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The development of novel antibacterial drugs needs urgent action due to the global emergence of antibiotic resistance. In this challenge, actinobacterial strains from arid ecosystems are proving to be promising sources of new bioactive metabolites. The identified Streptomyces rochei strain CMB47, isolated from coal mine Saharan soil, provided an ethyl acetate extract which tested against a series of pathogens. It displayed a minimum inhibitory concentration of

Vancomycin is a last-resort antibiotic for the treatment of many Gram-positive bacterial infections, while remaining inactive against Gram-negative strains. Resistance to vancomycin in Gram-positive stains continues to develop. This thesis describes the recent developments in semisynthetically modifying glycopeptide antibiotics to improve their antibacterial activity. Furthermore, the development of several semisynthetic glycopeptide antibiotics are described including the guanidino lipoglycopeptides, the vancomyxins, and the vancomycin-sideromycins. The guanidino lipoglycopeptides are readily synthesized from vancomycin and display potent in vitro and in vivo activity against Gram-positive bacteria, including vancomycin-resistant strains. Assessment of the activity, properties, and mechanism of action of the guanidino lipoglycopeptides shows the potential of these novel glycopeptides to become best-in class. The vancomyxins, which consist of covalently conjugated vancomycin and outer membrane disruptor polymyxin nonapeptide, display enhanced activity against Gram-negative bacterial strains compared to vancomycin monotherapy or co-administration of the two components. The vancomycin-sideromycins are also aimed at conferring antibacterial activity against Gram-negative bacteria by exploiting an iron-uptake system. Overall, a variety of semisynthetic vancomycin derivatives, aimed at overcoming vancomycin resistance or sensitizing Gram-negative strains, are developed and assessed on their activity in this work.

Skin and soft tissue infections (SSTIs) are associated with significant morbidity and healthcare costs, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin is a preferred antimicrobial therapy for the management of complicated SSTIs (cSSTIs) caused by MRSA, with linezolid and daptomycin regarded as alternative therapeutic options. Due to the increased rates of antimicrobial resistance in MRSA, several new antibiotics with activity against MRSA have been recently introduced in clinical practice, including ceftobiprole, dalbavancin, and tedizolid. We evaluated the in vitro activities of the aforementioned antibiotics against 124 clinical isolates of MRSA obtained from consecutive patients with SSTIs during the study period (2020–2022). Minimum inhibitory concentrations (MICs) for vancomycin, daptomycin, ceftobiprole, dalbavancin, linezolid and tedizolid were evaluated by the MIC Test Strip using Liofilchem strips. We found that when compared to the in vitro activity of vancomycin (MIC90 = 2 μg/mL), dalbavancin possessed the lowest MIC90 (MIC90 = 0.094 μg/mL), followed by tedizolid (MIC90 = 0.38 μg/mL), linezolid, ceftobiprole, and daptomycin (MIC90 = 1 μg/mL). Dalbavancin demonstrated significantly lower MIC50 and MIC90 values compared to vancomycin (0.064 vs. 1 and 0.094 vs. 2, respectively). Tedizolid exhibited an almost threefold greater level of in vitro activity than linezolid, and also had superior in vitro activity compared to ceftobiprole, daptomycin and vancomycin. Multidrug-resistant (MDR) phenotypes were detected among 71.8% of the isolates. In conclusion, ceftobiprole, dalbavancin and tedizolid exhibited potent activity against MRSA and are promising antimicrobials in the management of SSTIs caused by MRSA.

Yanling Liu, Wenhui Li, Qian Dong, Yangqun Liu, Xiaohua Ye School of Public Health, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Yangqun Liu; Xiaohua YeSchool of Public Health, Guangdong Pharmaceutical University, 283# Jianghai Dadao, Haizhu District, Guangzhou, People’s Republic of ChinaTel +862034055355Email 136437677@qq.com; smalltomato@163.comBackground: The distinction between livestock-associated and human-associated methicillin-resistant Staphylococcus aureus (MRSA) has become more and more blurred. This study aimed to reveal the transmission risk of livestock-associated and non-livestock-associated S. aureus (including MRSA and multidrug-resistant S. aureus [MDRSA]) by occupational pig exposure.Methods: A total of 591 pig-exposed workers and 1178 non-exposed workers were enrolled in this study. All nasal S. aureus isolates were tested for antibiotic susceptibility and molecular characteristics. Logistic regression models were used to examine the dose–response relationships between occupational pig exposure and S. aureus carriage.Results: Pig-exposed workers had significantly higher carriage rates of MRSA (OR=6.29, 95% CI: 3.38∼ 11.68) and MDRSA (OR=3.17, 95% CI: 2.03∼ 4.96) than non-exposed workers. Notably, we found dose–response relationships between occupational pig exposure and MRSA or MDRSA carriage. Using genotypic and phenotypic markers for differentiating livestock-associated and non-livestock-associated S. aureus, we also revealed dose–response relationships occupational pig exposure and livestock-associated or non-livestock-associated S. aureus carriage.Conclusion: Our findings provide sufficient epidemiological evidence for revealing the high transmission risk of livestock-associated S. aureus and the low transmission risk of non-livestock-associated S. aureus by occupational pig exposure.Keywords: livestock, human, methicillin-resistant S. aureus, multidrug-resistant S. aureus, transmission

Yanling Liu, Wenhui Li, Qian Dong, Yangqun Liu, Xiaohua Ye School of Public Health, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Yangqun Liu; Xiaohua YeSchool of Public Health, Guangdong Pharmaceutical University, 283# Jianghai Dadao, Haizhu District, Guangzhou, People’s Republic of ChinaTel +862034055355Email 136437677@qq.com; smalltomato@163.comBackground: The distinction between livestock-associated and human-associated methicillin-resistant Staphylococcus aureus (MRSA) has become more and more blurred. This study aimed to reveal the transmission risk of livestock-associated and non-livestock-associated S. aureus (including MRSA and multidrug-resistant S. aureus [MDRSA]) by occupational pig exposure.Methods: A total of 591 pig-exposed workers and 1178 non-exposed workers were enrolled in this study. All nasal S. aureus isolates were tested for antibiotic susceptibility and molecular characteristics. Logistic regression models were used to examine the dose–response relationships between occupational pig exposure and S. aureus carriage.Results: Pig-exposed workers had significantly higher carriage rates of MRSA (OR=6.29, 95% CI: 3.38∼ 11.68) and MDRSA (OR=3.17, 95% CI: 2.03∼ 4.96) than non-exposed workers. Notably, we found dose–response relationships between occupational pig exposure and MRSA or MDRSA carriage. Using genotypic and phenotypic markers for differentiating livestock-associated and non-livestock-associated S. aureus, we also revealed dose–response relationships occupational pig exposure and livestock-associated or non-livestock-associated S. aureus carriage.Conclusion: Our findings provide sufficient epidemiological evidence for revealing the high transmission risk of livestock-associated S. aureus and the low transmission risk of non-livestock-associated S. aureus by occupational pig exposure.Keywords: livestock, human, methicillin-resistant S. aureus, multidrug-resistant S. aureus, transmission

The species of the genus Tabernaemontana have a long tradition of use in different pathologies of infectious origins; the antibacterial, antifungal, and antiviral effects related to the control of the pathologies where the species of this genus are used, have been attributed to the indole monoterpene alkaloids, mainly those of the iboga type. There are more than 1000 alkaloids isolated from different species of Tabernaemontana and other genera of the Apocynaceae family, several of which lack studies related to antibacterial activity. In the present study, four monoterpene indole alkaloids were isolated from the seeds of the species Tabernaemontana cymosa Jacq, namely voacangine (1), voacangine-7-hydroxyindolenine (2), 3-oxovoacangine (3), and rupicoline (4), which were tested in an in vitro antibacterial activity study against the bacteria S. aureus, sensitive and resistant to methicillin, and classified by the World Health Organization as critical for the investigation of new antibiotics. Of the four alkaloids tested, only voacangine was active against S. aureus, with an MIC of 50 µg/mL. In addition, an in silico study was carried out between the four isolated alkaloids and some proteins of this bacterium, finding that voacangine also showed binding to proteins involved in cell wall synthesis, mainly PBP2 and PBP2a.

The objective of this study was to characterize an endophytic fungi producing-bioactive compound from the aquatic plant, Nelumbo nucifera. All parts of such plant were cleaned with surface sterilization technique and cultured on potato dextrose agar to isolate endophytic fungi. The identification was characterized by morphological and molecular technique. Fungal isolates were screened to discover antimicrobial activities by disc diffusion method against Methicillin-resistant Staphylococcus aureus DMST20651 (MRSA). MIC and MBC for those crude fungal extracts were determined. Finally, the chemical profile of crude extract was determined by gas chromatography and mass spectrometry. Six endophytic fungi were isolated from the surface-satirized parts of N. nucifera. Based on disc diffusion assay, the highest antibacterial activity against MRSA was isolate ST9.1 identified as Aspergillus cejpii. Results demonstrated that the ethyl acetate extraction had more active fractions with MIC of 2.5 mg/ml and MBC concentration of 50.0 mg/ml. The crude extracts were developed to identify the chemical constituents by gas chromatography and mass spectrometry. The major component of crude extract of endophytic fungi was 5-(1H-Indol-3-yl)-4,5-dihydro-[1,2,4]triazin-3-ylamine (C11H11N5). Thus, the plant could be used in the treatment of infectious diseases caused by bacterial pathogen.

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.

Objectives Diabetic foot ulcers (DFUs) often lead to hospital admissions, amputations and deaths; however, there is no up-to-date information on microbial isolates from DFUs and no mention of utilization of molecular techniques in Sub-Saharan Africa. We conducted a cross-sectional study among 83 adult patients at a tertiary hospital in Kenya over 12 months. The study aimed to isolate, identify bacteria, their antibiotic susceptibility patterns in active DFUs, and to compare standard microbiological methods versus a real-time PCR commercial kit in the detection of Staphylococcus aureus DNA and methicillin-resistant S. aureus (MRSA) DNA. Results Eighty swabs (94%) were culture-positive; 29% were Gram-positive and 65% were Gram-negative. The main organisms isolated were S. aureus (16%), Escherichia coli (15%), Proteus mirabilis (11%), Klebsiella pneumoniae (7%) and Pseudomonas aeruginosa (7%). The bacterial isolates showed resistance to commonly used antibiotics such as ampicillin, amoxicillin, cefepime, ceftazidime, cefuroxime, clindamycin, erythromycin, piperacillin–tazobactam, tetracycline and trimethoprim–sulphamethoxazole (TMPSMX). Thirty-one percent of the S. aureus isolated and 40% of the Gram-negatives were multi-drug resistant organisms (MDROs). There was a high prevalence of nosocomial bacteria. MRSA were not identified using culture methods but were identified using PCR. PCR was more sensitive but less specific than culture-based methods to identify S. aureus. Electronic supplementary material The online version of this article (10.1186/s13104-019-4278-0) contains supplementary material, which is available to authorized users.

Purulent-necrotic complications in patients with diabetic foot syndrome is one of the main causes resulting in amputation and disability, or even lethal outcome. Our study was aimed at investigating a role played by MRSA and related molecular genetic features, as well as antibiotic resistance in developing purulent-necrotic forms of the diabetic foot syndrome in Krasnoyarsk, in the 20102016 period. A microbiota profile related to purulent-necrotic complications, antibiotic susceptibility, as well as the molecular genetic features of methicillin-resistant Staphylococcus aureus were examined in 240 patients with diabetic foot syndrome. A bacteriological method was used to investigate microbiota profile related to purulent complications. Antibiotic sensitivity was analyzed by disc-diffusion method; staphylococcal antibiotic sensitivity was evaluated by screening, PCR, solid medium serial dilution, in accordance with the CLSI and EUCAST international recommendations. Genotyping and examining molecular genetic features were performed by using PCR, M-PCR, and sequencing. The data were analyzed by using WHONET (WHO) software. Significance level was set at p 0.05. It was found that microbiota profile linked to purulent-necrotic forms of the diabetic foot syndrome was presented by various Gram-negative microorganisms including Enterobacteriaceae spp. and non-fermenting bacteria accounting for 34.4% and 19.1%, respectively, as well as Gram-positive microorganisms found in 46.5% cases, including S. aureus (18.4% cases). Moreover, microorganisms were characterized by multiresistance to diverse antimicrobial drugs: percent-age of BLDS- and MBL-producers as well as MRSA comprised 36.4%, 30.3%, and 36.4%, respectively. Further, MRSA ST239/spa3(t037)/agr1/SCCmecIII.1.1.2(IIIA)/coaIV/tst+ clone dominated in patients with purulent-necrotic forms of diabetic foot syndrome admitted to the right-bank and left-bank hospitals in the city of Krasnoyarsk that was characterized by a high virulence level and multidrug resistance. Next, subdominant MRSA genetic variants were presented by ST8/spa1(t008)/agr1/SCCmecIV.3.1.1/CoaIII and ST12/spanew(t156)/agr1/SCCmecUT/coaIorVII characterized by resistance to 12 groups of antimicrobials apart from -lactams. Importantly, similar MRSA genetic variants earlier isolated in patients with other nosological entities common in this geographic region were also mainly verified in patients with purulent-necrotic forms of diabetic foot syndrome admitted to Krasnoyarsk hospitals. In particular, it was demonstrated that MRSA isolates predominantly belonging to the same genetic variants were detected in patients with purulent-necrotic forms of diabetic foot syndrome hospitalized both at the right-bank and left-bank hospitals of the city of Krasnoyarsk. Thus, long-term hospitalization of patients with purulent-necrotic forms of diabetic foot syndrome as well as subsequent repeated admittance to other hospitals in the city of Krasnoyarsk facilitates inter-hospital bacterial strain transmission.

Introduction Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious processes seen in the clinical setting. For patients with complicated ABSSSIs deemed to require intravenous antibiotics, vancomycin remains the mainstay therapy. Ceftaroline has been shown to be non-inferior to vancomycin and may result in faster resolution of signs of infection. Methods Multicenter, prospective, open-label, randomized trial of ceftaroline versus vancomycin for the treatment of adult patients admitted for management of ABSSSIs from April 2012 to May 2016; 166 patients in the clinically evaluable (CE) group were needed to determine a 20% difference in primary outcome of clinical response at day 2 or 3 of antibiotics. Clinical response was defined as cessation of spread of lesion and improvement in systemic signs/symptoms of infection. A secondary outcome was a ≥ 20% reduction in lesion size at day 2 or 3 of antibiotics. Results One hundred seventy-four patients were enrolled in the intention-to-treat (ITT) group and 108 were CE. Among CE patients, 54 were randomized to ceftaroline and 54 to vancomycin. Baseline characteristics were similar except patients in the ceftaroline arm were older and had a non-significantly higher degree of comorbidities (median Charlson score 2 vs. 4, respectively). Cellulitis was the most common type of ABSSSI (85.2% vs. 79.6%, respectively). Rapid diagnostic testing of available cultures (n = 55) demonstrated high agreement with clinical microbiology for identification of Staphylococcus aureus (100%) and MRSA (100%). There was no significant difference in primary outcome of day 2 or 3 clinical response (50.0% vs. 51.9%). Conclusion Early clinical response between vancomycin- and ceftaroline-treated ABSSSIs was similar. Patients with ABSSSIs rarely remained hospitalized for > 2–3 days, thus limiting our ability to critically assess clinical outcomes. Trial Registration ClinicalTrials.gov identifier, NCT02582203. Funding Allergan plc.

Objectives Genetic determinants conferring resistance to macrolide, lincosamide, and streptogramin B (MLSB) via ribosomal modification such as, erm, msrA/B and ereA/B genes are distributed in bacteria. The main goals of this work were to evaluate the dissemination of MLSB resistance phenotypes and genotypes in methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from clinical samples. Methods A total of 106 MRSA isolates were studied. Isolates were recovered from 3 hospitals in Tehran between May 2016 to July 2017. The prevalence of MLSB-resistant strains were determined by D-test, and then M-PCR was performed to identify genes encoding resistance to macrolides, lincosamides, and streptogramins in the tested isolates. Results The frequency of constitutive resistance MLSB, inducible resistance MLSB and MSB resistance were 56.2%, 22.9%, and 16.6%, respectively. Of 11 isolates with the inducible resistance MLSB phenotype, ermC, ermB, ermA and ereA were positive in 81.8%, 63.6%, 54.5% and 18.2% of these isolates, respectively. In isolates with the constitutive resistance MLSB phenotype, the prevalence of ermA, ermB, ermC, msrA, msrB, ereA and ereB were 25.9%, 18.5%, 44.4%, 0.0%, 0.0%, 11.1% and 0.0%, respectively. Conclusion Clindamycin is commonly administered in severe MRSA infections depending upon the antimicrobial susceptibility findings. This study showed that the D-test should be used as an obligatory method in routine disk diffusion assay to detect inducible clindamycin resistance in MRSA so that effective antibiotic treatment can be provided.

During August 1, 2014-July 31, 2015, in 2 counties in Minnesota, USA, incidence of invasive methicillin-susceptible Staphylococcus aureus (MSSA) (27.1 cases/100,000 persons) was twice that of invasive methicillin-resistant S. aureus (13.1 cases/100,000 persons). MSSA isolates were more genetically diverse and susceptible to more antimicrobial drugs than methicillin-resistant S. aureus isolates.

Considering the prevalence of resistance to antibiotics, the discovery of effective agents against resistant pathogens is of extreme urgency. Herein, 26mecA-positive methicillin-resistantS. aureus(MRSA) isolated from clinical samples were identified, and their resistance to 11 antibiotics was investigated. Next, the antibacterial and anti-biofilm activity of the ethanolic extract ofM. communison these strains was evaluated. Furthermore, the effect of this extract on the expression of biofilm-associated genes,icaA,icaD,bap,sarA, andagr, was studied. According to the results, all isolated strains were multidrug-resistant and showed resistance to oxacillin and tetracycline. Also, 96.15 and 88.46 % of them were resistant to gentamicin and erythromycin. However, the extract could effectively combat the strains. The minimum inhibitory concentration (MIC) against different strains ranged from 1.56 to 25 mg/ml and the minimum bactericidal concentration (MBC) was between 3.125 and 50 mg/ml. Even though most MRSA (67 %) strongly produced biofilm, the sub-MIC concentration of the extract destroyed the pre-formed biofilm and affected the bacterial cells inside the biofilm. It could also inhibit biofilm development by significantly decreasing the expression oficaA,icaD,sarAandbapgenes involved in biofilm formation and development. In conclusion, the extract inhibits biofilm formation, ruins pre-formed biofilm, and kills cells living inside the biofilm. Furthermore, it down-regulates the expression of necessary genes and nips the biofilm formation in the bud.

Staphylococcus aureus is a notorious pathogen that colonizes implants (orthopedic and breast implants) and wounds with a vicious resistance to antibiotic therapy. Methicillin-resistant S. aureus (MRSA) is a catastrophe mainly restricted to hospitals and emerged to community reservoirs, acquiring resistance and forming biofilms. Treating biofilms is problematic except via implant removal or wound debridement. Nanoparticles (NPs) and nanofibers could combat superbugs and biofilms and rapidly diagnose MRSA. Nanotheranostics combine diagnostics and therapeutics into a single agent. This comprehensive review is interpretative, utilizing mainly recent literature (since 2016) besides the older remarkable studies sourced via Google Scholar and. We unravel the molecular S. aureus resistance and complex biofilm. The diagnostic properties and detailed antibacterial and antibiofilm NP mechanisms are elucidated in exciting stories. We highlight the challenges of bacterial infections nanotheranostics. Finally, we discuss the literature and provide “three action appraisals”. (i) The first appraisal consists of preventive actions (two wings), avoiding unnecessary hospital visits, hand hygiene, and legislations against over-the-counter antibiotics as the general preventive wing. Our second recommended preventive wing includes preventing the adverse side effects of the NPs from resistance and toxicity by establishing standard testing procedures. These standard procedures should provide breakpoints of bacteria’s susceptibility to NPs and a thorough toxicological examination of every single batch of synthesized NPs. (ii) The second appraisal includes theranostic actions, using nanotheranostics to diagnose and treat MRSA, such as what we call “multifunctional theranostic nanofibers. (iii) The third action appraisal consists of collaborative actions.

Background Blood stream infections (BSIs) due to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are associated with high mortality ranging from 10 to 60%. The current anti-MRSA agents have limitations with regards to safety and tolerability profile which limits their prolonged usage. Levonadifloxacin and its oral prodrug alalevonadifloxacin, a novel benzoquinolizine antibiotic, have recently been approved for acute bacterial skin and skin structure infections including diabetic foot infections and concurrent bacteremia in India.Methods The present study assessed the potency of levonadifloxacin, a novel benzoquinolizine antibiotic, against Gram-positive blood stream clinical isolates (n = 31) collected from January to June 2019 at a tertiary care hospital in Mumbai, India. The susceptibility of isolates to antibacterial agents was defined following the Clinical and Laboratory Standard Institute interpretive criteria (M100 E29).Results High prevalence of MRSA (62.5%), quinolone-resistant Staphylococcus aureus (QRSA) (87.5%), and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) (82.35%) were observed among bacteremic isolates. Levonadifloxacin demonstrated potent activity against MRSA, QRSA, and MR-CoNS strains with significantly lower minimum inhibitory concentration MIC50/90 values of 0.5/1 mg/L as compared with levofloxacin (8/32 mg/L) and moxifloxacin (2/8 mg/L).Conclusion Potent bactericidal activity coupled with low MICs support usage of levonadifloxacin for the management of BSIs caused by multidrug resistant Gram-positive bacteria.

Background: Staphylococcus aureus (S. aureus) is one of the most important pathogens in burn infections colonized in the nose and increase the risk of infections. Methods: Overall, 85 S. aureus isolates were isolated from clinical and nasal hospitalized patients and health care workers (HCWs) in a burn unit and non-burn units in Isfahan from June 2016 and September 2016. Genes encoding penicillin-binding protein 2a (mecA) and adhesive surface proteins, including fibronectin-binding proteins (fnbA, fnbB), fibrinogen binding protein (fib), laminin-binding protein(eno), collagen binding protein (cna), elastin binding protein (ebps), intracellular adhesion operon (icaA and icaD) were detected using PCR method. Results: The rate of methicillin-resistant S. aureus (MRSA) among burn and non-burn isolates were 62% (18/29) and 25% (14/56), respectively. The most prevalent MSCRAMMs genes in burn units were eno (86%) and fib (66%). The most common gene pattern in burn center was icaA+fib+eno. The frequency of icaD, fib and ebpS was higher in clinical samples than nasal samples. No relation was found between the MSCRAMMs genes in the burn unit and non-burn units. Conclusion: The high prevalence of MRSA in burn center can be a new challenge for clinicians. The higher frequency of icaD, fib and ebpS in clinical isolates than nasal isolates may reflect the important role of these genes in colonization and pathogenesis of S. aureus.

Staphylococcus aureus is a notorious pathogen that colonizes implants (orthopedic and breast implants) and wounds with a vicious resistance to antibiotic therapy. Methicillin-resistant S. aureus (MRSA) is a catastrophe mainly restricted to hospitals and emerged to community reservoirs, acquiring resistance and forming biofilms. Treating biofilms is problematic except via implant removal or wound debridement. Nanoparticles (NPs) and nanofibers could combat superbugs and biofilms and rapidly diagnose MRSA. Nanotheranostics combine diagnostics and therapeutics into a single agent. This comprehensive review is interpretative, utilizing mainly recent literature (since 2016) besides the older remarkable studies sourced via Google Scholar and PubMed. We unravel the molecular S. aureus resistance and complex biofilm. The diagnostic properties and detailed antibacterial and antibiofilm NP mechanisms are elucidated in exciting stories. We highlight the challenges of bacterial infections nanotheranostics. Finally, we discuss the literature and provide “three action appraisals”. (i) The first appraisal consists of preventive actions (two wings), avoiding unnecessary hospital visits, hand hygiene, and legislations against over-the-counter antibiotics as the general preventive wing. Our second recommended preventive wing includes preventing the adverse side effects of the NPs from resistance and toxicity by establishing standard testing procedures. These standard procedures should provide breakpoints of bacteria’s susceptibility to NPs and a thorough toxicological examination of every single batch of synthesized NPs. (ii) The second appraisal includes theranostic actions, using nanotheranostics to diagnose and treat MRSA, such as what we call “multifunctional theranostic nanofibers. (iii) The third action appraisal consists of collaborative actions.

Methicillin‐resistant S. aureus has been reported as the main pathogen involved in chronic infections, osteomyelitis, and prosthetic joint infections. The host/pathogen interaction is dynamic and requires several changes to promote bacterial survival. Here, we focused on the internalization and persistence behavior of well‐characterized Staphylococcus aureus invasive strains belonging to the main ST‐MRSA‐SCCmec clones. To overcome the limitations of the cell culture method, we comparatively analyzed the ability of internalization within human MG‐63 osteoblasts with imaging flow cytometry (IFC). After evaluation by cell culture assay, the MRSA clones in the study were all able to readily internalize at 3h postinfection, the persistence of intracellular bacteria was evaluated at 24h both by routine cell culture and IFC assay, after vancomycin‐BODIPY staining. A statistical difference of persistence was found in ST5‐SCCmecII (26.59%), ST228‐SCCmecI (20.25%), ST8‐SCCmecIV (19.52%), ST239‐SCCmecIII (47.82%), and ST22‐SCCmecIVh (50.55%) showing the same ability to internalize as ATCC12598 (51%), the invasive isolate used as control strain for invasion and persistence assays. We demonstrated that the intracellular persistence process depends on the total number of infected cells. Comparing our data obtained by IFC with those of the cell culture assay, we obtained greater reproducibility rates and a number of intracellular bacteria, with the advantage of analyzing live host cells. Moreover, with some limitations related to the lack of whole‐genome sequencing analysis, we validated the different proclivities to persist in the main Italian HA‐MRSA invasive isolates and our results highlighted the heterogeneity of the different clones to persist during cell infection., MRSA has been reported as the main pathogen involved in osteomyelitis and prosthetic joint infections. The host/pathogen interaction is dynamic and requires several changes to promote bacterial survival. Here, we focused on the internalization and persistence behavior of Staphylococcus aureus invasive strains belonging to the major MRSA clones, within human MG‐63 osteoblasts. We used imaging flow cytometry, a technique able to analyze living host cells. We demonstrated that the intracellular persistence process is different among clones and depends on the total number of infected cells instead of the number of intracellular bacteria.

The prevalence of Staphylococcus aureus as an aggressive pathogen resistant to multiple antibiotics causing nosocomial and community-acquired infections is increasing with limited therapeutic options. Macrolide-lincosamide streptogramin B (MLSB) family of antibiotics represents an important alternative therapy for staphylococcal infections. This study was conducted over a period of five years from August 2013 to July 2018 to investigate the prevalence and molecular epidemiology in Iran of inducible resistance in S. aureus. In the current study, 126 inducible methicillin-resistant S. aureus (MRSA) (n = 106) and methicillin-sensitive S. aureus (MSSA) (n = 20) isolates were characterized by in vitro susceptibility analysis, resistance and virulence encoding gene distribution, phenotypic and genotypic analysis of biofilm formation, prophage typing, S. aureus protein A locus (spa) typing, staphylocoagulase (SC) typing, staphylococcal cassette chromosome mec (SCCmec) typing, and multilocus sequence typing. Of the 126 isolates, 76 (60.3%) were classified as hospital onset, and 50 (39.7%) were classified as community onset (CO). Biofilm formation was observed in 97 strains (77%). A total of 14 sequence types (STs), 26 spa types, 7 coagulase types, 9 prophage types, 3 agr types (no agr IV), and 9 clonal complexes (CCs) were identified in this study. The prevalence of the inducible MLSB (iMLSB) S. aureus increased from 7.5% (25/335) to 21.7% (38/175) during the study period. The iMLSB MRSA isolates were distributed in nine CCs, whereas the MSSA isolates were less diverse, which mainly belonged to CC22 (7.95%) and CC30 (7.95%). High-level mupirocin-resistant strains belonged to ST85-SCCmec IV/t008 (n = 4), ST5-SCCmec IV/t002 (n = 4), ST239-SCCmec III/t631 (n = 2), and ST8-SCCmec IV/t064 (n = 2) clones, whereas low-level mupirocin-resistant strains belonged to ST15-SCCmec IV/t084 (n = 5), ST239-SCCmec III/t860 (n = 3), and ST22-SCCmec IV/t790 (n = 3) clones. All the fusidic acid–resistant iMLSB isolates were MRSA and belonged to ST15-SCCmec IV/t084 (n = 2), ST239-SCCmec III/t030 (n = 2), ST1-SCCmec V/t6811 (n = 1), ST80-SCCmec IV/t044 (n = 1), and ST59-SCCmec IV/t437 (n = 1). The CC22 that was predominant in 2013–2014 (36% of the isolates) had almost disappeared in 2017–2018, being replaced by the CC8, which represented 39.5% of the 2017–2018 isolates. This is the first description of temporal shifts of iMLSB S. aureus isolates in Iran that identifies predominant clones and treatment options for iMLSB S. aureus–related infections.

Zhiyao Chen, Changlin Han, Xiaobin Huang, Yangqun Liu, Dan Guo, Xiaohua Ye Laboratory of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China Background: Methicillin-resistant Staphylococcus aureus (MRSA) causes a wide variety of serious infections worldwide. There are few studies on the prevalence, antimicrobial susceptibility, and molecular characteristics of MRSA contamination in the environment of airports.Materials and methods: A cross-sectional survey was conducted in Guangzhou Baiyun Airport. Environmental surface sampling was conducted in frequently touched locations for S. aureus analysis. All isolates were characterized by multilocus sequence typing (MLST) and tested for antimicrobial susceptibility, resistance genes, and virulence genes. Data were analyzed by chi-squared test and correspondence analysis.Results: Of the 1,054 surface samples, the contamination rate was 7.2% (76/1,054) for S. aureus and 2.2% (23/1,054) for MRSA. There were 62.9% (56/89) S. aureus isolates classified as multidrug resistant (MDR), with six linezolid-resistant isolates and two cfr-carrying isolates. The most prevalent S. aureus genotypes were CC6 (ST6), CC59 (ST59), and CC188 (ST188), with ST59-MRSA-IV (pvl–) as the predominant MRSA. There were significant differences between methicillin-resistant and methicillin-sensitive isolates in rates of resistance to tetracycline (P

Yu-Tsung Huang,1–3 Chun-Hsing Liao,1,4 Shey-Ying Chen,5 Chia-Jui Yang,1,4 Hsin-Sui Hsu,1 Lee-Jene Teng,2,3 Po-Ren Hsueh2,6 1Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 3Department of Clinical Laboratory Science and Medical Biotechnology College of Medicine, National Taiwan University, Taipei, Taiwan; 4Department of Internal Medicine, College of Medicine, Yang-Ming University, Taipei, Taiwan; 5Department of Emergency Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: This study investigated molecular characteristics of rifampin (RIF)-resistant (RIF-R) Staphylococcus aureus isolates recovered from patients receiving RIF-containing regimens for tuberculosis (TB). Patients and methods: Patients with TB who received RIF-containing regimens from November 2009 to May 2011 at a medical center were enrolled. Nasal swabs for S. aureus culture were obtained at the time of enrollment, and then every two months until two months after RIF treatment had been completed. Genetic relatedness of the isolates was determined using pulsed-field gel electrophoresis, multilocus sequence typing, and gene typing of spa and SCCmec. The presence of RIF resistance-associated mutations in rpoB, and fusidic acid resistance genes fusB and fusC in the S. aureus isolates were analyzed. Results: Among the 200 patients enrolled in this study, 152 completed follow-ups during treatment, and 114 completed two months of follow-up after discontinuing use of RIF. At enrollment, ten patients (5%) had nasal colonization with S. aureus, namely eight with methicillin-susceptible S. aureus (MSSA), and two with methicillin-resistant S. aureus (MRSA, ST59-SCCmecIV-RIF-susceptible). All these patients were decolonized after RIF usage. Two patients with MSSA colonization at enrollment showed recolonization with genetically unrelated MSSA strains two months after completion of RIF treatment. There were five ST45-SCCmecVT-RIF-R strains from two patients isolated during RIF exposure. Sequencing of rpoB in the RIF-R S. aureus isolates revealed different mutation sites between the MSSA and MRSA isolates. Conclusion: RIF-R S. aureus strains are more likely to result in persistent nasal carriage in TB patients receiving RIF treatment. Monitoring of emergence and possible dissemination of the MRSA ST45 strains among TB patients treated with RIF in Taiwan is warranted. Keywords: Staphylococcus aureus, methicillin-resistant S. aureus, rifampin resistance, tuberculosis, nasal carriage, Taiwan

Yu-Tsung Huang,1–3 Chun-Hsing Liao,1,4 Shey-Ying Chen,5 Chia-Jui Yang,1,4 Hsin-Sui Hsu,1 Lee-Jene Teng,2,3 Po-Ren Hsueh2,6 1Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 3Department of Clinical Laboratory Science and Medical Biotechnology College of Medicine, National Taiwan University, Taipei, Taiwan; 4Department of Internal Medicine, College of Medicine, Yang-Ming University, Taipei, Taiwan; 5Department of Emergency Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: This study investigated molecular characteristics of rifampin (RIF)-resistant (RIF-R) Staphylococcus aureus isolates recovered from patients receiving RIF-containing regimens for tuberculosis (TB). Patients and methods: Patients with TB who received RIF-containing regimens from November 2009 to May 2011 at a medical center were enrolled. Nasal swabs for S. aureus culture were obtained at the time of enrollment, and then every two months until two months after RIF treatment had been completed. Genetic relatedness of the isolates was determined using pulsed-field gel electrophoresis, multilocus sequence typing, and gene typing of spa and SCCmec. The presence of RIF resistance-associated mutations in rpoB, and fusidic acid resistance genes fusB and fusC in the S. aureus isolates were analyzed. Results: Among the 200 patients enrolled in this study, 152 completed follow-ups during treatment, and 114 completed two months of follow-up after discontinuing use of RIF. At enrollment, ten patients (5%) had nasal colonization with S. aureus, namely eight with methicillin-susceptible S. aureus (MSSA), and two with methicillin-resistant S. aureus (MRSA, ST59-SCCmecIV-RIF-susceptible). All these patients were decolonized after RIF usage. Two patients with MSSA colonization at enrollment showed recolonization with genetically unrelated MSSA strains two months after completion of RIF treatment. There were five ST45-SCCmecVT-RIF-R strains from two patients isolated during RIF exposure. Sequencing of rpoB in the RIF-R S. aureus isolates revealed different mutation sites between the MSSA and MRSA isolates. Conclusion: RIF-R S. aureus strains are more likely to result in persistent nasal carriage in TB patients receiving RIF treatment. Monitoring of emergence and possible dissemination of the MRSA ST45 strains among TB patients treated with RIF in Taiwan is warranted. Keywords: Staphylococcus aureus, methicillin-resistant S. aureus, rifampin resistance, tuberculosis, nasal carriage, Taiwan

Objective(s):Staphylococcus aureus is a Gram-positive pathogen, well known for its resistance andversatile lifestyle. Under unfavourable conditions, it adapts biofilm mode of growth. For staphylococcal biofilm formation, production of extracellular polymeric substances (EPS) is a pre-requisite, which is regulated by ica operon-encoded enzymes. This study was designed to know the impact of ascorbic acid on biofilm formation and colony spreading processes of S. aureus and MRSA. Materials and Methods: The isolates of methicillin-resistant S. aureus (MRSA) used in present study, were recovered from different food samples. Various selective and differential media were used for identification and confirmation of S. aureus. Agar dilution method was used for determination of oxacillin and ascorbic acid resistance level. MRSA isolates were re-confirmed by E-test and by amplification of mecA gene. Tube methods and Congo-Red agar were used to study biofilm formation processes. Gene expression studies were carried on real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results: The results revealed the presence of mecA gene belonging to SCCmecA type IV along with agr type II in the isolates. In vitro studies showed the sub-inhibitory concentration of oxacillin induced biofilm production. However, addition of sub-inhibitory dose of ascorbic acid was found to inhibit EPS production, biofilm formation and augment colony spreading on soft agar plates. The inhibition of biofilm formation and augmentation of colony spreading observed with ascorbic acid alone or in combination with oxacillin. Moreover, gene expression studies showed that ascorbic acid increases agr expression and decreases icaA gene expression. Conclusion:The present study concluded thatascorbic acid inhibits biofilm formation, promotes colony spreading and increases agr gene expression in MRSA.

Atopic dermatitis (AD) is an inflammatory skin disease that is usually accompanied by Staphylococcus aureus infection due to cutaneous barrier-function damage. Benzenoid compounds from Antrodia cinnamomea are known to exhibit antibacterial and anti-inflammatory activities. This study sought to investigate the potential of benzenoids for treating bacteria-infected AD. The compounds were screened against methicillin-resistant S. aureus (MRSA). Coenzyme Q0 (CoQ0), a key ingredient in A. cinnamomea, showed the strongest MRSA growth inhibition. We further tested the inhibitory effect of CoQ0 on planktonic and biofilm MRSA. The work was also performed to explore the potential effectiveness of CoQ0 on AD using activated keratinocytes and in vivo experimental AD mice as the models. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CoQ0 against MRSA were 7.81 μg/ml. CoQ0 was found to eradicate biofilm MRSA efficiently and reduce the biofilm thickness. CoQ0 killed MRSA by inhibiting DNA polymerase and topoisomerases. A proteomic assay showed that CoQ0 also reduced the ribosomal proteins. In the anti-inflammation study, CoQ0 was found to downregulate the expression of interleukin (IL)-6, chemokine (C-C motif) ligand (CCL)5, and CCL17 in HaCaT cells. CoQ0 at 0.5 μg/ml could recover the filaggrin decreased by HaCaT activation to the normal control. We established a bacteria-infected AD-like model in mice using ovalbumin (OVA) and topically applied MRSA. Topical CoQ0 delivery lessened the MRSA presence in the AD-like lesions by >90%. The erythema, barrier function, and epidermal thickness of the AD-like wounds were improved by CoQ0 through the reduction of IL-1β, IL-4, IL-6, IL-10, interferon (IFN)-γ, and by neutrophil infiltration in the lesional skin. CoQ0 is therefore regarded as effective in mitigating AD symptoms associated with bacterial load.

Introduction:Staphylococcus aureus (S. aureus)is known as one of the most important hospital pathogens responsible for a wide range of infections. Limited data concerning the prevalence of nasal carriage ofS. aureusand its molecular characteristics are available in Zabol province, Iran. Therefore, the aim of the present study was to determine the prevalence of nasal carriage ofS. aureusand its molecular characteristics isolated from health care workers (HCWs). Methods:totally, 251 nasal swabs were collected from HCWs at a referral hospital, from March to September 2017. Disk diffusion method was used to identify Methicillin-ResistantS. aureus(MRSA). PCR amplification method was used for the detection of following genes;sea, seb, sec, sed, see, tst, eta, etb, lukF-PV, lukS-PVand SCCmec types. Results:of 251 collected swabs, 31 (12.4%) cases were identified asS. aureuscarriers, which 14 (14/31; 45.2%) isolates were MRSA. The most prevalent detected genes wereseaandtst, with 22.6% and 9.7%, respectively. The most prevalent SCCmec type was SCCmec type IV (28.6%). Conclusion:we found that the prevalence of MRSA nasal carriage is at high level and must be considered as a significant health care problem at the investigated hospital. Strict implementation of infection-control policies and rational use of antibiotics are the main pillars for controlling the spread ofS. aureusat hospital.

The objective of this study was to investigate the development of a surface plasmon resonance (SPR) sensor platform equipped with multiple channels for the simultaneous determination of methicillin-resistant S. aureus (MRSA), methicillin-susceptible S. aureus (MSSA) and vancomycin-resistant Enterococcus (VRE), and vancomycin-susceptible Enterococcus (VSE). Drug resistance of S. aureus strains against cefoxitin and Enterococcus strains against vancomycin were investigated both using the minimum inhibitory concentration method (MIC) assay and the SPR system equipped with single and multiple channels. The MIC values of MRSA and MSSA ranged from 32 µg/mL to >128 µg/mL and from 1 µg/mL to 4 µg/mL, respectively. The MIC values of VRE and VSE were between 64 to >128 µg/mL and 2–4 µg/mL, respectively. With the multiple-channel system, the angle shifts of MRSA, MSSA, VRE and VSE were found to be −0.030° and −0.260°, −0.010° and −0.090° respectively. The antibiotic-resistant and susceptible strains were distinguished within 3 h for S. aureus strains and within 6 h for Enterococcus strains.

Staphylococcus aureus , including methicillin-resistant strains, has been detected in food products of animal origin globally. Limited data have been reported on the factors contributing to antibiotic resistance of food-borne pathogens in South Africa. The primary aim of this study was to determine the prevalence of S. aureus , including antibiotic-resistant strains, in poultry meat products as well as the evaluation of potential risk factors for contamination of poultry meat products with antibiotic-resistant S. aureus isolates. A cross-sectional investigation was conducted in municipalities located across the nine provinces of South Africa, which included abattoirs, meat processing facilities, retail outlets and cold stores at the major ports of entry into South Africa. Staphylococcus aureus isolates obtained from various poultry meat products were tested for susceptibility to 14 antibiotic compounds representing 10 antibiotic classes using the Kirby–Bauer disc diffusion method. Potential risk factors were evaluated using a logistic regression model. Of the 311 samples tested, 34.1% ( n = 106) were positive for S. aureus (95% confidence interval [CI], 28.9% – 39.7%). Seventy-two of the 106 isolates were randomly selected for antibiotic sensitivity testing. Twenty-one per cent ( n = 15) of the isolates selected for sensitivity testing were methicillin-resistant strains (95% CI, 12.2% – 32.0%). Multi-drug resistance was detected in 22.2% ( n = 16) of these isolates tested (95% CI, 13.3% – 33.6%). Origin of the product ( p = 0.160), type of meat product ( p = 0.962), type of facility ( p = 0.115) and facility hygiene practices ( p = 0.484) were not significantly associated with contamination of poultry meat products with methicillin-resistant strains. The study provides baseline data for further studies on antibiotic resistance risk assessments for food-borne pathogens, including S. aureus , which should guide the implementation plans of the South African National Antimicrobial Resistance Strategy Framework, 2017–2024.

Atopic dermatitis (AD) is an inflammatory skin disease that is usually accompanied by Staphylococcus aureus infection due to cutaneous barrier-function damage. Benzenoid compounds from Antrodia cinnamomea are known to exhibit antibacterial and anti-inflammatory activities. This study sought to investigate the potential of benzenoids for treating bacteria-infected AD. The compounds were screened against methicillin-resistant S. aureus (MRSA). Coenzyme Q0 (CoQ0), a key ingredient in A. cinnamomea, showed the strongest MRSA growth inhibition. We further tested the inhibitory effect of CoQ0 on planktonic and biofilm MRSA. The work was also performed to explore the potential effectiveness of CoQ0 on AD using activated keratinocytes and in vivo experimental AD mice as the models. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CoQ0 against MRSA were 7.81 μg/ml. CoQ0 was found to eradicate biofilm MRSA efficiently and reduce the biofilm thickness. CoQ0 killed MRSA by inhibiting DNA polymerase and topoisomerases. A proteomic assay showed that CoQ0 also reduced the ribosomal proteins. In the anti-inflammation study, CoQ0 was found to downregulate the expression of interleukin (IL)-6, chemokine (C-C motif) ligand (CCL)5, and CCL17 in HaCaT cells. CoQ0 at 0.5 μg/ml could recover the filaggrin decreased by HaCaT activation to the normal control. We established a bacteria-infected AD-like model in mice using ovalbumin (OVA) and topically applied MRSA. Topical CoQ0 delivery lessened the MRSA presence in the AD-like lesions by >90%. The erythema, barrier function, and epidermal thickness of the AD-like wounds were improved by CoQ0 through the reduction of IL-1β, IL-4, IL-6, IL-10, interferon (IFN)-γ, and by neutrophil infiltration in the lesional skin. CoQ0 is therefore regarded as effective in mitigating AD symptoms associated with bacterial load.

Skin and soft tissue infections (SSTIs) are a serious health issue for military personnel. Of particular importance are those caused by methicillin-resistant Staphylococcus aureus and Panton-Valentine leucocidin (PVL)-positive S. aureus (PVL-SA), as they have been associated with outbreaks of SSTIs. A prospective observational study was conducted in Royal Marine (RM) recruits to investigate the prevalence of PVL-SA carriage and any association with SSTIs.A total of 1012 RM recruits were followed through a 32-week training programme, with nose and throat swabs obtained at weeks 1, 6, 15 and 32. S. aureus isolates were characterized by antibiotic susceptibility testing, spa typing, presence of mecA/C and PVL genes. Retrospective review of the clinical notes for SSTI acquisition was conducted.S. aureus colonization decreased from Week 1 to Week 32 (41% to 26%, p 0.0001). Of 1168 S. aureus isolates, three out of 1168 (0.3%) were MRSA and ten out of 1168 (0.9%) PVL-positive (all MSSA) and 169 out of 1168 (14.5%) were resistant to clindamycin. Isolates showed genetic diversity with 238 different spa types associated with 25 multi-locus sequence type (MLST) clonal complexes. SSTIs were seen in 35% (351/989) of recruits with 3 training days lost per recruit. SSTI acquisition rate was reduced amongst persistent carriers (p 0.0283).Nose and throat carriage of MRSA and PVL-SA was low among recruits, despite a high incidence of SSTIs being reported, particularly cellulitis. Carriage strains were predominantly MSSA with a marked diversity of genotypes. Persistent nose and/or throat carriage was not associated with SSTI acquisition. Putative person-to-person transmission within troops was identified based on spa typing requiring further research to confirm and explore potential transmission routes.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is an important issue with significant morbidity and mortality in clinical practice, especially in diabetes mellitus (DM). Studies focusing on S. aureus pneumonia in DM is limited, we sought to make a relatively comprehensive exploration of clinical characteristics, antimicrobial resistance, and risk factors for mortality of S. aureus pneumonia in DM and non-diabetics mellitus (non-DM). Methods: A retrospective study was conducted in Ruijin Hospital from 2014 to 2017. The characteristics of DM and non-DM patients were assessed, including demographics, comorbidities, using of invasive mechanical ventilation, Hemoglobin A1c (HbA1C), confusion, urea, respiratory rate, blood pressure, age ≥65 years (CURB-65) score, length of hospital stay, clinical outcomes, antimicrobial susceptibility. Independent risk factors for mortality were identified by univariate and multivariate logistic regression analysis. Results: A total of 365 patients with S. aureus pneumonia were included in our study, including 144 with DM and 221 non-DM. DM patients were more susceptible to MRSA infection (65.3% vs. 56.1%, P > 0.05), suffered from much severer pneumonia with a higher CURB-65 score, invasive mechanical ventilation rate (46.5% vs. 28.1%, P 0.05); almost all DM patients had higher antimicrobial resistance than non-DM patients, the DM group had a higher coinfection rate (47.2% vs. 45.7%, P > 0.05), and Acinetobacter baumannii was the most common bacterium in DM, while Klebsiella pneumoniae ranked first in patients with non-DM. Independent risk factors for pneumonia-related mortality were MRSA and CURB-65. Higher HbA1c levels were linked to a higher MRSA infection and co-infection rate and more severe pneumonia, leading to an increase in mortality. Conclusions: DM patients with poor glucose control are more susceptible to MRSA infection. They suffer from higher antimicrobial resistance, a higher co-infection rate, and much severer pneumonia than non-DM. MRSA itself is an independent risk factor for mortality in all patients. Key words: Methicillin-resistant S. aureus; Pneumonia; Diabetics mellitus; Co-infection; Risk factor; HbA1c

The aims of this study were to determine the antimicrobial susceptibility profile and genetic diversity of Staphylococcus spp. isolated from dairy cows in Minas Gerais, Brazil, and to assess the relationship among the isolates? susceptibility profiles and pulsed‐field gel electrophoresis (PFGE) genotypes. Seventy‐nine isolates were used, including S. aureus (n = 71) and coagulase‐negative staphylococci (CoNS) (n = 8). Susceptibility to 12 antimicrobial agents was performed. All Staphylococcus spp. were subjected to PFGE. Staphylococcus aureus and CoNS isolates exhibited full susceptibility only to cephalothin. The greatest percentages of resistance among Staphylococcus spp. were observed to penicillins, folate pathway inhibitors, and tetracyclines. Twelve S. aureus and four CoNS were classified as multidrug resistance strains. Percentage of MRSA was also higher among CoNS (75%), compared to S. aureus isolates (2.81%). Adopting 100% of similarity, 34 different genotypes were identified. Association of minimum‐spanning tree (MST) analysis with data from municipalities, herds, methicillin‐resistant S. aureus (MRSA), and resistance patterns for all isolates did not show any clustering. However, a clustering pattern of bacterial species was observed. Results from this study indicate a high frequency of antimicrobial resistance, especially among CoNS, and a high genetic diversity among Staphylococcus spp. isolated from dairy cows with mastitis in Minas Gerais, Brazil. Made available in DSpace on 2020-01-08T18:21:47Z (GMT). No. of bitstreams: 1 Dornelesetal2019MicrobiologyOpen.pdf: 645952 bytes, checksum: c3171aa1751b55fe26724a420df8d4c3 (MD5) Previous issue date: 2019

Purpose This work presents the preparation of a nanocomposite of ampicillin-conjugated gold nanoparticles (AuNPs) and self-assembled rosette nanotubes (RNTs), and evaluates its antibacterial properties against two strains of drug-resistant bacteria (Staphylococcus aureus [S. aureus], methicillin-resistant S. aureus [MRSA]). Materials and methods Small, nearly monodisperse AuNPs (1.43±0.5 nm in diameter) nucleated on the surface of polyethylene glycol-functionalized RNTs in a one-pot reaction. Upon conjugation with ampicillin, their diameter increased to 1.86±0.32 nm. The antibacterial activity of the nanocomposite against S. aureus and MRSA was tested using different concentrations of ampicillin. The cytocompatibility of the nanocomposite was also tested against human dermal fibroblasts. Results Based on bacterial inhibition studies, the nanocomposite demonstrated enhanced antibiotic activity against both bacterial strains. The minimum inhibitory concentration (MIC) of the nanocomposite against S. aureus was found to be 0.58 μg/mL, which was 18% lower than ampicillin alone. The nanocomposite also exhibited a 20 hrs MIC of 4 μg/mL against MRSA, approximately 10–20 times lower than previously reported values for ampicillin alone. In addition, at concentrations of 4 μg/mL of ampicillin (70 μg/mL of AuNPs), the nanocomposite showed negligible cytotoxic effects. Conclusion Our findings offer a new approach for the treatment of drug-resistant bacteria by potentiating inhibitory effects of existing antibiotics, and delivering them using a non-toxic formulation.

Staphylococcus aureus is a notorious pathogen that colonizes implants (orthopedic and breast implants) and wounds with a vicious resistance to antibiotic therapy. Methicillin-resistant S. aureus (MRSA) is a catastrophe mainly restricted to hospitals and emerged to community reservoirs, acquiring resistance and forming biofilms. Treating biofilms is problematic except via implant removal or wound debridement. Nanoparticles (NPs) and nanofibers could combat superbugs and biofilms and rapidly diagnose MRSA. Nanotheranostics combine diagnostics and therapeutics into a single agent. This comprehensive review is interpretative, utilizing mainly recent literature (since 2016) besides the older remarkable studies sourced via Google Scholar and PubMed. We unravel the molecular S. aureus resistance and complex biofilm. The diagnostic properties and detailed antibacterial and antibiofilm NP mechanisms are elucidated in exciting stories. We highlight the challenges of bacterial infections nanotheranostics. Finally, we discuss the literature and provide “three action appraisals”. (i) The first appraisal consists of preventive actions (two wings), avoiding unnecessary hospital visits, hand hygiene, and legislations against over-the-counter antibiotics as the general preventive wing. Our second recommended preventive wing includes preventing the adverse side effects of the NPs from resistance and toxicity by establishing standard testing procedures. These standard procedures should provide breakpoints of bacteria’s susceptibility to NPs and a thorough toxicological examination of every single batch of synthesized NPs. (ii) The second appraisal includes theranostic actions, using nanotheranostics to diagnose and treat MRSA, such as what we call “multifunctional theranostic nanofibers. (iii) The third action appraisal consists of collaborative actions.

Staphylococcus aureus is an increasingly important pathogen, due to the arsenal of virulence factors which presents, in addition to its high capacity to generate antimicrobial resistance. The objectives of this research were: confirm methicillin resistance by amplification the mecA gene and the presence of genes that encode Panton Valentine leucocidin (PVL) virulence factor. These genes have been investigated using polymerase chain reaction (PCR). All isolates showed the mecA gene, 50% of these strains were carrying the gene for PVL. 54,17% of the samples from pediatric patients, yield positive for this leukocidin. The highest percentage of isolation was found in samples of skin and soft tissues (85.7%). Resumen: Staphylococcus aureus se presenta como un patógeno cada vez más importante, debido al arsenal de factores de virulencia que presenta, sumado a su elevada capacidad de generar resistencia a los antimicrobianos Los objetivos de esta investigación fueron: confirmar la resistencia a meticilina mediante la amplificación del gen mecA y detectar la presencia de los genes que codifican el factor de virulencia leucocidina de Panton Valentine (PVL). Se investigaron estos genes empleando la reacción en cadena de polimerasa (PCR). Todos los aislamientos presentaron el gen mecA, el 50% de estas cepas resultó portador del gen para PVL. El 54,17% de las muestras de pacientes pediátricos, dio positivo para esta leucocidina. El mayor porcentaje de aislamiento se encontró en muestras de piel y tejidos blandos (85,7%).

Staphylococcus aureus se presenta como un patógeno cada vez más importante, debido al arsenal de factores de virulencia que presenta, sumado a su elevada capacidad de generar resistencia a los antimicrobianos Los objetivos de esta investigación fueron: confirmar la resistencia a meticilina mediante la amplificación del gen mecA y detectar la presencia de los genes que codifican el factor de virulencia leucocidina de Panton Valentine (PVL). Se investigaron estos genes empleando la reacción en cadena de polimerasa (PCR). Todos los aislamientos presentaron el gen mecA, el 50% de estas cepas resultó portador del gen para PVL. El 54,17% de las muestras de pacientes pediátricos, dio positivo para esta leucocidina. El mayor porcentaje de aislamiento se encontró en muestras de piel y tejidos blandos (85,7%). Staphylococcus aureus is an increasingly important pathogen, due to the arsenal of virulence factors which presents, in addition to its high capacity to generate antimicrobial resistance. The objectives of this research were: confirm methicillin resistance by amplification the mecA gene and the presence of genes that encode Panton Valentine leucocidin (PVL) virulence factor. These genes have been investigated using polymerase chain reaction (PCR). All isolates showed the mecA gene, 50% of these strains were carrying the gene for PVL. 54,17% of the samples from pediatric patients, yield positive for this leukocidin. The highest percentage of isolation was found in samples of skin and soft tissues (85.7%).

We describe a case of methicillin-resistant Staphylococcus aureus (MRSA) enterocolitis in a healthy adult with previous antibiotic exposure. Colonoscopy revealed diffuse colitis and mild ileitis without ulceration. Stool cultures demonstrated abundant growth of MRSA and absent normal flora. Oral vancomycin treatment was effective and seems to be the consensus choice for therapy.

Side-chain derivatives of eurotiumide A, a dihydroisochroman-type natural product, have been synthesized and their antimicrobial activities described. Sixteen derivatives were synthesized from a key intermediate of the total synthesis of eurotiumide A, and their antimicrobial activities against two Gram-positive bacteria, methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA), and a Gram-negative bacterium, Porphyromonas gingivalis, were evaluated. The results showed that derivatives having an iodine atom on their aromatic ring instead of the prenyl moiety displayed better antimicrobial activity than eurotiumide A against MSSA and P. gingivalis. Moreover, we discovered that a derivative with an isopentyl side chain, which is a hydrogenated product of eurotiumide A, is the strongest antimicrobial agent against all three strains, including MRSA.

Background Pemphigus vulgaris (PV) is a potentially fatal autoimmune vesiculobullous disease. Staphylococcus aureus is the most common cause of cutaneous bacterial infection in pemphigus. Methicillin-resistant S. aureus (MRSA) is a common multidrug-resistant bacterium. MRSA infection is high among dermatology inpatients and vesiculobullous diseases patients are the commonest infected. Objective This study aimed at determining the causative organisms of the secondary bacterial skin infections in PV patients, identifying MRSA, doing antibiotic sensitivity pattern for MRSA, and determining the risk factors for acquiring MRSA infection among PV patients in the locality. Patients and methods This cross-sectional study included 54 PV patients. All patients were subjected to history taking, general, and dermatological examinations. Pemphigus disease area index score was calculated. Three swabs for bacterial culture and antibiotic sensitivity testing were obtained (one from vesicle or bulla, one from pustule, and the third from the nose). Results In all, 51 (94.4%) patients showed positive cultures for S. aureus either as nasal carrier, skin colonization, or skin infection. There was overlap as some patients showed more than one type of positive culture at the same time. Of the patients, 19 out of 51 patients (37.25%) had positive cultures for MRSA. All MRSA strains were sensitive to vancomycin. Also, they had good sensitivity to trimethoprim–sulfamethoxazole, amikacin, ciprofloxacin, and erythromycin, while all MRSA strains were resistant to cefoxitin and ampicillin. Hospitalization, previous antibiotics use in the last 4 weeks prior to this study, length of hospital stay, history of hospital-acquired infections, and community-acquired infections were significantly higher among MRSA-positive patients. Conclusion There is high MRSA infection/colonization among PV patients. MRSA responds to cheap antibiotics as trimethoprim–sulfamethoxazole, amikacin, and ciprofloxacin.

Zhiyao Chen, Changlin Han, Xiaobin Huang, Yangqun Liu, Dan Guo, Xiaohua Ye Laboratory of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China Background: Methicillin-resistant Staphylococcus aureus (MRSA) causes a wide variety of serious infections worldwide. There are few studies on the prevalence, antimicrobial susceptibility, and molecular characteristics of MRSA contamination in the environment of airports.Materials and methods: A cross-sectional survey was conducted in Guangzhou Baiyun Airport. Environmental surface sampling was conducted in frequently touched locations for S. aureus analysis. All isolates were characterized by multilocus sequence typing (MLST) and tested for antimicrobial susceptibility, resistance genes, and virulence genes. Data were analyzed by chi-squared test and correspondence analysis.Results: Of the 1,054 surface samples, the contamination rate was 7.2% (76/1,054) for S. aureus and 2.2% (23/1,054) for MRSA. There were 62.9% (56/89) S. aureus isolates classified as multidrug resistant (MDR), with six linezolid-resistant isolates and two cfr-carrying isolates. The most prevalent S. aureus genotypes were CC6 (ST6), CC59 (ST59), and CC188 (ST188), with ST59-MRSA-IV (pvl–) as the predominant MRSA. There were significant differences between methicillin-resistant and methicillin-sensitive isolates in rates of resistance to tetracycline (P

Side effects of chemical preservatives and drug resistance have raised interest in use of herbal products. This study aimed to examine the chemical composition and antibacterial effects of Cuminum cyminum, Mentha spicata, and Mentha longifolia essential oils individually and in combination with sodium benzoate against methicillin-resistant Staphylococcus aureus and Yersinia enterocolitica. The essential oils were analyzed by gas chromatography-mass spectrometry. Disc diffusion and microdilution assays were used for in vitro antimicrobial screening. The main components were cumin aldehyde, carvone, and pulegone in C. cyminum, M. spicata, and M. longifolia essential oils, respectively. Antibacterial data analysis showed significant differences between different antibacterial effects of essential oils individually and in combination with sodium benzoate. In terms of individual effects, antibacterial effect of M. longifolia and C. cyminum essential oils were the highest against methicillin-resistant S. aureus and Y. enterocolitica, respectively. The antibacterial effects of sodium benzoate combined with essential oils showed significant differences with the individual effect of sodium benzoate in most cases. The results indicated that the combined effect of these essential oils with sodium benzoate could reduce the use of sodium benzoate as an antimicrobial agent, which could decrease its possible side effects. Thus, for more significant effects, these essential oils could be combined with other agents for the preservation of drug and food products.

Background Antimicrobial resistance is a serious threat against humankind and the search for new therapeutics is needed. This study aims to investigate the antimicrobial and antioxidant activities of ethanol extracts and compounds isolated from Dissotis senegambiensis and Amphiblemma monticola, two Cameroonian Melastomataceae species traditionally used for the treatment of fever, malaria and infectious diseases. Methods The plant extracts were prepared by maceration in ethanol. Standard chromatographic and spectroscopic methods were used to isolate and identify fourteen compounds from the two plant species [1–6 (from D. senegambiensis), 3, 4 and 7–14 (from A. monticola)]. A two-fold serial micro-dilution method was used to determine the minimum inhibitory concentration (MIC) against four bacterial strains including two resistant bacterial strains, methicillin resistant S. aureus (MRSA3) and methicillin resistant S. aureus (MRSA4) and three yeast strains. Results The fractionation of EtOH extracts afforded fourteen compounds belonging to triterpenoid and phenolic derivatives. The ethanol extracts, compounds 3, 5–8, 10 and the mixture of 10 + 12 were active against all the tested bacterial and fungal species. Compound 7 (MIC = 16–32 μg/mL) and 10 (MIC = 8–16 μg/mL) displayed the largest antibacterial and antifungal activities, respectively. Compounds 7, 10 and the mixture of 10 + 12 showed prominent antibacterial activity against methicillin- resistant S. aureus (MRSA) which is in some cases equal to that of ciprofloxacin used as reference antibacterial drug. Compound 8 also showed high radical-scavenging activities and ferric reducing power when compared with vitamin C and butylated hydroxytoluene used as reference antioxidants. The tested samples were non-toxic to normal cells highlighting their good selectivity. Conclusions The result of this investigation reveals the potential of D. senegambiensis and A. monticola as well as the most active compounds in the search for new antimicrobial and antioxidant agents. So, further investigations are needed. Electronic supplementary material The online version of this article (10.1186/s12906-018-2229-2) contains supplementary material, which is available to authorized users.

Objective(s): Staphylococcus aureus is a Gram-positive pathogen, well known for its resistance and versatile lifestyle. Under unfavourable conditions, it adapts biofilm mode of growth. For staphylococcal biofilm formation, production of extracellular polymeric substances (EPS) is a pre-requisite, which is regulated by ica operon-encoded enzymes. This study was designed to know the impact of ascorbic acid on biofilm formation and colony spreading processes of S. aureus and MRSA. Materials and Methods: The isolates of methicillin-resistant S. aureus (MRSA) used in present study, were recovered from different food samples. Various selective and differential media were used for identification and confirmation of S. aureus. Agar dilution method was used for determination of oxacillin and ascorbic acid resistance level. MRSA isolates were re-confirmed by E-test and by amplification of mecA gene. Tube methods and Congo-Red agar were used to study biofilm formation processes. Gene expression studies were carried on real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results: The results revealed the presence of mecA gene belonging to SCCmecA type IV along with agr type II in the isolates. In vitro studies showed the sub-inhibitory concentration of oxacillin induced biofilm production. However, addition of sub-inhibitory dose of ascorbic acid was found to inhibit EPS production, biofilm formation and augment colony spreading on soft agar plates. The inhibition of biofilm formation and augmentation of colony spreading observed with ascorbic acid alone or in combination with oxacillin. Moreover, gene expression studies showed that ascorbic acid increases agr expression and decreases icaA gene expression. Conclusion: The present study concluded that ascorbic acid inhibits biofilm formation, promotes colony spreading and increases agr gene expression in MRSA.

Staphylococcus aureus is an extraordinarily versatile pathogen responsible for staphylococcal food poisoning, hospital and community infections, as well as toxic shock syndrome. S . aureus is considered the most effective food-borne bacterial pathogen that has ever evolved. The S . aureus metagenome contains 10s of genes encoding staphylococcal enterotoxins, which are responsible for the clinical symptoms associated with staphylococcal food poisoning. S. aureus may be present in food products, being a potential vehicle for transmission. Antibiotics are widely used not only in humans but also in animal husbandry and other agricultural activities. The occurrence of multiresistant strains in food(s) has been increasing; contaminated food is considered an important vehicle for antimicrobial resistance. Methicillin-resistant S. aureus (MRSA) was first recognized in animal infections in 1972 in milk from mastitic cows in Belgium. Animal-associated MRSA infections in humans were first reported during 2003–05 in the Netherlands. Presently, it was reported that livestock-associated MRSA CC398 in pork identifies a potential pathway from farms to the wider population through retail pork. MRSA commonly carry enterotoxin genes but there has been only one report of food intoxication due to MRSA. Antibiotic resistance associated to enterotoxins genes made S. aureus an evolving threat.

Blood platelets are critical for hemostasis and thrombosis and play diverse roles during immune responses. Despite these versatile tasks in mammalian biology, their skills on a cellular level are deemed limited, mainly consisting in rolling, adhesion, and aggregate formation. Here, we identify an unappreciated asset of platelets and show that adherent platelets use adhesion receptors to mechanically probe the adhesive substrate in their local microenvironment. When actomyosin-dependent traction forces overcome substrate resistance, platelets migrate and pile up the adhesive substrate together with any bound particulate material. They use this ability to act as cellular scavengers, scanning the vascular surface for potential invaders and collecting deposited bacteria. Microbe collection by migrating platelets boosts the activity of professional phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection. In addition to their role in thrombosis and hemostasis, platelets can also migrate to sites of infection to help trap bacteria and clear the vascular surface.

Background Patients with methicillin-resistant S. aureus (MRSA) are thought to incur additional costs for hospitals due to longer stay and contact isolation. The aim of this study was to assess the costs associated with MRSA in Norwegian hospitals. Methods Analyses were based on data fromSouth-Eastern Norway for the year 2012 as registered in the Norwegian Surveillance System for Communicable Diseases and the Norwegian Patient Registry. We used a matched case-control method to compare MRSA diagnosed inpatients with non-MRSA inpatients in terms of length of stay, readmissions within 30 days from discharge, as well as the Diagnosis-Related Group (DRG) based costs. Results Norwegian patients with MRSA stayed on average 8 days longer in hospital than controls, corresponding to a ratio of mean duration of 2.08 (CI 95%, 1.75–2.47) times longer.A total of 14% of MRSA positive inpatients were readmitted compared to 10% among controls. However, the risk of readmission was not significantly higher for patients with MRSA. DRG based hospital costs were 0.37 (95% CI, 0.19–0.54) times higher among cases than controls, with a mean cost of EUR13,233(SD 26,899) and EUR7198(SD 18,159) respectively. Conclusion The results of this study indicate that Norwegian patients with MRSA have longer hospital stays, and higher costs than those without MRSA.

Staphylococcus aureus is a common colonizer in pigs, with methicillin-resistant S. aureus (MRSA) in particular being a potential health risk to humans. To reduce the exposure to humans, the colonization in pigs should be reduced. The aim of this study was to quantitatively compare the susceptibility of pig lineages for S. aureus colonization, and if the absence of S. aureus could be associated with the presence or absence of other staphylococcal species. Nasal samples (n = 129) were obtained from seven different pig lineages in the Netherlands, France, and Germany. S. aureus and other staphylococci were enumerated from these samples by real-time (RT)-PCR and culture. Associations were explored between the presence of S. aureus and other staphylococci. S. aureus was detected by RT-PCR on all farms and in samples from pigs of all lineages. Twenty-five percent of the pigs from lineage F (from two farms) were colonized with S. aureus, while in all other lineages it was more than 50% (p