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Paecilomyces lilacinus Vaginitis in an Immunocompetent Patient

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Paecilomyces lilacinus, a saprobic filamentous fungus, found in soil, decaying vegetation, saunas, and laboratories (as an airborne contaminant), is an infrequent cause of human disease (1,2). Most cases of disease caused by the genus Paecilomyces occur in patients who have compromised immune systems, indwelling foreign devices, or intraocular lens implants (2,3). Rarely has disease been reported in immunocompetent hosts without any identifiable risk factor. We describe the first case of P. lilacinus isolated from a vaginal culture in a patient with vaginitis and review the published literature addressing P. lilacinus infections in immunocompetent patients. Our review demonstrates that the reports of P lilacinus infections in immunocompetent hosts have become more frequent in the last several years. This trend indicates that P. lilacinus may be an emerging pathogen.
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Paecilomyces
lilacinus Vaginitis
in an Immuno-
competent Patient
Jeanne Carey,* Ron D’Amico,*
Deanna A. Sutton,† and Michael G. Rinaldi†‡
Paecilomyces lilacinus, an environmental mold found
in soil and vegetation, rarely causes human infection. We
report the first case of P. lilacinus isolated from a vaginal
culture in a patient with vaginitis.
P
aecilomyces lilacinus, a saprobic filamentous fungus,
found in soil, decaying vegetation, saunas, and labora-
tories (as an airborne contaminant), is an infrequent cause
of human disease (1,2). Most cases of disease caused by
the genus Paecilomyces occur in patients who have com-
promised immune systems, indwelling foreign devices, or
intraocular lens implants (2,3). Rarely has disease been
reported in immunocompetent hosts without any identifi-
able risk factor.
We describe the first case of P. lilacinus isolated from a
vaginal culture in a patient with vaginitis and review the
published literature addressing P. lilacinus infections in
immunocompetent patients. Our review demonstrates that
the reports of P. lilacinus infections in immunocompetent
hosts have become more frequent in the last several years.
This trend indicates that P. lilacinus may be an emerging
pathogen.
Case Report
A 48-year-old woman reported vaginal itching and dis-
charge of 5 months’ duration. Her symptoms had been
recalcitrant to several courses of therapy for a presumptive
diagnosis of candidal vaginitis. She had been treated ini-
tially with fluconazole, then sequentially with topical
clotrimazole, ticoconazole ointment, and intravaginal
boric acid gel. Her medical history was notable for mild
gastritis (treated with omeprazole) and irregular uterine
bleeding, controlled with hormone replacement therapy (a
transdermal estrogen/progesterone combination). The
patient was in a monogamous relationship with her hus-
band but reported abstinence for several months because of
the severity of her vaginal symptoms.
On physical examination, vaginal erythema with a
white liquid vaginal discharge was observed. Although a
potassium hydroxide (KOH) preparation was not obtained
at baseline, the discharge grew P. lilacinus in pure culture.
The patient was treated empirically with itraconazole,
200 mg orally twice a day for 3 weeks. At the end of ther-
apy, she reported complete resolution of her vaginal dis-
charge and a significant decrease in her vaginal pruritus. A
repeat vaginal culture was not obtained at her first follow-
up appointment after completion of itraconazole therapy
because the vaginal vault contained a large amount of
blood. At an appointment 6 months later, she remained free
of vaginal discharge; a vaginal fungal culture and KOH
preparation performed at that time were negative.
The results of laboratory studies, including serum pro-
tein electrophoresis (with immunoglobulin [Ig] G, IgA,
IgM) C3, C4, erythrocyte sedimentation rate, a complete
blood count, CD4 cell count, and CD8 cell count were all
within normal limits. Results of a test for antibodies to
HIV were negative. An anergy panel (with Candida and
Trichophytin used as controls) was reactive. A purified
protein derivative was not placed because the patient had a
history of a positive test result.
The patient’s isolate was forwarded to the Fungus
Testing Laboratory, Department of Pathology, University
of Texas Health Science Center at San Antonio, Texas, for
confirmation of the identity and antifungal susceptibility
testing, and accessioned into the stock collection as
UTHSC 01-872. The isolate was initially subcultured onto
potato flakes agar (PFA, prepared in house), which was
prepared in-house, at 25°C, 30°C, 35°C, and 40°C (ambi-
ent air with alternating daylight and darkness). The isolate
was subsequently plated onto carnation leaf agar (CLA
[prepared in-house]) and malt agar (Remel, Lenexa, KS) at
25°C. Temperature studies were repeated after initial
observations.
The case isolate was evaluated for susceptibility to anti-
fungal agents by using the National Committee for Clinical
Laboratory Standards broth macrodilution method M38-P
(4). Briefly, the case isolate and the P. variotii control
organism, UTHSC 90-450, were grown on PFA for 7 to 10
days at 25°C to induce conidial formation. The mature
PFA isolate and control slants were overlaid with sterile
distilled water, and suspensions were made by gently
scraping the colonies with the tip of a Pasteur pipette.
Heavy hyphal fragments were allowed to settle, and the
upper, homogeneous conidial suspensions were removed.
Conidia were counted with a hemacytometer, and the
inoculum was standardized to 1.0 x 10
5
CFU/mL. Conidial
suspensions were further diluted 1:10 in medium for a final
inoculum concentration of 1.0 x 10
4
CFU/mL. Final drug
concentrations were 0.03–16 µg/mL for amphotericin B
(Bristol-Myers Squibb, Princeton, NJ), ketoconazole
Emerging Infectious Diseases • Vol. 9, No. 9, September 2003 1155
DISPATCHES
*Beth Israel Medical Center, New York, New York, USA;
†University of Texas Health Science Center at San Antonio, San
Antonio, Texas, USA; and ‡Audie L. Murphy Division, South Texas
Veterans Health Care System, San Antonio, Texas, USA
(Janssen Pharmaceutica, Titusville, NJ) and clotrimazole
(Schering-Plough, Kenilworth, NJ), 0.125–64 µg/mL for
5-flucytosine (Roche Laboratories, Nutley, NJ), flucona-
zole, voriconazole (Pfizer, Inc., New York, NY), and ter-
conazole (Ortho-McNeil Pharmaceuticals, Inc., Raritan,
NJ), and 0.015–8 µg/mL for itraconazole (Janssen
Pharmaceutica) and posaconazole (Schering-Plough).
Results
Growth of the isolate on PFA produced a buff-colored
to slightly lavender, somewhat granular colony after 7
days’ incubation at 25°C. Repeat subcultures with extend-
ed incubation (up to 2 weeks) yielded colonies which were
more definitely mauve-colored, consistent with those typ-
ically seen with P. lilacinus (Figure 1). The isolate failed to
produce sporodochia on carnation leaf agar (CLA, pre-
pared in-house), a feature seen with Fusarium species
(many of which are lavender) and failed to produce a dif-
fusing yellow pigment on malt agar, a characteristic seen
with the closely related P. marquandii. The conidiogenous
cells from the initial slide culture, held 7 days and prepared
from a PFA block, consisted predominately of single, long,
tapering phialides, somewhat atypical for the species.
Repeat PFA slide cultures from subcultures displaying a
more typical macroscopic structure yielded complex fruit-
ing heads with verticillate conidiophores and divergent
phialides, typical for P. lilacinus (Figure 2). Conidiophore
roughness, a feature described for P. lilacinus, was not
observed, however, even after repeated subculturing and
examinations. Smooth-walled, elliptical conidia occurred
in long, tangled chains and measured approximately 2.0 X
2.5 µm. No chlamydospores were observed on any of the
media examined. Temperature studies performed on two
separate occasions (PFA) indicated 4+ growth at 25°C and
30°C, 2+ growth at 35°C, and no growth at 40°C.
Species of Paecilomyces known to produce pinkish to
purplish colonies include P. javanicus, P. fimetarius, P.
fumosoroseus, P. lilacinus, and P. marquandii. The first
three species were excluded from consideration on the
basis of the size of the conidia, as well as the lack of syn-
nematal production for P. fumosoroseus (5). P. marquandii
differs from P. lilacinus by the production of an intense
yellow diffusible pigment, smooth-walled hyaline conidio-
phores, and the production of chlamydospores. Although
the isolate in this case did display smooth conidiophores,
no yellow pigment or chlamydospores were observed. The
existence of intergrading forms between P. lilacinus and P.
marquandii has been described (6). In such strains, charac-
teristics of both species may be observed. On the basis of
the characteristics above, the isolate was identified as P.
lilacinus.
In vitro 48-hour to 72-hour MIC data in µm/mL for the
isolate were as follows: amphotericin B, >16; 5-flucyto-
sine (5-FC), >64; ketoconazole, 0.5/0.5; fluconazole,
32/64; itraconazole, 0.5/0.5; clotrimazole, 0.06/0.25;
voriconazole, 0.25/0.25; terconazole, 4/8; and posacona-
zole, 0.125/0.125.
Conclusions
P. lilicanus rarely causes human infection. A MedLine
review of English-language literature from 1966 to 2003
yielded approximately 60 reports of P. lilacinus infections
in patients who were immunocompromised, had under-
gone ophthalmologic surgery, or had indwelling foreign
devices (2,3). A Medline review in the same time period
indicated only six cases of P. lilacinus infections among
patients who lacked a readily identifiable risk factor. A
review of the bibliographies of relevant articles yielded
three additional reports, for a total of nine cases in appar-
ently immunocompetent hosts. The salient features of
these cases, as well as ours, are summarized in the Table.
The source of infection in most cases, including ours, is
not easily identifiable. P. lilacinus has been isolated as a
benign commensal organism on the toenails of immuno-
1156 Emerging Infectious Diseases • Vol. 9, No. 9, September 2003
DISPATCHES
Figure 1. Macroscopic structure of case isolate after 2 weeks’ incu-
bation at 25°C on potato flakes agar, prepared in house.
Figure 2. Divergent phialides and long, tangled chains of elliptical
conidia borne from more complex fruiting structures characteristic
of Paecilomyces lilacinus, 460X.
competent hosts (15). In some cases, however, P. lilacinus
has been pathogenic and has been implicated as a cause of
onychomycosis in an immunocompetent adult (14). The
low pathogenicity of this fungus in normal hosts is demon-
strated by the indolent nature of two of the cutaneous
infections listed in the Table (8,9), which were character-
ized by many years of chronic infection.
All isolates of the genus Paecilomyces should be tested
for fungal susceptibility since clinical isolates of P. lilaci-
nus frequently display considerable resistance. Isolates of
P. lilacinus, for example, are usually resistant to ampho-
tericin B and 5-flucytosine and susceptible to miconazole
and ketoconazole, whereas isolates of the species P. vari-
otii are usually susceptible to amphotericin B and 5-flucy-
tosine (16). On the basis of breakpoints established for
other fungi, the case isolate appeared resistant to ampho-
tericin B, 5-flucytosine, fluconazole, and possibly tercona-
zole. The approved azoles, itraconazole, ketoconazole, and
clotrimazole, appeared susceptible, as did the investiga-
tional triazoles, voriconazole, and posaconazole.
Although the source isolate was susceptible to clotri-
mazole, the patient’s symptoms did not resolve after clotri-
mazole treatment. However, the duration of therapy with
this agent and the degree of the patient’s adherence to the
treatment regimen are unknown; one or both of these fac-
tors may have contributed to treatment failure.
Our review demonstrates that reports of P. lilacinus
infections in immunocompetent hosts appear to be increas-
ing. The four earliest cases occurred from 1972 to 1984,
with one case reported every 3–5 years. The eight subse-
quent cases occurred between 1996 and 2002, for an aver-
age of slightly more than one new case per year.
We report the first case of P. lilacinus isolated from a
vaginal culture in a patient with vaginitis, whose symp-
toms failed to improve after treatment with fluconazole.
Her symptoms resolved after treatment with itraconazole,
to which the case isolate was susceptible. P. lilacinus has
been described as an emerging opportunistic pathogen in
humans (17). In May 2002, the first case of disseminated
P. lilacinus infection in an HIV-infected patient was report-
ed (18). Our review suggests that P. lilacinus may be an
emerging pathogen in immunocompetent adults as well.
Acknowledgments
The authors thank David C. Perlman for his helpful com-
ments and critical review of the manuscript and Carmen
Yampierre for performing the initial microbiologic processing of
the Paecilomyces lilacinus isolate.
Dr. Carey is an attending physician in the Division of
Infectious Diseases at Beth Israel Medical Center in New York.
Her research interests include tuberculosis and hepatitis among
drug users.
References
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Emerging Infectious Diseases • Vol. 9, No. 9, September 2003 1157
DISPATCHES
Table. Clinical features of cases of Paecilomyces lilacinus infections in immunocompetent hosts
Patient age, gender, and reference no.
Y
Type of infection
Treatment
Outcome
48-year-old woman (our case)
2002
Vaginitis
Iraconazole
Cure
36-year-old man (3)
1999
Cutaneous
Itraconazole
Cure
59-year-old woman (7)
2001
Cutaneous
Itraconazole
Cure
20-year-old woman (8)
1977
Cutaneous
Griseofulvin
Improvement, but not cure
19-year-old man (9)
1984
Cutaneous
Griseofulvin, then ketoconazole
Improvement
57-year-old man (10)
1999
Lung abscess
Surgery
Cure
20-year-old man (11)
1972
Pulmonary effusion
Amphotericin B
Cure
47-year-old woman (12)
1980
Sinusitis
Surgical debridement
Cure
34-year-old man (13)
1997
Endophthalmitis
Fluconazole, ketoconazole,
itraconazole
Progression of disease
59-year-old woman (14)
1998
Onychomycosis
Terbinafine, various topical
therapies, nail clipping
Progression of disease
1158 Emerging Infectious Diseases • Vol. 9, No. 9, September 2003
DISPATCHES
10. Ono N, Sato K, Yokomise H, Tamura K. Lung abscess caused by
Paecilomyces lilacinus. Respiration 1999;66:85–7.
11. Fenech FF, Mallia CP. Pleural effusion caused by Penicillium lilac-
inum. Br J Dis Chest 1972;66:284–90.
12. Rockhill RC, Klein MD. Paecilomyces lilacinus as the cause of
chronic maxillary sinusitis. J Clin Microbiol 1980;11:737–9.
13. Okhravi N, Dart JK, Towler HM, Lightman S. Paecilomyces lilacinus
endophthalmitis with secondary keratitis. Arch Ophthalmol
1997;115:1320–4.
14. Fletcher CL, Hay RJ, Midgley G, Moore M. Onychomycosis caused
by infection with Paecilomyces lilacinus [Letter]. Br J Dermatol
1998;139:1133–5.
15. Abdel-Hafez AI, El-Sharouny HMM. Keratinophilic and saprophytic
fungi isolated from students’ nails in Egypt. J Basic Microbiol
1990;30:3–11.
16. Padhye AA. Hyalophomycosis. In: Balows A, Hausler WJ Jr, Ohashi
M, Torano A, editors. Laboratory diagnosis of infectious diseases:
principles and practice, Vol I, bacterial, mycotic and parasitic dis-
eases. New York: Springer-Verlag; 1988. p. 654–62.
17. Safdar A. Progressive cutaneous hyalohyphomycosis due to
Paecilomyces lilacinus: rapid response to treatment with caspofungin
and itraconazole. Clin Infect Dis 2002;34:1415–7.
18. Lovell RD, Moll M, Allen J, Cicci LG. Case report: disseminated
Paecilomyces lilacinus infection in a patient with AIDS. AIDS Read
2002;12:212–21.
Address for correspondence: Jeanne Carey, Beth Israel Medical Center,
Division of Infectious Diseases, 17 Baird Hall, 350 East 17th Street,
New York, N.Y. 10003, USA; fax: 212-420-2032; email:
jcarey@bethisraelny.org
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... The most common cases are those of ocular infections, followed by cutaneous and sub-cutaneous infections [6]. In addition, other diseases caused by P. lilacinum infections have also been reported, such as sinusitis, nasal septal perforation, osteomyelitis, onychomycosis, fungaemia, endocarditis, and vaginitis [6][7][8][9][10][11][12]. The pathogenicity is not clear, but this fungus can infect both immunocompromised and immunocompetent individuals [6,12]. ...
... In addition, other diseases caused by P. lilacinum infections have also been reported, such as sinusitis, nasal septal perforation, osteomyelitis, onychomycosis, fungaemia, endocarditis, and vaginitis [6][7][8][9][10][11][12]. The pathogenicity is not clear, but this fungus can infect both immunocompromised and immunocompetent individuals [6,12]. The most common portals of entry include skin breakdown, inhalation, and medical instrumentation. ...
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In cobweb rhinitis, it should be emphasized that during the last 10 years, there are an increasing number of the patients complaining of subjective feeling of the bilateral nasal stuffiness where, at the same time, all of them have been showing an unusual clinical picture within the nasal cavities, resembling very much the spider web (a cobweb). There haven’t been found any other possible mechanical obstructions like nasal polyps, septal deformities, or tumors. The cobweb in the nose is not an impressive finding and could be easily overlooked, especially in those colleagues who never have heard of this entity, or they simply do not believe in something like that. In all of the patients, there was one unusual clinical finding in the nose: almost transparent but still whitish, very delicate mucous filaments extending between the medial surfaces of the anterior thirds of the inferior turbinates on one side and septal mucosa of the corresponding region at the other side, resembling a cobweb. Once again, cobweb rhinitis is always located in the anterior third of the nasal cavity.
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those who deal with infectious diseases on a daily This two volume work stems from the belief of the Editors that infectious diseases are not only very basis. much with us today but, more importantly, that they There are several excellent textbooks dealing will continue to playa significant global role in mor­ with medical microbiology, and there are equally well-recognized books devoted to infectious dis­ bidity and mortality in all people. A continuing need for an informed and knowledgeable community of eases. The Editors of this work, on the other hand, laboratory scientists is fundamental. Data describing were persuaded that there was a need for a publica­ the global impact of infectious diseases are difficult tion that would bring together the most pertinent and to come by. Fortunately, a recent thoughtful and relevant information on the principles and practice of provocative publication by Bennett et al. (1987) pro­ the laboratory diagnosis of infectious diseases and vides us with data derived from several consultants include clinical relationships. While this two volume that clearly delineate the impact of infectious dis­ text is directed toward the role of the laboratory in eases on the United States today.
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