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Objectives: This study aimed to determine the feasibility of capturing antimicrobial usage data from prisons for inclusion in the Antimicrobial Use and Resistance in Australia (AURA) surveillance system and to analyse 2021 and 2022 South Australian (SA) usage data for notable trends. Methods: Monthly antimicrobial supply data for eight SA prisons were collected. Antimicrobial volume was converted into the World Health Organization metric, defined daily doses (DDD). Usage rates were calculated relative to prison occupied bed days (OBD). Results: Annual usage of systemic antimicrobials across eight SA prisons totalled 26,448 DDD and 23,526 DDD in 2021 and 2022 respectively. Antibacterials accounted for 80.6% of all antimicrobials dispensed during the study period. The average antibacterial usage rate in female prisons was higher on average than in male prisons. The state-wide systemic antibacterial usage rate in SA prisons declined by 11.3% from 23.8 DDDs/1000 OBD in 2021 to 21.1 DDDs/1000 OBD. Doxycycline, amoxicillin, flucloxacillin, amoxicillin-clavulanic acid, and cefalexin accounted for 72% of the total systemic antibacterial usage rate. Variation in the oral and topical antifungal agents used and the rate of use was observed between prisons. Conclusions: This SA pilot study demonstrates the feasibility of including prisons in routine national antimicrobial surveillance using similar methodology to hospital surveillance. The contributing facilities comprised 6.1% of all Australian prison beds, and extrapolation of the results suggests that the identified gap in surveillance may equate to over 400,000 DDD per annum in prisons nationwide, equating to approximately 5% of hospital inpatient antimicrobial usage. What is known about the topic? Surveillance of antimicrobial use is a useful tool to identify overuse or inappropriate use and enable targeted interventions to optimise antimicrobial prescribing and reduce the risk of antimicrobial resistance. What does this paper add? The methodology currently used to monitor antimicrobial use in Australian hospitals could be utilised to conduct facility-level surveillance in Australian prisons and would provide a mechanism to benchmark use between facilities and identify unexpected or inappropriate use. What are the implications for practitioners? Surveillance of antimicrobial use in prisons would support prison healthcare workers to monitor use over time, identify any increasing or unexpected trends in use, and target educational interventions to ensure compliance with antimicrobial prescribing guidelines. [ABSTRACT FROM AUTHOR]

Background: Multi-drug resistant Staphylococcus aureus is one of the most common causes of nosocomial and community-acquired infections, with high morbidity and mortality. Treatment of such infections is particularly problematic; hence, it is complicated by antibiotic resistance, and there is currently no reliable vaccine. Furthermore, it is well known that S. aureus produces an exceptionally large number of virulence factors that worsen infection. Consequently, the urgent need for anti-virulent agents that inhibit biofilm formation and virulence factors has gained momentum. Therefore, we focused our attention on an already-approved antibiotic and explored whether changing the dosage would still result in the intended anti-virulence effect. Methods: In the present study, we determined the antibiotic resistance patterns and the MICs of oxacillin against 70 MDR S. aureus isolates. We also investigated the effect of sub-MICs of oxacillin (at 1/4 and 1/8 MICs) on biofilm formation using the crystal violet assay, the phenol-sulphuric acid method, and confocal laser scanning microscopy (CLSM). We examined the effect of sub-MICs on virulence factors and bacterial morphology using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and electron microscopy, respectively. Moreover, we studied the effect of sub-MICs of oxacillin (OX) in-vivo using a wound infection model. Results: Oxacillin at 1/2 MIC showed a significant decrease in bacterial viability, while 1/4 and 1/8 MICs had negligible effects on treated bacterial isolates. Treatment of MDR isolates with 1/4 or 1/8 MICs of oxacillin significantly reduced biofilm formation (64% and 40%, respectively). The treated MDR S. aureus with sub-MICs of OX exhibited a dramatic reduction in several virulence factors, including protease, hemolysin, coagulase, and toxic shock syndrome toxin-1 (TSST-1) production. The sub-MICs of OX significantly decreased (P < 0.05) the gene expression of biofilm and virulence-associated genes such as agrA, icaA, coa, and tst. Furthermore, oxacillin at sub-MICs dramatically accelerated wound healing, according to the recorded scoring of histological parameters. Conclusion: The treatment of MDR S. aureus with sub-MICs of oxacillin can help in combating the bacterial resistance and may be considered a promising approach to attenuating the severity of S. aureus infections due to the unique anti-biofilm and anti-virulence activities. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the presence of Staphylococcus aureus from the production chain of artisanal Coalho cheese, and to analyse the phenotypic profile of the strains, virulence factors and antimicrobial susceptibility profile. From the 52 samples collected, typical colonies of Staphylococcus spp. were isolated. From these positive S. aureus isolates, the genes encoding for enterotoxin production and antibiotic resistance were characterised. Additionally, agr locus typing was also performed. A significant presence of the sea enterotoxin producing gene, a higher incidence of the mecA gene and agr III group was identified. There was multiple resistance to penicillin, oxacillin, erythromycin and clindamycin in 79% of isolates. These results indicate that the artisanal Coalho cheese production process is associated with high contamination levels and significant potential for the isolated strains to produce enterotoxins. Therefore, there is cause for concern regarding the quality of the artisanal Coalho cheese produced. [ABSTRACT FROM AUTHOR]

Background Successful use of carbapenems in combination with cefazolin or oxacillin for treatment of MSSA bacteraemia has been described; however, comparative data to standard treatment approaches are lacking. Methods This was a multicentre, retrospective study of adult patients with MSSA bacteraemia for >48 h. Standard treatment was considered monotherapy with cefazolin, oxacillin or nafcillin. Combination therapy was defined as the addition of ertapenem or meropenem to standard treatment for at least 24 h. The primary outcome was duration of bacteraemia defined as time from administration of an antibiotic with in vitro activity to first negative blood culture. Time to blood culture sterilization was compared through risk-set matching with aid of a propensity score. Results Overall, 238 patients were included; 66% (157/238) received standard treatment and 34% (81/238) received combination therapy. The median (IQR) time to carbapenem initiation was 4.7 (3.63–6.5) days. Patients who received combination therapy were younger (P  = 0.012), more likely to have endocarditis (P  = 0.034) and had longer median duration of bacteraemia (P  < 0.001). After applying risk-set matching, patients who received combination therapy experienced faster time to blood culture sterilization compared with control patients [HR = 1.618 (95% CI; 1.119–2.339) P  = 0.011]. Using a paired hazard model, 90 day mortality rates were not statistically different among patients who received combination therapy versus matched controls [HR = 1.267 (95% CI; 0.610–2.678), P  = 0.608]. Discussion Carbapenem combination therapy resulted in faster time to blood culture sterilization, but no differences in overall mortality rates. Randomized trials are critical to determine the utility of carbapenem combination therapy. [ABSTRACT FROM AUTHOR]

One of the complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA) is periprosthetic joint infection (PJI). Numerous studies have been performed to explore the value of biological parameters in the early identification of infection rates after THA and TKA. This study investigates alterations in inflammatory markers associated with PJI. This retrospective study focused on a cohort of patients with hip and knee arthroplasty treated between 2016 and 2022. CRP, ESR, and fibrinogen were observed preoperatively, on days one, three, six, and twenty-one postoperatively. From a total of 4076 THA and TKA performed during this period, 62 patients were identified with periprosthetic infections. We also identified the pathogens responsible for infections in order to assess if asymptomatic preoperative infections were involved in PJI. In patients with acute infections following TKA, days one and three postoperative recorded a CRP value below the expected range. The value of CRP in patients with early infection after THA was significantly increased on day six postoperative. ESR and fibrinogen values were not statistically significantly correlated with early PJI. The CRP level in acute PJI shows different patterns than those shown in the literature. [ABSTRACT FROM AUTHOR]

Abstract Background Multi-drug resistant Staphylococcus aureus is one of the most common causes of nosocomial and community-acquired infections, with high morbidity and mortality. Treatment of such infections is particularly problematic; hence, it is complicated by antibiotic resistance, and there is currently no reliable vaccine. Furthermore, it is well known that S. aureus produces an exceptionally large number of virulence factors that worsen infection. Consequently, the urgent need for anti-virulent agents that inhibit biofilm formation and virulence factors has gained momentum. Therefore, we focused our attention on an already-approved antibiotic and explored whether changing the dosage would still result in the intended anti-virulence effect. Methods In the present study, we determined the antibiotic resistance patterns and the MICs of oxacillin against 70 MDR S. aureus isolates. We also investigated the effect of sub-MICs of oxacillin (at 1/4 and 1/8 MICs) on biofilm formation using the crystal violet assay, the phenol-sulphuric acid method, and confocal laser scanning microscopy (CLSM). We examined the effect of sub-MICs on virulence factors and bacterial morphology using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and electron microscopy, respectively. Moreover, we studied the effect of sub-MICs of oxacillin (OX) in-vivo using a wound infection model. Results Oxacillin at 1/2 MIC showed a significant decrease in bacterial viability, while 1/4 and 1/8 MICs had negligible effects on treated bacterial isolates. Treatment of MDR isolates with 1/4 or 1/8 MICs of oxacillin significantly reduced biofilm formation (64% and 40%, respectively). The treated MDR S. aureus with sub-MICs of OX exhibited a dramatic reduction in several virulence factors, including protease, hemolysin, coagulase, and toxic shock syndrome toxin-1 (TSST-1) production. The sub-MICs of OX significantly decreased (P

Staphylococcus aureus is a pathogenic bacterium‐contaminating milk and milk products causing food poisoning primarily due to its enterotoxins. A cross‐sectional study was conducted from November 2021 to June 2022 in Wolaita Sodo Town, to detect Methicillin‐resistant Staphylococcus aureus (MRSA) in raw cow's milk and assess their resistance levels to different antimicrobials. Purposive sampling was used to select 34 dairy farms. Accordingly, 419 raw milk samples from the farm and collection centers were collected. Isolates of S. aureus showing resistance to Cefoxitin were classified as MRSA. From the total 419 samples, 22.19% (93/419) were contaminated with S. aureus in dairy cows. The prevalence of S. aureus in raw milk, bulk milk from the farm, and bulk tank milk from the collection centers was 16.9%, 2.1%, and 3.1%, respectively. The risk of S. aureus contamination in dairy farm owners and milkers who do not take food safety training was 5.303 times higher than the risk of S. aureus contamination in dairy farm owners and milkers who take food safety training. The risk of S. aureus contamination in dairy farms kept under poor management system was 7.34 times more than that of dairy farms kept under good management. The cefoxitin disk diffusion method was used to detect MRSA, 57.14% being resistant to Cefoxitin in total while approximately 87.5% were sensitive to Sulfamethoxazole‐trimethoprim and Gentamycin, while Erythromycin registered 75%, Ciprofloxacin 62.5%, Chloramphenicol 62.5%, and Tetracycline 25%. This study revealed that MRSA exhibited a notable multidrug resistance pattern, encompassing resistance to multiple drugs, with a prevalence of 75%. Significantly, the hands of milkers and the milking containers emerged as pivotal sources of contamination. This underscores the crucial importance of maintaining stringent hygienic practices during the milking process, with particular emphasis on thorough cleaning and decontamination of utensils. [ABSTRACT FROM AUTHOR]

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The guanidine core has been one of the most studied functional groups in medicinal chemistry, and guanylation reactions are powerful tools for synthesizing this kind of compound. In this study, a series of five guanidine-core small molecules were obtained through guanylation reactions. These compounds were then evaluated against three different strains of Escherichia coli, one collection strain from the American Type Culture Collection (ATCC) of E. coli ATCC 35218, and two clinical extended-spectrum beta-lactamase (ESBL)-producing E. coli isolates (ESBL1 and ESBL2). Moreover, three different strains of Pseudomonas aeruginosa were studied, one collection strain of P. aeruginosa ATCC 27853, and two clinical multidrug-resistant isolates (PA24 and PA35). Among Gram-positive strains, three different strains of Staphylococcus aureus, one collection strain of S. aureus ATCC 29213, and two clinical methicillin-resistant S. aureus (MRSA1 and MRSA2) were evaluated. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) experiments were reported, and the drop plate (DP) method was used to determine the number of viable suspended bacteria in a known beaker volume. The results from this assessment suggest that guanidine-core small molecules hold promise as therapeutic alternatives for treating infections caused by clinical Gram-negative and Gram-positive bacteria, highlighting the need for further studies to explore their potential. The results from this assessment suggest that the chemical structure of CAPP4 might serve as the basis for designing more active guanidine-based antimicrobial compounds, highlighting the need for further studies to explore their potential. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus can colonize and infect a variety of animal species. In dairy herds, it is one of the leading causes of mastitis cases. The objective of this study was to characterize the S. aureus isolates recovered from nasal swabs of 249 healthy cows and 21 breeders of 21 dairy farms located in two provinces of Algeria (Tizi Ouzou and Bouira). Methods: The detection of enterotoxin genes was investigated by multiplex PCRs. Resistance of recovered isolates to 8 antimicrobial agents was determined by disc-diffusion method. The slime production and biofilm formation of S. aureus isolates were assessed using congo-red agar (CRA) and microtiter-plate assay. Molecular characterization of selected isolates was carried out by spa-typing and Multi-Locus-Sequence-Typing (MLST). Results: S. aureus was detected in 30/249 (12%) and 6/13 (28.6%) of nasal swabs in cows and breeders, respectively, and a total of 72 isolates were recovered from positive samples (59 isolates from cows and 13 from breeders). Twenty-six of these isolates (36.1%) harbored genes encoding for staphylococcal enterotoxins, including 17/59 (28.8%) isolates from cows and 9/13 (69.2%) from breeders. Moreover, 49.1% and 92.3% of isolates from cows and breeders, respectively, showed penicillin resistance. All isolates were considered as methicillin-susceptible (MSSA). Forty-five (76.3%) of the isolates from cows were slime producers and 52 (88.1%) of them had the ability to form biofilm in microtiter plates. Evidence of a possible zoonotic transmission was observed in two farms, since S. aureus isolates recovered in these farms from cows and breeders belonged to the same clonal lineage (CC15-ST15-t084 or CC30-ST34-t2228). Conclusions: Although healthy cows in this study did not harbor methicillin-resistant S. aureus isolates, the nares of healthy cows could be a reservoir of enterotoxigenic and biofilm producing isolates which could have implications in human and animal health. [ABSTRACT FROM AUTHOR]

A multifunctional surface-enhanced Raman scattering (SERS) platform integrating sensitive detection and drug resistance analysis was developed for Gram-positive bacteria. The substrate was based on self-assembled Ti3C2Tx@Au NPs films and capture molecule phytic acid (IP6) to achieve specific capture of Gram-positive bacteria and different bacteria were analyzed by fingerprint signal. It had advantages of good stability and homogeneity (RSD = 8.88%). The detection limit (LOD) was 102 CFU/mL for Staphylococcus aureus and 103 CFU/mL for MRSA, respectively. A sandwich structure was formed on the capture substrate by signal labels prepared by antibiotics (penicillin G and vancomycin) and non-interference SERS probe molecules (4-mercaptobenzonitrile (2223 cm−1) and 2-amino-4-cyanopyridine (2240 cm−1)) to improve sensitivity. The LOD of Au NPs@4-MBN@PG to S. aureus and Au NPs@AMCP@Van to MRSA and S. aureus were all improved to 10 CFU/mL, with a wide dynamic linear range from 108 to 10 CFU/mL (R2 ≥ 0.992). The SERS platform can analyze the drug resistance of drug-resistant bacteria. Au NPs@4-MBN@PG was added to the substrate and captured MRSA to compare the SERS spectra of 4-MBN. The intensity inhomogeneity of 4-MBN at the same concentrations of MRSA and the nonlinearity at the different concentrations of MRSA revealed that MRSA was resistant to PG. Finally, the SERS platform achieved the determination of MRSA in blood. Therefore, this SERS platform has great significance for the determination and analysis of Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

Purpose: 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. Conclusion: Using cefazolin rather than flucloxacillin as a first line agent for treatment of MSSA-BSI is supported by these clinical data. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [R4W4] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [R4W4] against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) by a checkered board assay. [R4W4] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against E. coli (FICI = 0.3) but not against MRSA (FICI = 0.75). Moreover, we investigated the mechanism of action of [R4W4] against MRSA by applying biophysical assays to evaluate zeta potential, cytoplasmic membrane depolarization, and lipoteichoic acid (LTA) binding affinity. [R4W4] at a 16 mg/mL concentration stabilized the zeta potential of MRSA −31 ± 0.88 mV to −8.37 mV. Also, [R4W4] at 2 × MIC and 16 × MIC revealed a membrane perturbation process associated with concentration-dependent effects. Lastly, in the presence of BODIPY-TR-cadaverine (BC) fluorescence dyes, [R4W4] exhibited binding affinity to LTA comparable with melittin, the positive control. In addition, the antibacterial activity of [R4W4] against MRSA remained unchanged in the absence and presence of LTA, with an MIC of 8 µg/mL. Therefore, the [R4W4] mechanism of action is deemed bactericidal, involving interaction with bacterial cell membranes, causing concentration-dependent membrane perturbation. Additionally, after 30 serial passages, there was a modest increment of MRSA strains resistant to [R4W4] and a change in antibacterial effectiveness MIC [R4W4] and vancomycin by 8 and 4 folds with a slight change in Levofloxacin MIC 1 to 2 µg/mL. These data suggest that [R4W4] warrants further consideration as a potential AMP. [ABSTRACT FROM AUTHOR]

The mec-independent oxacillin non-susceptible S. aureus (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure. However, the responsible molecular mechanisms are still very little understood. Here, we studied four clinical ST8-MSSA-t024 isolates recovered during the course of antibiotic treatment from a patient suffering successive episodes of bacteremia. The first isolates (SAMS1, SAMS2, and SAMS3) were susceptible to cefoxitin and oxacillin. The last one (SA2) was susceptible to cefoxitin, resistant to oxacillin, lacked mec genes, and had reduced susceptibility to teicoplanin. SA2 showed higher β-lactamase activity than SAMS1. However, β-lactamase hyperproduction could not be linked to oxacillin resistance as it was not inhibited by clavulanic acid, and no genetic changes that could account for its hyperproduction were found. Importantly, we hereby report the in vivo acquisition and coexistence of different adaptive mutations in genes associated with peptidoglycan synthesis (pbp2, rodA, stp1, yjbH, and yvqF/vraT), which is possibly related with the development of oxacillin resistance and reduced susceptibility to teicoplanin in SA2. Using three-dimensional models and PBP binding assays, we demonstrated the high contribution of the SA2 PBP2 Ala450Asp mutation to the observed oxacillin resistance phenotype. Our results should be considered as a warning for physicians and microbiologists in the region, as MIONSA detection and treatment represent an important clinical challenge. [ABSTRACT FROM AUTHOR]

Recently, OTULIN haploinsufficiency was linked to enhanced susceptibility to Staphylococcus aureus infections accompanied by local necrosis and systemic inflammation. The pathogenesis observed in haploinsufficient patients differs from the hyperinflammation seen in classical OTULIN-related autoinflammatory syndrome (ORAS) patients and is characterized by increased susceptibility of dermal fibroblasts to S. aureus alpha toxin-inflicted cytotoxic damage. Immunological abnormalities were not observed in OTULIN haploinsufficient patients, suggesting a non-hematopoietic basis. In this research report, we investigated an Otulin+/- mouse model after in vivo provocation with lipopolysaccharide (LPS) to explore the potential role of hematopoietic-driven inflammation in OTULIN haploinsufficiency. We observed a hyperinflammatory signature in LPS-provoked Otulin+/- mice, which was driven by CD64+ monocytes and macrophages. Bone marrow-derived macrophages (BMDMs) of Otulin+/- mice demonstrated higher proinflammatory cytokine secretion after in vitro stimulation with LPS or polyinosinic:polycytidylic acid (Poly(I:C)). Our experiments in full and mixed bone marrow chimeric mice suggest that, in contrast to humans, the observed inflammation was mainly driven by the hematopoietic compartment with cell-extrinsic effects likely contributing to inflammatory outcomes. Using an OTULIN haploinsufficient mouse model, we validated the role of OTULIN in the regulation of environmentally directed inflammation. [ABSTRACT FROM AUTHOR]

Introduction: The use of antimicrobials is a permanent challenge as it is constantly confronted with the ability of bacteria to develop resistance mechanisms. Objective: The objective of this research was to evaluate the antimicrobial effect of polyphenolic extracts present in Ananas comosus crown. Materials and Methods: 3.5 kg of Ananas comosus pineapple crown leaves were collected and taken to a tray dryer to reduce humidity, then, they were milled until a fine flour was obtained, for the extraction process of the oleaginous extract a Soxhlet equipment was used, using 70% ethanol as solvent, The identification of phenolic compounds was carried out by ultra-high resolution liquid chromatography with an Orbitrap mass detector. The microbiological analysis was evaluated by the standardized method of diffusion with discs using Mueller-Hinton agar, for which the Staphylococcus aureus strain (ATCC 25923) was used, using oxacillin as a positive control and DMSO as a negative control. Results: from the drying obtained, the humidity was reduced by 50%, with which the dry matter obtained was ground and used to carry out the extraction process of the oleaginous extract, obtaining 63 ml of which 27 phenolic compounds were identified. As for the microbiological analysis carried out, inhibition halos varying between 4.5 mm and 6.0 mm were observed. Conclusion: Finally, it was concluded that the polyphenols present in the extract of Ananas comosus showed antibacterial activity on Staphylococcus aureus, with a greater inhibition effect observed when a higher concentration of the extract was applied. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes (L. monocytogenes) poses a significant threat to food safety due to its ability to cause severe human illness and its resistance to various antibiotics and environmental conditions. This study investigated the prevalence, serotype distribution, virulence gene profiles, and antimicrobial resistance patterns of L. monocytogenes in ready-to-eat (RTE) food products from Romania. A total of 8151 samples were analyzed, including various processed dairy, bovine, poultry, pork, and fish products. Bacterial isolation was conducted using the classical standard method, followed by confirmation through biochemical and molecular testing. Among the isolated strains, serotypes 1/2a, 1/2b, and 1/2c were identified, with a prevalence of 75% for serotype 1/2a. Additionally, virulence genes specific to listeriolysin O (hlyA) and regulatory factor A (prfA) were detected in all isolates. Antimicrobial susceptibility testing revealed varying resistance patterns among the L. monocytogenes strains. Trimethoprim-sulfamethoxazole and oxacillin showed the highest prevalence of resistance at 26.92% and 23.07%, respectively. However, all strains remained susceptible to ciprofloxacin, levofloxacin, and moxifloxacin. Notably, 23.07% of the isolates exhibited multidrug resistance, with the most common pattern being resistance to oxacillin, penicillin, and tetracycline. Analysis of antimicrobial resistance genes identified tetracycline resistance genes, particularly tet(C), tet(M), and tet(K), in a significant proportion of isolates. The presence of ampC and dfrD genes was also notable, indicating potential mechanisms of resistance. These results emphasize the necessity for ongoing surveillance of L. monocytogenes in RTE foods and emphasize the importance of thorough monitoring of antimicrobial resistance to guide public health strategies within the European Union. [ABSTRACT FROM AUTHOR]

Avian cellulitis is one of the most important field problems facing the poultry sector. Sever financial losses resulted from the condemnation of the broiler carcasses infected with cellulitis lesions. In light of this, the current study was aimed to isolation and identification of the bacterial species causing cellulitis in broiler chickens in Dakahlia and Sharkia Governorates, Egypt. The bacterial isolates were tested for their antimicrobial susceptibility and molecular detection of some virulence and antimicrobial resistance genes. In addition to evaluate the antibacterial activity of quaternary ammonium compounds and glutaraldehyde (TH4 ®) against the bacterial isolates. Four bacterial species were isolated; E. coli, S. aureus, P. aeruginosa and Proteus mirabilis with percentages of (75%), (20%), (6%) and (5%) respectively. E. coli was recorded as the most predominant isolated bacteria in this study with12 different sero- groups (O1, O2, O26, O55, O78, O91, O121, O125, O126, O128, O153 and O158). E. coli O78 and O91 were the most prevalent identified sero- groups. The antimicrobial susceptibility testing revealed higher resistances against doxycycline and ampicillin (95.6%), amoxicillin (90.7%), norfloxacin (84%), oxytetracycline (79.1%) and amikacin (71.6%) in E. coli, doxycycline (73.3%), oxytetracycline (80%),ampicillin(75%), streptomycin (80%), erythromycin (73.3%), and oxacillin (86.7%) in S. aureus, doxycycline (83.3%), oxytetracycline (77.8%), ampicillin (83.3%), amoxicillin (88.9%), neomycin (72.2%) and erythromycin (77.8%) in P. aeruginosa and doxycycline, oxytetracycline, ampicillin, amoxicillin, streptomycin and erythromycin (100% for each of them) in Proteus mirabilis. All isolated bacterial species were multidrug resistance (MDR). The molecular identification showed the detection of virulence genes: iutA in E. coli, nuc in S. aureus, toxA in P. aeruginosa and rsbA in Proteus mirabilis., with percentage of (100%). blaTEM, tetA (A), qnrA, tetK, mecA, aac(6') aph (2"), ereA and aada1 resistance genes were reported in this study. Quaternary ammonium compounds in combination glutaraldehyde (TH4 ®) with 2% concentration showed the highest antibacterial activity against the examined multidrug resistant bacterial isolates. These results suggested for application of 2% TH4 ® to achieve effective disinfectant programs in poultry farms. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR), caused by microbial infections, has become a major contributor to morbid rates of mortality worldwide and a serious threat to public health. The exponential increase in resistant pathogen strains including Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) poses significant hurdles in the health sector due to their greater resistance to traditional treatments and medicines. Efforts to tackle infectious diseases caused by resistant microbes have prompted the development of novel antibacterial agents. Herein, we present selenium and copper oxide monometallic nanoparticles (Se-MMNPs and CuO-MMNPs), characterized using various techniques and evaluated for their antibacterial potential via disc diffusion, determination of minimum inhibitory concentration (MIC), antibiofilm, and killing kinetic action. Dynamic light scattering (DLS), scanning electron microscopy (SEM/EDX), and X-ray diffraction (XRD) techniques confirmed the size-distribution, spherical-shape, stability, elemental composition, and structural aspects of the synthesized nanoparticles. The MIC values of Se-MMNPs and CuO-MMNPs against S. aureus and E. coli were determined to be 125 μg/mL and 100 μg/mL, respectively. Time–kill kinetics studies revealed that CuO-MMNPs efficiently mitigate the growth of S. aureus and E. coli within 3 and 3.5 h while Se-MMNPs took 4 and 5 h, respectively. Moreover, CuO-MMNPs demonstrated better inhibition compared to Se-MMNPs. Overall, the proposed materials exhibited promising antibacterial activity against S. aureus and E. coli pathogens. [ABSTRACT FROM AUTHOR]

Background. Pasteurella species are frequently encountered as serious diseases in small ruminants. It is the main cause of respiratory pasteurellosis in sheep and goats of all age groups. Methods. The cross-sectional study was conducted from December 2022 to April 2023 in Haramaya district, eastern Ethiopia, to isolate and identify Pasteurella multocida and Mannheimia haemolytica and estimate their prevalence, associated risk factors, and antimicrobial sensitivity of isolates in small ruminants using a purposive sampling method. A total of 384 samples (156 nasal swabs from clinic cases and 228 lung swabs from abattoir cases) were collected. STATA 14 software was used to analyze the data. In addition, multivariable logistic regression analysis was performed to assess an association of risk factors. Results. Out of the 384 samples examined, 164 were positive for pasteurellosis, resulting in a 42.70% prevalence. Similarly, 63 (38.4%) of the 164 positive results were from nasal swabs, while 101 (61.6%) came from lung samples. M. haemolytica accounted for 126 (76.82%) of the isolates, while P. multocida accounted for 38 (23.17%). Of the 63 nasal swab isolates, 33 (37%) were from goats and 30 (42.8%) were from sheep. And 17 (10.89%) and 46 (29.58%), respectively, were P. multocida and M. haemolytica. Of the 46 (40%) of the 101 (44.3%) isolates of the pneumonic lung, samples were from goats, while 55 (48.47%) were from sheep. In this study, the risk factors (species, age, and body condition score) were found to be significant (p < 0.05). Pasteurella isolates evaluated for antibiotic susceptibility were highly resistant to oxacillin (90.90%), followed by gentamycin (72.72%), and penicillin (63.63%). However, the isolates were highly sensitive to chloramphenicol (90.90%), followed by tetracycline (63.63%), and ampicillin (54.54%). Conclusion. This study showed that M. haemolytica and P. multocida are the common causes of mannheimiosis and pasteurellosis in small ruminants, respectively, and isolates were resistant to commonly used antibiotics in the study area. Thus, an integrated vaccination strategy, antimicrobial resistance monitoring, and avoidance of stress-inducing factors are recommended. [ABSTRACT FROM AUTHOR]

Aims The purpose was to evaluate the antimicrobial activity of highly soluble polypyrrole (Hs-PPy), alone or combined with oxacillin, as well as its antibiofilm potential against methicillin-resistant Staphylococcus aureus strains. Furthermore, the in silico inhibitory mechanism in efflux pumps was also investigated. Methods and results Ten clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and two reference strains were used. Antimicrobial activity was determined by broth microdilution, and the combination effect with oxacillin was evaluated by the checkerboard assay. The biofilm formation capacity of MRSA and the interference of Hs-PPy were evaluated. The inhibitory action of Hs-PPy on the efflux pump was evaluated in silico through molecular docking. Hs-PPy showed activity against the isolates, with inhibitory action between 62.5 and 125 µg ml−1 and bactericidal action at 62.5 µg ml−1, as well as synergism in association with oxacillin. The isolates ranged from moderate to strong biofilm producers, and Hs-PPy interfered with the formation of this structure, but not with mature biofilm. There was no in silico interaction with the efflux protein EmrD, the closest homolog to NorA. Conclusions Hs-PPy interferes with biofilm formation by MRSA, has synergistic potential, and is an efflux pump inhibitor. [ABSTRACT FROM AUTHOR]

The continued use of antibiotics is bringing extensive resistance in methicillinresistant Staphylococcus aureus (MRSA) of dairy animals and demands inclusion of non-antibiotic sources in treatment protocols. The current study aims to explore antibacterial potential of berberine (BR), artesunate (AR), and quercetin (QT) and extent of their resistance modulation capacity in combination with β-lactam antibiotics against MRSA. For this study, a total of 674 milk samples from dairy cows were collected for isolation of MRSA and thereafter phytochemicals (drugs) alone and in combination with β-lactams (penicillin, oxacillin, cefoxitin, ampicillin) were evaluated against MRSA. The synergy testing showed all synergistic effects except AR with penicillin which was additive effect. The synergism of antibiotics and phytochemicals was further confirmed by time-kill assay. The killing kinetics revealed a zero bacterial count at 16h of incubation in all combinations. Additionally, the killing synergy showed a significant decline i.e. less than 60% in case of BR in combination with oxacillin and penicillin at the initial 2h of incubation followed by AR and QT in combination with ampicillin. The study thus revealed potential antibacterial effects of berberine, artesunate, and quercetin along with significant resistance modulation in terms of highly synergistic combinations with antibiotics focused on novel insights into alternatives to antimicrobials to pave the road for antimicrobial stewardship against ailments like mastitis. [ABSTRACT FROM AUTHOR]

Background Managing drug–food interactions may help to achieve the optimal action and safety profile of β-lactam antibiotics. Methods We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 β-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices. Results Eighteen of 25 β-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or C max decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or C max increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed β-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor). Conclusions Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low. [ABSTRACT FROM AUTHOR]

Background: There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. Methods: BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student's t-test. Results: The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. Conclusions: Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells. [ABSTRACT FROM AUTHOR]

The antibacterial activity of Cinnamaldehyde against Methicillin-resistant Staphylococcus aureus in Bovine Mastitis is investigated in this study, providing insights into inhibition mechanisms and elucidating the effects on bacterial cell membranes. The Minimum Inhibitory Concentration and Minimum Bactericidal Concentration were determined in this study. In addition, growth curves and a time-kill assay were constructed to assess the antibacterial activity of Cinnamaldehyde. The study revealed that the MIC values ranged from 62.5 to 125 μg/mL, and the MBC values ranged from 125 to 250 μg/mL. The presence of sublethal concentrations of Cinnamaldehyde impeded bacterial growth, while high concentrations demonstrated a significant and rapid bactericidal effect. Subsequently, we examined cell morphology using SEM and TEM, evaluated membrane integrity via laser confocal fluorescence microscopy, and measured levels of β-galactosidase, extracellular DNA release, LDH activity, and ROS, to assess the antibacterial mechanism of Cinnamaldehyde. The findings indicated that with higher concentrations of Cinnamaldehyde, Methicillin-resistant Staphylococcus aureus demonstrated significant morphological alterations and disruption of both the cell wall and membrane. Furthermore, Cinnamaldehyde disrupted the integrity of membranes and increased permeability of the outer membrane in a manner dependent on its concentration. Cinnamaldehyde notably triggered the release of β-galactosidase, extracellular DNA, and LDH, in addition to elevating cellular ROS levels. Finally, the effect of Cinnamaldehyde on the transcription levels of genes related to cell membrane synthesis was assessed using RT-qPCR, and the effect of Cinnamaldehyde on the total protein content of Methicillin-resistant Staphylococcus aureus cells was assessed using WB. The RT-qPCR results showed that Cinnamaldehyde at 1xMIC notably upregulated the transcription levels of genes related to fatty acid biosynthesis in Methicillin-resistant Staphylococcus aureus cell membranes, with a significant or highly significant effect. The WB results showed that Cinnamaldehyde exerts its antibacterial action by suppressing protein expression in Methicillin-resistant Staphylococcus aureus. These findings illustrate that Cinnamaldehyde exerts a potent inhibitory effect on Methicillin-resistant Staphylococcus aureus, establishing a fundamental foundation for the potential use of Cinnamaldehyde essential oil as an antibacterial agent in the treatment of bovine mastitis, in accordance with established scientific standards. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) has become a global health crisis in need of novel solutions. To this end, antibiotic combination therapies, which combine multiple antibiotics for treatment, have attracted significant attention as a potential approach for combating AMR. To facilitate advances in antibiotic combination therapies, most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however, there remains a need for automated high-throughput platforms that can create and examine antibiotic combinations on-demand, at scale, and with minimal reagent consumption. To address these challenges, we have developed a Robotic-Printed Combinatorial Droplet (RoboDrop) platform by integrating a programmable droplet microfluidic device that generates antibiotic combinations in nanoliter droplets in automation, a robotic arm that arranges the droplets in an array, and a camera that images the array of thousands of droplets in parallel. We further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination testing. As a demonstration, we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin, penicillin, and oxacillin against a model E. coli strain. We therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR. We report the robotic-printed combinatorial droplet platform as a potential solution to automate and miniaturize the screening of antibiotic combinations to identify synergistic combinations for combating antimicrobial resistance. [Display omitted] [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is an important microbe which has the ability to cause a mastitis in cows and causes huge economic losses. This microorganism has a growing ability to resist antimicrobial agents which let to hinder the treatments programs. The study aimed to isolate and identify the prevalence of multi-drug resistant S. aureus in mastitic cows' milk in delta region (Dakahlia and Damietta governorates). A two hundred milk samples were randomly selected from clinical mastitic and sub-clinical mastitic infected cows (one hundred from each); these infected cows farms located at Dakahlia and Damietta governorates during the period of November 2020 to March 2021. The samples were diagnosed using routine culture methods to isolate S. aureus. All suspected colonies were subjected to biochemical analysis for the basic identification of S. aureus colonies. The biochemically identified S. aureus colonies were confirmed by using molecular marker targeting thermonuclease-nuc gene by PCR. All the confirmed S. aureus isolates were subjected to antimicrobial sensitivity testing against eighteen antimicrobial agents by using Kirby-Bauer disc diffusion method. Out of the 200 tested milk sample, a forty-six were identified as S. aureus isolate revealed a total prevalence 23%. S. aureus prevalence rate in clinical mastitic and sub-clinical mastitic samples was 37 (80.4%), and 9 (19.6%), respectively. S. aureus isolates revealed a high resistant against oxacillin, ampicillin, and ceftiofur, and moderate resistance against tetracycline, amoxicillin-clavulanic acid, cefotaxime, cefuroxime, vancomycin, and gentamycin, while a high sensitivity of S. aureus was displayed against ciprofloxacin, SXT and marbofloxacin. All examined S. aureus isolates were sensitive against imipenem. Multidrug resistance (MDR) was displayed in all the isolates. Building food tracking and farm animal surveillance systems is essential to improving the healthiness processing and guaranteeing that consumers receive safe food. [ABSTRACT FROM AUTHOR]

Bacterial sialadenitis is common in diabetics, and Staphylococcus aureus (SA) is the causative agent. Prescription of empiric antibiotics to eliminate bacteria is the best treatment in these cases. The purpose of this study was to investigate the effect of Minimum Inhtionibitory Concentration (MIC) of second, third, and fourth generation of cephalosporins as well as oxacillin against SA. Methods: In this study, 247 samples were collected from the parotid duct opening from type II diabetes patients. The samples were transferred to the laboratory in BHIB medium and were subjected to culture and biochemical diagnostic tests to isolate and detect SAMIC of Cefuroxime, Ceftriaxone, cefepime, cloxacillin, oxacillin against SA determined by broth microdilution method. The results were analyzed by SPSS18. Results: Among 247 type 2 diabetic patients, Staphylococcus aureus was isolated from 61 patients (39 women, 22 men). 51, 46, 52 and 60 people were sensitive to 2nd, 3rd, 4th generation cephalosporin antibiotics and oxacillin, respectively. Of these, the lowest to the highest average MIC values were related to oxacillin, cefuroxime, cefepime and ceftriaxone. The average MIC in three antibiotics, oxacillin, methicillin, and cloxacillin, respectively was 0.71±0.69, 6.24±4.04, 40.08± 33.23. The type of antibiotic used had a significant relationship with resistance and sensitivity. Sensitivity to oxacillin, methicillin and cloxacillin was observed in in 98.4%, 85.2% and 75.4% of patients. Conclusions: Oxacillin showed significantly the lowest MIC compared to methicillin and cloxacillin. Therefore, it can be a recommended antibiotic for infections caused by staph aureus to be administered to diabetics. Based on our results, oxacillin can be a suitable treatment option in diabetic patients with bacterial sialadenitis. If oxacillin is not available, second generation cephalosporin (cefuroxime) can be used against SA. [ABSTRACT FROM AUTHOR]

Background: The preferred antibiotic salvage regimen for persistent methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) is unclear. Ertapenem with cefazolin or an antistaphylococcal penicillin has been primarily described, but identifying alternative carbapenem-sparing options may support antibiotic stewardship efforts and decrease the risk of antibiotic-associated Clostridioides difficile infection. Objective: We sought to evaluate the effectiveness and safety of daptomycin plus oxacillin (D/O) for persistent MSSAB. Methods: This was a single-center, retrospective cohort of patients with persistent MSSAB who received D/O between January 1, 2014, and January 1, 2023. Adult patients were included if they had blood cultures positive for MSSA ≥72 hours and received D/O combination for ≥48 hours. Patients were excluded if they were pregnant, incarcerated, or received another antibiotic considered to have excellent activity against MSSA. The primary outcome was time to MSSA bacteremia clearance post-daptomycin initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day all-cause mortality, MSSA bacteremia-related mortality, 90-day readmission for MSSAB, and incidence of antibiotic-associated adverse effects. Time to MSSAB clearance post-D/O initiation was plotted using Kaplan-Meier estimation. Results: Seven unique patient encounters were identified including 4 with endocarditis. Despite a median MSSA bacteremia duration of 7.8 days, median clearance was 2 days post-daptomycin initiation. All achieved microbiological cure, and no adverse effects were reported. Ninety-day all-cause mortality, MSSAB-related mortality, and 90-day readmission for MSSAB occurred in 28.6%, 14.3%, and 14.3% of patients, respectively. Conclusions and Relevance: D/O was an effective, well-tolerated salvage regimen in this cohort and may represent a carbapenem-sparing option for persistent MSSAB. [ABSTRACT FROM AUTHOR]

Rationale: Acute respiratory distress syndrome (ARDS) has an unacceptably high mortality rate (35%) and is without effective therapy. Orai1 is a Ca2+ channel involved in store-operated Ca2+ entry (SOCE), a process that exquisitely regulates inflammation. Orai1 is considered a druggable target, but no Orai1-specific inhibitors exist to date. Objectives: To evaluate whether ELD607, a first-in-class Orai1 antagonist, can treat ARDS caused by bacterial pneumonia in preclinical models. Methods: ELD607 pharmacology was evaluated in HEK293T cells and freshly isolated immune cells from patients with ARDS. A murine acute lung injury model caused by bacterial pneumonia was then used: mice were infected with Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant S. aureus, or multidrug-resistant P. aeruginosa and then treated with ELD607 intranasally. Measurements and Main Results: ELD607 specifically inhibited SOCE in HEK293T cells with a half-maximal inhibitory concentration of 9 nM. ELD607 was stable in ARDS airway secretions and inhibited SOCE in ARDS immune cells. In vivo, inhaled ELD607 significantly reduced neutrophilia and improved survival. Surprisingly, Orai1 inhibition by ELD607 caused a significant reduction in lung bacteria, including methicillin-resistant S. aureus. ELD607 worked as an immunomodulator that reduced cytokine levels, reduced neutrophilia, and promoted macrophage-mediated resolution of inflammation and clearance of bacteria. Indeed, when alveolar macrophages were depleted with inhaled clodronate, ELD607 was no longer able to resolve inflammation or clear bacteria. Conclusions: These data indicate that specific Orai1 inhibition by ELD607 may be a novel approach to reduce multiorgan inflammation and treat antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

This review concerns the rare, acquired, usually iatrogenic, high-anion-gap metabolic acidosis, pyroglutamic acidosis. Pyroglutamate is a derivative of the amino acid glutamate, and is an intermediate in the 'glutathione cycle', by which glutathione is continuously synthesized and broken down. The vast majority of pyroglutamic acidosis cases occur in patients on regular, therapeutic doses of paracetamol. In about a third of cases, flucloxacillin is co-prescribed. In addition, the patients are almost always seriously unwell in other ways, typically with undernourishment of some form. Paracetamol, with underlying disorders, conspires to divert the glutathione cycle, leading to the overproduction of pyroglutamate. Hypokalaemia is seen in about a third of cases. Once the diagnosis is suspected, it is simple to stop the paracetamol and change the antibiotic (if flucloxacillin is present), pending biochemistry. N-acetyl-cysteine can be given, but while the biochemical justification is compelling, the clinical evidence base is anecdotal. [ABSTRACT FROM AUTHOR]

Various bacterial species form a microbiome in the skin. In the past, dead Staphylococcus aureus derived from atopic dermatitis (AD) are taken up by keratinocytes; however, whether live S. aureus can be taken up by keratinocytes is unknown. This study aimed to examine whether live AD strains of S. aureus internalize into the keratinocytes and how the internalization changes under conditions in which other bacterial species including S. epidermidis are present. HaCaT cells were cultured with live S. aureus and S. epidermidis (live or heat-treated) or their culture supernatants. After coculture, the change in the amount of S. aureus in the cytoplasm of HaCaT cells was analyzed using, a high-throughput imaging system, Opera Phenix™. Live S. aureus were taken up in the cytoplasm of HaCaT cells. Coculturing live S. aureus with live S. epidermidis or the culture supernatants decreased the abundance of S. aureus in the cytoplasm. The heat-treated culture supernatants of live S. epidermidis or culture supernatants of other S. strains did not decrease the abundance of S. aureus in the cytoplasm. Live S. aureus was internalized into the cytoplasm of HaCaT cells as does heat-treated S. aureus. In addition, the heat-sensitive substances secreted by coculture with S. epidermidis and keratinocytes inhibited the uptake of S. aureus by keratinocytes. • HaCaT cells internalized live AD strains of Staphylococcus (S.) aureus. • The coexistence of S. epidermidis inhibits uptake of S. aureus into HaCaT cells. • Co-culture supernatant with S. epidermidis and HaCaT cells inhibits the uptake. • S. epidermidis alone does not inhibit uptake of S. aureus. • The factors that inhibit the uptake of S. aureus are inactivated by heat treatment. [ABSTRACT FROM AUTHOR]

Objective: To discuss the genotype distribution of methicillin-resistant Staphylococcus aureus (MRSA) in a tertiary hospital and to discuss the correlation among different molecular types of the strains, and to construct the resistance profile model under different genetic backgrounds. Methods: A total of 204 strains of Staphylococcus aureus (S. aureus) from 25 departments of the hospital were selected. The automatic VITEK 2 Compact system and E-test strips were used to detect the antimicrobial susceptibility of the strains. The detection of mecA gene by the polymerase chain reaction (PCR) method was used as the confirmatory experiment, the abilities of cefoxitin (FOX) and (or) oxacillin (OXA) were compared as phenotypic detection methods to screen MRSA. The molecular typing of MRSA strains was carried out by PCR method, including Staphylococcal protein A gene (spa) determination, accessory gene regulator (agr) typing, multilocus sequence typing (MLST), and staphylococcal chromosomal cassettes mec (SCCmec) typing. The resistance profile was constructed combing with antimicrobial susceptibility tests results and molecular typing results. Results: A total of 39 MRSA strains were obtained by detecting the mecA gene. A total of 51 phenotypic MRSA strains were identified by testing FOX and OXA. In spa typing, 57 different types were identified, including 5 new types (t20226, t20227, t20228, t20229, and t20230), with the main types being t309 (30. 9%), t078 (11. 8%), and t437 (11. 8%). In agr typing, 94. 9% of MRSA belonged to agr Ⅰ. The MLST analysis results of MRSA populations showed that ST59 clone (61. 5%) was the most prevalent, followed by ST72 (20. 5%). A total of 87. 2% of MRSA carried type Ⅳ SCCmec, with subtypes Ⅳ a accounting for 24 strains and subtype Ⅳ F accounting for 10 strains. Conclusion: The main genotype of MRSA is ST59-t437-agr Ⅰ-Ⅳ a and its resistance profile is primarily characterized by resistance to FOX-OXA-penicillin (PEN) -erythromycin (ERY) -clindamycin (CLI) . [ABSTRACT FROM AUTHOR]

This study aimed to determine resistance to antimicrobials of Staphylococcus aureus strains isolated from clinical specimens in Lithuanian hospitals and to identify the genes conferring resistance and virulence. The study was carried out from June 2019 to September 2021. S. aureus strains were isolated from skin, soft tissues, blood, lower respiratory tract, urine and other specimens. Antibiotic susceptibility testing was performed using the disc diffusion method according to EUCAST guidelines. All isolates were analyzed for detection of the ermA, ermC, mecA, mecC, tetK, tetM, and lukF-PV genes by multiplex real-time PCR. The 16S rRNA coding sequence was applied as an internal PCR control. Altogether, 745 S. aureus strains were analyzed. Antimicrobial susceptibility testing revealed that all isolates were susceptible to rifampin and vancomycin. Of the 745 strains, 94.8% were susceptible to tetracycline, 94.5% to clindamycin, and 88.3% to erythromycin. The lowest susceptibility rate was found for penicillin (25.8%). Six percent of the tested strains were methicillin-resistant S. aureus (MRSA). The majority of methicillin-resistant strains were isolated from skin and soft tissues (73.3%), with a smaller portion isolated from blood (17.8%) and respiratory tract (8.9%). The ermC gene was detected in 41.1% of erythromycin-resistant S. aureus strains, whereas ermA was detected in 32.2% of erythromycin-resistant S. aureus strains. 69.2% of tetracycline-resistant S. aureus strains had tetK gene, and 28.2% had tetM gene. 7.3% of S. aureus isolates harbored lukF-PV gene. The frequency of the pvl gene detection was significantly higher in MRSA isolates than in methicillin-susceptible S. aureus isolates (p < 0.0001). [ABSTRACT FROM AUTHOR]

Objectives: The current study was conducted to evaluate the antibacterial potential of leaf and fruit extracts of Zanthoxylum armatum against two pathogenic bacterial isolates, Staphylococcus aureus and Staphylococcus epidermidis. Methods: Twelve commercially available antibiotics were tested S. aureus and S. epidermidis by antimicrobial susceptibility test (AST). Qualitative analysis of phytochemicals was performed to evaluate the presence of certain secondary metabolites. The activity of Z. armatum extracts against S. aureus and S. epidermidis was measured as a maximum zone of inhibition exhibited by each leaf and fruit extract. An in-silico study was conducted on flavonoids and alkaloids to show their binding affinity with the PBP2a receptor protein of S. aureus and TcaR of S. epidermidis. Results: The AST revealed that S. aureus was resistant to Penicillin, Ampicillin, Clindamycin, Vancomycin, Rifampicin, Novobiocin, and Oxacillin, whereas S. epidermidis was resistant to Streptomycin, Oxacillin, Tetracycline, and Novobiocin. Qualitative analysis of phytochemicals resulted in the presence of Saponins, fixed oils, flavonoids, alkaloids, starch, and fatty acids in both leaf and fruit extracts. The maximum zone of inhibition against S. aureus was produced by methanolic leaf extracts of Z. armatum and chloroform fruit extracts. For S. epidermidis, the best activity was exhibited by benzene leaf extracts and methanolic fruit extracts. An in-silico study showed that flavonoids Nitidine and Nevadensin exhibited binding affinity with the PBP2a receptor protein higher than selected antibiotics, ie, Penicillin, Chloramphenicol, and Oxacillin. TcaR of S. epidermidis interacted with Tambuletin, followed by Nitidine and Kaempferol. Conclusion: After in vitro testing, in silico analysis advised extracting and purifying the bioactive components from Z. armatum extracts that showed significant interaction with bacterial virulence proteins for use as natural antibiotics against antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

Background: Determining oxacillin susceptibility using reference methods and automated systems is crucial for treating invasive infections caused by Staphylococcus aureus. This study compares the oxacillin susceptibility results from the two automated systems with agar dilution and correlates them with genotypes of invasive S. aureus. Methods: Non-duplicate S. aureus invasive isolates were collected over an 11-year period. The oxacillin susceptibility was determined with Phoenix 100 (Jan 2011 to Aug 2018) or Vitek 2 (Sep 2018 to Dec 2021), and susceptibility for oxacillin and cefoxitin was determined with agar dilution. Methicillin-resistant S. aureus (MRSA) was confirmed with mecA existence, and the genotype was determined using SCCmec. The association between genotype and antibiotic susceptibility using two automated systems and agar dilution was evaluated. Results: A total of 842 invasive S. aureus, including 443 mecA+ MRSA and 399 mecA- MSSA, were collected. The susceptibility rates of oxacillin determined by two automated systems and agar dilution were 68.8% (76.8% for Phoenix 100 and 57.6% for Vitek 2) and 54.0%, respectively. When compared with the oxacillin susceptibility using agar dilution, the categorical agreement for Phoenix 100 and Vitek 2 were 0.46% and 0.88%, respectively (p < 0.001). One hundred and forty-three isolates were misinterpreted as oxacillin-susceptible S. aureus (OSSA) using automated systems while comparing with agar dilution, among which molecularly community-associated MRSA (CA-MRSA) outnumbered healthcare-associated MRSA (HA-MRSA) (99 vs 34, p < 0.001). There were 70 mecA+ OSSA (OS-MRSA) using agar dilution, among which 42 harbored SCCmec types were predominantly categorized as CA-MRSA (38, p < 0.001). Conclusion: The categorical agreement of Vitek 2 in determining oxacillin susceptibility and predicting mecA existence is comparable with agar dilution, whereas Phoenix 100 is not. Most of those ORSA determined by agar dilution but misinterpreted as OSSA by automated systems and OS-MRSA are categorized as CA-MRSA. [ABSTRACT FROM AUTHOR]

Synergistic bioassay-guided isolation of the extracts of Artemisia rupestris L, which belongs to the family Asteraceae, afforded two acetylenic spiroketal enol ethers, namely rupesdiynes A (1) and B (2). Their structures were determined based on spectroscopic analysis and experimental and calculated ECD investigations. The two compounds exhibited synergistic activity and were able to reduce the minimum inhibitory concentration (MIC) of oxacillin four-fold, with a fractional inhibitory concentration index (FICI) of 0.5 in combination with oxacillin against the oxacillin-resistant EMRSA-16. Biofilm formation inhibitory and Ethidium bromide (EtBr) efflux assay were further employed to verify the possible mechanism of the synergistic antibacterial effect. Additionally, molecular docking studies were conducted to investigate the binding affinities of the two compounds with penicillin-binding protein 2a (PBP2a) of EMRSA-16. Taken together, rupesdiynes A (1) and rupesdiyne B (2) showed moderate synergistic activity against EMRSA-16 with oxacillin via inhibiting biofilm formation and efflux pump activity, respectively. [ABSTRACT FROM AUTHOR]

Background: The emergence and rapid spread of multi-drug resistant (MDR) bacterial strains, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), have posed a significant challenge to the medical community due to their ability to form biofilm and develop resistance to common antibiotics. Traditional antibiotics that were once effective in treating bacterial infections are now becoming increasingly ineffective, leading to severe consequences for patient outcomes. This concerning situation has called for urgent research to explore alternative treatment strategies. Recent studies have shown that antimicrobial peptides (AMPs) hold promise as effective agents against biofilm-associated drug-resistant infections as well as to enhance the efficacy of conventional antibiotics. Accordingly, we aimed to investigate the antimicrobial and antibiofilm effects of melittin AMP, both alone and in combination with penicillin and oxacillin, against biofilm-forming MDR-MRSA and -VRSA. Methods: In this study, we investigated the kinetics of biofilm formation and assessed various parameters related to the antimicrobial and antibiofilm efficacy of melittin and antibiotics, both alone and in combination, against MDR-MRSA and -VRSA. The antimicrobial parameters included the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Fractional Inhibitory Concentration Index (FICi), Fractional Bactericidal Concentration Index (FBCi), and the antibiofilm activity of melittin and antibiotics indicated by the Minimum Biofilm Inhibitory Concentration (MBIC), Minimal Biofilm Eradication Concentration (MBEC), Fractional Biofilm Inhibitory Concentration Index (FBICi), and Fractional Biofilm Eradication Concentration Index (FBECi). Results: The MIC results showed that all S. aureus isolates were resistant to penicillin (>0.25 mg/mL), and 66% of isolates were resistant to oxacillin. The geometric means of the MIC values for penicillin, oxacillin, and melittin were 19.02, 16, and 1.62 mg/ml, respectively, and the geometric means of the MBC values for penicillin, oxacillin, and melittin were 107.63, 49.35, and 5.45 mg/ml, respectively. The study revealed that the combination indexes of melittinpenicillin and melittin-oxacillin, as determined by FIC values against all isolates, were 0.37 and 0.03, respectively. Additionally, melittin-penicillin and melittinoxacillin exhibited combination indexes based on FBC values against all isolates at 1.145 and 0.711, respectively. Besides, melittin inhibited the biofilm formation of all S. aureus isolates, with MBIC values ranging from 10 to 1.25 mg/mL, and MBEC values ranging from 40 to 10 mg/mL. Generally, the combination indexes of melittin-penicillin and melittin-oxacillin, determined using FBIC values against all isolates, were 0.23 and 0.177, respectively. Moreover, melittin-penicillin and melittin-oxacillin typically had combination indexes based on FBEC values against all isolates at 5 and 2.97, respectively. Conclusion: In conclusion, our study provides evidence that melittin is effective against both planktonik and biofilm forms of MRSA and VRSA and exhibits significant synergistic effects when combined with antibiotics. These results suggest that melittin and antibiotics could be a potential candidate for further investigation for in vivo infections caused by MDR S. aureus. Furthermore, melittin has the potential to restore the efficacy of penicillin and oxacillin antibiotics in the treatment of MDR infections. Applying AMPs, like melittin, to revive beta-lactam antibiotics against MRSA and VRSA is an innovative approach against antibiotic-resistant bacteria. Further research is needed to optimize dosage and understand melittin mechanism and interactions with beta-lactam antibiotics for successful clinical applications. [ABSTRACT FROM AUTHOR]

Background Ceftriaxone is a convenient option for methicillin-sensitive Staphylococcus aureus (MSSA) outpatient parenteral antimicrobial therapy (OPAT), but population-based studies for its effectiveness are lacking. Methods In this retrospective cohort, a large insurance claims database was queried from 2010 to 2018 for adults with MSSA bloodstream infection (BSI). Patients discharged on OPAT on cefazolin or oxacillin/nafcillin were compared with ceftriaxone with respect to 90-day hospital readmission with the same infection category and 90-day all-cause readmission using logistic regression models. Results Of 1895 patients with MSSA BSI, 1435 (75.7%) patients received cefazolin, oxacillin, or nafcillin and 460 (24.3%) ceftriaxone. Readmission due to the same infection category occurred in 366 (19.3%), and all-cause readmission occurred in 535 (28.3%) within 90 days. Risk factors significantly associated with readmission with the same infection category were the oldest sampled age group (61–64 years: adjusted odds ratio [aOR], 1.47 [95% confidence interval {CI}, 1.01–2.14]), intensive care unit stay during index admission (aOR, 2.33 [95% CI, 1.81–3.01]), prosthetic joint infection (aOR, 1.96 [95% CI, 1.18–2.23]), central line–associated BSI (aOR, 1.72 [95% CI, 1.33–2.94]), and endocarditis (aOR, 1.63 [95% CI, 1.18–2.23]). Ceftriaxone was not associated with increased risk of readmission with the same infection category (aOR, 0.89 [95% CI,.67–1.18]), or 90-day all-cause readmission (aOR, 0.86 [95% CI,.66–1.10]) when compared with oxacillin/nafcillin/cefazolin. Conclusions In this cohort of MSSA BSI patients discharged on OPAT, there were no differences in outcomes of readmission with the same infection and 90-day all-cause readmission in patients treated with ceftriaxone compared to oxacillin/nafcillin or cefazolin. Patients with complicated BSIs such as endocarditis and epidural abscess were more likely to be prescribed cefazolin or oxacillin/nafcillin. [ABSTRACT FROM AUTHOR]

The aim of our study was to characterize the composition and certain bioactivities of the essential oil of Ambrosia artemisiifolia. Eighty organic compounds were identified in the essential oils obtained by hydrodistillation and microwave-assisted isolation. Germacrene D was the main component in both oils. The essential oil obtained by hydrodistillation exerted antibacterial activity against two S. aureus strains, with MIC values of 0.015% for the methicillin-susceptible strain and 0.25% for the methicillin-resistant strain. In the biofilm formation assay, a dose-dependent inhibition was observed in case of the K. pneumoniae ATCC 600,703. In the ethidium bromide accumulation assay, a dose-dependent inhibition activity was observed against the bacterial efflux pump of the Gram-negative bacteria E. coli ATCC 25,922. The essential oil displayed strong in vitro cytotoxicity against the multidrug-resistant (MDR) Colo 320 cancer cell line with an IC50 value of 0.0103%. The essential oil showed strong inhibition on the proliferation of the doxorubicin-sensitive Colo 205 cells (IC50 values of 0.054%) and in the case of MDR Colo 320 colonic adenocarcinoma cells (IC50 values of 0.008%). This is the first report of the cytotoxic and antiproliferative activities of the essential oil from these species. [ABSTRACT FROM AUTHOR]

The continuous rise in bacterial infections and antibiotic resistance is the driving force behind the search for new antibacterial agents with novel modes of action. Antimicrobial peptides (AMPs) have recently gained attention as promising antibiotic agents with the potential to treat drug-resistant infections. Several AMPs have shown a lower propensity towards developing resistance compared to conventional antibiotics. However, these peptides, especially acyldepsipeptides (ADEPs) present with unfavorable pharmacokinetic properties, such as high toxicity and low bioavailability. Different ways to improve these peptides to be drug-like molecules have been explored, and these include using biocompatible nano-carriers. ADEP1 analogues (SC005-8) conjugated to gelatin-capped Silver/Indium/Sulfide (AgInS2) quantum dots (QDs) improved the antibacterial activity against Gram-negative (Escherichia coli and Pseudomonas aeruginosa), and Gram-positive (Bacillus subtilis, Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus) bacteria. The ADEP1 analogues exhibited minimum inhibition concentrations (MIC) between 63 and 500 µM, and minimum bactericidal concentrations (MBC) values between 125 and 750 µM. The AgInS2-ADEP1 analogue conjugates showed enhanced antibacterial activity as evident from the MIC and MBC values, i.e., 1.6–25 µM and 6.3–100 µM, respectively. The AgInS2-ADEP1 analogue conjugates were non-toxic against HEK-293 cells at concentrations that showed antibacterial activity. The findings reported herein could be helpful in the development of antibacterial treatment strategies. [ABSTRACT FROM AUTHOR]

Bloodstream infections by bacteria, especially multidrug-resistant bacteria, remain a worldwide public health concern. We evaluated the antibacterial activity of ceftobiprole and comparable drugs against different bloodstream isolates and different sequence types of methicillin-resistant Staphylococcus aureus (MRSA) in China. We found that MRSA, methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-susceptible coagulase-negative Staphylococcus (MSCNS) displayed ceftobiprole sensitivity rates of >95%, which are similar to the rates for linezolid, daptomycin, and vancomycin. Of the tested MRCNS strains, 90.4% were sensitive to ceftobiprole. The sensitivities of ST59, ST398, and ST22 MRSA to ceftobiprole were higher than that of ST239. Ceftobiprole's MIC50/90 value against Enterococcus faecalis was 0.25/2 mg/L, whereas Enterococcus faecium was completely resistant to this drug. Ceftobiprole exhibited no activity against ESBL-positive Enterobacterales, with resistance rates between 78.6% and 100%. For ESBL-negative Enterobacterales, excluding Klebsiella oxytoca, the sensitivity to ceftobiprole was comparable to that of ceftazidime, ceftriaxone, and cefepime. The MIC50/90 value of ceftobiprole against Pseudomonas aeruginosa was 2/16 mg/L, and for Acinetobacter baumannii, it was 32/>32 mg/L. Thus, ceftobiprole shows excellent antimicrobial activity against ESBL-negative Enterobacterales and Pseudomonas aeruginosa (comparable to that of ceftazidime, ceftriaxone, and cefepime); however, it is not effective against ESBL-positive Enterobacterales and Acinetobacter baumannii. These results provide important information to clinicians. [ABSTRACT FROM AUTHOR]

ABSTRACT The emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) has imposed further challenges to the clinical management of MRSA infections. When exposed to β-lactam antibiotics, these strains can easily acquire reduced β-lactam susceptibility through chromosomal mutations, including those in RNA polymerase (RNAP) genes such as rpoBC, which may then lead to treatment failure. Despite the increasing prevalence of such strains and the apparent challenges they pose for diagnosis and treatment, there is limited information available on the actual mechanisms underlying such chromosomal mutation-related transitions to reduced β-lactam susceptibility, as it does not directly associate with the expression of mecA. This study investigated the cellular physiology and metabolism of six missense mutants with reduced oxacillin susceptibility, each carrying respective mutations on RpoBH929P, RpoBQ645H, RpoCG950R, RpoCG498D, RpiAA64E, and FruBA211E, using capillary electrophoresis-mass spectrometry-based metabolomics analysis. Our results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides. These mutations also led to the accumulation of UDP-Glc/Gal and UDP-GlcNAc, which are precursors of UTP-associated peptidoglycan and wall teichoic acid. Excessive amounts of building blocks then contributed to the cell wall thickening of mutant strains, as observed in transmission electron microscopy, and ultimately resulted in decreased susceptibility to β-lactam in OS-MRSA.IMPORTANCEThe emergence of oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) strains has created new challenges for treating MRSA infections. These strains can become resistant to β-lactam antibiotics through chromosomal mutations, including those in the RNA polymerase (RNAP) genes such as rpoBC, leading to treatment failure. This study investigated the mechanisms underlying reduced β-lactam susceptibility in four rpoBC mutants of OS-MRSA. The results showed that rpoBC mutations caused RNAP transcription dysfunction, leading to an intracellular accumulation of ribonucleotides and precursors of peptidoglycan as well as wall teichoic acid. This, in turn, caused thickening of the cell wall and ultimately resulted in decreased susceptibility to β-lactam in OS-MRSA. These findings provide insights into the mechanisms of antibiotic resistance in OS-MRSA and highlight the importance of continued research in developing effective treatments to combat antibiotic resistance.

Human infections with methicillin-resistant Staphylococcus aureus (MRSA) are commonly treated with vancomycin, and strains with decreased susceptibility, designated as vancomycin-intermediate S. aureus (VISA), are associated with treatment failure. Here, we profiled the phenotypic, mutational, and transcriptional landscape of 10 VISA strains adapted by laboratory evolution from one common MRSA ancestor, the USA300 strain JE2. Using functional and independent component analysis, we found that: 1) despite the common genetic background and environmental conditions, the mutational landscape diverged between evolved strains and included mutations previously associated with vancomycin resistance (in vraT, graS, vraFG, walKR, and rpoBCD) as well as novel adaptive mutations (SAUSA300_RS04225, ssaA, pitAR, and sagB); 2) the first wave of mutations affected transcriptional regulators and the second affected genes involved in membrane biosynthesis; 3) expression profiles were predominantly strain-specific except for sceD and lukG, which were the only two genes significantly differentially expressed in all clones; 4) three independent virulence systems (φSa3, SaeR, and T7SS) featured as the most transcriptionally perturbed gene sets across clones; 5) there was a striking variation in oxacillin susceptibility across the evolved lineages (from a 10-fold increase to a 63-fold decrease) that also arose in clinical MRSA isolates exposed to vancomycin and correlated with susceptibility to teichoic acid inhibitors; and 6) constitutive expression of the VraR regulon explained cross-susceptibility, while mutations in walK were associated with cross-resistance. Our results show that adaptation to vancomycin involves a surprising breadth of mutational and transcriptional pathways that affect antibiotic susceptibility and possibly the clinical outcome of infections.

The ability of Staphylococcus epidermidis and S. aureus to form strong biofilm on plastic devices makes them the major pathogens associated with device-related infections (DRIs). Biofilm-embedded bacteria are more resistant to antibiotics, making biofilm infections very difficult to effectively treat. Here, we evaluate the in vitro activities of anti-staphylococcal drug oxacillin and antimicrobial peptide nisin, alone and in combination, against methicillin-resistant S. epidermidis (MRSE) clinical isolates and the methicillin-resistant S. aureus ATCC 43,300. The minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentrations (MBEC) of oxacillin and nisin were determined using the microbroth dilution method. The anti-biofilm activities of oxacillin and nisin, alone or in combination, were evaluated. In addition, the effects of antimicrobial agents on the expression of icaA gene were examined by quantitative real-time PCR. MIC values for oxacillin and nisin ranged 4–8 µg/mL and 64–128 µg/mL, respectively. Oxacillin and nisin reduced biofilm biomass in all bacteria in a dose-dependent manner and this inhibitory effect was enhanced with combinatorial treatment. MBEC ranges for oxacillin and nisin were 2048–8192 µg/mL and 2048–4096 µg/mL, respectively. The addition of nisin significantly decreased the oxacillin MBECs from 8- to 32-fold in all bacteria. At the 1× MIC and 1/2× MIC, both oxacillin and nisin decreased significantly the expression of icaA gene in comparison with untreated control. When two antimicrobial agents were combined at 1/2× MIC concentration, the expression of icaA were significantly lower than when were used alone. Nisin/conventional oxacillin combination showed considerable anti-biofilm effects, including inhibition of biofilm formation, eradication of mature biofilm, and down-regulation of biofilm-related genes, proposing its applications for treating or preventing staphylococcal biofilm-associated infections, including device-related infections. [ABSTRACT FROM AUTHOR]

Assessment of pathogens diversity and evolving drug-resistant pattern is quite essential in the systematic management of infections. To regulate the pyogenic infection, 1350 (783 males and 567 females) pus samples collected from individuals attending a tertiary care hospital in Northern Kerala. Pathogens isolated from the collected pus samples were identified based on the colony morphology, microscopic examination, and biochemical characteristics. About 84.44% of samples showed significant bacteria. The causative organisms were Staphylococcus aureus (28%), Escherichia coli (13%), Pseudomonas aeruginosa (12%), Klebsiella pneumonia (10%), coagulase negative Staphylococcus sp. (8%), Proteus mirabilis (6%), Streptococcus sp. (2%), Enterococcus faecalis (2%), Acenitobactor baumanii (1%), Citrobactor koseri (2%), Enterococcus faecium (2%), Enterococcus sp. (2%), Morganella morganii (1%), Proteus vulgaris (2%), and other less prominent bacteria (3%). The drugresistant pattern of pathogens analyses against 29 contemporary antibiotics. Pathogenic Gram-negative bacteria (GNB) were sensitive to amikacin > imipenem > meropenem > tazobactum > gentamycin > chloramphenicol> ciprofloxacin > levofloxacin and resistant to clindamycin, erythromycin, linezolid, oxacillin, penicillin, and vancomycin. Gram-Positive Bacteria (GPB) were susceptible to linezolid > vancomycin > tetracycline > clindamycin > chloramphenicol > gentamycin > ciprofloxacin, and resistant to amikacin, imipenem, meropenem, and tazobactum. Overall, the study concludes that MDR S. aureus was the predominant cause of pyogenic infections, drug resistance pattern of the pathogens in the selected region and raises concerns for the need to analyze signaling mechanism that transforms a susceptible strain into a resistant to develop a suitable treatment strategy. [ABSTRACT FROM AUTHOR]