Λοιμώδης ενδοκαρδίτιδα

Παρουσίαση με θέμα: "Λοιμώδης ενδοκαρδίτιδα"— Μεταγράφημα παρουσίασης:

1 Λοιμώδης ενδοκαρδίτιδα
Σαμπατάκου Ελένη Επίκουρη Καθηγήτρια ΙΓΝΑ

2 Disclosures/ conflict of interest
Grants/ research support from: Astellas Gilead Consultant/ speaker for: Pfizer BMS MSD ViiV

3 Επιδημιολογία ενδοκαρδίτιδας
Επίπτωση: 3-7/ Αύξηση ηλικίας – Μεταξύ χρηστών ενδοφλέβιων ουσιών η συχνότητα είναι: / άτομα-έτη Αυξημένη επίπτωση λοιμώξεων από σταφυλοκόκκους Αύξηση αντοχής στα αντιμικροβιακά Βακτηριαιμία σχετιζόμενη με υγειονομική περίθαλψη Changing over the past decade due to: Increased longevity New predisposing factors Nosocomial infections Ποιοί έχουν αυξημένο κίνδυνο; >65y με εκφυλιστικές βαλβιδοπάθειες IVDU Προσθετικές Βαλβίδες/Βηματοδότες/Απινιδωτές Χρονίως αιμοκαθαιρόμενοι

4 Διάκριση ενδοκαρδίτιδας
ΑΡΙΣΤΕΡΩΝ ΦΥΣΙΚΩΝ ΒΑΛΒΙΔΩΝ 70% θνητότητα: 15% κοινότητα, 30% HCA ΑΡΙΣΤΕΡΩΝ ΠΡΟΣΘΕΤΙΚΩΝ ΒΑΛΒΙΔΩΝ Θνητότητα: >30% ΔΕΞΙΩΝ ΚΟΙΛΟΤΗΤΩΝ 5-10% συγγενείς καρδιοπάθειες, ivdu, βηματοδότης, εμφ.απινιδωτής, κφγ, AIDS Θνητότητα<10% (50% AIDS) Λ.Ε σχετιζόμενη με υγειονομική περίθαλψη: 30% θνητότητα ~30% Ηλικία, υποκείμενα νοσήματα, λοίμωξη σε προσθετική βαλβίδα, λοίμωξη από S. aureus, P. aeruginosa, ή ανθεκτικά παθογόνα σχετίζονται με κακή πρόγνωση Η επιβίωση σε ασθενείς με ενδοκαρδίτιδα σε φυσική βαλβίδα από viridans streptococci, HACEK, ή Enterococci ανέρχεται σε 85-90% 4

5 Τροποποιημένα κριτήρια Duke για την κλινική διάγνωση ενδοκαρδίτιδος
Μείζονα κριτήρια Θετικές αιμοκαλλιέργειες Απομόνωση μικροοργανισμού τυπικού για ενδοκαρδίτιδα από 2 διαφορετικές καλλιέργειες αίματος ή Συνεχής βακτηριαιμία (πλειοψηφία των αιμοκαλλιεργειών θετικές) Αντισώματα φάσης Ι έναντι Coxiella burnetii > 1:800 ή μία θετική καλ/γεια Προσβολή ενδοκαρδίου (ΤΤΕ, ΤΕΕ) Εκβλάστηση, παραβαλβιδικό απόστημα, νέα ανεπάρκεια βαλβίδας Blood culture positive for IE Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or community-acquired enterococci in the absence of a primary focus, or microorganisms consistent with IE from persistently positive blood cultures defined as follows: at least 2 positive cultures of blood samples drawn >12 h apart or all 3 or a majority of ≥4 separate cultures of blood (with first and last sample drawn at least 1 h apart) Single positive blood culture for Coxiella burnetii or anti–phase 1 IgG antibody titer ≥1:800 Evidence of endocardial involvement Echocardiogram positive for IE (TEE recommended for patients with prosthetic valves, rated at least possible IE by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients)

6 Τροποποιημένα κριτήρια Duke για την κλινική διάγνωση ενδοκαρδίτιδος
Ελάσσονα κριτήρια Υποκείμενη καρδιακή πάθηση, χρήστης ΕΦ ουσιών, προηγούμενο επεισόδιο ενδοκαρδίτιδας Πυρετός>38°C Αγγειακά φαινόμενα: Σηπτικά έμβολα, μυκωτικά ανευρύσματα, ενδοκράνια αιμορραγία, αιμορραγίες επιπεφυκότων, βλάβες Janeway Ανοσολογικές εκδηλώσεις: Σπειραματονεφρίτιδα, οζίδια του Osler, κηλίδες του Roth, ΡΠ Μικροβιολογική απόδειξη: Θετικές καλλιέργειες αίματος που δεν πληρούν τα μείζονα κριτήρια Predisposition, predisposing heart condition, or IDU Fever, temperature >38°C Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions Immunological phenomena: glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor Microbiological evidence: positive blood culture but does not meet a major criterion as noted above

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8 ανάλογα με την κλινική εικόνα
Παθογόνα αίτια ανάλογα με την κλινική εικόνα Oξεία ενδοκαρδίτιδα Υποξεία ενδοκαρδίτιδα Viridans streptococci HACEK Coagulase (-) Staphylococci (CoNS) Enterococci Bartonella T. whipplei C. burnetii S. aureus β-hemolytic streptococci Str. pneumoniae Gram negative Acute: S aureus, β-hemolytic streptococci, and aerobic Gram negative subacute (weeks) presentation of NVE, coverage of S aureus, VGS, HACEK, and enterococci is reasonable Streptococci Viridans streptococci/α-haemolytic streptococci S. mitis, S. sanguis, S. oralis S. bovis Associated with colonic carcinoma Enterococci E. faecalis, E. faecium Associated with GU/GI tract procedures Approx. 10% of patients with enterococcal bacteraemia develop endocarditis Staphylococci Staphylococcci have surpassed viridans streptococci as the most common cause of infective endocarditis S. aureus Native valves acute endocarditis Coagulase-negative staphylococci Prosthetic valve endocarditis 8

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10 Prospective randomized Korea Systemic emboli
Prospective, randomized study, 76 pts ( Sept 2006-March 2011) Patients with left-sided infective endocarditis, severe valve disease, and large vegetations to early surgery . The primary end point in-hospital death and recurrence οr embolic events within 6 weeks Early-surgery within 48 hours The primary end point occurred in 1 patient (3%) in the early surgery group as compared with 9 (28%) in the conventional-treatment group ( P = 0.03). There was no significant difference in all-cause mortality at 6 months (3% and 5%,) The rate of the composite end point of death from any cause, Prospective randomized Korea Systemic emboli Risk depends on valve (mitral>aortic), size of vegetation, (high risk if >10 mm) 20-40% of patients with endocarditis, risk decreases once appropriate antimicrobial therapy started. Indications: Congestive cardiac failure perivalvular invasive disease uncontrolled infection despite maximal antimicrobial therapy Pseudomonas aeruginosa, Brucella species, Coxiella burnetti, Candida and fungi Presence of prosthetic valve endocarditis unless late infection Large vegetation Major embolus Heart block METHODS We randomly assigned patients with left-sided infective endocarditis, severe valve disease, and large vegetations to early surgery (37 patients) or conventional treatment (39). The primary end point was a composite of in-hospital death and embolic events that occurred within 6 weeks after randomization. RESULTS All the patients assigned to the early-surgery group underwent valve surgery within 48 hours after randomization, whereas 30 patients (77%) in the conventional-treatment group underwent surgery during the initial hospitalization (27 patients) or during follow-up (3). The primary end point occurred in 1 patient (3%) in the earlysurgery group as compared with 9 (23%) in the conventional-treatment group (hazard ratio, 0.10; 95% confidence interval [CI], 0.01 to 0.82; P = 0.03). There was no significant difference in all-cause mortality at 6 months in the early-surgery and conventional-treatment groups (3% and 5%, respectively; hazard ratio, 0.51; 95% CI, 0.05 to 5.66; P = 0.59). The rate of the composite end point of death from any cause, embolic events, or recurrence of infective endocarditis at 6 months was 3% in the early-surgery group and 28% in the conventional-treatment group (hazard ratio, 0.08; 95% CI, 0.01 to 0.65; P = 0.02). CONCLUSIONS As compared with conventional treatment, early surgery in patients with infective endocarditis and large vegetations significantly reduced the composite end point of death from any cause and embolic events by effectively decreasing the risk of systemic embolism. (EASE ClinicalTrials.gov number, NCT )

11 Διάρκεια θεραπείας μετά από Κ/Χ επέμβαση για ΛΕ?
Διάρκεια 2 εβδομάδων φαίνεται επαρκής σε ασθενείς μετά από Κ/Χ επέμβαση λόγω ΛΕ -ιδιαίτερα από VGS or Str. gallolyticus (bovis)- με αρνητικές καλ/γειες ιστών βαλβίδας Παρουσία βακτηρίων σε ιστολογική εξέταση ή σε Gram χρώση βαλβίδας με αρνητικές καλ/γειες δεν αποτελούν κριτήριο για παράταση του χρόνου αγωγής μετά την Κ/Χ επέμβαση This, however, has been challenged by retrospectively collected data from 2 different medical centers116,117 Whether a 2-week treatment course would be sufficient after valve surgery in patients with positive valve cultures either was not addressed in 1 survey116 or included only 5 patients in the other.117 For patients with NVE who undergo valve resection with prosthetic valve replacement or repair with an annuloplasty ring, there is a lack of consensus as to whether the postoperative treatment regimen should be one that is recommended for prosthetic valve treatment rather than one that is recommended for native valve treatment. In regimens that contain combination antimicrobial therapy, it is reasonable to administer agents at the same time or temporally close together to maximize the synergistic killing effect on an infecting pathogen. It is reasonable that the counting of days for the duration of antimicrobial therapy begin on the first day on which blood cultures are negative in cases in which blood cultures were initially positive (Class IIa; Level of Evidence C). . If operative tissue cultures are positive, then an entire antimicrobial course is reasonable after valve surgery (Class IIa; Level of Evidence B). 5. If operative tissue cultures are negative, it may be reasonable to count the number of days of antimicrobial therapy administered before surgery in the overall duration of therapy (Class IIb; Level of Evidence C). 6. It is reasonable to time the administration of antimicrobial therapy at the same time or temporally close together for regimens that include >1 antimicrobial agent (Class IIa; Level of Evidence C). 11

12 “Culture Negative” ενδοκαρδίτιδα
Ποσοστό 5-10% ασθενών με ΛΕ έχουν στείρες καλ/γειες Επιλογή αγωγής δυσχερής ( ευρύ φάσμα παθογόνων, τοξικότητα φαρμάκων ) Μοριακές τεχνικές? Χρόνος λήψης απάντησης? Οξεία ΛΕ σε φυσική βαλβίδα ( St. aureus, Streptococcus sp, Gram (-) Μη λοιμώδη αίτια: αντιφωσφολιπιδαιμικό σύνδρομο, νεοπλασίες, μυξωματώδεις βλάβες, μαραντική ενδοκαρδίτιδα, αυτοάνοσα νοσήματα, θρόμβοι Εμπειρική θεραπεία αφού ληφθούν αιμ/γειες!!!!! ΑΜΒ μειώνουν τις θετικές καλ/γειες 35-40% Οξεία ΛΕ σε φυσική βαλβίδα ( St. aureus, Streptococcus sp, Gram (-) vanco plus maxipime Υποξεία σε φυσικη βαλβίδα St aureus, VGS, Hacek, enterococci ( vanco και begalin) Σε προσθετική: staph, enterococci gram negative within 1 year ( vanco+rifa +genta+cefepime) 1 year valve replacement staph, VGS, enteroc ( vanco+ceftriaxone Αυτοάνοσα: reymatic carditis, SEL, polyarteritis nodosa, Behcet )

13 Θεραπευτικές αρχές “Inoculum Effect” Bακτηριοκτόνα φάρμακα
Διάρκεια θεραπείας Συγκέντρωση φαρμάκου PK/PD και δοσολογία

14 Περιστατικό 1 Ασθενής 35 ετών, IVDU, προσέρχεται με πυρετό έως
39ο C από τριημέρου. Σε αιμ/γειες απομόνωση st. aureus (4/4). Έπεται αντιβιόγραμμα Εκβλάστηση 10mm στην τριγλώχινα σε ΤΤΕ Εμπειρική έναρξη με τι? Αντισταφυλ/κική πενικιλλίνη και βανκομυκίνη Βανκομυκίνη και γενταμυκίνη Δαπτομυκίνη Δαπτομυκίνη και αμινογλυκοσίδη Άλλο

15 Περιστατικό 1 Απομόνωση MSSA. Ποιο σχήμα θα χορηγήσετε?
Αντισταφυλ/κική πενικιλλίνη για 6 εβδομάδες Αντισταφυλ/κική πενικιλλίνη και γενταμυκίνη για 2 εβδ Βανκομυκίνη και γενταμυκίνη για 6 εβδομ Βανκομυκίνη για 6 εβδομ Αντισταφ/κή πενικιλλίνη για 2 εβδομ Σιπροφλοξασίνη και ριφαμπικίνη per os Δαπτομυκίνη και αμινογλ για 6εβδ Δαπτομυκίνη για 2 εβδ

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17 IE Caused by Staphylococci in the Absence of Prosthetic Valves
Right-Sided IE in IDUs Combined short-course (2 weeks) β-lactam plus aminoglycoside therapy was highly effective in several studies. In patients for whom parenteral antibiotic therapy is problematic, oral treatment (ciprofloxacin plus rifampin) may be a reasonable option. Gentamicin is not recommended (Class III; Level of Evidence B). In 1 study, 92 patients provided such combination therapy had excellent outcomes, even HIV-infected patients and those who had large tricuspid valve vegetations (>10 mm in diameter). In contrast, short-course regimens with glycopeptides (teicoplanin or vancomycin) plus gentamicin appeared to be less effective for right-sided S aureus IE caused by either MSSA or MRSA strains.91 These glycopeptides may be less effective because of limited bactericidal activity, poor penetration into vegetations, or increased drug clearance among IDUs. A growing body of evidence suggests that the addition of adjunctive aminoglycoside therapy not only is unnecessary for patients with uncomplicated right-sided native valve S aureus IE but may cause harm.1 Two studies have evaluated the use of predominantly oral 4-week antibiotic regimens (featuring ciprofloxacin plus rifampin) for the therapy of uncomplicated right-sided MSSA IE in IDUs.149,150 In each study, including one in which >70% of patients were HIV seropositive,149 cure rates were >90%. However, the relatively high rate of quinolone resistance among contemporary S aureus strains has made this alternative treatment strategy problematic. 17

18 Open, randomized study, Barcelona, Spain ( no 90) .
Measurements: Clinical or microbiological evidence of infection , relapse or death. After 2 weeks of therapy Τreatment was successful in 89% (34 / 38 pts) with monotherapy vs 86% (31 /36 pts) with combination Three patients died: one in the cloxacillin group and two in the combination therapy group. In monotherapy, 34 /37(92%) were cured, and 3 (8%) needed prolonged Rx In the combination: 32/34 (94%) were cured and 2 (6%) Rx for 4 weeks Background: It is often difficult to administer extended antibiotic therapy in the hospital for right-sided Staphylococcus aureus endocarditis. Although the effectiveness of single-drug therapy given for 4 to 6 weeks and that of two-drug therapy given for 2 weeks have been shown, no data are available on the effectiveness of short-course single-drug therapy. Objective: To compare the efficacy of cloxacillin alone with that of cloxacillin plus gentamicin for the 2-week treatment of right-sided S. aureus endocarditis in intravenous drug users. Design: Open, randomized study. Setting: An academic tertiary care hospital in Barcelona, Spain. Patients: 90 consecutive intravenous drug users who had isolated tricuspid valve endocarditis caused by methicillinsusceptible S. aureus, had no allergy to study medications, and had no systemic infectious complications that required prolonged therapy. An efficacy subset consisted of 74 of these patients who did not meet an exclusion criterion. Intervention: Cloxacillin (2 g intravenously every 4 hours for 14 days) alone or combined with gentamicin (1 mg/kg of body weight intravenously every 8 hours for 7 days). Measurements: Clinical or microbiological evidence of active infection after 2 weeks of therapy, relapse of staphylococcal infection, or death. Results: In an analysis of the efficacy subset, treatment was successful in 34 of the 38 patients who received cloxacillin alone (89% [95% CI, 75% to 97%]) and 31 of the 36 patients who received cloxacillin plus gentamicin (86% [CI, 71% to 95%]). Three patients died: one in the cloxacillin group and two in the combination therapy group. Of the 37 patients who completed 2-week treatment with cloxacillin, 34 (92%) were cured, and 3 (8%) needed prolonged treatment to cure the infection. Of the 34 patients who completed 2-week treatment with cloxacillin plus gentamicin, 32 (94%) were cured and 2 (6%) required treatment for 4 weeks. One patient in the combination group had relapse. Conclusions: A penicillinase-resistant penicillin used as single-agent therapy for 2 weeks was effective for most patients with isolated tricuspid endocarditis caused by methicillin-susceptible S. aureus. Adding gentamicin did not appear to provide any therapeutic advantages. Additional studies to confirm the therapeutic equivalence ofshort-course therapy with penicillinase-resistant penicillin alone and therapy with combined regimens are warranted.

19 Βανκομυκίνη: Πόσο ασφαλής επιλογή?
Βανκομυκίνη: Πόσο ασφαλής επιλογή? Βreakpoints: CLSI Guidelines παθογόνο Susceptibility MIC breakpoint (µg/ml) VSSA Susceptible ≤2 hVISA Heteroresistant 1–2a VISA Intermediate 4–8 VRSA Resistant ≥16 a Αποτελείται από υποπληθυσμούς(≤1 σε 1,000,000) που αναπτύσσονται σε θρεπτικά υλικά με >2 µg/ml vancomycin

20 MICs σε Vanco και κλινική έκβαση σε βακτηριαιμία από MRSA
1/10 ασθενείς έχει κλινική επιτυχία με βανκομυκίνη, όταν η MIC είναι 1-2 1 Sakoulas, J Clin Microbiol 2004 2 Moise-Broder, Clin Infect Dis 2004

21 Ανασκόπηση 62 κλινικών περπτώσεων από 36
αναφορές λοιμώξεων από MRSA Όταν στελέχη MRSA είναι hVISA σε παρατεταμένη βακτηριαιμία μπορεί να προδιαθέτει σε ανάπτυξη αντοχής σε Daptomycin !!!!! Σημασία υποδοσολογικών σχημάτων Daptomycin? ( ≤ 6mg/kg/d ) Συνδυασμός daptomycin με β-λακτάμη?

22 Περιστατικό 2 Aσθενής 82 ετών με ιστορικό κυστεοσκοπήσεων
λόγω θηλωμάτων , προσέρχεται με πυρετό, έκπτωση επιπέδου συνείδησης. Από αιμ/γειες απομόνωση E. faecalis (3/4). ΤΕΕ: εκβλάστηση μιτροειδούς βαλβίδος eGFR 45ml/min/m2

23 Περιστατικό 2 1. Αμπικιλλίνη και γενταμυκίνη (τροποποιημένη δόση) 2 εβδομάδες 2. Κρυσταλλική πενικιλλίνη και γενταμυκίνη 6 εβδομάδες 3. Aμπικιλλίνη και γενταμυκίνη 6 εβδ 4. Αμπικιλλίνη και κεφτριαξόνη για 6 εβδομάδες 5. Δαπτομυκίνη για 6 εβδ 6. Λινεζολίδη για 6 εβδ Γενταμυκινη ClCr >60 every 8 h ClCr every 12 20-40 ever 24 <20 loading dose, then monitor levels

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25 Enterococcal Endocarditis Susceptible to Penicillin, Vanco, and Aminoglycosides
1. Therapy with ampicillin or aqueous crystalline penicillin G plus gentamicin or ampicillin plus ceftriaxone is reasonable (Class IIa; Level of Evidence B). 2. Either 4 or 6 weeks of therapy is reasonable for NVE, if ampicillin or penicillin plus gentamicin is used (Class IIa; Level of Evidence B). 3. Six weeks of therapy if ampicillin plus ceftriaxone is selected as the treatment regimen, regardless of symptom duration (Class IIa; Level of Evidence B). 4 or 6 weeks of therapy is reasonable for NVE, depending on the duration of IE symptoms before Patients with <3 months’ duration of symptoms were treated successfully with 4 weeks of antimicrobial therapy. Patients with ≥3 months’ duration of symptoms were successfully treated with 6 weeks of therapy 4. Six weeks of antimicrobial therapy is reasonable for PVE (Class IIa; Level of Evidence B). 5. Streptomycin should be avoided in patients with creatinine clearance <50 mL/min (Class III; Level of Evidence B). 6. If the strain of Enterococcus is susceptible to both gentamicin and streptomycin, it is reasonable to use gentamicin rather than streptomycin for therapy (Class IIa; Level of Evidence C). 7. When gentamicin therapy is not an option, then a double–β-lactam regimen (see later section) is reasonable (Class IIa; Level of Evidence B). 25

26 Enterococcal Endocarditis Susceptible to Penicillin,
Vancomycin, and Aminoglycosides Patients with preexisting (Clcr 30–50 mL/min) or <30 mL/min) renal failure may not be able to safely complete a 4- to 6-week course of gentamicin therapy Alternative regimens that should be considered include the use of streptomycin, short course gentamicin (2–3 weeks), and use of a non–aminoglycoside-containing double–β-lactam regimen.

27 Αγωγή με 2–β-λακτάμες σε ΛΕ από E faecalis
Συνδυασμός ampicillin και imipenem δρά συνεργικά σε MDR πειραματική ενδοαρδίτιδα (1) ampicillin-ceftriaxone αποτελεσματική σε πειραματική ΛΕ gentamicin-S και R από E faecalis (2) Σε 2 πολυκεντρικές μελέτες σε Ισπανία και Ιταλία, σύγκριση ampicillin-ceftriaxone με ampicillin-gentamicin σε ΛΕ gentamicin-S και R (3,4) 1. Brandt et al. JID 1996, 2. Gavalda et al. AAC 1999 3 . Gavalda et al An Intern Med 2007, 4 Fernandez-Hidalgo et al. CID 2013 Because there are few therapeutic alternatives to aminoglycoside- containing regimens, combinations of β-lactams were tested in vitro and in animal models of enterococcal experimental IE. Despite these limitations, these 2 studies provide important data. First, these are the largest series of E faecalis IE reported to date, 43 patients in 1 study 190 and 272 in the other study.191 Second, high-level aminoglycoside-resistant E faecalis IE treated with ampicillin-ceftriaxone therapy was present in 50% of the patients in the smaller study and 33% of patients in the larger study. Third, none of the patients in either study developed nephrotoxicity with ampicillin-ceftriaxone therapy, whereas 20 of 87 (23%) ampicillin-gentamicin–treated patients developed nephrotoxicity (P<0.001). Fourth, in the larger study, the median age was 70 years in both treatment groups; however, patients in the ampicillin-ceftriaxone group were generally sicker and had more comorbid conditions (eg, chronic renal failure [P=0.004], neoplasm [P=0.015], and nosocomial acquisition of infection [P=0.006]). Fifth, in 1 study, PVE was present in 59 (37%) and 30 (34%) of patients treated with ampicillin-ceftriaxone and ampicillin gentamicin, respectively, with similar success rates. Sixth, in the larger study, there were no significant differences between ampicillin-ceftriaxone and ampicillin-gentamicin in the need for surgery, complications (except for fewer cases of renal failure in the ampicillin-ceftriaxone group), relapse, or mortality. Finally, the overall microbiological cure and success rates for ampicillin-ceftriaxone therapy in both studies were similar to rates in previously reported studies in patients treated with aminoglycoside-containing regimens.190,191 The major advantages of the ampicillin-ceftriaxone regimen are the lower risk of nephrotoxicity and the lack of need for measuring aminoglycoside serum concentrations. The potential disadvantage is the possibility of hypersensitivity reactions to 2 separate β-lactams. Because it would likely not be possible to discriminate between hypersensitivities related to ampicillin or to ceftriaxone, both drugs might have to be discontinued with substitution of vancomycin-gentamicin therapy. At this time, the writing group does not have a preference for one regimen over the other but rather advocates an individualized approach to regimen selection for each patient. The likely mechanism of double–β-lactam combinations against enterococci is saturation of different penicillin-binding proteins. These in vitro and in vivo studies provided the rationale for double–β-lactam therapeutic trials in humans with E faecalis IE caused by gentamicin-susceptible or high-level gentamicin-resistant strains. Both of these clinical studies had significant limitations: They were observational, largely retrospective, and nonrandomized; the regimens were not standardized among the different centers; discontinuation of gentamicin therapy was at the discretion of the investigators and not always the result of gentamicin-associated nephrotoxicity; and the serum concentrations of gentamicin were not assessed or reported in all study sites. 27

28 ↑ Creat ≥ 25%: 23% AG vs 0%, AC. P < .001)
An observational, nonrandomized, comparative multicenter cohort study ( 17 Spanish and 1 Italian hospitals.) patients: 246 (159 vs 87) Νo differences in mortality (22% vs 21%, , p:0.81) οn Rx or at 3 months follow up (8% vs 7%, p:0.72), Rx failure (1% vs 2%, p:0.54), relapses (3% vs 4$, p:0,67) ↑ Creat ≥ 25%: 23% AG vs 0%, AC. P < .001) Background. The aim of this study was to compare the effectiveness of the ampicillin plus ceftriaxone (AC) and ampicillin plus gentamicin (AG) combinations for treating Enterococcus faecalis infective endocarditis (EFIE). Methods. An observational, nonrandomized, comparative multicenter cohort study was conducted at 17 Spanish and 1 Italian hospitals. Consecutive adult patients diagnosed of EFIE were included. Outcome measurements were death during treatment and at 3 months of follow-up, adverse events requiring treatment withdrawal, treatment failure requiring a change of antimicrobials, and relapse. Results. A larger percentage of AC-treated patients (n = 159) had previous chronic renal failure than AG-treated patients (n = 87) (33% vs 16%, P = .004), and AC patients had a higher incidence of cancer (18% vs 7%, P = .015), transplantation (6% vs 0%, P = .040), and healthcare-acquired infection (59% vs 40%, P = .006). Between AC and AG-treated EFIE patients, there were no differences in mortality while on antimicrobial treatment (22% vs 21%, P = .81) or at 3-month follow-up (8% vs 7%, P = .72), in treatment failure requiring a change in antimicrobials (1% vs 2%, P = .54), or in relapses (3% vs 4%, P = .67). However, interruption of antibiotic treatment due to adverse events was much more frequent in AG-treated patients than in those receiving AC (25% vs 1%, P < .001), mainly due to new renal failure (≥25% increase in baseline creatinine concentration; 23% vs 0%, P < .001). Conclusions. AC appears as effective as AG for treating EFIE patients and can be used with virtually no risk of renal failure and regardless of the high-level aminoglycoside resistance status of E. faecalis.

29 Native or Prosthetic Valve ΙΕ or Other Prosthetic Material From
Enterococcus Species Caused by Strains Resistant to Penicillin, Aminoglycosides, and Vancomycin Linezolid 600 mg IV or orally every 12 h >6 Class IIb; Level of Evidence C Cardiac valve replacement may be necessary for cure. Daptomycin 10–12 mg/kg per dose >6 Class IIb; Level of Evidence C Linezolid use may be associated with potentially severe bone marrow suppression, neuropathy, and numerous drug interactions. Patients with IE caused by these strains should be treated by a care team including specialists in infectious diseases, cardiology, cardiac surgery, clinical pharmacy, and, in children, pediatrics. 29

30 Γλυκοπεπτίδια βραδείας δράσης, Νέα εποχή!!!!
Vancomycin & Teicoplanin οι παλιοί εκπρόσωποι Πρόσφατα εγκεκριμένα Telavancin : 2009 για cSSSIs (MRSA), για HAP (2013) Συστήνεται περιορισμένη χρήση Oritavancin : FDA Approved August 2014, EMA Approved May 2015 ( ABSSSI ) Dalbavancin : FDA Approved May 2014, EMA March 2015 ( ABSSSI, in phase III for CABP ) Telavancin is a new intravenous lipoglycopeptide antibiotic with activity against staphylococci (including methicillin-resistant strains), streptococci, and vancomycin-susceptible enterococci. It is dosed once daily and does not require serum-level monitoring. Indication: Telavancin is FDA approved for the treatment of complicated skin and skin-structure infections (cSSTIs) in adults. It was found to be noninferior to vancomycin for this purpose in a pooled analysis of two randomized controlled trials. The FDA recently denied approval of telavancin for nosocomial pneumonia, requesting additional dat This class of drugs inhibit the synthesis of cell walls in susceptible microbes by inhibiting peptidoglycan synthesis. They bind to the amino acids within the cell wall preventing the addition of new units to the peptidoglycan. In particular they bind to acyl-D-alanyl-D-alanine in peptidoglycan Telavancin Άπαξ ημερησίως με έγκριση για επιπλεγμένες λοιμώξεις SSSIs , περιλαμβανομένων MSSA, MRSA 2 φάσης ΙΙΙ RCTs (ATTAIN I,II) για HAP,VAP: σύσταση FDA για περιορισμένη χρήση Warnings: 1.Συχνότερη ↑ Creat 1.5 fold vs Vanco (15 vs 7%), νεφροτοξικότητα (3.1 vs 1.1%) 2.↓ δραστικότητα σε Ν.Α vs Vanco 3. απουσία δεδομένων αποτελεσματικότητας σε μικροβιαιμία 4. τερατογένεση: κατηγορία C Προς το παρόν συστήνεται η χρήση σε σοβαρές λοιμώξεις από MRSA, με Vanco MIC ≥1μg/mL, σε λοιμώξεις από hVISA, MRSA που δεν απαντούν σε Vanco και βακτηριαιμία από Gram(+) και με δυσανεξία σε άλλο εγκεκριμένο ΑΜΒ. Προβλήματα παραγωγής….

31 H διάγνωση και θεραπεία της ενδοκαρδίτιδας απαιτούν συνεργασία

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