Vol. 30, No. 9
JOURNAL OF CLINICAL MICROBIOLOGY, Sept. 1992,/p. 2479-2483
0095-1137/92/092479-05$02.00/0 Copyright © 1992, American Society for Microbiology
Paecilomyces lilacinus Catheter-Related Fungemia in Immunocompromised Pediatric Patient
an
TAN,`*
ANGELA K. OGDEN,1 JILL TILLMAN,2 GAIL J. DEMMLER,1'2'3 AND MICHAEL G. RINALDI4 Departments of Pediatrics1 and Pathology,3 Baylor College ofMedicine, and Pathology Laboratories, Texas Children's Hospital,2 Houston, Texas 77030, and Department of Pathology, University of Texas Health Science Center, San Antonio, Texas 78284-7750 TINA Q.
Received 24 February 1992/Accepted 2 June 1992
Paecilomyces lilacinus catheter-related fungemia in an immunocompromised child is reported. The presence of a central venous catheter and the patient's immunocompromised status were felt to be predisposing factors for this unusual infection. To our knowledge, this is the first description of P. lilacinus catheter-related fungemia, and our patient may be the youngest reported patient with this mycosis who was cured. urine culture were obtained, and broad-spectrum antimicrobial therapy consisting of vancomycin (10 mg/kg of body weight per dose) and gentamicin (2.5 mg/kg per dose) was administered intravenously every 8 h. The initial blood culture from his Portacath grew a mould, as well as a branching gram-positive rod, which was later identified as a Streptomyces species and ascertained to be a contaminant. A repeat blood culture obtained through the Portacath on hospital day 3 also grew a mould, and on hospital day 6, the Portacath was removed and treatment with amphotericin B was begun. A peripheral blood culture obtained at the time of Portacath removal also became positive for the same mould. No evidence of disseminated fungal infection was seen on ophthalmologic exam, abdominal and renal ultrasound examinations, computed tomography scans, or echocardiogram. Antibiotics were discontinued after cultures were negative for bacterial pathogens at 72 h, and the patient received 10 mg of amphotericin B per kg (total cumulative dose). Three blood cultures obtained after the Portacath was removed were sterile. The patient tolerated his therapy well, there were no complications, and he was discharged home. Since discharge, the patient has been well and is growing and developing appropriately, with no recurrence of infection. The mould isolated from the patient's blood cultures was tentatively identified as a Penicillium species. It was sent to a reference mycology laboratory (Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio) for further identification and was subsequently identified as Paecilomyces lilacinus. Prior to 1974, this organism was often referred to as Penicillium lilacinum. The genus Paecilomyces Bainer includes up to 17 species of saprobic moulds and is likely closely related to the genus Penicillium Link. Of Paecilomyces species, Paecilomyces lilacinus (Thom) Samson, Paecilomyces variotii Bainer, Paecilomyces viridis Segretain ex Samson, Paecilomyces marquandii (Massee) Hughes, and Paecilomyces javanicus (Friedrichs et Bally) Brown et Smith (felt by many authorities to be a species of Penicillium) have been associated with human mycotic infections. The species-inciting disease in this case report, Paecilomyces lilacinus, has been subjected to various nomenclatural dispositions which currently still exist among experts. The species was originally described in 1910 as Penicillium lilacinum Thom (32). For a considerable period following the original description, the fungus main-
Paecilomyces species are ubiquitous saprobic fungi that found worldwide in soil and on decomposing vegetation. They are common contaminants of sterile solutions and clinical specimens because they are extremely resistant to the majority of commercial sterilizing techniques (3). While recognized as insect and animal pathogens, Paecilomyces species are very rarely pathogenic in humans. There are, however, sporadic reports of endophthalmitis (13, 15-17, 19, 27, 35) following intraocular lens implantation, endocarditis (2, 9, 12, 14, 30, 34) following cardiac valve replacement, orbital cellulitis (1), pulmonary (5, 6) and cutaneous (10, 11, 31) infections, chronic maxillary sinusitis (26, 28), and peritonitis (4) due to Paecilomyces species in humans. The majority of these infections occurred in adult patients with impaired host defenses or following foreign body implants, factors which predisposed them to opportunistic infections. In this report, we describe an 18-month-old immunocompromised child who developed fungemia caused by Paecilomyces lilacinus, the source of which was, most likely, his central venous catheter. Case report. Our patient was an 18-month-old white male with obstructive uropathy secondary to embryonal rhabdomyosarcoma group III involving the bladder and prostate. A tunneled central venous catheter (Hickman) was placed at the time of the tumor biopsy and debulking to administer chemotherapy. This catheter, however, was removed 3 months later when he developed a catheter-associated chest wall abscess and sepsis due to Klebsiella pneumoniae. A totally implantable central venous catheter (Portacath) was therefore placed 1 month later for the continuation of his chemotherapy. On 20 August 1991, the patient was admitted to Texas Children's Hospital for fever of 101.9°F, malaise, decreased appetite, and neutropenia secondary to chemotherapy. Physical examination revealed only mild nasal congestion and rhinorrhea. His peripheral white blood cell count was 1,630/mm3 with 24 polymorphonuclear cells, 11 band forms, 34 lymphocytes, 28 mononuclear cells, and 3 eosinophils with an absolute neutrophil count of 570. His platelet count was 318,000/mm3, with a hematocrit of 25.8% and a hemoglobin value of 8.8 g/dl. Chest radiograph and urinalysis results were normal. Blood culture from his Portacath and a are
*
Corresponding author. 2479
2480
NOTES
tained its standing as a Penicillium sp. in the mycological literature (23, 33). In 1974, Samson transferred the species into the genus Paecilomyces as Paecilomyces lilacinus (Thom) Samson (29). Since then, authorities have disagreed as to the proper name and assignment of this species. Pitt feels that the species is a Paecilomyces sp. (20), while Ramirez (22) places the entity in the genus Penicillium, as do Onions and Brady (18). The reasons for disparity among experts are complex, but for this species, Samson felt that the microscopic morphology was closely aligned with the features of Paecilomyces species, namely, "stiff verticillate conidiophores, phiatides with a distinct neck, purple or vinaceous color of the conidial heads, and divergent or tangled conidial chains" (29). Penicillia, in contrast, exhibit flask-shaped phialides with distinct short necks arranged in penicillate (brushlike) clusters. If one supports the view that this species belongs in the genus Penicillium, it would be placed in the section Divaricatum, with penicillate heads branching in a spreading, divergent, and irregular manner. In this case, Paecilomyces lilacinus would be similar to Penicillium janthinellum but would lack the green conidial color (18). The major distinction between the genera Penicillium and Paecilomyces, morphologically, is the very distinct, often elongated neck protruding from the phialides of the latter genus. We concur with those placing the species in the genus Paecilomyces. Ongoing studies employing the techniques of contemporary molecular biology may help to resolve the issue of the appropriate classification of this species (21). Paecilomyces lilacinus grows rapidly on Sabouraud dextrose agar, producing a white floccose colony that gradually becomes lilac or vinaceous in color, from which its name was derived (Fig. 1). Colony size, color, temperature response, and growth rate are highly variable (23). The temperature range for growth is from 8 to 38°C. For our patient, blood cultures were all initially grown in BACTEC NR6 bottles, and all became positive with visible turbidity and
J. CLIN. MICROBIOL.
fungal elements at the bottom of the bottles in 3 to 4 days after collection. Gram-stained smear of the contents of the BACTEC bottles showed hyphal elements (Fig. 2), and this material was subcultured onto Sabouraud dextrose agar plates and incubated at 30°C. This subculture grew in 2 days, and a scotch tape preparation with lactophenol cotton blue, as well as a slide culture, was performed and showed morphology resembling Penicillium species. Upon receipt in the reference laboratory, the mould was subcultured to potato flakes agar (24) and Czapek agar (7) and incubated at 25°C, and mounts in lactophenol cotton blue were observed after 5 days of growth. Colonies on both media were floccose, at first white and then gradually turning purplish; the reverse was dark purple (Fig. 1). The conidial heads were irregular and divergent, often exhibiting one level of branching below the conidiogenous cells. Conidiophores were finely to coarsely rough, with characteristic conidiogenous cells tapering abruptly to a long slender tip, which was 7 to 8 ,um long; conidia were mostly elliptical to subglobose and smooth (2.5 to 3 by 2 ,m) (Fig. 3). A species of Paecilomyces morphologically very similar to Paecilomyces lilacinus is Paecilomyces marquandii. It is usually easily distinguished from Paecilomyces lilacinus by the formation of colonies with bluer surface color and bright-yellow reverse pigmentation. The isolate from this case did not exhibit either of these features. A Paecilomyces species was first recognized to cause human disease in 1963, when a case of fatal endocarditis following mitral valve replacement was reported (34). To date, only 47 case reports or small series of human infection due to Paecilomyces species have been reported in the literature (3), with the majority occurring in association with prosthesis implants or immunosuppression. Paecilomyces lilacinus previously has been associated with respiratory, ocular, and cutaneous infections (Table 1). The largest series of reported infections occurred in 1975 with an outbreak of Paecilomyces lilacinus endophthalmitis (19, 35). Thirteen
2481
NOTES
VOL. 30, 1992
1
...
11
"'W "lk' IEL-.
ww-
AiL.
v
t
FIG. 2. Gram-stained
Magnification
x
smear
^
~~~~~~~OI
of blood culture from
a
BACTEC
NR6 bottle
showing hyphal
elements with free and attached conidia.
100
cases were diagnosed, all following cataract extraction and intraocular lens implantation. The source of the contamination was traced to bicarbonate neutralizing solution used to bathe the lenses prior to implantation (35). The prognosis of infection caused by Paecilomyces species has been for the most part dismal. To date, all cases of Paecilomyces endocarditis have had a fatal outcome. In three other cases of Paecilomyces infection, the fungus was directly or indirectly related to the death of the patient (3). In 8 of the 13 cases of endophthalmitis, the patients' eyes were enucleated, and in 3 of the remaining 5 cases, the patients lost visual function. Therefore, 30 of the 47 cases of reported infection due to Paecilomyces species resulted in a poor clinical outcome (3, 35). In contrast, our patient did well and responded to prompt removal of his implantable central venous catheter and a short course of amphotericin B therapy. It is clinically important to accurately identify the species causing the mycosis because of the extreme variation in resistance patterns to antifungal agents by the members of this genus. Data from in vitro susceptibility testing in animals and humans (7, 8, 12, 17, 19, 36) clearly indicate susceptibility trends: Paecilomyces lilacinus and Paecilomyces marquandii are highly resistant to polyene antibiotics and to flucytosine, while Paecilomyces variotii appears
universally susceptible to amphotericin B and to flucytosine. Susceptibility of Paecilomyces lilacinus isolates to antifungal drugs seems to vary according to the different reports. Despite relative in vitro resistance, patients with Paecilomy-
TABLE 1. Reported cases of Paecilomyces lilacinus infections System or fluid involved
s. Clcal dsease . .
Respiratory
Pleural effusion Sinusitis
Ocular
Endophthalmitis Keratitis Orbital granuloma
Integument
Bloodb
No. of
reported cases 2 1 19 5 1
Nail infection Hyalohyphomycosis: deep
7 3
cellulitisa Cutaneous infection
1
Fungemia, catheter associated
1
a Sites: left forearm, right hand, and left cheek. b The case presented in this study.
2482
NOTES
J. CLIN. MICROBIOL.
.......... .. ._Am
*
FIG.
3. Paecilomyces lilacinus, potato flakes agar,
25°C,
.. ... .'\,: :'iM
5 days, showing conidiophores, divergent conidiogenous cells, elongate phialide
necks and ellipsoid conidia by Nomarski differential interference microscopy. Magnification, x 400.
ces lilacinus infection have been successfully treated with amphotericin B. In most cases, patients were begun on antifungal therapy before the identity and susceptibility patterns of the organism were available. A further difficulty involves the current lack of standardization of in vitro antifungal susceptibility testing methods and correlation of in vitro results with patients' therapeutic responses (25). Antifungal susceptibility studies were not performed for the isolate from this case. In addition, when infection is associated with a prosthetic implant, early surgical excision of the implant is advisable since the device may enhance the invasive potential of this normally noninvasive organism. In summary, we report a case of Paecilomyces lilacinus catheter-related fungemia in an immunocompromised pediatric patient where prompt removal of his catheter and antifungal therapy with amphotericin B were curative. Reports of immunocompromised patients being infected with unusual opportunistic organisms are becoming more commonplace, and medical and laboratory personnel should be aware that Paecilomyces species can be human pathogens under certain circumstances. We thank Edward Mason, Jr., for his valuable review of this
manuscript.
REFERENCES 1. Agrawal, P. K., B. Lal, S. Wahab, O. P. Srivastrava, and S. C. Misra. 1979. Orbital paecilomycosis due to Paecilomyces lilacinus (Thom) Samson. Sabouraudia 17:363-370. 2. Allevato, P. A., J. M. Ohorodnik, E. Mezger, and J. F. Eisses. 1984. Paecilomyces javanicus endocarditis of native and prosthetic aortic valve. Am. J. Clin. Pathol. 82:247-252. 3. Castro, L. G., A. Salebrian, and M. N. Sotto. 1990. Hyalohyphomycosis by Paecilomyces lilacinus in a renal transplant patient and a review of human Paecilomyces species infections. J. Med. Vet. Mycol. 28:15-26. 4. Crompton, C. H., R. C. Summerbell, and M. M. Silver. 1991. Peritonitis with Paecilomyces complicating peritoneal dialysis. Pediatr. Infect. Dis. J. 10:869-871. 5. Dekhkan-Khodzhaeva, N. A., S. S. Shamsier, R. Y. Shakirova, G. I. Macavova, and S. N. Mingbaeva. 1982. The role of Paecilomyces in the etiology of prolonged and recurrent bronchopulmonary diseases in children. Pediatria 9:12-14. 6. Fenech, F. F., and C. P. Mallia. 1972. Pleural effusion caused by Penicillium lilacinum. Br. J. Dis. Chest 66:284-290. 7. Gordon, M. A. 1984. Paecilomyces lilacinus (Thom) Samson from systemic infection in an armadillo (Dasypus novemcinctus). Sabouraudia 22:109-116. 8. Gordon, M. A., and S. W. Norton. 1985. Corneal transplant infection by Paecilomyces lilacinus. Sabouraudia 23:295-301. 9. Haldane, E. V., J. L. MacDonald, W. 0. Gittens, K. Yuce, and
VOL. 30, 1992
10.
11.
12. 13.
14.
15.
16. 17. 18.
19. 20.
C. E. Rooyen. 1974. Prosthetic valvular endocarditis due to the fungus Paecilomyces. Can. Med. Assoc. J. 111:963-968. Harris, L. F., B. M. Dan, L. B. Lefhowitz, Jr., and R. H. Alford. 1979. Paecilomyces cellulitis in a renal transplant patient: successful treatment with intravenous miconazole. South. Med. J. 72:897-989. Jade, K. B., M. F. Lyons, and J. W. Gnann, Jr. 1986. Paecilomyces lilacinus cellulitis in an immunocompromised patient. Arch. Dermatol. 122:1169-1170. Kalish, S. B., R. Goldschmidt, C. Li, R. Knop, F. V. Cook, G. Wilner, and T. A. Victor. 1982. Infective endocarditis caused by Paecilomyces vanotdi. Am. J. Clin. Pathol. 78:249-252. Levin, P. S., W. E. Beebe, and R. L. Abbott. 1987. Successful treatment of Paecilomyces lilacinus endophthalmitis following cataract extraction with intraocular lens implantation. Ophthalmic Surg. 18:217-219. McClellan, J. R., J. D. Hamilton, J. A. Alexander, W. G. Wolfe, and J. B. Reed. 1976. Paecilomyces variotii endocarditis on a prosthetic aortic valve. J. Thorac. Cardiovasc. Surg. 71:472475. Miller, G. R., G. Rebell, R. C. Magoon, S. M. Kulvin, and R. K. Forester. 1978. Intravitreal mycotic therapy and the cure of mycotic endophthalmitis caused by a Paecilomyces lilacinus contaminated pseudophakes. Ophthalmic Surg. 9:54-63. Mosier, M., B. Lusk, T. H. Pettit, D. H. Howard, and J. Rhodes. 1977. Fungal endophthalmitis following intraocular lens implantation. Am. J. Ophthalmol. 83:1-8. O'Day, D. M. 1977. Fungal endophthalmitis caused by Paecilomyces lilacinus after intraocular lens implantation. Am. J. Ophthalmol. 83:130-131. Onions, A. H. S., and B. L. Brady. 1987. Taxonomy of Penicillium and Acremonium, p. 1-36. In J. F. Peberdy (ed.), Penicillium and Acremonium, vol. I. Biotechnology handbooks. Plenum Press, New York. Pettit, T. H., R. J. Olson, R. Y. Foos, and W. J. Martin. 1980. Fungal endophthalmitis following intraocular lens implantation. A surgical epidemic. Arch. Ophthalmol. 98:1025-1039. Pitt, J. I. 1979. The genus Penicilium and its teleomorphic states Eupenicillium and Talaromyces. Academic Press, New York.
NOTES
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21. Pitt, J. I. and R. A. Samson. 1990. Approaches to Penicillium and Aspergillus systematics. Stud. Mycol. 32:77-90. 22. Ramirez, C. 1982. Manual and atlas of the penicillia. Elsevier, Amsterdam. 23. Raper, K. B., and C. Thom. 1949. A manual of the Penicillia, p. 284-288. Williams & Wilkins, Baltimore. 24. Rinaldi, M. G. 1982. The use of potato flakes agar in clinical mycology. J. Clin. Microbiol. 15:1159-1160. 25. Rinaldi, M. G. 1991. Aspects of the laboratory evaluation of antifungal antimicrobials. Cliniguide Fungal Infect. 2:1-5. 26. Rockhill, R. C., and M. D. Klein. 1980. Paecilomyces lilacinus as the cause of chronic maxillary sinusitis. J. Clin. Microbiol. 11:737-743. 27. Rodrigues, M. M., and D. MacLeod. 1975. Exogenous fungal endophthalmitis caused by Paecilomyces. Am. J. Ophthalmol. 79:687-690. 28. Rowley, S. D., and C. G. Strom. 1982. Paecilomyces fungus infection of the maxillary sinus. Laryngoscope 92:332-334. 29. Samson, R. A. 1974. Paecilomyces and some allied hyphomycetes. Stud. Mycol. 6:1-119. 30. Silver, M. D., P. G. Tuffnell, and W. G. Bigelow. 1971. Endocarditis caused by Paecilomyces variotii affecting an aortic valve allograft. J. Thorac. Cardiovasc. Surg. 61:278-281. 31. Takayasu, S., M. Akagi, and Y. Shimzu. 1977. Cutaneous mycosis caused by Paecilomyces lilacinus. Arch. Dermatol. 113:1687-1690. 32. Thom, C. 1910. Cultural studies of species of Penicillium. Bull. Bur. Anim. Indus. 118:73-75. 33. Thom, C. 1930. The penicillia. Williams & Wilkins, Baltimore. 34. Uys, C. J., P. A. Don, V. Schrire, and C. N. Barnard. 1963. Endocarditis following cardiac surgery due to the fungus Paecilomyces. South Afr. Med. J. 21:1276-1280. 35. Webster, R. G., Jr., W. J. Martin, T. H. Pettit, J. Rhodes, B. Boni, T. Midura, and M. D. Skinner. 1975. Eye infection after plastic lens implantation. Morbid. Mortal. Weekly Rep. 24:437438. 36. Weitzman, I. 1986. Saprophytic molds as agents of cutaneous and subcutaneous infections in the immunocompromised host. Arch. Dermatol. 122:1161-1168.
JOURNAL OF CLINICAL MICROBIOLOGY, Sept. 1992,/p. 2479-2483
0095-1137/92/092479-05$02.00/0 Copyright © 1992, American Society for Microbiology
Paecilomyces lilacinus Catheter-Related Fungemia in Immunocompromised Pediatric Patient
an
TAN,`*
ANGELA K. OGDEN,1 JILL TILLMAN,2 GAIL J. DEMMLER,1'2'3 AND MICHAEL G. RINALDI4 Departments of Pediatrics1 and Pathology,3 Baylor College ofMedicine, and Pathology Laboratories, Texas Children's Hospital,2 Houston, Texas 77030, and Department of Pathology, University of Texas Health Science Center, San Antonio, Texas 78284-7750 TINA Q.
Received 24 February 1992/Accepted 2 June 1992
Paecilomyces lilacinus catheter-related fungemia in an immunocompromised child is reported. The presence of a central venous catheter and the patient's immunocompromised status were felt to be predisposing factors for this unusual infection. To our knowledge, this is the first description of P. lilacinus catheter-related fungemia, and our patient may be the youngest reported patient with this mycosis who was cured. urine culture were obtained, and broad-spectrum antimicrobial therapy consisting of vancomycin (10 mg/kg of body weight per dose) and gentamicin (2.5 mg/kg per dose) was administered intravenously every 8 h. The initial blood culture from his Portacath grew a mould, as well as a branching gram-positive rod, which was later identified as a Streptomyces species and ascertained to be a contaminant. A repeat blood culture obtained through the Portacath on hospital day 3 also grew a mould, and on hospital day 6, the Portacath was removed and treatment with amphotericin B was begun. A peripheral blood culture obtained at the time of Portacath removal also became positive for the same mould. No evidence of disseminated fungal infection was seen on ophthalmologic exam, abdominal and renal ultrasound examinations, computed tomography scans, or echocardiogram. Antibiotics were discontinued after cultures were negative for bacterial pathogens at 72 h, and the patient received 10 mg of amphotericin B per kg (total cumulative dose). Three blood cultures obtained after the Portacath was removed were sterile. The patient tolerated his therapy well, there were no complications, and he was discharged home. Since discharge, the patient has been well and is growing and developing appropriately, with no recurrence of infection. The mould isolated from the patient's blood cultures was tentatively identified as a Penicillium species. It was sent to a reference mycology laboratory (Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio) for further identification and was subsequently identified as Paecilomyces lilacinus. Prior to 1974, this organism was often referred to as Penicillium lilacinum. The genus Paecilomyces Bainer includes up to 17 species of saprobic moulds and is likely closely related to the genus Penicillium Link. Of Paecilomyces species, Paecilomyces lilacinus (Thom) Samson, Paecilomyces variotii Bainer, Paecilomyces viridis Segretain ex Samson, Paecilomyces marquandii (Massee) Hughes, and Paecilomyces javanicus (Friedrichs et Bally) Brown et Smith (felt by many authorities to be a species of Penicillium) have been associated with human mycotic infections. The species-inciting disease in this case report, Paecilomyces lilacinus, has been subjected to various nomenclatural dispositions which currently still exist among experts. The species was originally described in 1910 as Penicillium lilacinum Thom (32). For a considerable period following the original description, the fungus main-
Paecilomyces species are ubiquitous saprobic fungi that found worldwide in soil and on decomposing vegetation. They are common contaminants of sterile solutions and clinical specimens because they are extremely resistant to the majority of commercial sterilizing techniques (3). While recognized as insect and animal pathogens, Paecilomyces species are very rarely pathogenic in humans. There are, however, sporadic reports of endophthalmitis (13, 15-17, 19, 27, 35) following intraocular lens implantation, endocarditis (2, 9, 12, 14, 30, 34) following cardiac valve replacement, orbital cellulitis (1), pulmonary (5, 6) and cutaneous (10, 11, 31) infections, chronic maxillary sinusitis (26, 28), and peritonitis (4) due to Paecilomyces species in humans. The majority of these infections occurred in adult patients with impaired host defenses or following foreign body implants, factors which predisposed them to opportunistic infections. In this report, we describe an 18-month-old immunocompromised child who developed fungemia caused by Paecilomyces lilacinus, the source of which was, most likely, his central venous catheter. Case report. Our patient was an 18-month-old white male with obstructive uropathy secondary to embryonal rhabdomyosarcoma group III involving the bladder and prostate. A tunneled central venous catheter (Hickman) was placed at the time of the tumor biopsy and debulking to administer chemotherapy. This catheter, however, was removed 3 months later when he developed a catheter-associated chest wall abscess and sepsis due to Klebsiella pneumoniae. A totally implantable central venous catheter (Portacath) was therefore placed 1 month later for the continuation of his chemotherapy. On 20 August 1991, the patient was admitted to Texas Children's Hospital for fever of 101.9°F, malaise, decreased appetite, and neutropenia secondary to chemotherapy. Physical examination revealed only mild nasal congestion and rhinorrhea. His peripheral white blood cell count was 1,630/mm3 with 24 polymorphonuclear cells, 11 band forms, 34 lymphocytes, 28 mononuclear cells, and 3 eosinophils with an absolute neutrophil count of 570. His platelet count was 318,000/mm3, with a hematocrit of 25.8% and a hemoglobin value of 8.8 g/dl. Chest radiograph and urinalysis results were normal. Blood culture from his Portacath and a are
*
Corresponding author. 2479
2480
NOTES
tained its standing as a Penicillium sp. in the mycological literature (23, 33). In 1974, Samson transferred the species into the genus Paecilomyces as Paecilomyces lilacinus (Thom) Samson (29). Since then, authorities have disagreed as to the proper name and assignment of this species. Pitt feels that the species is a Paecilomyces sp. (20), while Ramirez (22) places the entity in the genus Penicillium, as do Onions and Brady (18). The reasons for disparity among experts are complex, but for this species, Samson felt that the microscopic morphology was closely aligned with the features of Paecilomyces species, namely, "stiff verticillate conidiophores, phiatides with a distinct neck, purple or vinaceous color of the conidial heads, and divergent or tangled conidial chains" (29). Penicillia, in contrast, exhibit flask-shaped phialides with distinct short necks arranged in penicillate (brushlike) clusters. If one supports the view that this species belongs in the genus Penicillium, it would be placed in the section Divaricatum, with penicillate heads branching in a spreading, divergent, and irregular manner. In this case, Paecilomyces lilacinus would be similar to Penicillium janthinellum but would lack the green conidial color (18). The major distinction between the genera Penicillium and Paecilomyces, morphologically, is the very distinct, often elongated neck protruding from the phialides of the latter genus. We concur with those placing the species in the genus Paecilomyces. Ongoing studies employing the techniques of contemporary molecular biology may help to resolve the issue of the appropriate classification of this species (21). Paecilomyces lilacinus grows rapidly on Sabouraud dextrose agar, producing a white floccose colony that gradually becomes lilac or vinaceous in color, from which its name was derived (Fig. 1). Colony size, color, temperature response, and growth rate are highly variable (23). The temperature range for growth is from 8 to 38°C. For our patient, blood cultures were all initially grown in BACTEC NR6 bottles, and all became positive with visible turbidity and
J. CLIN. MICROBIOL.
fungal elements at the bottom of the bottles in 3 to 4 days after collection. Gram-stained smear of the contents of the BACTEC bottles showed hyphal elements (Fig. 2), and this material was subcultured onto Sabouraud dextrose agar plates and incubated at 30°C. This subculture grew in 2 days, and a scotch tape preparation with lactophenol cotton blue, as well as a slide culture, was performed and showed morphology resembling Penicillium species. Upon receipt in the reference laboratory, the mould was subcultured to potato flakes agar (24) and Czapek agar (7) and incubated at 25°C, and mounts in lactophenol cotton blue were observed after 5 days of growth. Colonies on both media were floccose, at first white and then gradually turning purplish; the reverse was dark purple (Fig. 1). The conidial heads were irregular and divergent, often exhibiting one level of branching below the conidiogenous cells. Conidiophores were finely to coarsely rough, with characteristic conidiogenous cells tapering abruptly to a long slender tip, which was 7 to 8 ,um long; conidia were mostly elliptical to subglobose and smooth (2.5 to 3 by 2 ,m) (Fig. 3). A species of Paecilomyces morphologically very similar to Paecilomyces lilacinus is Paecilomyces marquandii. It is usually easily distinguished from Paecilomyces lilacinus by the formation of colonies with bluer surface color and bright-yellow reverse pigmentation. The isolate from this case did not exhibit either of these features. A Paecilomyces species was first recognized to cause human disease in 1963, when a case of fatal endocarditis following mitral valve replacement was reported (34). To date, only 47 case reports or small series of human infection due to Paecilomyces species have been reported in the literature (3), with the majority occurring in association with prosthesis implants or immunosuppression. Paecilomyces lilacinus previously has been associated with respiratory, ocular, and cutaneous infections (Table 1). The largest series of reported infections occurred in 1975 with an outbreak of Paecilomyces lilacinus endophthalmitis (19, 35). Thirteen
2481
NOTES
VOL. 30, 1992
1
...
11
"'W "lk' IEL-.
ww-
AiL.
v
t
FIG. 2. Gram-stained
Magnification
x
smear
^
~~~~~~~OI
of blood culture from
a
BACTEC
NR6 bottle
showing hyphal
elements with free and attached conidia.
100
cases were diagnosed, all following cataract extraction and intraocular lens implantation. The source of the contamination was traced to bicarbonate neutralizing solution used to bathe the lenses prior to implantation (35). The prognosis of infection caused by Paecilomyces species has been for the most part dismal. To date, all cases of Paecilomyces endocarditis have had a fatal outcome. In three other cases of Paecilomyces infection, the fungus was directly or indirectly related to the death of the patient (3). In 8 of the 13 cases of endophthalmitis, the patients' eyes were enucleated, and in 3 of the remaining 5 cases, the patients lost visual function. Therefore, 30 of the 47 cases of reported infection due to Paecilomyces species resulted in a poor clinical outcome (3, 35). In contrast, our patient did well and responded to prompt removal of his implantable central venous catheter and a short course of amphotericin B therapy. It is clinically important to accurately identify the species causing the mycosis because of the extreme variation in resistance patterns to antifungal agents by the members of this genus. Data from in vitro susceptibility testing in animals and humans (7, 8, 12, 17, 19, 36) clearly indicate susceptibility trends: Paecilomyces lilacinus and Paecilomyces marquandii are highly resistant to polyene antibiotics and to flucytosine, while Paecilomyces variotii appears
universally susceptible to amphotericin B and to flucytosine. Susceptibility of Paecilomyces lilacinus isolates to antifungal drugs seems to vary according to the different reports. Despite relative in vitro resistance, patients with Paecilomy-
TABLE 1. Reported cases of Paecilomyces lilacinus infections System or fluid involved
s. Clcal dsease . .
Respiratory
Pleural effusion Sinusitis
Ocular
Endophthalmitis Keratitis Orbital granuloma
Integument
Bloodb
No. of
reported cases 2 1 19 5 1
Nail infection Hyalohyphomycosis: deep
7 3
cellulitisa Cutaneous infection
1
Fungemia, catheter associated
1
a Sites: left forearm, right hand, and left cheek. b The case presented in this study.
2482
NOTES
J. CLIN. MICROBIOL.
.......... .. ._Am
*
FIG.
3. Paecilomyces lilacinus, potato flakes agar,
25°C,
.. ... .'\,: :'iM
5 days, showing conidiophores, divergent conidiogenous cells, elongate phialide
necks and ellipsoid conidia by Nomarski differential interference microscopy. Magnification, x 400.
ces lilacinus infection have been successfully treated with amphotericin B. In most cases, patients were begun on antifungal therapy before the identity and susceptibility patterns of the organism were available. A further difficulty involves the current lack of standardization of in vitro antifungal susceptibility testing methods and correlation of in vitro results with patients' therapeutic responses (25). Antifungal susceptibility studies were not performed for the isolate from this case. In addition, when infection is associated with a prosthetic implant, early surgical excision of the implant is advisable since the device may enhance the invasive potential of this normally noninvasive organism. In summary, we report a case of Paecilomyces lilacinus catheter-related fungemia in an immunocompromised pediatric patient where prompt removal of his catheter and antifungal therapy with amphotericin B were curative. Reports of immunocompromised patients being infected with unusual opportunistic organisms are becoming more commonplace, and medical and laboratory personnel should be aware that Paecilomyces species can be human pathogens under certain circumstances. We thank Edward Mason, Jr., for his valuable review of this
manuscript.
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