Pediatr Blood Cancer 2005;44:1–3
Myositis Complicating Viridans Streptococcal
Sepsis in Childhood Leukemia
John T. Sandlund, MD,1,4Scott C. Howard, MD,1,2,4Nobuko Hijiya, MD,1,4Ching-Hon Pui, MD,1,4
Jerry L. Shenep, MD,3,4and Elisabeth E. Adderson, MD3,4*
Bacteremia or sepsis caused by viridans streptococci
commonly complicates the intensive therapy of pediatric
tions are rare. Here, we report two children with focal
myositis associated with viridans streptococcal sepsis, in
one case complicated by rhabdomyolysis.
A 15-year-old boy was diagnosed with acute myeloid
leukemia in October 2003. He was admitted to hospital
15 days following his second consolidation therapy that
absolute neutrophil count of 0/ml. He was noted to have
Grade II mucositis. Penicillin-susceptible a-hemolytic
streptococci (not further speciated) and Bacillus cereus
were isolated from peripheral blood and central line
cultures. Subsequent blood cultures were negative after
vancomycin and cefepime therapy was commenced, but
he remained febrile and complained of pain in the right
lower extremities was unremarkable. His creatine kinase
was normal on the sixth day of hospitalization, however,
magnetic resonance imaging (MRI) of the right lower
extremity demonstrated a bright abnormality on STIR
sequences and mild enhancement with gadolinium, con-
for an additional 10 days. His fever and calf pain resolved
completely over 8 days. His subsequent chemotherapy
was complicated by hepatosplenic candidiasis, but he
remains otherwise well and in remission.
of acute lymphoblastic leukemia in December 2003 and
treated with intensive chemotherapy, including high-dose
cytarabine. She was admitted to hospital 14 days after the
start of her most recent chemotherapy with fever to 408C,
light touch of both calves with no swelling or erythema,
and a negative Homan sign. At the time of admission her
absolute neutrophil count was 0/ml. Streptococcus mitis,
susceptible to cefotaxime and vancomycin, was isolated
from blood cultures drawn from a central venous catheter
Hematogenous focal infections are a rare
complication of bacteremia or sepsis caused by
viridans-group streptococci. We describe two
patients with acute leukemia who developed
myositis during a-hemolytic streptococcal bac-
teremia. Children complaining of severe muscle
pain associated with viridans streptococcal
infections should be carefully evaluated for the
presence of focal pyogenic complications and
rhabdomyolysis. The severity of infectious myo-
sitis is highly variable, depending on the etio-
logic organism and host immunity, making
individualized treatment the most effective
? 2004 Wiley-Liss, Inc.
leukemia; myositis; viridans streptococcus
1Department of Hematology-Oncology, St. Jude Children’s Research
Hospital, Memphis, Tennessee
2Department of International Outreach, St. Jude Children’s Research
Hospital, Memphis, Tennessee
3Department of Infectious Diseases, St. Jude Children’s Research
Hospital, Memphis, Tennessee
4Department of Pediatrics, University of Tennessee Health Science
Center, Memphis, Tennessee
C-H Pui is the American Cancer Society F.M. Kirby Clinical Research
Grant sponsor: National Institutes of Health; Grant number: P30
CA21765;Grant sponsor: American Cancer Society FM Kirby Clinical
Research Professorship; Grant sponsor: American Lebanese Syrian
Associated Charities (ALSAC).
*Correspondence to: Elisabeth E. Adderson, Department of Infectious
Diseases, 332 N. Lauderdale St., Memphis, TN 38120.
Received 26 April 2004; Accepted 1 September 2004
? 2004 Wiley-Liss, Inc.
and peripheral vein. She was empirically treated with
vancomycin, meropenem, and tobramycin. Although
subsequent blood cultures were sterile, the patient
continued to be highly febrile and complained of severe
pain in the left hip and leg. Her serum creatine kinase
concentration was 1,013 units/L (normal 30–135) and
urine myoglobin 232 mg/L (normal <29) on the second
and third days of hospitalization, respectively. Doppler
analysis of the common femoral, superficial femoral, and
common popliteal veins confirmed normal venous flow in
each extremity. MRI demonstrated high T2 signal in the
enhancement with gadolinium contrast (Fig. 1). No fluid
collections were present within joints or soft tissues. She
was treated with urinary alkalinization and aggressive
to a normal concentration over 8 days and her fever and
myalgia resolved over 9 days. Shewas treated with a total
23 days of antibiotic therapy. Unfortunately, her malig-
nancy responded poorly to salvage chemotherapy and
she expired of complications of progressive leukemia
2 months later.
Intensive therapy for childhood leukemia has resulted
in dramatic improvements in long-term survival over the
past 2 decades [1,2]. However, this success has been
complicated by an increasing frequency of infectious
complications [3–6]. Bacteremia caused by viridans-
patients in 1978, and these bacteria are now responsible
for 9–30% of bloodstream infections in these persons
The viridans streptococci include members of the
mutans, salivarius, anginosus (milleri), sanguinus, and
mitis groups . Most strains are alpha-hemolytic,
leucine aminopeptidase positive, and pyrrolidonylaryla-
midase negative, and fail to grow in 6.5% NaCl broth.
Viridans streptococci normally colonize the oral cavity,
gastrointestinal tract, and vagina . In nonimmuno-
compromised patients these bacteria are generally of low
virulence. The anginosus (milleri) group, however, is
associated with endocarditis and odontogenic and brain
It is not surprising, given the natural habitat of viridans
streptococci that bacteremia caused by these organisms in
immunocompromised patients is associated with chemo-
therapeutic regimens causing mucositis, most notably
those including high-dose cytarabine, and with profound
with viridans streptococcal sepsis, but the proportion of
these that represent true pulmonary infection, rather than
acute respiratory distress syndrome is not clear . The
incidence of shock and acute respiratory distress syn-
drome associated with viridans sepsis range from 13% to
33% and 0% to 28%, respectively [8,11,15]. Other than
pneumonia and meningitis (observed in up to 2.5% of
patients), focal complications of viridans-group strepto-
cocci in immunocompromised persons are rare. To our
knowledge, this is the first report of myositis related to a-
hemolytic streptococcal bacteremia in immunocompro-
mised patients. Marino and coworkers , however,
reported an adult who developed multiorgan failure and
diffuse rhabdomyolysis during viridans streptococcal
sepsis shortly after receiving a bone marrow transplant
for acute myeloid leukemia. Our experience suggests that
severe myalgiaand rhabdomyolysis may be a direct result
of viridans streptococcal infection.
The relative roles of Bacillus cereus and viridans
streptococcus in the first patient’s myositis cannot be
viridans streptococci in the second patient underpins the
association of viridans streptococci and myositis. Al-
though our patients developed symptoms within a few
days of one another, it is likely that their similar pre-
a different strain of bacteria. However, it is also possible
that two different streptococcal species share a virulence
factor that promotes soft tissue tropism.
Infectious myositis may be caused by a variety of
bacteria, viruses, and parasites. The spectrum of these
infections range from classical bacterial pyomyositis,
caused most commonly by Staphylococcus aureus or
Group A Streptococcus pyogenes, to the self-limited
‘‘benign acute childhood myositis’’ associated with re-
spiratory viral infections, particularly influenza .
Infection is an uncommon cause of rhabdomyolysis,
accounting for less than 8% of episodes in adults and
rhabdomyolysis more frequently complicates gram posi-
trates increased STIR signal in the right calf muscles (arrow). MRI of
Case 2 (right panel) shows high T2 signal in the muscles of the legs,
greatest on the left side.
Lower extremity MRIs: MRI of Case 1 (left panel) demons-
2 Sandlund et al.
induce muscle damage is not completely understood. Download full-text
Pyogenic bacteria are able to directly invade tissues
whereas others, most notably Clostridium species, secrete
myotoxins or cytolysins capable of injuring myocytes
The optimal management of serious focal infections in
immunocompromised persons is controversial. Surgical
therapy is recommended for most patients with pyogenic
myositis, especially those complicated by tissue necrosis
or abscess formation . That our patients responded
well to antibiotic therapy alone suggests that prompt
initiation of antibiotic therapy may allow some cases of
myositis to be managed without surgical intervention.
Alternatively, it is conceivable that our patient’s
symptoms resulted from an inappropriate inflammatory
response to a relatively small microbial burden, instead of
the large numbers of bacteria and direct tissue damage
typically observed in pyogenic myositis in immunocom-
petent hosts. MRI or computerized tomography may be
helpful in identifying focal fluid collections that require
incision and drainage; however, neither modality can be
and close follow-up is mandatory with repeat imaging in
patients with persistent symptoms. As in the case of deep
soft tissue infections in immunocompetent persons, if the
severity and extent of infection cannot be confidently
ascertained, surgical exploration and debridement of any
devitalized tissue is indicated.
Clinicians should be aware that myositis may compli-
cate viridans streptococcal sepsis in childhood leukemia,
setting should be evaluated for the presence of rhabdo-
N Engl J Med 2004;350:1535–1548.
2. Hann IM, Webb DK, Gibson BE, et al. MRC trials in childhood
acute myeloid leukaemia. Ann Hematol 2004;83:S108–S112.
tive study of 288 episodes of bacteremia in neutropenic cancer
patients in a single institution. Eur J Microbiol Inf Dis 1996;15:
4. Howard SC, Pedrosa M, Lins M, et al. Establishment of a pediatric
leukemia in a resource poor area. JAMA 2004;291:2471–2475.
5. Lehrnbecher T, Varwig D, Kaiser J, et al. Infectious complications
in pediatric acute myeloid leukemia: Analysis of the prospective
multi-institutional clinical trial AML-BFM93. Leukemia 2004;18:
6. Wehl G, Allerberger F, Heitger A, et al. Trends in infection morbi-
dity in a pediatric oncology ward, 1986–1995. Med Pediatr Oncol
7. Pizzo PA, Lakisch S, WitebskyFG. Alpha-hemolytic streptococci:
Clinical significance in the cancer patient. Med Pediatr Oncol
8. Ahmed R, Hassall T, Morland B. Viridans streptococcus bacter-
emia in children on chemotherapy for cancer: An underestimated
problem. Pediatr Hematol Oncol 2003;20:439–444.
9. Sotiropoulos SV, Jackson MA, Woods GM, et al. Alpha-
streptococcal septicemia in leukemic children treated with
continuous or large dosage intermittent cytosine arabinoside.
Pediatr Inf Dis J 1989;8:755–758.
10. Tunkel AR, Sepkowitz KA. Infections caused by viridans strepto-
cocci in patients with neutropenia. Clin Inf Dis 2002;34:1524–
11. Paganini H, Staffolani V, Zubizarreta P,et al. Viridans streptococci
study of predisposing factors. Eur J Cancer 2003;39:1284–1289.
12. Facklam R. What happened to the streptococci: Overview of
taxonomic and nomenclature changes. Clin Microbiol Rev 2002;
13. Shenep JL. Viridans-group streptococcal infections in immuno-
compromised hosts. Int JAntimicrob Agents 2000;14:129–135.
14. Sotiropoulos SV, Jackson MA, Woods GM, et al. Alpha-
streptococcal septicemia in leukemic children treated with con-
tinuous or large dosage intermittent cytosine arabinoside. Pediatr
Infect Dis J 1989;8:755–758.
15. Okamoto Y, Ribeiro RC, Srivastava DK, et al. Viridans strepto-
coccal sepsis: Clinical features and complications in childhood
acute myeloid leukemia. J Pediatr Hem Oncol 2003;25:696–703.
16. Martino R, Nomdedeu J, Sureda A, et al. Acute rhabdomyolysis
complicating viridans streptococal shock syndrome. Acta Haema-
17. Nizet V. Myositis and pyomyositis. In: Long SS, Pickering LK,
Prober CG, editors. Principles and practice of pediatric infectious
diseases. New York: Churchill Livingstone; 2003. pp 458–462.
18. Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdo-
myolysis. Medicine 1982;61:141–152.
19. Betrosian A, Thireos E, Kofinas G, et al. Bacterial sepsis-induced
rhabdomyolysis. Intens Care Med 1999;25:469–474.
20. Friman G, Ilback NG, Beisel W. Effects of Streptococcus
pneumoniae, Salmonella typhimurium and Francisella tularensis
infections on oxidative, glycolytic and lysosomal enzyme activity
in red and white skeletal muscle in the rat. Scand J Infect Dis
21. Gubbay AJ, Isaacs D. Pyomyositis in children. Pediatr Infect Dis
22. Falasca GF, Reginato AJ. The spectrum of myositis and rhabdo-
23. May DA, Disler DG, Jones EA, et al. Abnormal signal intensity in
skeletal muscle at MR imaging: Patterns, pearls, and pitfalls.
Viridans Streptococcal Myositis3