Invasive candidiasis outbreak in a neonatal intensive care unit (NICU), a descriptive study from tertiary care teaching hospital of western part of Maharashtra

 

 

Abstract               Background: Candidemia outbreaks are frequent event take place in NICU accounting about 9-13%. Especially non-albicans Candida species emerged as an important cause of various outbreaks in NICU. There are various predisposing factors which may be a culprit for an outbreak. Early on detection and source of infection is helpful in effective management of candidemia outbreak. Material and methods: There was remarkable increase in number of candida isolates from blood cultures in Microbiology laboratory. Different laboratory procedures were performed to identify these isolates till species level and also antifungal susceptibility test was done further. Environmental samples were collected from NICU to trace the cause of outbreak. Results: Candidemia incidence in current outbreak was 7.71%. The most common species involved was C.glabrata in 43(81.13%) followed by C.tropicalis 10(18.87%). Among environmental samples these isolates were isolated from in use Total Parenteral Nutrition (TPN) and Dextrose solution used in NICU. Conclusion: NICU is always vulnerable unit where standard safety precautions should be at utmost level. Any minor breach in practices can lead to major events. Therefore, if needed surveillance should be done to evaluate source of infection before time and also for effective management of such events.

Key Word: Candidemia , NICU, outbreak

 

 

 

INTRODUCTION

Blood stream infections (BSIs) are the major problem in Intensive Care Units of the hospital especially Neonatal Intensive Care Unit (NICU). Though bacteria are traditionally the common cause of BSIs, fungal infections are increasing their occurrence in the event. It accounts for about 9-13% of BSI in neonates. They have been found to be the cause for various outbreaks that occurred in NICU.^1,2,3,4 Invasive Candidiasis in neonates is a severe and frequent cause of late onset sepsis. Among fungal BSIs Candida species, especially non-albicans species is the major cause of infections. Non-albicans Candida species emerged as an important cause of Candidiasis includes C. parapsilosis, C. tropicalis, C. krusei and C. glabrata. This rise of non-albicans Candida species is a concern in the management of Candidiasis event as few species are predominately resistant to anti-fungal drugs such as C.krusei being intrinsically resistant to Fluconazole.^1,3,5,6 In addition, Various predisposing factors are accountable for occurrence of Candidiasis outburst in neonates such as preterm babies or prematurity, low birth weight (LBW), intramedical devices, broad spectrum antibiotics, total parenteral nutrition (TPN), mechanical ventilation, prolonged hospitalization, history of surgical procedure and intestinal colonization. It is important to identify risk factors which are likely to influence health outcomes in these patients.^2,3,5,7,8 Early and prompt diagnosis of such cases can help in effective management of outbreak. Here we report an invasive Candidiasis outbreak in NICU from tertiary care teaching hospital.

 

MATERIAL AND METHODS

In Microbiology laboratory we observed dramatic increase in isolation of Candida strains during Nov-2016 and December-2016, from blood culture of NICU patients compared to the previous laboratory data. Different laboratory procedures were performed (detail procedure given below) to identify the pathogen to the species level and their antifungal susceptibility pattern for epidemiological purpose as well as for effective management. An outbreak was suspected, so we started working on parameters to control the outbreak. We conducted a survey in NICU. Different environmental samples were taken to know the exact source of an outbreak.

Sample collection: Blood cultures were collected from suspected clinical sepsis cases by venipuncture for using all aseptic precautions and transported to laboratory for further processing.

Microbiological processing: Blood cultures were incubated at 37°C in the laboratory. Subcultures were made on 3rd, 5th and 7th day onto the routine media such as Blood agar, MacConkey Agar and Sabaraud’s Dextrose agar (SDA) with chloramphenicol and incubated at 37°C. Candida isolates were identified by standard methods including colony morphology on SDA, chromogenic media (Hichrome, Himedia Pvt. Ltd.), germ tube formation, chlamydospore formation on corn meal agar(HiMedia).^9,10,11 Antifungal susceptibility testing was performed for fluconazole (25 mg), itraconazole (ITR, 10 mg), voriconazole(VRC 1 mg), ketoconazole(KTC, 10 mg) and amphotericin B (AMB, 100 units) using standard disc diffusion method on Muller-Hinton agar supplemented with 2% dextrose and methylene blue (5 mg/ml) according to CLSI guidelines and Zone diameters were interpreted as per standard guidelines.¹²

Environmental surveillance: Swabs from potential environmental reservoirs such as nearby surfaces and equipments which included Health Care worker’s (HCW’s) hands, beds, incubators, ventilators and ventilator tubings, ante-cubital fossa and intravenous medication vials were screened. Simultaneously intravenous fluid administration set and intravenous solutions were collected and processed further. Intravenous solutions collected were Dextrose and Total Parenteral Nutrition (TPN) fluids. In the laboratory, different environmental samples collected were inoculated on Sheep blood agar and Sabouraud dextrose agar. Further identification and speciation of fungal isolates was done as per standard microbiological techniques. After analysing results outbreak situation was confirmed. Hospital infection control guidelines were provided to the NICU. The concerned staff was trained regarding universal safety precautions to be taken before performing any procedures in babies. At the end of Jan-2017 isolation rate decreased. But again few cases were identified during month of February to June 2017. So again in July-2017 we assessed possible risk factors and tried to re-investigate an outbreak. This time while taking environmental samples we also included inuse total parenteral nutrition (multi-electrolyte fluids) and dextrose solution started to the babies. These samples were included to know the source of colonization as they are extremely good source of nutrients for growth of Candida. Data from this investigation were analyzed to formulate outbreak control measures.^{7,8, 13,14}

 

RESULTS

Following earlier cluster of Candidemia cases in NICU, there were constantly new cases found during outbreak. Overall 53 episodes of Candidemia were reported from NICU during November 2016 to July 2017.A total of 687 blood cultures were sent from NICU from clinical septicemia cases during this period, overall incidence of Candidemia found to be 7.71%. (Table 1) The most common species isolated was C.glabrata in 43(81.13%) followed by C.tropicalis 10(18.87%). We analysed susceptibility testing against antifungals also, results are given as in below Table 3. Environmental samples were collected to find out source of an outbreak. Different samples collected and results has been tabulated in Table 4.

Table 1: overall blood culture results

 

 

 

 

 

Table 2: Distribution of Various Candida Species

 

 

Table 3: Anti-Fungal Susceptibility Pattern Of Isolates

 

Table 4: Environmental Sampling Results

 

DISCUSSION

Outbreaks of invasive candidiasis in hospitalized patients have been reported in various hospitals. Among such outbreaks Candida especially non-albicans candida species were found to be the culprit. Different possible factors associated with outbreaks were increased use of intramedical devices, colonization of animate and inanimate objects, cross-infection via the hands of health care workers or total parenteral nutrition solutions that may be contaminated during preparation or intravenous administration.⁸ Candidemia event had been very common in NICU due to babies’ susceptibility to trivial infections. This may be due to various predisposing factors such as low birth weight, preterm birth, broad spectrum antibiotics, prolonged hospital stay, various intramedical procedures which makes them vulnerable. These various factors prone neonatal babies to septicemia or blood stream infections. Overall prevalence rate of Candidemia in NICU varies from 9- 13%.^1,2,3,4 In our study, we found prevalence of Candidemia 7.71% which is correlating with other studies. Few studies have reported greater incidence upto 18% such as by Kothari et al.¹⁵ This may be due to non-adherance to aspetic precautions to be followed before various procedures. In reported previous outbreaks, non-albicans candida species were commonly isolated as a cause in the event. In our institute, we had also observed non-albicans Candida species as a common offender. Trend of candida species predominance may vary according to geographical distribution, as in western countries like USA and other countries C.albicans, C.parpasilosis^4,5,8,16 were commonly involved while in Asian countries like India change of trend had been observed. In these countries, recently there has been increased predominance of C.glabrata and C.tropicalis in outbreak in NICU.^3,5,8 In the present study most common species isolated was C.glabrata(81.13%) followed by C.tropicalis(18.87%). Our findings are correlating with various studies such as Trick et al¹⁷, Kapila at al¹⁸ and Sardana et al¹⁹. Though few isolated outbreaks had different findings such as Banerji et al¹¹, Basu et al⁽²⁰⁾ and Narain et al²¹ have reported C.albicans predominance, while Juyal et al³, observed predominance of C.parapsilosis in the event. In few studies C.tropicalis and other species had been isolated as a causative agent.^1,22 Due to clustering of cases we did environmental surveillance in NICU to detect the source of event. Various samples were collected as shown in Table 4. We did not find any Candida isolation in any samples except multi-electrolyte fluid i.e. total parenteral nutrition which had isolated C.glabrata and dextrose solution which grew C.tropicalis with similar susceptibility pattern. It was hypothesized that these solutions may have been contaminated during pre-infusion set preparation or dilution.^8,16 So we advised NICU staff to follow strict aseptic precautions during IV set preparation and strict adherence to hand hygiene practice before and after administration of fluid. At the same time, NICU staff were trained regarding intravenous line care also. After few weeks of following standard safety precautions, we observed significant decrease in incidence of Candidemia cases from NICU and outbreak was curtailed.

 

CONCLUSION

As neonates are vulnerable to various opportunistic infections including fungal as well as bacterial infections, highest attention must be paid to NICU standard precautions. One should always look for any alarming sign of outbreak and need of necessary surveillance protocol to be followed so as to reduce the event. Breach in safety precautions leads to the spread of infection, so strict adherence to standard work precautions most of the times helps in preventing outbreak in NICU.

Nevertheless, our study emphasizes the importance of passive surveillance by laboratory findings in timely detection of outbreaks.

 

REFERENCES

1. Shrivastava G, Bajpai T, Bhatambare GS, Chitnis V, Deshmukh AB. Neonatal Candidemia: clinical importance of species identification. Sifa Medical Journal. 2015 May 1;2(2):37.
2. Roilides E, Farmaki E, Evdoridou J, Francesconi A, Kasai M, Filioti J, Tsivitanidou M, Sofianou D, Kremenopoulos G, Walsh TJ. Candida tropicalis in a neonatal intensive care unit: epidemiologic and molecular analysis of an outbreak of infection with an uncommon neonatal pathogen. Journal of clinical microbiology. 2003 Feb 1; 41 (2):735-41.
3. Juyal D, Adekhandi S, Negi V, Sharma N. An outbreak of neonatal candidemia due to non-albicans Candida species in a resource constrained setting of Uttarakhand State, India. Journal of clinical neonatology. 2013 Oct; 2(4):183.
4. Dizbay M, Kalkanci A, Sezer BE, Aktas F, Aydogan S, Fidan I, Kustimur S, Sugita T. Molecular investigation of a fungemia outbreak due to Candida parapsilosis in an intensive care unit. Brazilian Journal of Infectious Diseases. 2008 Oct; 12(5):395-9.
5. Caggiano G, Lovero G, De Giglio O, Barbuti G, Montagna O, Laforgia N, Montagna MT. Candidemia in the Neonatal Intensive Care Unit: A Retrospective, Observational Survey and Analysis of Literature Data. BioMed research international. 2017; 2017.
6. Pinhati HM, Casulari LA, Souza AC, Siqueira RA, Damasceno CM, Colombo AL. Outbreak of candidemia caused by fluconazole resistant Candida parapsilosis strains in an intensive care unit. BMC infectious diseases. 2016 Dec; 16(1):433.
7. Hammoud MS, Al-Taiar A, Fouad M, Raina A, Khan Z. Persistent candidemia in neonatal care units: risk factors and clinical significance. International Journal of Infectious Diseases. 2013 Aug 1; 17(8):e624-8.
8. Giri S, Kindo AJ. A review of Candida species causing blood stream infection. Indian journal of medical microbiology. 2012 Jul 1;30(3):270.
9. Bailey and Scott’s. Diagnostic Microbiology. In: Betty A, Forbes Daniel, Sahmalice S, editors. 11th ed. Weissfelp.
10. das Neves Miranda L, Rodrigues EC, Costa SF, van der Heijden IM, Dantas KC, Lobo RD, Basso M, Varkulja GF, Krebs VL, Gibelli MA, Criado PR. Candida parapsilosis candidaemia in a neonatal unit over 7 years: a case series study. BMJ open. 2012 Jan 1;2(4):e000992.
11. Banerjee B, Saldanha Dominic RM, Baliga S. Clinico-microbiological study of candidemia in a tertiary care hospital of southern part of India. Iranian journal of microbiology. 2015 Feb;7(1):55.
12. Rex JH, Ghannoum MA, Alexander BD, Andes D, Brown SD, Diekema DJ, et al. Method for Antifungal Disk Diffusion Susceptibility Testing of Yeasts: Approved Guideline. 2nd ed. Pennsylvania: Clinical and Laboratory Standards Institute (CLSI); 2009. p. 1-23
13. Mendiratta DK, Rawat V, Thamke D, Chaturvedi P, Chhabra S, Narang P. Candida colonization in preterm babies admitted to neonatal intensive care unit in the rural setting. Indian journal of medical microbiology. 2006 Oct 1;24(4):263.
14. DiazGranados CA, Martinez A, Deaza C, Valderrama S. An outbreak of Candida spp. bloodstream infection in a tertiary care center in Bogotá, Colombia. Brazilian Journal of Infectious Diseases. 2008 Oct;12(5):390-4.
15. Kothari A, Sagar V. Epidemiology of Candida bloodstream infections in a tertiary care institute in India. Indian journal of medical microbiology. 2009 Apr 1;27(2):171.
16. Guducuoglu H, Gultepe B, Otlu B, Bektas A, Yildirim O, Tuncer O, Berktas M. Candida albicans outbreak associated with total parenteral nutrition in the neonatal unit. Indian journal of medical microbiology. 2016 Apr 1; 34(2):202.
17. Trick WE, Fridkin SK, Edwards JR, Hajjeh RA, Gaynes RP, National Nosocomial Infections Surveillance System Hospitals. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989–1999. Clinical infectious diseases. 2002 Sep 1; 35(5):627-30.
18. Kapila S, Goel SP, Prakash A. Identification of Candida species in neonatal septicaemia. International Journal of Contemporary Pediatrics. 2016 Dec 28; 3(2):601-5.
19. Sardana V, Pandey A, Madan M, Goel SP, Asthana AK. Neonatal candidemia: A changing trend. Indian Journal of Pathology and Microbiology. 2012 Jan 1; 55(1):132.
20. Basu S, Kumar R, Tilak R, Kumar A. Candida blood stream infection in neonates: Experience from a tertiary care teaching hospital of central India. Indian pediatrics. 2017 Jul 1; 54(7):556-9.
21. Narain S. Neonatal systemic candidiasis in a tertiary care centre. Indian journal of medical microbiology. 2003 Jan 1; 21(1):56.
22. Yadav S, Dahiya S, Budhani D. Candidemia in neonatal intensive care unit: a cause of concern. International Journal of Research in Medical Sciences. 2017 Apr 26; 5(5):2165-7.