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Risk factors, incidence and result of candidemia in a Turkish serving to add force care unit: a five-year that affects the past cohort study

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Oleh: Atta Ur Rahman

February 4, 2015

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Nur Yapar, MD*, Mert Akan, MD**, Vildan Avkan-Oguz, MD*,

Cem M. Ergon, MD***, Munir Hancer, MD****, Mine Doluca, MD*****

*Professor, Dept of Infectious Diseases and Clinical Microbiology

**Assistant Professor, Dept of Anesthesiology and Reanimation,

***Associate Professor, ****Consultant, *****Professor

Dept of Microbiology and Clinical Microbiology

Faculty of Medicine / Intensive Care Unit of Anesthesiology, Dokuz Eylül University, Faculty of Medicine, Izmir (Turkey)

Correspondence: Dr. Mert Akan, Department of Anesthesiology, Dokuz Eylül University, Faculty of Medicine

Balcova, 35340, Izmir, Turkey; Tel: +90 (232) 4122954; Fax: +90 (232) 4122800; E-mail-bag: mert.akan@deu.edu.tr

ABSTRACT

Background: Invasive fungal infections are of high standing and life threatening infections seen in immunocompromised and critically seriously indisposed patients. Candida species are the greatest part common fungal pathogens among those patients and the in the greatest degree commonly recognized clinical manifestation is candidemia. The scope of this study was to explore the incidence, risk factors and 30-age mortality associated with candidemia in the intensifying care unit (ICU).

Materials and Methods: A retroactive cohort study in a tertiary care hospital ICU was undertaken from January 2004 to December 2008. Demographic and clinical facts were collected from medical and microbiology laboratory records retrospectively.

Results: In five years bound, 66 candidemia cases were identified among 1076 cases. Overall incidence of candidemia was 12.3 by means of 1000 admissions and 23.1/10000 persevering days. Candida albicans was the most common species (53.1%) isolated from relationship specimens followed by Candida parapsilosis (21.1%). The frequencies of tracheotomy, femoral artery catheterisation, red royal line cell transfusions, parenteral nutrition, abdominal surgery, and prior use of antibiotics were significantly ~-pitched in candidemia group. In multivariate logistic regression model, parenteral nutrition and use of open spectrum antibiotic combinations were found to subsist associated with candidemia. Crude mortality duty at 30th day was 43.9% and human nature rate of candidemia associated with C. albicans was significantly higher than through non-albicans Candida strains.

Key talk: Candidemia; Intensive care units; Incidence; Risk factors; Mortality

Citation: Yapar N, Akan M, Avkan-Oguz V, Ergon CM, Hancer M, Doluca M. Risk factors, incidence and issue of candidemia in a Turkish intensifying care unit: a five-year that affects the past cohort study. Anaesth Pain & Intensive Care 2014;18(3):265-71

INTRODUCTION

In comparison with advances organ transplantation and cancer handling, survival rates of immunocompromised patients at hazard of fungal infections have improved. Likewise, in novel years the use of invasive monitoring and offensive therapeutic techniques increased in the serving to add force care units (ICUs) and this too contributed to an increase in the proportion of patients susceptible to fungal infections.1-4 Invasive fungal infections are material and life threatening infections seen in immunocompromised and critically evil patients. Candida species are the greatest number common fungal pathogens isolated from those patients and the principally commonly recognized clinical manifestation is candidemia.3Candida kind are the fourth leading cause of nosocomial progeny stream infections (BSIs) in USA and sixth in Turkey.5,6 In a prospective survey conducted by European Confederation of Medical Mycology (ECMM) in seven European countries, incidence rates of candidemia were reported betwixt 0.20 and 0.38 by 1000 hospital admissions. Of those patients, 40.2% was hospitalized in emphatic care units.7 In our hospital, the incidence of candidemia was reported because 0.56/1000 hospital admissions in 2000-2003 phrase and 53.8% of the patients through candidemia were hospitalized in ICU.8Candida infections are besides associated with high mortality rates, increased fulness of hospital stay and health care costs.4,5,9-11

METHODOLOGY

Data aggregation:

Crude mortality rate from candidemia was defined for example the death rate within 30 days following the first isolation of Candida spp. fashion blood culture.

Cultivation of blood samples:

BACTEC 9240 (in addition, aerobic/F, Becton Dickinson, Sparks, MD, USA) disposition culture system was used for attractive blood samples. For this purpose, 10 ml of mettle taken from peripheral veins and placed lines was inoculated into the scantling bottles and sent to microbiology laboratory. Bottles were in that case placed in a BACTEC blood civilization device in laboratory and incubated because seven days. 0.1-ml aliquotswere withdrawn from each positive bottle if growth signal was flagged ~ dint of. the system and they were subcultured without ceasing to blood agar (Becton Dickinson, BD Diagnostics, Heidelberg, Germany), chocolate agar (Becton Dickinson, BD Diagnostics, Heidelberg, Germany) and Eosin Methylene Blue agar (Becton Dickinson, BD Diagnostics, Heidelberg, Germany). Agar plates were incubated at 37ºC in favor of 24-48 hours and the growing on the plates were evaluated. If rising growth was obtained, agar plates were processed in Mycology laboratory.

Identification of yeasts:

Statistical algebra:

The chi-square test or Fisher’s punctual test was used for evaluating positive variables and the t-test against continuous variables. Fisher’s Exact trial is employed when sample sizes are dull, in practice. Therefore we used this example for small sample sizes. A p-account of <0.05 was considered statistically expressive. Variables that found as significant in these tests were considered in the manner that candidates for the multivariate analysis. To scrutinize risk factors independently associated with candidemia, we performed multivariate, backwards stepwise, logistic regression analysis. All statistical analyses were performed by Statistical Package for the Social Sciences (SPSSTM, Version 15.0, Chicago, Il, USA) and CDC software EPI INFOTM (rendition 6.0, Atlanta,GA,USA).

RESULTS

Incidences

During five year study phrase, 5353 patients admitted to the ICU were included in the study and 1076 of them were hospitalized besides than two days. Of these1076 patients, 66 developed candidemia. The median interval from ICU admission to the onset of candidemia was 15 (3-188) days.

Total incidence scold of candidemia was 12.3 by 1000 admissions and 23.1/10 000 uncomplaining days. A significant increase in candidemia incidence was notorious between year 2004 and 2005 (p=0.03). After which, there was a gradual decline in candidemia (Figure 1).

Figure 1: Annual incidence rates of candidemia

Risk-factors-incidence-figure1

Demographic and clinical characteristics

Of the 66 candidemia cases, 53% (n=35) were males and 47% (n=31) were the fair sex. Mean age was 54.4 (SD±23.9) years in candidemia clump and 53.2 (SD±23.0) years in dominion government group. Of the candidemia cases, 43.9% (n=29) were surgical and 56.1% (n=37) were medicinal patients. There was no statistically significant difference in terms of demographic features or underlying illnesses betwixt cases and controls (Table 1).

Table 1: Patient characteristics and underlying diseases

Parameter

Cases
n (%)

Controls
n (%)

p

Age

54.4±23.9

53.2±23.0

0.698

Gender (Male)

35 (53)

637 (63)

0.103

Diabetes mellitus

9 (13.6)

165 (16.3)

0.564

Chronic renal failure

5 (7.5)

52 (5.1)

0.394

COPD*

6 (9)

118 (11.7)

0.523

Trauma

8 (12.1)

213 (21.1)

0.08

Corticosteroid therapy

5 (7.5)

50 (4.9)

0.378

Cancer chemotherapy

7 (10.6)

51 (5)

0.053

Liver transplantation

7 (10.6)

87 (8.6)

0.579

Malignancy

20 (30.3)

210 (20.8)

0.06

APACHE II  (coarse)

22.9±6.8

20.4±7.6

0.04

*COPD: Chronic obstructive pulmonic disease

Fungal isolates

Table 2: Number of Candida fashion isolated from blood in years

Candida form

Years

2004

2005

2006

2007

2008

Total

Candida  albicans

6

8

7

10

4

35

Candida  parapsilosis

1

3

6

1

3

14

Candida  tropicalis

1

2

1

1

0

5

Candida glabrata

0

0

2

1

1

4

Candida  utilis

0

1

1

2

0

4

Candida  lusitaniae

0

2

0

0

0

2

Candida  krusei

0

1

0

0

0

1

Candida  kefyr

0

0

1

0

0

1

Total

8

17

18

15

8

66

Risk-factors-incidence-figure2

Figure 2: Species partition of isolates [*Others: C. utilis, C. lusitaniae, C. krusei, C. kefyr ]

Risk Factors

At at the outset, we performed chi-square test notwithstanding evaluation of invasive procedures and curative approaches as possible risk factors. The frequencies of tracheotomy, femoral artery catheterization, RBC transmission, TPN, abdominal surgery, and previous application of antibiotics were significantly high in candidemia cluster (Table 3). In multivariate logistic return. model, TPN (p= 0.02, OR= 1.86, 95% CI= 1.07-3.23) and prior use of broad spectrum antibiotic combinations (greater degree of than two antibiotics) (p<0.001, OR=3.2, 95% CI=1.86-5.53) were associated with an increased risk of candidemia.

Table 3: Invasive procedures and therapy of patients

Invasive procedures and therapy

Cases
n (%)

Controls
n (%)

p

Presence of urinary catheter

65 (98.4)

995 (92.4)

0.984

Presence of CVC

66 (100)

956 (88.8)

0.054

Mechanical airing

64 (96.9)

936 (86.9)

0.187

Hemodialysis

10 (15.1)

108 (10.0)

0.261

Tracheotomy

24 (36.3)

192 (17.8)

<0.01

Erythrocyte transmission

51 (77.2)

556 (51.6)

<0.01

Prior surgical procedures (entire)

45 (68.2)

618 (57.4)

0.25

Abdominal surgery

34 (51.5)

376 (34.9)

0.02

Neurosurgery

5 (7.5)

84 (7.8)

0.832

Nasogastric hollow cylinder

64 (96.9)

950 (88.2)

0.326

TPN

42 (63.6)

413 (38.3)

<0.01

Catheterization of femoral artery

15 (22.7)

123 (11.4)

0.01

Previous conversion to an act of antibiotics

64 (96.9)

843 (78.3)

<0.01

Antibiotic combinations (>2 antibiotics)

39 (59.1)

246 (22.8)

<0.01

Third race cephalosporins

14 (21.2)

181 (16.8)

0.501

Quinolones

17 (25.7)

199 (18.4)

0.234

Glycopeptides

42 (63.6)

232 (21.5)

<0.01

Carbapenems

29 ((43.9)

163 (15.1)

<0.01

Metronidazole

8 (12.1)

123 (11.4)

0.989

Beta lactam beta lactamase inhibitors

33 (50)

323 (30.0)

<0.01

Aminoglycosides

25 (37.9)

181 (16.8)

<0.01

Antifungal agents

6 (9)

68 (6.3)

0.463

Outcome

Mean length of stay of patients was 30.9±33. days in candidemia form into ~s and 12.9±13 days in direct group (p<0.001). Crude mankind rate on day 30 was 43.9% (29 at a loss of 66) in the candidemia assign places to whereas it was 32.2% (326 of 1010) in the control group. There was no significant dispute between the mortality rates of candidemia and reign over groups (p=0.05). Twenty public of 35 patients (57.1%) and 9 ~right of 31 (29%) died in C. albicans dispose and non-albicans Candida group, particularly. Mortality rate of candidemia associated through C. albicans was significantly higher than with non-albicans Candida strains (p=0.02, OR=3.26, 95%CI=1.05-10.4).

DISCUSSION

The middle interval from ICU admission to onset of candidemia was 15 (3-188) days in our study what one. is comparable to formerly published reports [10]. The method interval between ICU admission and candidemia was 19.0±2.9 days in a French study [17]. Anunnatsiri et al. [19]mould that median duration of hospitalization prior to candidemia was 16.5 days. In our study, medial sum length of hospital stay was 18 days longer in candidemia patients than ascendency consistent with the literature [20].

Candida parapsilosis is known to be firmly fixed to bio prosthetic surfaces such during the time that catheters forming a biofilm layer of glycosylated serum and can cause epidemics especially in pediatric ICUs [3,5]. The commonness of this pathogen can be explained ~ dint of. inadequate catheter care, increase in use of parenteral nutrition or poor contamination control practices mentioned above. The retrospective nature of our study limits the research of these factors.

Candida glabrata is undivided of the fluconazole resistant non-albicans Candida variety was not common in our study dispose. This pathogen has become an material and common species in the United States [24]. In exhibition of differences, it is much less common purpose of BSIs in most other countries. In more studies from Latin America, Asia-Pacific, Europe and Turkey common occurrence of candidemia due to C. glabrata was reported between 4% and 10% [5,8,25,26]. In Artemis Disk Global Antifungal Surveillance Program, a entire of 201 653 isolates were collected from 133 centers between January 2001 and December 2007. The oftenness of C. glabrata isolation was depress in Turkey (3.1%) than other countries [27]. The reasons in quest of the frequency variation of C. glabrata are not undeniable but may include prior azole exposing., age, geographic location, blood culture systems used instead of diagnosis or other unknown features [5].

Risk factors in the place of candidemia can be divided in to two groups: Host related factors and underlying hale condition conditions; health-care associated factors such as catheters, surgical interventions and medications. In our study, there was no statistically significant difference in articles of agreement of underlying illnesses between the cases and controls unless for higher APACHE II scores in candidemia group than in controls.ACHE II scores of cases were significantly higher than check patients. However we could not obtain APACHE II scores of all patients from of the healing art records reviewed retrospectively which is united of the limitations of our study.

Predisposing factors on the side of candida BSIs described in literature are: anterior exposure to antibiotics or antifungals, central venose or urinary catheters, total parenteral nutrition, steroids, prolonged hospitalization, abdominal surgery, immunosuppressive therapy, and renal failure [5,16,23,28]. We mould similar risk factors in our study cluster. However, central venous catheterization and blind ventilation were not found to subsist significant in our study. In multivariate calculus, TPN and previous use of uncontracted spectrum antibiotic combinations especially containing glycopeptides, carbapenems, aminoglycosides and beta lactam- beta lactamase inhibitors were mould to be independently associated with an increased risk of candidemia.

Mortality was significantly higher ~ the sake of patients infected with C. albicans than the others infected through non-albicans Candida species in the study presented in the present state. This is in contrast to the study ~ the agency of Bassetti et al. [23] who set up that crude mortality was 55% in all patients with candidemia although, there was in ~ degree statistically significant difference between the humanity rates of albicans and non-albicans candidemia patients. Similarly, Chow et al. [30] form in a mould the mortality rates of BSIs directly to C. albicans and non-albicans Candida class 58% and 57% respectively. In exhibition of differences, Dimopoulos et al. [18] reported significantly bragging mortality for BSIs due to non-albicans class. In our study , the most common non-albicans Candida isolate was C. parapsilosis which has relatively low mortality among others and this could control on mortality rates.

CONCLUSION

In finale, candidemia is an important and life menace infection in the ICU. According to our study, in our hospital C. albicans is the sovereign species and we found no grow in annual rates of azole resistant non-albicans Candida kind during the study period. Important put in peril factors were invasive procedures and medications. Candidemia should be suspected in patients with these expose to danger factors and diagnostic/therapeutic interventions should exist performed immediately.

Acknowledgement: The authors would like to express gratitude to Prof. Dr. Reyhan Ucku despite her support on statistical analyses.

Conflict of Interest: There is none potential conflict of interest or beginning of funding to declare.

REFERENCES

Richardson MD. Changing patterns and trends in systemic fungal infections. J Antimicrob Chemother 2005;56:i5-11. [PubMed] [Free FullText]

De Pauw BE. Increasing fungal infections in the emphatic care unit. Surgical Infections 2006;7:S93-96. [PubMed]

Pappas PG. Invasive candidiasis. Infect Dis Clin N Am 2006;29:485-506. [PubMed]

Tufano R. Focus up~ the body risk factors for fungal infections in ICU patients. Minerva Anestesiol 2002;68:269-272. [PubMed]

Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistive public health problem. Clin Microbiol Rev 2007;20:133-163. [PubMed] [Free Full Text]

Inan D, Saba R, Yalcin AN, Yilmaz M, Ongut G. Device-associated nosocomial contamination rates in Turkish medical-surgical capable of intensification care units. Infect Control Hosp Epidemiol 2006;27:343-348. [PubMed]

Tortorano MA, Peman J, Bernhardt H, et al. Epidemiology of candidaemia in Europe: Results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based watch study. Eur J Clin Microbiol Infect Dis 2004;23:317-322. [PubMed]

Yapar N, Uysal U, Yucesoy M, Cakir N, Yuce A. Nosocomial bloodstream infections associated by Candida species in a Turkish literary institution hospital. Mycoses 2006;49:134-138. [PubMed]

Guery BP, Arendrup MC, Auzinger G, Azoulay E, Borges Sá M, Johnson EM. Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part II. Treatment Intensive Care Med 2009;35:206-214. [PubMed]

Bouza E, Munoz P. Epidemiology of candidemia in intensifying care units. Int J Antimicrob Agents 2008;32:S87-91. [PubMed]

Petri MG, König J, Moecke HP, et al. Epidemiology of invasive mycosis in ICU patients: a coming multicenter study in 435 non-neutropenic patients. Intensive Care Med 1997;23:317-325. [PubMed]

De Pauw B, Walsh TJ, Donnely JP, et al. Revised definitions of invasive fungal ailment from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813-1821.

Winn WC, Allen SD, Janda WM, Koneman EW, Procop G, Schreckenberger PC, Woods G. In: The Color Atlas and Textbook of Diagnostic Microbiology. 6th ed. Philadelphia: JB Lippincott Co; 2006:1216-1230.

Larone DH. In: Medically Important Fungi: A Guide to Identification. 4th ed. Washington, DC: ASM compel; 2002:109-143.

Guery BP, Arendrup MC, Auzinger G, Azoulay E, Borges Sá M, Johnson EM. Management of invasive candidiasis and candidemia in ripe non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis. Intensive Care Med 2009;35:55-62. [PubMed]

Luzzati R, Allegranzi B, Antozzi L, et al. Secular trends in nosocomial candidaemia in non-neutropenic patients in an Italian tertiary hospital. Clin Microbiol Infect Dis 2005;11:908-913. [PubMed]

Bougnoux ME, Kac G, Aegerter P, d’Enfert C, Fagon JY, CandiRea Study Group. Candidemia and candiduria in critically with difficulty patients admitted to intensive care units in France: incidence, corpuscular diversity, management and outcome. Intensive Care Med 2008;34:292-299. [PubMed]

Dimopoulos G, Ntziora F, Rachiotis G, Armaganidis A, Falagas ME. Candida albicans against non-albicans intensive care unit-acquired bloodstream infections: Differences in put to hazard factors and outcome. Anesth Analg 2008;106:523-529. [PubMed]

Anunnatsiri S, Chetchotisakd P, Mootsikapun P. Fungemia in non-HIV infected patients: a five-year overlook. Int J Infect Dis 2009;13:90-96. [PubMed]

Zaoutis TE, Argon J, Chu J, et al. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a inclination analysis. Infect Dis 2005;41:1232-1239. [PubMed] [Free Full Text]

Leroy O, Gangneux JP, Montravers P, et al. Epidemiology, treatment, and risk factors for death of invasive Candida infections in important care: A multicenter, prospective, observational study in France (2005-2006). Crit Care Med 2009;37:1612-1618. [PubMed]

Xess I, Jain N, Hasan F, Mandal P, Banarjee U. Epidemiology of candidemia in a tertiary care middle of north India: 5-year study. Infection 2007;35:256-259. [PubMed]

Bassetti M, Trecarichi EM, Righi E, et al. Incidence, peril factors, and predictors of outcome of candidemia. Survey in 2 Italian literary institution hospitals. Diagn Microbiol Infect Dis 2007;58:325-331. [PubMed]

Moran C, Grussemeyer CA, Spalding JR, Benjamin DK, Reed SD. Comparison of costs, amplification of stay and mortality associated with Candida glabrata and Candida albicans bloodstream infections. Am J Infect Control 2010;38:78-80. [PubMed] [Free Full Text]

Comert F, Kulah C, Aktas E, Eroglu O, Ozlu N. Identification of Candida description isolated from patients in intensive care unit and in vitro susceptibility to fluconazole in opposition to a 3-tear period. Mycoses 2006;50:52-57. [PubMed]

Bakir M, Cerikcioglu N, Barton R, Yagci A. Epidemiology of candidemia in a Turkish tertiary care hospital. APMIS 2006;114:601-610. [PubMed]

Pfaller MA1, Diekema DJ, Gibbs DL, Newell VA, Barton R, Bijie H,. Geographic departure in the frequency of isolation and fluconazole and voriconazole susceptibilities of Candida glabrata: each assessment from the ARTEMIS DISK global antifungal direction program. Diagn Microbiol Infect Dis 2010;67:162-171. [PubMed]

Ostorsky-Zeichner L, Pappas PG. Invasive candidiasis in the capable of intensification care unit. Crit Care Med 2006;34:857-862. [PubMed]

Aliyu SH, Enoch DA, Abubakar II, et al. Candidaemia in a broad teaching hospital. A clinical audit. Q J Med 2006;99:655-663. [PubMed] [Free Full Text]

Chow JK, Golan Y, Ruthazer R, et al. Factors associated by candidemia caused by non-albicans Candida shape versus Candida albicans in the intensifying care unit. Clin Infect Dis 2008;46:1206-1213. [PubMed] [Free Full Text]

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Margolis commented, "Vessix's pre-clinical data is the most robust I be seized of seen in the field of renal denervation towards hypertension.