The extension of multidrug-resistant strains of Staphylococcus aureus (S. aureus) is one of the main health challenges in the world, which requires serious solutions to deal with it. Combination therapies using conventional antibiotics and new antibacterial compounds that target different bacterial pathways are effective methods against resistant bacterial infections. Gallium is an iron-like metal that competes with iron for uptake into bacteria and has the potential to disrupt iron-dependent vital processes in bacteria. In this study, we explored the antibacterial effects of gallium nitrate (Ga(NO3)3) and vancomycin alone and in combination with each other on methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) using microdilution assay and checkerboard test, respectively. Then, their effect on the formation and destruction of biofilms was investigated. Finally, the amount of ROS production in the presence of these two compounds in bacteria was evaluated. The results indicated that the vancomycin/ Ga(NO3)3 combination reduced the MIC of vancomycin in the MRSA strain and had an additive effect on it. Vancomycin plus Ga(NO3)3 reduced the formation of biofilms and increased the destruction of biofilms formed in both strains, especially in the MRSA strain. ROS production was also higher in the combination of vancomycin with Ga(NO3)3 compared to vancomycin alone, especially in MRSA. Therefore, our results showed that Ga(NO3)3 enhances the antibacterial activity of vancomycin and this combination therapy can be considered as a new strategy for the treatment of MRSA infections.

Staphylococcus aureus bacteraemia (SAB) is a bloodstream infection that carries a high risk of exacerbating a diseased state and may result in an increased death rate. The aim of this study was to assess mortality risk in Methicillin Resistant Staphylococcus aureus (MRSA) bacteraemia compared to Methicillin Susceptible Staphylococcus aureus (MSSA) bacteraemia through meta-meta-analyses. The study followed PRISMA guidelines, conducting a comprehensive search in Scopus, PubMed, and Google Scholar. It included full-text systematic reviews and meta-analyses comparing MRSA vs. MSSA bacteraemia, excluding reviews without data pooling and unclear selection criteria. Validity was assessed using QUOROM and AMSTAR. Edwards\' Venn diagrams were used to visualized overlaps between primary studies. Aggregated odds ratio (OR) and risk ratios with 95% confidence intervals were calculated using the random-effect model. Heterogeneity was evaluated using the Higgins I2 statistic. The study included 3 meta-analysis studies, a total of 38,159 patients, with 9,056 having MRSA bacteraemia and 29,103 having MSSA bacteraemia. Data were collected from 46 different outcome studies published between 2001 and 2022. The meta-analyses used 7 to 33 primary studies from 1990 to 2020, with no overlap. Odds ratios (ORs) ranged from 1.78 to 2.92, while relative risks (RR) ranged from 1.57 to 2.37 for the included meta-anlysis. The pooled analysis confirmed a higher risk of mortality in patients with MRSA bacteraemia (OR: 2.35, RR: 2.01, HR: 1.61) compared to MSSA bacteraemia. Heterogeneity among the studies was considerable (I2: 90-91%). The study strongly supports that most patient deaths from SAB are linked to MRSA rather than MSSA. This highlights the significant public health problem posed by SAB, with difficult and often unsuccessful treatment leading to increased mortality and high healthcare costs.

Methicillin-resistant Staphylococcus aureus (MRSA) is a predominant nosocomial infection-causing bacteria. The aim of this study was to develop a novel single-bacteria multiplex digital PCR assays (SMD-PCR), which is capable of simultaneously detecting and discriminating Methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA. This protocol employed TaqMan probes to detect SAOUHSC_00106 and mecA genes, with the latter being linked to methicillin resistance. A total of 72 samples from various specimen types were evaluated. The accuracy rates for the sputum samples, pus samples, swab samples, ear secretion samples, and catheter samples were 94.44%, 100%, 92%, 100%, and 100%, respectively. Our results showed that the clinical practicability of SMD-PCR has applicability to the rapid detection of MRSA without DNA extraction or bacterial culture, and can be utilized for the rapid detection of Staphylococcus aureus and the timely identification of MRSA in clinical samples, thereby providing an advanced platform for the rapid diagnosis of clinical MRSA infection.

UNASSIGNED: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections.
UNASSIGNED: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV-Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied.
UNASSIGNED: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 µM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy.
UNASSIGNED: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.

BACKGROUND: Staphylococcus aureus is a notorious multidrug resistant pathogen prevalent in healthcare facilities worldwide. Unveiling the mechanisms underlying biofilm formation, quorum sensing and antibiotic resistance can help in developing more effective therapy for S. aureus infection. There is a scarcity of literature addressing the genetic profiles and correlations of biofilm-associated genes, quorum sensing, and antibiotic resistance among S. aureus isolates from Malaysia.
METHODS: Biofilm and slime production of 68 methicillin-susceptible S. aureus (MSSA) and 54 methicillin-resistant (MRSA) isolates were determined using a a plate-based crystal violet assay and Congo Red agar method, respectively. The minimum inhibitory concentration values against 14 antibiotics were determined using VITEK® AST-GP67 cards and interpreted according to CLSI-M100 guidelines. Genetic profiling of 11 S. aureus biofilm-associated genes and agr/sar quorum sensing genes was performed using single or multiplex polymerase chain reaction (PCR) assays.
RESULTS: In this study, 75.9% (n = 41) of MRSA and 83.8% (n = 57) of MSSA isolates showed strong biofilm-forming capabilities. Intermediate slime production was detected in approximately 70% of the isolates. Compared to MSSA, significantly higher resistance of clindamycin, erythromycin, and fluoroquinolones was noted among the MRSA isolates. The presence of intracellular adhesion A (icaA) gene was detected in all S. aureus isolates. All MSSA isolates harbored the laminin-binding protein (eno) gene, while all MRSA isolates harbored intracellular adhesion D (icaD), clumping factors A and B (clfA and clfB) genes. The presence of agrI and elastin-binding protein (ebpS) genes was significantly associated with biofilm production in MSSA and MRSA isolates, respectively. In addition, agrI gene was also significantly correlated with oxacillin, cefoxitin, and fluoroquinolone resistance.
CONCLUSIONS: The high prevalence of biofilm and slime production among MSSA and MRSA isolates correlates well with the detection of a high prevalence of biofilm-associated genes and agr quorum sensing system. A significant association of agrI gene was found with cefoxitin, oxacillin, and fluoroquinolone resistance. A more focused approach targeting biofilm-associated and quorum sensing genes is important in developing new surveillance and treatment strategies against S. aureus biofilm infection.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become a major public health problem all over the world. After the 2019 coronavirus illness (COVID-19), the pandemic may have influenced research priorities and resource allocation, potentially affecting the ability to monitor MRSA trends.
OBJECTIVE: The study aimed to evaluate the prevalence of S. aureus, including MRSA infections, and their antimicrobial susceptibilities over the years 2019 and 2020 in a tertiary hospital in Makkah City, KSA.
METHODS: A total of 2128 and 1515 laboratory (lab) samples were collected during the years 2019 and 2020, respectively. From these samples, the prevalence of S. aureus, including MRSA, and their antibiotic susceptibility were identified using standard, automated, and molecular microbiological methods.
RESULTS: The present study shows that the lab prevalence of all S. aureus during 2019 was found to be 35.5%, of which MRSA was 44.8%. During 2020, the frequency of S. aureus strains was 16%, of which MRSA was 41.2%. The most common MRSA isolated during both years were colonizing pus swabs and urine samples. The results showed that MRSA susceptibility against antimicrobial agents in 2019 was as follows: vancomycin (100%), linezolid (100%), trimethoprim-sulfamethoxazole (88%), and doxycycline (34.2%). The MRSA strains isolated during 2020 were as follows: vancomycin (100%), linezolid (96%), trimethoprim-sulfamethoxazole (100%), and doxycycline (24.3%). There was no significant difference in the incidence and antimicrobial resistance rates of MRSA over the two years.
CONCLUSIONS: It was concluded that the prevalence rates of MRSA have not increased in 2020 when compared to 2019. Vancomycin, linezolid, trimethoprim-sulfamethoxazole, and doxycycline remain susceptible to the positive collected MRSA strains. There was no significant difference between the prevalence and antimicrobial resistance rates of MRSA between 2019 and 2020. Continued research efforts are needed to address this persistent public health threat. Strategies to control the spread of MRSA should include early detection of MRSA and surveillance, even during pandemics.

BACKGROUND: First-line treatments for methicillin-susceptible S. aureus (MSSA) bacteraemia are nafcillin, oxacillin, or cefazolin. Regional shortages of these antibiotics force clinicians to use other options like dicloxacillin and cephalotin. This study aims to describe and compare the safety and efficacy of cephalotin and dicloxacillin for the treatment of MSSA bacteraemia.
METHODS: This retrospective study was conducted in a referral centre in Mexico City. We identified MSSA isolates in blood cultures from 1 January 2012 to 31 December 2022. Patients ≥ 18 years of age, with a first episode of MSSA bacteraemia, who received cephalotin or dicloxacillin as the definitive antibiotic treatment, were included. The primary outcome was in-hospital all-cause mortality.
RESULTS: We included 202 patients, of which 48% (97/202) received cephalotin as the definitive therapy and 52% (105/202) received dicloxacillin. In-hospital all-cause mortality was 20.7% (42/202). There were no differences in all-cause in-hospital mortality between patients receiving cephalotin or dicloxacillin (20% vs. 21%, p = 0.43), nor in 30-day all-cause mortality (14% vs. 18%, p = 0.57) or 90-day all-cause mortality (24% vs. 22%, p = 0.82). No severe adverse reactions were associated with either antibiotic.
CONCLUSIONS: Cephalotin and dicloxacillin were equally effective for treating MSSA bacteraemia, and both showed an adequate safety profile.

The availability of stability data for the use of continuous intravenous flucloxacillin in an elastomeric device has enabled the treatment of serious Methicillin Sensitive Staphylococcus aureus (MSSA) in the outpatient parenteral antimicrobial therapy (OPAT) setting. This service review aimed to evaluate current standard of care to establish the clinical effectiveness and complication rates associated with its use since its introduction at our institution. A retrospective review of clinical outcomes and adverse events/complications, was undertaken for all patients who received continuous infusion flucloxacillin for complicated MSSA infection between January 2019 and July 2022 via our OPAT service. Thirty-nine patients were included. An OPAT treatment outcome of \'Treatment aim attained uncomplicated\' was achieved in 29/39 (74%) patients. Two patients had an OPAT treatment outcome of treatment aim not attained, both of which required unexpected hospital re-admission. An adverse event/complication occurred in 8 patients. There were two relapses in the 12-month follow-up period. Our review supports the assertion that continuous infusion flucloxacillin is clinically effective and well tolerated for the treatment of complicated MSSA infection in the OPAT setting.

OBJECTIVE: Antistaphylococcal penicillins and cefazolin have been used as first line therapy in Methicillin-susceptible Staphylococcus aureus bloodstream infection. While efficacy of both regimens seems to be similar, the compounds may differ with regard to tolerability. This study aims to describe the clinical use of cefazolin and flucloxacillin, focussing on discontinuation or change of anti-infective agent due to adverse events.
METHODS: This observational prospective study was conducted at two German tertiary care centres with an internal recommendation of flucloxacillin for MSSA-BSI in one, and of cefazolin in the other centre. Adverse events were registered weekly under treatment and at a 90-day follow-up. Descriptive analysis was complemented by a propensity score analysis comparing adverse events (stratified rank-based test applied to the sum of Common Terminology Criteria for adverse events ratings per patient).
RESULTS: Of 71 patients included, therapy was initiated with flucloxacillin in 56 (79%), and with cefazolin in 15 (21%). The propensity score analysis indicates a statistically significant difference concerning the severity of adverse events between the treatment groups in favour of cefazolin (p = 0.019). Adverse events led to discontinuation of flucloxacillin in 7 individuals (13% of all patients receiving flucloxacillin). Clinical outcome was not different among treatment groups.
CONCLUSIONS: Using cefazolin rather than flucloxacillin as a first line agent for treatment of MSSA-BSI is supported by these clinical data.

Background: Staphylococcus aureus is a human pathogen responsible for high mortality rates. The development of new antimicrobials is urgent. Materials & methods: The authors evaluated the activity of hydralazine along with its synergism with other drugs and action on biofilms. With regard to action mechanisms, the authors evaluated cell viability, DNA damage and molecular docking. Results: MIC and minimum bactericidal concentration values ranged from 128 to 2048 μg/ml. There was synergism with oxacillin (50%) and vancomycin (25%). Hydralazine reduced the viability of biofilms by 50%. After exposure to hydralazine 2× MIC, 58.78% of the cells were unviable, 62.07% were TUNEL positive and 27.03% presented damage in the comet assay (p < 0.05). Hydralazine showed affinity for DNA gyrase and TyrRS. Conclusion: Hydralazine is a potential antibacterial.
Staphylococcus aureus is a bacterium that can cause infection. Infections of S. aureus are becoming difficult to treat, but developing new drugs is a challenge. Repurposing them may be easier. This study looks at the possibility of using hydralazine, a type of medicine used to treat high blood pressure, against S. aureus. The authors found that hydralazine can kill S. aureus and can be used with other antibiotics, including oxacillin and vancomycin. Hydralazine interferes with important processes for the multiplication and survival of this bacterium. These results are preliminary but encouraging. Further studies are needed to confirm the use of hydralazine as a new treatment for S. aureus infections.