scholarly journals Novel Antibiotic Combinations of Diverse Subclasses for Effective Suppression of Extensively Drug-Resistant Methicillin-Resistant Staphylococcus aureus (MRSA)

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Shumyila Nasir ◽  
Muhammad Sufyan Vohra ◽  
Danish Gul ◽  
Umm E Swaiba ◽  
Maira Aleem ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clavulanic Acid ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Development Of Resistance ◽  
Amoxicillin Clavulanic Acid ◽  
Combination Antibiotics ◽  
Time Kill

The emergence of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), the chief etiological agent for a range of refractory infections, has rendered all β-lactams ineffective against it. The treatment process is further complicated with the development of resistance to glycopeptides, primary antibiotics for treatment of MRSA. Antibiotic combination therapy with existing antimicrobial agents may provide an immediate treatment option. Minimum inhibitory concentrations (MICs) of 18 different commercially available antibiotics were determined along with their 90 possible pairwise combinations and 64 triple combinations to filter out 5 best combinations. Time-Kill kinetics of these combinations were then analyzed to find collateral bactericidal combinations which were then tested on other randomly selected MRSA isolates. Among the top 5 combinations including levofloxacin-ceftazidime; amoxicillin/clavulanic acid-tobramycin; amoxicillin/clavulanic acid-cephradine; amoxicillin/clavulanic acid-ofloxacin; and piperacillin/tazobactam-tobramycin, three combinations were found to be collaterally effective. Levofloxacin-ceftazidime acted synergistically in 80% of the tested clinical MRSA isolates. First-line β-lactams of lower generations can be used effectively against MRSA infection when used in combination. Antibiotics other than glycopeptides may still work in combination.

scholarly journals Promising Antibiofilm Agents: Recent Breakthrough against Biofilm Producing Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 667 ◽  
Author(s):  
Marwa I. Abd El-Hamid ◽  
El-sayed Y. El-Naenaeey ◽  
Toka M kandeel ◽  
Wael A. H. Hegazy ◽  
Rasha A. Mosbah ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Proteinase K ◽  
Zno Nps ◽  
Methicillin Resistant ◽  
Biofilm Production ◽  
Antibiofilm Agents

Multidrug resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) is a superbug pathogen that causes serious diseases. One of the main reasons for the lack of the effectiveness of antibiotic therapy against infections caused by this resistant pathogen is the recalcitrant nature of MRSA biofilms, which results in an increasingly serious situation worldwide. Consequently, the development of innovative biofilm inhibitors is urgently needed to control the biofilm formation by this pathogen. In this work, we thus sought to evaluate the biofilm inhibiting ability of some promising antibiofilm agents such as zinc oxide nanoparticles (Zno NPs), proteinase K, and hamamelitannin (HAM) in managing the MRSA biofilms. Different phenotypic and genotypic methods were used to identify the biofilm producing MDR MRSA isolates and the antibiofilm/antimicrobial activities of the used promising agents. Our study demonstrated strong antibiofilm activities of ZnO NPs, proteinase K, and HAM against MRSA biofilms along with their transcriptional modulation of biofilm (intercellular adhesion A, icaA) and quorum sensing (QS) (agr) genes. Interestingly, only ZnO NPs showed a powerful antimicrobial activity against this pathogen. Collectively, we observed overall positive correlations between the biofilm production and the antimicrobial resistance/agr genotypes II and IV. Meanwhile, there was no significant correlation between the toxin genes and the biofilm production. The ZnO NPs were recommended to be used alone as potent antimicrobial and antibiofilm agents against MDR MRSA and their biofilm-associated diseases. On the other hand, proteinase-K and HAM can be co-administrated with other antimicrobial agents to manage such types of infections.

scholarly journals Livestock-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) in Purulent Subcutaneous Lesions of Farm Rabbits

Foods ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 439 ◽  
Author(s):  
Vanessa Silva ◽  
Telma de Sousa ◽  
Paula Gómez ◽  
Carolina Sabença ◽  
Madalena Vieira-Pinto ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Spa Typing ◽  
Disk Diffusion Method ◽  
Methicillin Resistant ◽  
Resistance To Penicillin ◽  
Mrsa Strains

Methicillin-resistant Staphylococcus aureus (MRSA) are one of the main pathogens associated with purulent infections. MRSA clonal complex 97 (CC97) has been identified in a wide diversity of livestock animals. Therefore, we aimed to investigate the antibiotic resistance profiles of MRSA strains isolated from purulent lesions of food-producing rabbits. Samples from purulent lesions of 66 rabbits were collected in a slaughterhouse in Portugal. Samples were seeded onto ORSAB plates with 2 mg/L of oxacillin for MRSA isolation. Susceptibility to antibiotics was tested by the disk diffusion method against 14 antimicrobial agents. The presence of resistance genes, virulence factors and the immune evasion cluster (IEC) system was studied by polymerase chain reaction. All isolates were characterized by multilocus sequence typing (MLST), agr and spa typing. From the 66 samples analyzed, 16 (24.2%) MRSA were detected. All strains were classified as multidrug-resistant as they were resistant to at least three classes of antibiotics. All isolates showed resistance to penicillin, erythromycin and clindamycin. Seven isolates were resistant to gentamicin and harbored the aac(6′)-Ie-aph (2″)-Ia gene. Resistance to tetracycline was detected in 10 isolates harboring the tet(K) gene. The IEC genes were detected in three isolates. MRSA strains belonged to CC97, CC1, CC5, CC15 or CC22. The isolates were assigned to six different spa types. In this study we found a moderate prevalence of multidrug-resistant MRSA strains in food-producing rabbits. This may represent concern for food safety and public health, since cross-contamination may occur, leading to the spread of MRSA and, eventually, the possibility of ingestion of contaminated meat.

Oxazolidinone-containing Hybrids with Antibacterial Activity Against Methicillin-resistant Staphylococcus aureus (MRSA): A Mini-review

2020 ◽  
Vol 20 ◽  
Author(s):  
Dan Jiang ◽  
Bi Liu ◽  
Tao Gao
Keyword(s):  
Staphylococcus Aureus ◽  
Side Effects ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
High Efficiency ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Wide Range ◽  
Clinically Significant ◽  
Set Up

: The increasing danger by methicillin-resistant Staphylococcus aureus (MRSA) and the limited therapeutic op-tions towards invasive MRSA infections make an urgent demand for the development of novel anti-MRSA agents. Oxazol-idinone derivatives could inhibit protein synthesis by acting on the ribosomal 50S subunit of the bacteria and prevent for-mation of a functional 70S initiation complex, so oxazolidinones are a novel class of antimicrobial agents with potential activity against a wide range of clinically significant multidrug-resistant Gram-positive pathogens. However, oxazolidinones such as linezolid are associated with significant adverse events, and myelosuppression represents the main unfavorable side effects. Moreover, MRSA isolates which are resistant to oxazolidinones have already emerged. Hybridization of oxazoli-dinone with other antibacterial pharmacophores has the potential to interact with multiple targets or to counterbalance the known side effects associated with each pharmacophore. Thus, oxazolidinone-containing hybrids are useful scaffolds for the development of novel anti-MRSA agents. This review covers the recent advances of oxazolidinone-containing hybrids with anti-MRSA activity developed in last decade to set up the direction for the design and development of oxazolidinone-containing hybrids with high efficiency and low toxicity.

scholarly journals Evaluation of Bacterial Infections in Bahraini Pediatric Patients From A Tertiary Care Hospital – A Prospective Study

2021 ◽  
Vol 33 (2) ◽  
Keyword(s):  
Staphylococcus Aureus ◽  
Prospective Study ◽  
Clavulanic Acid ◽  
Pediatric Patients ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Care Hospital ◽  
Methicillin Resistant ◽  
E Coli ◽  
Amoxicillin Clavulanic Acid ◽  
Susceptibility Patterns

Background & Objective: Children are prone to a plethora of infections. This study aimed to evaluate the prevalence of most common microorganisms isolated from the bacterial cultures infecting pediatric patients and their resistance to antibiotics in Bahrain. Methods: This prospective study included 1146 isolates collected from pediatric patients of Bahrain. Demographic details such as age, gender, and nationality were recorded for each of the patients. Samples were cultured using different nutrient media (MacConkey agar, Sheep blood agar etc.), and analysis was done using standard microbiological techniques and Vitex automated analyzer. Application of Kirby- Bauer procedure and Vitex aided in the assessment of antibiotic resistance of the isolates. Proportion test was used to calculate the study outcomes. P value < 0.05 was considered statistically significant. Results: Streptococcus group A (52.98%) and E. coli (35.97%) were the two most common microorganisms observed in pediatric patients. A high prevalence of Extended-spectrum beta-lactamases (ESBL), Campylobacter sp., and Methicillin-resistant Staphylococcus aureus (MRSA) were also observed (P<0.001). A majority of the organisms were identified from urine (27.66%) and throat cultures (25.22%). E-coli showed significant resistance towards trimethoprim /sulfamethoxazole (22.97%) and amoxicillin/ clavulanic acid (20.19%). Susceptibility patterns of gentamicin, amoxicillin, trimethoprim, ciprofloxacin showed significant association with the isolates. Odds of susceptibility of amoxicillin/ clavulanic acid (2.89 times), trimethoprim/sulfamethoxazole (2.29 times) was more for gram-positive isolates but for ciprofloxacin (2.08 times), which was more for gram-negative isolates. Conclusion: Antimicrobial susceptibility patterns were unique among the pediatric patients of Bahrain. Keywords: Anti-bacterial Agents, Antimicrobial Stewardship, Escherichia coli, Child, Methicillin- Resistant Staphylococcus aureus.

scholarly journals In Vitro Synergy of Pongamia pinnata Extract in Combination with Antibiotics for Inhibiting and Killing Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 103 ◽  
Author(s):  
Po-An Su ◽  
Shun-Lai Li ◽  
Hung-Jen Tang ◽  
Chi-Chung Chen ◽  
Ying-Chen Lu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Seed Coat ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Pongamia Pinnata ◽  
Multiple Drug ◽  
Methicillin Resistant ◽  
Time Kill

Aims: Currently, we face the serious problem of multiple drug-resistant pathogens. The development of new antimicrobial agents is very costly and time-consuming. Therefore, the use of medicinal plants as a source of alternative antibiotics or for enhancing antibiotic effectiveness is important. Methods: The antibacterial effects of aqueous extracts of the seed coat of Pongamia pinnata (Linn.) Pierre in combination with several antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) were tested by broth dilution, checkerboard, and time-kill methods. Results: For the combinations of P. pinnata with ampicillin, meropenem, cefazolin, cefotaxime, cefpirome, and cefuroxime, 70% to 100% were synergistic, with a fractional inhibitory concentration (FIC) index of < 0.5. For the time-kill method with 0.5× minimum inhibitory concentration (MIC) of P. pinnata in combination with 8, 4, 2, and 1 µg mL−1 of the various antibiotics, almost all of the combinations showed synergistic effects, even with the lowest concentrations of P. pinnata, except for aztreonam. No antagonistic effect was observed for these combinations. Conclusions: Based on these findings, aqueous seed coat extracts of P. pinnata have good potential for the design of new antimicrobial agents.

scholarly journals The Prevalence of Virulence Determinants and Antibiotic Resistance Patterns in Methicillin—Resistant Staphylococcus aureus in a Nursing Home in Poland

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 427
Author(s):  
Martyna Kasela ◽  
Agnieszka Grzegorczyk ◽  
Bożena Nowakowicz-Dębek ◽  
Anna Malm
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Pulse Field ◽  
Virulence Determinants ◽  
Gene Encoding ◽  
Methicillin Resistant ◽  
Pulse Field Gel Electrophoresis

Nursing homes (NH) contribute to the regional spread of methicillin-resistant Staphylococcus aureus (MRSA). Moreover, residents are vulnerable to the colonization and subsequent infection of MRSA etiology. We aimed at investigating the molecular and phenotypic characteristics of 21 MRSA collected from the residents and personnel in an NH (Lublin, Poland) during 2018. All MRSA were screened for 20 genes encoding virulence determinants (sea-see, eta, etb, tst, lukS-F-PV, eno, cna, ebpS, fib, bbp, fnbA, fnbB, icaADBC) and for resistance to 18 antimicrobials. To establish the relatedness and clonal complexes of MRSA in NH we applied multiple-locus variable-number tandem-repeat fingerprinting (MLVF), pulse field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. We identified four sequence types (ST) among two clonal complexes (CC): ST (CC22) known as EMRSA-15 as well as three novel STs—ST6295 (CC8), ST6293 (CC8) and ST6294. All tested MRSA were negative for sec, eta, etb, lukS-F-PV, bbp and ebpS genes. The most prevalent gene encoding toxin was sed (52.4%; n = 11/21), and adhesins were eno and fnbA (100%). Only 9.5% (n = 2/21) of MRSA were classified as multidrug-resistant. The emergence of novel MRSA with a unique virulence and the presence of epidemic clone EMRSA-15 creates challenges for controlling the spread of MRSA in NH.

scholarly journals A Molecular Insight into the Synergistic Mechanism of Nigella sativa (Black Cumin) with β-Lactam Antibiotics against Clinical Isolates of Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 11 (7) ◽  
pp. 3206
Author(s):  
Lorina I. Badger-Emeka ◽  
Promise Madu Emeka ◽  
Hairul Islam M. Ibrahim
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanism Of Action ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Nigella Sativa ◽  
Synergistic Effects ◽  
Diffusion Method ◽  
Methicillin Resistant ◽  
Cell Wall Disruption ◽  
Time Kill ◽  
Insight Into

Methicillin-resistant Staphylococcus aureus (MRSA) infection is detrimental to hospitalized patients. With diminishing choices of antibiotics and the worry about resistance to colistin in synergistic combined therapy, there are suggestions for the use of herbal derivatives. This investigation evaluated the synergistic effects of Nigella sativa (NS) in combination with beta-lactam (β-lactam) antibiotics on extreme drug-resistant (XDR) MRSA isolates. NS concentrations of 10, 7.5, 5.0, 2.5, 1.0, and 0.1 µg/mL, alone and in combination with β-lactam antibiotics, were used to determine the antimicrobial susceptibility of MRSA isolates by the well diffusion method. Time–kill assays were performed using a spectrophotometer, with time–kill curves plotted and synergism ascertained by the fractional inhibitory concentration (FIC). Scanning and transmission electron microscopy were used to gain insight into the mechanism of action of treated groups. Isolates were inhibited by the NS concentrations, with differences in the zones of inhibition being statistically insignificant at p < 0.05. There were statistically significant differences in the time–kill assay for the MRSA isolates. In addition, NS combined with augmentin showed better killing than oxacillin and cefuroxime. The mechanism of action shown by the SEM and TEM results revealed cell wall disruption, which probably created interference that led to bacterial lysis.

scholarly journals Trans-Cinnamaldehyde Exhibits Synergy with Conventional Antibiotic against Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 22 (5) ◽  
pp. 2752
Author(s):  
Shu Wang ◽  
Ok-Hwa Kang ◽  
Dong-Yeul Kwon
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Synergistic Effects ◽  
Regulatory Gene ◽  
Western Blot Assay ◽  
Methicillin Resistant ◽  
Wide Range ◽  
Kill Curve ◽  
Conventional Antibiotics ◽  
Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide and has acquired multiple resistance to a wide range of antibiotics. Hence, there is a pressing need to explore novel strategies to overcome the increase in antimicrobial resistance. The present study aims to investigate the efficacy and mechanism of plant-derived antimicrobials, trans-cinnamaldehyde (TCA) in decreasing MRSA’s resistance to eight conventional antibiotics. A checkerboard dilution test and time–kill curve assay are used to determine the synergistic effects of TCA combined with the antibiotics. The results indicated that TCA increased the antibacterial activity of the antibiotics by 2-16-fold. To study the mechanism of the synergism, we analyzed the mecA transcription gene and the penicillin-binding protein 2a level of MRSA treated with TCA by quantitative RT-PCR or Western blot assay. The gene transcription and the protein level were significantly inhibited. Additionally, it was verified that TCA can significantly inhibit the biofilm, which is highly resistant to antibiotics. The expression of the biofilm regulatory gene hld of MRSA after TCA treatment was also significantly downregulated. These findings suggest that TCA maybe is an exceptionally potent modulator of antibiotics.

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