Group D Streptococcus (GDS) Infections (Streptococcus bovis/Streptococcus gallolyticus)

Background

Group D Streptococcus (GDS) infections in humans are most often associated with bacteremia, with or without endocarditis. Other less-common infections involving group D streptococci include urinary tract infections, meningitis, neonatal sepsis, spontaneous bacterial peritonitis, septic arthritis, and vertebral osteomyelitis. Traditionally, group D streptococcal infections have predominantly been caused by Streptococcus bovis, but recent taxonomy changes have produced confusion among clinicians.

S bovis is well-established in the literature as a cause of bacteremia and endocarditis and has a well-known association with gastrointestinal malignancy. For simplicity, S bovis is the terminology used throughout this article.

• References

Pathophysiology

The portal of entry for S bovis bacteremia is the gastrointestinal tract. The urinary tract, hepatobiliary tree and the oropharynx can also be sources of infection in some cases. S bovis bacteremia, with or without endocarditis, is strongly associated with an underlying malignancy or premalignant lesions of the colon. S bovis has also been isolated more frequently from the stools of patients with such malignancies.

Associations with nonmalignant diseases of the colon have also been reported. A similar relationship between bacteremia (or endocarditis) and chronic liver disease has been established.^[1] In rare cases, gastric cancer has been found upon investigation following S bovis bacteremia.^[2] Every patient with S bovis bacteremia, with or without endocarditis, should undergo evaluation for gastrointestinal malignancy.

• References

Epidemiology

Frequency

United States

Isolation of S bovis from microbiology specimens, particularly blood cultures, is uncommon. The SENTRY Antimicrobial Surveillance Program in the United States does not list group D streptococci among the 10 most common organisms that cause bloodstream infections, accounting for no more than 1% of all cases.^[3] According to the SCOPE Program, streptococci accounted for 6% of all blood culture isolates among 30 US hospitals, with S bovis accounting for 2.4% of those streptococci.^[4]

Despite these findings, the microorganisms most commonly implicated as etiologic agents in subacute infective endocarditis occurring on native valves in patients who were not intravenous drug users were Streptococcus viridans and S bovis. Since 1997, a review of the International Collaboration on Endocarditis merged database (ICE-MD) found that S bovis accounted for 16.7% of all streptococcal infective endocarditis cases reported in the United States.^[5] However, this study reported findings from only two US hospitals.

International

SENTRY data indicate that S bovis was isolated in 1.3% and 6.9% of streptococcal bloodstream infections in Canada and Latin America, respectively. Kupferwasser et al compared patients with S bovis endocarditis with patients with endocarditis secondary to other causative microorganisms. In this German study, 177 cases of definite infective endocarditis were reported between 1983 and 1996, with 22 cases (12.5%) caused by S bovis.^[6]

More-recent studies have shown an increasing proportion of infective endocarditis caused by S bovis, particularly in France and neighboring areas of southern Europe. An analysis of 559 cases of infective endocarditis in France in 1999 found that 25% were caused by S bovis.^[7] A Spanish study recently reported similar findings.^[8]

Mortality/Morbidity

Morbidity: A study by Kupferwasser et al showed that S bovis endocarditis is a severe infection. The duration of fever and the increased acute-phase reactants after the onset of treatment were longer than with infective endocarditis caused by other bacteria. Involvement of multiple valves and valvular damage resulting in moderate-to-severe regurgitation were also more common. Embolic events were less common and correlated with the smaller sizes of S bovis vegetations observed on transesophageal echocardiograms. Gastrointestinal lesions were observed in nearly 50% of patients with S bovis endocarditis.^[6]

Mortality: Mortality rates from the same study were 45% for S bovis endocarditis and 25% for non– S bovis endocarditis. This is higher than the 7.5-38% mortality range reported previously. The increased mortality was related to the virulence of S bovis and to a more common occurrence of underlying extracardiac disease of which patients died during follow-up care.^[6]

Race

Streptococcus group D infections have no known racial predilection.

Sex

Streptococcus group D infections have no reported sexual predilection.

Age

Nearly all individuals with S bovis endocarditis are older than 50 years, with a mean age of 67 years and age range of 49-76 years. This once meant that patients with S bovis endocarditis were on average older than patients with endocarditis caused by other species. However, the mean age for all cases of endocarditis has recently increased, making patients with S bovis endocarditis generally no older than those with endocarditis from other causes.^[9]

• References

History

Meningitis, peritonitis, septic arthritis, urinary tract infections, and neonatal sepsis due to group D streptococci have clinical features referable to the site of infection. When due to group D streptococcal infection, the clinical features do not differ from other bacterial causes of these infections.

The following are findings associated with group D streptococcal endocarditis:

• Subacute endocarditis with persistent fever lasting days or weeks
• Associated with nonspecific symptoms, including anorexia, weight loss, fatigue, night sweats, and weakness

The following are findings associated with group D streptococcal bacteremia:

• Fever
• Only possible to distinguish from endocarditis with patient history and echocardiography

• References

Physical

Group D streptococcal bacteremia manifests as fever without localizing signs.

The following are the physical findings of group D streptococcal endocarditis:

• A minority of patients with group D streptococcal endocarditis have heart murmurs at presentation. Murmurs usually develop with time.
• Classic peripheral signs occasionally observed include splinter hemorrhages, conjunctival petechiae, Osler nodules, Janeway lesions, and Roth spots. At least one of these manifestations occurs in approximately 50% of cases.
• Embolic phenomena may include neurologic manifestations, septic infarctions, or vascular occlusion.
• Renal failure may be present and may be caused by an immune-complex glomerulonephritis.
• If cerebral hemorrhage is observed, it is a consequence of a ruptured mycotic aneurism.

• References

Causes

Group D streptococci, along with other catalase-negative, gram-positive cocci, belong to the family Streptococcaceae. Group D streptococci may also be referenced as the S bovis–Streptococcus equinus complex.^[10] S bovis has recently been reclassified as Streptococcus gallolyticus, but references to S bovis remain prevalent in the clinical literature. S equinus is almost never isolated from human specimens.

Group D streptococci share many features with enterococci. In the mid 1980s, Streptococcus faecalis, Streptococcus faecium, and others were reclassified under the newly created genus Enterococcus.

Similar to enterococci, S bovis possesses the group D lipoteichoic acid antigen in its cell wall. It also shares the ability to hydrolyze esculin in the presence of bile. Unlike enterococci, S bovis fails to grow in broth containing a concentration of 6.5% sodium chloride and is negative for the pyrrolidonyl arylamidase reaction.

S bovis was traditionally differentiated into two biotypes, termed S bovis or S bovis I (now termed S gallolyticus subspecies gallolyticus) and S bovis variant or S bovis II. S bovis II was further differentiated into 2 sub-biotypes, S bovis II/1 (now termed Streptococcus infantarius) and S bovis II/2 (now termed S gallolyticus subspecies pasteurianus or Streptococcus pasteurianus).

In a study of patients with S bovis bacteremia, Ruoff et al demonstrated the following:^[11]

• S bovis I is most often associated with endocarditis and/or malignant or premalignant colonic lesions.
• S bovis II (mainly sub-biotype II/1) is most often associated with a bacteremia of hepatobiliary origin.

• References

Laboratory Studies

Basic laboratory studies to evaluate for Streptococcus group D infections should include CBC count, electrolyte evaluation, creatinine level, and LFTs.

Blood cultures

Blood cultures are the most important tests.

Blood culture results are usually positive during the first 24-48 hours. In cases of endocarditis and sustained bacteremia, blood culture results are positive.

Gram stain from the blood culture bottles demonstrates gram-positive cocci in pairs or chains. S bovis cannot be differentiated from other streptococci using Gram staining.

Differentiating S bovis from Streptococcus salivarius is sometimes very difficult because S salivarius yields a positive reaction on the bile-esculin test. This happens with approximately 20% of the isolates.

Sensitivity testing is recommended, although most S bovis strains are exquisitely sensitive to penicillin. In a study by Mouton et al on 19 strains of S bovis, the minimal inhibitory concentrations (MICs) 50 and 90 were, respectively, 0.06 mg/L (susceptible) and 1 mg/L (intermediate susceptibility). The highest MIC was 2 mg/L (resistant).^[12]

• References

Imaging Studies

Echocardiography

Transthoracic or transesophageal (more sensitive) echocardiography frequently permits visualization of vegetations. Echocardiography should be performed in all patients with S bovis bacteremia.

An absence of vegetation does not rule out infective endocarditis. For more information on echocardiography findings, see Infective Endocarditis.

Colonoscopy

This test is used to detect malignant lesions of the colon.

Colonoscopy should be performed in all patients with S bovis bacteremia or endocarditis.

Regular-interval follow-up colonoscopy should be performed in patients in whom no lesion is found on initial investigation.

Esophagogastroduodenoscopy

Esophagogastroduodenoscopy (EGD) is used to detect malignant lesions of the esophagus, stomach, and duodenum.

EGD should be performed in patients with S bovis bacteremia or endocarditis who have no evidence of colonic malignancy.

Liver ultrasonography and CT scanning

Both of these studies should be performed in cases of associated hepatobiliary disease.

Usually, liver ultrasonography is performed first, followed by CT scanning.

• References

Other Tests

Consider referral of the organism for formal MIC testing if the response to antibiotic therapy is unfavorable.

• References

Medical Care

Most S bovis isolates are susceptible to penicillin (MIC ≤ 0.1 mg/L) and should be treated with intravenous penicillin G or ceftriaxone for 4 weeks. An alternative for only uncomplicated cases of native-valve endocarditis is a 2-week course of therapy with a combination of penicillin G or ceftriaxone and gentamicin. For moderately susceptible isolates (MIC >0.1 mg/L, MIC ≤ 0.5 mg/L), penicillin or ceftriaxone and gentamicin should be administered for 4 weeks and 2 weeks, respectively.^[13]

• References

Surgical Care

Surgical valve replacement is indicated in some cases, particularly for heart failure or complications of endocarditis (see Complications).

Mycotic aneurysm clipping after cerebral arteriography may be indicated.

Based on the findings from the evaluation of the gastrointestinal tract, colon or hepatobiliary surgery may be indicated.

• References

Consultations

Consult an infectious diseases specialist to confirm the diagnosis of Streptococcus group D infection and to recommend treatment for endocarditis or bacteremia.

Consult a cardiologist to evaluate heart function, including echocardiography findings.

A cardiovascular surgeon can assist with valvular replacement, if indicated. Having the cardiac surgeon involved from the start is a good practice in case the patient's heart condition abruptly deteriorates.

Obtain a consultation with a neurosurgeon for possible clipping if mycotic aneurysms are present.

Obtain a consultation with a general surgeon or gastroenterologist to investigate and treat colonic or hepatobiliary disease.

• References

Medication Summary

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.

• References

Penicillin G (Pfizerpen)

• Dosing, Interactions, etc.

Clinical Context:  Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

• References

Ceftriaxone (Rocephin)

• Dosing, Interactions, etc.

Clinical Context:  Alternative to penicillin. Third-generation cephalosporin equally effective against infections caused by S bovis. Has advantage of once daily administration. For penicillin IgE–mediated hypersensitivity, cross-reactions with third-generation cephalosporins are very rare.

• References

Vancomycin (Lyphocin, Vancocin, Vancoled)

• Dosing, Interactions, etc.

Clinical Context:  A glycopeptide very active against isolates of S bovis. Useful for patients who are allergic to penicillin.

• References

Gentamicin (Garamycin, Gentacidin)

• Dosing, Interactions, etc.

Clinical Context:  Should be used together with penicillin when bacterial isolates are only moderately susceptible to penicillin or to reduce treatment duration from 4 wk to 2 wk when infection is fully susceptible to penicillin. Preferred aminoglycoside for synergy. Should be administered at lower dosage (3 mg/kg/d) than for treatment of infections caused by gram-negative organisms (5 mg/kg/d).

• References

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

• References

Further Outpatient Care

Patients who are stable and infected with a penicillin-sensitive strain of S bovis and whose conditions have improved with antibiotic therapy can be discharged to complete their intravenous treatment on an outpatient basis.

• References

Further Inpatient Care

Approximately 72 hours after beginning antibiotics, run two series of blood cultures. If the results are positive, repeat every 3-4 days until the results are negative.

Monitor serum creatinine levels closely in patients receiving gentamicin and vancomycin.

• References

Complications

Complications of S bovis infection are similar to those of S viridans endocarditis.

S bovis subacute bacterial endocarditis can involve the heart, kidneys, CNS, spleen, lungs, and eyes. Mycotic aneurysms are potential complications. See the following:

• Heart: Destruction of the valve leaflets and rupture of the chordae tendineae, papillary muscles, or interventricular septum may cause intractable heart failure. Other rare complications of SBE include myocarditis, pericarditis, and myocardial infarction. Ring abscesses (mainly with prosthetic valve endocarditis) could extend to the septum and cause atrioventricular blockade.
• Kidneys: Embolization could cause kidney infarction or abscesses. Immune complexes are responsible for glomerulonephritis.
• CNS: Cerebral emboli can cause cerebral infarction, arteritis, mycotic aneurysms, hemorrhage, cerebritis, and meningitis.
• Spleen: Splenic infarction or abscesses may occur.
• Lungs: With right-sided endocarditis, pulmonary emboli are common and may cause infarction or septic emboli.
• Eyes: Endogenous endophthalmitis may occur.
• Mycotic aneurysms: Found most commonly in the CNS, they also occur in the abdominal aorta; the sinus of Valsalva; and splenic, coronary, pulmonary, and mesenteric arteries.

• References

Prognosis

See Mortality/Morbidity.

S bovis endocarditis is an aggressive disease with significant mortality.

Heart failure is a frequent complication and an indication for valve replacement.

In a study by Kupferwasser et al, 73% of patients with S bovis endocarditis underwent surgical treatment, but only 34%, 34%, and 41% of patients with endocarditis caused by other streptococci, staphylococci, or other bacteria underwent surgery, respectively.^[6]

• References