International guidelines recommend the initiation of empirical antibiotherapy for possible associated bacterial pneumonia in COVID-19 critically ill yet further suggesting a rapid reassessment upon source documentation [1]. In this prospective cohort analysis, we investigated the respiratory co-infection rate in COVID-19 critically ill through the use of rapid molecular testing and measured its impact on antibiotic management.
This preliminary analysis was conducted over a 1-month period at the intensive care unit (ICU) of the Cliniques universitaires Saint-Luc and included all COVID-19 adult patients from whom a lower respiratory tract sample could be obtained. Specimens were conveyed to the microbiology laboratory where a FilmArray Pneumonia Panel plus test (FA-PNEU, BioFire Diagnostics, Salt Lake City, UT, USA) was performed. The FA-PNEU is an automated multiplex PCR test allowing direct detection of 15 bacteria with a semi-quantitative value, 3 atypical bacteria, 9 viruses, and 7 antimicrobial resistance genes within 1 h and 15 min [2]. FA-PNEU testing was done 24/7, and results were immediately called to the intensive care physician pursuing antimicrobial optimization.
Forty-one COVID-19 patients were admitted to ICU, and 32 could be included upon respiratory sample availability. The study population was comparable to previously described COVID-19 critically ill in terms of age, sex ratio, severity scores, comorbidities, and symptoms [3]. FA-PNEU was performed within a mean of 10 days following symptoms’ onset and a mean of 1 day following ICU admission. FA-PNEU results identified 13/32 (40.6%) patients with a bacterial co-infection as detailed in Table 1. Staphylococcus aureus, Haemophilus influenza, and Moraxella catarrhalis were the principal bacteria identified with significant genome copies. None of the 32 FA-PNEU tests identified atypical bacteria neither other respiratory viruses. Direct communication of FA-PNEU results led to speeded-up antibiotic modifications in 15/32 (46.9%) patients.
Table 1.
FA-PNEU results and antibiotic management (this table should appear after the result section)
| Patient no. | Sample type | FA-PNEU results | Treatment switch initiated by FA-PNEU results | |
|---|---|---|---|---|
| Detected pathogens (106 ≥ 107) | Initial antibiotherapy | Subsequent antibiotherapy | ||
| 1 | Sputum | – | None | None |
| 2 | ETA | Pseudomonas aeruginosa | None | Ceftazidime |
| 3 | ETA | Moraxella catarrhalis | None | Cefuroxime |
| 4 | ETA | – | None | None |
| 5 | ETA | – | None | None |
| 6 | Sputum | – | None | None |
| 7 | ETA | – | None | None |
| 8 | ETA | – | Cefuroxime | None |
| 9 | Sputum | Haemophilus influenza | None | Cefuroxime |
| 10 | ETA | – | None | None |
| 11 | ETA | – | Cefuroxime | None |
| 12 | ETA | M. catarrhalis | Cefuroxime | Cefuroxime |
| 13 | ETA | Staphylococcus aureus | None | Flucloxacilline |
| 14 | ETA | – | None | None |
| 15 | ETA | – | None | None |
| 16 | ETA | Streptococcus agalactiae | Cefuroxime | Cefuroxime |
| 17 | Sputum | – | None | None |
| 18 | ETA | S. aureus | None | Flucloxacilline |
| 19 | ETA | – | Cefuroxime | None |
| 20 | ETA | – | None | None |
| 21 | ETA | S. aureus | Amoxicilline - clavulanic acid | Amoxicilline - clavulanic acid |
| 22 | Sputum | H. influenza | None | Cefuroxime |
| 23 | ETA | H. influenza | None | Cefuroxime |
| 24 | ETA | – | Cefuroxime | None |
| 25 | ETA | S. aureus | Cefuroxime | Flucloxacilline |
| 26 | ETA | – | None | None |
| 27 | Sputum | S. aureus + mecA/C | None | Vancomycine |
| 28 | Sputum | – | None | None |
| 29 | Sputum | – | None | None |
| 30 | Sputum | – | Piperacilline-tazobactam | None |
| 31 | ETA | – | None | None |
| 32 | ETA | S. aureus + mecA/C − H. influenza | None | Vancomycine + cefuroxime |
ETA endotracheal aspirate, FA-PNEU FilmArray Pneumonia Panel plus test
It is a known difficulty to adjudicate on the presence of a co-infection in COVID-19 patients particularly in critically ill. Clinical presentation, inflammatory markers, and bilateral radiological infiltrates lead to misperception and cannot be used in the diagnosis of a bacterial superinfection. As a consequence, empirical antibiotherapy is quasi-systematically initiated until microbiological documentation of co-infecting pathogens. Yet, current data on co-infections is limited. With the focus on intensive care settings, a case series in February 2020 analyzing 21 COVID-19 ICU patients reported no bacterial respiratory co-infections but 3 influenza infections [4]. A similar case series investigated in March 2020 stated none of the 15 COVID-19 critically ill had a bacterial co-infection neither were they tested positive for respiratory viruses [5]. No information however was available on how patients were tested neither on treatment strategy. In our setting applying generalized molecular screening for co-infection, the rate was 40.6% and the main detected pathogens were causal agents of community-acquired pneumonia.
As rapid molecular testing was performed within the shortest possible time following ICU admission, a majority of our patients did not receive empirical antibiotherapy while awaiting FA-PNEU result. Ultimately one third of the patients remained antibiotic-free over the entire process, and 5 patients had their antibiotics stopped following a negative FA-PNEU result. These antibiotic savings are crucial for COVID-19 critically ill known to have a long ICU stay with reported nosocomial infection rates as high as 31% [6].
To conclude, bacterial documentation is essential to assess co-infection in COVID-19 critically ill. The use of molecular diagnostic tools and the initiation of narrow-spectrum antibiotics are key elements of COVID-19 antimicrobial stewardship guidelines in critically ill. Studies on larger populations and in different geographical areas should be performed to outline analogous antibiotic saving strategies.
Acknowledgements
We thank all interns from the intensive care units for their collaboration in the inclusion of the critically ill. We also thank all laboratory technicians and interns from the clinical laboratory who performed the testing. Ultimately, we thank all patients and their family that participated in this study.
Abbreviations
- ICU
Intensive care unit
- FA-PNEU
FilmArray Pneumonia Panel plus test
Authors’ contributions
AV and PFL designed the study. LG, XW, CC, and PFL included the patients. AV and AS collected and summarized the clinical data. AV and PFL drafted the manuscript. AS, LG, XW, and CC revised the final manuscript. The authors read and approved the final manuscript.
Funding
This work was funded by the BioFire Diagnostics (Salt Lake City, UT, USA) as they supplied 2 FilmArray systems and the tests. The Biofire Diagnostics did not have any role in the design of the study neither in the collection, analysis, and interpretation of data.
Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Ethics approval and consent to participate
The study was approved by the Hospital–Faculty Ethics Committee Saint-Luc – UCL (National number: B403). The patient or his family signed an informed consent prior to inclusion.
Consent for publication
Not applicable
Competing interests
The authors declare that they have no competing interests.
Footnotes
Publisher’s Note
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References
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Data Availability Statement
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.