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  Trends in Neonatal Septicemia: Emergence of Non-albicans Candida
                 Jyotsna Agarwal, Seema Bansal, *GK Malik and Amita Jain
        From the Departments of Microbiology and *Pediatrics, King George’s Medical University,
                                       Lucknow 226 003, India.
     Correspondence to: Dr. Amita Jain, Professor, Post Graduate Department of Microbiology, King
       George’s Medical University, Lucknow 226 003, India. E-mail: amita602002@yahoo.com
          Manuscript received: October 24, 2003, Initial review completed: December 11, 2003;
                                 Revision accepted: January 13, 2004.

     In a prospective analysis, blood from 660 neonates admitted to Neonatal Intensive Care Unit
     (NICU) of a teaching hospital with clinical suspicion of septicemia was cultured to look for
     etiological agents with particular reference to role of Candida species. Blood culture specimens
     from two different sites at same time were obtained to rule out possibility of a Candida isolate being
     a mere contaminant. Due to technical difficulties, this was possible in only 338 neonates (Group I);
     from remaining 322 neonates only single specimen was available (Group II). Candida was isolated
     from total 90 neonates (isolation rate 13.6%) and it was the single most common isolate. Majority
     were non-albicans Candida (germ tube test negative - 76/90). In group I, Candida was isolated
     from 66 neonates, of these 49 grew Candida in both specimens (significant candidemia). 44
     records were available for analysis. Low birth weight was found in 73.3%. Crude mortality was
     52.6%. A peak in isolation rate of Candida was noted (isolation rate 27%, p<0.05) in month of
     February. In Group I, 49 of the total 66 (74.2%) isolates of Candida were significant, suggesting
     that three in every four Candida isolated from blood can be significant. Non-albicans Candida are
     emerging as important pathogens for neonatal septicemia.
     Key words: Candida species, Candidemia, Neonatal septicemia, Neonatal ICU



    Over the last 2 decades, yeasts have                    (NICU)(5,6). Common use of broad-spectrum
become important nosocomial pathogen,                       antibiotics, low birth weight (LBW), pre-
Candida species being the most frequent                     maturity and intravenous catheter etc. makes
isolate. This rise is largely attributed to                 neonates prone to candidemia(2,7-12).
extensive use of broad-spectrum antibiotics                     Here we are presenting our findings that
and advances in medical field, which contri-                were observed while investigating the causes
bute towards the large pool of susceptible                  of septicemia in a neonatal ICU.
population available for these opportunistic
                                                            Subjects and Methods
pathogens(1,2).     Recently,    non-albicans
Candida have emerged as important                               The study was conducted in Microbiology
opportunistic pathogen, notably C. tropicalis,              and Pediatrics department at KGMU,
C. glabrata and C. parapsilosis(3). This could              Lucknow, India. This is a tertiary care, 2500
be because of selection of lesser susceptible               bedded hospital. In a prospective analysis
non-albicans species due to frequent use of                 between August 2002 to April 2003; blood
fluconazole(4). Importance of Candida spp                   from 660 neonates (<28 days) admitted in
in nursery and intensive care setup is                      NICU with clinical suspicion of septicemia
increasingly being recognized. Candida spp                  was collected for culture. We were noticing an
account for 9 to 13% of all blood stream                    increase in the isolation rate of non-albicans
isolates in neonatal intensive care unit                    Candida over last few months from cases of

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neonatal septicemia. Since Candida can be                  Candida from their blood, 49 of these
part of skin flora of neonates admitted in                 neonates grew Candida in both specimens i.e.,
hospital, its isolation from blood culture may             significant candidemia (14.5 %). In remaining
reflect contamination from skin flora. To rule             17 cases, Candida was isolated from only
out this, we planned present study with the aim            single specimen. From Group II Candida was
of collecting two blood culture specimens                  isolated in 24/322 neonates. Majority of the
from each neonate enrolled. Due to technical               isolates were non-albicans Candida (GTT
difficulties of collecting blood from a sick               negative, 76/90).
neonate; two specimens each were received
                                                               Of 49 neonates who had significant
from only 338 neonates (Group I); 2 mL of
                                                           candidemia, records of 44 were available for
venous blood was collected for culture under
                                                           analysis, one of these neonate had two
aseptic conditions simultaneously from two
                                                           episodes of candidemia, so a total of 43 cases
different sites. From remaining 322 neonates,
                                                           were further analyzed. Mean age of neonate at
only single specimen of blood was available
                                                           the time of investigation was 3.4 days (ranging
for culture (Group II).
                                                           from just born to 19 days), male is to female
    Blood specimen was inoculated into                     ratio was 1:2. Average duration of stay in ICU
culture bottle with 20 mL of brain heart                   was 9.6 days. Other associated findings were
infusion broth and subcultures were made on                LBW 73.3% (P<0.05), prematurity 38.6%,
5% sheep blood agar and Sabouraud’s                        perinatal asphyxia 35.7%, respiratory distress
dextrose agar after 24 hours and on 6th                    33.3%, jaundice 28.5% and meconium
day(13). Significant candidemia was defined                aspiration in 11.9% of neonates.
as growth of Candida in both samples from a
                                                               Crude mortality rate was 52.6% in culture
patient to rule out the possibility of the isolate
                                                           proven significant candidemia group. Details
being a contaminant from skin flora. Germ
                                                           of anti-fungal treatment were not available.
tube test was put for all Candida isolates and
                                                           On further analysis we noticed a peak in
they were reported as C. albicans or non-
                                                           isolation rate of Candida in month of
albicans Candida. Significant Candida
                                                           February, 14 of the 52 blood specimen
recovered from fourteen cases of candidemia
                                                           received in this month grew Candida
during the month of February were further
                                                           (isolation rate 27%) and it was found to be
identified using sugar fermentation and
                                                           significantly higher than in any other month (P
assimilation tests(14).
                                                           <0.05). These 14 Candida isolates were
Results                                                    further speciated, and 9 were found to be C.
                                                           tropicalis, four C.glabrata and one isolate
    Blood cultures from 660 cases with
                                                           was C.guillermondii.
clinical suspicion of septicemia were
processed. Candida was isolated from a total               Discussion
of 90 neonates (isolation rate 13.6%); Gram
                                                               In the present study Candida was the
negative and Gram positive organisms from
                                                           commonest isolate from neonates clinically
158 and 129 neonates (isolation rate 23.9%
                                                           suspected to have septicemia. Majority (76/
and 19.5%) respectively. Infection rate due to
                                                           90) of the isolates were non-albicans Candida.
Candida was calculated to be 77/1000
                                                           Blood stream infection cases due to non-
discharges in NICU.
                                                           albicans Candida have been reported to range
   Of 338 neonates in Group 1, 66 grew                     from 14-100%(1). In a retrospective analysis

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                                          Key Messages
   • Non-albicans Candida are gaining importance as cause of neonatal septicemia.
   • Upto three fourth of Candida species isolated from single blood culture specimen from neonates
     with clinically suspected septicemia, may be significant.



in an NICU, authors found >11 fold increase              isolation rate was between 8-16% in accord-
in rate of candidemia over a fifteen year period         ance with other published reports(5,6,10).
(2.5/1000 discharges in 1981 to 28.5/1000                High rate of fungemia (22.8%) in neonates has
discharges in 1995(15). A shift from                     been reported by a group and they also noted
C.albicans to non-albicans was noted by this             that 71.4% of neonates were colonized with
group, C. parapsisosis being most prevalent              yeasts within 24 hours of admission and
isolate in latter years. Similar trend was also          colonization was more in LBW babies(12).
observed by an Indian group in their study
                                                             Candidemia is generally associated with
done over a period of ten years(6). Previous
                                                         high rnortality. In our study crude mortality
study during year 2001 from our hospital
                                                         rate of 52.6% was observed in neonates with
showed candidemia to be present in 6% of
                                                         significant candidemia Reported attributable
neonates with suspected septicemia(17),
                                                         mortality ranges from 6-22%. Mortality rates
Candida was not further identified. There is
                                                         as high as 60-80% have been reported in
marked increase in rate of blood stream
                                                         candidemia in adult patients(21).
infection caused by Candida, over last two
years at our center.                                         Several risk factors have been cited as
                                                         predisposing to candidemia in neonates
    Various workers have reported Candida as             including underlying illness, LBW, broad-
cause for neonatal septicemia. Systemic                  spectrum antibiotic, asphyxia neonatorum,
candidiasis in 3.2% of admissions in NICU                invasive interventions, hyperalimentation and
has been reported by one group(18), in their             TPN, etc. (2,7-12). In our study LBW was the
study mean age at the time of infection was              commonest associated finding present in
10.4 days, 95% had LBW and 94% of                        73.3% neonates with candidemia.
neonates were preterm. They found Candida
attributed mortality to be 17%, C. tropicalis,               The findings from Group I, in which 49 of
C. albicans and C. guillermondii were the                the total 66 (74.2%) isolates of Candida were
commonest isolates. Systemic candidiasis was             significant, suggests that three in every four
found in 0.57% of neonatal admissions in a               Candida isolated from blood culture is a
prospective multicenter analysis, C. albicans            significant isolate. This is an important finding
being the commonest species and LBW the                  that emerges from this study, as Candida
commonest associated factor(19).                         isolated from single blood culture is some-
                                                         times ignored as a mere skin contaminant.
    An outbreak of candidemia during month
                                                         Contributors: JA analyzed and interpreted the data.
of February (isolation rate 27%) was largely             SB and GKM were involved in acquisition of data. JA
responsible for overall high infection rate due          and SB drafted the manuscript. AJ conceived and
to Candida in this study (77/1000 discharges             designed the study, revised it critically and interpreted
in NICU); apart from that one month the                  data. All authors finally approved the manuscript.

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Funding: None.                                                 12.   Singh K, Chakrabarti A, Narang A, Gopalan S.
Competing interests: None stated.                                    Yeast colonization and fungemia in preterm
                                                                     neonates in a tertiary care centre. Indian J Med
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  • 1. BRIEF REPORTS Trends in Neonatal Septicemia: Emergence of Non-albicans Candida Jyotsna Agarwal, Seema Bansal, *GK Malik and Amita Jain From the Departments of Microbiology and *Pediatrics, King George’s Medical University, Lucknow 226 003, India. Correspondence to: Dr. Amita Jain, Professor, Post Graduate Department of Microbiology, King George’s Medical University, Lucknow 226 003, India. E-mail: amita602002@yahoo.com Manuscript received: October 24, 2003, Initial review completed: December 11, 2003; Revision accepted: January 13, 2004. In a prospective analysis, blood from 660 neonates admitted to Neonatal Intensive Care Unit (NICU) of a teaching hospital with clinical suspicion of septicemia was cultured to look for etiological agents with particular reference to role of Candida species. Blood culture specimens from two different sites at same time were obtained to rule out possibility of a Candida isolate being a mere contaminant. Due to technical difficulties, this was possible in only 338 neonates (Group I); from remaining 322 neonates only single specimen was available (Group II). Candida was isolated from total 90 neonates (isolation rate 13.6%) and it was the single most common isolate. Majority were non-albicans Candida (germ tube test negative - 76/90). In group I, Candida was isolated from 66 neonates, of these 49 grew Candida in both specimens (significant candidemia). 44 records were available for analysis. Low birth weight was found in 73.3%. Crude mortality was 52.6%. A peak in isolation rate of Candida was noted (isolation rate 27%, p<0.05) in month of February. In Group I, 49 of the total 66 (74.2%) isolates of Candida were significant, suggesting that three in every four Candida isolated from blood can be significant. Non-albicans Candida are emerging as important pathogens for neonatal septicemia. Key words: Candida species, Candidemia, Neonatal septicemia, Neonatal ICU Over the last 2 decades, yeasts have (NICU)(5,6). Common use of broad-spectrum become important nosocomial pathogen, antibiotics, low birth weight (LBW), pre- Candida species being the most frequent maturity and intravenous catheter etc. makes isolate. This rise is largely attributed to neonates prone to candidemia(2,7-12). extensive use of broad-spectrum antibiotics Here we are presenting our findings that and advances in medical field, which contri- were observed while investigating the causes bute towards the large pool of susceptible of septicemia in a neonatal ICU. population available for these opportunistic Subjects and Methods pathogens(1,2). Recently, non-albicans Candida have emerged as important The study was conducted in Microbiology opportunistic pathogen, notably C. tropicalis, and Pediatrics department at KGMU, C. glabrata and C. parapsilosis(3). This could Lucknow, India. This is a tertiary care, 2500 be because of selection of lesser susceptible bedded hospital. In a prospective analysis non-albicans species due to frequent use of between August 2002 to April 2003; blood fluconazole(4). Importance of Candida spp from 660 neonates (<28 days) admitted in in nursery and intensive care setup is NICU with clinical suspicion of septicemia increasingly being recognized. Candida spp was collected for culture. We were noticing an account for 9 to 13% of all blood stream increase in the isolation rate of non-albicans isolates in neonatal intensive care unit Candida over last few months from cases of INDIAN PEDIATRICS 712 VOLUME 4 __JULY 1 , 2 0 1 7 04
  • 2. BRIEF REPORTS neonatal septicemia. Since Candida can be Candida from their blood, 49 of these part of skin flora of neonates admitted in neonates grew Candida in both specimens i.e., hospital, its isolation from blood culture may significant candidemia (14.5 %). In remaining reflect contamination from skin flora. To rule 17 cases, Candida was isolated from only out this, we planned present study with the aim single specimen. From Group II Candida was of collecting two blood culture specimens isolated in 24/322 neonates. Majority of the from each neonate enrolled. Due to technical isolates were non-albicans Candida (GTT difficulties of collecting blood from a sick negative, 76/90). neonate; two specimens each were received Of 49 neonates who had significant from only 338 neonates (Group I); 2 mL of candidemia, records of 44 were available for venous blood was collected for culture under analysis, one of these neonate had two aseptic conditions simultaneously from two episodes of candidemia, so a total of 43 cases different sites. From remaining 322 neonates, were further analyzed. Mean age of neonate at only single specimen of blood was available the time of investigation was 3.4 days (ranging for culture (Group II). from just born to 19 days), male is to female Blood specimen was inoculated into ratio was 1:2. Average duration of stay in ICU culture bottle with 20 mL of brain heart was 9.6 days. Other associated findings were infusion broth and subcultures were made on LBW 73.3% (P<0.05), prematurity 38.6%, 5% sheep blood agar and Sabouraud’s perinatal asphyxia 35.7%, respiratory distress dextrose agar after 24 hours and on 6th 33.3%, jaundice 28.5% and meconium day(13). Significant candidemia was defined aspiration in 11.9% of neonates. as growth of Candida in both samples from a Crude mortality rate was 52.6% in culture patient to rule out the possibility of the isolate proven significant candidemia group. Details being a contaminant from skin flora. Germ of anti-fungal treatment were not available. tube test was put for all Candida isolates and On further analysis we noticed a peak in they were reported as C. albicans or non- isolation rate of Candida in month of albicans Candida. Significant Candida February, 14 of the 52 blood specimen recovered from fourteen cases of candidemia received in this month grew Candida during the month of February were further (isolation rate 27%) and it was found to be identified using sugar fermentation and significantly higher than in any other month (P assimilation tests(14). <0.05). These 14 Candida isolates were Results further speciated, and 9 were found to be C. tropicalis, four C.glabrata and one isolate Blood cultures from 660 cases with was C.guillermondii. clinical suspicion of septicemia were processed. Candida was isolated from a total Discussion of 90 neonates (isolation rate 13.6%); Gram In the present study Candida was the negative and Gram positive organisms from commonest isolate from neonates clinically 158 and 129 neonates (isolation rate 23.9% suspected to have septicemia. Majority (76/ and 19.5%) respectively. Infection rate due to 90) of the isolates were non-albicans Candida. Candida was calculated to be 77/1000 Blood stream infection cases due to non- discharges in NICU. albicans Candida have been reported to range Of 338 neonates in Group 1, 66 grew from 14-100%(1). In a retrospective analysis INDIAN PEDIATRICS 713 VOLUME 4 __JULY 1 , 2 0 1 7 04
  • 3. BRIEF REPORTS Key Messages • Non-albicans Candida are gaining importance as cause of neonatal septicemia. • Upto three fourth of Candida species isolated from single blood culture specimen from neonates with clinically suspected septicemia, may be significant. in an NICU, authors found >11 fold increase isolation rate was between 8-16% in accord- in rate of candidemia over a fifteen year period ance with other published reports(5,6,10). (2.5/1000 discharges in 1981 to 28.5/1000 High rate of fungemia (22.8%) in neonates has discharges in 1995(15). A shift from been reported by a group and they also noted C.albicans to non-albicans was noted by this that 71.4% of neonates were colonized with group, C. parapsisosis being most prevalent yeasts within 24 hours of admission and isolate in latter years. Similar trend was also colonization was more in LBW babies(12). observed by an Indian group in their study Candidemia is generally associated with done over a period of ten years(6). Previous high rnortality. In our study crude mortality study during year 2001 from our hospital rate of 52.6% was observed in neonates with showed candidemia to be present in 6% of significant candidemia Reported attributable neonates with suspected septicemia(17), mortality ranges from 6-22%. Mortality rates Candida was not further identified. There is as high as 60-80% have been reported in marked increase in rate of blood stream candidemia in adult patients(21). infection caused by Candida, over last two years at our center. Several risk factors have been cited as predisposing to candidemia in neonates Various workers have reported Candida as including underlying illness, LBW, broad- cause for neonatal septicemia. Systemic spectrum antibiotic, asphyxia neonatorum, candidiasis in 3.2% of admissions in NICU invasive interventions, hyperalimentation and has been reported by one group(18), in their TPN, etc. (2,7-12). In our study LBW was the study mean age at the time of infection was commonest associated finding present in 10.4 days, 95% had LBW and 94% of 73.3% neonates with candidemia. neonates were preterm. They found Candida attributed mortality to be 17%, C. tropicalis, The findings from Group I, in which 49 of C. albicans and C. guillermondii were the the total 66 (74.2%) isolates of Candida were commonest isolates. Systemic candidiasis was significant, suggests that three in every four found in 0.57% of neonatal admissions in a Candida isolated from blood culture is a prospective multicenter analysis, C. albicans significant isolate. This is an important finding being the commonest species and LBW the that emerges from this study, as Candida commonest associated factor(19). isolated from single blood culture is some- times ignored as a mere skin contaminant. An outbreak of candidemia during month Contributors: JA analyzed and interpreted the data. of February (isolation rate 27%) was largely SB and GKM were involved in acquisition of data. JA responsible for overall high infection rate due and SB drafted the manuscript. AJ conceived and to Candida in this study (77/1000 discharges designed the study, revised it critically and interpreted in NICU); apart from that one month the data. All authors finally approved the manuscript. INDIAN PEDIATRICS 714 VOLUME 4 __JULY 1 , 2 0 1 7 04
  • 4. BRIEF REPORTS Funding: None. 12. Singh K, Chakrabarti A, Narang A, Gopalan S. Competing interests: None stated. Yeast colonization and fungemia in preterm neonates in a tertiary care centre. Indian J Med REFERENCES Res 1999; 110: 169-173. 1. Pfaller MA. Epidemiology and control of 13. Collee JG, Duguid JP, Fraser AG, Marmion fungal infection. Clin Infect Dis 1994; 199: BP, Simmons A. Laboratory strategy in the S8-13. diagnosis of infective syndromes. Collee JG, Fraser AG, Marmion BP, Simmons A (editors). 2. Fraser VJ, Jones M, Dunkel J, Strofer S, In: Mackie and McCartney Practical Medical Medoff G, Dunagan C. Candidemia in a Microbiology. 14th ed. Singapore: Churchill tertiary care hospital: Epidemiology, risk Livingstone; 1996. p 53-94. factors and predictor of mortality. Clin Infect Dis 1992; 15: 414-421. 14. McGinnis MR, Yeast Identification. In: Laboratory Handbook of Medical Mycology. 3. Garbino J, Kolarova L, Rohner P, Lew D, New York: Academic Press; 1980. p. 337- Pichna P, Pittet D. Secular trends of candi- 373. demia over 12 years in adult patients at a tertiary care hospital. Medicine 2002; 81: 15. Kossoff EH, Buescher ES, Karlowicz MG. 425-433. Candidemia in a neonatal intensive care unit: trends during 15 years and clinical features of 4. Wingard JR. Importance of Candida spp. other 111 cases. Pediatr Infect Dis J 1998; 17: 504- than C. albicans as pathogens in oncology 508. patients. Clin Infect Dis 1995; 20: 115-125. 16. Chakrabarti A, Chander J Kasturi P, Panigrahi 5. Beck Sague CM, Azini P, Fonseca SN. Blood D. Candidernia: a 10 year study in an Indian stream infection in neonatal intensive care unit teaching hospital. Mycoses 1992; 35: patients: results of multicenter study. Pediatr 47-51. Infect Dis J 1994; 13: 1110-1116. 17. Jain A, Roy I, Gupta MK, Kumar M, Agarwal 6. Stoll BJ, Gordon T, Korones SB. Early onset SK. Prevalence of extended spectrum b- sepsis in very low birth weight neonates: a lactamase producing Gram-negative bacteria in report from the National Institute of Child septicemic neonates in a tertiary care hospital. J Health and Human Development Neonatal Med Microbiol 2003; 52: 421-425. Research Network. J Pediatr 1996; 129: 72-75. 18. Narang A, Agarwal PB, Chakrabarti A, Kumar 7. Smith H, Congdon P. Neonatal systemic P. Epidemiology of systemic candidiasis in a candidiasis. Arch Dis Child 1985; 60: 365-369. tertiary care neonatal unit. J Trop Ped 1998; 44: 8. Leibovitz E, Iuster-Reicher A, Amitai M, 104-108. Mogilner B. Systemic Candida infections 19. Lopez Sastre JB, Coto Cotallo GD, Fernandez associated with use of peripheral venous Colomer B. Neonatal invasive candidiasis: a catheters in neonates: a 9 year experience. Clin prospective multicenter study of 118 cases. Am Infect Dis 1992; 14: 485-491. J Perinatol 2003: 20: 153-164. 9. Stamos JK, Rowley AH. Candidemia in a 20. Goon All, Walsh TJ. Fungal infections in pediatrics population. Clin Infect Dis 1995; 20: pediatrics patients. In: Anaissie EJ, McGinnis 571-575. MR, Pfaller MA, editors. Clinical Mycology. 10. Roy A, Maiti PK, Adhya S, Bhattacharya A, Philadelphia: Churchill Livingstone; 2003. p Chakraborty G, Ghosh E. Neonatal candi- 417-442. demia. Indian J Pediatr 1993; 60: 799-801. 21. Wey SB, Motomi M, Pfaller MA, Woolson RF, 11. Gupta N, Mittal N, Sood P, Kumar S, Kaur R, Wenzel RP. Hospital acquired candidemia. Mathur MD. Candidemia in neonatal Intensive The attributable mortality and excess length care unit. Indian J Pathol Microbiol 2001; 44: of stay. Arch Intern Med 1988; 148: 2642- 45-48. 2645. INDIAN PEDIATRICS 715 VOLUME 4 __JULY 1 , 2 0 1 7 04