By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

SYNOPSIS: In a retrospective study, the investigators failed to find evidence of benefit of adjunctive rifampin therapy in patients with staphylococcal prosthetic valve endocarditis.

SOURCE: Le Bot A, Lecomte R, Gazeau P, et al. Is rifampin use associated with better outcome in staphylococcal prosthetic valve endocarditis? A multicenter retrospective study. Clin Infect Dis 2021;72:e249-e255.

Le Bot and colleagues retrospectively examined 180 episodes of prosthetic valve endocarditis (PVE) managed at three French referral centers from 2000-2018 to evaluate the role of adjunctive rifampin therapy, which was administered during 101 episodes (56.1%). The mean age was 70.4 years, and approximately three-fourths were male. A bioprosthesis was affected in 111 patients (61.7%). Cerebral emboli occurred in 53 patients (29.4%).

The etiologic agent was Staphylococcus aureus in 114 episodes (63.3%), and 17 (14.9%) of these were methicillin-resistant. The remaining 66 episodes (36.7%) were due to coagulase negative staphylococci (CoNS), 39 (59.0%) of which were methicillin-resistant.

All patients received antibiotics intravenously as recommended by international (U.S. and European) guidelines: cefazolin or an antistaphylococcal penicillin with gentamicin for methicillin-susceptible infection and, for those that were methicillin-resistant, a glycopeptide or daptomycin with gentamicin.1 The baseline characteristics of those who did and did not receive rifampin were similar, with the exception of the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), which was etiologic in 14/64 (21.9%) and 3/50 (6.0%), respectively (P = 0.04). No isolate was rifampin-resistant. Rifampin was initiated a median of seven days after diagnosis of PVE at a median dose of 1,200 mg per day for a median duration of 33 days. However, it was discontinued in 31 (30.9%) patients because of severe adverse events, the most frequent of which was hepatotoxicity in 11 patients. Fifty-one (28.3%) patients underwent valve surgery, 94% of them within 60 days of diagnosis of PVE.

The overall in-hospital mortality was 23.6%, increasing to 35.4% at 12 months with no significant difference related to use of rifampin, with the exception of hospital length of stay, which was nine days longer among rifampin recipients. Relapse occurred in 6/101 (5.9%) rifampin recipients and 7/79 (8.5%; P = 0.65) of those who did not receive rifampin. None of the six relapse isolates associated with rifampin therapy were resistant to this rifamycin. Only three factors were independently and significantly associated with greater 12-month mortality: cerebral emboli, definite endocarditis by Duke criteria, and MRSA infection.  

COMMENTARY

Guidelines of both the American Heart Association and the European Society for Cardiology recommend that staphylococcal PVE be treated with a triple antibiotic combination. They each recommend intravenous (IV) cefazolin or an antistaphylococcal penicillin for methicillin-susceptible infections or either a glycopeptide or daptomycin for those caused by methicillin-resistant organisms, either combined with IV gentamicin for the first two weeks with rifampin for the entire six-week duration of therapy and state that these are Class I recommendations. This three-drug recommendation may have arisen originally from a report of small numbers of patients with methicillin-resistant CoNS PVE, with most of the patients having undergone valve replacement and, thus, making the results uninterpretable as I indicated in a review a dozen years ago.2 Furthermore, my interpretation of the use of gentamicin for these infections is that it clearly adds toxicity in the absence of demonstrated clinical benefit. This is consistent with a report by the Spanish Collaboration on Endocarditis.3

Le Bot and colleagues, reviewing the most recent literature regarding the use of rifampin, together with their own experience, reach a similar conclusion, as do Galar et al.1 Remember “primum non nocere” drop the rifampin and gentamicin. 

REFERENCES

  1. Galar A, Weil AA, Dudzinski DM, et al. Methicillin-resistant Staphylococcus aureus prosthetic valve endocarditis: Pathophysiology, epidemiology, clinical presentation, diagnosis, and management. Clin Microbiol Rev 2019;32:e00041-18.
  2. Deresinski S. Vancomycin in combination with other antibiotics for the treatment of serious methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 2009;49:1072-1079.
  3. Ramos-Martínez A, Muñoz Serrano A, de Alarcón González A, et al; Spanish Collaboration on Endocarditis – Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES). Gentamicin may have no effect on mortality of staphylococcal prosthetic valve endocarditis. J Infect Chemother 2018;24:555-562.