Caggiano, Giuseppina

Coretti, C

Montagna, Maria Teresa

English

Journal of Preventive Medicine and Hygiene (JPMH)

38J prev med hyg 2011; 52: 38-39The incidence of invasive fungal infections (IFIs) in critically ill patients has constantly increased over re-cent decades, but their diagnosis still presents prob-lems: conventional diagnostic (microscopic examina-tion, fungal cultures) is sometimes insensitive, some procedures (e.g. tissue biopsy) require an aggressive approach not compatible with the critical condition of the patients, so the diagnosis is often based on clini-cal suspicion or is made too late. Additional markers have been proposed in early diagnosis (mannan, galac-tomannan, 1→3-beta-D-glucan antigen tests, specific antibodies or DNA fungal detection) but some of these still require further evaluation [1-5]. Recently, the role of procalcitonin (PCT) as a surrogate marker of fungal infections has been examined. Its quantitative evalua-tion is considered a valid biological marker in different bacterial diseases[6-8] and it may distinguish bacter-emia from non-infectious inflammatory conditions [9]. Regarding fungal infection, literature data are still few and controversial: some authors have reported that se-rum PCT values are lower during fungal infection than in bacterial infection [10-12].With the aim of evaluating the diagnostic usefulness of PCT in critically ill patients, we checked for the presence of PCT, compared to Candida mannan (CM), 1→3-beta-D-glucan (BDG) and galactomannan (GM) antigens, in three different groups of patients, all with proven/prob-able IFIs already diagnosed. Overall 20 subjects were investigated for serum PCT and circulating antigens at the same time of mycoses diagnosis: 8 neutropenic hae-matologic adult patients (HAE: 7 suffering from acute myelogenic leukemia and 1 from acute lymphoblastic leukemia), 6 preterm infants hospitalized in Neonatal Intensive Care Unit (NICU: 4 very low birth weight and 2 extremely low birth weight) and 6 patients admitted to the Intensive Care Unit (ICU: 4 previously exposed to abdominal surgical procedures and 2 to poly-trauma).PCT values ranging from 0.5 to 1.0 ng/ml were con-sidered moderately elevated, values > 1.0 ng/ml highly elevated. Regarding circulating antigens, samples were judged positive when levels of BDG were ≥ 80 pg/ml, CM ≥ 0.5 ng/ml, and GM when Index value was ≥ 0.5.Our study has two main limitations: first, the small size of examined cases, because unsupported by statistical evaluation, might have hidden some differences between different groups with fungal disease; second, our analy-sis was carried out in selected patients, excluding the cases of documented bacterial sepsis, in order to avoid other causes of a PCT increase.In 8 HAE patients with fungal disease (5 pulmonary as-pergillosis and 3 Candida blood stream infection (BSI), 2 by Candida krusei and 1 by Candida parapsilosis), PCT value remained always very low (< 0.5 ng/ml); BDG and galactomannan tests were positive in patients with pul-monary aspergillosis, while the patients with Candida parapsilosis/Candida krusei BSIs resulted negative for mannan and positive for the BDG test.Among 6 NICU patients with BSIs caused by Candida albicans or Candida parapsilosis (3 cases respectively), PCT values were slightly increased in 4 cases (range 0.55-1.27 ng/ml); one patient showed very high values (17.1 ng/ml) but a severe bacterial BSI was confirmed at the same time; while the PCT values resulted always < 0.5 ng/ml for another patient. In all 6 neonates with Candida BSI, the BDG test resulted positive at diagno-sis, while the CM antigen resulted > 0.5 ng/ml only in 3 patients with Candida albicans infection.Among 6 ICU patients (5 with Candida albicans BSI and 1 with pulmonary aspergillosis), PCT values were very low (range 0.05-0.33 ng/ml) in the BSI patients; BDG and CM antigen were always positive. In contrast, the patient with aspergillosis showed a higher PCT value (1.91 ng/ml) and was BDG/GM positive.Although it is known that PCT is also synthesized to some extent by leukocytes [13], some studies have shown that PCT may be an infection marker in neu-tropenic patients [14-16]. Our data highlight low PCT levels in neutropenic haematologic patients, so its value might be underestimated.In different adult patients, Petrikkos et al. [10] found PCT values lower in the early phase of IFIs. Besides, they report that the evaluation of mannan antigen in par-allel may help to discriminate between invasive fungal and bacterial infections, especially in the case of Can-dida albicans infection. Also Di Stefano [11] observed that PCT values are lower during fungal than in bacterial infection in preterm infants. Our data suggest that low or slightly increased PCT levels (HAE and NICU patients with Candida BSIs respectively), evaluated in tandem with circulating antigens (CM, GM, and BDG), could help to indicate fungal infection and expand the labora-tory research.In surgical patients with clinical signs of sepsis and risk factors for fungal infections, Martini et al. [12] consider a PCT value less than 2ng/ml as cut-off point to distin-guish between sepsis due to Candida infection and sepsis of bacterial origin. In surgical patients with candidemia we found very low PCT levels (from 0.05 to 0.33 ng/ShOrt cOmmunicatiOnProcalcitonin: a possible marker of invasive fungal infection in high risk patients?M.T. MONTAGNA, C. CORETTI, G. CAGGIANODepartment of Biomedical Science and Human Oncology, Hygiene Section, University of Bari “Aldo Moro”, Bari, ItalyprocalcItonIn Serum levelS In patIentS wIth IfIS39ml) and higher values only in the patient suffering from aspergillosis (1.91 ng/ml).In conclusion, our study suggests that PCT valuation in the serum of onco-haematologic or surgical patients, in contrast to circulating antigens, is not essential to di-agnose a deep mycosis. The role of PCT in serum of critically ill patients depends on the population exam-ined and its clinical setting. In fact, its valuation could be useful in premature infants being characterized by insufficiently specific symptoms. PCT values from 0.5 to 1 ng/ml could focus the suspicion of an infectious process other than the bacterial sepsis and lead us to assess fungal circulating antigens to consider a fungal sepsis. Based on this observation, other studies on larger numbers of cases (especially in NICU patients) are war-ranted to analyze the predictive value of PCT in fungal diseases.n	 Received on February 8, 2011. Accepted on February 28, 2011.n	 Acknowledgements. This work was supported by a grant from Gilead Sciences Srl, Milan, Italy. n	 Correspondence: Maria Teresa Montagna, Department of Bio-medical Science and Human Oncology, Hygiene Section, piazza G. Cesare 11, 70124 Bari, Italy - Tel./Fax: +39 80 5478476 - E-mail: montagna@igiene.uniba.itReferences[1] Prella M, Bille J, Pugnale M, et al. Early diagnosis of invasive candidiasis with mannan antigenemia and antimannan anti-bodies. Diagn Microbiol Infect Dis 2005;51:95-101.[2] Maertens J, Theunissen K, Lodewyck T, et al. Advances in the serological diagnosis of invasive Aspergillus infections in pa-tients with haematological disorders. Mycoses 2007;50(Sup-pl 1):2-17.[3] Laín A, Elguezabal N, Moragues MD, et al. Contribution of se-rum biomarkers to the diagnosis of invasive candidiasis. Expert Rev Mol Diagn 2008;8:315-25.[4] Ellis M, Al-Ramadi B, Bernsen R, et al. Prospective evalua-tion of mannan and anti-mannan antibodies for diagnosis of invasive Candida infections in patients with neutropenic fever. J Med Microbiol 2009;58:606-15.[5] Pontón J. Usefulness of biological markers in the diagnosis of invasive candidiasis. Rev Iberoam Micol 2009;26:8-14.[6] Christ-Crain M, Muller B. Procalcitonin in bacterial in-fections – hype, hope, more or less? Swiss Med Wkly 2005;135:451-60[7] Jensen JU, Heslet L, Jensen TH, et al. Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med 2006;34:2596-602.[8] Kato M, Kaneko S, Takagaki K, et al. Procalcitonin as a bi-omarker for toxic shock syndrome. Acta Derm Venereol 2010;90:441-3.[9] Meisner M, Adina H, Schmidt J. Correlation of procalcitonin and C-reactive protein to inflammation, complications, and outcome during the intensive care unit course of multiple-trau-ma patients. Crit Care 2006;10:R1.[10] Petrikkos GL, Christofilopoulou SA, Tentolouris NK, et al. Value of measuring serum procalcitonin, C-reactive protein, and mannan antigens to distinguish fungal from bacterial in-fections. Eur J Clin Microbiol Infect Dis 2005;4:272-5.[11] Di Stefano G, Curreri R, Betta P, et al. Procalcitonin serum levels in perinatal bacterial and fungal infection of preterm in-fants. Acta Paediatric 2004;93:216-9.[12] Martini A, Gottin L, Menestrina N, et al. Procalcitonin levels in surgical patients at risk of candidemia. J Infect 2010;60:425-30.[13] Oberhoffer M, Stonans I, Russwurm S, et al. Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cy-tokines in vitro. J Lab Clin Med 1999;134:49-55.[14] Giamarellos-Bourboulis EJ, Grecka P, Poulakou G, et al. As-sessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia. Clin Infect Dis 2001;32:1718-25.[15] Christofilopoulou S, Charvalos E, Petrikkos G. Could procal-citonin be a predictive biological marker in systemic fungal in-fections? Study of 14 cases. Eur J Intern Med 2002;13:493-5.[16] Giamarellou H, Giamarellos-Bourboulis EJ, Repoussis P, et al. Potential use of procalcitonin as a diagnostic criterion in fe-brile neutropenia: experience from a multicentre study. Clin Microbiol Infect 2004;10:628-33.

Procalcitonin: a possible marker of invasive fungal infection in high risk patients?

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Procalcitonin: a possible marker of invasive fungal infection in high risk patients?

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