Efficacy of Tigecycline Alone and in Combination with Gentamicin in the Treatment of Experimental Endocarditis Due to Linezolid-Resistant Enterococcus faecium
Abstract:bWe evaluated the efficacy of tigecycline in a rabbit model of experimental endocarditis caused by a linezolid-resistant clinical strain of Enterococcus faecium. Tigecycline-treated animals had a 2.8-log 10 -CFU/g reduction in microbial counts in excised vegetations compared with controls. Addition of gentamicin caused a further arithmetical reduction in colony counts. The therapeutic effect was sustained 5 days after completion of treatment, as shown by relapse studies performed in treatment groups.
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“…Tigecycline, a novel glycylcycline, has been shown in experimental studies to be effective against a broad range of multidrug-resistant (MDR) Enterobacteriaceae such as carbapenem-resistant K. pneumoniae, either alone or in combination with other antimicrobial agents [3,4]. Moreover, several experimental reports suggest that it can be a possible salvage therapeutic option to treat IE due to MDR bacteria [5,6]. Here we report the case of patient admitted to the ICU of Habib Bourguiba University Hospital because of severe head injury.…”
“…Tigecycline, a novel glycylcycline, has been shown in experimental studies to be effective against a broad range of multidrug-resistant (MDR) Enterobacteriaceae such as carbapenem-resistant K. pneumoniae, either alone or in combination with other antimicrobial agents [3,4]. Moreover, several experimental reports suggest that it can be a possible salvage therapeutic option to treat IE due to MDR bacteria [5,6]. Here we report the case of patient admitted to the ICU of Habib Bourguiba University Hospital because of severe head injury.…”
“…Tigecycline has also been evaluated in combination with gentamicin. In a rabbit model of endocarditis caused by VRE faecium , tigecycline produced a significant decrease in bacterial load of vegetation in comparison to no treatment, and addition of gentamicin led to further reduction in colony count . Interestingly, sustainable antimicrobial activity of tigecycline alone and in combination with gentamicin was observed on day 5 after completion of treatment.…”
Section: Combination Antibiotic Therapymentioning
confidence: 97%
“…In a rabbit model of endocarditis caused by VRE faecium, tigecycline produced a significant decrease in bacterial load of vegetation in comparison to no treatment, and addition of gentamicin led to further reduction in colony count. 69 Interestingly, sustainable antimicrobial activity of tigecycline alone and in combination with gentamicin was observed on day 5 after completion of treatment. Similarly, in an in vitro, time-kill analysis including two strains of VRE faecium evaluating tigecycline and tigecycline combinations, addition of gentamicin improved bactericidal activity of tigecycline against both strains, even though the degree of enhancement was minimal in one strain.…”
Enterococcus species are the second most common cause of nosocomial infections in the United States and are particularly concerning in critically ill patients with preexisting comorbid conditions. Rising resistance to antimicrobials that were historically used as front-line agents for treatment of enterococcal infections, such as ampicillin, vancomycin, and aminoglycosides, further complicates the treatment of these infections. Of particular concern are Enterococcus faecium strains that are associated with the highest rate of vancomycin resistance. The introduction of antimicrobial agents with specific activity against vancomycin-resistant Enterococcus (VRE) faecium including daptomycin, linezolid, quinupristin-dalfopristin, and tigecycline did not completely resolve this clinical dilemma. In this review, the mechanisms of action and resistance to currently available anti-VRE antimicrobial agents including newer agents such as oritavancin and dalbavancin will be presented. In addition, novel combination therapies including b-lactams and fosfomycin, and the promising results from in vitro, animal studies, and clinical experience in the treatment of VRE faecium will be discussed.
“…Immunosuppression, prior surgery and previous exposure to β-lactam antibiotics have been recently identified as the predictors of linezolid resistance development against vancomycin-resistant enterococci [175], and no worse outcomes have been found for those strains developing resistance to linezolid [176,177]. Tigecycline, alone or combined with gentamicin, has shown good activity against linezolid-resistant E. faecium strains [178]. However, some authors suggest using linezolid with precaution in VRE endocarditis until more data are made available [43].…”
The Enterococcus species is the third main cause of infective endocarditis (IE) worldwide, and it is gaining relevance, especially among healthcare-associated cases. Patients with enterococcal IE are older and have more comorbidities than other types of IE. Classical treatment options are limited due to the emergence of high-level aminoglycosides resistance (HLAR), vancomycin resistance and multidrug resistance in some cases. Besides, few new antimicrobial alternatives have shown real efficacy, despite some of them being recommended by major guidelines (including linezolid and daptomycin). Ampicillin plus ceftriaxone 2 g iv./12 h is a good option for Enterococcus faecalis IE caused by HLAR strains, but randomized clinical trials are essential to demonstrate its efficacy for non-HLAR EFIE and to compare it with ampicillin plus short-course gentamicin. The main mechanisms of resistance and treatment options are also reviewed for other enterococcal species.
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