The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of March 16, 2022, SARS-CoV-2 has infected over 462 million worldwide and caused almost 6. In an attempt to reduce mortality due to COVID-19, antibiotics were initially used to treat COVID-19 patients with moderate to severe illness.
In a recent Antimicrobial Resistance & Infectious Control study, researchers discuss the impact of this extensive use of antibiotics on the rise of antimicrobial resistance (AMR).
Study: Antimicrobial Resistance (AMR) In COVID-19 Patients: A Systematic Review and Meta-Analysis (November 2019-June 2021). Image Credit: Kateryna Kon / Shutterstock.com
Antimicrobials were prescribed for a number of reasons to treat COVID-19, including the similarity of its symptoms to those of bacterial pneumonia or coinfections, as well as the inclusion of antibiotics in some protocols for COVID-19 treatment. The free use of antimicrobials could have boosted AMR, leading to the emergence of resistant variants of highly pathogenic bacteria.
To help understand the extent to which COVID-19-associated antimicrobial therapy led to AMR, the current study reviewed available literature on coinfections in COVID-19 patients, the type of antimicrobial therapies used, and the percentage of AMR reports.
In the current study, scientists examined 38 studies, of which a third reported the use of matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-ToF MS) to identify the organism exhibiting AMR. Most studies dealt perfunctorily or not at all with microbiological identification and definitions used for AMR.
Overall, almost 75% of patients had confirmed COVID-19, while the incidence of coinfection ranged from 2.5% to 100% between studies. Bacterial and fungal coinfections were reported, but not parasites.
In larger studies, 0.2-100% showed coinfection with a resistant microbe. Higher rates of these types of coinfections were reported when the patients had acute respiratory distress syndrome (ARDS), ventilator-associated pneumonia, or bloodstream infections. In one interesting study, 5% of patients on tocilizumab had coinfection with resistant bacteria.
About 25% of patients in these studies experienced both bacterial and fungal infections along with COVID-19, though the proportion of each varied widely between studies. Patients admitted to the intensive care unit (ICU) had a higher proportion of AMR than other COVID-19 patients. Similarly, ICU patients in COVID-19-dedicated ICUs tended to have higher AMR percentages as compared to those in regular medical facilities.
AMR was also higher in North America, Asia, and other non-European regions to a lesser extent as compared to Europe. However, none of these trends were statistically significant.
Of almost 390 studies, 1,960 unique organisms were reported, of which approximately 30% were resistant to one or more antimicrobials. Of the Gram-negative organisms, Klebsiella pneumoniae and Acinetobacter baumannii were the most commonly identified and were reported in approximately 150 -170 cases, while Pseudomonas aeruginosa and Escherichia coli were present in 40-60 cases. Among these, resistance was found to occur through several mechanisms, including beta-lactamase, carbapenamase, and extended-spectrum beta-lactamase (ESBL) activity.
The most common Gram-positive resistant organism was methicillin-resistant Staphylococcus aureus (MRSA), which was identified in over 130 cases, followed by coagulase-negative staphylococci and vancomycin-resistant Enterococcus (VRE) species, especially E. faecium, which was highly resistant. Candida auris, C. albicans, and other Candida species showing resistance to one or more antifungals were also identified.
Of all patients included in the reviewed studies, age and sex were available for just over a hundred patients, of which over 50% were males with a median age of 65 years. While 80% of these patients had other underlying illnesses, all but 20 presented with illness due to the coinfecting organism. The most common was A. baumannii, followed by K. pneumoniae and C. auris, whereas the other infecting organisms were reported in less than ten patients each.
Five patients had mixed infections, such as P. aeruginosa and C. auris infection, with or without VRE, or MRSA with C. albicans.
Less than 50% of patients in these studies were on tocilizumab, which is an interleukin-6 (IL-6) receptor blocker. Notably, about 20% of patients received tocilizumab in addition to steroids, whereas over 50% also received other drug combinations. Mechanical ventilation was required for 90% of patients.
Over 50% of all coinfected patients died, almost all of whom were infected with resistant organisms.
Previous evidence of coinfection during influenza outbreaks has been presented. The results of the current study show that there was a relatively high incidence of AMR, as shown by microbiological tests, during the first 1.5 years of the COVID-19 pandemic. This agrees with prior research on AMR and adds an estimate of the true prevalence of this phenomenon among COVID-19 patients.
The researchers add that almost all patients with COVID-19 were placed on antimicrobials, mostly Azithromycin, before or during hospital admission. The increased proportion of AMR among ICU COVID-19 patients is not unexpected, given their likelihood of receiving both immunosuppressive drugs and antimicrobials, which raises the chances of coinfection. Among patients on mechanical ventilation, the risk is still higher.
Low-income settings increase the chances of poor sanitation, increased proximity with livestock, and low levels of surveillance, which leads to a higher probability of AMR. In fact, healthcare settings, socioeconomic status, prior antibiotic usage, and the duration of hospitalization are all risk factors for coinfection. This could help identify patients at higher risk when they present with an infection like COVID-19.
Given the difficulty differentiating viral pneumonia from bacterial pneumonia, it is challenging to avoid unnecessary usage of antimicrobials until confirmation of SARS-CoV-2 is obtained.”
The use of infection control and prevention strategies, as well as strict limits on antibiotic usage, may help reduce AMR in this subset of patients and, as a result, reduce morbidity and mortality rates among this subset of COVID-19 patients.
- Kariyawasam, R. M., Julien, D. A., Jelinski, D. C., et al. (2022). Antimicrobial Resistance (AMR) In COVID-19 Patients: A Systematic Review and Meta-Analysis (November 2019-June 2021). Antimicrobial Resistance & Infection Control. doi:10.1186/s13756-022-01085-z.