Paecilomyces lilacinus Catheter-Related Fungemia in an
Immunocompromised Pediatric PatientTINA Q. 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 ofPathology,
University of Texas Health Science Center, San Antonio, Texas 78284-7750
Received 24 February 1992/Accepted 2 June 1992
Paecilomyces lilacinus catheter-related fungemia in an immunocompromised child is reported. The presenceof a central venous catheter and the patient's immunocompromised status were felt to be predisposing factorsfor this unusual infection. To our knowledge, this is the first description of P. lilacinus catheter-relatedfungemia, and our patient may be the youngest reported patient with this mycosis who was cured.
Paecilomyces species are ubiquitous saprobic fungi thatare found worldwide in soil and on decomposing vegetation.They are common contaminants of sterile solutions andclinical specimens because they are extremely resistant tothe majority of commercial sterilizing techniques (3). Whilerecognized as insect and animal pathogens, Paecilomycesspecies 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 peri-tonitis (4) due to Paecilomyces species in humans. Themajority of these infections occurred in adult patients withimpaired host defenses or following foreign body implants,factors which predisposed them to opportunistic infections.
In this report, we describe an 18-month-old immunocom-promised child who developed fungemia caused by Paecil-omyces lilacinus, the source of which was, most likely, hiscentral venous catheter.
Case report. Our patient was an 18-month-old white malewith obstructive uropathy secondary to embryonal rhabdo-myosarcoma group III involving the bladder and prostate. Atunneled central venous catheter (Hickman) was placed atthe time of the tumor biopsy and debulking to administerchemotherapy. This catheter, however, was removed 3months later when he developed a catheter-associated chestwall abscess and sepsis due to Klebsiella pneumoniae. Atotally implantable central venous catheter (Portacath) wastherefore placed 1 month later for the continuation of hischemotherapy.On 20 August 1991, the patient was admitted to Texas
Children's Hospital for fever of 101.9°F, malaise, decreasedappetite, and neutropenia secondary to chemotherapy.Physical examination revealed only mild nasal congestionand rhinorrhea. His peripheral white blood cell count was1,630/mm3 with 24 polymorphonuclear cells, 11 band forms,34 lymphocytes, 28 mononuclear cells, and 3 eosinophilswith an absolute neutrophil count of 570. His platelet countwas 318,000/mm3, with a hematocrit of 25.8% and a hemo-globin value of 8.8 g/dl. Chest radiograph and urinalysisresults were normal. Blood culture from his Portacath and a
* Corresponding author.
urine culture were obtained, and broad-spectrum antimicro-bial therapy consisting of vancomycin (10 mg/kg of bodyweight per dose) and gentamicin (2.5 mg/kg per dose) wasadministered intravenously every 8 h.The initial blood culture from his Portacath grew a mould,
as well as a branching gram-positive rod, which was lateridentified as a Streptomyces species and ascertained to be a
contaminant. A repeat blood culture obtained through thePortacath on hospital day 3 also grew a mould, and onhospital day 6, the Portacath was removed and treatmentwith amphotericin B was begun. A peripheral blood cultureobtained at the time of Portacath removal also becamepositive for the same mould. No evidence of disseminatedfungal infection was seen on ophthalmologic exam, abdom-inal and renal ultrasound examinations, computed tomogra-phy scans, or echocardiogram. Antibiotics were discontin-ued after cultures were negative for bacterial pathogens at 72h, and the patient received 10 mg of amphotericin B per kg(total cumulative dose). Three blood cultures obtained afterthe Portacath was removed were sterile. The patient toler-ated his therapy well, there were no complications, and hewas discharged home. Since discharge, the patient has beenwell and is growing and developing appropriately, with norecurrence of infection. The mould isolated from the pa-tient's blood cultures was tentatively identified as a Penicil-lium species. It was sent to a reference mycology laboratory(Fungus Testing Laboratory, University of Texas HealthScience Center at San Antonio) for further identification andwas subsequently identified as Paecilomyces lilacinus. Priorto 1974, this organism was often referred to as Penicilliumlilacinum.The genus Paecilomyces Bainer includes up to 17 species
of saprobic moulds and is likely closely related to the genusPenicillium Link. Of Paecilomyces species, Paecilomyceslilacinus (Thom) Samson, Paecilomyces variotii Bainer,Paecilomyces viridis Segretain ex Samson, Paecilomycesmarquandii (Massee) Hughes, and Paecilomyces javanicus(Friedrichs et Bally) Brown et Smith (felt by many authori-ties to be a species of Penicillium) have been associated withhuman mycotic infections. The species-inciting disease inthis case report, Paecilomyces lilacinus, has been subjectedto various nomenclatural dispositions which currently stillexist among experts. The species was originally described in1910 as Penicillium lilacinum Thom (32). For a considerableperiod following the original description, the fungus main-
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tained its standing as a Penicillium sp. in the mycologicalliterature (23, 33). In 1974, Samson transferred the speciesinto the genus Paecilomyces as Paecilomyces lilacinus(Thom) Samson (29). Since then, authorities have disagreedas to the proper name and assignment of this species. Pittfeels that the species is a Paecilomyces sp. (20), whileRamirez (22) places the entity in the genus Penicillium, as doOnions and Brady (18).The reasons for disparity among experts are complex, but
for this species, Samson felt that the microscopic morphol-ogy was closely aligned with the features of Paecilomycesspecies, namely, "stiff verticillate conidiophores, phiatideswith a distinct neck, purple or vinaceous color of the conidialheads, and divergent or tangled conidial chains" (29). Peni-cillia, in contrast, exhibit flask-shaped phialides with distinctshort necks arranged in penicillate (brushlike) clusters. Ifone supports the view that this species belongs in the genusPenicillium, it would be placed in the section Divaricatum,with penicillate heads branching in a spreading, divergent,and irregular manner. In this case, Paecilomyces lilacinuswould be similar to Penicillium janthinellum but would lackthe green conidial color (18).The major distinction between the genera Penicillium and
Paecilomyces, morphologically, is the very distinct, oftenelongated neck protruding from the phialides of the lattergenus. We concur with those placing the species in the genusPaecilomyces. Ongoing studies employing the techniques ofcontemporary molecular biology may help to resolve theissue of the appropriate classification of this species (21).Paecilomyces lilacinus grows rapidly on Sabouraud dex-
trose agar, producing a white floccose colony that graduallybecomes lilac or vinaceous in color, from which its namewas derived (Fig. 1). Colony size, color, temperature re-sponse, and growth rate are highly variable (23). The tem-perature range for growth is from 8 to 38°C. For our patient,blood cultures were all initially grown in BACTEC NR6bottles, and all became positive with visible turbidity and
fungal elements at the bottom of the bottles in 3 to 4 daysafter collection. Gram-stained smear of the contents of theBACTEC bottles showed hyphal elements (Fig. 2), and thismaterial was subcultured onto Sabouraud dextrose agarplates 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 showedmorphology 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 cottonblue were observed after 5 days of growth. Colonies on bothmedia were floccose, at first white and then gradually turningpurplish; the reverse was dark purple (Fig. 1). The conidialheads were irregular and divergent, often exhibiting onelevel of branching below the conidiogenous cells. Conidio-phores were finely to coarsely rough, with characteristicconidiogenous cells tapering abruptly to a long slender tip,which was 7 to 8 ,um long; conidia were mostly elliptical tosubglobose and smooth (2.5 to 3 by 2 ,m) (Fig. 3).A species ofPaecilomyces morphologically very similar to
Paecilomyces lilacinus is Paecilomyces marquandii. It isusually easily distinguished from Paecilomyces lilacinus bythe formation of colonies with bluer surface color andbright-yellow reverse pigmentation. The isolate from thiscase did not exhibit either of these features.A Paecilomyces species was first recognized to cause
human disease in 1963, when a case of fatal endocarditisfollowing mitral valve replacement was reported (34). Todate, only 47 case reports or small series of human infectiondue to Paecilomyces species have been reported in theliterature (3), with the majority occurring in association withprosthesis implants or immunosuppression. Paecilomyceslilacinus previously has been associated with respiratory,ocular, and cutaneous infections (Table 1). The largest seriesof reported infections occurred in 1975 with an outbreak ofPaecilomyces lilacinus endophthalmitis (19, 35). Thirteen
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t ^ ~~~~~~~OI
FIG. 2. Gram-stained smear of blood culture from a BACTEC NR6 bottle showing hyphal elements with free and attached conidia.
Magnification x 100
cases were diagnosed, all following cataract extraction andintraocular lens implantation. The source of the contamina-tion was traced to bicarbonate neutralizing solution used tobathe the lenses prior to implantation (35).The prognosis of infection caused by Paecilomyces spe-
cies has been for the most part dismal. To date, all cases ofPaecilomyces endocarditis have had a fatal outcome. Inthree other cases of Paecilomyces infection, the fungus wasdirectly or indirectly related to the death of the patient (3). In8 of the 13 cases of endophthalmitis, the patients' eyes were
enucleated, and in 3 of the remaining 5 cases, the patientslost visual function. Therefore, 30 of the 47 cases of reportedinfection due to Paecilomyces species resulted in a poor
clinical outcome (3, 35). In contrast, our patient did well andresponded to prompt removal of his implantable centralvenous catheter and a short course of amphotericin Btherapy.
It is clinically important to accurately identify the speciescausing the mycosis because of the extreme variation inresistance patterns to antifungal agents by the members ofthis genus. Data from in vitro susceptibility testing in ani-mals and humans (7, 8, 12, 17, 19, 36) clearly indicatesusceptibility trends: Paecilomyces lilacinus and Paecilomy-ces marquandii are highly resistant to polyene antibioticsand to flucytosine, while Paecilomyces variotii appears
universally susceptible to amphotericin B and to flucytosine.Susceptibility of Paecilomyces lilacinus isolates to antifun-gal 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 . . s. No. offluid involved Clcal dsease reported cases
necks and ellipsoid conidia by Nomarski differential interference microscopy. Magnification, x400.
ces lilacinus infection have been successfully treated withamphotericin B. In most cases, patients were begun onantifungal therapy before the identity and susceptibilitypatterns of the organism were available. A further difficultyinvolves the current lack of standardization of in vitroantifungal susceptibility testing methods and correlation ofin vitro results with patients' therapeutic responses (25).Antifungal susceptibility studies were not performed for theisolate from this case. In addition, when infection is associ-ated with a prosthetic implant, early surgical excision of theimplant is advisable since the device may enhance theinvasive potential of this normally noninvasive organism.
In summary, we report a case of Paecilomyces lilacinuscatheter-related fungemia in an immunocompromised pedi-atric patient where prompt removal of his catheter andantifungal therapy with amphotericin B were curative. Re-ports of immunocompromised patients being infected withunusual opportunistic organisms are becoming more com-monplace, and medical and laboratory personnel should beaware that Paecilomyces species can be human pathogensunder certain circumstances.
We thank Edward Mason, Jr., for his valuable review of thismanuscript.
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