|
Indian Pediatr 2012;49: 745-747
|
|
A Fatal Outbreak of Trichosporon asahii Sepsis
in a Neonatal Intensive Care Unit
|
Vipin M Vashishtha, Amol Mittal and *Amit Garg
From the Department of Pediatrics, Mangla
Hospital and Research Center, Shakti Chowk, Bijnor, and
*Department of Microbiology, LLRM Medical College, Meerut; Uttar
Pradesh, India.
Correspondence to: Dr Vipin M Vashishtha,
Director and Consultant Pediatrician, Mangla Hospital and
Research Center, Shakti Chowk, Bijnor 246 701, India.
Email:
[email protected]
Received: October 31, 2011;
Initial review: March 15, 2012;
Accepted: April 09, 2012.
|
We describe an outbreak of Trichosporon asahii in 8 newborn
infants with sepsis. Six out of these 8 infants died. The organism was
identified on specific culture and morphologic characteristics. The
organism was sensitive to amphotericin-B but resistant to fluconazole.
Laminar flow unit was suspected to be the source of the outbreak.
Key words: India, Neonate, Outbreak, Sepsis,
Trichosporon asahii.
|
Trichosporon asahii
is an uncommon cause of fungal sepsis among
newborn infants, but, it is now emerging as an
important life-threatening opportunistic
systemic pathogen, especially in immuno-compromised
hosts [1]. Trichosporonosis is usually an
insidious disease and its diagnosis is likely to
be missed, particularly in developing countries,
because of lack of awareness and lack of
acquaintance with the salient diagnostic feature
of the etiologic agent. Barring a few isolated
case-reports, there is no information on the
prevalence of disseminated trichosporonosis in
India. We report a fatal outbreak of T.
asahii sepsis in eight newborns in our
neonatal intensive care unit (NICU).
Case Report
Eight newborn infants
admitted between 17th
to 28th
August, 2011 in our NICU were found to be
infected with T. asahii (Table
I).
TABLE I Clinical Characteristics of Neonates with T. asahii Sepsis
Case |
NICU |
Mode of |
Birth weight
|
Diagnosis
(at admission) |
Mechanical |
Outcome |
No. |
Stay (d) |
delivery |
(grams) |
|
ventilation |
|
1*. |
10 d |
Vaginal |
2400 |
Term-SGA with PNA
with Sepsis |
No |
Improved |
2. |
9 d |
Vaginal |
1200 |
Preterm (35 week)
SGA with Polycythemia |
No |
Died |
|
|
|
|
with Sepsis |
|
|
3. |
5 d |
LSCS |
1250 |
Preterm (32 week)
SGA with PNA with PPROM |
Yes |
Died |
|
|
|
|
with RDS |
|
|
4$. |
21 d |
Vaginal |
1080 |
Preterm (29 week)
SGA Breech presentation with |
Yes |
Died |
|
|
|
|
PNA with PPROM |
|
|
5$. |
20 d |
LSCS |
1720 |
Preterm (34 week) SGA
with BOH with PPROM |
No |
Improved |
6$. |
6 d |
LSCS |
1235 |
Preterm (28 week)
AGA with PNA with twin |
Yes |
Died |
|
|
|
|
pregnancy with PPROM
with anemia |
|
|
7. |
7 d |
Vaginal |
1550 |
Preterm (31 weeks)
SGA with RDS (HMD) |
Yes |
Died |
8. |
7 d |
LSCS |
2890 |
Term AGA with MSAF
with PNA |
No |
Died |
LSCS-
Lower segment caesarean section;
SGA-Small for gestational age;
AGA-Appropriate for gestational age;
PNA-Perinatal asphyxia; PPROM-Prolonged
premature rupture of membranes,
RDS-Respiratory distress syndrome; BOH-
Bad obstetric history; MSAF- Meconium-stained
amniotic fluid; $ Received Total
parenteral nutrition; *Did not receive
treatment with H2 –blockers. |
The first case was already on
broad-spectrum antibiotics for last 12 days
prior to admission. The blood culture grew non-albicans
candida species (unidentified) after 24
hours of aerobic incubation at 30º. Institution
of conventional IV amphotericin-B along with
supportive therapy led to clinical improvement.
The baby was later discharged at day 10 of
treatment with follow-up advice of continuing
amphotericin-B therapy for full 21 days. The
Candida species on culture were later
identified as colonies of T. asahii.
Initial cultures of the
second case were sterile. Baby improved
following partial exchange transfusion with
normal saline along with empiric antimicrobials,
but later developed feeding intolerance,
abdominal distension, hematemesis and refractory
shock. Amphotericin B added empirically failed
to improve general condition and ultimately the
baby died. The repeat blood culture grew
colonies of T. asahii.
The third case had early
onset sepsis. Initial blood culture grew E.
coli which was sensitive to common beta-lactams.
A dose of surfactant, assisted ventilation and
appropriate antibiotics resulted in significant
improvement. Later, the infant developed
features of sepsis along with massive pulmonary
hemorrhage and succumbed to his illness despite
starting IV amphotericin B. The repeat blood
culture again grew T. asahii.
The fourth case developed
fulminant sepsis after 48 hours of admission
caused by extended-spectrum beta-lactamase
producing Klebsiella pneumoniae. A course
of meropenem and supportive therapy including
ventilatory support resulted in improvement.
Enteral feeds were started and the baby was
weaned off from the ventilator. However, at 11 th
day of life, the baby again showed worsening of
clinical and laboratory parameters. Repeat
culture revealed growth of Trichosporon spp.
Liposomal Amphotericin B was added in the
regimen but the baby did not respond, and
ultimately died at the age of 21 days.
The next infant had features
of early onset sepsis but cultures were
negative. The baby improved after a 7-day course
of empiric antibiotics. Four days later, the
baby was readmitted in the NICU for the
treatment of jaundice and later developed
necrotizing enterocolitis (NEC), cholestasis and
signs of sepsis. The repeat blood culture
revealed Trichosporon spp. With the
addition of amphotericin-B in the regimen, the
infant gradually responded, blood culture became
sterile at 10 th
day of therapy, and the baby was discharged at
20th
day of life with follow up advice of completing
IV amphotericin B course for total 21 days.
The sixth case was second
born twin delivered to a third-gravida mother.
After packed cell transfusion and supportive
treatment, the infant stabilized. However, the
baby later developed respiratory distress that
necessitated assisted ventilation. After weaning
off from the ventilator, the baby developed
repeated apneic spells and repeat culture grew
fungal colonies identified as T. ashii.
Addition of IV amphotericin-B to the
antimicrobial regimen failed to salvage the baby
who developed massive gastrointestinal
hemorrhage, perforation and shock, and died
after 6 days of admission.
The next case was a premature
infant who developed Hyaline membrane disease
soon after birth and was treated successfully
with surfactant and assisted ventilation. Later,
the infant developed signs of sepsis in form of
apnea, pallor and hypotension. Repeat culture
grew yeast colonies, identified as as
Trichosporon spp. The baby developed massive
pulmonary hemorrhage and died at the age of 7
days despite adding IV amphotericin-B to the
regimen.
The last case was a term
neonate who developed meconium aspiration
syndrome and was treated with high-flow oxygen,
antibiotics and IV fluids. Five days later, the
infant started exhibiting dullness, apnea, and
later gastrointestinal bleeding. The repeat
blood culture grew colonies of Trichosporon
spp. Amphotericin B was added to the
regimen. However, the baby developed features of
disseminated intravascular coagulation and died
at the post-natal age of 7 days.
Identification of T asahii:
The blood culture was done by automated BacT/ALERT
3D 120 blood culture
System. Gram stain showed elongated
blastoconidia and septate pseudohyphae. Broth
from the positive blood cultures bottles were
sub-cultured on blood agar and Sabouraud’s
dextrose agar (SDA) with chromphenicol. The
colonies of yeast like fungi were isolated after
24 hrs of incubation. Identification and
sensitivity was done by Vitek 2 Compact. The
macroscopic and microscopic morphology of T.
asahii was compatible with the standard
description of the species.
Discussion
Trichosporon asahii is
opportunistic yeast described as an emerging
pathogen in disseminated nosocomial infections
in NICUs [2-7]. Clinical manifestations of
infection with this microorganism are
non-specific and infections often results in
poor prognosis [2,6,7]. This is probably the
first report of an invasive outbreak in a
neonatal unit in India. Case 1 probably
represented the index case; responsible for
spreading the infection in other neonates who
had nosocomial sepsis during the course of their
stay.
Literature search revealed
reports of T.asahii neonatal infection in
15 preterm newborns. Of these, 11 weighed less
than 1,000 g at birth and only one weighed more
than 1,500 g at birth. All deaths (seven)
occurred in the extremely low birth weight
group. However, in our series, the preterm
infants were not extremely premature and had
comparatively higher weights, and even full term
neonates were affected. Trichosporon
infections in neonates have been almost
uniformly fatal. In our series also, six out of
eight neonates died. Many of our patients had
one or more of the risk factors often blamed for
nosocomial sepsis and fungal diseases [8].
August is the month of the
year which has very high humidity and high rates
of neonatal admissions. Due to high work load, a
breach in asepsis protocol might have occurred.
Surprisingly on performing microbial
surveillance, we found that one surface culture
from laminar flow unit yielded positive growth
of Candida spp with morphological
features similar to T. asahii. We stopped
using laminar flow for preparing intravenous
fluids and the entire unit was thoroughly
fumigated with formaldehyde. Hence, it can be
presumed that laminar flow unit was probably the
source of this outbreak.
Most strains of T. asahii
may be confused with Candida spp. on
initial culture examinations. Therefore, delays
in appropriate treatment may occur. Several
studies have demonstrated low in vitro
sensitivity of T. asahii to commonly used
antifungal agents [1,3,9]. The fungus is known
for varied susceptibility to amphotericin B and
laboratory studies have shown that it is
relatively resistant to this agent [1,9]. On the
other hand, many authors have described good
results of early administration of amphotericin
B [2,4]. In our series also, all the isolates
were sensitive to amphotericin-B, but resistant
to fluconazole and flucytosine. However, a
favourable clinical response was observed in
only two cases despite using amphotericin B
quite early on the first suspicion of nosocomial
sepsis in most neonates. The in vivo
resistance of the drug can be explained due to
formation of a biofilm by Trichosporon spp
[10], which may explain persistence of the
infection in spite of in vitro
sensitivity of the drug.
Since there are no
pathognomonic clinical features, the diagnosis
of disseminated trichosporonosis depends
primarily upon clinical suspicion, to be
followed by intensive mycological
investigations. Infection with this agent should
be taken into consideration when dealing with
low birth weight preterm infants, particularly
those with nosocomial sepsis having cocktail of
broad spectrum antibiotics for a prolonged
period but still with unfavourable clinical
progress.
Funding: None;
Competing interests: None stated.
References
1. Guého E, Improvisi L, de
Hoog GS, Dupont B. Trichosporon on humans: a
practical account. Mycoses. 1994;37:3-10.
2. Gökahmetoglu S, Nedret Koç
A, Günes T, Cetin N. Trichosporon mucoides
infection in three premature newborns. Mycoses.
2002;45:123-5.
3. Panagopoulou P, Evdoridou
J, Bibashi E, Filioti J, Sofianou D,
Kremenopoulos G, et al. Trichosporon
asahii: an unusual cause of invasive
infection in neonates. Pediatr Infect Dis J.
2002;21:169-70.
4. Yildiran A, Kücüködük S,
Saniç A, Belet N, Güvenli A. Disseminated
Trichosporon asahii infection in a preterm.
Am J Perinatol. 2003;20:269-71.
5. Maheshwari A, Stromquist
CI, Pereda L, Emmanuel PJ. Mixed infection with
unusual fungi and staphylococcal species in two
extremely premature neonates. J Perinatol.
2004;24:324-6.
6. Téllez-Castillo CJ, Gil-Fortuño
M, Centelles-Sales I, Sabater-Vidal S, Pardo
Serrano F. Trichosporon asahii fatal
infection in a preterm newborn. Rev Chilena
Infectol. 2008;25: 213-5.
7. Pereira DN, Nader SS,
Nader P, Martins PG, Furlan SP, Hentges CR.
Disseminated Trichosporon spp infection in
preterm newborns: a case report. J Pediatr (Rio
J). 2009;85:459-61.
8. Saiman L, Ludington E,
Pfaller M, Rangel-Frausto S, Wiblin RT, Dawson
J, et al. Risk factors for candidemia in
neonatal intensive care unit patients. The
National Epidemiology of Mycosis Survey Study
Group. Pediatr Infect Dis J. 2000;19:319-24.
9. Walsh TJ, Melcher GP,
Rinaldi MG, Lecciones J, McGough DA, Kelly P,
et al. Trichosporon beigelii: an
emerging pathogen resistant to amphotericin B. J
Clin Microbiol. 1990;28:1616-22.
10. Di Bonaventura G, Pompilio
A, Picciani C, Iezzi M, D’Antonio D, Piccolomini
R. Biofilm formation by the emerging fungal
pathogen Trichosporon asahii: development,
architecture, and antifungal resistance.
Antimicrob Agents Chemother. 2006;50:3269-76.
|
|
|
|