High Rate of Ceftobiprole Resistance among Clinical Methicillin-Resistant
            <i>Staphylococcus aureus</i>
            Isolates from a Hospital in Central Italy

Morroni, Gianluca; Brenciani, Andrea; Brescini, Lucia; Fioriti, Simona; Simoni, Serena; Pocognoli, Antonella; Mingoia, Marina; Giovanetti, Eleonora; Barchiesi, Francesco; Giacometti, Andrea; Cirioni, Oscar

doi:10.1128/aac.01663-18

Cited by 27 publications

(20 citation statements)

References 22 publications

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“…CP009361.1) revealed aa alterations in PBP1, PBP2, PBP3 and PBP4, even though none of these differences were within the functional transglycosylase or transpeptidase domains [1,2,66,67,68]. Since Morroni et al compared the PBPs of ceftobiprole-resistant MRSA isolates with the vancomycin-resistant mecA -carrying MRSA Mu50 [69], a comparison of our isolates with Mu50 (acc. no.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Equine Staphylococcus aureus Isolates Exhibiting Reduced Oxacillin Susceptibility

Scholtzek

Hanke

Walther

et al. 2019

Toxins

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The detection of borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a challenge to both, veterinary and human laboratories. Between 2015 and 2017, 19 equine S. aureus with elevated minimal inhibitory concentrations for oxacillin were detected in routine diagnostics. The aim of this study was to characterize these isolates to identify factors possibly associated with the BORSA phenotype. All S. aureus were subjected to antimicrobial susceptibility testing and whole genome sequencing (WGS). A quantifiable β-lactamase activity assay was performed for a representative subset of 13 isolates. The WGS data analysis of the 19 BORSA isolates identified two different genomic lineages, sequence type (ST) 1 and ST1660. The core genome multilocus sequence typing (cgMLST) revealed a close relatedness of all isolates belonging to either ST1 or ST1660. The WGS analysis identified the resistance genes aadD, dfrG, tet(L), and/or blaZ and aacA-aphD. Phenotypic resistance to penicillins, aminoglycosides, tetracyclines, fluoroquinolones and sulfamethoxazole/trimethoprim was observed in the respective isolates. For the penicillin-binding proteins 1–4, amino acid substitutions were predicted using WGS data. Since neither transglycosylase nor transpeptidase domains were affected, these alterations might not explain the BORSA phenotype. Moreover, β-lactamase activity was found to be associated with an inducible blaZ gene. The lineage-specific differences regarding the expression profiles were noted.

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Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Equine Staphylococcus aureus Isolates Exhibiting Reduced Oxacillin Susceptibility

Scholtzek

Hanke

Walther

et al. 2019

Toxins

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“…In any case, the mecC -MRSA human prevalence detected in most of the studies was very low. Several studies did not identify any mecC -positive S. aureus among included human isolates/samples ( Table 2 ) [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. In studies in which this gene was detected ( Table 1 ), the prevalence identified, considering the total number of isolates/samples included, was < 1% in most of the cases [ 24 , 27 , 28 , 29 , 32 , 33 , 37 , 40 , 41 , 42 , 43 ], similar to that identified in the first study in which mecC was discovered (approximately 0.04%) [ 16 ].…”

Section: Detection Of Mecc -Mrsa Isolates In Humentioning

confidence: 99%

Human mecC-Carrying MRSA: Clinical Implications and Risk Factors

et al. 2020

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A new methicillin resistance gene, named mecC, was first described in 2011 in both humans and animals. Since then, this gene has been detected in different production and free-living animals and as an agent causing infections in some humans. The possible impact that these isolates can have in clinical settings remains unknown. The current available information about mecC-carrying methicillin resistant S. aureus (MRSA) isolates obtained from human samples was analyzed in order to establish its possible clinical implications as well as to determine the infection types associated with this resistance mechanism, the characteristics of these mecC-carrying isolates, their possible relation with animals and the presence of other risk factors. Until now, most human mecC-MRSA infections have been reported in Europe and mecC-MRSA isolates have been identified belonging to a small number of clonal complexes. Although the prevalence of mecC-MRSA human infections is very low and isolates usually contain few resistance (except for beta-lactams) and virulence genes, first isolates harboring important virulence genes or that are resistant to non-beta lactams have already been described. Moreover, severe and even fatal human infection cases have been detected. mecC-carrying MRSA should be taken into consideration in hospital, veterinary and food safety laboratories and in prevention strategies in order to avoid possible emerging health problems.

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“…Of these, only the oxazolidinones, now nearly 20 years old, were a completely new class [9]. Clinical resistance has already been observed for all nine of these drugs, though it can be difficult to predict how quickly or widely some of these resistances will spread [10,11,12,13,14,15,16,17,18,19]. Side effects such as renal toxicity and cross-resistance (e.g.…”

Section: Introductionmentioning

confidence: 99%

Design and Preclinical Development of a Phage Product for the Treatment of Antibiotic-Resistant Staphylococcus aureus Infections

Lehman

G²,

Rankin³

et al. 2019

Viruses

125

118

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Bacteriophages, viruses that only kill specific bacteria, are receiving substantial attention as nontraditional antibacterial agents that may help alleviate the growing antibiotic resistance problem in medicine. We describe the design and preclinical development of AB-SA01, a fixed-composition bacteriophage product intended to treat Staphylococcus aureus infections. AB-SA01 contains three naturally occurring, obligately lytic myoviruses related to Staphylococcus phage K. AB-SA01 component phages have been sequenced and contain no identifiable bacterial virulence or antibiotic resistance genes. In vitro, AB-SA01 killed 94.5% of 401 clinical Staphylococcus aureus isolates, including methicillin-resistant and vancomycin-intermediate ones for a total of 95% of the 205 known multidrug-resistant isolates. The spontaneous frequency of resistance to AB-SA01 was ≤3 × 10−9, and resistance emerging to one component phage could be complemented by the activity of another component phage. In both neutropenic and immunocompetent mouse models of acute pneumonia, AB-SA01 reduced lung S. aureus populations equivalently to vancomycin. Overall, the inherent characteristics of AB-SA01 component phages meet regulatory and generally accepted criteria for human use, and the preclinical data presented here have supported production under good manufacturing practices and phase 1 clinical studies with AB-SA01.

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High Rate of Ceftobiprole Resistance among Clinical Methicillin-Resistant Staphylococcus aureus Isolates from a Hospital in Central Italy

Cited by 27 publications

References 22 publications

Molecular Characterization of Equine Staphylococcus aureus Isolates Exhibiting Reduced Oxacillin Susceptibility

Molecular Characterization of Equine Staphylococcus aureus Isolates Exhibiting Reduced Oxacillin Susceptibility

Human mecC-Carrying MRSA: Clinical Implications and Risk Factors

Design and Preclinical Development of a Phage Product for the Treatment of Antibiotic-Resistant Staphylococcus aureus Infections

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