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Streptomyces Pneumonia in a Patient with Human Immunodeficiency Virus
Infection: Case Report and Review of the Literature on Invasive Streptomyces
Infections
Eileen F. Dunne, William J. Burman,
and Michael L. Wilson
From the Department of Public Health, Denver Health and Hospitals;
and the Departments of Medicine (Division of Infectious Diseases) and
Pathology, University of Colorado Health Sciences Center, Denver,
Colorado
Streptomyces species are most widely known for their production of antimicrobial substances and,
apart from mycetoma, have rarely been reported as a cause of infection. We describe a patient
with early human immunodeficiency virus infection who presented with fever, cough, and nodular
pulmonary infiltrates. Open lung biopsy revealed necrotic tissue and a sulfur granule; aerobic
bacterial cultures yielded Streptomyces species. The patient was treated successfully with clarithromycin for 6 months. We review the clinical presentation and treatment of invasive streptomyces
infections.
Members of the genus Streptomyces are aerobic actinomycetes known for the production of antibiotics used to treat
bacterial, mycobacterial, fungal, and parasitic infections. Streptomyces species can also cause human disease. Mycetoma, a
chronic suppurative infection of the skin and underlying soft
tissue, is the most common presentation of streptomyces infection; visceral infections with these organisms appear to be rare.
We report a case of pneumonia caused by Streptomyces species
in a patient with HIV infection, and we review the literature
on invasive streptomyces infections.
Case Report
A 43-year-old male presented with complaints of progressive
weight loss over 2 months, night sweats and fatigue of 2 weeks’
duration, a nonproductive cough, dyspnea, and pleuritic chest
pain. HIV infection had been diagnosed 8 years previously;
his most recent CD4 cell count was 800/mm3. Notable findings
of the initial physical examination included a temperature of
38.97C, diffuse inspiratory crackles, and a right-sided pleural
friction rub. The patient had no evidence of dental abnormalities. Laboratory tests revealed a WBC count of 15,800
cells/mm3 and modest increases in levels of alkaline phosphatase, lactate dehydrogenase, and hepatic transaminases. A chest
radiograph (figure 1A) showed multiple, 0.5 – 3.0-cm, nodular
opacities in both lung fields; a CT scan of the chest did not
show any cavitation within these lesions or any intrathoracic
lymphadenopathy (figure 1B). An initial sputum culture yielded
normal oral flora.
Received 16 September 1997; revised 11 February 1998.
Reprints or correspondence: Dr. William J. Burman, Denver Public Health,
605 Bannock Street, Denver Colorado 80204.
Clinical Infectious Diseases 1998;27:93–6
q 1998 by the Infectious Diseases Society of America. All rights reserved.
1058–4838/98/2701–0019$03.00
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Therapy with ceftriaxone and prophylactic doses of trimethoprim-sulfamethoxazole (TMP-SMZ) was started while
awaiting further diagnostic studies. An open lung biopsy revealed acute and organizing pneumonia with focal necrosis and
a sulfur granule (figure 2). Within the sulfur granule there was
evidence of branching organisms with a beaded appearance on
gram staining. Aerobic culture of the tissue biopsy specimen
on blood agar yielded a beaded gram-positive bacterium that
did not stain partially acid fast. All anaerobic, fungal, and
mycobacterial cultures of the operative specimen were negative. This organism was identified as Streptomyces on the basis
of morphology; negative partial acid-fast staining; sensitivity
to lysozyme; and hydrolysis of xanthine, tyrosine, and casein
[1]. The organism was confirmed to be a Streptomyces species
at the Centers for Disease Control and Prevention (CDC) on
the basis of cell-wall studies that demonstrated the presence of
L-diaminopimelic acid [1, 2]. A susceptibility panel performed
with use of the broth microdilution technique at the CDC
showed that the isolate was susceptible to TMP-SMZ (MIC,
õ0.06/1.19 mg/mL), imipenem (MIC Å 0.25 mg/mL), ceftriaxone (MIC, õ1.0 mg/mL), and clarithromycin (MIC, õ0.13
mg/mL) [3].
The patient’s condition improved clinically after treatment
with ceftriaxone, which was switched to that with oral
TMP-SMZ (double-strength t.i.d.). He subsequently developed
fevers and a rash, necessitating discontinuation of TMP-SMZ.
He was then treated with clarithromycin (500 mg b.i.d.) on the
basis of the in vitro susceptibility data as well as intolerance
of TMP-SMZ, and his symptoms abated within 1 month. The
nodular infiltrates resolved after 3 months. Treatment with clarithromycin was discontinued after 6 months, and no signs of
relapse have been observed in follow-up evaluations performed
over 8 months.
Discussion and Review of the Literature
The aerobic actinomycetes, including Streptomyces and
Nocardia species, are bacteria that belong in the order Actino-
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Figure 1. A, Anteroposterior chest radiograph obtained on admission demonstrates multiple 0.5 – 3.0-cm nodules in both lungs of a patient
with streptomyces pneumonia. B, CT of the chest below the carina showing these nodules without evidence of cavitation.
mycetales. At one time these microorganisms were classified
as fungi because they possess true aerial hyphae, but they are
now recognized as bacteria. Most actinomycetes are grampositive, filamentous, partially acid-fast, branched bacteria.
Species of the genus Streptomyces are characterized by formation of extensive, branched aerial hyphae with long chains of
conidia and the cell-wall peptidoglycan L-diaminopimelic acid
[1, 2]. The natural habitat of most Streptomyces species is the
soil, where they are found on surfaces that support their mycelial growth [4]. More than 3,100 Streptomyces species have
been described [5]. Initially, identification to the species level
was based on subjectively chosen morphological features. Recently, morphological characteristics have given way to more
objective classification methods such as rapid enzyme tests of
fluorophores [5, 6]. Currently, the species taxonomy is chang-
Figure 2. Hematoxylin-eosin-stained section from the open lung
biopsy specimen showing necrosis, neutrophilic inflammation, and a
sulfur granule in the center of the field (original magnification, 1400).
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ing rapidly as new techniques allow more specific differentiation.
The clinical significance of recovering this organism is often
unclear because there have been many reports of isolation of
Streptomyces species without definitive evidence of its pathogenic role. S. violaceoruber, S. coelicolor, and S. albus have
been isolated from dental caries, blood, tonsils, skin, and sputum [4]. S. candidus has been isolated from the purulent exudate
of a fractured patella, S. horton from pus, and S. willmorei
from a liver abscess [4]. In addition, S. gedaensis has been
recovered from sputum and abscesses [4]. However, none of
these reports described the Streptomyces species as the principal pathogen. Therefore, the role of Streptomyces species in
visceral infections has been controversial in the setting of
mixed infections in which other probable primary pathogens
have also been isolated.
The present case was unusual, as only three other cases of
streptomyces pneumonia have been described [7 – 9]. It clearly
illustrates the potential of Streptomyces species to cause invasive infection. Streptomyces was determined to be the primary
pathogen because the histopathological finding of a sulfur granule was compatible with the presence of this organism, other
pathogens were excluded by culture, and Streptomyces species
were isolated in pure culture of the tissue specimens. In addition, the response to therapy was dramatic, although the therapy
was active against organisms other than Streptomyces species.
Histopathologic examination of the lung biopsy specimen
revealed a sulfur granule, a finding typical of visceral actinomyces infection and visceral botryomycosis caused by bacteria
such as Staphylococcus aureus and species of Pseudomonas
or Proteus. In contrast, Nocardia species have been reported
to cause sulfur granules in mycetomas but not in visceral infections [10]. Thus, we may add Streptomyces species to the list
of potential pathogens causing sulfur granules in visceral infection.
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Streptomyces Pneumonia
To identify all reports of invasive disease due to Streptomyces species, we performed a MEDLINE search of the worldwide literature through January 1997 and reviewed the references from previous papers on Streptomyces. Mycetomas are
the most common clinical presentation of streptomyces infection, and S. somaliensis has been identified as one of the principal etiologic agents of actinomycetoma in South America, Africa, India, Mexico, Malaysia, and the United States [11, 12].
The clinical presentation, microbiology, and treatment of mycetoma have been reviewed previously; thus, we did not include
this manifestation of streptomyces infection in our review. We
defined invasive disease as infection other than superficial skin
infections or mycetoma.
There have been only a few reports of Streptomyces species
causing infection other than mycetoma (table 1). Streptomyces
species have been described as the cause of septicemia and
primary lung involvement [7]; Streptomyces was cultured in a
case of chronic pericarditis in which extensive disease was
observed in histopathologic specimens [13]; a brain abscess
has been attributed to S. griseus [14]; an abdominal abscess
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with peritonitis was caused by S. somaliensis [15]; and a case
of endocarditis has been attributed to Streptomyces species
[16]. In the majority of these cases, the outcome was good, with
resolution of the infection. Treatment included many different
antimicrobials, some with in vitro activity against Streptomyces
species.
Infections caused by aerobic actinomycetes in patients with
HIV disease have been attributed predominantly to Nocardia
and Rhodococcus species. There have been only three case
reports of streptomyces infection in HIV-infected patients. A
report by Caron and colleagues [8] described a man with advanced HIV infection and nodular infiltrates on a chest radiograph. Streptomyces species grew in culture of a bronchoscopic
specimen [8]. Ahmed and colleagues [9] described a case of
streptomyces pneumonia and monoarthritis in a patient with
advanced HIV disease. A case of lymphadenitis was attributed
to Streptomyces species in an HIV-infected patient; however,
Mycobacterium tuberculosis also grew in culture [17]. It is of
interest that rhodococcus and nocardia infections in HIV-positive patients can present as nodular infiltrates, similar to the
Table 1. Summary of data from cases of invasive infection with Streptomyces species.
Case
no.
Reference
Etiologic
organism
Presentation
Culture
Underlying
condition
Treatment
1
[PR]
Streptomyces
species
Pneumonia
Lung biopsy
specimen
HIV infection*
2
[7]
Streptomyces
species
Pneumonia,
sepsis
Blood
None
3
[8]
Streptomyces
species
Pneumonia
Bronchoscopic
specimen
HIV infection†
4
[9]
Streptomyces
species
Pneumonia,
monoarthritis
Bronchial washings,
knee aspirate
HIV infection‡
5
[13]
Pericarditis
Oxacillin, drainage
[14]
Brain abscess
Pericardial biopsy
specimen
Abscess
None
6
Streptomyces
species
S. griseus
None
7
8
[15]
[16]
S. somaliensis
Streptomyces
species
Peritonitis
Endocarditis
Abscess
Blood
None
Prosthetic
aortic valve
9
[17]
Streptomyces
species
Lymphadenitis
Cervical lymph
node
HIV infectionx
Penicillin,
streptomycin,
oxytetracycline,
drainage
Sulfadiazine
Vancomycin,
gentamicin; then
amikacin, imipenem
TMP-SMZ
Duration of
treatment
(mo)
Outcome
6
Pneumonia resolved
1
Pneumonia resolved
1
Pneumonia resolved
TMP-SMZ,
ceftriaxone; then
clarithromycin
Penicillin, sulfadiazine,
streptomycin,
aureomycin
Cefuroxime, amikacin;
then amoxicillin/
clavulanate
Piperacillin/
tazobactam; then
imipenem
NOTE. NA Å data not available; TMP-SMZ Å trimethoprim-sulfamethoxazole.
* CD4 cell count, ú400/mm3.
†
CD4 cell count, 100/mm3.
‡
CD4 cell count, 122/mm3.
§
Poor dentition noted, believed to be the route of infection.
x
CD4 cell count, 83/mm3.
#
Mycobacterium tuberculosis isolated from lymph node as well; patient also treated with isoniazid, rifampin, and nystatin.
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NA
NA
Resolution of
pneumonia,
arthritis, and
fever in 4 – 5 d
NA
3
Abscess resolved§
NA
6
NA
NA
NA
Progressive wasting
for 15 mo
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Dunne, Burman, and Wilson
findings in our case and the case reported by Caron and colleagues [8].
Invasive streptomyces infection may be more common than
these isolated case reports suggest. Many Streptomyces species
have been found in clinical isolates, most commonly S. griseus
and S. somaliensis [5, 18, 19]. The reference laboratory of the
CDC has summarized the characteristics of aerobic actinomycetes sent for species identification and susceptibility testing
between October 1985 and February 1988. S. griseus represented 7.7% of the clinical isolates, following only Nocardia
and Actinomadura species in frequency [18]. Unfortunately,
because of the lack of clinical information regarding these
isolates, it is not known whether S. griseus was a primary
pathogen. However, the frequency of S. griseus in the latter
study suggests that streptomyces infections are underreported.
Because of the paucity of well-documented cases, treatment
recommendations for streptomyces infections must be based on
in vitro data [18, 19] and analogies from treatment of nocardia
infections [20]. In the CDC evaluation of aerobic actinomycetes, a spectrum of antimicrobials were tested against
S. griseus [18]. On the basis of in vitro MICs and expected
serum concentrations, the most active drugs appeared to be
minocycline, imipenem, erythromycin, and doxycycline, with
ú80% of strains susceptible. The aminoglycoside tested in this
study appeared to have very favorable MICs as well. We used
a macrolide for therapy in our patient on the basis of this in
vitro data as well as the susceptibilities obtained from the CDC.
It is of interest that 29% of the S. griseus strains in the
above study were resistant to TMP-SMZ. This finding may be
important because TMP-SMZ is often considered the drug of
choice for treatment of nocardiosis. In the event that pathology
could be attributed to an actinomycete and the laboratory
distinction between actinomycetes has not yet been made,
TMP-SMZ may not be the best choice. Aminoglycosides, however, appear to have very effective MICs for actinomycetes
and may be appropriate for first-line therapy.
Because of these in vitro results and the limited clinical
experience, the best treatment options for visceral streptomyces
infection might be macrolides, minocycline, doxycycline, ceftriaxone, amikacin, or imipenem. In contrast to the treatment
of nocardiosis, TMP-SMZ may not be optimal treatment for
invasive infection with Streptomyces species [18]. Recommendations for duration of treatment of streptomyces infections
can only be extrapolated from experience with the treatment
of nocardiosis. Given the good results of therapy for nocardiosis [20], a 6 – 12-month course of antibiotics should be adequate for treatment of invasive streptomyces infection. Clearly,
further experience with invasive streptomyces infection is nec-
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essary to delineate the course of infection, treatment, and outcome.
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