Increase in methicillin-resistant Staphylococcus spp. colonization among pregnant individuals during COVID-19 pandemic.

Methicillin-resistant Staphylococcus (MRS) has been associated with neonatal infections, with colonization of the anovaginal tract being the main source of vertical transmission. The COVID-19 pandemic has altered the frequency of antibiotic usage, potentially contributing to changes in the dynamics of bacterial agents colonizing humans. Here we determined MRS colonization rates among pregnant individuals attending a single maternity in Rio de Janeiro, Brazil before (January 2019-March 2020) and during (May 2020-March 2021) the COVID-19 pandemic. Anovaginal samples (n = 806 [521 samples before and 285 during the pandemic]) were streaked onto chromogenic media. Colonies were identified by MALDI-TOF MS. Detection of mecA gene and SCCmec typing were assessed by PCR and antimicrobial susceptibility testing was done according to CLSI guidelines. After the onset of the pandemic, MRS colonization rates increased significantly (p < 0.05) from 8.6% (45) to 54.7% (156). Overall, 215 (26.6%) MRS isolates were detected, of which S. haemolyticus was the most prevalent species (MRSH, 84.2%; 181 isolates). SCCmec type V was the most frequent among MRS (63.3%; 136), and 31.6% (68) of MRS strains had a non-typeable SCCmec, due to new combinations of ccr and mecA complexes. Among MRS strains, 41.9% (90) were resistant to at least 3 different classes of antimicrobial agents, and 60% (54) of them were S. haemolyticus harboring SCCmec V. MRS colonization rates and the emergence of multidrug-resistant variants detected in this study indicate the need for continuing surveillance of this important pathogen within maternal and child populations.

Epidemiological and microbiological characteristics of S. aureus pediatric infections in Colombia 2018-2021, a national multicenter study (Staphylored Colombia).

Background: Staphylococcus aureus infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on pediatric patients across Colombia from 2018 to 2021. The aim of this study was to describe the epidemiological and microbiological characteristics of S. aureus in this patient group. Methods: We analyzed S. aureus isolates from WHONET-reporting centers. An "event" was a positive culture isolation in a previously negative individual after 2 weeks. We studied center characteristics, age distribution, infection type, and antibiotic susceptibilities, comparing methicillin sensitive (MSSA) and resistant S. aureus (MRSA) isolates. Results: Isolates from 20 centers across 7 Colombian cities were included. Most centers (80%) served both adults and children, with 55% offering oncology services and 85% having a PICU. We registered 8,157 S. aureus culture isolations from 5,384 events (3,345 MSSA and 1,961 MRSA) in 4,821 patients, with a median age of 5 years. Blood (26.2%) and skin/soft tissue (18.6%) were the most common infection sources. Most isolates per event remained susceptible to oxacillin (63.2%), clindamycin (94.3%), and TMP-SMX (98.3%). MRSA prevalence varied by city (<0.001), with slightly higher rates observed in exclusively pediatric hospitals. In contrast, the MRSA rate was somewhat lower in centers with Antimicrobial Stewardship Program (ASP). MRSA was predominantly isolated from osteoarticular infections and multiple foci, while MSSA was more frequently associated with recurrent infections compared to MRSA. Conclusions: This is the largest study of pediatric S. aureus infections in Colombia. We found MSSA predominance, but resistance have important regional variations. S. aureus remains susceptible to other commonly used antibiotics such as TMP-SMX and clindamycin. Ongoing monitoring of S. aureus infections is vital for understanding their behavior in children. Prospective studies within the Staphylored LATAM are underway for a more comprehensive clinical and genetic characterization.

New Synergistic Combination Therapy of Mupirocin and α-Pinene Against Multidrug-Resistant Clinical Strains of Methicillin-Resistant Staphylococcus aureus.

OBJECTIVE: Increased mupirocin use leads to mupirocin resistance and is associated with persistence of methicillin-resistant Staphylococcus aureus (MRSA) carriers, prolonged hospitalization, and significant economic burdens for health systems. The study aimed to investigate the antimicrobial activity of compounds of Salvia rosmarinus L. ("rosemary", formerly Rosmarinus officinalis), alone or in combination with mupirocin, against multidrug resistant MRSA using isolates obtained from pediatric patients. METHODS: The in vitro antibacterial activity of the monoterpene α-pinene (α-Pi), a rosemary essential oil constituent, alone and in combination with mupirocin, was evaluated by determining the minimum inhibitory concentrations and minimum bactericidal concentrations (MBCs) and the fractional inhibitory concentration indices (FICIs) and fractional bactericidal concentration indices against multidrug-resistant clinical MRSA strains. The in vivo efficacy of α-Pi, alone and in combination with mupirocin, to eradicate MRSA infection was determined using an optimized mouse model of MRSA-infected wounds. Mouse skin samples (obtained via biopsy) were assessed for toxicity, and rabbit skin samples for irritation. RESULTS: Both in vitro and in vivo, α-Pi was active against MRSA strains and acted synergistically with mupirocin against MRSA strains. Mupirocin-monoterpene combinations exhibited FICI values of 0.2 to 0.4, reducing the MBC of topical mupirocin 33-fold. A topical formulation containing α-Pi and mupirocin enhanced the efficacy of mupirocin in an in vivo MRSA-infected mouse skin model without significantly harming the skin of mice and rabbits. CONCLUSIONS: A topical formulation combining mupirocin and α-Pi may aid in the development of innovative agents for treating MRSA infections.

Inhibition of Shikimate Kinase from Methicillin-Resistant Staphylococcus aureus by Benzimidazole Derivatives. Kinetic, Computational, Toxicological, and Biological Activity Studies.

Antimicrobial resistance (AMR) is one of the biggest threats in modern times. It was estimated that in 2019, 1.27 million deaths occurred around the globe due to AMR. Methicillin-resistant Staphylococcus aureus (MRSA) strains, a pathogen considered of high priority by the World Health Organization, have proven to be resistant to most of the actual antimicrobial treatments. Therefore, new treatments are required to be able to manage this increasing threat. Under this perspective, an important metabolic pathway for MRSA survival, and absent in mammals, is the shikimate pathway, which is involved in the biosynthesis of chorismate, an intermediate for the synthesis of aromatic amino acids, folates, and ubiquinone. Therefore, the enzymes of this route have been considered good targets to design novel antibiotics. The fifth step of the route is performed by shikimate kinase (SK). In this study, an in-house chemical library of 170 benzimidazole derivatives was screened against MRSA shikimate kinase (SaSK). This effort led to the identification of the first SaSK inhibitors, and the two inhibitors with the greatest inhibition activity (C1 and C2) were characterized. Kinetic studies showed that both compounds were competitive inhibitors with respect to ATP and non-competitive for shikimate. Structural analysis through molecular docking and molecular dynamics simulations indicated that both inhibitors interacted with ARG113, an important residue involved in ATP binding, and formed stable complexes during the simulation period. Biological activity evaluation showed that both compounds were able to inhibit the growth of a MRSA strain. Mitochondrial assays showed that both compounds modify the activity of electron transport chain complexes. Finally, ADMETox predictions suggested that, in general, C1 and C2 can be considered as potential drug candidates. Therefore, the benzimidazole derivatives reported here are the first SaSK inhibitors, representing a promising scaffold and a guide to design new drugs against MRSA.

Co-resistance to methicillin and clindamycin among coagulase-negative staphylococci isolates recovered from pet food in Brazil.

Pet food have been considered as possible vehicles of bacterial pathogens. The sudden boom of the pet food industry due to the worldwide increase in companion animal ownership calls for pet food investigations. Herein, this study aimed to determine the frequency, antimicrobial susceptibility profile, and molecular characteristics of coagulase-negative staphylococci (CoNS) in different pet food brands in Brazil. Eighty-six pet food packages were screened for CoNS. All isolates were identified at species level by MALDI-TOF MS and species-specific PCR. Antimicrobial susceptibility testing was performed by disc diffusion and broth microdilution (vancomycin and teicoplanin only) methods. The D-test was used to screen for inducible clindamycin phenotype (MLS-B). SCCmec typing and detection of mecA, vanA, vanB, and virulence-encoding genes were done by PCR. A total of 16 (18.6 %) CoNS isolates were recovered from pet food samples. Isolates were generally multidrug-resistant (MDR). All isolates were completely resistant (100 %) to penicillin. Resistances (12.5 % - 75 %) were also observed for fluoroquinolones, sulfamethoxazole-trimethoprim, tetracycline, rifampicin, erythromycin, and tobramycin. Isolates were susceptible to vancomycin (MICs <0.25-1 µg/mL) and teicoplanin (MICs <0.25-4 µg/mL). Intriguingly, 3/8 (37.5 %) CoNS isolates with the ERYRCLIS antibiotype expressed MLS-B phenotype. All isolates harboured blaZ gene. Seven (43.8 %) isolates carried mecA; and among them, the SCCmec Type III was the most frequent (n = 5/7; 71.4 %). Isolates also harboured seb, see, seg, sej, sem, etb, tsst, pvl, and hla toxin virulence-encoding genes (6.3 % - 25 %). A total of 12/16 (75 %) isolates were biofilm producers, while the icaAB gene was detected in an S. pasteuri isolate. Herein, it is shown that pet food is a potential source of clinically important Gram-positive bacterial pathogens. To the best of our knowledge, this is the first report of MLS-B phenotype and MR-CoNS in pet food in Latin America.

In Vitro Antimicrobial Photodynamic Therapy for Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) Inhibition Using a Green Light Source.

Photodynamic therapy (PDT) has been based on using photosensitizers (PS) and applying light of a specific wavelength. When this technique is used for treating infections, it is known as antimicrobial photodynamic therapy (aPDT). Currently, the use of lighting sources for in vitro studies using aPDT is generally applied in multiwell cell culture plates; however, depending on the lighting arrangement, there are usually errors in the application of the technique because the light from a well can affect the neighboring wells or it may be that not all the wells are used in the same experiment. In addition, one must be awarded high irradiance values, which can cause unwanted photothermal problems in the studies. Thus, this manuscript presents an in vitro antimicrobial photodynamic therapy for a Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) inhibition study using an arrangement of thermally isolated and independently illuminated green light source systems for eight tubes in vitro aPDT, determining the effect of the following factors: (i) irradiance level, (ii) exposure time, and (iii) Rose Bengal (RB) concentration (used as a PS), registering the Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) inhibition rates. The results show that in the dark, RB had a poor antimicrobial rate for P. aeruginosa, finding the maximum inhibition (2.7%) at 30 min with an RB concentration of 3 µg/mL. However, by applying light in a correct dosage (time × irradiance) and the adequate RB concentration, the inhibition rate increased by over 37%. In the case of MRSA, there was no significant inhibition with RB in complete darkness and, in contrast, the rate was 100% for those experiments that were irradiated.

Interaction of beauvericin in combination with antibiotics against methicillin-resistant Staphylococcus aureus and Salmonella typhimurium.

Multidrug resistance in bacteria is a major challenge worldwide, increasing both mortality by infections and costs for the health systems. Therefore, it is of utmost importance to find new drugs against resistant bacteria. Beauvericin (BEA) is a mycotoxin produced by entomopathogenic and other fungi of the genus Fusarium. Our work determines the effect of BEA combined with antibiotics, which has not been previously explored. The combination analysis included different antibiotics against non-methicillin-resistant Staphylococcus aureus (NT-MRSA), methicillin-resistant Staphylococcus aureus (MRSA), and Salmonella typhimurium. BEA showed a synergy effect with oxacillin with a fractional inhibitory concentration index (FICI) = 0.373 and an additive effect in combination with lincomycin (FICI = 0.507) against MRSA. In contrast, it was an antagonist when combined with ciprofloxacin against S. typhimurium. We propose BEA as a molecule with the potential for the development of new therapies in combination with current antibiotics against multidrug-resistant bacteria.

Antimicrobial resistance of Enterobacteriaceae and Staphylococcus spp. isolated from raw cow's milk from healthy, clinical and subclinical mastitis udders.

Mastitis is the most common disease of dairy cattle and can be manifested in clinical and subclinical forms. The overuse of antimicrobials in the treatment and prevention of mastitis favours antimicrobial resistance and milk can be a potential route of dissemination. This study aimed to evaluate the biological quality of bulk tank milk (BTM) and the microbiological quality and signs of mastitis of freshly milked raw milk. In addition, to evaluate antimicrobial resistance in Enterobacteriaceae and Staphylococcus spp. isolated from freshly milked raw milk. None of the farms were within the official Brazilian biological quality limits for BTM. Freshly milked raw milk with signs of clinical (CMM), subclinical (SCMM) and no signs (MFM) of mastitis were detected in 6.67%, 27.62% and 65.71% samples, respectively. Most samples of freshly milked raw milk showed acceptable microbiological quality, when evaluating the indicators total coliforms (78.10%), Escherichia coli (88.57%) and Staphylococcus aureus (100%). Klebsiella oxytoca and S. aureus were the most prevalent microorganisms in SCMM and MFM samples. Antimicrobial resistance and multidrug resistance (MDR) were observed in 65.12% and 13.95% of Enterobacteriaceae and 84.31% and 5.88% of Staphylococcus spp., respectively, isolated from both SCMM and MFM samples. Enterobacteriaceae resistant to third-generation cephalosporin (3GCR) (6.98%) and carbapenems (CRE) (6.98%) and methicillin-resistant S. aureus (MRSA) (4.88%) were observed. Antimicrobial-resistant bacteria can spread resistance genes to previously susceptible bacteria. This is a problem that affects animal, human and environmental health and should be evaluated within the one-health concept.

Detection of Vancomycin Resistance among Methicillin-Resistant Staphylococcus aureus Strains Recovered from Children with Invasive Diseases in a Reference Pediatric Hospital.

Vancomycin is the cornerstone in treating methicillin-resistant Staphylococcus aureus (MRSA) infections. However, therapeutic failures can occur when MRSA strains with decreased susceptibility to glycopeptides (DSG) are involved. The aim of this study was to detect and characterize DSG in MRSA recovered from children with invasive diseases at a reference pediatric hospital between 2009 and 2019. Fifty-two MRSA strains were screened using agar plates with vancomycin 3 and 4 mg/L (BHI-3 and BHI-4); the VITEK2 system; and standard and macro E-tests. Suspicious hVISA were studied by population analysis profiling-area under the curve (PAP-AUC), and wall thickness was analyzed by transmission electron microscopy. Neither VRSA nor VISA were detected in this set. As only three strains met the hVISA criteria, the PAP-AUC study included 12 additional MRSA strains that grew one colony on BHI-4 plates or showed minimum inhibitory concentrations of vancomycin and/or teicoplanin ≥ 1.5 mg/L. One strain was confirmed as hVISA by PAP-AUC. The wall thickness was greater than the vancomycin-susceptible control strain; it belonged to ST30 and carried SCCmec IV. As expected, a low frequency of hVISA was found (1.9%). The only hVISA confirmed by PAP-AUC was not detected by the screening methods, highlighting the challenge that its detection represents for microbiology laboratories.

Detection of mecA Genes in Hospital-Acquired MRSA and SOSA Strains Associated with Biofilm Formation.

Methicillin-resistant (MR) Staphylococcus aureus (SA) and others, except for Staphylococcus aureus (SOSA), are common in healthcare-associated infections. SOSA encompass largely coagulase-negative staphylococci, including coagulase-positive staphylococcal species. Biofilm formation is encoded by the icaADBC operon and is involved in virulence. mecA encodes an additional penicillin-binding protein (PBP), PBP2a, that avoids the arrival of ß-lactams at the target, found in the staphylococcal cassette chromosome mec (SCCmec). This work aims to detect mecA, the bap gene, the icaADBC operon, and types of SCCmec associated to biofilm in MRSA and SOSA strains. A total of 46% (37/80) of the strains were S. aureus, 44% (35/80) S. epidermidis, 5% (4/80) S. haemolyticus, 2.5% (2/80) S. hominis, 1.25% (1/80) S. intermedius, and 1.25% (1/80) S. saprophyticus. A total of 85% were MR, of which 95.5% showed mecA and 86.7% ß-lactamase producers; thus, Staphylococcus may have more than one resistance mechanism. Healthcare-associated infection strains codified type I-III genes of SCCmec; types IV and V were associated to community-acquired strains (CA). Type II prevailed in MRSA mecA strains and type II and III in MRSOSA (methicillin-resistant staphylococci other than Staphylococcus aureus). The operon icaADBC was found in 24% of SA and 14% of SOSA; probably the arrangement of the operon, fork formation, and mutations influenced the variation. Methicillin resistance was mainly mediated by the mecA gene; however, there may be other mechanisms that also participate, since biofilm production is related to genes of the icaADBC operon and methicillin resistance was not associated with biofilm production. Therefore, it is necessary to strengthen surveillance to prevent the spread of these outbreaks both in the nosocomial environment and in the community.

Risk factors for therapeutic failure in adults with methicillin-resistant Staphylococcus aureus (MRSA) infection treated with vancomycin in a high-complexity hospital in Cali, Colombia.

Objective: To determine the risk factors associated with therapeutic failure of vancomycin in hospitalized adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Design: Case-control study. Setting: Conducted in a high complexity hospital in Cali, Colombia. Participants: Adult hospitalized from January 1, 2015, to December 31, 2021, with MRSA infections with confirmed microbiological isolation. Methods: Cases were patients with therapeutic failure of vancomycin (mortality, poor clinical improvement, change of antibiotic used, early relapse, or persistence of positive blood cultures) and control patients were those who did not present failure. Significant variables from the bivariate analysis were included in a multiple analysis with an asymmetric logistic regression model. Results: A total of 105 patients were included in the study, 28 in the treatment group and 77 in the control group. The median age was 49 years and 59 (56%) of participants were men. The following variables: age (OR 1.034; 95% CI 1.007-1.061, p=0.011), osteomyelitis/ septic arthritis (OR 6.035; 95% CI 2.282-15.956, p=0.000) and minimum inhibitory concentration (MIC) (OR 5.971; 95% CI 1.321-26.979, p=0.020) were found to be independent risk factors associated with therapeutic failure of vancomycin. Vancomycin trough levels were not different between cases and controls (OR 0.976; 95% CI 0.911-1.044, p=0.478). Conclusions: When a multiple analysis was performed to control for confounding factors, only 3 variables were found to be significant and were considered risk factors for therapeutic failure of vancomycin in adult patients with MRSA infection: age, MIC, and osteomyelitis/ septic arthritis.

Effects of antimicrobial photodynamic therapy with photodithazine® on methicillin-resistant Staphylococcus aureus (MRSA): Studies in biofilms and experimental model with Galleria mellonella.

Staphylococcus aureus infections are a severe health problem due to the high mortality rate. Conventional treatment of these infections is via the administration of antibiotics. However, its indiscriminate use can select resistant microorganisms. Thus, it is necessary to develop alternatives for antibiotic therapy. Antimicrobial Photodynamic Therapy (aPDT), a therapeutic method that associates a photosensitizer (PS), a light source with adequate wavelength to the PS, interacts with molecular oxygen generating reactive oxygen species responsible for cell inactivation, is a viable alternative. This work aimed to analyze, in vitro and in vivo, the action of aPDT with PS Photodithazine® (PDZ) on the methicillin-resistant S. aureus (MRSA) strain. In the in vitro method, the S. aureus biofilm was incubated with PDZ at 50 and 75 µg.mL-1 for 15 min, adopting the light dose of 25, 50, and 100 J/cm2. In addition, PS interaction, formation of reactive oxygen species (ROS), bacterial metabolism, adhesion, bacterial viability, and biofilm structure were evaluated by scanning electron microscopy. Subsequently, the strain was inoculated into models of Galleria mellonella, and the survival curve, health scale, blood cell analysis, and CFU/mL of S. aureus in the hemolymph were analyzed after aPDT. In the in vitro results, bacterial reduction was observed in the different PDZ concentrations, highlighting the parameters of 75 µg.mL-1 of PDZ and 100 J/cm2. As for in vivo results, aPDT increased survival and stimulated the immune system of G. mellonella infected by S. aureus. aPDT proved effective in both models, demonstrating its potential as an alternative therapy in treating MRSA bacterial infections.

Antimicrobial photodynamic therapy with Brazilian green propolis controls intradermal infection induced by methicillin-resistant Staphylococcus aureus and modulates the inflammatory response in a murine model.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of skin and soft tissue infections worldwide. This microorganism has a wide range of antibiotics resistance, a fact that has made the treatment of infections caused by MRSA difficult. In this sense, antimicrobial photodynamic therapy (aPDT) with natural products has emerged as a good alternative in combating infections caused by antibiotic-resistant microorganisms. The objective of the present study was to evaluate the effects of aPDT with Brazilian green propolis against intradermal MRSA infection in a murine model. Initially, 24 Balb/c mice were infected intradermally in the ears with 1.5 × 108 colony-forming units of MRSA 43300. After infection, they were separated into 4 groups (6 animals per group) and treated with the vehicle, only Brazilian green propolis, only blue LED light or with the aPDT protocol (Brazilian green propolis + blue LED light). It was observed in this study that aPDT with Brazilian green propolis reduced the bacterial load at the site of infection. Furthermore, it was able to inhibit weight loss resulting from the infection, as well as modulate the inflammatory response through greater recruitment of polymorphonuclear cells/neutrophils to the infected tissue. Finally, aPDT induced an increase in the cytokines IL-17A and IL-12p70 in the draining retromaxillary lymph node. Thus, aPDT with Brazilian green propolis proved to be effective against intradermal MRSA infection in mice, reducing bacterial load and modulating the immune response in the animals. However, more studies are needed to assess whether such effects are repeated in humans.

Genomic epidemiology of the primary methicillin-resistant Staphylococcus aureus clones causing invasive infections in Paraguayan children.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major human pathogens. It could carry numerous resistance genes and virulence factors in its genome, some of which are related to the severity of the infection. An observational, descriptive, cross-sectional study was designed to molecularly analyze MRSA isolates that cause invasive infections in Paraguayan children from 2009 to 2013. Ten representative MRSA isolates of the main clonal complex identified were analyzed with short-read paired-end sequencing and assessed for the virulome, resistome, and phylogenetic relationships. All the genetically linked MRSA isolates were recovered from diverse clinical sources, patients, and hospitals at broad gap periods. The pan-genomic analysis of these clones revealed three major and different clonal complexes (CC30, CC5, and CC8), each composed of clones closely related to each other. The CC30 genomes prove to be a successful clone, strongly installed and disseminated throughout our country, and closely related to other CC30 public genomes from the region and the world. The CC5 shows the highest genetic variability, and the CC8 carried the complete arginine catabolic mobile element (ACME), closely related to the USA300-NAE-ACME+, identified as the major cause of CA-MRSA infections in North America. Multiple virulence and resistance genes were identified for the first time in this study, highlighting the complex virulence profiles of MRSA circulating in the country. This study opens a wide range of new possibilities for future projects and trials to improve the existing knowledge on the epidemiology of MRSA circulating in Paraguay. IMPORTANCE: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is a public health problem worldwide. The most frequent MRSA clones identified in Paraguay in previous studies (including community and hospital acquired) were the Pediatric (CC5-ST5-IV), the Cordobes-Chilean (CC5-ST5-I), the SouthWest Pacific (CC30-ST30-IV), and the Brazilian (CC8-ST239-III) clones. In this study, the pan-genomic analysis of the most representative MRSA clones circulating in invasive infection in Paraguayan children over the years 2009-2013, such as the CC30-ST30-IV, CC5-ST5-IV, and CC8-ST8-IV, was carried out to evaluate their genetic diversity, their repertoire of virulence factors, and antimicrobial resistance determinants. This revealed multiple virulence and resistance genes, highlighting the complex virulence profiles of MRSA circulating in Paraguay. Our work is the first genomic study of MRSA in Paraguay and will contribute to the development of genomic surveillance in the region and our understanding of the global epidemiology of this pathogen.

El desarrollo y los complejos mecanismos de resistencia de S. aureus: una amenaza persistente en la era de los antibióticos

Introducción: S. aureus ha emergido como una amenaza persistente, demostrando una notable habilidad para desarrollar resistencia a lo largo de la evolución de los antibióticos. Desde los primeros enfrentamientos con la penicilina hasta los desafíos actuales con cepas resistentes a la vancomicina y la daptomicina, el estudio de los mecanismos de resistencia de este patógeno ha adquirido una importancia crítica. Objetivos: documentar los cambios en los patrones de resistencia de S. aureus a lo largo del tiempo, además de identificar las etapas críticas en el desarrollo de la resistencia a diferentes antibióticos. Materiales y métodos: el proceso de selección de artículos revisados se llevó a cabo identificando artículos publicados entre 2010 y 2023. Se utilizaron varias bases de datos relevantes, incluyendo PubMed, Scopus, Embase, Cochrane Library y Scielo. Se incluyeron estudios observacionales, artículos de revisión y guías clínicas. Se desarrollaron estrategias de búsqueda específicas para cada base de datos utilizando palabras clave y términos de búsqueda relacionados con S. aureus y su resistencia antimicrobiana, así como los tipos de estudios de interés. Se extrajeron datos relevantes de los estudios seleccionados, incluyendo información sobre los patrones de resistencia, mecanismos de resistencia, impacto clínico y estrategias terapéuticas. Los datos recopilados se analizaron y sintetizaron para documentar los cambios en los patrones de resistencia de S. aureus a lo largo del tiempo y para identificar las etapas críticas en el desarrollo de la resistencia a diferentes antibióticos. Resultados: se incluyeron 100 artículos donde se evidencia una evolución temporal de la resistencia, desde las primeras cepas resistentes a la penicilina hasta las actuales cepas resistentes a la vancomicina y la daptomicina. Estos estudios proporcionaron un análisis detallado de los mecanismos moleculares clave que impulsan la resistencia antimicrobiana, tales como la producción de beta-lactamasas, las alteraciones en las proteínas de unión a penicilina y las modificaciones en la membrana celular. Los hallazgos destacan una evolución significativa en la capacidad de S. aureus para adaptarse a diferentes antibióticos a lo largo del tiempo, subrayando la complejidad y la diversidad de los mecanismos de resistencia desarrollados por esta bacteria. Conclusiones: la evolución de la resistencia de S. aureus ha seguido un patrón marcado por etapas críticas, desde la aparición de cepas productoras de penicilinasa tras la introducción de la penicilina, hasta el surgimiento de MRSA con la meticilina y de VISA y VRSA con la vancomicina. Estos cambios destacan la capacidad de adaptación de S. aureus a nuevas presiones antibióticas. La revisión subraya la necesidad urgente de desarrollar estrategias antimicrobianas innovadoras y sostenibles para controlar esta creciente amenaza. Comprender los mecanismos de resistencia es crucial para desarrollar enfoques más efectivos y personalizados en el tratamiento de las infecciones por este germen.

Introduction: S. aureus has emerged as a persistent threat, demonstrating a remarkable ability to develop resistance throughout the evolution of antibiotics. From the first confrontations with penicillin to the current challenges with strains resistant to vancomycin and daptomycin, the study of the resistance mechanisms of this pathogen has acquired critical importance. Objectives: To document changes in S. aureus resistance patterns over time and identify critical stages in the development of resistance to different antibiotics. Materials and methods: The reviewed articles were selected by identifying articles published between 2010 and 2023. Several relevant databases were used, including PubMed, Scopus, Embase, Cochrane Library, and SciELO. Observational studies, review articles, and clinical guidelines were included. Specific search strategies were developed for each database using keywords and search terms related to S. aureus and its antimicrobial resistance as well as the types of studies of interest. Relevant data were extracted from the selected studies, including information on resistance patterns, resistance mechanisms, clinical impact, and therapeutic strategies. The collected data were analyzed and synthesized to document changes in S. aureus resistance patterns over time and identify critical stages in the development of resistance to different antibiotics. Results: One hundred articles were included where a temporal evolution of resistance is evident, from the first strains resistant to penicillin to the current strains resistant to vancomycin and daptomycin. These studies provided a detailed analysis of the key molecular mechanisms driving antimicrobial resistance, such as beta-lactamase production, alterations in penicillin-binding proteins, and cell membrane modifications. The findings highlight a significant evolution in the ability of S. aureus to adapt to different antibiotics over time, underscoring the complexity and diversity of resistance mechanisms developed by this bacterium. Conclusions: The evolution of S. aureus resistance has followed a pattern marked by critical stages, from the appearance of penicillinase-producing strains after the introduction of penicillin to the emergence of MRSA with methicillin and of VISA and VRSA with vancomycin. These changes highlight the ability of S. aureus to adapt to new antibiotic pressures. The review highlights the urgent need to develop innovative and sustainable antimicrobial strategies to control this growing threat. Understanding resistance mechanisms is crucial to developing more effective and personalized approaches for the treatment of infections caused by this germ.

Photodynamic inactivation of methicillin-resistant Staphylococcus aureus by using Giemsa dye as a photosensitizer.

The rise of antibiotic-resistant bacteria calls for innovative approaches to combat multidrug-resistant strains. Here, the potential of the standard histological stain, Giemsa, to act as a photosensitizer (PS) for antimicrobial photodynamic inactivation (aPDI) against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains is reported. Bioassays were performed using various Giemsa concentrations (ranging from 0.0 to 20.0 µM) under 625 nm illumination at a light dose of 30 J cm-2. Remarkably, Giemsa completely inhibited the growth of MSSA and MRSA bacterial colonies for concentrations at 10 µM and higher but exhibited no inhibitory effect without light exposure. Partition coefficient analysis revealed Giemsa's affinity for membranes. Furthermore, we quantified the production of reactive oxygen species (ROS) and singlet oxygen (1O2) to elucidate the aPDI mechanisms underlying bacterial inactivation mediated by Giemsa. These findings highlight Giemsa stain's potential as a PS in aPDI for targeting multidrug-resistant bacteria.

QSAR Studies, Synthesis, and Biological Evaluation of New Pyrimido-Isoquinolin-Quinone Derivatives against Methicillin-Resistant Staphylococcus aureus.

According to the WHO, antimicrobial resistance is among the top 10 threats to global health. Due to increased resistance rates, an increase in the mortality and morbidity of patients has been observed, with projections of more than 10 million deaths associated with infections caused by antibacterial resistant microorganisms. Our research group has developed a new family of pyrimido-isoquinolin-quinones showing antibacterial activities against multidrug-resistant Staphylococcus aureus. We have developed 3D-QSAR CoMFA and CoMSIA studies (r2 = 0.938; 0.895), from which 13 new derivatives were designed and synthesized. The compounds were tested in antibacterial assays against methicillin-resistant Staphylococcus aureus and other bacterial pathogens. There were 12 synthesized compounds active against Gram-positive pathogens in concentrations ranging from 2 to 32 µg/mL. The antibacterial activity of the derivatives is explained by the steric, electronic, and hydrogen-bond acceptor properties of the compounds.

First Isolation of Methicillin-Resistant Livestock-Associated Staphylococcus aureus CC398 and CC1 in Intensive Pig Production Farms in Argentina.

Since the mid-2000s, livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been identified among pigs worldwide, CC398 being the most relevant LA-MRSA clone. In the present work, nasal swabs were taken from healthy pigs of different age categories (25 to 154 days) from 2019 to 2021 in four intensive farms located in three provinces of Argentina. The aim of the present study was to characterize the first LA-MRSA isolates that colonized healthy fattening pigs in Argentina in terms of their resistance phenotype and genotype and to know the circulating clones in the country. Antimicrobial susceptibility, presence of the mecA gene and PCR screening of CC398 were evaluated in all the isolates. They were resistant to cefoxitin, penicillin, tetracycline, chloramphenicol and ciprofloxacin but susceptible to nitrofurantoin, rifampicin, vancomycin and linezolid. Furthermore, 79% were resistant to clindamycin and lincomycin, 68% to erythromycin, 58% to gentamicin and 37% to trimethoprim/sulfamethoxazole. All the isolates were multidrug resistant. The clonal relation was assessed by SmaI-PFGE (pulsed-field gel electrophoresis) and a representative isolate of each PFGE type was whole genome sequenced by Illumina. MLST (multilocus sequence typing), resistance and virulence genes and SCCmec typing were performed on sequenced isolates. The isolates were differentiated in three clonal types by PFGE, and they belonged to sequence-type ST398 (58%) and ST9, CC1 (42%) by MLST. SCCmec typeV and several resistance genes detected showed complete correlation with resistance phenotypes. The present study revealed that LA-MRSA colonizing healthy pigs in Argentina belongs to CC398 and CC1, two MRSA lineages frequently associated to pigs in other countries.

Síndrome de compresión medular de etiología infecciosa

El síndrome de compresión medular es una urgencia neuroquirúrgica debido a que un diagnóstico precoz y un tratamiento temprano podría revertir las incapacitantes secuelas ocasionadas por esta enfermedad. Las causas de este síndrome pueden ser traumática, metastásica, infecciosa y vascular (hematomas). La etiología infecciosa no es frecuente y el principal germen involucrado suele ser Staphylococcus aureus. A continuación presentamos el caso de una paciente de 58 años con síndrome de compresión medular de etiología infecciosa quien fue ingresada en el Servicio de Clínica Médica del Centro Médico Nacional.

Spinal cord compression syndrome is a neurosurgical emergency because early diagnosis and early treatment could reverse the disabling consequences caused by this disease. The causes of this syndrome can be traumatic, metastatic, infectious, and vascular (hematomas). Infectious etiology is not frequent and the main germ involved is usually Staphylococcus aureus. Below we present the case of a 58-year-old patient with spinal cord compression syndrome of infectious etiology who was admitted to the Medical Clinic Service of the National Medical Center.

The Diversity and Zoonotic Potential of Staphylococcus pseudintermedius in Humans and Pet Dogs in Trinidad and Tobago.

Staphylococcus pseudintermedius is an opportunistic pathogen that is frequently isolated from canines. It is of escalating interest because of its increasing antimicrobial resistance and zoonotic potential. Although many published articles are available that describe isolates obtained from diseased dogs and humans, this study focused on isolates obtained from healthy dogs and their owners who presented at clinics for routine veterinary care and utilized whole genome sequencing-based analyses for strain comparisons. A total of 25 humans and 27 canines were sampled at multiple sites, yielding 47 and 45 isolates, respectively. Whole genome sequence analysis was performed. We detected mostly new sequence types (STs) and a high diversity. Strains carried few antimicrobial resistance genes and plasmids, albeit three MRSP strains were found that belonged to two internationally distributed STs. The virulence content did not provide insights toward a tendency to colonization of humans but supported that there may be differences in the surface proteins between carrier strains and those causing pyoderma. We identified 13 cases in which humans were infected with strains from the dog they owned.