p.32 抽出テキスト

7.4. Streptococcus pneumoniae, β-haemolytic streptococci (groups A, B, C, and G) Infective endocarditis due to Streptococcus pneumoniae has become rare. It is associated with meningitis and pneumonia in up to 30% of cases,293–296 which requires special consideration in cases with penicillin resistance. Treatment of penicillin-susceptible strains is similar to that of oral streptococci (see Recommendation Table 7), except for the use of short-term 2-week therapy, which has not been thoroughly investigated. The same holds true for penicillin-susceptible increased exposure or resistant strains without meningitis, although for resistant strains some authors recommend high doses of cephalosporins (e.g. cefotaxime or ceftriaxone) or vancomycin.295 In cases with meningitis, penicillin must be avoided because of its poor penetration into the cerebrospinal fluid, and should be replaced with ceftriaxone or cefotaxime alone, or in association with vancomycin according to the antibiotic susceptibility pattern.297,298 After 10–14 days of therapy and when meningitis is not associated, OPAT or outpatient oral antibiotic therapy should be considered if clinically stable (see Section 7.13). Infective endocarditis due to group A, B, C, or G streptococci, including the Streptococcus anginosus group (S. constellatus, S. anginosus, and S. intermedius) is relatively rare.299,300 Group A streptococci are uniformly susceptible to beta-lactams, whereas other serogroups may display some degree of resistance. Infective endocarditis due to group B streptococci was once associated with the peripartum period, but it now occurs in all adults, especially the elderly. Groups B, C, and G streptococci and S. anginosus induce abscesses that require adjunctive surgery.300 Mortality from group B PVE is very high and cardiac surgery is recommended.301 Antibiotic treatment is similar to that of oral streptococci (see Recommendation Table 7), except that short-term (2 weeks) therapy is not recommended and gentamicin should be given for 2 weeks.

7.5 Granulicatella and Abiotrophia

(formerly nutritionally variant streptococci) Granulicatella and Abiotrophia induce IE with a prolonged course and are associated with large vegetations (>10 mm), and consequently with high rates of complications and valve replacement (around 50%).302,303 This is possibly due to delayed diagnosis and treatment. Antibiotic recommendations include penicillin G, ceftriaxone, or vancomycin for 6 weeks, combined with an aminoglycoside for at least the first 2 weeks in case of PVE (for doses, please see Recommendation Table 7).302–304

7.6 Staphylococcus aureus and

coagulase-negative staphylococci Staphylococcus aureus is usually responsible for acute and destructive IE,305 whereas CoNS can induce more protracted valve infections.306,307 Of note, the addition of an aminoglycoside in staphylococcal NVE is no longer recommended because it increases renal toxicity.264,308 Short-term (2-week) and oral treatments have been proposed for uncomplicated right-sided native valve methicillinsusceptible S. aureus (MSSA) IE (see also Section 12.4.2), but these regimens cannot be applied to left-sided IE. For penicillin-allergic patients with MSSA IE, penicillin desensitization can be attempted in stable patients or cefazolin can be used since vancomycin is inferior to betalactams.309 If beta-lactams cannot be given, where available, daptomycin should be chosen and given in combination with another effective antistaphylococcal drug to increase activity and avoid the development of resistance.310 Staphylococcus lugdunensis is mostly methicillinsusceptible and can be treated with cloxacillin.

Staphylococcus aureus PVE carries a very high risk of mortality (>45%),305,312,313 and often requires early valve replacement. Other differences in comparison with NVE include the overall duration of therapy, the use of aminoglycosides, and the addition of rifampin after 3–5 days of effective antibiotic therapy once the bacteraemia has been cleared.264,314–318 The rationale supporting this recommendation is based on the antagonistic effect of the antibiotic combinations with rifampin against planktonic/replicating bacteria as has been demonstrated in foreign body infection models and clinically in prosthetic orthopaedic and vascular infections.319 However, a recent study has shown that the addition of aminoglycosides to a regimen containing vancomycin or cloxacillin plus rifampicin in S. aureus PVE was not associated with a better outcome.320 In addition, the risk of nephrotoxicity associated with the use of aminoglycosides should be taken into consideration. Adding rifampin to the treatment of staphylococcal PVE is standard practice despite the weak evidence.261,321 The potential side effects and drug interactions of rifampin should also be considered. In patients with PVE who are allergic to penicillin, daptomycin can be given combined with ceftaroline or fosfomycin or with gentamicin (for 2 weeks) plus rifampin for at least 6 weeks. After 10–14 days of therapy, OPAT or outpatient oral antibiotic therapy should be considered if clinically stable (see Section 7.13).

7.7 Methicillin-resistant staphylococci

Methicillin-resistant S. aureus (MRSA) produces low-affinity penicillinbinding proteins (PBPs), which confer cross-resistance to most betalactams. Methicillin-resistant S. aureus is usually resistant to multiple antibiotics, leaving vancomycin, daptomycin, ceftaroline, and dalbavancin to treat severe infections.322–324 However, it should be noted that subpopulations susceptible with increased exposure and resistant to vancomycin have emerged worldwide and are associated with IE treatment failures.325–328 The prevalence of MRSA causing IE that is susceptible with increased exposure or resistant to vancomycin ranges between 19% and 34%. In addition, among patients with IE caused by MRSA, those isolates with a population analysis profile MIC ≥4 mg/L were associated with treatment failure defined by persistent bacteriaemia for ≥7 days or MRSA-attributable mortality.325 Nephrotoxicity is of concern when using trough monitoring of levels of vancomycin as a surrogate marker of the area under the curve relative to the MIC (AUC/MIC). Therefore, it is recommended to use a target of AUC/ MIC between 400 and 600 mg*h/L (assuming an MIC of 1 mg/L) that should be achieved with 48 h of therapy.329 When the MIC is >1 mg/ L, the probability of achieving an AUC/MIC ≥400 is unlikely. In that clinical scenario, changing therapy should be considered due to the high risk of nephrotoxicity with higher doses of vancomycin. Daptomycin is a lipopeptide antibiotic approved for S. aureus bacteraemia and right-sided IE.330 Cohort studies of S. aureus and CoNS IE have shown that daptomycin is at least as effective as vancomycin,327,328 and, in two cohort studies of MRSA bacteraemia with high vancomycin MICs (>1 mg/ L),331,332 daptomycin was associated with better outcomes (including survival) compared with vancomycin. Importantly, daptomycin needs to be administered in appropriate doses and combined with other antibiotics to avoid further resistance in patients with IE.330,333 Therefore, daptomycin should be given at high doses (10 mg/kg), and most experts recommend its combination with beta-lactams334 or fosfomycin335 (beta-lactams [and probably fosfomycin] increase membrane

ESC Guidelines                                                                                                                                                                                          3979

Downloaded from academic.oup.com/eurheartj/article/44/39/3948/7243107 by guest on 07 October 2026