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Impact of restricting procalcitonin measurements in a Swiss tertiary-care hospital on antibiotic use, clinical outcomes, and costs: An interrupted time-series analysis

Published online by Cambridge University Press:  02 December 2020

Mohamed Abbas
Affiliation:
Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland Faculty of Medicine, University of Geneva, Geneva, Switzerland
Nathalie Vernaz
Affiliation:
Finance Department and Medical Direction, Geneva University Hospitals, Geneva, Switzerland
Elodie von Dach
Affiliation:
Clinical Trials Unit, Geneva University Hospitals, Geneva, Switzerland
Nicolas Vuilleumier
Affiliation:
Faculty of Medicine, University of Geneva, Geneva, Switzerland Division of Laboratory Medicine, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland
Stephan J. Harbarth
Affiliation:
Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland Faculty of Medicine, University of Geneva, Geneva, Switzerland Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland
Benedikt D. Huttner
Affiliation:
Faculty of Medicine, University of Geneva, Geneva, Switzerland Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland
Corresponding
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Abstract

We evaluated the impact of a restriction of procalcitonin measurements on antibiotic use, length of stay, mortality, and cost in a Swiss tertiary-care hospital using interrupted time-series analysis. There was no significant change in level or slope for rates of antibiotic consumption, and costs decreased considerably, by ~54,488 CHF (US$55,714) per month.

Type
Concise Communication
Creative Commons
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2020. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

Appropriate use of antibiotics through antibiotic stewardship is essential to curb the increase in antimicrobial resistance. Reference Holmes, Moore and Sundsfjord1,Reference Dyar, Huttner, Schouten and Pulcini2 Clinicians often face uncertainty whether a bacterial infection is present or not in a given patient. Biomarkers such as procalcitonin (PCT), by serving as decisional support, may potentially help avoid unnecessary antimicrobial prescribing. Reference Christ-Crain and Müller3,Reference Neeser, Branche, Mueller and Schuetz4

Evidence from meta-analyses of randomized clinical trials (RCTs) suggests that PCT-guided therapy reduces antibiotic use without harm to patients and may even have potential benefits. Reference Schuetz, Wirz and Sager5 The vast majority of these studies were, however, undertaken in patients with lower respiratory tract infections (LRTIs) in the emergency department or sepsis/septic shock in the intensive care unit (ICU). Reference de Jong, van Oers and Beishuizen6,Reference van der Does, Rood, Haagsma, Patka, van Gorp and Limper7

Diagnostic stewardship, that is, the responsible use of diagnostic tests to avoid unnecessary costs and negative consequences associated with false-positive findings, is also a key priority for healthcare systems in an era in which “less is more” and where “smarter medicine” campaigns advocate for rational use of resources. Reference Lehmann, Berner and Bogner8 Overuse and misuse of procalcitonin is frequent in routine practice, Reference Garin, Poffet, Harbarth and Perrier9 as is the case with many other diagnostic tests. Reference Huang, Yealy and Filbin10,Reference Bremmer, Moffa and Ma11 Furthermore, its added value over C-reactive protein remains controversial. Reference Afshari and Harbarth12,Reference Albrich and Harbarth13

The primary objective of this study was to analyze the effect of restricting PCT measurements on antibiotic use. Secondary objectives were to assess the impact of the restriction on clinical outcomes and costs.

Methods

This quasi-experimental study was conducted in Geneva University Hospitals (HUG), a tertiary care center in Switzerland. HUG had an antibiotic stewardship program over the entire study period with regularly updated guidelines, review of all positive blood cultures, and dedicated stewardship rounds in certain high-risk wards (eg, ICU). Although the infectious diseases (ID) service issued guidance on the use of PCT (Appendix online), PCT results were not reviewed by the ABS program. The estimated PCT reagent (technical laboratory supplies) cost in our hospital is ~400’000 CHF (US$408,998) per year, which represents 2.4% of the global annual reagent budget. In contrast, total antibiotic expenditure is ~1.5 million CHF (US$1.53 million) per year. Because of this substantial burden, PCT measurements were restricted as of February 3, 2016, except for the pediatric emergency department, the adult and pediatric ICUs and transplant units. PCT measurements could still be prescribed in other wards with prior approval by an ID consultant and the head of the laboratory division, at their discretion.

We obtained numbers of PCT measurements from the laboratory database as well as patient-level (admission/discharge dates, ward location, in-hospital mortality) and systemic (oral and parenteral) antibiotic administration (ATC class J01 and oral metronidazole) data from the electronic health record system.

We included patients in all inpatient wards (and the emergency department) in HUG, except those with preintervention low PCT test usage, defined as <1 PCT measurement per week, on average, over a 12-month period.

The primary outcome was the change in antibiotic use in defined daily doses (DDD) per 1,000 patient days (PD) per month. The secondary outcomes included days of therapy (DOT) per 1,000 PD per month, in-hospital mortality, length of stay (LOS), and cost savings.

Statistical analysis

We conducted an interrupted time-series analysis of monthly rates of antibiotic use in DDD per 1,000 PD before and after the start of the intervention using a Prais-Winsten regression, which is based on generalized least-squares method accounting for serial autocorrelation. We used the Durbin-Watson d statistic to evaluate how well the model took into account first-order correlation. We hypothesized the absence of an impact on antibiotic use and overall in-hospital mortality in wards where PCT was discontinued.

We calculated monthly LOS as a ratio of total patient days and number of admissions. In-hospital mortality was calculated as a monthly proportion of deaths by admission. We estimated the cost savings as a percentage reductions of PCT-reagent–related costs and in percentage reductions of the department’s global reagent costs. Costs are provided in Swiss Francs (CHF) and US dollars (US$) with an exchange rate of 1CHF = US$0.978 (ie, the average exchange rate for 2018, OECD).

The study period was from January 2014 to May 2018, with >24 data points on either side of the intervention, which provided sufficient statistical power to analyze the primary outcome. Reference Bernal, Cummins and Gasparrini14 Data on in-hospital mortality were only available from January 2015 onward. All statistical analyses were performed using Stata version 14 software (StataCorp, College Station, TX) and, in particular, the “itsa” command.

Ethics

The study was approved by the Ethics Committee of Canton of Geneva (no. 2017-02274), which granted a waiver of informed consent.

Results

After the intervention, we observed an immediate statistically significant decrease in the level of PCT measurements per month (−637.4; 95% CI, 539.7–735.0) without a statistically significant change in slope (−0.05; 95% CI, −8.2 to 8.1) (Fig. 1A; Supplementary Tables 1 and 2 online).

Fig. 1. Changes in (A) monthly number of procalcitonin (PCT) measurements; (B) monthly rate of antibiotic consumption, measured in defined daily doses (DDD) per 1,000 patient days, before and after restriction of PCT measurements.

Before the intervention, we observed an increasing trend of monthly antibiotic use of 4.3 DDD per 1,000 PD (95% CI, 1.4–7.1). After the intervention, there was a nonsignificant decrease in level of antibiotic use by 47 DDD per 1,000 PD (95% CI, −1.0 to 95.6), followed by an upward change in slope of 1.6 DDD per 1,000 PD (95% CI, −0.2 to 3.5) which was not statistically significant (Fig. 1B; Supplementary Table 2 online). The Durbin-Watson d statistic changed from 1.25 to 1.67, indicating that the model performed well despite residual positive autocorrelation. When analyzed by DOT, there was significant decrease in level of 36.6 DOT per 1,000 PD (95% CI, 2.8–70.3) and a significant decrease in slope of 3.6 DOT per 1,000 PD (95% CI, 1.0–6.1) after the intervention (Supplementary Table 2 and Supplementary Fig. 1 online).

During the study period, we observed a pre-existing decreasing trend of in-hospital mortality from 7.40 deaths per 100 admissions to 5.02 deaths per 100 admissions (P < .001), with no significant change associated with the intervention (Supplementary Table 2 and Supplementary Fig. 2 online). There was also a pre-existing decreasing trend in LOS from 5.12 to 3.77 days (P < .001) over the study period, with a significant decrease in level after the intervention of 0.4 days (95% CI, 0.2–0.6) (Supplementary Table 2 and Supplementary Fig. 2 online).

The annual PCT-reagent costs decreased from ~400,000 CHF (~US$409,000) to 100,000 CHF (~US$102,000), corresponding to a 75% decrease. The proportion of PCT reagent costs in the global department reagent budget decreased from 2.4% to 0.8%.

Discussion

In this study, the restriction of PCT measurements in a large tertiary-care center in Switzerland did not influence overall antibiotic use and was not associated with increases in LOS or mortality. Meanwhile, the intervention led to significant cost savings.

Although PCT has been repeatedly suggested as means to reduce antibiotic exposure and potentially mortality, mainly in LRTIs, in meta-analyses of RCTs Reference Schuetz, Wirz and Sager5,Reference Meier, Branche and Neeser15 the value of PCT in real-world clinical settings has been questioned. A study including >20,000 septic ICU patients suggested that PCT use was associated with increased antibiotic consumption and poorer clinical outcomes, Reference Chu, Mehta and Walkey16 highlighting either the importance of improving implementation of adequate PCT-based strategies prior to widespread adoption or as “worst-case scenario,” the limited clinical value of PCT use.

During the study period, we observed pre-existing decreasing trends in mortality and LOS, with no effect of the intervention on in-hospital mortality but a decrease in level of LOS after the intervention. The latter effect may be an artefact; it is unclear how PCT prescription restriction would be associated with decreased LOS. Nevertheless, it is reassuring that we did not observe increases in in-hospital mortality and LOS associated with the intervention.

The main strength of our study was that the “top-down” decision to discontinue PCT measurements offered a natural quasi-experimental study design; this allowed the use of interrupted time-series, which is a robust methodology. Reference de Kraker, Abbas, Huttner and Harbarth17 One of the limitations of this study is that it evaluated hospital-level changes in antibiotic prescribing practices and therefore was prone to ecologic bias. Our negative finding does not exclude the possibility that PCT may have an impact on the management of individual patients. Also, we did not evaluate protocol adherence (ie, whether PCT levels influenced prescribing behavior), even though we suspect it to be low, as in other real-world studies. Reference Garin, Poffet, Harbarth and Perrier9,Reference Farooq and Colón-Franco18 However, since one aim of antimicrobial stewardship is to reduce overall antibiotic use, we feel that the ecologic perspective is still justified. Finally, our single-center study was conducted in a setting where antibiotic use is relatively low; thus, the generalizability of our results may be limited.

Our results do not suggest that PCT is useless; other evidence suggests that when used in specific indications, it may be an effective tool to reduce antibiotic exposure, and thus may be cost-effective. Reference Westwood, Ramaekers and Whiting19 Appropriate, evidence-based, indications of PCT include (1) initiation of antibiotic therapy in acute LRTI, including community-acquired pneumonia and COPD exacerbation and (2) reducing duration of antibiotic therapy in ICU patients with ventilator-associated pneumonia or sepsis. Like all diagnostic tests, PCT needs to be used intelligently and in conjunction with other information to have a real impact on patient outcomes. To prevent overuse and misuse of PCT, institutions may need “diagnostic stewardship” teams to enforce restrictions on use or provide real-time review of cases. Further real-life diagnostic-stewardship studies on how to implement PCT-guided therapy are needed to further inform best practices.

Supplementary material

To view supplementary material for this article, please visit https://doi.org/10.1017/ice.2020.1314

Acknowledgments

We would like to thank Dr Angela Huttner (Division of Infectious Diseases, University of Geneva Hospitals, Geneva, Switzerland) for providing input regarding the elaboration of the protocol.

Financial support

This work was partly supported by the Research Fund of the Department of Internal Medicine of the University Hospital and the Faculty of Medicine of Geneva; this Fund received an unrestricted grant from AstraZeneca Switzerland.

Conflicts of interest

All authors report no conflicts of interest relevant to this article.

Footnotes

PREVIOUS PRESENTATION. An abstract of this study was accepted for the 30th European Conference on Clinical Microbiology and Infectious Diseases.

References

Holmes, AH, Moore, LS, Sundsfjord, A, et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 2016;387:176187.CrossRefGoogle Scholar
Dyar, OJ, Huttner, B, Schouten, J, Pulcini, C, ESGAP. What is antimicrobial stewardship? Clin Microbiol Infect 2017;23:793798.CrossRefGoogle Scholar
Christ-Crain, M, Müller, B. Procalcitonin in bacterial infections—hype, hope, more or less? Swiss Med Wkly 2005;135:451460.Google Scholar
Neeser, O, Branche, A, Mueller, B, Schuetz, P. How to implement procalcitonin testing in my practice. Clin Microbiol Infect 2019;25:12261230.CrossRefGoogle Scholar
Schuetz, P, Wirz, Y, Sager, R, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis 2018;18:95107.CrossRefGoogle ScholarPubMed
de Jong, E, van Oers, JA, Beishuizen, A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016;16:819827.CrossRefGoogle Scholar
van der Does, Y, Rood, PP, Haagsma, JA, Patka, P, van Gorp, EC, Limper, M. Procalcitonin-guided therapy for the initiation of antibiotics in the ED: a systematic review. Am J Emerg Med 2016;34:12861293.CrossRefGoogle Scholar
Lehmann, C, Berner, R, Bogner, JR, et al. The “Choosing Wisely” initiative in infectious diseases. Infection 2017;45:263268.CrossRefGoogle ScholarPubMed
Garin, N, Poffet, V, Harbarth, S, Perrier, A. Antibiotic decision making after procalcitonin measurement in a general internal medicine department: an observational study (abstract A-648-0003-00604). Geneva, Switzerland: European and Swiss Congress of Internal Medicine (ESCIM 2014); 2014.Google Scholar
Huang, DT, Yealy, DM, Filbin, MR, et al. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med 2018;379:236249.CrossRefGoogle Scholar
Bremmer, DN, Moffa, MA, Ma, K, et al. Acute exacerbations of chronic obstructive pulmonary disease with a low procalcitonin concentration: impact of antibiotic therapy. Clin Infect Dis 2019;68:725730.CrossRefGoogle Scholar
Afshari, A, Harbarth, S. Procalcitonin as diagnostic biomarker of sepsis. Lancet Infect Dis 2013;13:382384.CrossRefGoogle Scholar
Albrich, WC, Harbarth, S. Pros and cons of using biomarkers versus clinical decisions in start and stop decisions for antibiotics in the critical care setting. Intensive Care Med 2015;41:17391751.CrossRefGoogle Scholar
Bernal, JL, Cummins, S, Gasparrini, A. Interrupted time series regression for the evaluation of public health interventions: a tutorial. Int J Epidemiol 2017;46:348355.Google Scholar
Meier, MA, Branche, A, Neeser, OL, et al. Procalcitonin-guided antibiotic treatment in patients with positive blood cultures: a patient-level meta-analysis of randomized trials. Clin Infect Dis 2019;69:388396.CrossRefGoogle Scholar
Chu, DC, Mehta, AB, Walkey, AJ. Practice patterns and outcomes associated with procalcitonin use in critically ill patients with sepsis. Clin Infect Dis 2017;64:15091515.CrossRefGoogle Scholar
de Kraker, MEA, Abbas, M, Huttner, B, Harbarth, S. Good epidemiological practice: a narrative review of appropriate scientific methods to evaluate the impact of antimicrobial stewardship interventions. Clin Microbiol Infect 2017;23:819825.CrossRefGoogle ScholarPubMed
Farooq, A, Colón-Franco, JM. Procalcitonin and its limitations: why a biomarker’s best isn’t good enough. J Appl Lab Med 2019;3(4):716.CrossRefGoogle Scholar
Westwood, M, Ramaekers, B, Whiting, P, et al. Procalcitonin testing to guide antibiotic therapy for the treatment of sepsis in intensive care settings and for suspected bacterial infection in emergency department settings: a systematic review and cost-effectiveness analysis. Health Technol Assess 2015;19(96):vxxv, 1–236.CrossRefGoogle Scholar

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