Antimicrobial therapy of streptococcal endocarditis

INTRODUCTION — 

Issues related to the antimicrobial therapy of streptococcal endocarditis will be reviewed here; the content reflects American and European guidelines [1,2].

General issues related to echocardiography are discussed separately. (See "Role of echocardiography in infective endocarditis".)

Issues related to clinical manifestations and diagnosis of native valve endocarditis (NVE), complications of NVE, and indications for surgery are discussed separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Complications and outcome of infective endocarditis" and "Surgery for left-sided native valve infective endocarditis".)

Issues related to clinical manifestations and diagnosis of prosthetic valve endocarditis (PVE), complications of PVE, and indications for surgery are discussed separately. (See "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis" and "Complications and outcome of infective endocarditis" and "Prosthetic valve endocarditis: Surgical management".)

Issues related to right-sided infective endocarditis (IE) are discussed separately. (See "Right-sided native valve infective endocarditis".)

Issues related to management of cardiac device infections are discussed separately. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Infections involving cardiac implantable electronic devices: Treatment and prevention".)

Issues related to management of mycotic aneurysm and brain abscess are discussed separately. (See "Overview of infected (mycotic) arterial aneurysm" and "Treatment and prognosis of bacterial brain abscess".)

GENERAL MANAGEMENT CONSIDERATIONS — 

An overview of the management of infective endocarditis (IE) in adults is presented separately. (See "Overview of management of infective endocarditis in adults" and "Antimicrobial therapy of left-sided native valve endocarditis", section on 'General considerations' and "Antimicrobial therapy of prosthetic valve endocarditis", section on 'General considerations'.)

Management considerations include:

●Assessing the clinical response to therapy

●Tailoring antibiotic therapy

●Duration of therapy

●Logistics for completing therapy

●Role of therapy

●Follow-up

●Relapse

VIRIDANS STREPTOCOCCI AND STREPTOCOCCUS BOVIS/STREPTOCOCCUS EQUINUS COMPLEX

Nomenclature and minimum inhibitory concentration (MIC) breakpoints

●Members of viridans streptococci group – Members include Streptococcus mitis, Streptococcus mutans, Streptococcus oralis, Streptococcus sanguinis, Streptococcus gordonii, Streptococcus sobrinus, and the Streptococcus milleri group (Streptococcus anginosus, Streptococcus constellatus, and Streptococcus intermedius).

●Nomenclature – The nomenclature of the S. bovis/S. equinus complex is summarized in the table (table 1). Streptococcus gallolyticus subspecies gallolyticus has the strongest association with IE [3,4]. (See "Infections due to Streptococcus bovis/Streptococcus equinus complex (SBSEC; formerly group D streptococci)".)

●MIC breakpoints – The MIC breakpoints differ between the guidelines published by the American Heart Association (AHA) and European Committee on Antimicrobial Susceptibility Testing (EUCAST), which have been adopted by the European Society of Cardiology (ESC) [1,2,5]; the MIC breakpoints are summarized in the tables (table 2 and table 3 and table 4 and table 5 and table 6 and table 7).

Native valve endocarditis

Penicillin-susceptible strains — MIC breakpoints and treatment regimens for native valve endocarditis (NVE) due to highly penicillin-susceptible streptococci are summarized in the table (table 2) [1,2].

●Clinical approach – For treatment of patients with NVE due to highly penicillin-susceptible streptococci (defined by the AHA as MIC ≤0.12 mcg/mL), we are in agreement with the AHA and ESC which favor aqueous penicillin G (adult dosing: 12 to 18 million units daily intravenously [IV], either continuously or in four to six equally divided doses) or ceftriaxone for four weeks [1,2]. For transitioning from inpatient to outpatient therapy, parenteral ceftriaxone (adult dosing: 2 g once daily IV) may be used in place of penicillin.

For patients with uncomplicated NVE in the absence of underlying kidney or cranial nerve VIII disease, those who have a prompt response to initial therapy may be treated with a shortened (two-week) duration of combination therapy (beta-lactam plus gentamicin). In such cases, gentamicin may be given as a single daily dose (3 mg/kg per day, with appropriate monitoring). In a randomized trial including 61 patients with NVE due to penicillin-susceptible streptococci treated with a four-week ceftriaxone regimen or a two-week combination of ceftriaxone plus gentamicin, cure rates were similar [6].

In choosing between a four-week beta-lactam regimen and a two-week combination regimen, the risks of longer treatment duration must be weighed against the risks of gentamicin toxicity. (See 'Weighing risks and benefits of gentamicin' below.)

●Patients with penicillin allergy – Patients with penicillin allergy (in the absence of immediate-type hypersensitivity) may be treated with ceftriaxone. For patients with immediate-type hypersensitivity, we favor desensitization to penicillin if feasible. (See "Rapid drug desensitization for immediate hypersensitivity reactions".)

Alternatively, patients may be treated with vancomycin for four weeks. Daptomycin should not be used routinely as an alternative to vancomycin. (See 'No role for daptomycin' below.)

Relatively penicillin-resistant strains — MIC breakpoints and treatment regimens for NVE due to relatively penicillin-resistant streptococci are summarized in the table (table 3) [1,2].

●Clinical approach – For treatment of patients with NVE due to relatively penicillin-resistant streptococci (defined by the AHA as MIC >0.12 mcg/mL and <0.5 mcg/mL), we are in agreement with the AHA which recommends aqueous penicillin G (adult dosing: 24 million units daily IV, either continuously or in four to six equally divided doses) for a total of four weeks, in combination with gentamicin for the first two weeks [1]. (See 'Use of gentamicin' below.)

A reasonable alternative regimen is ceftriaxone monotherapy for four weeks (if the isolate is susceptible) [1,7].

●Patients with penicillin allergy – Patients with immediate-type hypersensitivity to beta-lactams may be treated with vancomycin monotherapy for four weeks. Penicillin desensitization and combination therapy with gentamicin are an alternative [1]. (See "Rapid drug desensitization for immediate hypersensitivity reactions".)

Daptomycin should not be used routinely as an alternative to vancomycin. (See 'No role for daptomycin' below.)

Fully penicillin-resistant strains — MIC breakpoints and treatment regimens for NVE due to fully penicillin-resistant streptococci are summarized in the table (table 4).

●Clinical approach – For treatment of patients with NVE due to fully penicillin-resistant streptococci (defined by the AHA as MIC ≥0.5 mcg/mL), we are in agreement with the ESC approach which consists of treatment with aqueous penicillin G (adult dosing: 24 million units daily IV, either continuously or in four to six equally divided doses) or ceftriaxone (2 g per 24 hours IV) for four weeks, combined with gentamicin (3 mg/kg per 24 hours IV in one dose) for at least two weeks [2]. Another approach is to use vancomycin monotherapy, particularly in patients with a contraindication to gentamicin. In rare cases when the penicillin MIC is ≥2 mcg/mL and gentamicin is not contraindicated, a beta-lactam-gentamicin combination regimen may be preferable [8]. (See 'Use of gentamicin' below.)

The combination of ampicillin and ceftriaxone is not an acceptable regimen for treatment of NVE due to penicillin-resistant streptococci, given insufficient clinical experience with this approach. (See "Antimicrobial therapy of left-sided native valve endocarditis", section on 'Enterococci'.)

●Patients with penicillin allergy – For patients with penicillin allergy, IV vancomycin for four weeks is warranted [1,2]. Alternatively, penicillin desensitization can be performed to facilitate use of a beta-lactam-gentamicin combination regimen; this may be particularly relevant for patients with IE due to isolates with penicillin MIC ≥2 mcg/mL [8]. (See "Rapid drug desensitization for immediate hypersensitivity reactions".)  

Daptomycin should not be used routinely as an alternative to vancomycin. (See 'No role for daptomycin' below.)

Prosthetic valve endocarditis

Penicillin-susceptible strains — MIC breakpoints and treatment regimens for prosthetic valve endocarditis (PVE) due to highly penicillin-susceptible streptococci are summarized in the table (table 5). In general, a treatment duration of six weeks is advised.

●Clinical approach – For treatment of streptococcal PVE due to penicillin-susceptible streptococci (defined by the AHA as MIC ≤0.12 mcg/mL), we agree with the AHA, which recommends a beta-lactam antibiotic (eg, penicillin, ampicillin, or ceftriaxone) for six weeks, with the option to add gentamicin for the initial two weeks [1].

Issues related to use of gentamicin, including testing for high-level gentamicin resistance, are discussed below. (See 'Use of gentamicin' below.)

●Patients with penicillin allergy – An alternative regimen for beta-lactam-intolerant patients consists of vancomycin monotherapy for six weeks.

Relatively penicillin-resistant strains — MIC breakpoints and treatment regimens for PVE due to relatively penicillin-resistant streptococci are summarized in the table (table 6).

●Clinical approach – The preferred regimen for streptococcal PVE due to relatively penicillin-resistant strains (defined by the AHA as MIC >0.12 mcg/mL and <0.5 mcg/mL) consists of combination therapy with a beta-lactam antibiotic (eg, penicillin, ampicillin, or ceftriaxone) for six weeks and gentamicin for at least two weeks. (See 'Use of gentamicin' below.)

If gentamicin is relatively contraindicated (see 'Weighing risks and benefits of gentamicin' below), or the isolate has high-level gentamicin resistance, monotherapy with vancomycin may be given [9].

●Patients with penicillin allergy – An alternative regimen for beta-lactam-intolerant patients consists of vancomycin monotherapy for six weeks. Another approach is desensitization followed by beta-lactam-gentamicin combination therapy. Daptomycin should not be substituted for vancomycin. (See 'No role for daptomycin' below.)

Fully penicillin-resistant strains — MIC breakpoints and treatment regimens for PVE due to fully penicillin-resistant streptococci are summarized in the table (table 7).

●Clinical approach – For patients with PVE due to fully penicillin-resistant streptococci (defined by the AHA as MIC ≥0.5 mcg/mL), management consists of combination therapy with a beta-lactam antibiotic (eg, penicillin, ampicillin, or ceftriaxone) and gentamicin (in the absence of high-level resistance), both for six weeks. (See 'Use of gentamicin' below.)

●Alternative regimen – If the patient is intolerant of penicillin and ceftriaxone, or if gentamicin cannot be used, vancomycin monotherapy should be used [8]. For patients in whom gentamicin can be used, another approach is desensitization followed by beta-lactam-gentamicin combination therapy. In rare cases when the penicillin MIC is ≥2 mcg/mL and gentamicin is not contraindicated, a beta-lactam-gentamicin combination regimen may be preferable [8]. (See 'Use of gentamicin' below.)

In general, we do not favor combination treatment with vancomycin plus gentamicin (despite synergistic bactericidal activity against penicillin-resistant streptococci), given the increased risk of nephrotoxicity with this approach.

Use of gentamicin — Considerations for use of gentamicin include testing for high-level resistance, side effects, and approach to dosing and monitoring.

Rationale for use in combination therapy — Combination beta-lactam-gentamicin therapy is used to achieve synergistic killing of streptococci [10]. Gentamicin synergizes with cell wall inhibitors (ie, beta-lactams) for bactericidal activity.

This approach is based on in vitro studies, in vivo studies using experimental endocarditis models, clinical series, and clinical experience [11,12]. However, there are no trials demonstrating the superiority of combination therapy over penicillin monotherapy.

Testing for high-level gentamicin resistance — Various genetic pathways mediate high-level resistance to streptomycin (and less frequently to gentamicin) in a small percentage of streptococci that cause endocarditis; in these isolates, the presence of high-level gentamicin resistance abrogates the bactericidal synergy of combination therapy [13-16].

For these reasons, laboratory testing for high-level gentamicin resistance should be performed prior to initiation of combination therapy, if possible. However, the optimal approach to screening streptococci for high-level gentamicin resistance is uncertain; there is no Clinical Laboratory Standards Institute guidance for testing that identifies strains where synergy will not occur.

Detection of high-level gentamicin resistance using either of the following methods suggests inadequate bactericidal synergy with combination therapy; in such cases, gentamicin toxicity is likely to exceed therapeutic benefit.

●Bacterial growth on brain-heart infusion agar plates in the setting of high gentamicin concentrations. Brain-heart infusion agar plates are commercially available for high-level resistance screening in enterococci.

●Streptococcal gentamicin MIC ≥512 mcg/mL (using EUCAST methodology) may predict loss of synergy; however, this correlation has not been established definitively [17].

Weighing risks and benefits of gentamicin — The decision to use gentamicin involves careful consideration of risk for kidney toxicity and ototoxicity (based on age and underlying medical conditions), balanced against the anticipated benefit of bactericidal synergy. Use of gentamicin is relatively contraindicated in the setting of baseline kidney function impairment and/or cranial nerve VIII dysfunction [9].

Gentamicin dosing and monitoring

●Frequency – The optimal approach to gentamicin dosing is uncertain. To reduce the risk of kidney injury, we favor administration of gentamicin as a single daily dose (rather than in three divided doses) [2]. We favor this approach based on general studies indicating decreased risk of nephrotoxicity with extended-interval dosing [18].  

●Monitoring – Kidney function and gentamicin serum concentrations should be monitored at least once per week. When given in a single daily dose, pre-dose (trough) concentrations should be <1 mcg/mL. We do not measure peak levels; per AHA guidelines, there are no optimal peak drug concentrations for single daily dosing. Per ESC guidelines, post-dose (peak, one hour after injection) serum concentrations should be approximately 10 to 12 mcg/mL.

No role for daptomycin — Daptomycin should not be used routinely as an alternative to vancomycin for the treatment of endocarditis caused by viridans streptococci. Emergence of stable high-level resistance to daptomycin has been observed in at least 25 percent of the S. mitis group isolates (S. mitis, S. oralis, and S. sanguinis) with exposure to daptomycin in vitro and in experimental endocarditis models. Resistance has also emerged in Streptococcus parasanguinis, Abiotrophia spp, and Granulicatella adiacens [8,19,20].

STREPTOCOCCUS PNEUMONIAE

Regimen selection — The approach to regimen selection for treatment of S. pneumoniae endocarditis depends on the following factors [1,2]:

●Presence or absence of meningitis – Pneumococcal endocarditis typically occurs in the context of pneumococcal pneumonia and may be complicated by concurrent meningitis [21].

●Beta-lactam susceptibility – S. pneumoniae strains relatively or fully resistant to penicillin are emerging; such strains may also be resistant to other beta-lactams and other antimicrobial agents.

Data to inform the optimal approach to the treatment of cases due to these isolates are limited [22,23].

Absence of meningitis

●Penicillin-susceptible strains (per the American Heart Association [AHA], minimum inhibitory concentration [MIC] ≤0.1 mcg/mL) – For treatment of infective endocarditis (IE) due to these strains, we treat with penicillin (12 to 18 million units per 24 hours continuously or in four to six divided doses) or ceftriaxone (2 g every 24 hours).

●Relatively penicillin-resistant strains (per AHA, MIC >0.1 to 1 mcg/mL) – For treatment of IE due these strains, we treat with high dose penicillin (24 million units per 24 hours continuously or in four to six divided doses), high dose ceftriaxone (2 g every 12 hours), or vancomycin.

●Fully penicillin-resistant strains (per AHA, MIC ≥2 mcg/mL) – For treatment of IE due to these strains, we favor vancomycin. Data for IE due to fully penicillin-resistant pneumococci are limited to rare case reports in which vancomycin was commonly a part of the treatment regimen [24].

While in vitro beta-lactam resistance among pneumococci may be overcome by using higher doses of beta-lactams, clinical data on the efficacy of different doses for beta-lactams in this setting are limited [22].

●Patients with beta-lactam allergy – Patients with immediate-type hypersensitivity reaction to beta-lactams may be treated with vancomycin [1].

Presence of meningitis — In the setting of pneumococcal IE with concomitant meningitis, in vitro susceptibility to cefotaxime or ceftriaxone should be obtained; penicillin penetrates poorly into the cerebrospinal fluid. (See "Treatment of bacterial meningitis caused by specific pathogens in adults", section on 'Streptococcus pneumoniae'.)

●Ceftriaxone/cefotaxime-susceptible strains (per AHA, MIC <2 mcg/mL) – For treatment of IE in the setting of meningitis due to these strains, we treat with ceftriaxone (2 g intravenously [IV] every 12 hours) or cefotaxime (2 g IV every four to six hours) [1,2].

●Ceftriaxone/cefotaxime-resistant strains (per AHA, MIC ≥2 mcg/mL) – For treatment of IE in the setting of meningitis due to these strains, we treat with ceftriaxone or cefotaxime with the addition of vancomycin (table 8).

In addition, adjunctive rifampin (900 mg every 24 hours IV or by mouth in three divided doses) or a respiratory fluoroquinolone (ie, moxifloxacin or levofloxacin) may be warranted in patients who are severely ill or do not respond to initial treatment [1,2].

After sufficient treatment for meningitis (10 to 14 days), the remaining treatment course is directed towards treatment of IE; at that point, we continue with vancomycin monotherapy.

Duration of therapy — The duration of treatment for pneumococcal native valve endocarditis (NVE) is four weeks; the duration of treatment for pneumococcal prosthetic valve endocarditis (PVE) is six weeks.

Additional treatment considerations — Pneumococcal NVE is usually fulminant and causes severe valve damage and embolic complications; valve replacement may be necessary [25]. Therefore, vigilance for sudden valve dysfunction and the need for urgent valve surgery is warranted. (See "Surgery for left-sided native valve infective endocarditis".)

Issues related to extracardiac pneumococcal infection are discussed separately. (See "Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia in adults".)

STREPTOCOCCAL GROUPS A, B, C, F, AND G — 

Streptococcal groups A, B, C, F, and G are rare causes of infective endocarditis (IE) [21,26].

●Group A Streptococcus – These strains are highly susceptible to penicillin.

•Native valve endocarditis (NVE) – For treatment of NVE due to Streptococcus pyogenes, we are in agreement with the American Heart Association (AHA), which recommends treatment with aqueous penicillin G (24 million units intravenously [IV] continuously or in four to six divided doses) for four to six weeks; ceftriaxone (2 g IV every 24 hours) is a reasonable alternative [1]. We favor the longer course of therapy for patients with slow clinical response and/or extra cardiac sites of infection requiring prolonged treatment.  

•Prosthetic valve endocarditis (PVE) – For treatment of PVE due to S. pyogenes, we treat with penicillin or ceftriaxone for six weeks.

For patients who are intolerant of beta-lactams, vancomycin may be used.

●Streptococcal groups B, C, F, and G  

•NVE – For treatment of NVE due to streptococci belonging to serogroups B, C, F, and G, we treat with aqueous penicillin G (24 million units IV continuously or in four to six divided doses) for four to six weeks or ceftriaxone (2 g IV every 24 hours). We favor the longer course of therapy for patients with slow clinical response and/or have extra cardiac sites of infection requiring prolonged treatment.  

In addition, some experts favor adding gentamicin to a penicillin or cephalosporin for the first two weeks of therapy since some strains of groups B, C, F, and G streptococci are more resistant to penicillin than S. pyogenes [1]. We base this decision on susceptibility data, severity of clinical presentation, and risk for gentamicin nephrotoxicity.

•PVE – For treatment of PVE due to streptococci belonging to serogroups B, C, F, and G, we treat with penicillin or ceftriaxone for six weeks, with addition of gentamicin for the initial two weeks.

Rarely, high-level gentamicin resistance has been reported in these organisms; if gentamicin is to be used during the initial two weeks of therapy, the isolate should be screened for high-level gentamicin resistance if possible. (See 'Testing for high-level gentamicin resistance' above.)

STREPTOCOCCAL-LIKE ORGANISMS — 

Streptococcal-like organisms include Abiotrophia defectiva, Granulicatella spp, and Gemella spp.

The treatment regimen should be selected carefully based on the antimicrobial susceptibility of the isolate. This is particularly important for Abiotrophia defectiva and Granulicatella spp. Among G. adiacens, 40 percent are penicillin-susceptible; however, this does not predict ceftriaxone susceptibility. In contrast, A. defectiva is typically susceptible to ceftriaxone; however, this does not predict penicillin susceptibility. Both are generally susceptible to vancomycin [27].

●Native valve endocarditis (NVE) – Contingent on susceptibility, we are in agreement with the European Society of Cardiology (ESC) guidelines which suggest treating NVE due to A. defectiva or Granulicatella spp with aqueous penicillin G (adult dosing: 24 million units intravenously [IV] continuously or in four to six divided doses), ceftriaxone (2 g IV every 24 hours), or vancomycin for six weeks [2].

●Prosthetic valve endocarditis (PVE) – Contingent on susceptibility, we suggest treatment with a beta-lactam antibiotic (eg, aqueous penicillin G [adult dosing: 24 million units daily], ampicillin, or ceftriaxone) for six weeks, in combination for gentamicin (in the absence of high-level resistance) for at least the first two weeks, with longer duration of gentamicin for organisms with higher minimum inhibitory concentrations (MICs).

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment and prevention of infective endocarditis" and "Society guideline links: Outpatient parenteral antimicrobial therapy".)

SUMMARY AND RECOMMENDATIONS

●General treatment principles

•Antibiotic selection

-Beta-lactam therapy – Treatment of endocarditis due to penicillin-susceptible or relatively penicillin-resistant streptococci consists of beta-lactam therapy. For most patients with streptococcal endocarditis, we suggest completion of treatment with ceftriaxone rather than penicillin (Grade 2C), due to ease of dosing and favorable tolerability.

-Use of gentamicin – Adjunctive gentamicin may be warranted depending on the type of valve (native versus prosthetic), drug susceptibility data, and risk for kidney toxicity and/or ototoxicity. (See 'Use of gentamicin' above.)

•Fully penicillin-resistant streptococci – For treatment of infective endocarditis (IE) due to these organisms, we suggest combination therapy (beta-lactam plus gentamicin) (Grade 2C); vancomycin monotherapy is an alternative, particularly in patients with contraindications to gentamicin.

•Antibiotic duration – For treatment for native valve endocarditis (NVE), we suggest a treatment duration of at least four weeks (Grade 2C); for treatment of prosthetic valve endocarditis (PVE), we suggest a treatment duration of six weeks (Grade 2C).

●Viridans streptococci and the Streptococcus bovis/Streptococcus equinus complex – Antimicrobial dosing regimens for treatment of IE due to viridans group streptococci and the S. bovis/S. equinus complex are summarized in the tables (table 2 and table 3 and table 4 and table 5 and table 6 and table 7). (See 'Viridans streptococci and Streptococcus bovis/Streptococcus equinus complex' above.)

For treatment of IE due to viridans streptococci and the S. bovis/S. equinus complex that are fully penicillin-resistant, we suggest combination therapy (beta-lactam plus gentamicin) (Grade 2C); vancomycin monotherapy is an alternative.

●Streptococcus pneumoniae (see 'Streptococcus pneumoniae' above)

•Absence of meningitis (see 'Absence of meningitis' above)

-Penicillin-susceptible strains (per the American Heart Association [AHA], minimum inhibitory concentration [MIC] ≤0.1 mcg/mL) – Treatment of IE due to these strains consists of penicillin (12 to 18 million units per 24 hours) or ceftriaxone (2 g every 24 hours).  

-Relatively penicillin-resistant streptococci (per AHA, MIC 0.12 to 1 mcg/mL) – Treatment of IE due to these strains consists of high-dose penicillin (24 million units per 24 hours), high-dose ceftriaxone (2 g every 12 hours), or vancomycin.

-Fully penicillin-resistant strains (per AHA, MIC ≥2 mcg/mL) – Treatment of IE due to these organisms consists of vancomycin.

•Presence of meningitis (see 'Presence of meningitis' above)

-Cephalosporin-susceptible strains (per AHA, MIC <2 mcg/mL) – Treatment of IE due to these strains consists of ceftriaxone (2 g intravenously [IV] every 12 hours) or cefotaxime (2 g IV every four to six hours).  

-Cephalosporin-resistant strains (per AHA, MIC ≥2 mcg/mL) – Treatment of IE due to these strains consists of ceftriaxone or cefotaxime with the addition of vancomycin. In addition, adjunctive rifampin or a respiratory fluoroquinolone may be warranted in patients who are severely ill or do not respond to initial treatment. After sufficient treatment for meningitis (10 to 14 days), we continue with vancomycin monotherapy.

●Streptococcal groups A, B, C, F, and G (see 'Streptococcal groups A, B, C, F, and G' above)

•Antimicrobial selection  

-Group A Streptococcus – Treatment of IE due to these organisms consists of aqueous penicillin G (adult dosing: 24 million units daily) or ceftriaxone.

-Groups B, C, F, and G streptococci – Treatment of IE due to these organisms consists of aqueous penicillin G (adult dosing: 24 million units daily) or ceftriaxone. Adjunctive gentamicin for the first two weeks may be warranted, depending on drug susceptibility data and risk for kidney toxicity and/or ototoxicity.

•Duration of therapy – The duration of treatment for NVE caused due to these organisms is four to six weeks; we favor a longer course of therapy for patients with slow clinical response and/or extra cardiac sites of infection. The duration of treatment for PVE is six weeks.

●Streptococcal-like organisms – Streptococcal-like organisms include Abiotrophia defectiva, Granulicatella spp, and others. The treatment regimen should be selected carefully based on the antimicrobial susceptibility of the isolate. (See 'Streptococcal-like organisms' above.)

•Contingent on susceptibility, treatment of NVE and PVE due to A. defectiva or Granulicatella spp consists of aqueous penicillin G (adult dosing: 24 million units IV continuously or in four to six divided doses), ceftriaxone, or vancomycin for six weeks.

•For patients with PVE, adjunctive gentamicin may be warranted depending on drug susceptibility data and risk for kidney and/or ototoxicity.