%)4. Interestingly, despite the relatively low rates of bacterial co-infections with COVID-19, 72% of patients were treated with antibiotics for undefined durations. Additionally, there is an interesting trend in antimicrobial prescription practices observed when comparing bacterial infection rates stratified by location of care. In the community setting, three studies described decreased antimicrobial use and reduced diagnosable infections following “lockdowns,” and this trend persisted even as COVID-19 cases fell potentially due to the associated mitigation measures5,6,7. On the other hand, the high rates of reported hospital- acquired bacterial infections in patients admitted for COVID-19 (21-51%) may account for the higher rates of antimicrobial use seen in intensive care settings (65-95%)8,9,10. Unfortunately, the medical community now faces an increased risk of potential outbreaks of multi-drug resistant organisms, possibly due to infection control practices, double occupancy rooms, and potentially high rates of antimicrobial use, which could persist long after the COVID-19 pandemic.

A systematic review by Lansbury L et al. demonstrated that the overall proportion of COVID-19 patients who had a bacterial co-infection was lower when compared to influenza pandemics. Limited evidence of S. aureus, S.pneumoniae, or S. Pyogenes co-infection was present, supporting stopping empirical antibiotics treatments10. Additional evidence suggests that due to low overall rates of bacterial infections, early antimicrobial therapy does not appear to influence patient outcomes11. The Lansbury et al. study also estimated that only 3% of patients hospitalized with COVID-19 were co-infected with another respiratory virus which may be underestimated due to the lower rates of seasonal respiratory viruses seen in 2020 compared to pre-pandemic. It remains to be determined what the next influenza-like illness (ILI) season looks like as social distancing and other protective measures are relaxed.

The COVID-19 pandemic has highlighted the indisputable need for accurate, reliable, and time-sensitive diagnostics. Multiplex PCR or syndromic testing has the ability to identify and differentiate amongst >20 respiratory pathogens with a rapid turnaround time of under two hours. A study published early in the COVID-19 pandemic, utilizing a respiratory panel, found influenza accounted for ~30% of COVID-19 suspected cases. The authors concluded that syndromic testing provided an alternative diagnosis which facilitated prompt initiation of antiviral therapy and discontinuation of unnecessary antibiotics12. 

Respiratory panels have the ability to serve as a powerful tool in the differential diagnosis of patients suspected of COVID-19, in addition to aiding in epidemiological surveillance and public health measures. A respiratory panel can help guide clinical decision-making in both inpatient and outpatient settings. A rapid and accurate identification of the causative pathogen(s) may provide clinicians more confidence in discontinuing antimicrobial therapy, especially if a non-bacterial pathogen is identified. However, there needs to be a close collaboration between the laboratory and clinician in order to ensure the advanced molecular test results are transmitted and acted upon in real time. Laboratories must work with ASPs to ensure that syndromic panels are implemented appropriately in order to optimize laboratory workflow and maximize clinical outcomes. In a situation where time is of the essence of a diagnosis, such as a critically ill patient, a syndromic panel may aid in ASP efforts through faster and comprehensive identification of potential pathogens. However, well-designed, controlled trials are needed to support the hypothesis regarding the ability of a syndromic respiratory panel to reduce antimicrobial overprescribing.

References:

1. CDC. Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019

2. Chen N, Zhou M, Dong X, et al, Lancet 2020.a

3. Siddiqi HK, Mehra MR. J Heart Lung Transplant 2020.

4. Langford BJ, So M, Raybardhan S, et al. Clin Micro Infect 2020.

5. Zhu N, Aylin P, Rawson T, et al. Clin Micro Infect2020

6. Malcolm W, Seaton RA, Haddock G, et al. JAC-Antimicrobial Resistance 2020 (2).

7. King LM, Lovegrove MC, Shehab N, et al. Clin Infect Dis 2021

8. Zhou F, Yu T, Du R, et al.Lancet 2020

9. Contou D, Claudinon A, Pajot O, et al.Ann Intensive Care 2020.

10. Lansbury L, Lim B, Baskaran V, et al. J Infection 2020

11. RECOVERY Collaborative Group. Lancet 2021; 397:605-12.

12. Bordi L, Nicastri E, Scorzolini L et al. Euro Surveillance 2020.