Resistant Strains Research Articles

Linear and Polyvalent Peptides with Potent Antimicrobial Activity Against Sensitive and Multidrug-Resistant E. coli Clinical Isolates.

Peptides containing the sequences 20RRWQWR25 and 20RRWQWRMKKLG30 derived from Bovine lactoferricin (LfcinB) were synthesized and their antibacterial effect against reference strains and sensitive and resistant clinical isolates of E. coli was evaluated. Tetra-branched multiple antigen peptide (MAP) ((RRWQWR)2-K-Ahx-C)2 exhibited significant antibacterial activity against sensitive, resistant, and multidrug-resistant clinical isolates of E. coli. Peptide 3: RRWQWR-Nal-KKLG; MIC=16 µM, 26[F]: (RRWQWRFKKLG)2-K-Ahx; MIC=15 µM, 17: (RRWQWRFK)2-K-Ahx; MIC=9 µM, and LfcinB (20-25)2: (RRWQWR)2-K-Ahx; MIC=11 µM exhibited the highest antibacterial activity against E. coli strains, with bactericidal effect and haemolytic effect at MIC less than 5% and a therapeutic index >1. A synergistic effect of peptides 26[F] and 17 with ciprofloxacin (CIP) or ceftriaxone (CEF) was observed. Prolonged treatment of E. coli ATCC 25922 with sublethal concentrations of CIP induced resistance in this strain, whereas some peptides did not induce resistance. These peptides can be considered to be promising candidates for treating infections caused by resistant strains of E. coli.

Extract from Psidium guineense Sw leaves: An alternative against resistant strains of Staphylococcus aureus

Psidium guineense SW., commonly known as sour guava, is used in traditional medicine to address diverse health issues, such as inflammation, infections, and gastrointestinal disorders. Although previous research has highlighted the antimicrobial properties of the root extract and the antioxidant potential of its fruits, information regarding the activities associated with the leaf extract is lacking. The aim of the study was to use the traditional knowledge of the biological properties of P. guineense and investigate its antimicrobial activity, mechanism of action, synergistic effects, and antivirulence activity against Staphylococcus aureus. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined for S. aureus, including antibiotic-resistant isolates. The synergy between the extract and antibiotics was evaluated. A growth curve was constructed for S. aureus treated with the extract. The anti-hemolytic activity was assessed by inhibiting hemolysis in human blood, and the inhibition of staphyloxanthin (STX) was examined. The extract effectively inhibited all strains with MIC and MBC values ranging from 256 to 512 µg/mL and 512 to 1024 µg/mL, respectively. Antimicrobial synergy experiments demonstrated the enhanced effectiveness of antibiotics, especially ciprofloxacin, when combined with the P. guineense extract, especially with ciprofloxacin, resulting in complete synergy against all S. aureus strains. In growth curve tests, the extract inhibited growth at MIC of 256 µg/mL within 8 h and significantly delayed it at MIC/2 (128 µg/mL) within 12 h. In antivirulence tests, the extract effectively reduced hemolysis and STX production by S. aureus at MIC and MIC/2, indicating its potential as an antimicrobial agent with antivirulence properties. The extract effectively inhibited S. aureus, including drug-resistant strains with low MIC and MBC values, exhibiting strong antimicrobial and synergistic properties with antibiotics. also In addition, the extract accelerated recovery by limiting bacterial growth and exhibiting antivirulence capabilities, reducing the severe symptoms of S. aureus infections.

Laser NIR Irradiation Enhances Antimicrobial Photodynamic Inactivation of Biofilms of Staphylococcus aureus.

Photodynamic inactivation (PDI) is a powerful technique for eradicating microorganisms, and our group previously demonstrated its effectiveness against planktonic cultures of Staphylococcus aureus bacteria using 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl]porphyrin (TAPP) and visible light irradiation. However, biofilms exhibit a lower sensitivity to PDI, mainly due to limited penetration of the photosensitizer (PS). In the context of emerging antibacterial strategies, near-infrared treatments (NIRTs) have shown promise, especially for combating resistant strains. NIRT can act either through photon absorption by water, causing a thermal effect on bacteria, or by specific chromophores without a significant temperature increase. Our objective was to enhance biofilm sensitivity to TAPP-PDI by pretreatment with NIRT. This combined approach aims to disrupt biofilms and increase the efficacy of TAPP-PDI against bacterial biofilms. In vitro biofilm models of S. aureus RN6390 were utilized. NIRTs involved a 980 nm laser (continuous mode, 7.5 W/cm2, 30 s, totaling 225 J/cm2) post-TAPP exposure to enhance photosensitizer accumulation. Subsequent visible light irradiation at 180 J/cm2 was employed to perform PDI. Colony-forming unit counts evaluated the synergistic effect on bacterial viability. Scanning electron microscopy visualized the architectural changes in the biofilm structure. TAPP was extracted from bacteria to estimate the impact of NIRT on biofilm penetration. Using in vitro biofilm models, NIRT application following biofilm exposure to TAPP increased PS accumulation per bacteria. Under these conditions, NIRT induced a transient increase in the temperature of PBS to 46.0 ± 2.6°C (ΔT = 21.5°C). Following exposure to visible light, a synergistic effect emerged, yielding a substantial 4.4 ± 0.1-log CFU reduction. In contrast, the PDI and NIRT treatments individually caused a decrease in viability of 0.9 ± 0.1 and 0.8 ± 0.2-log respectively. Interestingly, preheating TAPP-PBS to 46°C had no significant impact on TAPP-PDI efficacy, suggesting the involvement of thermal and nonthermal effects of NIR action. In addition to the enhanced TAPP penetration, NIRT dispersed the biofilms and induced clefts in the biofilm matrix. Our findings suggest that NIR irradiation serves as a complementary treatment to PDI. This combined strategy reduces bacterial numbers at lower PS concentrations than standalone PDI treatment, highlighting its potential as an effective and resource-efficient antibacterial approach.

The effectiveness of the HB&L system in bacteriuria determining

Urinary tract infections (UTIs) are characterized by high prevalence in various populations, recurrent course, complications and accumulation of antibiotic resistant strains. Researchers continue to search for objective criteria for the laboratory diagnosis of associated diseases, including methods for determining bacteriuria The implementation of anautomatic bacteriological analyzer into the laboratory practice would make possible to organize screening studies of UTIs with high sensitivity and specificity, in parallel with studies of the resistant phenotypes’prevalence. This will help to create the basis for the development of highly effective and reasonable antibiotic therapy, and, in general, to improve the epidemiological situation associated with these infections.

Targeting the Ubiquitin Proteasome System to Combat Influenza A Virus: Hijacking the Cleanup Crew

ABSTRACTInfluenza A virus (IAV) remains a significant global public health threat, causing substantial illness and economic burden. Despite existing antiviral drugs, the emergence of resistant strains necessitates alternative therapeutic strategies. This review explores the complex interplay between the ubiquitin proteasome system (UPS) and IAV pathogenesis. We discuss how IAV manipulates the UPS to promote its lifecycle, while also highlighting how host cells utilise the UPS to counteract viral infection. Recent research on deubiquitinases as potential regulators of IAV infection is also addressed. By elucidating the multifaceted role of the UPS in IAV pathogenesis, this review aims to identify potential targets for novel therapeutic interventions.

Appropriateness of Empirical Antibiotic Use and Concordence with the WHO Aware Classification in Hospitalized Patients

Background: Antibiotic prescription trends analysis is essential for monitoring the sensitivity and resistance patterns of microorganisms discovered, regularly generating and updating antibiograms, and providing the context for antibiotic usage and prevalence. Specifically, consistent prescription patterns and antibiotic therapy practices with the WHO AWaRe (Access, Watch, and Reserve) classification of antibiotics and the national or WHO essential medicine list would enhance the prudent use of antibiotics, prevent the emergence and spread of antimicrobial resistance, and preserve antibiotic efficacy for future requirements. Objective: This study aimed to analyze selection of antibiotics for empirical use and definitive therapy and to evaluate rational use of antibiotics according to the WHO-AWaRe (Access, Watch, and Reserve) categories in hospitalized patients. Methodology: An observational and cross-sectional study was conducted in a 300 bedded multispecialty tertiary care hospital from October 2022 to March 2023 for a period of six months. Evaluation of demographic data based on antimicrobial susceptibility reports, pathogen characteristics, and infection site; evaluation of antibiotics administered before and after AST reports; and classification of antibiotics using WHO AWaRe metrics from the WHO essential medicines list. Descriptive statistics were applied for the data collected using Microsoft Excel. Results are expressed as total count, frequency, and percentages. Results: Antimicrobial susceptibility results from 162 patients were gathered from the laboratory. Of these 138 (85.18%) patients had positive results for Gram-negative bacteria and 24 (14.81%) for Gram-positive bacteria. The mean (SD) age of patients was 55 ± 28 years; predominantly male patients 92 (56.79%). 107 (66%) patients were hospitalized for 1-5 days. Monotherapy was given in 17 (10.5%) patients, Most of the patients were admitted into the general medicine 94 (58.02%), Bacteria were mainly isolated from urine (65 isolates, 40.1%), and a total of 36 organisms were isolated. The proportions of appropriate empirical therapy use were 84.05% for Gram-negative bacteria. A total of 706 antibiotics were prescribed out of which 334 are prescribed before AST and 372 are prescribed after AST. More prescribed empirical antibiotics were from the ‘Watch’ group (55.69%), followed by the ‘Access’ group (25.75%). ‘Reserve’ category (8.38%) and ‘not-recommended’ category (10.18%) antibiotics were also prescribed. A greater number of prescribed definitive antibiotics were from the ‘Watch’ group (48.11%). ‘Access’ group antibiotics should be preferable to the ‘Watch’ group. ‘Reserve’ antibiotics are always used as the last option when “Access” and “Watch” group antibiotics don’t work. Conclusion: The high use of empirical antibiotics especially from the ‘Watch’ category is a disturbing trend as observed in our study. . Increasing the use of ‘Access' antibiotics while limiting the use of ‘Watch' and ‘Reserve' antibiotics at the same time is the highest priority for preserving effectiveness of important antibiotics and minimizing the danger of AMR. Conducting such studies and analysis of such data periodically would pave the way for promotion of rational use of antimicrobials and help restrict the emergence of resistant strains of bacteria.

Susceptibility of Leishmania amazonensis Axenic Amastigotes to the Calpain Inhibitor MDL28170

Leishmaniasis encompasses a group of neglected diseases caused by flagellated protozoa belonging to the Leishmania genus, associated with high morbidity and mortality. The search for compounds with anti-Leishmania activity that exhibit lower toxicity and can overcome the emergence of resistant strains remains a significant goal. In this context, the calpain inhibitor MDL28170 has previously demonstrated deleterious effects against promastigote forms of Leishmania amazonensis, which led us to investigate its role on axenic amastigote forms. The calpain inhibitor MDL28170 was able to decrease the viability of amastigotes in a typically dose-dependent manner. The treatment with the IC50 dose (13.5 μM) for 72 h led to significant amastigote lysis and increased cell-to-cell aggregation. Ultrastructural analysis revealed several cellular alterations, including disruption of the trans-Golgi network and the formation of autophagosomes when treated with MDL28170 at ½ × IC50 dose. Additionally, mitochondrial swelling and the formation of concentric membranous structures inside the mitochondrion were observed after incubation with the IC50 dose. These results reinforce the potential application of the calpain inhibitor MDL28170 against L. amazonensis, highlighting its effectiveness and possible mechanism of action against the parasite.

Cytotoxic effects of ivermectin on Giardia lamblia: induction of apoptosis and cell cycle arrest

IntroductionGiardia lamblia is a flagellated protozoan parasite causing giardiasis, a common intestinal infection characterized by diarrhea, abdominal cramps, and nausea. Treatments employed to combat this parasitic infection have remained unchanged for the past 40 years, leading to the emergence of resistant strains and prompting the search for new therapeutic agents.MethodsThis study investigated the cytotoxic effects of ivermectin (IVM) on G. lamblia trophozoites. We conducted dose-response experiments to assess IVM-induced cytotoxicity. We utilized various biochemical and ultrastructural analyses to explore the underlying mechanisms of cell death, including reactive oxygen species (ROS) production, DNA fragmentation, cell cycle arrest, and apoptosis markers.ResultsOur findings demonstrate that IVM induces dose-dependent cytotoxicity and triggers cell death pathways. We found that IVM treatment generates elevated levels of reactive oxygen species (ROS), DNA fragmentation, and arrests of trophozoites in the cell cycle’s S phase. Additionally, ultrastructural analysis reveals morphological alterations consistent with apoptosis, such as cytoplasmic vacuolization, chromatin condensation, and tubulin distribution.DiscussionThe insights gained from this study may contribute to developing new therapeutic strategies against giardiasis, addressing the challenge posed by drug-resistant strains.

Nano Revolution: Harnessing Nanoparticles to Combat Antibiotic-resistant Bacterial Infections.

Nanoparticles, defined as particles ranging from 1 to 100 nanometers in size, are revolutionizing the approach to combating bacterial infections amid a backdrop of escalating antibiotic resistance. Bacterial infections remain a formidable global health challenge, causing millions of deaths annually and encompassing a spectrum from common illnesses like Strep throat to severe diseases such as tuberculosis and pneumonia. The misuse of antibiotics has precipitated the rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Mycobacterium tuberculosis (MDR-TB), and carbapenem-resistant Enterobacteriaceae (CRE), underscoring the critical need for innovative therapeutic strategies. Nanotechnology offers a promising avenue in this crisis. Nanoparticles possess unique physical and chemical properties that distinguish them from traditional antibiotics. Their high surface area to volume ratio, ability to be functionalized with various molecules, and distinctive optical, electronic, and magnetic characteristics enable them to exert potent antibacterial effects. Mechanisms include physical disruption of bacterial membranes, generation of Reactive Oxygen Species (ROS), and release of metal ions that disrupt bacterial metabolism. Moreover, nanoparticles penetrate biofilms and bacterial cell walls more effectively than conventional antibiotics and can be precisely targeted to minimize off-target effects. Crucially, nanoparticles mitigate the development of bacterial resistance by leveraging multiple simultaneous mechanisms of action, which make it challenging for bacteria to adapt through single genetic mutations. As research advances, nanotechnology holds immense promise in transforming antibacterial treatments, offering effective solutions that address current infections and combat antibiotic resistance globally. This review provides a comprehensive overview of nanoparticle applications in antibacterial therapies, highlighting their mechanisms, advantages over antibiotics, and future directions in healthcare innovation.

Genomic Epidemiology of Antimicrobial Resistance: Tracking the Global Spread of Resistant Pathogens

The rapid development and spread of antimicrobial resistance have been one of the most prominent health crises globally, which significantly challenges treating infectious diseases. This paper will address the contribution that genomic epidemiology makes to track and understand the global spread of antimicrobial-resistant pathogens. Genomic epidemiology, an area combining pathogen genomics with epidemiological data, allows for an extremely powerful approach in the identification of resistance mechanisms and tracing transmission routes for guiding public health interventions. This review Emphasizes major bacterial pathogens, such as Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae, which harbor major resistance genes: blaCTX-M, mecA, and blaKPC. These genes contribute to the worldwide dissemination of resistance, mainly through mechanisms involving horizontal gene transfer and selective antibiotic pressure. Thus, genomic surveillance, phylogenetic analysis, and bioinformatics approaches allow for the pinpointing of transmission hotspots, mapping of resistance gene distribution, and tracking of emerging resistant strains in real time. It also provides information on how genomic data are being used to improve antimicrobial stewardship programs and inform clinical treatment decisions. Public health responses can further be tailored by recognizing regional resistance patterns, hence enhancing interventions. However, several challenges persist—for example, the need for standardized sharing of data, interpretation of genomic data, and integration of these insights into public health systems, especially in low-resource settings. This abstract highlights the transformative impact of genomic epidemiology in the management of the AMR crisis while emphasizing the continued need for global cooperation, enhanced data infrastructures, and policy initiatives to ensure the effective use of genomic data in public health.

Rosmarinic Acid Exhibits Antifungal and Antibiofilm Activities Against Candida albicans: Insights into Gene Expression and Morphological Changes

Candida species, opportunistic pathogens that cause various infections, pose a significant threat due to their ability to form biofilms that resist antifungal treatments and immune responses. The increasing resistance of Candida spp. and the limited availability of effective treatments have prompted the research of natural compounds as alternative therapies. This study assessed the antifungal properties of RA against Candida species, focusing on its impact on C. albicans biofilms and the underlying mechanisms. The antifungal efficacy of RA was evaluated using the CLSI M27-A3 microdilution method on both fluconazole-susceptible and -resistant strains. Biofilm formation by C. albicans was assessed through a crystal violet assay, while its antibiofilm activity was analyzed using an MTT assay and field emission scanning electron microscopy (FESEM). Gene expression related to biofilm formation was studied using quantitative real-time PCR (qRT-PCR), and statistical analysis was performed with an ANOVA. Among the 28 Candida strains tested, RA exhibited minimum inhibitory concentration (MIC) values ranging from 160 to 1280 μg/mL. At a 640 μg/mL concentration, it significantly reduced the expression of genes associated with adhesion (ALS3, HWP1, and ECE1), hyphal development (UME6 and HGC1), and hyphal cAMP-dependent protein kinase regulators (CYR1, RAS1, and EFG1) in RAS1-cAMP-EFG1 pathway (p < 0.05). FESEM analysis revealed a reduction in hyphal networks and disruptions on the cell surface. Our study is the first to demonstrate the effects of RA on C. albicans adhesion, hyphae development, and biofilm formation through gene expression analysis with findings supported by FESEM. This approach distinguishes our study from previous studies on the effect of RA on Candida. However, the high MIC values of RA limit its antifungal potential. Therefore, more extensive research using innovative methods is required to increase the antifungal effect of RA.

Polydopamine-Mediated Antimicrobial Lipopeptide Surface Coating for Medical Devices.

Biofilm formation on medical implants such as catheters is a major issue which needs to be addressed as it leads to severe health care associated infections. This study explored the design and synthesis of a polydopamine-lipopeptide based antimicrobial coating. The coating was used to modify the surface of Ultrathane Catheters. The lipopeptide SL1.15 with an N-terminal cysteine was covalently conjugated to the polydopamine modified catheters via a Michael addition reaction between the thiol moiety in the peptide and the aromatic ring in the polydopamine layer. The immobilization of the peptide on the polydopamine coated catheters was confirmed using water contact angle, X-ray photoelectron spectroscopy, atomic force microscopy, and scanning electron microscopy (SEM). The antimicrobial activity of the coated catheters investigated using drug resistant and clinical strains of Gram-positive (MRSA and S. aureus) and Gram-negative (E. coli, A. baumannii, and P. aeruginosa) bacteria revealed that lipopeptide immobilization inhibited >90% bacterial adhesion to the catheter surface. Additionally, biofilm assays against MRSA and E. coli revealed that the lipopeptide immobilized catheters inhibited >85% bacterial growth after 1 week incubation. Finally, the cytotoxicity profile of the catheters using the human dermal fibroblast, and the human embryonic kidney cell lines demonstrated that the polydopamine-lipopeptide coating was not toxic after 72 h incubation.

Unleashing the synergistic effect of promising fungicides: a breakthrough solution for combating powdery mildew in pea plants

Pea powdery mildew, caused by Erysiphe pisi, is a major limitation to global pea production. The emergence of fungicide-resistant pathogen populations due to frequent and injudicious pesticide application highlights the importance of exploring the synergistic properties of fungicide combinations. This study investigated the efficacy of difenoconazole, thiophanate-methyl, and sulfur, both individually and in mixtures, against powdery mildew and assessed the interaction types between these fungicides. The results demonstrated that the combination of difenoconazole, thiophanate-methyl, and sulfur was the most effective in reducing, reducing disease severity to 6.10% and minimizing conidial production on foliage. Additionally, this fungicide combination reduced conidial germination by 89.26% in vitro and by 87.50% in a detached leaf assay compared to the control. The treatment also positively impacted leaf chlorophyll content (55.18), green pod yield (22.21 tons ha−1), seed yield (12.29 tons ha−1), and other yield-related parameters. Although statistically significant, this ternary fungicide combination was closely followed by the binary combination of thiophanate-methyl and sulfur, which was the only combination exhibiting synergism in both laboratory and field trials with a synergy factor (SF) > 1. In conclusion, this approach offers improved disease control as part of integrated disease management (IDM) while minimizing the risk of resistant pathogen strains.

Anti-quorum sensing activity of essential oils against multidrug-resistant Klebsiella pneumoniae: a novel approach to control bacterial virulence.

The increasing resistance of microbes to conventional drugs is a serious problem worldwide that has increased the need for alternative antimicrobial compounds. Naturally occurring essential oils (EOs) are considered an important component of traditional pharmacopeia because of their antimicrobial and antioxidant properties. This has attracted researchers to identify novel therapeutic anti-pathogenic agents that could act as non-toxic quorum sensing inhibitors, thus controlling infections without encouraging the development of bacterial resistance. This prompted to undertake the current investigation to unravel the efficacy of EOs as QS modulators in reducing the virulence of multidrug resistant (MDR) strains ofKlebsiella pneumoniae. The study highlighted the anti-QS activity of fifteen EOs in modulating the QS-related traits by a reduction in capsular polysaccharide, exopolysaccharide and siderophore production in addition to inhibition of biofilm formation. The overall results suggest using EOs to develop alternate intervention strategies to mitigate infections caused by MDR strains ofK. pneumoniae.

Current antibiotic resistance of Enterobacteriaceae isolated at Avicenna military hospital of Marrakesh

Enterobacteriaceae are bacteria found in the digestive system, known for causing infections and displaying antibiotic resistance. The World Health Organization (WHO) identifies strains resistant to third-generation cephalosporins and carbapenems as priority pathogens. This study, conducted at Avicenne Military Hospital of Marrakech, aimed to assess the epidemiological and antibiotic resistance profiles of Enterobacteriaceae over a two-year period (May 2020 - April 2022) to inform updated antibiotic use recommendations. This retrospective study analyzed 1,626 positive bacterial isolates from various hospital departments, including medical, surgical, intensive care, emergency units, and external samples. Of these, 1,163 (71.5%) were Enterobacteriaceae, predominantly Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, primarily isolated from urine, pus, and blood cultures. Antibiotic resistance was assessed, revealing that 614 (52.8%) of Enterobacteriaceae were extended-spectrum beta-lactamase producers (ESBL-E), and 115 (9.9%) were carbapenemase-producing Enterobacteriaceae (CPE). The study’s findings align with existing literature, showing a higher prevalence of Enterobacteriaceae in males and frequent isolation of Escherichia coli. The rise in multidrug-resistant Enterobacteriaceae, particularly ESBL-E and CPE, poses risks such as therapeutic failure, increased morbidity and mortality, and significant economic impacts. To address this, the study emphasizes the importance of early detection, infection control measures, responsible antibiotic prescribing, and collaborative efforts across hospital departments to reduce the spread of resistant strains.

Cannabinoids as Antibacterial Agents: A Systematic and Critical Review of In Vitro Efficacy Against Streptococcus and Staphylococcus

Background: Two major bacterial pathogens, Staphylococcus aureus and Streptococcus pyogenes, are becoming increasingly antibiotic-resistant. Despite the urgency, only a few new antibiotics have been approved to address these infections. Although cannabinoids have been noted for their antibacterial properties, a comprehensive review of their effects on these bacteria has been lacking. Objective: This systematic review examines the antibacterial activity of cannabinoids against S. aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains, and S. pyogenes. Methods: Databases, including CINAHL, Cochrane, Medline, Scopus, Web of Science, and LILACS, were searched. Of 3510 records, 24 studies met the inclusion criteria, reporting on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration of cannabinoids. Results: Cannabidiol (CBD) emerged as the most effective cannabinoid, with MICs ranging from 0.65 to 32 mg/L against S. aureus, 0.5 to 4 mg/L for MRSA, and 1 to 2 mg/L for VRSA. Other cannabinoids, such as cannabichromene, cannabigerol (CBG), and delta-9-tetrahydrocannabinol (Δ9-THC), also exhibited significant antistaphylococcal activity. CBD, CBG, and Δ9-THC also showed efficacy against S. pyogenes, with MICs between 0.6 and 50 mg/L. Synergistic effects were observed when CBD and essential oils from Cannabis sativa when combined with other antibacterial agents. Conclusion: Cannabinoids’ antibacterial potency is closely linked to their structure–activity relationships, with features like the monoterpene region, aromatic alkyl side chain, and aromatic carboxylic groups enhancing efficacy, particularly in CBD and its cyclic forms. These results highlight the potential of cannabinoids in developing therapies for resistant strains, though further research is needed to confirm their clinical effectiveness.

Unveiling environmental transmission risks: comparative analysis of azole resistance in Aspergillus fumigatus clinical and environmental isolates from Yunnan, China.

Azole resistance in Aspergillus fumigatus poses a significant clinical challenge globally. Our previous epidemiological analysis revealed a remarkably high frequency (~80%) of azole-resistant A. fumigatus in Yunnan's greenhouse environments, prompting increased local and regional research for targeted control strategies. In this study, we analyzed 94 clinical A. fumigatus isolates from Yunnan, comparing their susceptibility profiles and genotypic characteristics with environmental strains previously isolated. While the overall frequency of azole resistance in clinical isolates was lower than that in environmental samples, a significant prevalence of cross-resistance, with varying resistance patterns based on minimum inhibitory concentration (MIC) levels was observed, which exceeded rates in other regions of China. Specific mutation combinations in the cyp51A gene were linked to elevated MIC values in clinical and/or environmental samples, while some resistant strains with wild-type cyp51A remain unexplained, indicating a need for further investigation into their resistance mechanisms. The differences in unique genetic elements and the distinct genetic differentiation observed between clinical and environmental isolates can be attributed to Yunnan's unique geomorphology and potential genotype importation from other provinces and abroad. Extensive allele exchanges and sharing contributed to the selection of azole-resistant clinical isolates, suggesting a common environmental origin, and the transmission routes of local drug-resistant strains cannot be excluded. These findings emphasize the imperative for regional and targeted surveillance to monitor resistance trends and guide effective antifungal therapy, and management strategies to mitigate invasive aspergillosis risk in this region.IMPORTANCEAzole resistance in Aspergillus fumigatus is a major global health concern, with particularly high rates (~80%) observed in Yunnan's greenhouse environments. This study compares azole resistance in 94 clinical isolates from Yunnan with environmental strains, revealing lower clinical resistance but significant cross-resistance and distinct resistance patterns. Specific mutations in the cyp51A gene were associated with elevated minimum inhibitory concentration values, though some resistant strains had wild-type cyp51A, highlighting the need for further research. The unique genetic profiles and potential external genotype influences in Yunnan emphasize the need for targeted regional surveillance. Effective monitoring and control strategies are essential to manage and mitigate the risk of invasive aspergillosis.

Cefoxitin and Oxacillin Resistance Conundrums

Recently, mecA-negative Staphylococcus aureus strains with decreased susceptibility to oxacillin and cefoxitin have been sporadically reported worldwide. They are called as borderline oxacillin resistant Staphylococcus aureus (BORSA). Almost, more than 30% of such strains are often misinterpreted and reported as MRSA (methicillin resistant Staphylococcus aureus) due to the hyperproduction of beta-lactamase enzyme and other reasons which results in invitro reduced susceptibility to oxacillin as well as cefoxitin. Similar phenomenon is quite common in other staphylococci, micrococci and macrococci. In order to identify beta-lactamase hyperproducing staphylococci and other gram-positive cocci and to avoid false reporting as methicillin resistant, a one-year prospective study was conducted in Deccan college of medical sciences, Hyderabad, Telangana state, India in 2023. During one year duration, 5630 inpatient (IP) and 823 outpatient (OPD) samples accounting for total 6453 cultures were received in the microbiology laboratory. Out of this,100 cultures of different samples showing pure growth of gram-positive cocci suggestive of staphylococci, micrococci and other Gram-positive cocci were included in the present study and tested against different antibiotics panel as per CLSI guidelines (Clinical and Laboratory Standards Institute.) Inclusion of amoxiclav disc to the antibiotics test panel as per recommendation by the special phenotypic methods for the detection of antibacterial resistance in the manual of clinical microbiology was helpful to detect the beta-lactamase hyperproducers (BHP) and helped to report correct identification of the organisms and curtailed the mismanagement of more than 95% of the patients. Therefore, I do recommend to differentiate borderline from true methicillin resistant strains to streamline the antibiotic therapy and hence further avoidance of selection of the resistant strains.

Antibiotic resistant Pseudomonas aeruginosa in dental unit waterline: a case study in Milan (Italy)

Abstract P.aeruginosa (Pa) is one of the most serious cause of healthcare-associated bacteremia, well-known for its antibiotic resistance (AR). Pa has often been found in dental unit water representing a great risk in public health. Aims are to evaluate the presence of Pa in dental unit (DU) water and its phenotypic and genotypic properties. Pa isolates derive from a monitoring of DU water in an Italian hospital (Milan). Samples were collected on Monday and on Friday, before the beginning and after the end of activities. Resistant PA strains were characterized by phenotypic method using E-test for 6 different classes of antibiotics, and by genotypic method with Whole-genome sequencing (WGS). Resistance genes were annotated with ResFinder v. 4.5 and Sequence Type (ST) was determined using the PA MLST database. 70/272 strains were identified as Pa and 21 of them were AR to one or more antibiotics. They were detected in 10/44 (22.7%) DUs and 2/4 (50%) control sinks (1-2000UFC/100mL). WGS was obtained for 18 strains. 17 belonged to serogroup O11 and ST667 was prevalent (8/18) followed by ST395 (4/18). At the ground floor ST395 was the most prevalent, followed by ST667 and 260, while, at the first floor, ST309 and 667 were in the two controls and ST667, 3245 and 260 in the other DUs. Resistant genes blaPAO, aph(3’)-IIb, catB7 conferring resistance to β-lactams, aminoglycosides and amphenicol, respectively, were observed in all isolates. Only ST3245 strain did not show resistance to Fosfomycin. Genotypic and phenotypic analyses present some discrepancies with the presence of AR genes and no antibiotic resistance detection (4/18) or resistance to other different classes of antibiotics (6/18). The MLST analyses showed a high diversity, with the presence of strains sharing different antibiotic resistance mechanisms in DU water. Detection and analyses by WGS can help to track dissemination of genetic resistance determinants and potential emergence of high-risk clones. Key messages • Phenotypic and genotypic analyses in DU water are needed to evaluate risk for human health, in addition to routine microbial monitoring. • WGS can help to track dissemination of genetic resistance determinants and potential emergence of high-risk clones.

Non-Chemical Control of Nymphal Longhorned Tick, Haemaphysalis longicornis Neumann 1901 (Acari: Ixodidae), Using Diatomaceous Earth

The longhorned tick (LHT), Haemaphysalis longicornis Neumann (Acari: Ixodidae), is a serious invasive pest in North America where its geographical range is expanding with high densities associated with commercial animal production. There are only a few chemical pesticides available for LHT control, which can lead to the evolution of resistant strains. Diatomaceous earth (DE) was shown to be effective in killing some important tick species but was not examined for LHTs. When LHT nymphs were dipped for about 2–4 s into DE, transferred to Petri dishes (one tick/dish), and incubated at 30 °C and 70% relative humidity, the median survival time was 4.5 h. A locomotor activity assay showed that there was no difference in the overall distance traveled between the DE-treated and control ticks except during the first 2 h after exposure. In a field-simulated study in which a dose of 5.0 g DE/m2 was applied to pine needle litter infested with LHT, all the LHTs were dead at 24 h with no control mortality. Scanning electron micrographs showed the mineral adhering to all surfaces of the tick. The results indicated that DE is effective in killing nymphal LHTs and could be an alternative to the use of chemical acaricides with the advantage of managing pesticide resistance through the killing by a different mode of action and could be used for organically certified animal husbandry.