scholarly journals The treatment of resistant staphylococcal infections

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 150 ◽  
Author(s):  
Joseph John Jr
Keyword(s):  
Staphylococcus Aureus ◽  
Renal Dysfunction ◽  
Clinical Judgment ◽  
Methicillin Resistance ◽  
Standard Of Care ◽  
Staphylococcal Infection ◽  
Beta Lactam ◽  
Staphylococcal Infections ◽  
Beta Lactam Antibiotics ◽  
The Many

Staphylococcus aureus of the many staphylococcal species is the most common cause of both skin and soft tissue infection and severe staphylococcal infections including Staphylococcus aureus bacteremia (SAB). Many antibiotics are active against the staphylococci, yet over the last 40 years antibiotic resistance, particularly resistance to beta-lactam antibiotics, has plagued antimicrobial therapy. The term “methicillin resistance” is a historic term and now refers to the ability of staphylococci, in particular methicillin-resistant Staphylococcus aureus (MRSA), to resist the action of beta-lactam antibiotics. This resistance is encoded by the mecA gene carried in a complex genetic cassette, SCCmec. Vancomycin and old antibiotics remain the keystone of treatment for resistant staphylococci. Other newer agents, and some older agents, show good activity against resistant staphylococci which are the focus of this review: trimethoprim-sulfamethoxazole, ceftaroline, daptomycin, fosfomycin, linezolid, dalbavancin, televancin, and omadacycline. Other agents with novel mechanisms of action are under development, for use as single anti-staphylococcal agents or for combination use to augment the action of the primary anti-staphylococcal agent. Vancomycin therapy carries specific risks, particularly renal dysfunction, but despite its foibles, vancomycin remains the standard of care for the treatment of resistant staphylococcal infections. Some clinicians implement an early switch from vancomycin at the earliest signs of renal dysfunction. The near horizon holds promise also of augmentation of both cellular and humoral responses to staphylococcal infection. Pending newer clinical trials that show clear superiority of one anti-staphylococcal agent over another or over vancomycin, it will remain to expert clinical judgment in determining antibiotic choice and duration of anti-staphylococcal therapy.

Molecular Characterization of Methicillin Resistant and Extended Spectrum β-Lactamase Staphylococcus aureus Isolated from Burn Patients

2020 ◽  
pp. 145-151
Author(s):  
Shawnm Ahmed Aziz
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Vancomycin Resistance ◽  
World Health ◽  
Molecular Technique ◽  
Burn Patients ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum

Antibiotic resistance has become a major world health challenge and has limited the ability of physician's treatment. Staphylococcus aureus the most notorious pathogens causes morbidity and mortality especially in burn patients. However, Staphylococcus aureus rapidly acquired resistance to multiple antibiotics. Vancomycin, a glycopeptide antibiotic remains a drug of choice for treatment of severe Methicillin Resistance S. aureus infections. This study aimed to detect the emergence of beta-lactam and glycopeptide resistance genes. 50 clinical specimens of S. aureus collected from burn patients in burn and plastic surgery units in Sulaimani-Iraq city. All specimens were confirmed to be positive for S. aureus. All the isolates were assessed for their susceptibility to different antibiotics depending on NCCL standards, followed by Extended Spectrum Beta Lactamase detection by double disk diffusion synergy test. The production of β- lactamases was evaluated in the isolated strains by several routine methods and polymerase chain reaction. Among the isolates 94% were Methicillin resistance and 34.28% were Extended Spectrum Beta Lactamase producer. PCR based molecular technique was done for the bla genes related to β- lactamase enzymes by the specific primers, as well as genes which related to reduced sensitivity to Vancomycin were detected. The results indicated that all isolated showed the PBP1, PBP2, PBP3, PBP4, trfA and trfB, graSR, vraS except the vraR gene and the prolonged therapy of Methicillin resistance infection with teicoplanin have been associated with progress of resistance and the rise of tecoplanin resistance may be a prologue to evolving Vancomycin resistance. In conclusion, beta-lactam over taking can rise Vancomycin- Intermediate S. aureus strains leading to appearance of Vancomycin resistance although the treatment of Vancomycin resistant infections is challenging.

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.

Antimicrobial Resistance in Staphylococcus aureus at the University of Chicago Hospitals: A 15-Year Longitudinal Assessment in a Large University-Based Hospital

2003 ◽  
Vol 24 (6) ◽  
pp. 403-408 ◽  
Author(s):  
John B. Seal ◽  
Beatriz Moreira ◽  
Cindy D. Bethel ◽  
Robert S. Daum
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Tertiary Care ◽  
University Teaching ◽  
Annual Rate ◽  
University Of Chicago ◽  
Longitudinal Assessment ◽  
Beta Lactam ◽  
The University ◽  
The Impact

AbstractObjectives:To describe a longitudinal profile of resistance to beta-lactam antimicrobials among isolates of Staphylococcus aureus at a large university teaching hospital and to evaluate the impact of the methicillin resistance phenotype on resistance trends for non-beta-lactam antimicrobials.Design:Retrospective evaluation of antimicrobial susceptibility data for all 17,287 S. aureus isolates obtained from January 1986 through December 2000.Setting:The University of Chicago Hospitals, a family of tertiary-care, university-affiliated hospitals in Chicago, Illinois, consisting of 547 adult and pediatric beds.Results:The annual rate of resistance to methicillin increased from 13% in 1986 to 28% in 2000 (P < .001) and has not plateaued. For each non-beta-lactam antimicrobial tested, the annual rates of resistance were far higher among methicillinresistant S. aureus (MRSA) isolates than among methicillin-susceptible S. aureus (MSSA) isolates. The annual rates of resistance to the macrolide, lincosamide, and streptogramin (MLS) antimicrobials erythromycin and clindamycin increased among MSSA isolates (P < .01), but remained lower than 20%. Resistance to the MLS antimicrobials was higher among MRSA isolates (higher than 60%), but the annual rate decreased significantly during the study (P < .01).Conclusion:The prevalence of methicillin resistance among S. aureus isolates has continued to increase; resistance to non-beta-lactam antimicrobials is far more common among MRSA isolates. Recent decreases in the proportion of MRSA isolates resistant to non-beta-lactam antimicrobials suggest important changes in the epidemiology of this pathogen.

scholarly journals Full-Genome Sequencing Identifies in the Genetic Background Several Determinants That Modulate the Resistance Phenotype in Methicillin-Resistant Staphylococcus aureus Strains Carrying the Novel mecC Gene

2017 ◽  
Vol 61 (3) ◽  
Author(s):  
Catarina Milheiriço ◽  
Hermínia de Lencastre ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Genetic Background ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Content Type ◽  
Resistance Phenotype ◽  
Beta Lactam Antibiotics ◽  
Oxacillin Resistance ◽  
Mrsa Strains

ABSTRACT Most methicillin-resistant Staphylococcus aureus (MRSA) strains are resistant to beta-lactam antibiotics due to the presence of the mecA gene, encoding an extra penicillin-binding protein (PBP2A) that has low affinity for virtually all beta-lactam antibiotics. Recently, a new resistance determinant—the mecC gene—was identified in S. aureus isolates recovered from humans and dairy cattle. Although having typically low MICs to beta-lactam antibiotics, MRSA strains with the mecC determinant are also capable of expressing high levels of oxacillin resistance when in an optimal genetic background. In order to test the impact of extensive beta-lactam selection on the emergence of mecC-carrying strains with high levels of antibiotic resistance, we exposed the prototype mecC-carrying MRSA strain, LGA251, to increasing concentrations of oxacillin. LGA251 was able to rapidly adapt to high concentrations of oxacillin in growth medium. In such laboratory mutants with increased levels of oxacillin resistance, we identified mutations in genes with no relationship to the mecC regulatory system, indicating that the genetic background plays an important role in the establishment of the levels of oxacillin resistance. Our data also indicate that the stringent stress response plays a critical role in the beta-lactam antibiotic resistance phenotype of MRSA strains carrying the mecC determinant.

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