scholarly journals Clinical Isolate of Vancomycin-HeterointermediateStaphylococcus aureus Susceptible to Methicillin and In Vitro Selection of a Vancomycin-Resistant Derivative

2001 ◽  
Vol 45 (1) ◽  
pp. 349-352 ◽  
Author(s):  
Sophie Bobin-Dubreux ◽  
Marie-Elisabeth Reverdy ◽  
Chantal Nervi ◽  
Martine Rougier ◽  
Anne Bolmström ◽  
...  

ABSTRACT A Staphylococcus aureus strain with low-level heteroresistance to vancomycin (designated MER) but susceptible to methicillin was isolated from an outpatient with conjunctivitis who did not receive any glycopeptide antibiotics. Incubation of the parent strain, MER, with increasing concentrations of vancomycin led to rapid selection of a stable progeny homogeneously resistant to vancomycin. Electron micrographs of strain MER showed enhanced cell wall thickness and abnormal septations typically seen with methicillin-resistantS. aureus having intermediate susceptibility to vancomycin.

2020 ◽  
Vol 65 (9-10) ◽  
pp. 3-7
Author(s):  
V. V. Gostev ◽  
Yu. V. Sopova ◽  
O. S. Kalinogorskaya ◽  
M. E. Velizhanina ◽  
I. V. Lazareva ◽  
...  

Glycopeptides are the basis of the treatment of infections caused by MRSA (Methicillin-Resistant Staphylococcus aureus). Previously, it was demonstrated that antibiotic tolerant phenotypes are formed during selection of resistance under the influence of high concentrations of antibiotics. The present study uses a similar in vitro selection model with vancomycin. Clinical isolates of MRSA belonging to genetic lines ST8 and ST239, as well as the MSSA (ATCC29213) strain, were included in the experiment. Test isolates were incubated for five hours in a medium with a high concentration of vancomycin (50 μg/ml). Test cultures were grown on the medium without antibiotic for 18 hours after each exposure. A total of ten exposure cycles were performed. Vancomycin was characterized by bacteriostatic action; the proportion of surviving cells after exposure was 70–100%. After selection, there was a slight increase in the MIC to vancomycin (MIC 2 μg/ml), teicoplanin (MIC 1.5–3 μg/ml) and daptomycin (MIC 0.25–2 μg/ml). According to the results of PAP analysis, all strains showed an increase in the area under curve depending on the concentration of vancomycin after selection, while a heteroresistant phenotype (with PAP/AUC 0.9) was detected in three isolates. All isolates showed walK mutations (T188S, D235N, E261V, V380I, and G223D). Exposure to short-term shock concentrations of vancomycin promotes the formation of heteroresistance in both MRSA and MSSA. Formation of VISA phenotypes is possible during therapy with vancomycin.


Author(s):  
Melina Herrera ◽  
Sabrina Di Gregorio ◽  
Silvina Fernandez ◽  
Graciela Posse ◽  
Marta Mollerach ◽  
...  

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 637
Author(s):  
Vladimir Gostev ◽  
Olga Kalinogorskaya ◽  
Ksenia Ivanova ◽  
Ekaterina Kalisnikova ◽  
Irina Lazareva ◽  
...  

Selective pressure of beta-lactams is thought to be responsible for mutation selection in methicillin-susceptible Staphylococcus aureus (MSSA). We used next-generation sequencing to compare the genomes of beta-lactamase-positive (SA0707) and -negative (SA0937) MSSA isolates with their derivatives obtained after selection with oxacillin, ceftaroline, or meropenem. Selection with oxacillin and ceftaroline caused a rapid and significant (6–8 times) increase in the minimum inhibitory concentration (MICs) of oxacillin, penicillin, amoxicillin/clavulanate, and ceftaroline against the derivatives of both isolates, associated with growth impairment. Selection with meropenem caused a limited increase in the MICs of all beta-lactams against both isolates. During the initial stages of selection (after 5–15 passages), mutations were detected only in some reads, which indicated the heterogeneity of the population; however, during the later stages, either the population reversed to the wild type or fixation of the mutation was observed in the entire population. Selection with different beta-lactams caused diverse mutational events, but common mutations were detected in gdpP, all penicillin-binding proteins, cell wall regulators (vraST, graR), and deletions in the promoter region of pbp4. Therefore, the disk diffusion test with cefoxitin does not reveal resistance associated with these mechanisms in some cases, which can lead to the failure of beta-lactam therapy.


2006 ◽  
Vol 50 (9) ◽  
pp. 2951-2956 ◽  
Author(s):  
Paige M. Fox ◽  
Russell J. Lampen ◽  
Katrina S. Stumpf ◽  
Gordon L. Archer ◽  
Michael W. Climo

ABSTRACT VRS1 is the first isolated strain of vancomycin-resistant Staphylococcus aureus (VRSA) found to carry the vanA gene complex previously described in Enterococcus. Under vancomycin pressure, VRS1 makes aberrant cell walls consisting of stem tetrapeptide and depsipeptide that lack the terminal d-Ala-d-Ala residues targeted by vancomycin. Previous data have suggested that this aberrant cell wall is not cross-linked by PBP2a, the enzyme responsible for cell wall transpeptidation in the presence of β-lactam antibiotics. We examined the efficacy of treating VRS1 with a combination of vancomycin and β-lactam antibiotics in vitro and in vivo. We found that the MIC of oxacillin for VRS1 decreased from >256 μg/ml to <1 μg/ml in the presence of vancomycin. Using the rabbit model of endocarditis, we treated VRS1-infected rabbits with nafcillin alone, vancomycin alone, or a combination of nafcillin and vancomycin. Treatment with nafcillin in combination with vancomycin cleared bloodstream infections within 24 h and sterilized 12/13 spleens (92%), as well as 8/13 kidneys (62%), following 3 days of treatment. Mean aortic valve vegetation counts were reduced 3.48 log10 CFU/g with the combination therapy (compared to untreated controls) and were significantly lower than with either vancomycin or nafcillin given alone. VRS1 was extremely virulent in this model, as no untreated rabbits survived the 3-day trial. Treatment of clinical infections due to VRSA with the combination of vancomycin and β-lactams may be an option, based on these results.


Author(s):  
Kiran Babu Tiwari

Staphylococcus aureus, one notable example of nosocomial infections, has the characteristic ability to acquire antimicrobial resistance. Methicillin-resistant S. aureus have already become endemic worldwide, and vancomycin is the terminal antibiotic of choice for treatment of infections by these strains. Because of selection of vancomycin as the treatment option, n ow, the emergence of vancomycin resistance in S. aureus has been increasing elsewhere. Further, there is no consensus definition of minimum inhibitory concentration to determine the levels of vancomycin resistance in these strains making it difficult in interpretation and management of the resistant strains. As an intervention against cell wall physiology of the bacteria, vancomycin binds with terminal dipeptide of the peptidoglycan monomer. However, vancomycin-resistant strains possess a thickened cell wall with many free monomers capable of binding with the drug. The thickened cell wall not only traps more vancomycin molecules on the immediate cell surface, but also significantly impedes action of the drug towards inner layers of the peptidoglycan network on bacteria. Thus, the normal inner layers of peptidoglycan ensure the structural integrity of cell as a whole. Compounding with the stress selection of vancomycin-resistance in S. aureus, the novel mechanism allows the bacteria to reduce susceptibility to the drug easily; hence, emergence of vancomycin resistant strains in the hospital environment may occur faster than expected.  DOI: 10.3126/ijls.v3i0.2302


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