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Groups C and G Streptococci
PART III Etiologic Agents of Infectious Diseases SECTION A Bacteria
122 Groups C and G Streptococci David B. Haslam and Joseph W. St. Geme III
The β-hemolytic streptococci can be subdivided on the basis of whether they form large colonies or minute colonies on solid agar. Most notable among those β-hemolytic streptococci that form large colonies are Streptococcus pyogenes (group A) and Streptococcus agalactiae (group B). Among the remaining Lancefield-reactive β-hemolytic streptococci, groups C and G organisms are most commonly associated with human disease.1 In this chapter, groups C and G streptococci refer exclusively to the large-colony–forming “S. pyogenes-like” organisms. Minute-colony– forming species belonging to groups C and G are placed in the S. anginosus group (formerly Streptococcus milleri) (see Chapter 121). In some hospitals, group G streptococci cause more cases of invasive disease than does S. pyogenes,1 perhaps because these organisms are more commonly associated with infection in immunocompromised hosts.
CHARACTERISTICS OF THE PATHOGENS Groups C and G organisms, like all streptococci, are catalase-negative, gram-positive cocci. Human isolates are almost always β hemolytic on sheep blood agar culture, although rare isolates are α hemolytic or nonhemolytic. Groups C and G organisms resemble S. pyogenes on blood agar, thus necessitating biochemical testing and serologic analysis for definitive identification. Latex agglutination typically is used in clinical microbiology laboratories to determine the Lancefield grouping of large-colony β-hemolytic streptococci. Most groups C and G isolates are resistant to bacitracin, but significant fractions are susceptible, thereby making bacitracin susceptibility testing alone unreliable in distinguishing these organisms from S. pyogenes. Hydrolysis of L-pyrrolidonyl-Pnaphthylamide (PYR reaction) is a useful adjunctive test because the groups C and G organisms are PYR negative and S. pyogenes is PYR positive. Colony morphology and lack of acetoin production (negative results of the Voges-Proskauer [VP] test) differentiate large-colony groups C and G streptococci from the S. anginosus group (Table 122.1).
Speciation Large-colony Group C and G human isolates now are grouped together as Streptococcus dysgalactiae subsp. equisimilis.2 The remaining largecolony group C streptococci, predominantly animal pathogens, are grouped as S. dysgalactiae subsp. dysgalactiae. Nonhuman group G isolates are often considered part of a single species designated as Streptococcus canis and are genetically distinct from the S. dysgalactiae subsp. equisimilis group G organisms.
Virulence Properties Groups C and G streptococci share several virulence factors with S. pyogenes. Both group C and group G isolates produce streptolysin O
and can stimulate an increase in the anti–streptolysin O (ASO) titer. In addition, isolates of both groups produce degradative enzymes, including hyaluronidase. Group G isolates also produce streptolysin S and often produce DNAase that is antigenically similar to S. pyogenes DNAase B. Moreover, group G streptococci produce an M protein that is similar immunologically to that of S. pyogenes and can be responsible for the occasional association of group G isolates with postinfectious glomerulonephritis. Glomerulonephritis following group C streptococcal infection also is well described. Whereas these isolates fail to produce an M protein, they can produce endostreptosin, which is believed to be involved in the pathogenesis of S. pyogenes–induced glomerulonephritis. A toxic shock–like syndrome associated with group C and G streptococcal infection has been reported. Some of these cases have been associated with a strain that possesses genes homologous to the S. pyogenes streptococcal pyogenic exotoxins or that elaborates an unidentified substance with superantigen activity.3
EPIDEMIOLOGY Pharyngeal carriage of groups C and G streptococci is detected in up to 5% of healthy children. In tropical climates, the pharyngeal carriage rate is much higher. The skin, gastrointestinal tract, and vagina also are frequent sites of colonization with groups C and G streptococci. S. dysgalactiae subsp. equisimilis can be isolated from the umbilicus of healthy neonates but rarely causes invasive disease.
CLINICAL MANIFESTATIONS Groups C and G streptococci are associated with the same spectrum of illnesses caused by S. pyogenes. In children, these organisms are implicated most commonly in respiratory tract infections, particularly pharyngitis. The true incidence of pharyngitis caused by groups C and G streptococci is difficult to determine because asymptomatic colonization occurs.4 Nevertheless, compelling evidence implicates group C and G streptococci as true causes of pharyngitis. For example, several epidemics of group C and group G streptococcal pharyngitis have been reported. Even more convincing support comes from studies of foodborne outbreaks. The clinical presentation of pharyngitis resulting from groups C and G streptococci is indistinguishable from pharyngitis caused by S. pyogenes.5 Isolated case reports have described group C streptococcal pneumonia in children. Similar to group A streptococcal infection, tissue destruction is considerable. Abscess formation, empyema, and bacteremia are common. Despite effective antimicrobial therapy, these infections typically respond slowly, with persistent fever for >7 days.6 Other respiratory tract infections reported include epiglottitis7 and sinusitis.
TABLE 122.1 Differentiation of β-Hemolytic Group C and G Isolates From Streptococcus pyogenes and Streptococcus anginosus Lancefield Group
Bacitracin
Streptococcus pyogenes–like groups C and G, large-colony–forming (Streptococcus dysgalactiae subspecies equisimilis)
C or G
Resistanta
S. pyogenes
A
Sensitive
Minute-colony–forming groups C and G (Streptococcus anginosus group)
C or G
NA
Organism
a
PYR Test Result
VP Test Result
−
−
+
−
NA
+
Occasional isolates are susceptible to bacitracin. +, most isolates produce a positive reaction; −, most isolates produce a negative reaction; NA, data not available; PYR, L-pyrrolidonyl-β-naphthylamide; VP, Voges-Proskauer.
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Groups C and G streptococci also cause skin and soft tissue infections. These organisms can colonize the skin and gain access to subcutaneous tissues after a break in skin integrity. As with S. pyogenes infection, lymphangitis can complicate superficial infections caused by groups C and G organisms. Musculoskeletal infections, particularly pyogenic arthritis, occur occasionally, usually in adults with underlying disease.8 At least 3 well-documented pediatric cases resulting from group C streptococci have been described.9 Groups C and G streptococci can cause neonatal septicemia and account for up to 2% of cases in some series. Risk factors include prematurity, prolonged rupture of membranes, and maternal infection. The clinical course may be indistinguishable from early-onset group B Streptococcus infection and includes respiratory distress, hypotension, apnea, bradycardia, and disseminated intravascular coagulation. Neonatal streptococcal toxic shock syndrome caused by S. dysgalactiae subsp. equisimilis has been described.10 Endocarditis, bacteremia, central nervous system infections (particularly brain abscess), and toxic shock caused by groups C and G streptococci are described but are uncommon in children. These infections generally occur in children with immune deficits or in adolescents after delayed recognition of sinusitis. In addition to the postinfectious glomerulonephritis associated with infection with groups C and G streptococci, reactive arthritis has been described after group C streptococcal infection. No convincing evidence of acute rheumatic fever after infection with groups C and G streptococci has been found; therefore, antibiotic treatment is not indicated to prevent rheumatic fever.11
THERAPY Groups C and G streptococci are inhibited by low concentrations of penicillin (mean minimum inhibitory concentration <0.2 µg/mL), and penicillin is the drug of choice in most circumstances.12 However, some isolates demonstrate tolerance to penicillin, with a ratio of minimal bactericidal concentration to minimum inhibitory concentration as high as 512 : 1. Although the clinical significance of tolerance is unclear, one study demonstrated that in adults with endocarditis resulting from tolerant group C streptococci infection, treatment with penicillin and an aminoglycoside resulted in improved outcome. Other antibiotics with activity against groups C and G streptococci include other β-lactam agents, carbapenems, linezolid, quinupristindalfopristin, and vancomycin.13 Occasional isolates demonstrate tolerance to vancomycin. Chloramphenicol, clindamycin, and erythromycin have poor bactericidal activity, particularly against group G streptococci. Up to 70% of group C streptococci produce a chromosomally encoded factor that mediates resistance to tetracycline. All references are available online at www.expertconsult.com.
KEY REFERENCE 8. Loubinoux J, Plainvert C, Collobert G, et al. Adult invasive and noninvasive infections due to Streptococcus dysgalactiae subsp. equisimilis in France from 2006 to 2010. J Clin Microbiol 2013;51:2724–2727.
Groups C and G Streptococci
REFERENCES 1. Broyles LN, Van Beneden C, Beall B, et al. Population-based study of invasive disease due to beta-hemolytic streptococci of groups other than A and B. Clin Infect Dis 2009;48:706–712. 2. Jensen A, Kilian M. Delineation of Streptococcus dysgalactiae, its subspecies, and its clinical and phylogenetic relationship to Streptococcus pyogenes. J Clin Microbiol 2012;50:113–126. 3. Rantala S. Streptococcus dysgalactiae subsp. equisimilis bacteremia: an emerging infection. Eur J Clin Microbiol Infect Dis 2014;33:1303–1310. 4. Zaoutis T, Attia M, Gross R, et al. The role of group C and group G streptococci in acute pharyngitis in children. Clin Microbiol Infect 2004;10:37–40. 5. Lindbaek M, Hoiby EA, Lermark G, et al. Clinical symptoms and signs in sore throat patients with large colony variant beta-haemolytic streptococci groups C or G versus group A. Br J Gen Pract 2005;55:615–619. 6. Myers JP. Pleuropulmonary infections caused by group C streptococcus. Infect Dis Clin Pract (Baltim Md) 2011;19:88–95. 7. Lee TW, Sandoe JA. Epiglottitis caused by group C streptococcus. Acta Paediatr 2001;90:1085. 8. Loubinoux J, Plainvert C, Collobert G, et al. Adult invasive and noninvasive infections due to Streptococcus dysgalactiae subsp. equisimilis in France from 2006 to 2010. J Clin Microbiol 2013;51:2724–2727.
122
9. Arditi M, Shulman ST, David A, et al. Group C beta-hemolytic streptococcal infections in children: nine pediatric cases and review. Rev Infect Dis 1989;11: 34–45. 10. Yamaoka S, Ogihara T, Yasui M, et al. Neonatal streptococcal toxic shock syndrome caused by Streptococcus dysgalactiae subsp. equisimilis. Pediatr Infect Dis J 2010;29:979–981. 11. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation 2009;119:1541–1551. 12. Brandt CM, Spellerberg B. Human infections due to Streptococcus dysgalactiae subspecies equisimilis. Clin Infect Dis 2009;49:766–772. 13. Zaoutis T, Moore LS, Furness K, et al. In vitro activities of linezolid, meropenem, and quinupristin-dalfopristin against group C and G streptococci, including vancomycin-tolerant isolates. Antimicrob Agents Chemother 2001;45: 1952–1954.
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122 Groups C and G Streptococci David B. Haslam and Joseph W. St. Geme III
The β-hemolytic streptococci can be subdivided on the basis of whether they form large colonies or minute colonies on solid agar. Most notable among those β-hemolytic streptococci that form large colonies are Streptococcus pyogenes (group A) and Streptococcus agalactiae (group B). Among the remaining Lancefield-reactive β-hemolytic streptococci, groups C and G organisms are most commonly associated with human disease.1 In this chapter, groups C and G streptococci refer exclusively to the large-colony–forming “S. pyogenes-like” organisms. Minute-colony– forming species belonging to groups C and G are placed in the S. anginosus group (formerly Streptococcus milleri) (see Chapter 121). In some hospitals, group G streptococci cause more cases of invasive disease than does S. pyogenes,1 perhaps because these organisms are more commonly associated with infection in immunocompromised hosts.
CHARACTERISTICS OF THE PATHOGENS Groups C and G organisms, like all streptococci, are catalase-negative, gram-positive cocci. Human isolates are almost always β hemolytic on sheep blood agar culture, although rare isolates are α hemolytic or nonhemolytic. Groups C and G organisms resemble S. pyogenes on blood agar, thus necessitating biochemical testing and serologic analysis for definitive identification. Latex agglutination typically is used in clinical microbiology laboratories to determine the Lancefield grouping of large-colony β-hemolytic streptococci. Most groups C and G isolates are resistant to bacitracin, but significant fractions are susceptible, thereby making bacitracin susceptibility testing alone unreliable in distinguishing these organisms from S. pyogenes. Hydrolysis of L-pyrrolidonyl-Pnaphthylamide (PYR reaction) is a useful adjunctive test because the groups C and G organisms are PYR negative and S. pyogenes is PYR positive. Colony morphology and lack of acetoin production (negative results of the Voges-Proskauer [VP] test) differentiate large-colony groups C and G streptococci from the S. anginosus group (Table 122.1).
Speciation Large-colony Group C and G human isolates now are grouped together as Streptococcus dysgalactiae subsp. equisimilis.2 The remaining largecolony group C streptococci, predominantly animal pathogens, are grouped as S. dysgalactiae subsp. dysgalactiae. Nonhuman group G isolates are often considered part of a single species designated as Streptococcus canis and are genetically distinct from the S. dysgalactiae subsp. equisimilis group G organisms.
Virulence Properties Groups C and G streptococci share several virulence factors with S. pyogenes. Both group C and group G isolates produce streptolysin O
and can stimulate an increase in the anti–streptolysin O (ASO) titer. In addition, isolates of both groups produce degradative enzymes, including hyaluronidase. Group G isolates also produce streptolysin S and often produce DNAase that is antigenically similar to S. pyogenes DNAase B. Moreover, group G streptococci produce an M protein that is similar immunologically to that of S. pyogenes and can be responsible for the occasional association of group G isolates with postinfectious glomerulonephritis. Glomerulonephritis following group C streptococcal infection also is well described. Whereas these isolates fail to produce an M protein, they can produce endostreptosin, which is believed to be involved in the pathogenesis of S. pyogenes–induced glomerulonephritis. A toxic shock–like syndrome associated with group C and G streptococcal infection has been reported. Some of these cases have been associated with a strain that possesses genes homologous to the S. pyogenes streptococcal pyogenic exotoxins or that elaborates an unidentified substance with superantigen activity.3
EPIDEMIOLOGY Pharyngeal carriage of groups C and G streptococci is detected in up to 5% of healthy children. In tropical climates, the pharyngeal carriage rate is much higher. The skin, gastrointestinal tract, and vagina also are frequent sites of colonization with groups C and G streptococci. S. dysgalactiae subsp. equisimilis can be isolated from the umbilicus of healthy neonates but rarely causes invasive disease.
CLINICAL MANIFESTATIONS Groups C and G streptococci are associated with the same spectrum of illnesses caused by S. pyogenes. In children, these organisms are implicated most commonly in respiratory tract infections, particularly pharyngitis. The true incidence of pharyngitis caused by groups C and G streptococci is difficult to determine because asymptomatic colonization occurs.4 Nevertheless, compelling evidence implicates group C and G streptococci as true causes of pharyngitis. For example, several epidemics of group C and group G streptococcal pharyngitis have been reported. Even more convincing support comes from studies of foodborne outbreaks. The clinical presentation of pharyngitis resulting from groups C and G streptococci is indistinguishable from pharyngitis caused by S. pyogenes.5 Isolated case reports have described group C streptococcal pneumonia in children. Similar to group A streptococcal infection, tissue destruction is considerable. Abscess formation, empyema, and bacteremia are common. Despite effective antimicrobial therapy, these infections typically respond slowly, with persistent fever for >7 days.6 Other respiratory tract infections reported include epiglottitis7 and sinusitis.
TABLE 122.1 Differentiation of β-Hemolytic Group C and G Isolates From Streptococcus pyogenes and Streptococcus anginosus Lancefield Group
Bacitracin
Streptococcus pyogenes–like groups C and G, large-colony–forming (Streptococcus dysgalactiae subspecies equisimilis)
C or G
Resistanta
S. pyogenes
A
Sensitive
Minute-colony–forming groups C and G (Streptococcus anginosus group)
C or G
NA
Organism
a
PYR Test Result
VP Test Result
−
−
+
−
NA
+
Occasional isolates are susceptible to bacitracin. +, most isolates produce a positive reaction; −, most isolates produce a negative reaction; NA, data not available; PYR, L-pyrrolidonyl-β-naphthylamide; VP, Voges-Proskauer.
736
Groups C and G streptococci also cause skin and soft tissue infections. These organisms can colonize the skin and gain access to subcutaneous tissues after a break in skin integrity. As with S. pyogenes infection, lymphangitis can complicate superficial infections caused by groups C and G organisms. Musculoskeletal infections, particularly pyogenic arthritis, occur occasionally, usually in adults with underlying disease.8 At least 3 well-documented pediatric cases resulting from group C streptococci have been described.9 Groups C and G streptococci can cause neonatal septicemia and account for up to 2% of cases in some series. Risk factors include prematurity, prolonged rupture of membranes, and maternal infection. The clinical course may be indistinguishable from early-onset group B Streptococcus infection and includes respiratory distress, hypotension, apnea, bradycardia, and disseminated intravascular coagulation. Neonatal streptococcal toxic shock syndrome caused by S. dysgalactiae subsp. equisimilis has been described.10 Endocarditis, bacteremia, central nervous system infections (particularly brain abscess), and toxic shock caused by groups C and G streptococci are described but are uncommon in children. These infections generally occur in children with immune deficits or in adolescents after delayed recognition of sinusitis. In addition to the postinfectious glomerulonephritis associated with infection with groups C and G streptococci, reactive arthritis has been described after group C streptococcal infection. No convincing evidence of acute rheumatic fever after infection with groups C and G streptococci has been found; therefore, antibiotic treatment is not indicated to prevent rheumatic fever.11
THERAPY Groups C and G streptococci are inhibited by low concentrations of penicillin (mean minimum inhibitory concentration <0.2 µg/mL), and penicillin is the drug of choice in most circumstances.12 However, some isolates demonstrate tolerance to penicillin, with a ratio of minimal bactericidal concentration to minimum inhibitory concentration as high as 512 : 1. Although the clinical significance of tolerance is unclear, one study demonstrated that in adults with endocarditis resulting from tolerant group C streptococci infection, treatment with penicillin and an aminoglycoside resulted in improved outcome. Other antibiotics with activity against groups C and G streptococci include other β-lactam agents, carbapenems, linezolid, quinupristindalfopristin, and vancomycin.13 Occasional isolates demonstrate tolerance to vancomycin. Chloramphenicol, clindamycin, and erythromycin have poor bactericidal activity, particularly against group G streptococci. Up to 70% of group C streptococci produce a chromosomally encoded factor that mediates resistance to tetracycline. All references are available online at www.expertconsult.com.
KEY REFERENCE 8. Loubinoux J, Plainvert C, Collobert G, et al. Adult invasive and noninvasive infections due to Streptococcus dysgalactiae subsp. equisimilis in France from 2006 to 2010. J Clin Microbiol 2013;51:2724–2727.
Groups C and G Streptococci
REFERENCES 1. Broyles LN, Van Beneden C, Beall B, et al. Population-based study of invasive disease due to beta-hemolytic streptococci of groups other than A and B. Clin Infect Dis 2009;48:706–712. 2. Jensen A, Kilian M. Delineation of Streptococcus dysgalactiae, its subspecies, and its clinical and phylogenetic relationship to Streptococcus pyogenes. J Clin Microbiol 2012;50:113–126. 3. Rantala S. Streptococcus dysgalactiae subsp. equisimilis bacteremia: an emerging infection. Eur J Clin Microbiol Infect Dis 2014;33:1303–1310. 4. Zaoutis T, Attia M, Gross R, et al. The role of group C and group G streptococci in acute pharyngitis in children. Clin Microbiol Infect 2004;10:37–40. 5. Lindbaek M, Hoiby EA, Lermark G, et al. Clinical symptoms and signs in sore throat patients with large colony variant beta-haemolytic streptococci groups C or G versus group A. Br J Gen Pract 2005;55:615–619. 6. Myers JP. Pleuropulmonary infections caused by group C streptococcus. Infect Dis Clin Pract (Baltim Md) 2011;19:88–95. 7. Lee TW, Sandoe JA. Epiglottitis caused by group C streptococcus. Acta Paediatr 2001;90:1085. 8. Loubinoux J, Plainvert C, Collobert G, et al. Adult invasive and noninvasive infections due to Streptococcus dysgalactiae subsp. equisimilis in France from 2006 to 2010. J Clin Microbiol 2013;51:2724–2727.
122
9. Arditi M, Shulman ST, David A, et al. Group C beta-hemolytic streptococcal infections in children: nine pediatric cases and review. Rev Infect Dis 1989;11: 34–45. 10. Yamaoka S, Ogihara T, Yasui M, et al. Neonatal streptococcal toxic shock syndrome caused by Streptococcus dysgalactiae subsp. equisimilis. Pediatr Infect Dis J 2010;29:979–981. 11. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation 2009;119:1541–1551. 12. Brandt CM, Spellerberg B. Human infections due to Streptococcus dysgalactiae subspecies equisimilis. Clin Infect Dis 2009;49:766–772. 13. Zaoutis T, Moore LS, Furness K, et al. In vitro activities of linezolid, meropenem, and quinupristin-dalfopristin against group C and G streptococci, including vancomycin-tolerant isolates. Antimicrob Agents Chemother 2001;45: 1952–1954.
737.e1