Year : 2015 | Volume
: 8 | Issue : 4 | Page : 528--530
A case of Candida famata sepsis in a very low birth weight infant successfully treated with fluconazole following antifungal susceptibility testing
Shilpee Raturi1, Suresh Chandran2, Roopa Viswanathan3,
1 Department of Child Development, KK Women's and Children's Hospital, Singapore
2 Department of Neonatology, KK Women's and Children's Hospital, Singapore, Duke NUS Medical School and Yong Loo Lin School of Medicine, Singapore
3 Department of Microbiology, RIPAS Hospital, BA1710, Bandar Seri Begawan, Brunei Darussalam, Singapore
Department of Child Development, KK Women«SQ»s and Children«SQ»s Hospital, Level 5, Women«SQ»s Tower, 100 Bukit Timah Road, Singapore 229 899
Late onset of fungal sepsis in very low birth weight (VLBW) infants is common and has a high mortality and morbidity. Many of these infants were also receiving fluconazole prophylaxis. Amphotericin is often started when invasive neonatal candidiasis is suspected and has significant side effects. Antifungal susceptibility testing can be extremely useful in deciding optimal antifungal therapy. We report a case of successful treatment of fungal sepsis due to Candida famata in a VLBW infant where fluconazole was continued in therapeutic dose following sensitivity testing.
This case report highlights the growing number of cases arising due to nonalbicans Candida infections in the neonatal intensive care units and the usefulness of antifungal susceptibility testing in deciding optimal antifungal therapy and preventing the emergence of drug resistance.
|How to cite this article:|
Raturi S, Chandran S, Viswanathan R. A case of Candida famata sepsis in a very low birth weight infant successfully treated with fluconazole following antifungal susceptibility testing.Med J DY Patil Univ 2015;8:528-530
|How to cite this URL:|
Raturi S, Chandran S, Viswanathan R. A case of Candida famata sepsis in a very low birth weight infant successfully treated with fluconazole following antifungal susceptibility testing. Med J DY Patil Univ [serial online] 2015 [cited 2019 Aug 17 ];8:528-530
Available from: http://www.mjdrdypu.org/text.asp?2015/8/4/528/160828
Candida species infection is the third most common cause of late-onset sepsis in neonatal intensive care units, accounting for 9-13% of blood-stream infections (BSI).  With increasing survival of preterm infants and widespread use of fluconazole prophylaxis, nonalbicans Candida species are now emerging as frequent causes of candidemia.  Amphotericin B is considered as the gold standard for treating invasive neonatal candidiasis. However, it's use is limited by the dose-limiting toxicity and major side effects which include nephrotoxicity, thrombocytopenia, transfusion reactions and electrolyte disturbances.  Newer agents such as ravuconazole, an "extended-spectrum" triazole have been found to be effective against these rare and potentially "emerging" opportunistic pathogens. Being newer antifungal drugs, they should be carefully evaluated to control the emergence of drug resistance. 
Early identification of a number of Candida species directly from blood cultures is now possible with the development of specific fluorescent peptide nucleotide analog probes, thereby also reducing the need for broad-spectrum antifungals.  In neonates, a single culture of at least 1 ml of blood appears to be as sensitive in diagnosing bacterial and fungal sepsis as two separate peripheral blood cultures.  Although antifungal susceptibility tests are helpful for guiding the therapy, in vitro and in vivo differences should be taken into account in case of treatment failure with the use of agents found active in vitro.
A preterm male infant weighing 1420 g born at 30 weeks of gestation by spontaneous vaginal delivery was admitted to the neonatal intensive care unit. The maternal high vaginal swab was negative for Group B Streptococcus and Candida species. Placental histopathology was negative for chorioamnionitis. He required surfactant at birth for respiratory distress syndrome (RDS), followed by continuous positive airway pressure for 14 h and was depronged to room air on day 5. Due to prematurity and RDS antimicrobial therapy (crystalline penicillin [50 mg/kg/dose every 12 h] and gentamicin [4.5 mg/kg/dose every 36 h]) was initiated. Blood culture and surface swabs from the neck, axilla and groin at birth were sterile. Hence, first line antibiotics were discontinued on day 3 of life. Umbilical catheters placed at birth were removed on day 8 following insertion of a peripherally inserted central catheter (PICC). Total parenteral nutrition (TPN) was initiated on day 5. Cranial ultrasound scan done on day 2 was normal. Hemodynamically significant patent ductus arteriosus was closed with indomethacin in early 2 nd week of life. On day 19, he was noted to be lethargic, and laboratory analysis showed thrombocytopenia, leucopenia and prolonged prothrombin time. Blood and urine cultures were obtained. Lumbar puncture was deferred because of low platelet counts and deranged coagulation profile. Ultrasound of the liver and kidneys did not reveal any focus. Late-onset sepsis was suspected. Meropenem (20 mg/kg/dose every 12 h) was started along with oral nystatin (100,000 units every 6 h). PICC was accessed only once a day under strict aseptic precautions for a change of parenteral nutrition. On day 22 of life, vancomycin (10 mg/kg/dose every 12 h) was added because of clinical deterioration and presence of a PICC. Aerobic bacterial culture of blood by Bactec drawn from PICC grew yeast, which was further identified by API Candida system (bioMerieux) as Candida famata. It was also isolated from the peripheral blood sample. Hence, parenteral fluconazole was added in therapeutic dose (12 mg/kg/dose every 24 h). Antifungal testing was done using CLSI M27-A2 recommended RPMI-1640 medium (with glutamine and phenol red, without bicarbonate) supplemented with 0.2% glucose and fluconazole showed MIC of 32 µg/ml.  PICC was removed, and the catheter tip culture showed colonization with coagulase negative Staphylococcus. Antibiotics were stopped, and fluconazole continued for 3 weeks. Fungal sepsis resolved and subsequent blood, and urine fungal cultures were negative.
Neonatal Candida infection can be acquired vertically from maternal vaginal colonization/infection or nosocomially. In the above-reported case, use of lipids in the TPN and presence of PICC could have contributed to the nosocomially acquired fungal sepsis. The classic presentation of systemic candidiasis can be indistinguishable from bacterial sepsis as was seen in our patient. However, the presence of leucopenia was misleading, as fungal infections are often associated with leukocytosis.  Disseminated infection should be ruled out by evaluating cultures of urine and cerebrospinal fluid, ophthalmological examination, echocardiogram and renal ultrasound. Rarely, intrauterine infection in the premature infants can present as congenital candidiasis on the 1 st day of life as a life-threatening condition with pneumonitis and a pustular erythematous skin rash in the setting of neutrophilia. Therapeutic options for treating Candida species in neonates are usually limited to amphotericin B and fluconazole. However, these two drugs have limitations both in efficacy and in putative toxicity. New therapeutic alternatives include echinocandins, and they have been shown to have clinical efficacy and tolerability in critically ill neonatal patients.  However, long-term safety and ecological issues related to echinocandin use in neonates need to be addressed.
Candida famata, a hemiascomycetous commensal yeast, found in dairy products and the environment, accounts for 0.2-2% of invasive candidiasis.  A number of clinical cases from which this yeast was isolated have been reported including catheter-related BSI, peritonitis, ocular endophthalmitis and central nervous system infection.  Empirical amphotericin B is usually started for germ tube negative nonalbicans Candida. Sensitivity testing for Candida species assists in selecting the appropriate antifungal drug and conversion to fluconazole is reasonable provided the identified isolate is susceptible. The most common side effect associated with fluconazole is transient hepatotoxicity, which usually resolves after cessation of therapy. Removal or replacement of indwelling central venous catheters and prompt initiation of therapy is recommended for successful treatment of Candida famata fungemia and reducing mortality and neurodevelopmental impairment.
Fluconazole proved to be an effective antifungal drug for treating our patient. This case also helps to provide justification for antifungal susceptibility testing particularly in patients with nonalbicans candidemia. Optimal antifungal therapy can then be initiated which can substantially lower the morbidities and mortalities due to systemic fungal infections.
|1||Benjamin DK Jr, Stoll BJ, Fanaroff AA, McDonald SA, Oh W, Higgins RD, et al. Neonatal candidiasis among extremely low birth weight infants: Risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics 2006;117:84-92.|
|2||Juyal D, Sharma M, Pal S, Rathaur VK, Sharma N. Emergence of non-albicans Candida species in neonatal candidemia. N Am J Med Sci 2013;5:541-5.|
|3||Baley JE, Meyers C, Kliegman RM, Jacobs MR, Blumer JL. Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5-fluorocytosine in neonates. J Pediatr 1990;116:791-7.|
|4||Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ, Jones RN. In vitro susceptibilities of rare Candida bloodstream isolates to ravuconazole and three comparative antifungal agents. Diagn Microbiol Infect Dis 2004;48:101-5.|
|5||Rüchel R, Schaffrinski M. Versatile fluorescent staining of fungi in clinical specimens by using the optical brightener Blankophor. J Clin Microbiol 1999;37:2694-6.|
|6||Sarkar S, Bhagat I, DeCristofaro JD, Wiswell TE, Spitzer AR. A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis. J Perinatol 2006;26:18-22.|
|7||CLSI. Reference Method for broth dilution antifungal susceptibility testing of yeasts; Approved standard. CLSI document M27-A2. 2 nd ed. Pennsylvania, USA: CLSI; 2002.|
|8||Padovani EM, Michielutti F, Dall'Agnola A, Dal Moro A, Khoory BJ. Sepsis caused by Candida in the neonatal period. Pediatr Med Chir 1997;19:83-8.|
|9||Manzoni P, Rizzollo S, Franco C, Gallo E, Galletto P, Boano E, et al. Role of echinocandins in the management of fungal infections in neonates. J Matern Fetal Neonatal Med 2010;23 Suppl 3:49-52.|
|10||Beyda ND, Chuang SH, Alam MJ, Shah DN, Ng TM, McCaskey L, et al. Treatment of Candida famata bloodstream infections: Case series and review of the literature. J Antimicrob Chemother 2013;68:438-43.|
|11||Prinsloo B, Weldhagen GF, Blaine RW. Candida famata central nervous system infection. S Afr Med J 2003;93:601-2.|