Barchiesi et al. BMC Infectious Diseases (2016) 16:387 DOI 10.1186/s12879-016-1704-y RESEARCH ARTICLE Open Access Factors related to outcome of bloodstream infections due to Candida parapsilosis complex Francesco Barchiesi1* , Elena Orsetti1, Patrizia Osimani3, Carlo Catassi2, Fabio Santelli4 and Esther Manso5 Abstract Background: Although Candida albicans is the most common cause of fungal blood stream infections (BSIs), infections due to Candida species other than C. albicans are rising. Candida parapsilosis complex has emerged as an important fungal pathogen and became one of the main causes of fungemia in specific geographical areas. We analyzed the factors related to outcome of candidemia due to C. parapsilosis in a single tertiary referral hospital over a five-year period. Methods: A retrospective observational study of all cases of candidemia was carried out at a 980-bedded University Hospital in Italy. Data regarding demographic characteristics and clinical risk factors were collected from the patient’s medical records. Antifungal susceptibility testing was performed and MIC results were interpreted according to CLSI species-specific clinical breakpoints. Results: Of 270 patients diagnosed with Candida BSIs during the study period, 63 (23 %) were infected with isolates of C. parapsilosis complex which represented the second most frequently isolated yeast after C. albicans. The overall incidence rate was 0.4 episodes/1000 hospital admissions. All the strains were in vitro susceptible to all antifungal agents. The overall crude mortality at 30 days was 27 % (17/63), which was significantly lower than that reported for C. albicans BSIs (42 % [61/146], p = 0.042). Being hospitalized in ICU resulted independently associated with a significant higher risk of mortality (HR 4.625 [CI95% 1.015–21.080], p = 0.048). Conversely, early CVC removal was confirmed to be significantly associated with a lower risk of mortality (HR 0.299 [CI95% 0.102–0.874], p = 0.027). Finally, the type of primary antifungal therapy did not influence the outcome of infection. Conclusions: Candidemia due to C. parapsilosis complex, the second most commonly causative agent of yeast BSIs in our center, is characterized by a non-negligible mortality at 30 days. An early CVC removal is associated with a significant reduced mortality. Keywords: Candida paraspilosis complex, Candidemia, Risk factors, Mortality, Antifungal agents Background sensu strictu (the most frequent), Candida orthopsilosis Candida is an important cause of bloodstream infec- and Candida metapsilosis, has emerged as an important tions (BSIs) and it is the main agent of invasive fungal fungal pathogen and became one of the main causes of infection in hospitalized patients [1, 2]. Although Can- fungemia in tertiary-care hospitals [5–9]. Although the dida albicans is the most common cause of invasive mortality rate due to this species is generally lower than candidiasis, infections due to Candida species other that reported for other Candida species, C. parapsilosis than C. albicans are rising [3, 4]. In particular, Candida complex possesses several distinct features, such as its parapsilosis complex, which includes C. parapsilosis ability to develop biofilms on intravascular devices, high affinity for parenteral nutrition, and an intrinsic low sus- * Correspondence: [email protected] ceptibility to echinocandins [10–12]. 1Clinica Malattie Infettive; Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Umberto I°- G.M. Lancisi – G. Salesi, Ancona, Italy Full list of author information is available at the end of the article © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Barchiesi et al. BMC Infectious Diseases (2016) 16:387 Page 2 of 7 Table 1 Comparison of epidemiological, clinical characteristics and outcome of patients with BSIs due to Candida parapsilosis and Candida albicans Variables Patients with BSIs due to: C. parapsilosis (n = 63) C. albicans (n = 146) P valuea Age (years), median (IQR)b 67 (43–76) 51 (66–77) 0.133 Neonates (<3 months) 1 (2) 5 (3) 0.465 Elderly (>65 years) 32 (51) 72 (49) 0.844 Male sex, n (%) 35 (56) 91 (63) 0.358 Ward Internal Medicine, n (%) 25 (40) 52 (36) 0.448 Surgery, n (%) 17 (27) 32 (22) Intensive Care Unit, n (%) 21 (33) 62 (43) Comorbidities, n (%) 57 (90) 137 (94) 0.387 Chronic pulmonary diseases, n (%)c 9 (14) 11 (8) 0.127 Haematological malignancy, n (%) 1 (2) 8 (5) 0.203 Cardiovascular diseases, n (%)d 27 (43) 67 (46) 0.685 Neurological diseases, n (%)e 10 (16) 24 (16) 0.919 Gastrointestinal diseases, n (%)f 21 (33) 43 (29) 0.576 Diabetes mellitus, n (%) 8 (13) 28 (19) 0.254 Solid tumors, n (%) 15 (24) 43 (30) 0.403 Chronic renal failure, n (%) 7 (11) 12 (8) 0.504 Previous surgery (<30 days), n (%) 32 (51) 67 (46) 0.514 Gastrointestinal surgery, n (%) 8 (13) 19 (13) 0.950 Cardiovascular surgery, n (%) 13 (21) 28 (19) 0.807 Other surgery, n (%) g 12 (19) 24 (16) 0.646 Central venous catheter, n (%) 56 (89) 127 (87) 0.702 BSI CVC-related, n (%) 36 (64) 57 (45) 0.015 Other devices, n (%)h 57 (90) 129 (88) 0.653 Previous invasive procedures (<72 h), n (%)i 16 (25) 44 (30) 0.486 Parenteral nutrition, n (%) 43 (68) 105 (72) 0.592 Immunosuppressive therapy, n (%)j 18 (29) 56 (34) 0.174 Neutropenia, n (%) 4 (6) 7 (5) 0.644 Septic shock, n (%) 2 (3) 12 (8) 0.180 Prior antibiotic therapy, n (%) 58 (92) 139 (95) 0.370 Previous antifungal therapy (<30 days), n (%) 5 (8) 21 (14) 0.195 Concomitant bacteriemia, n (%) 15 (24) 40 (27) 0.588 Other coinfections, n (%)k 39 (62) 89 (61) 0.897 Appropriate antifungal therapy, n (%)l 38 (60) 92 (63) 0.712 Primary azole therapy 41 (65) 77 (53) 0.098 Primary echinocandin therapy 7 (11) 34 (23) 0.041 Primary polyene therapy 1 (2) 3 (2) 0.820 None 14 (22) 32 (22) 0.961 Barchiesi et al. BMC Infectious Diseases (2016) 16:387 Page 3 of 7 Table 1 Comparison of epidemiological, clinical characteristics and outcome of patients with BSIs due to Candida parapsilosis and Candida albicans (Continued) Overall mortality, n (%) 17 (27) 61 (42) 0.042 Early mortality (days 1–7), n (%) 4 (6) 24 (17) 0.049 Late mortality (days 8–30), n (%) 13 (21) 37 (25) 0.464 aComparisons between groups were performed using Wilcoxon rank sum test for quantitative variables and Chi-Square test (or Fisher Exact Test when expected frequencies were less than five) for qualitative variables bIQR, Interquartile range cChronic pulmonary diseases include asthma, chronic bronchitis, emphysema and lung fibrosis dCardiovascular diseases include heart failure, ischemic heart disease, endocarditis and arrhythmia eNeurological diseases include Parkinson’s disease, Alzheimer’s disease and paralysis fGastrointestinal diseases include Crohn’s disease, ulcerative colitis, chronic pancreatitis and gallbladder stones g Other surgery includes plastic surgery, thoracic surgery, orthopaedic surgery, urological surgery and neurosurgery h Other devices include urinary catheter, surgical drainage, cutaneous gastrostomy and tracheostomy tube iPrevious invasive procedures include endoscopy and positioning of any device jImmunosuppressive therapy include corticosteroids, calcineurin inhibitors and monoclonal antibodies kOther coinfections include bacterial and/or fungal infections in sites other than blood lAppropriate antifungal therapy was considered when the appropriate drug with adequate dosage was started ≤ 72 h from the first blood culture performed The aim of this study was to analyze the factors related Review Board of the Azienda Ospedaliero-Universitaria to outcome of candidemia due to C. parapsilsosis com- Ospeadali Riuniti Umberto I°-Lancisi-Salesi granted plex in a single institution over a five-year period. retrospective access to the data without need for individ- ual informed consent. Methods Study population and data collection Statistical analysis A retrospective observational study of all cases of candide- Quantitative data were shown as the median with inter- mia was carried out from January 1, 2010 to December 31, quartile ranges (Q1–Q3). Qualitative variables were 2014 (5-year period) in a single 980-bedded referral Uni- expressed as absolute and relative frequencies. Categorical versity Hospital in Ancona, Italy. A case of Candida BSI variables were compared using the χ2 test, whereas was defined as a peripheral isolation of Candida species Mann–Whitney U test or Fisher exact test were applied from blood culture in a patient with temporally related for continuous variables. Variables with a p ≤0.05 at the clinical signs and symptoms of infection. All Candida BSIs descriptive analysis were analyzed by Cox regression. All were identified through the microbiological laboratory statistical analyses were performed using the statistical database. Data regarding demographic characteristics and package SPSS for Windows v. 20 (SPSS Inc., Chicago, IL, clinical risk factors were collected from the patient’s med- USA). A P value of ≤0.05 was considered to represent stat- ical records. Appropriate antifungal therapy was consid- istical significance and all statistical tests were two-tailed. ered when an appropriate drug (based on subsequent in vitro susceptibility testing results) with adequate dosage Results was started within 72 h from the first blood culture per- Of 270 patients diagnosed with Candida BSIs during the formed. Adequate dosage of an antifungal agent was de- study period, 63 (23 %) were infected with isolates of C. fined according to IDSA 2009 guidelines [13]. Early parapsilosis complex (95 C.