Introduction: Febrile neutropenic patients are at risk of serious infections. The aim of the present study is to identify the frequency, species, and susceptibility patterns of candidemia in febrile neutropenic patients. Methods: This cross-sectional study was conducted on febrile neutropenic patients suspected with candidemia who had been referred to 3 educational hospitals during 9 months. Results: The blood samples of 80 febrile neutropenic patients with the mean age of 48§16.6 years were studied (60% female). Five (6.25%) episodes of candidemia were identified. The underlying disease was acute myeloid leukemia in 4 (80%) cases and all 5(100%) cases had central venous catheter and were receiving prophylactic ciprofloxacin and acyclovir. 100% of isolates were found to be susceptible to Voriconazole, 80% to Caspofungin, 60% to Amphotericin B, and 40% to Fluconazole. Conclusion: The frequency of candidemia among the studied febrile neutropenia patients was 6.25%, with 80% mortality rate, and themost frequently identified yeastwas Candida albicans (100% susceptible to Voriconazole)

Arab-Mazar, Zahra

Fatemi, Alireza

Ghajari, Ali

Lotfali, Ensieh

Yadegarynia, Davood

Yousefi, Maysam

English

Journals Portal, Shahid Beheshti University of Medical Sciences

Emergency. 2018; 6 (1): e39BRIEF REPORTCandidemia in Febrile Neutropenic Patients; a Brief Re-portMaysam Yousefi1,2, Davood Yadegarynia1, Ensieh Lotfali1,3∗ Zahra Arab-Mazar1, Ali Ghajari3, Alireza Fatemi11. Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medial Sciences, Tehran, Iran2. Assistant professor of infectious diseases, Research Center of tropical and infectious diseases, Kerman University of medical sciences,Kerman, Iran3. Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranReceived: February 2018; Accepted: June 2018; Published online: 19 June 2018Abstract: Introduction: Febrile neutropenic patients are at risk of serious infections. The aim of the present study isto identify the frequency, species, and susceptibility patterns of candidemia in febrile neutropenic patients.Methods: This cross-sectional study was conducted on febrile neutropenic patients suspected with candidemiawho had been referred to 3 educational hospitals during 9 months. Results: The blood samples of 80 febrileneutropenic patients with the mean age of 48±16.6 years were studied (60% female). Five (6.25%) episodesof candidemia were identified. The underlying disease was acute myeloid leukemia in 4 (80%) cases and all5(100%) cases had central venous catheter and were receiving prophylactic ciprofloxacin and acyclovir. 100%of isolates were found to be susceptible to Voriconazole, 80% to Caspofungin, 60% to Amphotericin B, and 40%to Fluconazole. Conclusion: The frequency of candidemia among the studied febrile neutropenia patients was6.25%, with 80% mortality rate, and the most frequently identified yeast was Candida albicans (100% susceptibleto Voriconazole).Keywords: Candidemia; febrile neutropenia; antifungal agents; drug resistance, multiple, fungal© Copyright (2018) Shahid Beheshti University of Medical SciencesCite this article as: Yousefi M, Yadegarynia D, Lotfali E, Arab-Mazar Z, Ghajari A, Fatemi A. Candidemia in Febrile Neutropenic Patients; aBrief Report. 2018; 6(1): e39.1. IntroductionFebrile neutropenic patients are at risk of serious infec-tions (1). Generally, bacteria are responsible for blood-stream infections (BSIs), but, 8% of all cases of infec-tious agents are Candida spp. (2, 3). Candida spp. that causecandidemia are the fourth most common agent of BSIs andthe fifth most common cause of nosocomial infection (4, 5).Candida albicans is the most important cause of BSIs; how-ever 45% are caused by non-albicans species such as Candidaglabrata, Candida krusei, Candida parapsilosis, and Candidatropicalis (6, 7).It appears that infection caused by species of Candida is as-sociated with a high crude mortality rate, globally (40% in the∗Corresponding Author: Ensieh Lotfali; Department of Medical Parasitologyand Mycology, School of Medicine, Shahid Beheshti University of Medical Sci-ences, Tehran, Iran, Tel: +98-2122439963 Fax: +98-2122439964 E-mail: en-siehlotfali@sbmu.ac.ir.United States)(8). The epidemiology of candidemia has beenextensively studied in developed countries, but there is a lackof data in developing ones. The aim of the present study is toidentify the frequency, species, and susceptibility patterns ofcandidemia in febrile neutropenic patients.2. Methods2.1. Study design and settingThis cross-sectional study was conducted on febrile neu-tropenic patients who had been referred to Khatam-al-Anbia, Shohadaye Tajrish, and Taleghani educational hos-pitals, Tehran, Iran, from November 2016 to August 2017.The Ethical Committee of Shahid Beheshti University ofMedical Sciences approved this study under the code:IR.SBMU.RETECH.REC.1396.192. All enrolled participantswere informed about the study and written informed consentwas obtained from them.This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).Downloaded from: www.jemerg.comM. Yousefi et al. 22.2. ParticipantsFebrile neutropenic patients suspected of candidemia (basedon clinical symptoms), referred to emergency departmentsor hospitalized in intensive care units (9) of the mentionedhospitals were enrolled to the study. Patients who had pro-longed fever in spite of receiving broad-spectrum antibioticsfor more than four days were considered as suspicious tocandidemia. Patients with chronic neutropenia were ex-cluded from this study since the incidence of neutropenia isunpredictable, and difficult to clearly identify and determine.There was not any sex or age limitation.2.3. Data gatheringDemographic and clinical data were collected includingage, sex, duration of stay in ICU, current history of broad-spectrum antibiotic therapy (for > 4 days), antifungal ther-apy, underlying diseases, and outcomes of sur–gical proce-dures. Source of data was the patient’s profile. An Assistantprofessor of infectious diseases (Dr. Yousefi) was responsi-ble for selecting suspected cases. Neutropenia was defined asneutrophil count <500/mm3 or <1000/mm3 with a predicteddecrease to <500/mm3 and fever was defined as single eleva-tion in oral temperature to ≥ 38.30 ◦C or a temperature of ≥38 ÂřC for ≥ 1 hour (10).2.4. Cultures10 ml of venous blood sample were obtained for each pa-tient aseptically via venipuncture according to a standardtechnique by using a sterile syringe after skin disinfection.Culture vials were placed in the BACTEC 9120 System (Bec-ton Dickinson Microbiology Systems, Maryland, DE, USA),and were controlled automatically every 10 minutes. TheBACTEC bottles that showed a sign of fungal growth weresub-cultured on the plates with the BHI agar (Merck, Ger-many) and Sabouraud Dextrose Agar with Chloramphenicol(SC) (Merck, Germany), separately. CHROM agar Candidamedium (CHROM agar Microbiology, Paris, France) was usedfor sub-culture of isolates, incubated at 35 ◦C for 48 h andfor preliminary species identification, production of specificcolony colors were analyzed. ITS1 and ITS4 universal primerswere used for polymerase chain reaction (PCR) and DNA se-quencing was also performed.2.5. Susceptibility testingIn vitro antifungal susceptibility test of the Candida iso–latesagainst amphotericin B (AMB) (Sigma-Aldrich, USA.), flu-conazole (FLU) (Sigma-Aldrich, USA.), voriconazole (VOR)(Pfizer Central Research, UK), and caspofungin (CAS) (Merck,USA.) were performed using micro-dilution method.2.6. Statistical analysisStatistical analyses were performed using SPSS software ver-sion 21.0. The findings were reported using descriptive statis-tics such as mean ± standard deviation or frequency and per-centage.3. Results:153 blood samples were collected from 80 febrile neu-tropenic patients (38 blood samples from emergency depart-ments and 115 from ICUs). The mean age of the patients was48±16.6 years (60% female).Five (6.25%) episodes of candidemia were identified duringthe study period. Baseline characteristics and outcome ofpatients with positive blood Culture are summarized in ta-ble 1. The underlying disease was acute myeloid leukemiain 4 (80%) cases and all 5(100%) cases had central venouscatheter and were receiving prophylactic ciprofloxacin andacyclovir. The mean dura-tion of hospital and ICU stay inpatients with candidemia were 42±5.4 and 26±4.9 days, re-spectively.Table 2 shows the in vitro susceptibility of 5 Candida spp.strains against antifungal agents. 100% of isolates were foundto be susceptible to Voriconazole, 80% to Caspofungin, 60%to Amphotericin B, and 40% to Fluconazole.4. DiscussionBased on the findings, the frequency of candidemia amongthe studied febrile neutropenia patients was 6.25%, with 80%mortality rate, and the most frequently identified yeast wasCandida albicans (100% susceptible to Voriconazole).The fourth most common pathogen isolated from the bloodof ICU patients is Candida albicans, with an attributed mor-tality range between 20–30%. (11-13). However, during re-cent years, the incidence of Candida spp. infections otherthan Candida albicans has significantly increased and Can-dida parapsilosis is currently one of the main causes of inva-sive candidiasis (14-16).The estimated rate of candidemia among ICU admitted pa-tients is between 0.5–32 cases per 1,000 admissions (17, 18).Ghahri et al. identified Candida parapsilosis as the mostprevalent Candida spp. from the blood samples of patientswith candidemia in Iran; but this was not the case in ourstudy (14).According to antifungal susceptibility tests, the most activeantifungal drug in isolated candida species was VOR; this re-sult was similar to a study by Labbe et al. (19).A study by Pfaller et al. on in vitro susceptibility results for1,184 isolates showed that VOR was considerably more po-tent than FLU (4). We also found similar results showing that100% of candida isolates were sensitive to VOR.This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).Downloaded from: www.jemerg.com3 Emergency. 2018; 6 (1): e39Table 1: Baseline characteristics and outcome of patients with positive blood CultureVariables Case 1 Case 2 Case 3 Case 4 Case 5Sex Female Female Female Male MaleAge (year) 61 34 26 48 71Hospitalization (day) 44 50 34 43 38ICU admission (day) 28 35 23 24 21Underlying disease AML AML AML AML ALLProphylaxisCiprofloxacin + + + + +Acyclovir + + + + +Fluconazole + – + – +Itraconazole – + – + –Co-trimoxazole – – – – +Medical device CVC CVC CVC CVC MV, CVCCandida Spp. C. albicans C. albicans C. albicans C. albicans C. glabrataOutcome Died Died Survived Died DiedICU: intensive care unit; CVC: central venous catheter; MV: mechanical ventilation; ALL: acute lymphoblasticleukemia; AML: acute myeloid leukemia.Table 2: In vitro susceptibility test results of the 5 Candida spp. strains against 4 antifungal agents.Antifungal agent Susceptible Dose dependent ResistantFluconazole 2 (40) 3 (60) 0 (0)Voriconazole 5 (100) 0 (0) 0 (0)Amphotericin B 3 (60) 1 (20) 1 (20)Caspofungin 4 (80) 0 (0) 1 (20)Data were reported as number (%).This investigation showed that FLU has the highest MIC GM(2.3); this result is similar to the study by Lobbe et al. that re-ported the highest MIC for FLU compared to other azole an-tifungal drugs such as VOR, ravuconazole, itraconazole, andposaconazole (19).A study by Pappas PG et al. proposed that in patients withpositive blood cultures that become positive more than 48hours after collection, FLU should probably be avoided; andit is more likely that patients are infected by Candida glabrata(20).A delay of ≥12 hours in the initial empiric antifungal treat-ment was associated with higher hospital mortality (21). Itseems that empiric antifungal therapy needs to be startedearly in order to decrease morbidity and mortality.5. LimitationsThis study had several limitations including the short dura-tion of survey followed by a low number of positive patients.Therefore, it was difficult to compare and interpret the find-ings, especially antifungal susceptibility patterns. However,based on the findings of this study, candidemia should beconsidered a significant problem in febrile neutropenic pa-tients.6. ConclusionBased on the finding, the frequency of candidemia amongthe studied febrile neutropenia patients was 6.25%, with 80%mortality rate, and the most frequently identified yeast wasCandida albicans (100% susceptible to Voriconazole).7. Appendix7.1. AcknowledgementsThe authors would like to express their gratitude to thosewho participted in data collection in selected hospitals. Thisarticle has been extracted from the thesis written by Dr.Maysam Yousefi in School of Medicine, Shahid Beheshti Uni-versity of Medical Sciences.7.2. Author contributionEnsieh Lotfali, Davood Yadegarynia, Meysam Yousefi de-signed the study. Zahra Arab-Mazar participated in acqui-sition of data. Ali Ghajari and Alireza Fatemi participated inmanagement of data. All authors approved the final versionof the manuscript to be published.7.3. Funding/SupportWe would like to express our gratitude to Infectious Dis-eases and Tropical Medicine Research Center, Shahid Be-This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).Downloaded from: www.jemerg.comM. Yousefi et al. 4heshti University of Medical Sciences for financially support-ing this research.7.4. Conflict of interestThe authors declare that they have no conflicts of interest.References1. Talcott JA, Siegel R, Finberg R, Goldman L. Risk assess-ment in cancer patients with fever and neutropenia: aprospective, two-center validation of a prediction rule.Journal of Clinical Oncology. 1992;10(2):316-22.2. Santucci S, Gobara S, Santos C, Fontana C, Levin A. Infec-tions in a burn intensive care unit: experience of sevenyears. Journal of Hospital Infection. 2003;53(1):6-13.3. Lotfi N, Shokohi T, Nouranibaladezaei SZ, Omran AN,Kondori N. High recovery rate of non-albicans Candidaspecies isolated from burn patients with candidemia inIran. Jundishapur journal of microbiology. 2015;8(10).4. Pfaller M, Diekema D, Jones R, Sader HS, Fluit A, Hol-lis R, et al. International Surveillance of BloodstreamInfections Due toCandida Species: Frequency of Oc-currence and In Vitro Susceptibilities to Fluconazole,Ravuconazole, and Voriconazole of Isolates Collectedfrom 1997 through 1999 in the SENTRY AntimicrobialSurveillance Program. Journal of Clinical Microbiology.2001;39(9):3254-9.5. Yapar N. Epidemiology and risk factors for invasive can-didiasis. Therapeutics and clinical risk management.2014;10:95.6. Zirkel J, Klinker H, Kuhn A, Abele-Horn M, Tappe D, Turn-wald D, et al. Epidemiology of Candida blood stream in-fections in patients with hematological malignancies orsolid tumors. Medical mycology. 2012;50(1):50-5.7. Das I, Nightingale P, Patel M, Jumaa P. Epidemiology, clin-ical characteristics, and outcome of candidemia: experi-ence in a tertiary referral center in the UK. InternationalJournal of Infectious Diseases. 2011;15(11):e759-e63.8. Edmond MB, Wallace SE, McClish DK, Pfaller MA, JonesRN, Wenzel RP. Nosocomial bloodstream infections inUnited States hospitals: a three-year analysis. Clinical in-fectious diseases. 1999;29(2):239-44.9. Voiculescu M, Iliescu L, Ionescu C, Micu L, Ismail G, Zilis-teanu D, et al. A cross-sectional epidemiological studyof HBV, HCV, HDV and HEV prevalence in the Sub-Carpathian and South-Eastern regions of Romania. JGastrointestin Liver Dis. 2010;19(1):43-8.10. Yadegarynia D, Fatemi A, Mahdizadeh M, MovahhedRK, Alizadeh MA. Current spectrum of bacterial infec-tions in patients with nosocomial fever and neutropenia.Caspian journal of internal medicine. 2013;4(3):698.11. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, WenzelRP, Edmond MB. Nosocomial bloodstream infections inUS hospitals: analysis of 24,179 cases from a prospectivenationwide surveillance study. Clinical infectious dis-eases. 2004;39(3):309-17.12. Zorgani A, Franka R, Zaidi M, Alshweref U, Elgmati M.Trends in nosocomial bloodstream infections in a burnintensive care unit: an eight-year survey. Annals of burnsand fire disasters. 2010;23(2):88.13. Zaoutis T. Candidemia in children. Current medical re-search and opinion. 2010;26(7):1761-8.14. Ghahri M, Mirhendi H, Zomorodian K, Kondori N. Identi-fication and antifungal susceptibility patterns of Candidastrains isolated from blood specimens in Iran. Archives ofClinical Infectious Diseases. 2013;8(3).15. Krcmery V, Barnes A. Non-albicans Candida spp. caus-ing fungaemia: pathogenicity and antifungal resistance.Journal of Hospital Infection. 2002;50(4):243-60.16. Nicholson A, Rainford L. The epidemiology of fungaemiaat the University Hospital of the West Indies, Kingston,Jamaica. West Indian Medical Journal. 2009;58(6):580-4.17. Tortorano A, Caspani L, Rigoni A, Biraghi E, Sicignano A,Viviani M. Candidosis in the intensive care unit: a 20-year survey. Journal of Hospital Infection. 2004;57(1):8-13.18. Kett DH, Azoulay E, Echeverria PM, Vincent J-L. Candidabloodstream infections in intensive care units: analysisof the extended prevalence of infection in intensive careunit study. Critical care medicine. 2011;39(4):665-70.19. Labbe A-C, Pepin J, Patino C, Castonguay S, RestieriC, Laverdiere M. A single-centre 10-year experiencewith Candida bloodstream infections. Canadian Jour-nal of Infectious Diseases and Medical Microbiology.2009;20(2):45-50.20. Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calan-dra TF, Edwards JE, et al. Clinical practice guidelines forthe management candidiasis: 2009 update by the Infec-tious Diseases Society of America. Clinical infectious dis-eases. 2009;48(5):503-35.21. Morrell M, Fraser VJ, Kollef MH. Delaying the empirictreatment of Candida bloodstream infection until posi-tive blood culture results are obtained: a potential riskfactor for hospital mortality. Antimicrobial agents andchemotherapy. 2005;49(9):3640-5.This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).Downloaded from: www.jemerg.com

Candidemia in Febrile Neutropenic Patients; a Brief Report

Abstract

Similar works

Full text

Available Versions

Journals Portal, Shahid Beheshti University of Medical Sciences

Directory of Open Access Journals