JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
CLINICAL CASE OF THE MONTH
Group G Streptococcal Bacteremia Secondary to a
Burn Wound Infection
IMAGE 1: Right forearm with second degree partial thickness burns.
Paige Deichmann; Amol Sura;
Charles Sanders, MD;
Nisha Aravindakshan-Patel, MD;
Fred Lopez, MD
CASE PRESENTATION
A 61-year-old man presented to the emergency department
with second degree burns along his right arm and hand. He
reported that his knees suddenly gave out while holding a pot
of soup resulting in the scalding liquid spilling over his arm.
His medical history is significant for alcohol abuse, chronic
obstructive pulmonary disease, atrial fibrillation, congestive
heart failure with preserved ejection fraction, chronic knee
instability, and degenerative joint disease of the spine.
Vital signs revealed a temperature of 101.5°F, pulse 110/minute,
blood pressure 123/83 mmHg, respiratory rate of 21/minute
and oxygen saturation of 99% on ambient air. On exam, he was
tremulous and had difficulty walking. His right upper extremity
had patchy areas of burns, with the largest lesion measuring
12 x 5 cm (Image 1 and 2). There were ruptured blisters along
his thumb and forearm and a non-ruptured blister on his index
finger. The wound bed appeared pale pink, and the surrounding
skin appeared intact with no signs of acute infection. He
also had a small abrasion on the right side of his scalp. His
complete blood count revealed a white blood cell count
of 11.4 (4-10 x 10^9/L). His renal function, electrolytes,
and liver enzymes were within normal range. He
was noted to be intoxicated with alcohol and he
had an elevated blood alcohol level of 41 mg/
dl (<15 mg/dl). A non-contrast computed
tomography (CT) of the head revealed
diffuse cerebral and cerebellar atrophy. He
was admitted for management of alcohol
withdrawal and wound care.
On day three of admission, he appeared
acutely ill and a temperature of 101.2°F was
recorded. Blood cultures were drawn and
empiric antibiotic therapy was initiated with
vancomycin and piperacillin-tazobactam.
Blood cultures revealed the growth of betahemolytic Group G Streptococcus (Image
3). Antibiotics were narrowed to intravenous
penicillin G and he was discharged home to
complete a two week course of antibiotics.
20 J La State Med Soc VOL 169 JANUARY/FEBRUARY 2017
IMAGE 2: Right hand with second degree partial thickness burns and ruptutred blisters.
IMAGE 3: Growth on a blood agar plate. Note the large, gray colonies surrounded by zones
of β-hemolysis, which is characteristic of Group G streptococcus
JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
DISCUSSION
Introduction
Each year in the United States, an estimated 486,000 people
sustain burns which require medical attention.1 With the loss
of a natural barrier to the environment the underlying dermis
and soft tissues are exposed to microbial colonization. The
most common organisms associated with noscomial burn
wound infections are Gram-positive organisms including
Staphylococcus aureus (23%), Enterococcus species (11%), and
coagulase-negative staphylococci (4.3%). Potential Gramnegative pathogens include Pseudomonas aeruginosa (19.3%),
Escherichia coli (7.2%), Serratia marcescens (3.5%), and Klebsiella
pneumonia (2.6%).2 Isolation of fungal pathogens, most
often Candida albicans (3.5%), is less common. Streptococcal
species-associated sepsis in burn patients have been reported
in the literature, but are usually due to Group A β-hemolytic
Streptococcus.3 Group G streptococcus is part of normal human
commensal flora of the skin, upper airway, gastrointestinal
tract, and genitourinary system. It most closely resembles
Group A streptococcus in genetic sequencing and also shares
many of the same virulence factors resulting in similar clinical
manifestations.4
MICROBIOLOGY
Taxonomy
Group G β-hemolytic streptococci were first identified by
Lancefield and Hare in 1935 and were not considered to be
pathogenic organisms.5,6 Today several species of streptococci
carry the Lancefield G carbohydrate antigen on their cell wall,
and are categorized as a Group G Streptococcus. These species
include Streptococcus dysgalactiae, Streptococcus canis, and the
Streptococcus anginosus group which includes S. anginosus,
S. constellatus, and S. intestinalis.4,7,8,9,10,11 Isolates found in
humans were initially categorized as Streptococcus dysgalactiae
subspecies which expressed either C or G antigens.
Sixty years later, Vandamme et al. further divided Streptococcus
dysgalactiae into two separate subspecies based on chemical
properties and appearance. Group G streptococcus generally
form large (>0.5mm) pearl gray colonies on sheep blood agar.12,13
In 1999, Vieira et al classified all β-hemolytic, large-colony
forming Group G streptococci found in human infections as
Streptococcus dysgalactiae subspecies equisimilis (SDSE)9,12,14,15,16
and Streptococcus dysgalactiae subspecies dysgalactiae (SDSD)
for animal isolates of Group C.17,18,19 The two subspecies are
clustered together on phylogenetic trees because they share
some genes but they do not have any identical alleles.18
Zoonotic infections with SDSD infection have been reported as
case reports in the the literature but are uncommon.20
In our patient’s case, the streptococcal isolate was identified
as beta-hemolytic based on the clear zones of total hemolysis
and demonstration of large colony types greater than 0.5 mm
with no odor. The isolate then underwent latex agglutination
testing which determined the Lancefield group as G. No
further taxonomic classification was performed to subspeciate
the isolate in our lab and is not usually performed in standard
clinical laboratories.19
Virulence Factors and Pathogenic Mechanisms
The majority of virulence factors found in Group G streptococci
are also found in Group A streptococci (i.e., Streptococci
pyogenes), including adhesions, the M protein, Streptolysin O
and Streptolysin S, C5a peptidase, streptokinase, and various
superantigens.10, These factors are shared via horizontal gene
transfer from S. pyogenes to SDSE via streptococcal phages.4,18
Accordingly, these genetic similarities result in Group A
streptococcus and Group G streptococcus sharing similar
clinical manifestations, including skin and soft tissue infections,
pharyngitis, bacteremia, and toxic shock-like syndrome.16,18,22,23
The clinical features of Group G streptococcal infections can
be attributed to its virulence factors which include adhesins,
toxins, and proteases. Adhesions facilitate invasion of bacteria
through damaged epithelial and mucosal surfaces.12 The M
protein virulence factor encoded by the emm gene facilitates
the characteristic spreading of SDSE infections by resisting
phagocytosis, inhibiting the complement cascade and disrupting
the coagulation system.10,12,16,24 This is further exacerbated by
streptokinase, which converts plasminogen to plasmin and
thereby prevents clot formation and facilitating spread of the
organism.10,12 Toxins of note in SDSE include Streptolysin O
and Streptolysin S. These toxins are involved in necrotizing soft
tissue infection and also are responsible for the phenotypic
β-hemolysis seen on blood agar plates.10,12 Superantigens also
play a significant role in more severe streptococcal infections
such as streptococcal toxic shock-like syndrome.
EPIDEMIOLOGY
Group G streptococci inhabit human epithelial and mucosal
surfaces. From these sites, the organism can invade into deeper
structures or into normally sterile sites, such as the blood stream,
to produce disease.25 Group G streptococcal infections are more
common in men than women16,19 and increase in incidence with
age. The organism can be transmitted from person to person.
The median reported age at presentation of patients with GGS
bacteremia varies in the literature, but generally falls between
ages 55-67.5,16,19,26,27 A distinctive feature of Group G streptococcal
infection is its association with underlying chronic illness. Of
patients with SDSE infection, some of the common coexisting
comorbidities include cardiovascular disease, diabetes mellitus,
malignancy, and alcohol abuse.5,16,19,28 Multiple sources have
reported an increase in the frequency of reports of Group G
streptococcal infections.21 The explanation for this increase
remains unclear; Rantala et al. hypothesized that the aging
population and increased survival of adults with chronic disease
could be a factor. Watsky et al suggests that although virulence
factors contribute to an organism’s pathogenicity it is disruption
of mucosal barriers which plays the major role in overcoming
host defense.29
J La State Med Soc VOL 168 JULY/AUGUST 2016
21
JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
CLINICAL PRESENTATION
Group A streptococci and Group G streptococci can cause
similar types of infections. Like Group A streptococci, Group
G streptococci can cause skin and soft tissue infections,
such as wound infections, erysipelas, cellulitis,19 bacteremia,
endocarditis,25 acute rheumatic fever, acute glomerulonephritis,
and toxic shock-like syndrome22 associated with necrotizing
fasciitis.10 The most common portal of entry in patients with
GGS bacteremia is the skin.16,19,26,27,28 This further highlights the
importance of dermatologic disease in the elderly populations
as a predisposing factor to infection. This includes lower leg
cellulitis and decubitis ulcers,27 and skin malignancies including
squamous cell cancer and mycosis fungoides.26 In patients with
Group G Streptococcal bacteremia, the mortality rate varies
between 2-18 percent.19
5.
6.
7.
8.
9.
10.
11.
TREATMENT
Group G streptococcal bacteremia are susceptible responsive
to β-lactam antibiotic therapy. Improvement in clinical course
can be seen within 24-48 hours of antibiotic therapy initiation.27
The drug of choice for GGS bacteremia is intravenous penicillin
G.19,26,28,30,31 Other effective treatment options include second
and third generation cephalosporins, vancomycin, and
fluoroquinolones.26,32 The resistance to macrolide antibiotics, like
erythromycin, varies; with some regions such as North American
reporting macrolide resistance as high as 19%.12 Thus, these
antibiotics may not serve as reliable empiric treatment options.
In cases of toxic shock-like syndrome with necrotizing fasciitis,
clindamycin is often added to β-lactam antibiotic therapy for
toxin inhibition by facilitating phagocytosis of streptococci by
inhibiting M protein and suppressing both penicillin binding
proteins needed for cell wall synthesis and tumor necrosis factor
production.33
CONCLUSION
Group G streptoccocus is a pathogen which should be
considered in the setting of burn wound infections. Infections
with this organism are typically seen in patients with chronic
underlying illness such as alcohol abuse, cardiovascular disease,
diabetes mellitus, and malignancy.
REFERENCES
1.
2.
3.
4.
National Hospital Ambulatory Medical Care Survey: 2011 Emergency
Department Summary Tables (accessed on March 1, 2016 at http://www.
cdc.gov/nchs/data/ahcd/nhamcs_emergency/2011_ed_web_tables.pdf
Mayhall CG. The epidemiology of burn wound infections: then and
now. Clin Infect Dis. 2003 Aug 15;37(4):543-50. Epub 2003 Jul 30.
Bang RL, Gang RK, Sanyal SC, Mokaddas E, Ebrahim MK. Burn septicaemia:
an analysis of 79 patients. Burns 1998 Jun;24(4):354-61.
Shimomura Y, Okumura K, Murayama SY, Yagi J, Ubukata K, Kirikae
T, Miyoshi-Akiyama T. Complete genome sequencing and analysis of a
Lancefield group G Streptococcus dysgalactiae subsp. equisimilis strain
causing streptococcal toxic shock syndrome (STSS). BMC Genomics. 2011
Jan 11; 12:17. doi: 10.1186/1471-2164-12-17.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
22 J La State Med Soc VOL 169 JANUARY/FEBRUARY 2017
Lancefield RC and Hare R. The serological differentiation of pathogenic
and non-pathogenic streptococci from parturient women. J Exp Med 1935;
61: 335-349 as read in Smyth EG, Pallett AP, and Davidson RN. Group G
Streptococcal endocarditis: two case reports, a review of the literature and
recommendations for treatment. J Infect Dis. 1988 16:169-176.
Bennett, JE, Dolin, R, and Blaser, MJ. Viridans Streptococci and Groups C and
G Streptococci. Mandell, Douglas and Bennett’s Principles and Practice of
Infectious Diseases. 8th edition 2173-2177.
Farrow, J. A. E., and M. D. Collins. 1984. Taxonomic studies on streptococci of
serological groups C, G, and L, and possibly related taxa. Sys Appl Microbiol.
5:483–493.
Kilpper-Balz, R., and K. H. Schleifer. 1984. Nucleic acid hybridization and cell
wall composition studies of pyogenic streptococci. FEMS Microbiol. Lett.
24:355–364
Facklam, R. What happened to the streptococci: overview of the taxonomic
and nomenclature changes. Clin Microbiol Rev. 2002; 15: 613-30.
Lo HH, Cheng WS. Distribution of virulence factors and association with
emm polymorphism or isolation site among beta-hemolytic group G
Streptococcus dysgalactiae subspecies equisimilis. APMIS. 2015 Jan;
123(1):45-52. doi: 10.1111/apm.12305.
Liao CH, Liu LC, Huang YT, Teng LJ, Hsueh PR. Bacteremia caused by group
G Streptococci, Taiwan. Emerg Infect Dis. 2008 May; 14(5):837-40. doi:
10.3201/eid1405.070130.
Brandt CM, Spellerberg B. Human infections due to Streptococcus
dysgalactiae subspecies equisimilis. Clin Infect Dis. 2009 Sep 1;49(5):76672. doi: 10.1086/605085.
Jorgensen, JH and Pfaller, MA (Eds.) Chapter 20: Streptococcus. Manual of
Clinical Microbiology. 11th ed.
Vieira VV, Teixeira LM, Zahner V, Momen H, Facklam RR, Steigerwalt
AG, Brenner DJ, Castro AC. Genetic relationships among the different
phenotypes of Streptococcus dysgalactiae strains. Int J Syst Bacteriol. 1998
Oct;48 Pt 4:1231-43.
Gherardi G, Imperi M, Palmieri C, Magi G, Facinelli B, Baldassarri L,
Pataracchia M, Creti R. Genetic diversity and virulence properties of
Streptococcus dysgalactiae subsp. equisimilis from different sources. J Med
Microbiol. 2014 Jan;63(Pt 1):90-8. doi: 10.1099/jmm.0.062109-0. Epub 2013
Rantala S,
Vahakuopus
S,
Vuopio-Varkila
J,
Vuento
R, Syrjanen J. Streptococcus dysgalactiae subsp. equisimilis Bacteremia,
Finland, 1995-2004. Emerg Infect Dis. 2010 May;16(5):843-6. doi: 10.3201/
eid1605.080803.
Vandamme P, Pot B, Falsen E, Kersters K, Devriese LA.Taxonomic study of
Lancefield streptococcal groups C, G, and L (Streptococcus dysgalactiae)
and proposal of S. dysgalactiae subsp. equisimilis subsp. Int J Syst Bacteriol.
1996 Jul; 46(3):774-81. Erratum in: Int J Syst Bacteriol 1997 Apr;47(2):605.
Jensen A, Kilian M. Delineation of Streptococcus dysgalactiae, its
subspecies, and its clinical and phylogenetic relationship to Streptococcus
pyogenes. J Clin Microbiol. 2012 Jan;50(1):113-26. doi: 10.1128/JCM.0590011. Epub 2011 Nov 9.
Rantala S. Streptococcus dysgalactiae subsp. equisimilis bacteremia: an
emerging infection. Eur J Clin Microbiol Infect Dis. 2014 Aug; 33(8):130310. doi: 10.1007/s10096-014-2092-0. Epub 2014 Mar 29. Review.
Koh, TH et al. 2009. Streptoccoccal cellulitis following preparation of fresh
raw seafood. Zoonoses Public Health 56:206-208.
Hule GP, Karmarkar MG, Cameron A, Hase N, Khopkar U, Mehta PR, McNeilly
CL, McMillan D, Sriprakash KS.Seropositivity for Antibodies to DRS-G, a
Virulence Factor from Streptococcus dysgalactiae subsp. equisimilis, Is an
Independent Risk Factor for Poststreptococcus Glomerulonephritis and
Chronic Kidney Disease in Mumbai, India. Clin Vaccine Immunol. 2015
Aug;22(8):938-42. doi: 10.1128/CVI.00275-15. Epub 2015 Jun 17.
Fernández-Aceñero MJ, Fernández-López P. Cutaneous lesions associated
with bacteremia by Streptococcus dysgalactiae. J Am Acad Dermatol. 2006
Nov; 55(5 Suppl):S91-2.
Mylvaganam H, Bruun T, Vindenes HA, Langeland N, Skrede S. Molecular
epidemiological investigation of an outbreak of invasive beta-haemolytic
streptococcal infection in western Norway. Clin Microbiol Infect. 2009 Mar;
15(3):245-52. doi: 10.1111/j.1469-0691.2008.02664.x.
Loubinoux J, Plainvert C, Collobert G, Touak G, Bouvet A, Poyart C; CNR-Strep
Network. Adult invasive and noninvasive infections due to Streptococcus
dysgalactiae subsp. equisimilis in France from 2006 to 2010. J Clin Microbiol.
2013 Aug; 51(8):2724-7. doi: 10.1128/JCM.01262-13.
Gavira, JM and Bisno L. 2000. Group C and G streptocci. P238-254. In DL
Stevens and EL Kaplan (Eds.) Streptococcal infections: clinical aspects,
microbiology and molecular pathogenesis. Oxford University Press, New
York, NY as cited in Lopardo HA, Vidal P, Sparo M, Jeric P, Centron D, Facklam
JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
26.
27.
28.
29.
30.
31.
32.
33.
RR, Paganini H, Pagniez NG, Lovgren M, Beall B. Six-month multicenter study
on invasive infections due to Streptococcus pyogenes and Streptococcus
dysgalactiae subsp. equisimilis in Argentina. J Clin Microbiol. 2005 Feb;
43(2):802-7.
Broyles LN, Van Beneden C, Beall B, Facklam R, Shewmaker PL, Malpiedi P,
Daily P, Reingold A, Farley MM.Population-based study of invasive disease
due to beta-hemolytic streptococci of groups other than A and B. Clin
Infect Dis. 2009 Mar 15;48(6):706-12. doi: 10.1086/597035.
Venezio FR, Gullberg RM, Westenfelder GO, Phair JP, Cook FV. Group G
streptococcal endocarditis and bacteremia. Am J Med. 1986 Jul; 81(1):29-34.
Watsky KL, Kollisch N, Densen P. Group G streptococcal bacteremia. The
clinical experience at Boston University Medical Center and a critical review
of the literature. Arch Intern Med. 1985 Jan;145(1):58-61.
Beebe, JL and Koneman, EW. Recovery of Uncommon Bactremia from
Blood: Association with Neoplastic Disease. Clinical Microbiology Reviews,
July 1995, 336-356.
Young K, Luni FK, Yoon Y. Toxic Shock Syndrome: An Unusual Organism. Am
J Med Sci. 2015 Aug 4. [Epub ahead of print]
Behera B, Mathur P, Bhardwaj, Jain N, Misra MC, Kapil A and Singh S.
Antibiotic susceptibilities, streptococcal pyrogenic exotoxin gene profiles
among clinical isolates of group C or G Streptoccocus dysgalactiae subsp.
equisimilis & of group G S. anginosus group at a tertiary care center. Indian
J Med Res 2014;139: 438-445.
Tsai CT, Chi CY, Ho CM, Lin PC, Chou CH, Wang JH, Wang JH, et al. Correlation
of virulence genes to clinical manifestation and outcome in patients with
Streptococcus dysgalactiae subspecies equisimilis bacteremia.
Kalyan S, Chow AW. Staphylococcal toxic shock syndrome toxin-1 induces
the translocation and secretion of high mobility group-1 protein from both
activated T cells and monocytes. Mediators Inflamm. 2008.
Paige Deichmann and Amol Sura are medical students at the Louisiana State
University School of Medicine in New Orleans; Dr. Sanders is the chair of the
department of medicine, the Edgar Hull professor of medicine, and a professor
of microbiology, immunology, and parasitology at the LSUHSC-New Orleans;
Dr Aravindakshan-Patel is a fellow in the section of infectious diseases at the
LSUHSC-New Orleans; Dr. Lopez is the Richard Vial professor and vice chair of
education in the department of medicine at LSUHSC-New Orleans.
J La State Med Soc VOL 169 JANUARY/FEBRUARY 2017
23