Procalcitonin for antimicrobial stewardship among cancer patients admitted with COVID-19
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Curated by eLife
eLife assessment
One must appreciate the challenges of antimicrobial stewardship in an immunocompromised population. This retrospective single-institution study provides support for the working hypothesis that initial procalcitonin levels might be used in cancer patients admitted with COVID-19 infection to omit, reduce, or de-escalate the need for empiric antimicrobial therapy. In the setting of a global pandemic, this is a common issue with COVID-19 patients in generally, but far more difficult in a cancer patient population. The results presented here support the authors' conclusions, however, future subgroup analysis of more specific scenarios among cancer patients with COVID-19 (e.g., neutropenia, active chemotherapy, and need for intensive care) are warranted.
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Abstract
Procalcitonin (PCT) has been used to guide antibiotic therapy in bacterial infections. We aimed to determine the role of PCT in decreasing the duration of empiric antibiotic therapy among cancer patients admitted with COVID-19.
Methods:
This retrospective study included cancer patients admitted to our institution for COVID-19 between March 1, 2020, and June 28, 2021, with a PCT test done within 72 hr after admission. Patients were divided into two groups: PCT <0.25 ng/ml and PCT ≥0.25 ng/ml. We assessed pertinent cultures, antibacterial use, and duration of empiric antibacterial therapy.
Results:
The study included 530 patients (median age, 62 years [range, 13–91]). All the patients had ≥1 culture test within 7 days following admission. Patients with PCT <0.25 ng/ml were less likely to have a positive culture than were those with PCT ≥0.25 ng/ml (6% [20/358] vs. 17% [30/172]; p<0.0001). PCT <0.25 ng/ml had a high negative predictive value for bacteremia and 30 day mortality. Patients with PCT <0.25 ng/ml were less likely to receive intravenous (IV) antibiotics for >72 hr than were patients with PCT ≥0.25 ng/ml (45% [162/358] vs. 69% [119/172]; p<0.0001). Among patients with PCT <0.25 ng/ml and negative cultures, 30 day mortality was similar between those who received IV antibiotics for ≥72 hr and those who received IV antibiotics for shorter durations (2% [2/111] vs. 3% [5/176], p=0.71).
Conclusions:
Among cancer patients with COVID-19, PCT level <0.25 ng/ml is associated with lower likelihood of bacterial co-infection and greater likelihood of a shorter antibiotic course. In patients with PCT level <0.25 ng/ml and negative cultures, an antibiotic course of >72 hr may not be necessary. PCT could be useful in enhancing antimicrobial stewardship in cancer patients with COVID-19.
Funding:
This research was supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports MD Anderson Cancer Center’s Clinical Trials Office.
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eLife assessment
One must appreciate the challenges of antimicrobial stewardship in an immunocompromised population. This retrospective single-institution study provides support for the working hypothesis that initial procalcitonin levels might be used in cancer patients admitted with COVID-19 infection to omit, reduce, or de-escalate the need for empiric antimicrobial therapy. In the setting of a global pandemic, this is a common issue with COVID-19 patients in generally, but far more difficult in a cancer patient population. The results presented here support the authors' conclusions, however, future subgroup analysis of more specific scenarios among cancer patients with COVID-19 (e.g., neutropenia, active chemotherapy, and need for intensive care) are warranted.
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Reviewer #1 (Public Review):
The authors aim was to determine the role of initial procalcitonin (PCT) measurements in cancer patients admitted with COVID-19 infection in reducing the intensity and duration of empiric antibiotic therapy. This was a retrospective study of all patients admitted to a single cancer center with COVID-19 infection and at least one PCT test within 72 hours of admission. The cut off PCT value to divide patients into two groups was 0.25 ng/ml (those with >= 0.25 ng/ml having a higher suspicion of bacterial infection). The study found that compared to patients with low PCT levels had shorter hospital stays, lower rate of mortality, and received less antibiotic therapy. The paper is well written, the study methods and statistics are sound, the population well characterized and large enough for valid comparison, and …
Reviewer #1 (Public Review):
The authors aim was to determine the role of initial procalcitonin (PCT) measurements in cancer patients admitted with COVID-19 infection in reducing the intensity and duration of empiric antibiotic therapy. This was a retrospective study of all patients admitted to a single cancer center with COVID-19 infection and at least one PCT test within 72 hours of admission. The cut off PCT value to divide patients into two groups was 0.25 ng/ml (those with >= 0.25 ng/ml having a higher suspicion of bacterial infection). The study found that compared to patients with low PCT levels had shorter hospital stays, lower rate of mortality, and received less antibiotic therapy. The paper is well written, the study methods and statistics are sound, the population well characterized and large enough for valid comparison, and the results support the authors conclusions. The study provides support that PCT can be used in this special at risk population as it has been used in other COVID-19 patient populations that have been better studied. The study has limitations that the authors report: retrospective, single center study, bacterial infections may have been missed (no uniformity of cultures collected), and empiric antimicrobial therapy was at the discretion of the treating team (no standardized empiric therapy). The findings of this study may not be generalizable to other cancer patient populations and there may be other confounding variables not identified.
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Reviewer #2 (Public Review):
This is a well written manuscript that provides a useful analysis on using PCT for guiding antibiotics use among cancer patients with COVID19, a very common issue with COVID 19 patients in general but more challenging in the cancer population. Analysis is relatively straight forward. Results support the claim that antibiotics for more than 72 hours may be unnecessary for cancer patients with negative cultures and PCT<0.25. This is can be useful clinically to limit unnecessary antibiotic use, however would only apply this as a very broad generalization. It would be interesting to see what outcomes are and if this applies for more specific and challenging but not uncommon clinical scenarios with cancer patients (i.e neutropenic patients, patients undergoing active therapy, ICU admission) where clinicians may …
Reviewer #2 (Public Review):
This is a well written manuscript that provides a useful analysis on using PCT for guiding antibiotics use among cancer patients with COVID19, a very common issue with COVID 19 patients in general but more challenging in the cancer population. Analysis is relatively straight forward. Results support the claim that antibiotics for more than 72 hours may be unnecessary for cancer patients with negative cultures and PCT<0.25. This is can be useful clinically to limit unnecessary antibiotic use, however would only apply this as a very broad generalization. It would be interesting to see what outcomes are and if this applies for more specific and challenging but not uncommon clinical scenarios with cancer patients (i.e neutropenic patients, patients undergoing active therapy, ICU admission) where clinicians may favor longer use of antibiotics.
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Reviewer #3 (Public Review):
In this retrospective study, the authors intend to demonstrate the utility of serum procalcitonin in reducing the use of antibacteral agents in cancer patients with COVID-19, by identifying the subset of their highly immunocompromised population where early discontinuation of antibacterial therapy would not be harmful.
This study has a large population size > 500 patients over the span of 16 months. The groups with low procalcitonin and high procalcitonin have similar baseline characteristics, which makes the subsequent comparisons valid and relevant. The authors have considered all the relevant variables that could affect the outcomes being studied, and used sound statistical methods.
This study has some limitations. It is retrospective by nature, with possibility for confounders. In addition to the …
Reviewer #3 (Public Review):
In this retrospective study, the authors intend to demonstrate the utility of serum procalcitonin in reducing the use of antibacteral agents in cancer patients with COVID-19, by identifying the subset of their highly immunocompromised population where early discontinuation of antibacterial therapy would not be harmful.
This study has a large population size > 500 patients over the span of 16 months. The groups with low procalcitonin and high procalcitonin have similar baseline characteristics, which makes the subsequent comparisons valid and relevant. The authors have considered all the relevant variables that could affect the outcomes being studied, and used sound statistical methods.
This study has some limitations. It is retrospective by nature, with possibility for confounders. In addition to the limitations mentioned by the authors, the study spans the period from March 2020 to June 2021 through which our knowledge of COVID has evolved, multiple variants have emerged, immunization has become available in the later part of the study period, more therapies (antivirals, monoclonal antibodies) became available, all of which have definitely affected COVID-related mortality, and could be an important confounder here. While the authors report the level of severity of the infection, using proxies such as supplemental oxygen and ICU admission, the use of COVID-directed therapies, including immunosuppressants such as steroids and tocilizumab (which in turn can increase the risk of bacterial infections and decrease the risk of mortality) is not reported. It also seems that the management of antibacterial therapy was left at the discretion of the treating physician, which can lead to a wide variety of practices, the nature of antibacterials administered is not reported here.
The results presented here support the conclusions made by the authors, and one has to appreciate the difficulty of antimicrobial stewardship efforts in an immunocompromised population such as the one being studied here. Many of these patients have been immunosuppressed for prolonged periods of time, could have profound defects in their immune systems, and could have had multiple previous infections, sometimes with atypical presentations. These patients are typically excluded from most large clinical trials, thus retrospective studies such as this one are usually the most informative pieces of literature available to support evidence-based medicine in this special patient population. I think this study should encourage clinicians to consider the use of serum procalcitonin as one additional clue to support their pursuit of antibacterial de-escalation or discontinuation in cancer patients with COVID-19.
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