Treatment of methicillin-resistant Staphylococcus aureus (MRSA): updated guidelines from the UK.
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ABSTRACT:
SUBMITTER: Brown NM
PROVIDER: S-EPMC8210269 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Staphylococcus aureus (S. aureus) is a Gram-positive bacterium that may cause life-threatening diseases and some minor infections in living organisms. However, it shows notorious effects when it becomes resistant to antibiotics. Strain variants of bacteria, viruses, fungi, and parasites that have become resistant to existing multiple antimicrobials are termed as superbugs. Methicillin is a semisynthetic antibiotic drug that was used to inhibit staphylococci pathogens. The S. aureus resistant to methicillin is known as methicillin-resistant Staphylococcus aureus (MRSA), which became a superbug due to its defiant activity against the antibiotics and medications most commonly used to treat major and minor infections. Successful MRSA infection management involves rapid identification of the infected site, culture and susceptibility tests, evidence-based treatment, and appropriate preventive protocols. This review describes the clinical management of MRSA pathogenesis, recent developments in rapid diagnosis, and antimicrobial treatment choices for MRSA.
| S-EPMC9137690 | biostudies-literature
Project description:The development of antibiotic resistance in Staphylococcus aureus, particularly in methicillin-resistant S. aureus (MRSA), has become a significant health concern worldwide. The acquired mecA gene encodes penicillin-binding protein 2a (PBP2a), which takes over the activities of endogenous PBPs and, due to its low affinity for β-lactam antibiotics, is the main determinant of MRSA. In addition to PBP2a, other genetic factors that regulate cell wall synthesis, cell signaling pathways, and metabolism are required to develop high-level β-lactam resistance in MRSA. Although several genetic factors that modulate β-lactam resistance have been identified, it remains unclear how they alter PBP2a expression and affect antibiotic resistance. This review describes the molecular determinants of β-lactam resistance in MRSA, with a focus on recent developments in our understanding of the role of mecA-encoded PBP2a and on other genetic factors that modulate the level of β-lactam resistance. Understanding the molecular determinants of β-lactam resistance can aid in developing novel strategies to combat MRSA.
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Project description:The herbal products proved to be more promising antimicrobials even though their antimicrobial activity is milder than commercially available antibiotics. Moreover, herbal drugs may act synergistically with antibiotics to kill microbes. In this study, we aimed to enhance the activity of penicillin against MRSA through combination with the active saponin fraction isolated from the Zygophyllum album plant. Three different types of metabolites (saponins, sterols, and phenolics) have been extracted from Zygophyllum album with ethanol and purified using different chromatographic techniques. The antibacterial activity of crude extract and the separated metabolites were checked against MRSA isolates, Saponin fraction (ZA-S) was only the active one followed by the crude extract. Therefore, the compounds in this fraction were identified using ultra-high-performance liquid chromatography connected to quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) operated in positive and negative ionization modes. UHPLC/QTOF-MS revealed the presence of major six ursane-type tritepenoidal saponins (Quinovic acid, Quinovic acid 3β-O-β-D-quinovopyranoside, Zygophylloside C, Zygophylloside G, Zygophylloside K and Ursolic acid), in addition to Oleanolic acid. Interaction studies between saponin fraction and penicillin against MRSA were performed through the checkerboard method and time-kill assay. According to checkerboard results, only three combinations showed a fractional inhibitory concentration index less than 0.5 at concentrations of (62.5 + 312.5, 62.5 + 156.25, and 62.5 + 78.125 of penicillin and ZA-S, respectively). Time kill assay results showed that the highest reduction in log10 colony-forming unit (CFU)/ml of initial inoculum of MRSA after 24 h occurred by 3.7 at concentrations of 62.5 + 312.5 (µg/µg)/ml of penicillin and ZA-S, respectively. Thus, the combination between saponin fraction of Zygophyllum album and penicillin with these concentrations could be a potential agent against MRSA that can serve as possible model for new antibacterial drug.
| S-EPMC7896049 | biostudies-literature
Project description:OBJECTIVES:To evaluate the association of USA300 genotype with outcomes in persons with MRSA bacteremia and examine the epidemiology of MRSA bacteremia over time. METHODS:Population-based surveillance for MRSA bacteremia was performed in 8-county Atlanta from 2005 to 2008. Cases of MRSA bacteremia were classified as healthcare-associated hospital-onset (HAHO), healthcare-associated community-onset (HACO), or community-associated (CA) disease. A survival analysis was performed on a nested cohort of cases with isolates characterized by pulse field gel electrophoresis (PFGE). RESULTS:4344 MRSA bacteremia cases were identified; 2579 (59.4%) HACO, 1144 (26.3%) HAHO; and 601 (13.8%) CA. Overall incidence rates of MRSA bacteremia declined from 33.9/100,000 in 2005-24.8/100,000 in 2008. Rates were highest in persons ? 65 years, blacks, males, and persons with AIDS. In multivariate analysis of 1104 cases, USA300 genotype was associated with increased in-hospital mortality (HR 1.63, 95% CI 1.19-2.23). USA300 strains were also associated with increased mortality when compared to USA100 strains (HR 1.79, 95% CI 1.24-2.58). CONCLUSIONS:MRSA bacteremia incidence declined over 4 years but CA disease rates remained stable. Persons with HIV, the elderly, and blacks were disproportionately affected. Bacteremia due to USA300 MRSA strains was associated with increased mortality, suggesting that USA300 strains may be more virulent.
| S-EPMC2975870 | biostudies-literature
Project description:Skin and chronic wound infections caused by highly antibiotic resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) are an increasing and urgent health problem worldwide, particularly with sharp increases in obesity and diabetes. New Zealand manuka honey has potent broad-spectrum antimicrobial activity, has been shown to inhibit the growth of MRSA strains, and bacteria resistant to this honey have not been obtainable in the laboratory. Combinational treatment of chronic wounds with manuka honey and common antibiotics may offer a wide range of advantages including synergistic enhancement of the antibacterial activity, reduction of the effective dose of the antibiotic, and reduction of the risk of antibiotic resistance. The aim of this study was to investigate the effect of Medihoney in combination with the widely used antibiotic rifampicin on S. aureus. Using checkerboard microdilution assays, time-kill curve experiments and agar diffusion assays, we show a synergism between Medihoney and rifampicin against MRSA and clinical isolates of S. aureus. Furthermore, the Medihoney/rifampicin combination stopped the appearance of rifampicin-resistant S. aureus in vitro. Methylglyoxal (MGO), believed to be the major antibacterial compound in manuka honey, did not act synergistically with rifampicin and is therefore not the sole factor responsible for the synergistic effect of manuka honey with rifampicin. Our findings support the idea that a combination of honey and antibiotics may be an effective new antimicrobial therapy for chronic wound infections.
| S-EPMC3585195 | biostudies-literature
Project description:Multidrug-resistant (MDR) bacteria have become a severe problem for public health. Developing new antibiotics for MDR bacteria is difficult, from inception to the clinically approved stage. Here, we have used a new approach, modification of an antibiotic, ciprofloxacin (CFX), with triphenylphosphonium (TPP, PPh3) moiety via ester- (CFX-ester-PPh3) and amide-coupling (CFX-amide-PPh3) to target bacterial membranes. In this study, we have evaluated the antibacterial activities of CFX and its derivatives against 16 species of bacteria, including MDR bacteria, using minimum inhibitory concentration (MIC) assay, morphological monitoring, and expression of resistance-related genes. TPP-conjugated CFX, CFX-ester-PPh3, and CFX-amide-PPh3 showed significantly improved antibacterial activity against Gram-positive bacteria, Staphylococcus aureus, including MDR S. aureus (methicillin-resistant S. aureus (MRSA)) strains. The MRSA ST5 5016 strain showed high antibacterial activity, with MIC values of 11.12 µg/mL for CFX-ester-PPh3 and 2.78 µg/mL for CFX-amide-PPh3. The CFX derivatives inhibited biofilm formation in MRSA by more than 74.9% of CFX-amide-PPh3. In the sub-MIC, CFX derivatives induced significant morphological changes in MRSA, including irregular deformation and membrane disruption, accompanied by a decrease in the level of resistance-related gene expression. With these promising results, this method is very likely to combat MDR bacteria through a simple TPP moiety modification of known antibiotics, which can be readily prepared at clinical sites.
| S-EPMC7693559 | biostudies-literature
Project description:BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing the previously dominant healthcare-associated (HA-MRSA) ST239. We previously showed that ST59 isolates tend to have a competitive advantage in growth experiments against ST239. However, the underlying genomic and phenotypic drivers of this replacement event are unclear.MethodsHere, we investigated the replacement of ST239 using whole-genome sequencing data from 204 ST239 and ST59 isolates collected in Chinese hospitals between 1994 and 2016. We reconstructed the evolutionary history of each ST and considered two non-mutually exclusive hypotheses for ST59 replacing ST239: antimicrobial resistance (AMR) profile and/or ability to colonise and persist in the environment through biofilm formation. We also investigated the differences in cytolytic activity, linked to higher virulence, between STs. We performed an association study using the presence and absence of accessory virulence genes.ResultsST59 isolates carried fewer AMR genes than ST239 and showed no evidence of evolving towards higher AMR. Biofilm production was marginally higher in ST59 overall, though this effect was not consistent across sub-lineages so is unlikely to be a sole driver of replacement. Consistent with previous observations of higher virulence in CA-MRSA STs, we observed that ST59 isolates exhibit significantly higher cytolytic activity than ST239 isolates, despite carrying on average fewer putative virulence genes. Our association study identified the chemotaxis inhibitory protein (chp) as a strong candidate for involvement in the increased virulence potential of ST59. We experimentally validated the role of chp in increasing the virulence potential of ST59 by creating Δchp knockout mutants, confirming that ST59 can carry chp without a measurable impact on fitness.ConclusionsOur results suggest that the ongoing replacement of ST239 by ST59 in China is not associated to higher AMR carriage or biofilm production. However, the increase in ST59 prevalence is concerning since it is linked to a higher potential for virulence, aided by the carriage of the chp gene.
| S-EPMC8555231 | biostudies-literature
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of health care-associated infections. Vancomycin remains an acceptable treatment option. There has been a welcome increase in the number of agents available for the treatment of MRSA infection. These drugs have certain differentiating attributes and may offer some advantages over vancomycin, but they also have significant limitations. These agents provide some alternative when no other options are available.
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Project description:One known and three new potent, selective, and nontoxic anti-MRSA metabolites, kaempferol 3-O-alpha-l-(2'',3''-di-E-p-coumaroyl)rhamnoside (1) (IC(50) 2.0 microg/mL), kaempferol 3-O-alpha-l-(2''-E-p-coumaroyl-3''-Z-p-coumaroyl)rhamnoside (2) (IC(50) 0.8 microg/mL), kaempferol 3-O-alpha-l-(2''-Z-p-coumaroyl-3''-E-p-coumaroyl)rhamnoside (3) (IC(50) 0.7 microg/mL), and kaempferol 3-O-alpha-l-(2'',3''-di-Z-p-coumaroyl)rhamnoside (4) (IC(50) 0.4 microg/mL), were isolated from the leaves of the common American sycamore, Platanus occidentalis. Compounds 2-4 are new. Due to the unusual selectivity, potency, and safety of the pure compounds and the semipure glycoside mixture against MRSA, it is clear that this represents a viable class of inhibitors to prevent growth of MRSA on surfaces and systemically.
| S-EPMC4883668 | biostudies-other
Project description:Resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA) often cause infections with high rates of mortality. Antimicrobial peptides are source of molecules for new antimi-crobials development, such as melittin, a fraction of venom from Apis mellifera bee. The aims of this work were to evaluate antibacterial and antibiofilm activity of melittin and its association with oxa-cillin (meltoxa) on MRSA isolates and to investigate mechanisms of action on MRSA by using proteomic analysis.
2023-05-25 | MSV000092035 | MassIVE