AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Streptococcus bovis is the main human pathogen among nonenterococcal group D streptococci. S bovis infection is a well-documented cause of infective endocarditis. S bovis also causes bacteremia without endocarditis and, less frequently, urinary tract infections, meningitis, neonatal sepsis, spontaneous bacterial peritonitis, and, rarely, septic arthritis, vertebral osteomyelitis, and peritonitis associated with continuous ambulatory peritoneal dialysis.

Pathophysiology

The portal of entry for S bovis bacteremia is the GI tract. Occasionally, the urinary tract, the hepatobiliary tree, or the oropharynx is the source of the bacteremia. A strong association exists between S bovis bacteremia with or without endocarditis and underlying malignancy or premalignant lesions of the colon. The organism has also been isolated more frequently from the stools of patients with such malignancies. A similar relationship between bacteremia (or endocarditis) and liver disease has been established. Association with nonmalignant diseases of the colon is also reported. Whether S bovis plays a causative role in colon cancers or is only a marker of the disease is unclear. In any event, every patient with S bovis bacteremia with or without endocarditis should be examined for a GI tract malignancy.

Frequency

United States

Isolation of S bovis from microbiology specimens, particularly blood cultures (BCs), is infrequent. The SENTRY Antimicrobial Surveillance Program in the United States does not list group D streptococci among the 20 most frequent organisms causing bloodstream infections. S bovis was identified in 0.8% of streptococcal bloodstream infections. Streptococcus pneumoniae was by far the most frequent isolate in that study. According to the SCOPE program from 30 US hospitals, streptococci accounted for 6% of all BC isolates and S bovis represented 2.4% of them. However, the microorganisms most commonly implicated as etiologic agents in subacute infective endocarditis occurring on native valves in patients who are not intravenous drug users were viridans streptococci and S bovis.

International

SENTRY data indicate that S bovis was identified in 1.3% and 6.9% of streptococcal blood stream infections in Canada and Latin America, respectively. In Germany, Kupferwasser et al compared patients with S bovis endocarditis with patients with endocarditis secondary to other causative microorganisms. In this study, 177 cases were reported, with 22 cases (12.5%) caused by S bovis.

Mortality/Morbidity

• Morbidity: The 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. Multiple valve involvement and valvular damage resulting in moderate-to-severe regurgitation were also more frequent. Embolic events were less frequent and were correlated with the smaller sizes of S bovis vegetations observed on transesophageal echocardiograms. GI lesions were observed in nearly 50% of patients with S bovis endocarditis.
• Mortality: Rates from the same study were 45% for S bovis and 25% for non-S bovis endocarditis. This is higher than the 7.5-38% mortality range reported previously. Mortality was related to the virulence of S bovis and to a more frequent occurrence of underlying extracardiac disease from which patients died during follow-up care.

Race

No racial predilection is recognized.

Sex

No significant sex difference is reported.

Age

Nearly all patients with S bovis endocarditis are older than 50 years. The mean age is 67 years, and the range is 49-76 years. This is significantly older than patients with endocarditis caused by other streptococci, staphylococci, or other bacteria.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Meningitis, peritonitis, septic arthritis, urinary tract infections, and neonatal sepsis due to group D streptococci do not have specific clinical features.

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

• Bacteremia
• • Fever
  • Only possible to distinguish from endocarditis through patient history/echocardiogram

Physical

Bacteremia manifests as fever without localizing signs.

• Endocarditis
• • A minority of patients have heart murmurs.
  • Classic peripheral signs occasionally observed include splinter hemorrhages, conjunctival petechiae, Osler nodules, Janeway lesions, and Roth spots. At least 1 of these manifestations occurs in approximately 50% of cases.
  • Embolic phenomena may include hematuria, neurologic manifestations, and splenomegaly.
  • Renal failure may be present and is caused by an immune complex glomerulonephritis.
  • If cerebral hemorrhage is observed, it is a consequence of a ruptured mycotic aneurism.

Causes

• Group D streptococci, along with other catalase-negative, gram-positive cocci, belong to the family Streptococcaceae.
• • S bovis and Streptococcus equinus are the 2 members of this class of streptococci.
  • S equinus is almost never isolated from human specimens.

• These bacteria share many features with enterococci, ie, nonenterococcal group D streptococci. In the mid 1980s, Streptococcus faecalis, Streptococcus faecium, and others were assigned to 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 is differentiated further into 2 biotypes termed S bovis or S bovis I and S bovis variant or S bovis II. The 2 sub-biotypes of S bovis II are termed S bovis II/1 and S bovis II/2.
• In a study of patients with S bovis bacteremia, Ruoff et al demonstrated the following:
• • 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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Basic laboratory studies should include CBC count, electrolyte evaluation, creatinine level, and LFTs.
• BCs are the most important tests.
• • BC results are usually positive during the first 24-48 hours. In cases of endocarditis and sustained bacteremia, BC results are positive.
  • Gram stain from the BC 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 for the bile-esculin test. This happens with approximately 20% of the isolates.
  • Sensitivity testing is recommended even though most 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).

Imaging Studies

• Echocardiography
• • Transthoracic or transesophageal (more sensitive) echocardiography frequently permits visualization of vegetations.
  • An absence of vegetation does not rule out the diagnosis. For more information on echocardiography findings, see Infective Endocarditis.

• Liver ultrasonography and CT scanning
• • Both studies should be performed in cases of associated hepatobiliary disease.
  • Usually, liver ultrasonography is performed first, followed by CT scanning.

• Barium enema
• • This test should help in detecting malignant lesions in the colon.
  • Barium enema should be performed on patients with S bovis bacteremia or endocarditis.
  • The only alternative to a barium enema is a colonoscopy.

Other Tests

• Determining the minimal bactericidal concentration, the peak serum bactericidal concentration, and the serum bactericidal concentration throughout the course of infection may be helpful for treating selected patients with S bovis subacute bacterial endocarditis (SBE), particularly in patients with suboptimal responses to treatment.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• The antimicrobial therapy for viridans streptococci and S bovis endocarditis is identical.

Surgical Care

• Surgical valve replacement is sometimes indicated, particularly for heart failure or complications of endocarditis (see Complications).
• Mycotic aneurysm clipping after a cerebral arteriogram may be indicated.
• Based on the findings from the GI tract workup, colon or hepatobiliary surgery may be indicated.

Consultations

• Consult an infectious diseases specialist to confirm the diagnosis and to recommend treatment for endocarditis or bacteremia.
• Consult a cardiologist to evaluate heart function, including echocardiogram 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.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Most S bovis isolates are susceptible to penicillin (MIC £0.1 mg/L) and should be treated with intravenous penicillin G for 4 wk. An alternative only for uncomplicated cases of native valve endocarditis is a 2-wk treatment with a combination of penicillin G and gentamicin. For moderately susceptible isolates (MIC >0.1 mg/L, MIC £0.5 mg/L), penicillin and gentamicin should be administered for 4 wk and 2 wk, respectively. For the rare isolates with a penicillin MIC >0.5 mg/L, the treatment should be as for enterococcal endocarditis (ampicillin/gentamicin for 6 wk).

Drug Category: Antibiotics

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

Drug Name	Ceftriaxone (Rocephin)
Description	Alternative to penicillin. Third-generation cephalosporin equally effective against infections caused by S bovis. Has advantage of qd administration. For penicillin IgE–mediated hypersensitivity, cross-reactions with third-generation cephalosporins are very rare.
Adult Dose	2 g IV q24h
Pediatric Dose	<4 weeks: Not established >4 weeks: 50-100 mg/kg/d IV q12-24h
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Obtain CBC counts at regular intervals for possible hematologic toxicity that may include neutropenia (when large doses are used) or Coombs-positive hemolytic anemia; monitor creatinine levels for interstitial nephritis and electrolytes for possible hypokalemia; reduce dosage with severe renal impairment (CrCl <10 mL/min) for CNS toxicity (seizures); administration can lead to pseudocholelithiasis

Drug Name	Vancomycin (Lyphocin, Vancocin, Vancoled)
Description	A glycopeptide very active against isolates of S bovis. Useful for patients who are allergic to penicillin.
Adult Dose	1 g IV q12h
Pediatric Dose	<4 weeks: Not established >4 weeks: 40 mg/kg/d IV q6-8h
Contraindications	Documented hypersensitivity
Interactions	Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal failure or neutropenia; red man syndrome is caused by rapid IV infusion (dose administered over a few min) but rarely happens when dose is administered over 2 h; red man syndrome is not an allergic reaction

Drug Name	Gentamicin (Garamycin, Gentacidin)
Description	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).
Adult Dose	3 mg/kg IV q24h
Pediatric Dose	<4 weeks: Not established >4 weeks: 1 mg/kg IV q8h
Contraindications	Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus, prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	A - Safe in pregnancy
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Approximately 72 hours after beginning antibiotics, run 2 series of BCs. If the results are positive, repeat every 3-4 days until the results are negative.
• Monitor serum creatinine levels closely in patients receiving gentamicin or vancomycin.

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 as outpatients.

Complications

• Complications for S bovis infection are similar to those of infective endocarditis caused by viridans streptococci.

• S bovis SBE can involve the heart, kidneys, CNS, spleen, lungs, and eyes. Mycotic aneurysms are potential complications.
• • 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 frequent and may cause infarction or septic emboli.
  • Eyes: 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.

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 the study by Kupferwasser et al, surgical treatment was performed in 73% of patients with S bovis endocarditis but only in 34%, 34%, and 41% of patients with endocarditis caused by other streptococci, staphylococci, or other bacteria, respectively.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to investigate the GI tract for possible diseases, either neoplastic or nonneoplastic, in patients with S bovis bacteremia/endocarditis

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Bayer AS, Scheld WM. Endocarditis and intravascular infections. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Disease. Vol 1. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000:. 857-902.
• Burns CA, McCaughey R, Lauter CB. The association of Streptococcus bovis fecal carriage and colon neoplasia: possible relationship with polyps and their premalignant potential. Am J Gastroenterol. Jan 1985;80(1):42-6. [Medline].
• Cunha BA. Antibiotic Essentials. 6^th ed. Royal Oak, Mich: Physicians Press; 2007.
• Cunha BA. Antimicrobial therapy of multidrug-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus. Med Clin North Am. Nov 2006;90(6):1165-82. [Medline].
• Cunha BA. New uses for older antibiotics: nitrofurantoin, amikacin, colistin, polymyxin B, doxycycline, and minocycline revisited. Med Clin North Am. Nov 2006;90(6):1089-107. [Medline].
• Cunha BA. Oral antibiotic therapy of serious systemic infections. Med Clin North Am. Nov 2006;90(6):1197-222. [Medline].
• Diekema DJ, Pfaller MA, Jones RN, et al. Trends in antimicrobial susceptibility of bacterial pathogens isolated from patients with bloodstream infections in the USA, Canada and Latin America. SENTRY Participants Group. Int J Antimicrob Agents. Feb 2000;13(4):257-71. [Medline].
• Diekema DJ, Pfaller MA, Jones RN; SENTRY Participants Group. Age-related trends in pathogen frequency and antimicrobial susceptibility of bloodstream isolates in North America: SENTRY Antimicrobial Surveillance Program, 1997-2000. Int J Antimicrob Agents. Dec 2002;20(6):412-8. [Medline].
• García-Porrúa C, González-Gay MA, Monterroso JR, et al. Septic arthritis due to Streptococcus bovis as presenting sign of 'silent' colon carcinoma. Rheumatology (Oxford). Mar 2000;39(3):338-9. [Medline].
• Gavin PJ, Thomson RB Jr, Horng SJ, Yogev R. Neonatal sepsis caused by Streptococcus bovis variant (biotype II/2): report of a case and review. J Clin Microbiol. Jul 2003;41(7):3433-5. [Medline].
• Gonzlez-Quintela A, Martinez-Rey C, Castroagudín JF, et al. Prevalence of liver disease in patients with Streptococcus bovis bacteraemia. J Infect. Feb 2001;42(2):116-9. [Medline].
• Grant RJ, Whitehead TR, Orr JE. Streptococcus bovis meningitis in an infant. J Clin Microbiol. Jan 2000;38(1):462-3. [Medline].
• Hechmann Wittrup I, Chenoufi Schaadt ML, Arpi M, Danneskiold-Samsoe B. Bacteremia complicated by vertebral osteomyelitis due to Streptococcus bovis. Eur J Clin Microbiol Infect Dis. May 1999;18(5):365-7. [Medline].
• Klein RS, Catalano MT, Edberg SC, et al. Streptococcus bovis septicemia and carcinoma of the colon. Ann Intern Med. Oct 1979;91(4):560-2. [Medline].
• Klein RS, Recco RA, Catalano MT, et al. Association of Streptococcus bovis with carcinoma of the colon. N Engl J Med. Oct 13 1977;297(15):800-2. [Medline].
• Kupferwasser I, Darius H, Muller AM, et al. Clinical and morphological characteristics in Streptococcus bovis endocarditis: a comparison with other causative microorganisms in 177 cases. Heart. Sep 1998;80(3):276-80. [Medline].
• Moellering RC Jr. Enterococcus species, Streptococcus bovis, and Leuconostoc species. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Disease. Vol 2. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000:. 2147-56.
• Moellering RC Jr, Watson BK, Kunz LJ. Endocarditis due to group D streptococci. Comparison of disease caused by streptococcus bovis with that produced by the enterococci. Am J Med. Aug 1974;57(2):239-50. [Medline].
• Mouton JW, Endtz HP, den Hollander JG, et al. In-vitro activity of quinupristin/dalfopristin compared with other widely used antibiotics against strains isolated from patients with endocarditis. J Antimicrob Chemother. May 1997;39 Suppl A:75-80. [Medline].
• Murray HW, Roberts RB. Streptococcus bovis bacteremia and underlying gastrointestinal disease. Arch Intern Med. Jul 1978;138(7):1097-9. [Medline].
• Pfaller MA, Jones RN, Doern GV, et al. Survey of blood stream infections attributable to gram-positive cocci: frequency of occurrence and antimicrobial susceptibility of isolates collected in 1997 in the United States, Canada, and Latin America from the SENTRY Antimicrobial Surveillance Progr. Diagn Microbiol Infect Dis. Apr 1999;33(4):283-97. [Medline].
• Pfaller MA, Jones RN, Doern GV, Kugler K. Bacterial pathogens isolated from patients with bloodstream infection: frequencies of occurrence and antimicrobial susceptibility patterns from the SENTRY antimicrobial surveillance program (United States and Canada, 1997). Antimicrob Agents Chemother. Jul 1998;42(7):1762-70. [Medline].
• Pfaller MA, Jones RN, Marshall SA, et al. Nosocomial streptococcal blood stream infections in the SCOPE Program: species occurrence and antimicrobial resistance. The SCOPE Hospital Study Group. Diagn Microbiol Infect Dis. Dec 1997;29(4):259-63. [Medline].
• Rehm SJ. Outpatient intravenous antibiotic therapy for endocarditis. Infect Dis Clin North Am. Dec 1998;12(4):879-901, vi. [Medline].
• Reynolds JG, Silva E, McCormack WM. Association of Streptococcus bovis bacteremia with bowel disease. J Clin Microbiol. Apr 1983;17(4):696-7. [Medline].
• Ruoff KL, Miller SI, Garner CV, et al. Bacteremia with Streptococcus bovis and Streptococcus salivarius: clinical correlates of more accurate identification of isolates. J Clin Microbiol. Feb 1989;27(2):305-8. [Medline].
• Selton-Suty C, Hoen B, Grentzinger A, et al. Clinical and bacteriological characteristics of infective endocarditis in the elderly. Heart. Mar 1997;77(3):260-3. [Medline].
• Siegman-Igra Y, Schwartz D. Streptococcus bovis revisited: a clinical review of 81 bacteremic episodes paying special attention to emerging antibiotic resistance. Scand J Infect Dis. 2003;35(2):90-3. [Medline].
• Terpenning MS, Buggy BP, Kauffman CA. Infective endocarditis: clinical features in young and elderly patients. Am J Med. Oct 1987;83(4):626-34. [Medline].
• Tripodi MF, Adinolfi LE, Ragone E, et al. Streptococcus bovis endocarditis and its association with chronic liver disease: an underestimated risk factor. Clin Infect Dis. May 15 2004;38(10):1394-400. [Medline].
• Vilaichone RK, Mahachai V, Kullavanijaya P, Nunthapisud P. Spontaneous bacterial peritonitis caused by Streptococcus bovis: case series and review of the literature. Am J Gastroenterol. Jun 2002;97(6):1476-9. [Medline].
• Wilson WR, Karchmer AW, Dajani AS, et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association. JAMA. Dec 6 1995;274(21):1706-13. [Medline].

Article Last Updated: May 8, 2007