The role of Staphylococcus aureus in cystic fibrosis pathogenesis and clinico-microbiological interactions.

Cystic fibrosis (CF) is a progressive and inherited disease that affects approximately 70000 individuals all over the world annually. A mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene serves as its defining feature. Bacterial infections have a significant impact on the occurrence and development of CF. In this manuscript, we discuss the role and virulence factors of Staphylococcus aureus as an important human pathogen with the ability to induce respiratory tract infections. Recent studies have reported S. aureus as the first isolated bacteria in CF patients. Methicillin-resistant Staphylococcus aureus (MRSA) pathogens are approximately resistant to all ß-lactams. CF patients are colonized by MRSA expressing various virulence factors including toxins, and Staphylococcal Cassette Chromosome mec (SCCmec) types, and have the potential for biofilm formation. Therefore, variations in clinical outcomes will be manifested. SCCmec type II has been reported in CF patients more than in other SCCmec types from different countries. The small-colony variants (SCVs) as specific morphologic subtypes of S. aureus with slow growth and unusual properties can also contribute to persistent and difficult-to-treat infections in CF patients. The pathophysiology of SCVs is complicated and not fully understood. Patients with cystic fibrosis should be aware of the intrinsic risk factors for complex S. aureus infections, including recurring infections, physiological issues, or coinfection with P. aeruginosa.

Enterotoxigenic methicillin resistant Staphylococcus aureus contamination in salted fish from Gwadar Balochistan / Contaminação de Staphylococcus aureus resistente à meticilina enterotoxigênica em peixes salgados de Gwadar Balochistan

Staphylococcus aureus is an important foodborne pathogen associated to food intoxication and other multiple infections in human being. Its presence in salted food is a serious issue due to its salt tolerance potential. A study was conducted to analyze the presence of enterotoxins producing drug resistance S. aureus in salted sea fish from Gwadar. Freshly persevered samples (n=50) of salted fish were subjected to analyze the presence of S. aureus using 16S rRNA and Nuc genes primers. The isolates were then evaluated for drug resistance and enterotoxins producing potential using specific primers for MecA (methicillin resistance gene), (SEA) staphylococcal enterotoxin A and (SEB) staphylococcal enterotoxin B genes. Total 13/50 (26%) of the samples were found positive for the presence of S. aureus, preliminary confirmed with biochemical profiling and finally with the help of target genes presence. The isolates were found showing 100% resistant to methicillin, which were molecularly confirmed by the presence of MecA gene present in genome. The isolates 5/13 (38%) were positive for SEA and 3/13 (23%) for SEB genes, whereas 2/13 (15%) were confirmed having both SEA and SEB genes in its genome. It was also confirmed that all the isolates were capable to form biofilm over the glass surfaces. It was concluded that the study confirmed the presence of enterotoxigenic methicillin resistance Staphylococcus aurous (MRSA) in salted fish product, that poses gross food safety concern. Preventive and control measures are necessary to handle this serious food safety concern.

Staphylococcus aureus é um importante patógeno de origem alimentar associado à intoxicação alimentar e outras infecções múltiplas em seres humanos. Sua presença em alimentos salgados é um problema sério devido ao seu potencial de tolerância ao sal. Um estudo foi realizado para analisar a presença de enterotoxinas produtoras de resistência a drogas S. aureus em peixes salgados do mar de Gwadar. Amostras recém-perseveradas (n = 50) de peixes salgados foram submetidas à análise da presença de S. aureus usando os primers dos genes 16S rRNA e Nuc. Os isolados foram então avaliados quanto à resistência a drogas e potencial de produção de enterotoxinas usando primers específicos para os genes MecA (gene de resistência à meticilina), (SEA) enterotoxina A estafilocócica e (SEB) enterotoxina B estafilocócica genes. Um total de 13/50 (26%) das amostras foi considerado positivas para a presença de S. aureus, confirmadas preliminarmente com perfis bioquímicos e finalmente com a ajuda da presença de genes-alvo. Os isolados foram encontrados com 100% de resistência à meticilina, os quais foram confirmados molecularmente pela presença do gene MecA no genoma. Os isolados 5/13 (38%) foram positivos para SEA e 3/13 (23%) para genes SEB, enquanto 2/13 (15%) foram confirmados tendo os genes SEA e SEB em seu genoma. Também foi verificado que todos os isolados foram capazes de formar biofilme sobre as superfícies de vidro. Concluiu-se que o estudo confirmou a presença de Staphylococcus aurous resistente à meticilina enterotoxigênica (MRSA) em produtos de peixe salgado, o que representa uma grande preocupação para a segurança alimentar. Medidas preventivas e de controle são necessárias para lidar com essa grave preocupação com a segurança alimentar.

The Untargeted Phytochemical Profile of Three Meliaceae Species Related to In Vitro Cytotoxicity and Anti-Virulence Activity against MRSA Isolates.

BACKGROUND: A high mortality rate is associated with about 80% of all infections worldwide, mainly due to antimicrobial resistance. Various antimicrobial and cytotoxic activities have been proposed for Meliaceae species. This study aimed to evaluate the in vitro anti-virulence and cytotoxic effect of the leaf extracts of Aphanamixis polystachya, Toona ciliata and Melia azedarach against five MRSA strains and on three cancer cell lines, followed by biological correlation to their encompassed phytoconstituents. MATERIAL AND METHODS: We explored three plants of this family against a panel of Methicillin-resistant Staphylococcus aureus (MRSA) strains and several cancer cell lines to select the most promising candidates for further in vivo and preclinical studies. The phytochemical composition was evaluated by UHPLC-QTOF-MS untargeted profiling. Cell viability was assessed by SRB assay. Minimum Inhibitory Concentration was carried out by using the agar micro-dilution technique. Inhibition of biofilm formation and preformed biofilm disruption were assessed spectrophotomertically, according to the Sultan and Nabil method (2019). RESULTS: A total of 279 compounds were putatively annotated to include different phytochemical classes, such as flavonoids (108), limonoids/terpenoids (59), phenolic acids (49) and lower-molecular-weight phenolics (39). A. polystachya extract showed the most potent cytotoxic activity against Huh-7, DU-145 and MCF-7 cell lines (IC50 = 3, 3.5 and 13.4 µg mL-1, respectively), followed by M. azedarach, with no effect recorded for T. ciliata extract. Furthermore, both A. polystachya and M. azedarach extracts showed promising anti-virulence and antimicrobial activities, with A. polystachya being particularly active against MRSA. These two latter extracts could inhibit and disrupt the biofilm, formed by MRSA, at sub-lethal concentrations. Interestingly, the extracts inhibited hemolysin-α enzyme, thus protecting rabbit RBCs from lysis. A. polystachya extract reduced the pigmentation and catalase enzyme activity of tested pigmented strains better than M. azedarach at both tested sub-MICs. Consequently, susceptibility of the extract-treated cells to oxidant killing by 200 mM H2O2 increased, leading to faster killing of the cells within 120 min as compared to the extract-non-treated cells, likely due to the lower antioxidant-scavenging activity of cells exhibiting less staphyloxanthin production. CONCLUSION: These findings suggested that both A. polystachya and M. azedarach natural extracts are rich in bioactive compounds, mainly limonoids, phenolics and oxygenated triterpenoids, which can combat MRSA biofilm infections and could be considered as promising sources of therapeutic cytotoxic, antibiofilm and anti-virulence agents.

Secondary Amine Pendant ß-Peptide Polymers Displaying Potent Antibacterial Activity and Promising Therapeutic Potential in Treating MRSA-Induced Wound Infections and Keratitis.

Interest in developing antibacterial polymers as synthetic mimics of host defense peptides (HPDs) has accelerated in recent years to combat antibiotic-resistant bacterial infections. Positively charged moieties are critical in defining the antibacterial activity and eukaryotic toxicity of HDP mimics. Most examples have utilized primary amines or guanidines as the source of positively charged moieties, inspired by the lysine and arginine residues in HDPs. Here, we explore the impact of amine group variation (primary, secondary, or tertiary amine) on the antibacterial performance of HDP-mimicking ß-peptide polymers. Our studies show that a secondary ammonium is superior to either a primary ammonium or a tertiary ammonium as the cationic moiety in antibacterial ß-peptide polymers. The optimal polymer, a homopolymer bearing secondary amino groups, displays potent antibacterial activity and the highest selectivity (low hemolysis and cytotoxicity). The optimal polymer displays potent activity against antibiotic-resistant bacteria and high therapeutic efficacy in treating MRSA-induced wound infections and keratitis as well as low acute dermal toxicity and low corneal epithelial cytotoxicity. This work suggests that secondary amines may be broadly useful in the design of antibacterial polymers.

Identification of structurally diverse menaquinone-binding antibiotics with in vivo activity against multidrug-resistant pathogens.

The emergence of multidrug-resistant bacteria poses a threat to global health and necessitates the development of additional in vivo active antibiotics with diverse modes of action. Directly targeting menaquinone (MK), which plays an important role in bacterial electron transport, is an appealing, yet underexplored, mode of action due to a dearth of MK-binding molecules. Here we combine sequence-based metagenomic mining with a motif search of bioinformatically predicted natural product structures to identify six biosynthetic gene clusters that we predicted encode MK-binding antibiotics (MBAs). Their predicted products (MBA1-6) were rapidly accessed using a synthetic bioinformatic natural product approach, which relies on bioinformatic structure prediction followed by chemical synthesis. Among these six structurally diverse MBAs, four make up two new MBA structural families. The most potent member of each new family (MBA3, MBA6) proved effective at treating methicillin-resistant Staphylococcus aureus infection in a murine peritonitis-sepsis model. The only conserved feature present in all MBAs is the sequence 'GXLXXXW', which we propose represents a minimum MK-binding motif. Notably, we found that a subset of MBAs were active against Mycobacterium tuberculosis both in vitro and in macrophages. Our findings suggest that naturally occurring MBAs are a structurally diverse and untapped class of mechanistically interesting, in vivo active antibiotics.

Differences Between Methicillin-susceptible Versus Methicillin-resistant Staphylococcus aureus Infections in Pediatrics: Multicenter Cohort Study Conducted in Bogotá, Colombia, 2014-2018.

BACKGROUND: The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) has changed in recent years. The present article is intended to establish differences between clinical, laboratory and imaging findings and outcomes of MSSA and MRSA infections, as well as among subgroups of infection such as skin and soft tissue infection, osteoarticular, bacteremia or pneumonia in a pediatric population from Bogota, Colombia. METHODS: Retrospective cohort study using clinical records of patients under 18 years of age treated at the participating centers in Bogota, Colombia, between 2014 and 2018. The first positive S. aureus culture was studied. MSSA and MRSA were compared. The χ2 test, Fisher exact test, and Kruskal-Wallis test were calculated, and the statistical significance was presented using the difference and its 95% CI. RESULTS: Five hundred fifty-one patients were included; 211 (38%) corresponded to MRSA and 340 (62%) to MSSA for a total of 703 cultures. A significantly higher probability of having an MSSA infection than MRSA was found in patients with previous heart disease (3.3% vs. 0.5%), neurologic disease (5.9% vs. 2.5%), recent major surgeries (11% vs. 5%) or who has an implanted device (11% vs. 4%). In contrast, in severe MRSA infections (bacteremia, osteoarticular infections and pneumonia), a higher rate of complications was seen (admission to the pediatric intensive care unit, mechanical ventilation and vasoactive support), and in osteoarticular MRSA, more than 1 surgery per case was seen (89% vs. 61%). Laboratory results and mortality were similar. CONCLUSIONS: MRSA was associated with a more severe course in bacteremia, osteoarticular infections and pneumonia. Some classical risk factors associated with MRSA infections were found to be related to MSSA. In general, with the exception of skin and soft tissue infection, there was an increased risk of pediatric intensive care unit admission and mechanical and inotropic support with MRSA in a pediatric population.

Bisdemethoxycurcumin Reduces Methicillin-Resistant Staphylococcus aureus Expression of Virulence-Related Exoproteins and Inhibits the Biofilm Formation.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen of nosocomial infection, which is resistant to most antibiotics. Presently, anti-virulence therapy and anti-biofilm therapy are considered to be promising alternatives. In the current work, we investigated the influence of bisdemethoxycurcumin (BDMC) on the virulence-related exoproteins and the biofilm formation using a reference strain and clinic isolated strains. Western blotting, quantitative RT-PCR, and tumor necrosis factor (TNF) release assay were performed to assess the efficacy of BDMC in reducing the expression of Staphylococcus enterotoxin-related exoproteins (enterotoxin A, enterotoxin B) and α-toxin in MRSA. The anti-biofilm activity of BDMC was evaluated through a biofilm inhibition assay. The study suggests that sub-inhibitory concentrations of BDMC significantly inhibited the expression of sea, seb, and hla at the mRNA level in MRSA. Moreover, the expression of virulence-related exoproteins was significantly decreased by down-regulating accessory gene regulator agr, and the inhibition of biofilms formation was demonstrated by BDMC at sub-inhibitory concentrations. Consequently, the study suggests that BDMC may be a potential natural antibacterial agent to release the pressure brought by antibiotic resistance.

Optimized Silica-Binding Peptide-Mediated Delivery of Bactericidal Lysin Efficiently Prevents Staphylococcus aureus from Adhering to Device Surfaces.

Staphylococcal-associated device-related infections (DRIs) represent a significant clinical challenge causing major medical and economic sequelae. Bacterial colonization, proliferation, and biofilm formation after adherence to surfaces of the indwelling device are probably the primary cause of DRIs. To address this issue, we incorporated constructs of silica-binding peptide (SiBP) with ClyF, an anti-staphylococcal lysin, into functionalized coatings to impart bactericidal activity against planktonic and sessile Staphylococcus aureus. An optimized construct, SiBP1-ClyF, exhibited improved thermostability and staphylolytic activity compared to its parental lysin ClyF. SiBP1-ClyF-functionalized coatings were efficient in killing MRSA strain N315 (>99.999% within 1 h) and preventing the growth of static and dynamic S. aureus biofilms on various surfaces, including siliconized glass, silicone-coated latex catheter, and silicone catheter. Additionally, SiBP1-ClyF-immobilized surfaces supported normal attachment and growth of mammalian cells. Although the recycling potential and long-term stability of lysin-immobilized surfaces are still affected by the fragility of biological protein molecules, the present study provides a generic strategy for efficient delivery of bactericidal lysin to solid surfaces, which serves as a new approach to prevent the growth of antibiotic-resistant microorganisms on surfaces in hospital settings and could be adapted for other target pathogens as well.

Decursinol Angelate Mitigates Sepsis Induced by Methicillin-Resistant Staphylococcus aureus Infection by Modulating the Inflammatory Responses of Macrophages.

The herbal plant Angelica gigas (A. gigas) has been used in traditional medicine in East Asian countries, and its chemical components are reported to have many pharmacological effects. In this study, we showed that a bioactive ingredient of A. gigas modulates the functional activity of macrophages and investigated its effect on inflammation using a sepsis model. Among 12 different compounds derived from A. gigas, decursinol angelate (DA) was identified as the most effective in suppressing the induction of TNF-α and IL-6 in murine macrophages. When mice were infected with a lethal dose of methicillin-resistant Staphylococcus aureus (MRSA), DA treatment improved the mortality and bacteremia, and attenuated the cytokine storm, which was associated with decreased CD38+ macrophage populations in the blood and liver. In vitro studies revealed that DA inhibited the functional activation of macrophages in the expression of pro-inflammatory mediators in response to microbial infection, while promoting the bacterial killing ability with an increased production of reactive oxygen species. Mechanistically, DA treatment attenuated the NF-κB and Akt signaling pathways. Intriguingly, ectopic expression of an active mutant of IKK2 released the inhibition of TNF-α production by the DA treatment, whereas the inhibition of Akt resulted in enhanced ROS production. Taken together, our experimental evidence demonstrated that DA modulates the functional activities of pro-inflammatory macrophages and that DA could be a potential therapeutic agent in the management of sepsis.

Inhibition of Bacterial Efflux Pumps by Crude Extracts and Essential Oil from Myristica fragrans Houtt. (Nutmeg) Seeds against Methicillin-Resistant Staphylococcus aureus.

Myristicafragrans Houtt. (Nutmeg) is a widely known folk medicine across several parts of Asia, particularly used in antimicrobial treatment. Bacterial resistance involves the expression of efflux pump systems (chromosomal norA and mepA) in methicillin-resistant Staphylococcus aureus (MRSA). Crude extract (CE) and essential oil (EO) obtained from nutmeg were applied as efflux pump inhibitors (EPIs), thereby enhancing the antimicrobial activity of the drugs they were used in. The major substances in CE and EO, which function as EPIs, in a descending order of % peak area include elemicin, myristicin, methoxyeugenol, myristicin, and asarone. Here, we investigated whether the low amount of CE and EO used as EPIs was sufficient to sensitize MRSA killing using the antibiotic ciprofloxacin, which acts as an efflux system. Interestingly, synergy between ciprofloxacin and CE or EO revealed the most significant viability of MRSA, depending on norA and mepA, the latter being responsible for EPI function of EO. Therefore, CE and EO obtained from nutmeg can act as EPIs in combination with substances that act as efflux systems, thereby ensuring that the MRSA strain is susceptible to antibiotic treatment.

Ward-level factors associated with methicillin-resistant Staphylococcus aureus acquisition-an electronic medical records study in Singapore.

BACKGROUND: Methicillin-Resistant Staphylococcus aureus (MRSA) is endemic in hospitals worldwide. Intrahospital transfers may impact MRSA acquisition risk experienced by patients. In this study, we investigated ward characteristics and connectivity that are associated with MRSA acquisition. METHODS: We analysed electronic medical records on patient transfers and MRSA screening of in-patients at an acute-care tertiary hospital in Singapore to investigate whether ward characteristics and connectivity within a network of in-patient wards were associated with MRSA acquisition rates over a period of four years. RESULTS: Most patient transfers concentrated in a stable core network of wards. Factors associated with increased rate of MRSA acquisition were MRSA prevalence among patients transferred from other wards (rate ratio (RR): 7.74 [95% confidence interval (CI): 3.88, 15.44], additional 5 percentage point), critical care ward (RR: 1.72 [95% CI: 1.09, 2.70]) and presence of MRSA cohorting beds (RR: 1.39 [95% CI: 1.03, 1.90]. Oncology ward (RR: 0.66 [95% CI: 0.46, 0.94]) (compared to medical ward), and median length of stay (RR: 0.70 [95% CI: 0.55, 0.90], additional 1.5 days) were associated with lower acquisition rates. In addition, we found evidence of interaction between MRSA prevalence among patients transferred from other wards and weighted in-degree although the latter was not associated with MRSA acquisition after controlling for confounders. CONCLUSION: Wards with higher MRSA prevalence among patients transferred from other wards were more likely to have higher MRSA acquisition rate. Its effect further increased in wards receiving greater number of patients. In addition, critical care ward, presence of MRSA cohorting beds, ward specialty, and median length of stay were associated with MRSA acquisition.

Infection control measures in nosocomial MRSA outbreaks-Results of a systematic analysis.

There is a lack of data on factors that contribute to the implementation of hygiene measures during nosocomial outbreaks (NO) caused by Methicillin-resistant Staphylococcus aureus (MRSA). Therefore, we first conducted a systematic literature analysis to identify MRSA outbreak reports. The expenditure for infection control in each outbreak was then evaluated by a weighted cumulative hygiene score (WCHS). Effects of factors on this score were determined by multivariable linear regression analysis. 104 NO got included, mostly from neonatology (n = 32), surgery (n = 27), internal medicine and burn units (n = 10 each), including 4,361 patients (thereof 657 infections and 73 deaths) and 279 employees. The outbreak sources remained unknown in 10 NO and were not reported from further 61 NO. The national MRSA prevalence did not correlate with the WCHS (p = .714). There were significant WCHS differences for internal medicine (p = 0.014), burn units (p<0.01), for Japanese NO (p<0.01), and NO with an unknown source (p<0.01). In sum, management of a NO due to MRSA does not depend on the local MRSA burden. However, differences of MRSA management among medical departments do exist. Strict adherence to the Outbreak Reports and Intervention Studies Of Nosocomial infection (ORION) statement is highly recommended for. The WCHS may also serve as a useful tool to quantify infection control effort and could therefore be used for further investigations.

Cigarette Smoke and Nicotine-Containing Electronic-Cigarette Vapor Downregulate Lung WWOX Expression, Which Is Associated with Increased Severity of Murine Acute Respiratory Distress Syndrome.

A history of chronic cigarette smoking is known to increase risk for acute respiratory distress syndrome (ARDS), but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures and thus an interesting candidate gene for the study of exposure-related lung disease. Lungs harvested from current versus former/never-smokers exhibited a 47% decrease in WWOX mRNA levels. Exposure to nicotine-containing e-cigarette vapor resulted in an average 57% decrease in WWOX mRNA levels relative to vehicle-treated controls. In separate studies, endothelial (EC)-specific WWOX knockout (KO) versus WWOX flox control mice were examined under ARDS-producing conditions. EC WWOX KO mice exhibited significantly greater levels of vascular leak and histologic lung injury. ECs were isolated from digested lungs of untreated EC WWOX KO mice using sorting by flow cytometry for CD31+ CD45-cells. These were grown in culture, confirmed to be WWOX deficient by RT-PCR and Western blotting, and analyzed by electric cell impedance sensing as well as an FITC dextran transwell assay for their barrier properties during methicillin-resistant Staphylococcus aureus or LPS exposure. WWOX KO ECs demonstrated significantly greater declines in barrier function relative to cells from WWOX flox controls during either methicillin-resistant S. aureus or LPS treatment as measured by both electric cell impedance sensing and the transwell assay. The increased risk for ARDS observed in chronic smokers may be mechanistically linked, at least in part, to lung WWOX downregulation, and this phenomenon may also manifest in the near future in chronic users of e-cigarettes.

Photodynamic Coatings on Polymer Microfibers for Pathogen Inactivation: Effects of Application Method and Composition.

A substantial increase in the risk of hospital-acquired infections (HAIs) has greatly impacted the global healthcare industry. Harmful pathogens adhere to a variety of surfaces and infect personnel on contact, thereby promoting transmission to new hosts. This is particularly worrisome in the case of antibiotic-resistant pathogens, which constitute a growing threat to human health worldwide and require new preventative routes of disinfection. In this study, we have incorporated different loading levels of a porphyrin photosensitizer capable of generating reactive singlet oxygen in the presence of O2 and visible light in a water-soluble, photo-cross-linkable polymer coating, which was subsequently deposited on polymer microfibers. Two different application methods are considered, and the morphological and chemical characteristics of these coated fibers are analyzed to detect the presence of the coating and photosensitizer. To discern the efficacy of the fibers against pathogenic bacteria, photodynamic inactivation has been performed on two different bacterial strains, Staphylococcus aureus and antibiotic-resistant Escherichia coli, with population reductions of >99.9999 and 99.6%, respectively, after exposure to visible light for 1 h. In response to the current COVID-19 pandemic, we also confirm that these coated fibers can inactivate a human common cold coronavirus serving as a surrogate for the SARS-CoV-2 virus.

Salvinorin A protects against methicillin resistant staphylococcus aureus-induced acute lung injury via Nrf2 pathway.

Salvinorin A (SA), a neoclerodane diterpene, is isolated from the dried leaves ofSalvia divinorum. SA has traditionally been used treatments for chronic pain diseases. Recent research has demonstrated that SA possesses the anti-inflammatory property. The present study aim to explore the effects and potentialmechanisms ofSA in protection against Methicillin Resistant Staphylococcus aureus (MRSA)-induced acute lung injury (ALI). Here, we firstly found that verylowdosesof SA (50 µg/kg) could markedly decrease the infiltration of pulmonary neutrophils, mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) and then attenuated ALI cause by MRSA infection in mice. In vitro findings revealed that SA attenuated lipoteichoicacid-induced apoptosis, inflammation and oxidative stress in RAW264.7 cells. Mechanism research revealed that SA increased both mRNA levels and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and up-regulated mRNA expression of its downstream genes (HO-1, Gclm, Trx-1, SOD1 and SOD2). Additionally, Nrf2 knockout mice abolished the inhibitory effect of SA on neutrophil accumulation and oxidative stress in MRSA-induced ALI. In conclusion, SA attenuates MRSA-induced ALI via Nrf2 signaling pathways.

Prevalência de Staphylococcus resistente à meticilina em profissionais de enfermagem: revisão integrativa / Prevalence of methicillin-resistant Staphylococcus in nursing professionals: an integrative review

Objetivo: estimar a prevalência de colonização por Staphylococcus resistente à meticilina entre profissionais de enfermagem conforme evidências científicas. Método: revisão integrativa da literatura, realizada em setembro de 2020, mediante acesso nas bases de dados LILACS, MEDLINE, CINAHL e Web of Science. Resultados: A prevalência de Staphylococcusaureus Resistente à Meticilina variou de 0 a 30,4%, com média de 8,4%; além disso, as pesquisas conduzidas mais recentemente (2015: 15,7%; 2016: 9,2%; 2017: 15,9%) e no continente asiático (14,57%) estimaram maiores prevalências médias. Conclusão: ainda são expressivas as prevalências de colonização por Staphylococcus resistente à meticilina entre profissionais de enfermagem verificadas nos diversos estudos realizados em âmbito nacional e internacional, o que reforça a necessidade de adoção de programas de vigilância ativa, como estratégia para detecção de casos assintomáticos e contribuição no rompimento da cadeia de transmissão das infecções

Objective: to estimate the prevalence of colonization by methicillin-resistant Staphylococcus aureus among nursing professionals according to scientific evidence. Method: integrative literature review conducted in September 2020 through access to the LILACS, MEDLINE, CINAHL and Web of Science databases. Results: the prevalence of methicillin-resistant Staphylococcus aureus ranged from 0 to 30.4%, mean of 8.4%. In addition, surveys conducted more recently (2015: 15.7%; 2016: 9.2%; 2017: 15.9%) and in Asia (14.57%) estimated higher mean prevalence rates. Conclusion: the prevalence of colonization by methicillin-resistant Staphylococcus among nursing professionals found in the various national and international studies is still significant, which reinforces the need to adopt active surveillance programs as a strategy to detect asymptomatic cases and contribute to break the chain of transmission of infections.

Evaluation of Cytotoxicity and α-Glucosidase Inhibitory Activity of Amide and Polyamino-Derivatives of Lupane Triterpenoids.

A series of two new and twenty earlier synthesized branched extra-amino-triterpenoids obtained by the direct coupling of betulinic/betulonic acids with polymethylenpolyamines, or by the cyanoethylation of lupane type alcohols, oximes, amines, and amides with the following reduction were evaluated for cytotoxicity toward the NCI-60 cancer cell line panel, α-glucosidase inhibitory, and antimicrobial activities. Lupane carboxamides, conjugates with diaminopropane, triethylenetetramine, and branched C3-cyanoethylated polyamine methyl betulonate showed high cytotoxic activity against most of the tested cancer cell lines with GI50 that ranged from 1.09 to 54.40 µM. Betulonic acid C28-conjugate with triethylenetetramine and C3,C28-bis-aminopropoxy-betulin were found to be potent micromolar inhibitors of yeast α-glucosidase and to simultaneously inhibit the endosomal reticulum α-glucosidase, rendering them as potentially capable to suppress tumor invasiveness and neovascularization, in addition to the direct cytotoxicity. Plausible mechanisms of cytotoxic action and underlying disrupted molecular pathways were elucidated with CellMinner pattern analysis and Gene Ontology enrichment analysis, according to which the lead compounds exert multi-target antiproliferative activity associated with oxidative stress induction and chromatin structure alteration. The betulonic acid diethylentriamine conjugate showed partial activity against methicillin-resistant S. aureus and the fungi C. neoformans. These results show that triterpenic polyamines, being analogs of steroidal squalamine and trodusquemine, are important substances for the search of new drugs with anticancer, antidiabetic, and antimicrobial activities.

Reduction in the infection rate of cranioplasty with a tailored antibiotic prophylaxis: a nonrandomized study.

BACKGROUND: Cranioplasty carries a high risk of surgical site infections (SSIs) for a scheduled procedure, particularly with antibiotic-resistant bacteria. METHODS: The goal of this retrospective study was to measure the effect of tailored antibiotic prophylaxis on SSIs resulting from cranioplasties. The authors collected a prospective database of cranioplasties from 2009 to 2018. Risk factors for SSI were registered, as well as infection occurring during the first year postoperatively. A new protocol was initiated in 2016 consisting of antibiotic prophylaxis tailored to the colonizing flora of the skin of the scalp and decolonization of patients who were nasal carriers of methicillin-resistant S. aureus (MRSA); infection rates were compared. RESULTS: One hundred nine cranioplasties were identified, 64 in the old protocol and 45 in the new protocol. Of the 109 cranioplasties, 16 (14.7%) suffered an infection, 14 (21.9%) in the old protocol group and 2 (4.4%) in the new protocol group (OR for the new protocol 0.166, 95% CI 0.036-0.772). Multiple surgeries (OR 3.44), Barthel ≤ 70 (OR 3.53), and previous infection (OR 3.9) were risk factors for SSI. Of the bacteria identified in the skin of the scalp, 22.2% were resistant to routine prophylaxis (cefazoline). Only one patient was identified as a nasal carrier of MRSA and was decolonized. CONCLUSIONS: A high percentage of bacteria resistant to routine prophylaxis (cefazoline) was identified in the skin of these patients' scalps. The use of tailored antibiotic prophylaxis reduced significantly the infection rate in this particular set of patients.

The Virulence Potential of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Cultured from the Airways of Cystic Fibrosis Patients.

Staphylococcus aureus is one of the most common pathogens that infects the airways of patients with cystic fibrosis (CF) and contributes to respiratory failure. Recently, livestock-associated methicillin-resistant S. aureus (LA-MRSA), usually cultured in farm animals, were detected in CF airways. Although some of these strains are able to establish severe infections in humans, there is limited knowledge about the role of LA-MRSA virulence in CF lung disease. To address this issue, we analyzed LA-MRSA, hospital-associated (HA-) MRSA and methicillin-susceptible S.aureus (MSSA) clinical isolates recovered early in the course of airway infection and several years after persistence in this hostile environment from pulmonary specimens of nine CF patients regarding important virulence traits such as their hemolytic activity, biofilm formation, invasion in airway epithelial cells, cytotoxicity, and antibiotic susceptibility. We detected that CF LA-MRSA isolates were resistant to tetracycline, more hemolytic and cytotoxic than HA-MRSA, and more invasive than MSSA. Despite the residence in the animal host, LA-MRSA still represent a serious threat to humans, as such clones possess a virulence potential similar or even higher than that of HA-MRSA. Furthermore, we confirmed that S. aureus individually adapts to the airways of CF patients, which eventually impedes the success of antistaphylococcal therapy of airway infections in CF.

Clinical and prognostic differences between methicillin-resistant and methicillin-susceptible Staphylococcus aureus infective endocarditis.

BACKGROUND: S. aureus (SA) infective endocarditis (IE) has a very high mortality, attributed to the age and comorbidities of patients, inadequate or delayed antibiotic treatment, and methicillin resistance, among other causes. The main study objective was to analyze epidemiological and clinical differences between IE by methicillin-resistant versus methicillin-susceptible SA (MRSA vs. MSSA) and to examine prognostic factors for SA endocarditis, including methicillin resistance and vancomycin minimum inhibitory concentration (MIC) values > 1 µg/mL to MRSA. METHODS: Patients with SA endocarditis were consecutively and prospectively recruited from the Andalusia endocarditis cohort between 1984 and January 2017. RESULTS: We studied 437 patients with SA endocarditis, which was MRSA in 13.5% of cases. A greater likelihood of history of COPD (OR 3.19; 95% CI 1.41-7.23), invasive procedures, or recognized infection focus in the 3 months before IE onset (OR 2.9; 95% CI 1.14-7.65) and of diagnostic delay (OR 3.94; 95% CI 1.64-9.5) was observed in patients with MRSA versus MSSA endocarditis. The one-year mortality rate due to SA endocarditis was 44.3% and associated with decade of endocarditis onset (1985-1999) (OR 8.391; 95% CI (2.82-24.9); 2000-2009 (OR 6.4; 95% CI 2.92-14.06); active neoplasm (OR 6.63; 95% CI 1.7-25.5) and sepsis (OR 2.28; 95% CI 1.053-4.9). Methicillin resistance was not associated with higher IE-related mortality (49.7 vs. 43.1%; p = 0.32). CONCLUSION: MRSA IE is associated with COPD, previous invasive procedure or recognized infection focus, and nosocomial or healthcare-related origin. Methicillin resistance does not appear to be a decisive prognostic factor for SA IE.