scholarly journals Phenotypic Detection of Hemin-Inducible Trimethoprim-Sulfamethoxazole Heteroresistance in Staphylococcus aureus

2021 ◽  
Author(s):  
Dennis Nurjadi ◽  
Quan Chanthalangsy ◽  
Elfi Zizmann ◽  
Vanessa Stuermer ◽  
Maximilian Moll ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Medicine ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Content Type ◽  
Therapeutic Challenge ◽  
Beta Lactam Antibiotics ◽  
Emergence Of Resistance ◽  
Antibiotic Agents

Staphylococcus aureus is one of most important pathogens in clinical medicine. Besides its virulence, the acquisition or emergence of resistance toward antibiotic agents, in particular to beta-lactam antibiotics (methicillin-resistant S. aureus [MRSA]), poses a major therapeutic challenge.

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.

scholarly journals Novel Combinations of Vancomycin plus Ceftaroline or Oxacillin against Methicillin-Resistant Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous VISA

2013 ◽  
Vol 57 (5) ◽  
pp. 2376-2379 ◽  
Author(s):  
B. J. Werth ◽  
C. Vidaillac ◽  
K. P. Murray ◽  
K. L. Newton ◽  
G. Sakoulas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Inverse Correlation ◽  
Fluorescent Dye ◽  
Beta Lactam ◽  
Significant Inverse Correlation ◽  
Methicillin Resistant ◽  
Content Type ◽  
Time Kill ◽  
Wall Interactions

ABSTRACTWe demonstrated a significant inverse correlation between vancomycin and beta-lactam susceptibilities in vancomycin-intermediateStaphylococcus aureus(VISA) and heterogeneous VISA (hVISA) isolates. Using time-kill assays, vancomycin plus oxacillin or ceftaroline was synergistic against 3 of 5 VISA and 1 of 5 hVISA isolates or 5 of 5 VISA and 4 of 5 hVISA isolates, respectively. Beta-lactam exposure reduced overall vancomycin-Bodipy (dipyrrometheneboron difluoride [4,4-difluoro-4-bora-3a,4a-diaza-s-indacene] fluorescent dye) binding but may have improved vancomycin-cell wall interactions to improve vancomycin activity. Further research is warranted to elucidate the mechanism behind vancomycin and beta-lactam synergy.

scholarly journals Efficacy of Fosfomycin Compared to Vancomycin in Treatment of Implant-Associated Chronic Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rats

2014 ◽  
Vol 58 (9) ◽  
pp. 5111-5116 ◽  
Author(s):  
Wolfgang Poeppl ◽  
Tilman Lingscheid ◽  
Dominik Bernitzky ◽  
Uwe Y. Schwarze ◽  
Oliver Donath ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Drug Control ◽  
Once Daily ◽  
Methicillin Resistant ◽  
Content Type ◽  
Titanium Wire ◽  
Experimental Rat Model ◽  
Vancomycin Group ◽  
Emergence Of Resistance

ABSTRACTFosfomycin monotherapy was compared to therapy with vancomycin for the treatment of implant-associated methicillin-resistantStaphylococcus aureus(MRSA) osteomyelitis in an experimental rat model. The proximal tibiae were inoculated with 15 μl of a suspension containing 1 × 108to 5 × 108CFU/ml of a clinical isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later, treatment was started for 28 days with either 50 mg/kg of body weight vancomycin intraperitoneally twice daily (n= 11) or 75 mg/kg fosfomycin intraperitoneally once daily (n= 10). Eleven animals were left untreated. After treatment, quantitative cultures from bone were found to be positive for MRSA in all animals in the untreated group (median, 3.29 × 106CFU/g of bone) and the vancomycin group (median, 3.03 × 105CFU/g of bone). In the fosfomycin group, MRSA was detectable in 2 out of 10 (20%) animals (3.42 × 102and 1.51 × 103CFU/g of bone). Vancomycin was superior to the no-drug control (P= 0.002), and fosfomycin was superior to the no-drug control and vancomycin (P< 0.001). The cultures from the wires were positive in all untreated animals (median, 2.5 × 103CFU/implant), in 10 animals in the vancomycin group (median, 1.15 × 103CFU/implant), and negative in all animals in the fosfomycin group. Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P= 0.324), and fosfomycin was superior to the no-drug control and vancomycin (P< 0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.

scholarly journals The Length of Lipoteichoic Acid Polymers Controls Staphylococcus aureus Cell Size and Envelope Integrity

2020 ◽  
Vol 202 (16) ◽  
Author(s):  
Anthony R. Hesser ◽  
Leigh M. Matano ◽  
Christopher R. Vickery ◽  
B. McKay Wood ◽  
Ace George Santiago ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Growth ◽  
Cell Size ◽  
Cell Envelope ◽  
Lipoteichoic Acid ◽  
Beta Lactam ◽  
Content Type ◽  
Beta Lactam Antibiotics ◽  
Outer Leaflet ◽  
Glycolipid Anchor

ABSTRACT The opportunistic pathogen Staphylococcus aureus is protected by a cell envelope that is crucial for viability. In addition to peptidoglycan, lipoteichoic acid (LTA) is an especially important component of the S. aureus cell envelope. LTA is an anionic polymer anchored to a glycolipid in the outer leaflet of the cell membrane. It was known that deleting the gene for UgtP, the enzyme that makes this glycolipid anchor, causes cell growth and division defects. In Bacillus subtilis, growth abnormalities from the loss of ugtP have been attributed to both the absence of the encoded protein and the loss of its products. Here, we show that growth defects in S. aureus ugtP deletion mutants are due to the long, abnormal LTA polymer that is produced when the glycolipid anchor is missing from the outer leaflet of the membrane. Dysregulated cell growth leads to defective cell division, and these phenotypes are corrected by mutations in the LTA polymerase gene, ltaS, that reduce polymer length. We also show that S. aureus mutants with long LTA are sensitized to cell wall hydrolases, beta-lactam antibiotics, and compounds that target other cell envelope pathways. We conclude that control of LTA polymer length is important for S. aureus physiology and promotes survival under stressful conditions, including antibiotic stress. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of community- and hospital-acquired infections and is responsible for a large fraction of deaths caused by antibiotic-resistant bacteria. S. aureus is surrounded by a complex cell envelope that protects it from antimicrobial compounds and other stresses. Here, we show that controlling the length of an essential cell envelope polymer, lipoteichoic acid, is critical for controlling S. aureus cell size and cell envelope integrity. We also show that genes involved in LTA length regulation are required for resistance to beta-lactam antibiotics in MRSA. The proteins encoded by these genes may be targets for combination therapy with an appropriate beta-lactam.

Genomic Overview into the Evolving Epidemiology of Methicillin-Resistant Staphylococcus aureus

2020 ◽  
Vol 21 (3) ◽  
pp. 125-131
Author(s):  
Yara El dessouky ◽  
Shaimaa Mouftah ◽  
Mohamed Elhadidy
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Human Infection ◽  
Emerging Infections ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Beta Lactam Antibiotics ◽  
Mrsa Strains ◽  
Hospital Acquired

Emerging infections represent an enormous challenge to both human and veterinary medicine. Identification of Methicillin-Resistant Staphylococcus aureus (MRSA) in various species and in food has raised concerns about the roles of animals in the epidemiology of MRSA. MRSA are a group of gram-positive bacteria, distinct from other strains of S. aureus in that this pathogen is resistant to methicillin, oxacillin, and all beta-lactam antibiotics. The severity of infections caused by MRSA depends on the strain responsible for the infection and can vary from soft tissue infections to bacteremia and sometimes pneumonia. MRSA strains are divided into clones, based on their genetic makeup. According to the setting of infection, MRSA are divided into three epidemiological types: hospital acquired (HA-MRSA), community acquired (CA-MRSA), and livestock acquired (LA-MRSA) (ie. Transmitted from animal carriers). The epidemiology of HA-MRSA, CA-MRSA, and LA-MRSA is blurred as different recent genetic studies have revealed significant overlap of identical clones between HA-MRSA and CA-MRSA, and the significant increase of human infection caused by LA-MRSA. Furthermore, the animal-human and animal-animal transmission of LA-MRSA has prompted further investigation to study the origin of this epidemiological type and the transmission dynamics. The genetic and virulence profiles of different types of MRSA vary widely, where community acquired and livestock acquired strains are more virulent than hospital acquired strains. This review sheds light on three epidemiological groups of MRSA (HA-MRSA, CA-MRSA, and LA-MRSA), and their most prevalent clonal clusters, that can consequently allow better understanding of their evolution, emergence, transmission, and global dissemination.

scholarly journals Rates of Carriage of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus in an Outpatient Population

2003 ◽  
Vol 24 (6) ◽  
pp. 439-444 ◽  
Author(s):  
Julie Kenner ◽  
Tasha O'Connor ◽  
Nicholas Piantanida ◽  
Joel Fishbain ◽  
Bardwell Eberly ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Risk Factor ◽  
Clinical Risk Factor ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics ◽  
Time Period ◽  
Clinical Illness ◽  
Mrsa Strains ◽  
Mrsa Colonization

AbstractObjectives:To assess the prevalence of and the clinical features associated with asymptomatic Staphylococcus aureus colonization in a healthy outpatient population, and to compare the characteristics of colonizing methicillin-resistant S. aureus (MRSA) strains with those of strains causing infection in our community and hospital.Setting:Outpatient military clinics.Methods:Specimens were obtained from the nares, pharynx, and axillae of 404 outpatients, and a questionnaire was administered to obtain demographic and risk factor information. MRSA strains were typed by pulsed-field gel electrophoresis (PFGE) and evaluated for antibiotic susceptibility. Antibiograms of study MRSA strains were compared with those of MRSA strains causing clinical illness during the same time period.Results:Methicillin-susceptible S. aureus (MSSA) colonization was present in 153 (38%) of the 404 asymptomatic outpatients, and MRSA colonization was present in 8 (2%). Detection of colonization was highest from the nares. No clinical risk factor was significantly associated with MRSA colonization; however, a tendency was noted for MRSA to be more common in men and in those who were older or who had been recently hospitalized. All colonizing MRSA strains had unique patterns on PFGE. In contrast to strains responsible for hospital infections, most colonizing isolates of MRSA were susceptible to oral antibiotics.Conclusions:MRSA and MSSA colonization is common in our outpatient population. Colonization is best detected by nares cultures and most carriers of MRSA are without apparent predisposing risk factors for acquisition. Colonizing isolates of MRSA are heterogeneous and, unlike nosocomial isolates, often retain susceptibility to other non-beta-lactam antibiotics.

Molecular Study of Immune Evasion Cluster Genes in Clinical Isolates of Staphylococcus aureus

2021 ◽  
Vol 10 ◽  
Author(s):  
Maysaa El Sayed Zaki ◽  
Samah Sabry El-Kazzaz
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Evasion ◽  
Clinical Isolates ◽  
Diffusion Method ◽  
Beta Lactam ◽  
Sensitivity Testing ◽  
Cross Sectional ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics ◽  
Immune Evasion Cluster

Aims: The aim of the present research was to highlight the prevalence of immune evasion cluster genes (IEC) sak, chp, scn, sea, sep among Staphylococcus aureus (S. aureus) clinical isolates. Background: The present study was a cross-sectional retrospective study, included one hundred isolates of S. aureus that were isolated from patients with nosocomial infections. S. aureus isolates were subjected to full microbiological identification and antibiotics sensitivity testing by the disc diffusion method. The presence of IEC genes scn, sea, sak, sep, chp was determined by polymerase chain reaction (PCR). Methods: The current study included 100 S. aureus isolates; 40% were classified as methicillin resistant. The isolates exhibited marked resistance to beta lactams antibiotics, the lowest resistance was to erythromycin, ciprofloxacin and vancomycin. The presence of one or more IEC was determined in 89 isolates. The prevalence of chp, sak, sea, sep and scn was 54%, 53%, 8%, 7% and 30%, respectively. Results: S. aureus isolates with IEC genes had increased resistance rates to the studied antibiotics; however, this increase was statistically insignificant either to beta-lactam antibiotics, such as amoxacillin/clavulinic acid (P=0.794), ampicillin (P=0.561), cefotaxim (P=0.271), ceftazidime (P=0.145), imipenem (P=0.589) or non beta-lactam antibiotics, such as amikacin (P=0.955) and trimethoprim/sulfamethoxazale (P=0.974). From 40 methicillin resistant Staphylococcus aureus (MRSA) strains, 37 isolates harbor one or more immune evasion cluster genes. Conclusion: The high prevalence of these genes among MRSA may explain its pathogenesis. There is a need for studies with a high number of isolates to verify the present findings.

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