Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.
Aged; Algorithms; Anti-Bacterial Agents/adverse effects; Humans; Intensive Care Units; Procalcitonin; Randomized Controlled Trials as Topic; age; antibiotic stewardship; older patients
Abstract :
[en] BACKGROUND: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. OBJECTIVE AND DESIGN: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. SUBJECTS AND METHODS: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. RESULTS: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). CONCLUSIONS: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.
Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.
Shehabi Y, Sterba M, Garrett PM et al. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. A randomized controlled trial. Am J Respir Crit Care Med 2014; 190: 1102-10.
Rhodes A, Evans LE, AlhazzaniW et al. Surviving sepsis campaign: InternationalGuidelines forManagement of Sepsis and Septic Shock: 2016. Intensive Care Med 2017; 43: 304-77.
Kumar A, Ellis P, Arabi Y et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009; 136: 1237-48.
Gregoriano C, Heilmann E, Molitor A, Schuetz P. Role of procalcitonin use in the management of sepsis. J Thorac Dis 2020; 12: S5-15.
Neeser O, Branche A, Mueller B, Schuetz P. How to: Implement procalcitonin testing in my practice. Clin Microbiol Infect 2019; 25: 1226-30.
Branche A, Neeser O, Mueller B, Schuetz P. Procalcitonin to guide antibiotic decision making. Curr Opin Infect Dis 2019; 32: 130-5.
Schuetz P, Birkhahn R, Sherwin R et al. Serial procalcitonin predicts mortality in severe sepsis patients: Results from the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) study. Crit Care Med 2017; 45: 781-9.
Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: A systematic review and meta-analysis. Lancet Infect Dis 2013; 13: 426-35.
Mitsuma SF, Mansour MK, Dekker JP et al. Promising new assays and technologies for the diagnosis and management of infectious diseases. Clin Infect Dis 2013; 56: 996-1002.
Annane D, Maxime V, Faller JP et al. Procalcitonin levels to guide antibiotic therapy in adults with nonmicrobiologically proven apparent severe sepsis: A randomised controlled trial. BMJ Open 2013; 3:e002186. doi: 10.1136/bmjopen-2012-002186.
Bloos F, Trips E, Nierhaus A et al. Effect of sodium selenite administration and procalcitonin-guided therapy onmortality in patients with severe sepsis or septic shock: A randomized clinical trial. JAMA Intern Med 2016; 176: 1266-76.
Bouadma L, Luyt CE, Tubach F et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): A multicentre randomised controlled trial. Lancet 2010; 375: 463-74.
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: 819-27.
Deliberato RO, Marra AR, Sanches PR et al. Clinical and economic impact of procalcitonin to shorten antimicrobial therapy in septic patients with proven bacterial infection in an intensive care setting. Diagn Microbiol Infect Dis 2013; 76: 266-71.
Hochreiter M, Schroeder S. Procalcitonin-based algorithm. Management of antibiotic therapy in critically ill patients. Anaesthesist 2011; 60: 661-73.
Schroeder S, Hochreiter M, Koehler T et al. Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: Results of a prospective randomized study. Langenbeck's archives of surgery/DeutscheGesellschaft fur. Chirurgie 2009; 394: 221-6.
Hochreiter M, Kohler T, Schweiger AM et al. Procalcitonin to guide duration of antibiotic therapy in intensive care patients: A randomized prospective controlled trial. Crit Care 2009; 13: R83.
Layios N, Lambermont B, Canivet JL et al. Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients. Crit Care Med 2012; 40: 2304-9.
Oliveira CF, Botoni FA, Oliveira CR et al. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: A randomized trial. Crit Care Med 2013; 41: 2336-43.
Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: A randomized trial. AmJ Respir Crit CareMed 2008; 177: 498-505.
Wirz Y, Meier MA, Bouadma L et al. Effect of procalcitoninguided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: A patientlevel meta-analysis of randomized trials. Crit Care 2018; 22: 191.
Schuetz P, Wirz Y, Sager R et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2017; 10: CD007498.
Schuetz P, Briel M, Christ-Crain M et al. Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: An individual patient data metaanalysis. Clin Infect Dis 2012; 55: 651-62.
Schuetz P, Christ-Crain M, Thomann R et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: The pro HOSP randomized controlled trial. JAMA 2009; 302: 1059-66.
Schuetz P, Briel M, Christ-Crain M, Wolbers M, Stolz D, TammMet al. Procalcitonin to initiate or withhold antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2008. https://doi.org/10.1002/14651858.CD007498.
Fuentes E, Fuentes M, AlarconM, Palomo I. Immune system dysfunction in the elderly. An Acad Bras Cienc 2017; 89: 285-99.
Ticinesi A, Lauretani F, Nouvenne A et al. C-reactive protein (CRP)measurement in geriatric patients hospitalized for acute infection. Eur J Intern Med 2017; 37: 7-12.
Heilmann E, Gregoriano C, Wirz Y et al. Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment: A patient-level meta-analysis from randomized controlled trials. Clin Chem Lab Med 2020.
Guertler C, Wirz B, Christ-Crain M, Zimmerli W, Mueller B, Schuetz P. Inflammatory responses predict long-term mortality risk in community-acquired pneumonia. Eur Respir J 2011; 37: 1439-46.
Schuetz P, Christ-Crain M, Muller B. Biomarkers to improve diagnostic and prognostic accuracy in systemic infections. Curr Opin Crit Care 2007; 13: 578-85.
Gavazzi G, FoR H, Stucker F, Graf JD, Michel JP, Krause KH. Response letter to Christ-Crain and MALler. J Am Geriatr Soc 2006; 54: 546-8.
Iankova I, Thompson-Leduc P, Kirson NY et al. Efficacy and safety of procalcitonin guidance in patients with suspected or confirmed sepsis: A systematic review and meta-analysis. Crit Care Med 2018; 46: 691-8.
Andriolo BN, Andriolo RB, Salomao R, Atallah AN. Effectiveness and safety of procalcitonin evaluation for reducing mortality in adults with sepsis, severe sepsis or septic shock. Cochrane Database Syst Rev 2017; 1: CD010959.
Schuetz P, Wirz Y, Sager R et al. Effect of procalcitoninguided antibiotic treatment on mortality in acute respiratory infections: A patient level meta-analysis. Lancet Infect Dis 2018; 18: 95-107.
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: 388-96.
Kutz A, Briel M, Christ-Crain M et al. Prognostic value of procalcitonin in respiratory tract infections across clinical settings. Crit Care 2015; 19: 74.
Schuetz P, Muller B, Christ-Crain M et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012; 9: Cd007498.
Stewart LA, Clarke M, Rovers M et al. Preferred reporting items for systematic review and meta-analyses of individual participant data: The PRISMA-IPD statement. JAMA 2015; 313: 1657-65.
Liberati A, Altman DG, Tetzlaff J et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration. BMJ (Clin Res Ed) 2009; b2700: 339.
Guyatt GH, Oxman AD, Vist GE et al. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336: 924-6.
Thompson SG, Turner RM, Warn DE. Multilevel models for meta-analysis, and their application to absolute risk differences. Stat Methods Med Res 2001; 10: 375-92.
Turner RM, Omar RZ, Yang M, GoldsteinH, Thompson SG. A multilevel model framework for meta-analysis of clinical trials with binary outcomes. Stat Med 2000; 19: 3417-32.
Schuetz P, Bolliger R, Merker M et al. Procalcitonin-guided antibiotic therapy algorithms for different types of acute respiratory infections based on previous trials. Expert Rev Anti-InfectTher 2018; 16: 555-64.
Stucker F, Herrmann F, Graf JD, Michel JP, Krause KH, Gavazzi G. Procalcitonin and infection in elderly patients. J Am Geriatr Soc 2005; 53: 1392-5.
FalconeM, Paul M, YahavDet al. Antimicrobial consumption and impact of antimicrobial stewardship programmes in longterm care facilities. Clin Microbiol Infect 2019; 25: 562-9.
Saeed K, Gonzalez Del Castillo J, Backous C et al. Hot topics on procalcitonin use in clinical practice, can it help antibiotic stewardship Int J Antimicrob Agents 2019; 54: 686-96.
Schuetz P, Bretscher C, Bernasconi L, Mueller B. Overview of procalcitonin assays and procalcitonin-guided protocols for the management of patients with infections and sepsis. Expert Rev Mol Diagn 2017; 17: 593-601.
