- Clinical labs classify streptococci by hemolytic characteristics on 5% sheep blood agar (eg beta-hemolysis), Lancefield Group antigens and other biochemical tests.
- Nomenclature and taxonomy of streptococci confusing because of many historical efforts at describing the class; taxonomic revisions continue as new phylogenetic information becomes available.
- Often described by blood agar hemolysis (1902) or Lancefield carbohydrate group antigens (1933). Organization into 4 groups by hemolysis, Lancefield and phenotype testing (1937):
- Pyogenic (beta-hemolytic) including Groups A, B, C, E, F & G
- Viridans group
- Lactococci (generally not human pathogens)
- 16S rRNA gene sequencing (1990’s) yield true phylogenetic relationships. Facklam classification presented here (see references).
- Viridans streptococci produce alpha (green-hence viridans) hemolysis on blood agar.
- Group A Streptococci: S. pyogenes (see separate pathogen module).
- Group B Streptococci: S. agalactiae, cause of neonatal sepsis/meningitis, puerperal sepsis, chorioamnionitis, also bacteremia (often without clear source), skin and soft-tissue infections, septic arthritis. Found in GI/GU tracts. More common in adults >65 and those w/ co-morbidities.
- Groups C, F, G Streptococci: bacteremia, endocarditis, septic arthritis, osteomyelitis, pharyngitis.
- Group D Streptococci (non-enterococcal), e.g., S. gallolyticus subsp. gallolyticus (formerly S. bovis biotype I): associated with colonic malignancy. Cause of endocarditis.
- S. intermedius/S. anginosus/S. constellatus group (microaerophilic strep; "S. milleri" no longer appropriate): propensity for invasion, meningitis, abscess production (e.g., head & neck infections), bacteremia. Rarely "contaminants" when present in blood cultures.
- S. suis: zoonotic pathogen associated with pig farming or exposure to contaminated pork products. Most prevalent in southeast Asia, where it is a common cause of meningitis, hearing loss, cutaneous lesions, and bacteremia.
- Viridans Streptococci: oropharynx/GI tract usual niche. Common cause of dental infections, subacute bacterial endocarditis, bacteremia. If isolated from CSF or respiratory sections, usually contaminants, but occasionally are responsible for disease. May also be common bloodstream contaminant, but need to clinically correlate.
- Abiotrophia and Granulicatella spp (formerly known as nutritionally-variant streptococci): endocarditis.
- Streptococcus pneumoniae (see separate pathogen module).
SITES OF INFECTION
- Blood: primary bacteremia, especially with neutropenia or malignancy
- Cardiovascular: endocarditis
- Head and neck: dental infections, deep neck space infections (including submandibular, retropharyngeal and lateral neck)
- Lung: pneumonia (rare) associated with oropharyngeal aspiration, abscess and empyema
- Abdomen: abscesses, cholangitis, visceral infections, GU tract
- Shock syndrome (low BP, rash, ARDS) due to viridans strep (e.g., S. mitis) most frequently described in cancer patients
- CNS: brain abscess, meningitis
- Musculoskeletal: septic arthritis, cellulitis
- GI tract: S. gallolyticus subsp. gallolyticus colonizes >55% of patients with colorectal cancer (10% of normal population)
- Cause of primary bacteremia, but up to 80% of cultures may represent contaminants or transient bacteremia. Don’t dismiss in cancer pts on chemotherapy. Continuous bacteremia = suspect endocarditis.
- Viridians group responsible for declining percentage of endocarditis compared to "enteric" strep such as S. gallolyticus subsp. gallolyticus and enterococci--probably due to aging population and less rheumatic heart disease
- For endocarditis use pathogen module of bloodstream isolate for therapy specifics.
- Therapy: β-lactams are preferred therapy.
- Penicillin G 2-4 million U IV q4h +/- gentamicin for synergy 1.0 mg/kg/q8h IV
- Ceftriaxone 2g IV once daily
- Vancomycin 15 mg/kg IV q12h (if PCN allergic)
- Tetracyclines, macrolides, clindamycin: use with caution as 25-50% isolates resistant.
- Note: TMP-SMX >75% resistance rates.
- There is increasing resistance to beta-lactams, esp. S. mitis (>40%).
- Duration 10-14 days (not endocarditis).
Streptococcus anginosus group
- Group comprises 3-15% of streptococcal isolates of endocarditis. See Endocarditis module for management, follow viridans Streptococci recommendations.
- Dental abscesses, sinusitis, fasciitis of head and neck: can be life threatening & require aggressive surgical management. See appropriate HEENT module for specific management.
- Bacteremia often associated with deep-seated abscess. Investigate for abscess--most often intraabdominal. Drainage is usually recommended.
- Brain abscesses often polymicrobial, but S. intermedius found in 50-80%. See Brain abscess module for management.
- Implicated in aspiration pneumonia, lung abscess and empyema.
- Treatment: penicillin G 2-4 million U IV q4h preferred.
- Alt: ceftriaxone 2g IV once daily; clindamycin 600-900mg IV q8h or 300-450mg PO four times a day or vancomycin 15 mg/kg IV q12h (PCN-allergic).
Group B Streptococcus (S. agalactiae)
- Bacteremia, soft tissue infections: PCN G 10-12 million units/d x 10d [e.g., give 2MU q4h or six divided doses/d ].
- Meningitis (adult): PCN G 20-24 million units/d x 14-21d.
- Osteomyelitis: PCN G 10-20 million units/d x 21-28d.
- Endocarditis: PCN G 20-24 million units/d x 4-6 wks AND gentamicin 1mg/kg q8h for first 2 wks.
- PCN allergic: may substitute vancomycin 15 mg/kg IV q 12h for PCN. Clindamycin can be considered, but rates of resistance vary. Consider confirming absence of inducible clindamycin resistance (typically associated with macrolide resistance) before using as monotherapy.
- Some use gentamicin (1 mg/kg q8h IV) additionally for any serious GBS infection.
- Prevention of perinatal infection:
- Indications for peripartum antibiotic prophylaxis to prevent early-onset (within seven days of birth) disease:
- Recovery of GBS from the urine during pregnancy
- Prior delivery of an infant who sustained invasive GBS disease
- Positive vaginal and/or rectal swabs at 35-37 weeks gestation (universal screening recommended if above criteria not met)
- If no screen result available prophylax if:
- < 37 weeks gestation
- Membrane rupture >18h
- Temperature >38C°
- No need for prophylaxis if cesarean delivery prior to rupture of amniotic membranes
- Recommended prophylactic regimens:
- Penicillin 5 million units IV x1, then 2.5-3.0 million units IV q4h until delivery
- Ampicillin 2 grams IV x1, then 1 gram IV q4h
- PCN allergic (non-anaphylactic, non-urticarial): cefazolin 2 grams IV x1, then 1 gram IV q8h
- PCN allergic (analphylactic or urticarial): clindamycin 900 mg IV q8h or vancomycin 1 g IV q12h (for clindamycin-resistant strains)
- D-test should be performed to confirm absence of inducible clindamycin resistance
- Erythromycin not recommended
Group D Streptococci
- Penicillin high-level resistance not described, some strains resistant to clindamycin.
- Bacteremia: PCN 12-18 million units/d IV x 10-14d.
- Endocarditis: PCN 14-18 million units/d IV x 4 weeks, may consider gentamicin 1mg/kg/ q8h to shorten duration to 2wks, OR use if PCN MIC >0.1, and definitely if MIC >0.5 and < 2 (rare).
Group C, E, F Streptococci:
- Bacteremia, cellulitis, septic arthritis or other serious infection: PCN 12-18 million units/d IV x 10-14d.
- Endocarditis: see Endocarditis module using viridans streptococci recommendations for specifics.
Abiotrophia and Granulicatella spp:
- Mainly a cause of endocarditis.
- Many isolates with some PCN resistance.
- See Endocarditis module using viridans Streptococci recommendations, though would not use 2wk "short-course" therapy.
General Considerations Regarding Streptococcal Endocarditis
- Four week duration of therapy considered standard. Short course (2 wk) possible if certain criteria met.
- Criteria favoring 2-wk short course beta-lactam + aminoglycoside combination for endocarditis:
- PCN sensitive oral viridans Streptococci or S. bovis (PCN MIC < 0.125mg/L).
- Native valve endocarditis.
- No heart failure, aortic insufficiency or conduction abnormality.
- No metastatic infectious foci.
- Quick clinical response and afebrile within 7d.
- Meningitis: Ceftriaxone 2 grams IV q12h x14 days; also consider penicillin G 24 million units/d x10-14 days.
- Patients who relapse after two weeks of therapy should received prolonged treatment (4-6 wks).
- Dexamethasone 0.4mg/kg q12h x 4d is standard recommendation for confirmed bacterial meningitis among adults in Southern Vietnam as morbidity and mortality has been shown to be reduced with administration.
Streptococcus pyogenes (Group A Strep)
Streptococcus pneumoniae (Pneumococcus)
Selected Drug Comments
Once a day IV/IM administered cephalosporin with activity against almost all strains of streptococci.
Active against most streptococci, though lower bioavailability and frequent dosing make it a choice for less serious infections.
In Europe, significant resistance described to macrolide class. In US smaller minority, in Japan nearly absent.
Available in both PO and IV forms. Well tolerated, but has a high incidence of C. difficile associated colitis. Not reliably active against S. viridans.
In Europe, significant resistance described to macrolide class. In US smaller minority, in Japan nearly absent.
May add for synergy in setting of endocarditis, serious bacteremia or if PCN MIC > 0.1.
Preferred therapy for susceptible strains of streptococci.
Active against all strains of streptococci. Must be given IV. Usually only used in settings of PCN allergy.
Has excellent in vitro MICs, but little published clinical experience with these Streptococcal spp., and now used infrequently due to hepatotoxicity concerns.
- A high proportion of blood cultures growing viridans streptococci may be due to cutaneous contamination, or transient oral bacteremia.
- Penicillin-resistance w/ viridans streptococci not due to beta-lactamase production (hence no benefit from using agents such as ampicillin/sulbactam).
- S. anginosus group especially confusing as can be either beta-hemolytic or non-hemolytic. Penicillin resistance is not an issue for the S. intermedius group.
- Recurrent invasive Group B Streptococcal infection described in 4% of nonpregnant adults within one year of first episode.
- Nutritionally-variant strains (Abiotrophia/Granulicatella) consider in "culture negative" endocarditis; special media historically required, though many modern broth micro systems should recover.
- While U.S. incidence rates of meningitis caused by Pneumococcus, Meningococcus, L. monocytogenes, and H. influenzae decreased significantly from 1998-2007, incidence rates for S. agalactiae meningitis (as well as bacterial meningitis incidence rates among infants < 2 months) did not decrease.
Basis for recommendation
- Baddour LM et al: Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 111:e394, 2005 [PMID:15956145]
Comment: Endocarditis treatment recommendations are based upon this document.
- Nguyen TH et al: Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med 357:2431, 2007 [PMID:18077808]
Comment: Although controversial, dexamethasone is now used as part of the treatment of adults with confirmed or suspected bacterial meningitis in southern Vietnam, in large part because of the positive impact on morbidity and mortality seen in cases of S. suis meningitis in this study.
- Shinzato T, Saito A: The Streptococcus milleri group as a cause of pulmonary infections. Clin Infect Dis 21 Suppl 3:S238, 1995 [PMID:8749672]
Comment: A study utilizing percutaneous microbiologic specimens of pulmonary infiltrates and pleural collections. A high proportion were found to involve organisms of the Streptococcus milleri group and synergy provided by oral anaerobic bacteria was demonstrated too.
- Boleij A et al: Novel clues on the specific association of Streptococcus gallolyticus subsp gallolyticus with colorectal cancer. J Infect Dis 203:1101, 2011 [PMID:21451000]
Interesting discussion of the pathogenic mechanisms by which (a) GI tract colonization with S. gallolyticus subsp. gallolyticus might increase among persons with colorectal cancer, and (b) increased incidence rates of endocarditis caused by this pathogen among these patients might be explained.
- Sendi P, Johansson L, Norrby-Teglund A: Invasive group B Streptococcal disease in non-pregnant adults : a review with emphasis on skin and soft-tissue infections. Infection 36:100, 2008 [PMID:18193384]
Comment: Comprehensive review of invasive S. agalactiae infections in non-pregnant adults. Authors note that diabetes and immunocompromise increase risk of infection. Bacteremia and skin/soft tissue infections are the most common kinds of infections, although toxic shock syndrome and necrotizing fasciitis are more recently recognized conditions related to this bacterium.
- Swenson FJ, Rubin SJ: Clinical significance of viridans streptococci isolated from blood cultures. J Clin Microbiol 15:725, 1982 [PMID:7068840]
Comment: Frequently cited paper indicating a high rate of rejection of blood cultures growing viridans streptococci as being contaminants (approximately 4 of 5 were felt to be such). This paper again highlights the "art" of medicine in the need to carefully weigh each situation rather than to have "knee jerk" responses to clinical microbiological data.
- Schattner A, Vosti KL: Bacterial arthritis due to beta-hemolytic streptococci of serogroups A, B, C, F, and G. Analysis of 23 cases and a review of the literature. Medicine (Baltimore) 77:122, 1998 [PMID:9556703]
Comment: Group A, B and G account for most cases, with only Group A associated with toxic-shock like features.
- Wertheim HF et al: Streptococcus suis: an emerging human pathogen. Clin Infect Dis 48:617, 2009 [PMID:19191650]
Comment: Interesting review article highlighting the emergence of S. suis as a zoonotic pathogen among pig farmers, particularly in southeast Asia, where it is a not uncommon cause of meningitis and hearing loss.
- Crum NF et al: Pneumonia outbreak associated with group a Streptococcus species at a military training facility. Clin Infect Dis 40:511, 2005 [PMID:15712072]
Comment: Largest outbreak of severe Group A strep pneumonia in > 30 years occurred in a military setting. This speaks to the potential for this organism to cause epidemic disease in close settings.
- Schoening TE, Wagner J, Arvand M: Prevalence of erythromycin and clindamycin resistance among Streptococcus agalactiae isolates in Germany. Clin Microbiol Infect 11:579, 2005 [PMID:15966978]
Comment: Levels of resistance seen with overall frequencies of erythromycin and clindamycin resistance were 11% and 4.7%, respectively. Inducible resistance was documented in some.
- Pfaller MA 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 Program. SENTRY Participants Group. Diagn Microbiol Infect Dis 33:283, 1999 [PMID:10212756]
Comment: Penicillin resistance among viridans group streptococci shown to have reached 48.5% in U.S among isolates tested.
- Edwards MS et al: Group B streptococcal colonization and serotype-specific immunity in healthy elderly persons. Clin Infect Dis 40:352, 2005 [PMID:15668856]
Comment: Raising rates of GBS infection in the elderly may be explained by the finding that colonization rates are similar, but elderly are more likely to be colonized by the V type that causes invasive disease.
- Elting LS, Bodey GP, Keefe BH: Septicemia and shock syndrome due to viridans streptococci: a case-control study of predisposing factors. Clin Infect Dis 14:1201, 1992 [PMID:1623076]
Comment: Report highlights the growing emergence of severe bacteremia (often continuous) in patients undergoing chemotherapy. Between 1972 and 1989, the incidence of viridans streptococcal bacteremia at the University of Texas M. D. Anderson Cancer Center in Houston increased from one case per 10,000 admissions to 47 cases per 10,000 admissions (P less than .0001). Risk factors also included TMP-SMX or FQ use, use of antacids leading others to suspect gastric source from chemotherapy-induced irritation. A shock syndrome w/hypotension, rash, palmar desquamation, ARDS developed in 26% of patients.
- Gold JS, Bayar S, Salem RR: Association of Streptococcus bovis bacteremia with colonic neoplasia and extracolonic malignancy. Arch Surg 139:760, 2004 [PMID:15249410]
Comment: Retrospective study highlights long known association with colon cancer (17/45 pts 41%), but also notes that 5/45 were found to have an extra-gastrointestinal malignancy.
- Facklam R: What happened to the streptococci: overview of taxonomic and nomenclature changes. Clin Microbiol Rev 15:613, 2002 [PMID:12364372]
Comment: Review will help reader navigate the treacherous waters of streptococcal nomenclature, but rest assured more changes will be forthcoming.
- Claridge JE et al: Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus ("Streptococcus milleri group") are of different clinical importance and are not equally associated with abscess. Clin Infect Dis 32:1511, 2001 [PMID:11317256]
Comment: The authors report data on 122 cases of Streptococcus milleri (now called either Streptococcus intermedius or S. anginosus Group) infection over a 1 year period. They found that 41/56 isolates of S. constellatus, 10/14 S. intermedius and 10/52 S. S. constellatus infections were associated with abscess formation. In addition, they note that S. intermedius was usually found as a monomicrobial pathogen, while S. constellatus and S. anginosus tended to cause polymicrobial infections.
- Thigpen MC et al: Bacterial meningitis in the United States, 1998-2007. N Engl J Med 364:2016, 2011 [PMID:21612470]
Nice epidemiologic summary of incidence rates of meningitis due to Pneumococcus, Meningococcus, L. monocytogenes, H. influenza, and S. agalactiae based upon laboratory- and population-based surveillance data. Rates of meningitis due to all pathogens save S. agalactiae decreased significantly over the interval.
- Colford JM, Mohle-Boetani J, Vosti KL: Group B streptococcal bacteremia in adults. Five years' experience and a review of the literature. Medicine (Baltimore) 74:176, 1995 [PMID:7623653]
Comment: This report is similar to five earlier studies showing that GBS in adult patients, most (66%) were more than 50 years old. Primary bacteremia was the most frequent clinical diagnosis, occurring in 7 (22%) of 32 patients. Nonhematologic cancer was the most frequently associated condition (25%). Nineteen percent of the patients had diabetes mellitis. The overall mortality rate was 31% and was significantly associated with increasing age.
- Verani JR et al: Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Recomm Rep 59:1, 2010 [PMID:21088663]
Excellent CDC guideline statement regarding the role of screening expectant mothers and administering prophylactic antibiotic therapy to reduce rates of invasive GBS disease among newborns. The universal screening strategy initially recommended in 1996 and revised twice since then has been associated with substantial rates in reduction of early-onset invasive GBS disease.
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