scholarly journals Methicillin-resistant staphylococci.

1988 ◽  
Vol 1 (2) ◽  
pp. 173-186 ◽  
Author(s):  
H F Chambers
Keyword(s):  
Methicillin Resistance ◽  
Test Methods ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics ◽  
Heterogeneous Expression ◽  
Extreme Variability ◽  
Resistance Trait ◽  
Resistant Strains ◽  
High Concentrations

Strains of staphylococci resistant to methicillin were identified immediately after introduction of this drug. Methicillin-resistant strains have unusual properties, the most notable of which is extreme variability in expression of the resistance trait. The conditions associated with this heterogeneous expression of resistance are described. Methicillin resistance is associated with production of a unique penicillin-binding protein (PBP), 2a, which is bound and inactivated only at high concentrations of beta-lactam antibiotics. PBP2a appears to be encoded by the mec determinant, which also is unique to methicillin-resistant strains. The relationships between PBP2a and expression of resistance and implications for the mechanism of resistance are discussed. The heterogeneous expression of methicillin resistance by staphylococci poses problems in the detection of resistant strains. Experience with several susceptibility test methods is reviewed and guidelines for performance of these tests are given. Treatment of infections caused by methicillin-resistant staphylococci is discussed. Vancomycin is the treatment of choice. Alternatives have been few because methicillin-resistant strains often are resistant to multiple antibiotics in addition to beta-lactam antibiotics. New agents which are active against methicillin-resistant staphylococci are becoming available, and their potential role in treatment is discussed.

scholarly journals Species-Specific Sensitivity of Coagulase-Negative Staphylococci to Single Antibiotics and Their Combinations

2011 ◽  
Vol 60 (2) ◽  
pp. 155-161 ◽  
Author(s):  
GRAŻYNA SZYMAŃSKA ◽  
MAGDALENA SZEMRAJ ◽  
ELIGIA M. SZEWCZYK
Keyword(s):  
University Hospital ◽  
Hospital Environment ◽  
Beta Lactam ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics ◽  
Resistant Strains ◽  
Staphylococcus Hominis ◽  
Species Specific

The activity of beta-lactam antibiotics (oxacillin, cloxacillin, cephalotin), vancomycin, gentamicin and rifampicin applied in vitro individually and in combination against 37 nosocomial methicillin-resistant strains of coagulase-negative staphylococci (CNS) was assessed to demonstrate the heterogeneity of this group of bacteria and estimate the chance of the efficacy of such therapy. The strains belonged to four species: Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus cohnii, Staphylococcus hominis. They originated from a hospital environment and from the skin of medical staff of the intensive care unit of a paediatric ward at a university hospital. All strains were methicillin-resistant, according to CLSI standards, but individual strains differed in MIC(ox) values. Susceptibility to other tested antibiotics was also characteristic for the species. The increased susceptibility to antibiotics in combinations, tested by calculating the fractional inhibitory concentration (FIC) index, concerned 26 out of 37 investigated strains and it was a feature of a particular species. Combinations of vancomycin and cephalotin against S. epidermidis and oxacillin with vancomycin were significant, as well as cephalotin and rifampicin in growth inhibition of multiresistant S. haemolyticus strains.

scholarly journals Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications.

1997 ◽  
Vol 10 (4) ◽  
pp. 781-791 ◽  
Author(s):  
H F Chambers
Keyword(s):  
Methicillin Resistance ◽  
Regulatory Elements ◽  
Cross Resistance ◽  
Multiple Drug ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Biochemical Basis ◽  
Methicillin Resistant ◽  
Resistant Strains ◽  
Investigational Agents

Methicillin resistance in staphylococci is determined by mec, composed of 50 kb or more of DNA found only in methicillin-resistant strains. mec contains mecA, the gene for penicillin-binding protein 2a (PBP 2a); mecI and mecR1, regulatory genes controlling mecA expression; and numerous other elements and resistance determinants. A distinctive feature of methicillin resistance is its heterogeneous expression. Borderline resistance, a low-level type of resistance to methicillin exhibited by strains lacking mecA, is associated with modifications in native PBPs, beta-lactamase hyperproduction, or possibly a methicillinase. The resistance phenotype is influenced by numerous factors, including mec and beta-lactamase (bla) regulatory elements, fem factors, and yet to be identified chromosomal loci. The heterogeneous nature of methicillin resistance confounds susceptibility testing. Methodologies based on the detection of mecA are the most accurate. Vancomycin is the drug of choice for treatment of infection caused by methicillin-resistant strains. PBP 2a confers cross-resistance to most currently available beta-lactam antibiotics. Investigational agents that bind PBP 2a at low concentrations appear promising but have not been tested in humans. Alternatives to vancomycin are few due to the multiple drug resistances typical of methicillin-resistant staphylococci.

scholarly journals A Plasmid-Borne System To Assess the Excision and Integration of Staphylococcal Cassette ChromosomemecMediated by CcrA and CcrB

2015 ◽  
Vol 197 (17) ◽  
pp. 2754-2761 ◽  
Author(s):  
Lei Wang ◽  
Mostafa H. Ahmed ◽  
Martin K. Safo ◽  
Gordon L. Archer
Keyword(s):  
Genomic Island ◽  
Tertiary Structure ◽  
Methicillin Resistance ◽  
Model System ◽  
Site Directed Mutagenesis ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Content Type ◽  
Terminal Domain ◽  
Beta Lactam Antibiotics

ABSTRACTResistance to methicillin and other β-lactam antibiotics in staphylococci is due tomecA, which is carried on a genomic island, staphylococcal cassette chromosomemec(SCCmec). The chromosomal excision and integration of SCCmecare mediated by the site-specific recombinase CcrAB or CcrC, encoded within this element. A plasmid-borne system was constructed to assess the activities of CcrA and CcrB in the excision and integration of SCCmecinEscherichia coliandStaphylococcus aureus. The excision frequency inE. colimediated by CcrAB from methicillin-resistantS. aureus(MRSA) strain N315 was only 9.2%, while the integration frequency was 31.4%. InS. aureusthe excision and integration frequencies were 11.0% and 18.7%, respectively. Truncated mutants identified the N-terminal domain of either CcrB or CcrA to be necessary for both integration and excision, while the C-terminal domain was important for recombination efficiency. Site-directed mutagenesis of the N-terminal domain identified S11 and R79 of CcrA and S16, R89, T149, and R151 of CcrB to be residues essential for catalytic activities, and the critical location of these residues was consistent with a model of the tertiary structure of the N terminus of CcrA and CcrB. Furthermore, CcrAB and CcrC, cloned from a panel of 6 methicillin-resistantS. aureusstrains and 2 methicillin-resistantStaphylococcus epidermidisstrains carrying SCCmectypes II, IV, and V, also catalyzed integration at rates 1.3 to 10 times higher than the rates at which they catalyzed excision, similar to the results from N315. The tendency of SCCmecintegration to be favored over excision may explain the low spontaneous excision frequency seen among MRSA strains.IMPORTANCESpontaneous excision of the genomic island (SCCmec) that encodes resistance to beta-lactam antibiotics (methicillin resistance) in staphylococci would convert a methicillin-resistant strain to a methicillin-susceptible strain, improving therapy of difficult-to-treat infections. This study characterizes a model system by which the relative frequencies of excision and integration can be compared. Using a plasmid-based model for excision and integration mediated by the recombinases CcrA and CcrB, integration occurred at a higher frequency than excision, consistent with the low baseline excision frequency seen in most strains. This model system can now be used to study conditions and drugs that may raise the SCCmecexcision frequency and generate strains that are beta-lactam susceptible.

scholarly journals Ceftobiprole Is Superior to Vancomycin, Daptomycin, and Linezolid for Treatment of Experimental Endocarditis in Rabbits Caused by Methicillin-Resistant Staphylococcus aureus

2009 ◽  
Vol 54 (2) ◽  
pp. 610-613 ◽  
Author(s):  
P. Tattevin ◽  
L. Basuino ◽  
D. Bauer ◽  
B. A. Diep ◽  
H. F. Chambers
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Group ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Rabbit Model ◽  
Laboratory Strain ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
High Affinity

ABSTRACT Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (P < 0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (P < 0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

scholarly journals Accumulation of Succinyl Coenzyme A Perturbs the Methicillin-Resistant Staphylococcus aureus (MRSA) Succinylome and Is Associated with Increased Susceptibility to Beta-Lactam Antibiotics

mBio ◽  
2021 ◽  
Author(s):  
Christopher Campbell ◽  
Claire Fingleton ◽  
Merve S. Zeden ◽  
Emilio Bueno ◽  
Laura A. Gallagher ◽  
...  
Keyword(s):  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Tca Cycle ◽  
Cell Wall Biosynthesis ◽  
Central Metabolism ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Lysine Succinylation ◽  
The Tca Cycle ◽  
Increased Susceptibility

mecA -dependent methicillin resistance in MRSA is subject to regulation by numerous accessory factors involved in cell wall biosynthesis, nucleotide signaling, and central metabolism. Here, we report that mutations in the TCA cycle gene, sucC , increased susceptibility to β-lactam antibiotics and was accompanied by significant accumulation of succinyl-CoA, which in turn perturbed lysine succinylation in the proteome.

scholarly journals Detection of mecA gene by latex agglutination and its molecular analysis by PCR in methicillin resistant staphylococcus aureus.

2020 ◽  
Vol 27 (07) ◽  
pp. 1363-1370
Author(s):  
Aneela Khawaja ◽  
Iffat Javed ◽  
Sohaila Mushtaq ◽  
Saeed Anwar ◽  
Faiqa Arshad ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Meca Gene ◽  
Latex Agglutination ◽  
Medical Institute ◽  
Cross Sectional ◽  
Methicillin Resistant ◽  
Agglutination Method ◽  
Resistant Strains

Antimicrobial resistance (AMR) is a devastating question that is threatening the health globally. The extensive and indiscriminative use of antibiotics has evolved a notorious resistance in Staphylococcus aureus.  This resistance developed through possession of mecA gene, which codes for modified penicillin binding protein (PBP2a) and the emergent strain being labeled “methicillin resistant Staphylococcus aureus”. Conventional phenotypic techniques for detection of MRSA rely on standardization of cultural characteristics. The drawbacks of diagnostic error to report MRSA include: poor prognosis, expensive treatment, dissemination of multi-drug resistant strains and even treatment failure. Latex agglutination method can be adopted as a more accurate and quick strategy for rapid detection of methicillin resistance. Objectives: To compare detection of mecA gene in methicillin resistant isolates of Staphylococcus aureus by latex agglutination and PCR; by assessing the sensitivity and specificity of both methods. Study Design: Descriptive Cross-Sectional study. Setting: Pathology Department, Post Graduate Medical Institute, Lahore. Period: From January 2015 to December 2015; according to standard operating procedures at Microbiology laboratory. Material & Methods: A total 713 consecutive, non-duplicate isolates of Staphylococcus aureus were processed. Methicillin resistance was determined using cefoxitin (30mg) by Kirby-Bauer method using CLSI guideline (2016), latex agglutination method; and PCR for mecA gene. Results: The results showed that out of 713 Staphylococcus aureus isolates, 92 (12.90%) isolates were resistant to cefoxitin and were labelled as MRSA. majority MRSA isolates recovered from pus (44.57%) and wound swab (20.65%), followed by blood (13.04%), fluid (8.70%), CSF (4.35%), CVP (3.26%), HVS (3.26%) and tracheal secretion (2.17%). By latex agglutination method, 87 (94.50%) were positive for PBP2a; while on PCR mecA gene was detected only in 82 (89.10%) MRSA isolates. When assessed with PCR (gold standard) the sensitivity and diagnostic accuracy of latex agglutination was 100% and 94.57%, respectively. Conclusion: Latex agglutination test can be employed as rapid and reliable diagnostic technique in MRSA isolates for mecA gene detection, where resources for molecular methods are inadequate. This can effectually lessen the misdiagnosis of resistant strains, and over/ ill-use of antibiotics.

scholarly journals Prevalence and characteristics of methicillin-resistant staphylococci in goats on the island of Tenerife, Spain

2019 ◽  
Vol 67 (3) ◽  
pp. 317-326
Author(s):  
Rossana Abreu ◽  
Cristobalina Rodríguez-Álvarez ◽  
María Lecuona ◽  
Beatriz Castro-Hernández ◽  
Juan Carlos González ◽  
...  
Keyword(s):  
Control Measures ◽  
Animal Origin ◽  
Beta Lactam ◽  
Coagulase Negative Staphylococci ◽  
Cross Sectional ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics ◽  
Resistance Patterns ◽  
Erythromycin A ◽  
Genotypic Characteristics

The aim of this study was to determine the prevalence of methicillin-resistant Staphylococcus (MRS) in healthy goats on the Island of Tenerife, Spain, as well as to identify the phenotypic and genotypic characteristics of the strains found. A cross-sectional prevalence study was conducted. A total of 158 goats from 15 different farms were sampled between September 2017 and January 2018. The percentage of positive samples of methicillin-resistant Staphylococcus aureus (MRSA) was 15.8% (25/158) and that of methicillin-resistant coagulase-negative staphylococci (MRCoNS) was 6.9% (11/158). All MRSA isolates from goats belonged to one clonal group showing Multi-Locus Sequence type 398. All strains studied (n = 36) were resistant to non-carbapenem beta-lactam antibiotics and susceptible to teicoplanin, linezolid, vancomycin, rifampicin, quinupristin-dalfospristin and mupirocine. In MRSA isolates, the highest percentage of resistance obtained, besides beta-lactam non-carbapenem antibiotics, was to trimethoprim-sulphamethoxazole and, in the case of MRCoNS isolates, to phosphomycin and erythromycin. A total of 12 resistance patterns were obtained, presenting differences between patterns obtained for MRSA and MRCoNS, with 7 different patterns for MRSA and 5 for MRCoNS. We therefore consider it essential to expand the epidemiological study of these strains of animal origin, as well as to increase surveillance and control measures at all stages of the food chain.

scholarly journals Ceftaroline resistance in Staphylococcus pseudintermedius gene mecA carriers

2018 ◽  
Vol 38 (12) ◽  
pp. 2233-2236
Author(s):  
Carolina B. Scherer ◽  
Larissa S. Botoni ◽  
Antônio U. Carvalho ◽  
Kelly M. Keller ◽  
Adriane P. Costa-Val
Keyword(s):  
Methicillin Resistance ◽  
Meca Gene ◽  
Disk Diffusion ◽  
Diffusion Test ◽  
Staphylococcus Pseudintermedius ◽  
Ceftaroline Fosamil ◽  
Disk Diffusion Test ◽  
Methicillin Resistant ◽  
Resistant Strains ◽  
Current Report

ABSTRACT: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) being a constant concern, ceftaroline fosamil has been recently approved as a new cephalosporin, active against MRSA, for use in humans; only rare cases of resistance have been reported till date. There is no report of resistance to ceftaroline in Staphylococcus pseudintermedius, which is the main bacterium causing dermatitis and otitis in dogs. To evaluate staphylococcal resistance to ceftaroline, 35 isolates of methicillin-resistant S. pseudintermedius (MRSP), carrying the mecA gene, from 26 dogs with folliculitis and nine dogs with external otitis, underwent disk diffusion test with cefoxitin, oxacillin, and ceftaroline. Tests with cefoxitin and oxacillin showed > 90% sensitivity in methicillin resistance detection. In the disk diffusion test, 97.14% (34/35) were resistant to cefoxitin, 94.29% (33/35) to oxacillin, and 31.43% (11/35) to ceftaroline. Of the ceftaroline-resistant strains, 27.27% (3/11) were obtained from the ears of dogs while the rest (8/11) were from the skin. The current report is the first description of MRSP resistance to ceftaroline.

scholarly journals Introduction of the mec Element (Methicillin Resistance) into Staphylococcus aureus Alters In Vitro Functional Activities of Fibrinogen and Fibronectin Adhesins

1998 ◽  
Vol 42 (3) ◽  
pp. 564-570 ◽  
Author(s):  
Pierre E. Vaudaux ◽  
Vincenza Monzillo ◽  
Patrice Francois ◽  
Daniel P. Lew ◽  
Tim J. Foster ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Bacterial Colonization ◽  
Protein A ◽  
Methicillin Resistant ◽  
Functional Activities ◽  
Extracellular Matrix Components ◽  
Resistant Strains ◽  
The Impact

ABSTRACT Some methicillin-resistant strains of Staphylococcus aureus are defective in the production of major surface components such as protein A, clumping factor, or other important adhesins to extracellular matrix components which may play a role in bacterial colonization and infection. To evaluate the impact of methicillin resistance (mec) determinants on bacterial adhesion mediated by fibrinogen or fibronectin adhesins, we compared the in vitro attachment of two genetically distinct susceptible strains (NCTC8325 and Newman) to protein-coated surfaces with that of isogenic methicillin-resistant derivatives. All strains containing an intactmec element in their chromosomes were found to be defective in adhesion to fibrinogen and fibronectin immobilized on polymethylmethacrylate coverslips, regardless of the presence or absence of additional mutations in the femA,femB, or femC gene, known to decrease expression of methicillin resistance in S. aureus. Western ligand affinity blotting or immunoblotting of cell wall-associated adhesins revealed similar contents of fibrinogen- or fibronectin-binding proteins in methicillin-resistant strains compared to those of their methicillin-susceptible counterparts. In contrast to methicillin-resistant strains carrying a mec element in their genomes, methicillin-resistant strains constructed in vitro, by introducing the mecA gene on a plasmid, retained their adhesion phenotypes. In conclusion, the chromosomal insertion of themec element into genetically defined strains of S. aureus impairs the in vitro functional activities of fibrinogen or fibronectin adhesins without altering their production. This effect is unrelated to the activity of the mecA gene.

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