Endocarditis Caused by Methicillin‐Resistant<i>Staphylococcus aureus:</i>Treatment Failure with Linezolid

Rúiz, María Elena; Guerrero, Isabel C.; Tuazon, Carmelita U.

doi:10.1086/342698

Cited by 92 publications

(45 citation statements)

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“…One study reported that vancomycin alone was more effective than either the combination of linezolid and vancomycin or linezolid alone for the treatment of MRSA endocarditis (18). Additionally, there have been several clinical reports of treatment failures (10,46,48). Our results are consistent with several published in vivo and in vitro studies suggesting that linezolid is bacteriostatic and may not be effective in patients with complicated sequestered infections such as infective endocarditis.…”

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confidence: 87%

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Impact of High-InoculumStaphylococcus aureuson the Activities of Nafcillin, Vancomycin, Linezolid, and Daptomycin, Alone and in Combination with Gentamicin, in an In Vitro Pharmacodynamic Model

LaPlante

Rybak

2004

Antimicrob Agents Chemother

262

209

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We evaluated the impact of high (9.5 log 10 CFU/g) and moderate (5.5 log 10 CFU/g) inocula of methicillinsusceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) on the activities of nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant (P < 0.01) bactericidal (99.9% kill) activities (decreases of 3.34 ؎ 1.1, 3.28 ؎ 0.4, and 3.34 ؎ 0.8 log 10 CFU/g, respectively). Bactericidal activity was demonstrated at 4 h for nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 ؎ 0.10 log 10 CFU/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin (P < 0.01) and 48 h for nafcillin (MSSA only) (P ‫؍‬ 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculum Staphylococcus aureus had a significant impact on the activities of nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.

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confidence: 87%

“…Pharmacodynamic analysis. Two SEVs were removed from each model, for six simulated vegetations at 0, 4,8,24,32,48, and 72 h. The SEVs were homogenized and diluted in cold saline and plated onto TSA plates. The pH was monitored throughout all experiments with daptomycin due to the possible effects on its activity (37).…”

mentioning

confidence: 99%

Impact of High-InoculumStaphylococcus aureuson the Activities of Nafcillin, Vancomycin, Linezolid, and Daptomycin, Alone and in Combination with Gentamicin, in an In Vitro Pharmacodynamic Model

LaPlante

Rybak

2004

Antimicrob Agents Chemother

262

209

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“…The current study supports prior in vitro data by demonstrating that daptomycin decreases the bacterial load in vivo faster than comparator agents, including linezolid. Resistance to linezolid and persistent MRSA bacteremia during linezolid therapy have been reported (41,45). Furthermore, linezolid has been associated with myelosuppression, including neutropenia (16,19), which could exacerbate preexisting immunosuppression in special populations, including cancer patients.…”

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confidence: 99%

Rapid Bactericidal Activity of Daptomycin against Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Peritonitis in Mice as Measured with Bioluminescent Bacteria

Mortin

Praagh

et al. 2007

Antimicrob Agents Chemother

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The rising rates of antibiotic resistance accentuate the critical need for new antibiotics. Daptomycin is a new antibiotic with a unique mode of action and a rapid in vitro bactericidal effect against gram-positive organisms. This study examined the kinetics of daptomycin's bactericidal action against peritonitis caused by methicillinsusceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in healthy and neutropenic mice and compared this activity with those of other commonly used antibiotics. CD-1 mice were inoculated intraperitoneally with lethal doses of MSSA (Xen-29) or MRSA (Xen-1), laboratory strains transformed with a plasmid containing the lux operon, which confers bioluminescence. One hour later, the animals were given a single dose of daptomycin at 50 mg/kg of body weight subcutaneously (s.c.), nafcillin at 100 mg/kg s.c., vancomycin at 100 mg/kg s.c., linezolid at 100 mg/kg via gavage (orally), or saline (10 ml/kg s.c.). The mice were anesthetized hourly, and photon emissions from living bioluminescent bacteria were imaged and quantified. The luminescence in saline-treated control mice either increased (neutropenic mice) or remained relatively unchanged (healthy mice). In contrast, by 2 to 3 h postdosing, daptomycin effected a 90% reduction of luminescence of MSSA or MRSA in both healthy and neutropenic mice. The activity of daptomycin against both MSSA and MRSA strains was superior to those of nafcillin, vancomycin, and linezolid. Against MSSA peritonitis, daptomycin showed greater and more rapid bactericidal activity than nafcillin or linezolid. Against MRSA peritonitis, daptomycin showed greater and more rapid bactericidal activity than vancomycin or linezolid. The rapid decrease in the luminescent signal in the daptomycin-treated neutropenic mice underscores the potency of this antibiotic against S. aureus in the immune-suppressed host.

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“…Vancomycin is the treatment of choice for serious infections caused by oxacillin-resistant Staphylococcus aureus, and some isolates are reported that are susceptible only to this antibiotic (8,12). Oxacillin-resistant S. aureus isolates with reduced susceptibility to vancomycin (vancomycin intermediate-resistance S. aureus [VISA] isolates; the vancomycin MIC increases from 1 to 8 g/ml) have been recovered from patients receiving prolonged courses of vancomycin (1)(2)(3).…”

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confidence: 99%

Microarray Transcription Analysis of Clinical Staphylococcus aureus Isolates Resistant to Vancomycin

Mongodin¹,

et al. 2003

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The transcriptomes of vancomycin intermediate-resistance Staphylococcus aureus (VISA) clinical isolates HIP5827 and Mu50 (MIC ‫؍‬ 8 g/ml) were compared to those of highly vancomycin-resistant S. aureus (VRSA; MIC ‫؍‬ 32 g/ml) passage derivatives by microarray. There were 35 genes with increased transcription and 16 genes with decreased transcription in common between the two VRSAs compared to those of their VISA parents. Of the 35 genes with increased transcription, 15 involved purine biosynthesis or transport, and the regulator (purR) of the major purine biosynthetic operon (purE-purD) was mutant. We hypothesize that increased energy (ATP) is required to generate the thicker cell walls that characterize resistant mutants.Vancomycin is the treatment of choice for serious infections caused by oxacillin-resistant Staphylococcus aureus, and some isolates are reported that are susceptible only to this antibiotic (8, 12). Oxacillin-resistant S. aureus isolates with reduced susceptibility to vancomycin (vancomycin intermediate-resistance S. aureus [VISA] isolates; the vancomycin MIC increases from 1 to 8 g/ml) have been recovered from patients receiving prolonged courses of vancomycin (1-3). A number of abnormalities have been noted among VISA isolates, including reduced rate of growth, decreased cell wall cross-linking (6, 16), increased cell wall thickness (4, 10), decreased autolysis (17), changes in penicillin binding proteins (6, 9, 15), and alterations in glutamate amidation of the peptidoglycan stem peptide (5). No unifying molecular hypothesis has been proposed that explains the VISA phenotype, but the current hypothesis is that the thickened, poorly cross-linked cell wall provides more peripheral targets for vancomycin, trapping the antibiotic before it can reach its site of lethal action at the cell membrane (17). It is also assumed that because of the long clinical vancomycin exposure times required to generate resistance, multiple genes and, probably, multiple metabolic pathways have been altered.We sought to assess genomic changes in gene transcription (the transcriptome) by DNA microarray and took a number of approaches different from those taken by others in trying to understand genomic changes associated with the VISA phenotype. First, we used clinical VISA isolates as parents rather than vancomycin-susceptible laboratory strains. There is evidence that there is something unique about VISA isolates that allows them to become resistant to vancomycin more easily than other S. aureus isolates (13). Second, we sought to amplify the phenotype by continued exposure of VISA isolates to vancomycin in vitro, further increasing the vancomycin MIC. We hypothesized that in this way, we would create isogenic strain sets that exaggerate the changes present in clinical VISA isolates. Third, we compared stable mutants of VISA strains for which vancomycin MICs were increased and we did not grow strains in the presence of the antibiotic, removing any direct effect of the antibiotic on transcription.Generation of mutant...

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Endocarditis Caused by Methicillin‐ResistantStaphylococcus aureus:Treatment Failure with Linezolid

Abstract: We describe 2 cases of endocarditis caused by methicillin-resistant Staphylococcus aureus that failed to respond to intravenous linezolid therapy but were successfully treated with trimethoprim-sulfamethoxazole plus gentamicin and vancomycin plus rifampin.

Cited by 92 publications

References 9 publications

Impact of High-InoculumStaphylococcus aureuson the Activities of Nafcillin, Vancomycin, Linezolid, and Daptomycin, Alone and in Combination with Gentamicin, in an In Vitro Pharmacodynamic Model

Impact of High-InoculumStaphylococcus aureuson the Activities of Nafcillin, Vancomycin, Linezolid, and Daptomycin, Alone and in Combination with Gentamicin, in an In Vitro Pharmacodynamic Model

Rapid Bactericidal Activity of Daptomycin against Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Peritonitis in Mice as Measured with Bioluminescent Bacteria

Microarray Transcription Analysis of Clinical Staphylococcus aureus Isolates Resistant to Vancomycin

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