Procalcitonin for selecting the antibiotic regimen in outpatients with low-risk community-acquired pneumonia using a rapid point-of-care testing: A single-arm clinical trial

Mar Masiá, Sergio Padilla, Victoria Ortiz de la Tabla, Matilde González, Cristina Bas, Félix Gutiérrez, Mar Masiá, Sergio Padilla, Victoria Ortiz de la Tabla, Matilde González, Cristina Bas, Félix Gutiérrez

Abstract

Objective: We aimed to assess the role of procalcitonin (PCT) to guide the initial selection of the antibiotic regimen for low-risk community-acquired pneumonia (CAP).

Methods: A single-arm clinical trial was conducted including outpatients with CAP and Pneumonia Severity Index risk classes I-II. Antimicrobial selection was based on the results of PCT measured with a rapid point-of-care testing. According to serum PCT levels, patients were assigned to two treatment strategies: oral azithromycin if PCT was <0.5 ng/ml, or levofloxacin if levels were ≥0.5 ng/ml. Primary outcome was clinical cure rate. Short-term and long-term outcomes were assessed. Results were compared with those of a historical standard-of-care control-group treated in our centre.

Results: Of 253 subjects included, 216 (85.4%) were assigned to azithromycin. Pneumococcal infection was diagnosed in 26 (12%) and 21 (56.8%) patients allocated to azithromycin and levofloxacin groups, respectively. No patients in the azithromycin group developed bacteraemia. Atypical organisms were more common in patients given azithromycin (18.5% vs 8.1%, respectively). The majority (93%) of patients with atypical pneumonia had low PCT levels. Clinical cure rates were 95.8% in the azithromycin group, 94.6% in the levofloxacin group, and 94.4% in the historical control group. No 30-day mortality or recurrences were observed, and the 3-year rates of recurrence and mortality were very low in both groups. Adverse events occurrence was also infrequent.

Conclusion: A PCT-guided strategy with a rapid point-of-care testing safely allowed selecting empirical narrow-spectrum antibiotics in outpatients with CAP.

Trial registration: The study is registered with ClinicalTrials.gov, number NCT02600806.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flowchart of patients with CAP.
Fig 1. Flowchart of patients with CAP.
PSI I-II indicate Pneumonia Severity Index risk classes I and II; CAP, community-acquired pneumonia; PCT, procalcitonin. 1Those cases were protocol violations, and were excluded from the study. 2One patient was diagnosed with pulmonary tuberculosis; another patient was diagnosed with pulmonary embolism.

References

    1. Woodhead M, Blasi F, Ewig S, Garau J, Huchon G, Ieven M, et al. Guidelines for the management of adult lower respiratory tract infections—full version. Clin Microbiol Infect. 2011;17 Suppl 6:E1–59
    1. Lim WS, Woodhead M. British Thoracic Society adult community acquired pneumonia audit 2009/10. Thorax. 2011;66:548–9 10.1136/thoraxjnl-2011-200081
    1. Spindler C, Strålin K, Eriksson L, Hjerdt-Goscinski G, Holmberg H, Lidman C, et al. Swedish guidelines on the management of community-acquired pneumonia in immunocompetent adults—Swedish Society of Infectious Diseases 2012. Scand J Infect Dis. 2012;44:885–902 10.3109/00365548.2012.700120
    1. Blasi F. Atypical pathogens and respiratory tract infections. Eur Respir J. 2004;24:171–81.
    1. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27–72.
    1. Doern GV, Richter SS, Miller A, Miller N, Rice C, Heilmann K, et al. Antimicrobial resistance among Streptococcus pneumoniae in the United States: have we begun to turn the corner on resistance to certain antimicrobial classes? Clin Infect Dis. 2005;41:139–48. 10.1086/430906
    1. Kim SH, Song JH, Chung DR, Thamlikitkul V, Yang Y, Wang H, et al. Changing trends in antimicrobial resistance and serotypes of Streptococcus pneumoniae isolates in Asian countries: an Asian Network for Surveillance of Resistant Pathogens (ANSORP) study. Antimicrob Agents Chemother. 2012;56:1418–26 10.1128/AAC.05658-11
    1. Gant CM, Rosingh AW, López-Hontangas JL, van der Heijden M, González-Morán F, Bijlsma JJ, et al. Serotype distribution and antimicrobial resistance of invasive pneumococcal disease strains in the Comunidad Valenciana, Spain, during the winter of 2009–2010: low PCV7 coverage and high levofloxacin resistance. Antimicrob Agents Chemother. 2012;56:4988–9. 10.1128/AAC.01201-12
    1. Becker KL, Nylen ES, White JC, Muller B, Snider RH Jr. Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab. 2004;89:1512–25 10.1210/jc.2002-021444
    1. Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, et al. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004;363:600–7. 10.1016/S0140-6736(04)15591-8
    1. Kristoffersen KB, Søgaard OS, Wejse C, Black FT, Greve T, Tarp B, et al. Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission—a randomized trial. Clin Microbiol Infect. 2009;15:481–7 10.1111/j.1469-0691.2009.02709.x
    1. Schuetz P, Müller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;9:CD007498
    1. Long W, Deng X, Zhang Y, Lu G, Xie J, Tang J. Procalcitonin guidance for reduction of antibiotic use in low-risk outpatients with community-acquired pneumonia. Respirology. 2011;16:819–24 10.1111/j.1440-1843.2011.01978.x
    1. Krüger S, Ewig S, Papassotiriou J, Kunde J, Marre R, von Baum H, et al. Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP–Results from the German competence network CAPNETZ. Respir Res. 2009; 10: 65 10.1186/1465-9921-10-65
    1. Müller F, Christ-Crain M, Bregenzer T, Krause M, Zimmerli W, Mueller B, et al. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest. 2010;138:121–9. 10.1378/chest.09-2920
    1. Prat C, Domínguez J, Andreo F, Blanco S, Pallarés A, Cuchillo F, et al. Procalcitonin and neopterin correlation with aetiology and severity of pneumonia. J Infect. 2006;52:169–77 10.1016/j.jinf.2005.05.019
    1. Masiá M, Gutiérrez F, Shum C, Padilla S, Navarro JC, Flores E, et al. Usefulness of procalcitonin levels in community-acquired pneumonia according to the patients outcome research team pneumonia severity index. Chest. 2005; 128:2223–9 10.1378/chest.128.4.2223
    1. Branche AR, Walsh EE, Vargas R, Hulbert B, Formica MA, Baran A, et al. Serum Procalcitonin Measurement and Viral Testing to Guide Antibiotic Use for Respiratory Infections in Hospitalized Adults: A Randomized Controlled Trial. J Infect Dis. 2015;212;1692–700. 10.1093/infdis/jiv252
    1. Gutiérrez F, Masiá M, Rodríguez JC, Mirete C, Soldán B, Padilla S, et al. Epidemiology of community-acquired pneumonia in adult patients at the dawn of the 21st century: a prospective study on the Mediterranean coast of Spain. Clin Microbiol Infect. 2005;11:788–800. 10.1111/j.1469-0691.2005.01226.x
    1. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336:243–50. 10.1056/NEJM199701233360402
    1. American College of Chest Physicians/Society of Critical Care Medicine: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992, 20: 864–874
    1. Said MA, Johnson HL, Nonyane BA, Deloria-Knoll M, O'Brien KL. Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques. PLoS One. 2013;8:e60273 10.1371/journal.pone.0060273
    1. Rozenbaum MH, Pechlivanoglou P, van der Werf TS, Lo-Ten-Foe JR, Postma MJ, Hak E. The role of Streptococcus pneumoniae in community-acquired pneumonia among adults in Europe: a meta-analysis. Eur J Clin Microbiol Infect Dis. 2013;32:305–16. 10.1007/s10096-012-1778-4
    1. Gutiérrez F, Masiá M, Rodríguez JC, Ayelo A, Soldán B, Cebrián L, et al. Evaluation of the immunochromatographic Binax NOW assay for detection of Streptococcus pneumoniae urinary antigen in a prospective study of community-acquired pneumonia in Spain. Clin Infect Dis. 2003;36:286–92. 10.1086/345852
    1. Borg MA, Tiemersma E, Scicluna E, van de Sande-Bruinsma N, de Kraker M, Monen J, et al. Prevalence of penicillin and erythromycin resistance among invasive Streptococcus pneumoniae isolates reported by laboratories in the southern and eastern Mediterranean region. Clin Microbiol Infect. 2009;15:232–7.
    1. Artiles F, Horcajada I, Cañas AM, Alamo I, Bordes A, González A, et al. Epidemiological features of invasive pneumococcal disease before and after the introduction of pneumococcal conjugate vaccine in Gran Canaria (Canary Islands). Enferm Infecc Microbiol Clin. 2009;27:14–21. 10.1016/j.eimc.2008.03.001
    1. Lonks JR, Garau J, Gomez L, Xercavins M, Ochoa de Echagüen A, et al. Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae. Clin Infect Dis. 2002;35:556–6 10.1086/341978
    1. Kelley MA, Weber DJ, Gilligan P, Cohen MS. Breakthrough pneumococcal bacteremia in patients being treated with azithromycin and clarithromycin. Clin Infect Dis. 2000;31:1008–11. 10.1086/318157
    1. File TM Jr, Marrie TJ. Does empiric therapy for atypical pathogens improve outcomes for patients with CAP? Infect Dis Clin North Am. 2013;27:99–114 10.1016/j.idc.2012.11.005
    1. Masiá M, Gutiérrez F, Padilla S, Soldán B, Mirete C, Shum C, et al. Clinical characterisation of pneumonia caused by atypical pathogens combining classic and novel predictors. Clin Microbiol Infect. 2007;13:153–61 10.1111/j.1469-0691.2006.01629.x
    1. Capelastegui A, España PP, Bilbao A, Gamazo J, Medel F, Salgado J, et al. Etiology of community-acquired pneumonia in a population-based study: link between etiology and patients characteristics, process-of-care, clinical evolution and outcomes. BMC Infect Dis. 2012;12:134 10.1186/1471-2334-12-134
    1. Almirall J, Boixeda R, Bolíbar I, Bassa J, Sauca G, Vidal J, et al. Differences in the etiology of community-acquired pneumonia according to site of care: a population-based study. Respir Med. 2007;101:2168–75 10.1016/j.rmed.2007.05.007
    1. Gutiérrez F, Masiá M. Improving outcomes of elderly patients with community-acquired pneumonia. Drugs Aging. 2008;25:585–610

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅