Skip to main page content

• HOME
• Current Issue
• Archive
• Alerts
• About ASM
• Contact us
• Tech Support
• Journals.ASM.org

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cheng, M.-F. Articles by Hsieh, K.-S. Search for Related Content PubMed PubMed Citation Articles by Cheng, M.-F. Articles by Hsieh, K.-S.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, April 2001, p. 1608-1611, Vol. 39, No. 4
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.4.1608-1611.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cryptococcus laurentii Fungemia in a Premature Neonate

Ming-Fang Cheng,^1,3 Christine C. Chiou,^1,3,* Yung-Ching Liu,^3,4 Hao-Zan Wang,¹ and Kai-Sheng Hsieh¹

Department of Pediatrics¹ and Microbiology Laboratory,⁴ Veterans General Hospital-Kaohsiung, Kaohsiung, and Division of Clinical Research, National Health Research Institutes,² and National Yang-Ming University,³ Taipei, Taiwan

Received 14 August 2000/Returned for modification 26 November 2000/Accepted 26 January 2001

	ABSTRACT

Top Abstract Text References

Cryptococcus spp. other than Cryptococcus neoformans are generally considered nonpathogenic to humans. There are only 15 case reports of disease in humans caused by Cryptococcus laurentii infection. Underlying diseases and predisposing risk factors seem to play an important role in these cases. Our patient is the first case of an extremely low birth weight infant with C. laurentii fungemia reported in the English literature. In our case, the MIC of amphotericin B for C. laurentii was 0.25 to 1 µg/ml and the patient had a good outcome following the administration of amphotericin B at 10 mg/kg combined with central venous catheter removal. There will undoubtedly be an increasing occurrence of unusual fungal infections accompanying further advances in medicine. A high degree of suspicion and improvements in the techniques for culture and identification will contribute to the earlier diagnosis and treatment of unusual fungal infections.

	TEXT

Top Abstract Text References

Cryptococcus spp. other than Cryptococcus neoformans were previously considered saprophytes and thought to be nonpathogenic to humans. However, infections caused by species other than C. neoformans have been increasingly recognized. We report a case of fungemia caused by Cryptococcus laurentii in a premature infant in which complete clinical resolution occurred after amphotericin B administration and central venous catheter removal. The organism was isolated twice from blood cultures drawn 2 days apart.

Case report. A female newborn with a gestation age of 27 weeks was admitted to our neonatal intensive care unit due to prematurity. The neonate was delivered via spontaneous vaginal delivery following premature rupture of the amniotic membrane. The birth weight was 940 g, and the Apgar score was 5 after 1 min. Physical examination was significant for rapidly progressive respiratory distress, and the patient was intubated soon after delivery and mechanically ventilated. Chest radiography confirmed grade III respiratory distress syndrome. Synthetic surfactant (colfosceril palmitate [Exosurf Neonatal]; Glaxo Wellcome, Inc.) was administered with a good response, and the patient was started on empiric antibiotic therapy with ampicillin and gentamicin. The hemogram on admission was normal, as was screening for toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex virus. Initial cultures of blood and cerebrospinal fluid (CSF)revealed no growth of bacteria or fungi.

Because of a transient worsening of the infant's ventilator settings at day 4 of life, coupled with yellowish endotracheal secretions and leukocytosis (absolute neutrophil count, 22,350/mm³), broad-spectrum antibiotic therapy was continued with gentamicin replaced with ceftizoxime. The patient improved clinically, was extubated for the first time on day 9, and was placed on nasal continuous positive airway pressure. However, on day 11, increasing respiratory distress was noted, necessitating reintubation and mechanical ventilation. Chest radiography demonstrated a new right upper lung opacification. A hemogram was normal. Due to growth of oxacillin-resistant Staphylococcus aureus in the culture of the tip of the removed endotracheal tube, antibiotic therapy was changed to ceftizoxime and teicoplanin. The patient's condition improved gradually over the next few days. On day 20, a repeat chest X-ray was normal. The infant was extubated, and antibiotic therapy was discontinued.

On the 25th day of life, the infant appeared less active and had occasional episodes of apnea and bradycardia. Over the following 24 h, a sepsis syndrome evolved with respiratory and circulatory insufficiency, hypothermia, abdominal distension, leukocytosis (white blood cell count, 19,080/mm³; 21% band forms), and thrombocytopenia (platelet count, 54,000/mm³). The infant was started on an empirical antibiotic regimen of ceftazidime and teicoplanin with no appreciable clinical response. Two sets of blood cultures (BACTEC 860 system; Becton Dickinson, Inc., Sparks, Md.) were drawn on days 27 and 29. Both sets of blood cultures were positive 72 h later and yielded the same encapsulated, round-to-oval, yeast-like fungus that grew at 37°C, produced urease, had a slight capsule, and was nonfermentative. Colonies were cream colored and darkened with age. The ID 32C system (bioMerieux Vitek, Inc., St. Louis, Mo.) was used to identify C. laurentii by noting the utilization of lactose and melibiose. A negative caffeic acid test and absence of KNO₃ utilization reliably differentiated this species from C. neoformans and C. albidus. The MICs of amphotericin B and fluconazole were determined by the broth microdilution method according to the National Committee for Clinical Laboratory Standards guidelines (12). The MIC of amphotericin B was 0.25 to 1 µg/ml, and that of fluconazole was 4 µg/ml. A central venous line, placed in the right cubital fossa shortly after birth, was removed, parenteral nutrition was temporarily discontinued, and amphotericin B administration was started. Examination of CSF obtained prior to the start of amphotericin B administration was negative by routine bacteriology culture, India ink stains, and cryptococcal antigen test. The tip of the withdrawn central venous line was negative by routine bacteriology culture. Therapy with amphotericin B (initial dosage; 0.1 mg/kg/day; maximum dosage, 1 mg/kg/day; total cumulative dose, 10 mg/kg) was rapidly successful and tolerated without nephrotoxicity. A repeat culture of blood drawn on the 37th day was negative, and the infant was weaned from pressure agents and extubated within 3 days after the start of antifungal therapy. The remaining course in the nursery was uneventful, and the infant was discharged at an age of 70 days. Regular postdischarge follow-up for 1 year showed age-appropriate development with no evidence of late complications of fungemia.

Discussion. Major risk factors for fungemia include intravascular catheters, parenteral hyperalimentation, and broad-spectrum antibiotics. Premature infants are at particularly increased risk due to their extremely low body weight, poor nutrition, enteral malabsorption, insufficient microbial defenses, and underdeveloped anatomic barriers (13, 16). All of these risk factors were present in our case.

Cryptococcosis is an infectious disease of worldwide occurrence caused by an encapsulated, basidiomycetous, yeast-like fungus. Cryptococci are generally found in soil contaminated by pigeon feces, as well as on the surfaces of certain vegetables and in milk from infected dairy cow herds (1). Cryptococci are transmitted to humans primarily through inhaled fomites, although direct entry through the digestive tract or skin can also occur. Species other than C. neoformans have generally been thought to be nonpathogenic to humans (2, 9, 14).

Including the present report, there are a total of 15 case reports of disease in humans caused by C. laurentii infection, 7 of which were of fungemia cases. These cases are summarized in Table 1. Underlying diseases and predisposing risk factors seem to have played an important role in these cases. Signs and symptoms varied considerably according to sites of infection. In fungemia patients, abnormal temperature and hypotension were the most common presentations. Measurement of cryptococcal antigen in serum or CSF was not reported in the majority of these cases; however, if reported, the results were consistently negative. One patient died due to the underlying disease, but the others recovered after treatment in these cases (2, 4-7, 9, 10, 14, 17; V. Kremery, Jr., A. Kunova, and J. Mardiak, Letter, Infection 25:130, 1997; R. E. Winn, M. G. Rinaldi, M. Galbraith, and J. H. Bower, Abstr. Annu. Meet. Am. Soc. Microbiol. 1985, abstr. F37, p. 370, 1985). Our patient is the first case of an extremely low birth weight infant with C. laurentii fungemia reported in the English literature.

View this table: [in this window] [in a new window]   TABLE 1.   Summary of data from cases of C. laurentii infection in humansa

In the clinical microbiology laboratory, the finding of a mucoid colony is usually the first clue to the presence of cryptococci and this suspicion is further heightened when encapsulated, budding yeasts are observed on an India ink preparation of the colony. There are 37 members of the genus Cryptococcus, and virtually all members of the genus assimilate inositol, produce urease, and are nonfermentative. The identification of C. laurentii specifically can be confirmed by using various biochemical tests, and most clinical laboratories use a battery of biochemical tests contained in commercially available kits. A negative caffeic acid test, absence of KNO₃ utilization, and the utilization of lactose and melibiose may differentiate C. laurentii from other species (8).

Because of the limited number of reported cases, there is no validated standard treatment for C. laurentii infection. Prompt removal of a central venous catheter is well documented as an important measure for clearing fungemia and preventing complications (3, 15). Correlations between in vitro antifungal susceptibility test results and treatment outcome do not exist for C. laurentii. The organism was susceptible to amphotericin B in this case and those previously reported, with MICs ranging from 0.037 to 1 µg/ml, but its susceptibility to fluconazole seemed to be equivocal, with MICs ranging from 4 to greater than 64 µg/ml (4, 6, 11, 12). We observed a favorable outcome following the administration of accumulative dose of 10 mg of amphotericin B per kg, combined with central venous catheter removal. Although we encountered no toxicity due to amphotericin B, detailed analysis of toxicity in premature neonates is limited and merits more attention.

Undoubtedly, there will be an increasing number of unusual fungal infections concomitant with further advances in medicine, especially in areas involving immunosuppressive therapy, use of corticosteroids and antibiotics, and widespread use of central venous catheters. Improvements in the identification of unusual pathogens will, in turn, contribute to the increased recognition of cases. However, a high degree of suspicion, particularly in predisposed patients, teamed with newly developed techniques for culture and identification, will likely allow earlier diagnosis and, it is hoped better treatment of such unusual fungal infections.

	ACKNOWLEDGMENTS

We thank Andreas H. Groll, National Cancer Institute, and L. Clifford McDonald, University of Louisville Hospital, for expert discussion and review of the manuscript. We are also indebted to Hsiu-Jung Lo and Tsai-Ling Lauderdale, National Health Research Institutes, Taipei, Taiwan, for editorial assistance.

	FOOTNOTES

^* Corresponding author. Present address: Infectious Disease Section, VA Medical Center, University Dr. C. Pittsburgh, PA 15240. Phone: (412) 688-6179. Fax: (412) 688-6950. E-mail: chenchia{at}yahoo.com.

	REFERENCES

Top Abstract Text References

1.	Chand-Goyal, T., and R. A. Spotts. 1996. Enumeration of bacterial and yeast colonists of apple fruits and identification of epiphytic yeasts on pear fruits in the Pacific Northwest United States. Microbiol. Res. 151:427-432[Medline].
2.	Custis, P. H., J. A. Haller, and E. de Juan, Jr. 1995. An unusual case of cryptococcal endophthalmitis. Retina 15:300-304[CrossRef][Medline].
3.	Dato, V. M., and A. S. Dajani. 1990. Candidemia in children with central venous catheters: role of catheter removal and amphotericin B therapy. Pediatr. Infect. Dis. J. 9:309-314[Medline].
4.	Johnson, L. B., S. F. Bradley, and C. A. Kauffman. 1998. Fungaemia due to Cryptococcus laurentii and a review of non-neoformans cryptococcaemia. Mycoses 41:277-280[Medline].
5.	Kamalam, A., P. Yesudian, and A. S. Thambiah. 1977. Cutaneous infection by Cryptococcus laurentii. Br. J. Dermatol. 97:221-223[CrossRef][Medline].
6.	Kordossis, T., A. Avlami, A. Velegraki, I. Stefanou, G. Georgakopoulos, C. Papalambrou, and N. J. Legakis. 1998. First report of Cryptococcus laurentii meningitis and a fatal case of Cryptococcus albidus cryptococcaemia in AIDS patients. Med. Mycol. 36:335-339[CrossRef][Medline].
7.	Kremery, V., I. Krupova, and D. W. Denning. 1999. Invasive yeast infections other than Candida spp. in acute leukaemia. J. Hosp. Infect. 41:181-194[CrossRef][Medline].
8.	Leslie, C., B. Albert, and S. Max. 1998. Microbiology and microbial infections, vol. 4. , p. 461-473. Arnold, London, England.
9.	Lynch, J. P., III, D. R. Schaberg, D. G. Kissner, and C. A. Kauffman. 1981. Cryptococcus laurentii lung abscess. Am. Rev. Respir. Dis. 123:135-138[Medline].
10.	Mocan, H., A. V. Murphy, T. J. Beattie, and T. A. McAllister. 1989. Fungal peritonitis in children on continuous ambulatory peritoneal dialysis. Scott. Med. J. 34:494-496[Medline].
11.	Morace, G., S. Manzara, and G. Dettori. 1991. In vitro susceptibility of 119 yeast isolates to fluconazole, 5-fluorocytosine, amphotericin B and ketoconazole. Chemotherapy 37:23-31[Medline].
12.	National Committee for Clinical Laboratory Standards. 1997. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A. National Committee for Clinical Laboratory Standards, Wayne, Pa.
13.	Pagano, L., A. Antinori, A. Ammassari, L. Mele, A. Nosari, L. Melillo, B. Martino, M. Sanguinetti, F. Equitani, F. Nobile, M. Carotenuto, E. Morra, G. Morace, and G. Leone. 1999. Retrospective study of candidemia in patients with hematological malignancies. Clinical features, risk factors and outcome of 76 episodes. Eur. J. Haematol. 63:77-85[Medline].
14.	Ritterband, D. C., J. A. Seedor, M. K. Shah, S. Waheed, and I. Schorr. 1998. A unique case of Cryptococcus laurentii keratitis spread by a rigid gas permeable contact lens in a patient with onychomycosis. Cornea 17:115-118[CrossRef][Medline].
15.	Sadiq, H. F., S. Devaskar, W. J. Keenan, and T. R. Weber. 1987. Broviac catheterization in low birth weight infants: incidence and treatment of associated complications. Crit. Care Med. 15:47-50[Medline].
16.	Saiman, L., E. Ludington, M. Pfaller, S. Rangel-Frausto, R. T. Wiblin, J. Dawson, H. M. Blumberg, J. E. Patterson, M. Rinaldi, J. E. Edwards, R. P. Wenzel, and W. Jarvis. 2000. Risk factors for candidemia in neonatal intensive care unit patients. The National Epidemiology of Mycosis Survey study group. Pediatr. Infect. Dis. J. 19:319-324[CrossRef][Medline].
17.	Sinnott, J. T., J. Rodnite, P. J. Emmanuel, and A. Campos. 1989. Cryptococcus laurentii infection complicating peritoneal dialysis. Pediatr. Infect. Dis. J. 8:803-805[Medline].

---

Journal of Clinical Microbiology, April 2001, p. 1608-1611, Vol. 39, No. 4
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.4.1608-1611.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

• Bialek, R., Weiss, M., Bekure-Nemariam, K., Najvar, L. K., Alberdi, M. B., Graybill, J. R., Reischl, U. (2002). Detection of Cryptococcus neoformans DNA in Tissue Samples by Nested and Real-Time PCR Assays. CVI 9: 461-469 [Abstract] [Full Text]  

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cheng, M.-F. Articles by Hsieh, K.-S. Search for Related Content PubMed PubMed Citation Articles by Cheng, M.-F. Articles by Hsieh, K.-S.