Chapter 287. Nongroup A or B Streptococcus

Nongroup A or B streptococci are a diverse group of gram-positive microorganisms that may be commensal or may be associated with severe, even life-threatening, infections.

Epidemiology

Nongroup A or B streptococci that are pathogenic for humans tend to fall into three categories: viridans streptococci, β-hemolytic streptococci groups C or G, and nonhemolytic group D. These organisms are normal resident flora of the mouth, gastrointestinal tract, or female genital tract. They are only occasionally found on the skin. Viridans streptococci, so named because of the Latin viridis, or green, comprise a group of at least 18 species, now subdivided into four groups: anginosis (previously milleri), mitis, salivarius, and mutans. Growth on blood agar may elicit α, γ, or occasionally β-hemolysis. β-Hemolytic groups C and G each comprise two strains, which are identifiable by colony size. Colonies greater than 0.5 mm are considered to be pathogenic, whereas colonies less than 0.5 mm are nonpathogens. Streptococcus bovis is the only nonhemolytic group D species; it must be differentiated from enterococci, which also carry group D antigens.

Viridans streptococci do not share any of the pathogenic features of pyogenic streptococci. Their propensity to cause disease is primarily related to a high frequency of transient bacteremia following dental procedures or loss of integrity of mucosal membranes. In a study of 735 children, the rates of bacteremia following various dental procedures were: polishing teeth, 24.5%; intraligamental injection, 96.6%; and toothbrushing, 38.5%. Viridans streptococci comprised 50% of the bloodstream isolates.1 Some strains of viridans streptococci, particularly S mutans, S sanguis, and S mitis, appear to have enhanced ability to adhere to damaged heart valves and vegetations. Large-colony groups C and G streptococci possess virulence factors in common with group A streptococci such as hemolysins, extracellular proteins, and M proteins.

Clinical Manifestations

Viridans streptococci have long been recognized as a major organism causing 22% to 38% of cases of bacterial endocarditis. The majority of children with bacterial endocarditis have underlying congenital heart defects and usually have undergone cardiac surgery (see Chapter 235).2 Rheumatic heart disease is the second most common cardiac abnormality predisposing to endocarditis. Fever and fatigue in the background of a changing cardiac exam are the most common presenting symptoms of endocarditis. An elevated erythrocyte sedimentation rate and anemia are the most common laboratory findings. When compared to infections with S aureus, those caused by viridans streptococci respond to therapy more quickly with more rapid defervescence and clearing of the bacteremia. Complications and need for heart surgery are significantly less frequent with viridans streptococcal infections.

Viridans streptococci are also important pathogens in some immunocompromised hosts. In cancer patients and children receiving hematopoietic stem cell transplants, viridans streptococci account for 5% to 30% of cases of bacteremia, mainly associated with indwelling vascular catheters, mucositis, gastrointestinal toxicity, and neutropenia.3,4 Pneumonia and septic shock are common complications. Rare cases of early-onset sepsis have been described in neonates. While large-colony group C and group G streptococci are implicated as a cause of pharyngitis in children and adults, they are most commonly associated with food-borne outbreaks. In a recent Delaware study, conducted over a 1-year period, of 2085 children with pharyngitis and 195 controls, large-colony group C or G streptococci were isolated from 3.1% of patients and 1.5% of controls, a difference that was not statistically significant.5 These organisms are not a cause of acute rheumatic fever. Infrequently, group C and group G streptococci cause a variety of pyogenic infections: pneumonia, epiglottitis, osteomyelitis, septic arthritis, pyomyositis, brain abscess, meningitis, cellulitis, endocarditis, sinusitis, urinary tract infections, bacteremia; and toxic shock syndrome.6-8 All of these occur very infrequently.

Group D streptococci (S bovis) are a rare cause of disease in children. There are few reports of endocarditis (seen mainly in adults), meningitis, or bacteremia, particularly in newborns.9

Diagnosis

Streptococci are readily recovered from standard blood culture media. Complex media containing 5% sheep’s blood are usually recommended for subculture of blood isolates and for the culture of streptococci from throat swabs. Colony size and hemolytic pattern determine the initial classification. There is no consensus on whether a predominance of large-colony group C or G streptococci from throat cultures should be reported. Viridans streptococci are usually differentiated from S pneumoniae by a lack of Optochin disk susceptibility or bile solubility, from S bovis by a lack of bile esculin reaction, and from enterococci by negative PYR (L-pyrrolidonyl-beta-naphthylamide) hydrolysis. Speciation of viridans streptococci may be accomplished through biochemical reactions available in several commercial kits. There are limited data to support the clinical relevance of speciation at this point. It is important, however, to realize that because viridans streptococci are not common skin flora, their recovery from blood culture should be carefully scrutinized before discounting them as contaminants.

Treatment

Group C and G streptococci remain susceptible to penicillin; first-generation cephalosporins and erythromycin are treatment alternatives for the penicillin-allergic individual. An increasing incidence of penicillin resistance is emerging among viridans streptococci and group D streptococci. Therapy must be guided by susceptibility testing, which is best performed with the E test or agar dilution. In a study of Japanese children, the recovery from throat cultures of intermediate (minimal inhibitory concentration [MIC] ⩾0.25 μg/mL) or high-level (MIC ⩾4 μg/mL) penicillin-resistant viridans streptococci increased significantly from 62.5% to 87.5% following a short course of oral cephalosporin therapy.10 High-level penicillin resistance occurred in 62.5% of blood culture isolates from neutropenic children. These findings are consistent with other reports of rising penicillin resistance, particularly among blood culture isolates of neutropenic hosts. In general, these organisms remain vancomycin susceptible. In institutions where penicillin resistance is frequent, vancomycin should be included in the broad-spectrum empiric antibiotic coverage of febrile neutropenic hosts pending antibiotic susceptibility data.

Treatment of native valve endocarditis resulting from viridans streptococci or S bovis is determined by antibiotic susceptibility. Highly penicillin-susceptible viridans streptococci or S bovis (MIC ⩽0.1 μg/mL) can be treated for 4 weeks with intravenous penicillin, or once daily with ceftriaxone. The addition of gentamicin to penicillin exerts a synergistic killing effect in vitro on viridans streptococci and S bovis. A 2-week regimen of the combination of penicillin or ceftriaxone and gentamicin is considered adequate therapy for patients without known extracardiac infection or a creatinine clearance <20 mL/min. For viridans streptococci or S bovis with MIC between 0.12 and 0.5 μg/mL, penicillin or ceftriaxone for 4 weeks with the addition of gentamicin for the first 2 weeks is recommended. For viridans streptococci with MIC greater than or equal to 0.5 μg/mL, 4 to 6 weeks of therapy are recommended with penicillin or ampicillin plus gentamicin, or with vancomycin plus gentamicin for those unable to tolerate penicillin.11