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Background: Resistance to carbapenem, the last line of treatment for gram-negative bacterial infections has been increasing globally and becoming a public health threat. Since integrons may aid in the transmission of resistance genes, the purpose of this study was to detect the frequency of class 1, 2, and 3 integrons as well as carbapenem-resistant genes in clinical isolates of P. aeruginosa that are resistant to carbapenem. Methods: This study was carried out on 97 clinical isolates of P. aeruginosa isolated from wound and urine samples. The antimicrobial susceptibility for all isolates was tested by the disc diffusion method. The presence of integrons and carbapenem-resistant genes among carbapenem-resistant P. aeruginosa isolates was evaluated by conventional PCR. Results: The antimicrobial resistance rate among P. aeruginosa clinical isolates was high, with imipenem resistance in 58.8% of the studied isolates. In this study, 86% of the carbapenem-resistant P. aeruginosa isolates carry carbapenemase genes, with blaVIM being the most common gene followed by the blaOXA−48 gene. Class 1 and class 2 integrons were reported in 37 (64.9%) and 10 (17.5%) of the tested carbapenem-resistant P. aeruginosa isolates, respectively. Conclusion: Our data reported a high prevalence of class 1 integrons in carbapenem-resistant P. aeruginosa clinical isolates, suggesting the important role of integrons in carbapenem-resistant gene transfer among such isolates. [ABSTRACT FROM AUTHOR]

The global public health addiction crisis has been stark, with over 932,400 deaths in the USA and Canada from opioid overdose since 1999–2020, surpassing the mortality rates at the top of the HIV/AIDS epidemic. Both nations exhibit opioid consumption rates significantly above the norm for developed countries. Analgesic type of opioids present both therapeutic benefits and substantial health risks, necessitating balanced drug regulation, careful prescribing, and dedicated opioid stewardship. The role of the cytochrome P450 2D6 (CYP2D6) system (Enzymatic functions) in metabolizing opioids highlights the potential of genotype-guided analgesia. By integrating Pharmacogenomics (PGx), this approach aims to optimize pain management, enhance safety, and reduce addiction risks. This understanding prompted the utilization of multifactor dimensionality reduction (MDR) to explore a range of phenotypes including PGx and gene–gene interactions (GGI) in a healthy cohort, thereby personalizing pain management strategies. The study sampled 100 unrelated healthy Western Iranians and 100 individuals from the 1000 Genome Project. Pre-testing involved searching for PGx annotations (variants associated with drug-gene-diseases) related to pain sensitivity and inflammation using the PharmGKB database, which identified 128 relevant genes. A questionnaire helped select 100 participants who had never used potent opioids but also other psychoactive agents (e.g., nicotine, amphetamines, etc.) and disease-related drugs. Whole-exome sequencing (WES) was then employed to analyze these genes in an Iranian cohort. Further analyses included MDR for identifying synergistic gene annotations and GGI for exploring complex gene interactions through the Visualization of Statistical Epistasis Networks (ViSEN). The study identified a Pain, Anti-Inflammatory, and Immunomodulating agents (PAIma) panel from the 128 genes, resulting in 55,590 annotations across 21 curated pathways. After filtering, 54 significant structural or regulatory variants were identified. This research also highlighted novel gene relationships involving the CYP3A5 gene, hsa-miR-355-5p, Paliperidone, and CYP2D6, which warrant further investigation. This study offers a novel pharmacogenetic framework that could potentially transform opioid prescribing practices to mitigate misuse and enhance personalized pain management. Further validation of these findings from multi countries and ethnic groups could guide clinicians in implementing DNA-based opioid prescribing, aligning treatment more closely with individual genetic profiles. [ABSTRACT FROM AUTHOR]

Overexpression of permeability-glycoprotein (P-gp) transporter leads to multidrug resistance (MDR) through cellular exclusion of chemotherapeutics. Co-administration of P-gp inhibitors and chemotherapeutics is a promising approach for improving the efficacy of therapy. Nevertheless, problems in pharmacokinetics, toxicity and solubility limit the application of P-gp inhibitors. Herein, we developed a novel all-in-one hybrid nanoparticle system to overcome MDR in doxorubicin (DOX)-resistant breast cancer. First, folic acid-modified DOX-loaded mesoporous silica nanoparticles (MSNs) were prepared and then loaded into PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles along with a P-gp inhibitor, elacridar. This hybrid nanoparticle system had high drug loading capacity, enabled both passive and active targeting of tumour tissues, and exhibited sequential and pH-triggered release of drugs. In vitro and in vivo studies in DOX-resistant breast cancer demonstrated the ability of the hybrid nanoparticles to reverse P-gp-mediated drug resistance. The nanoparticles were efficiently taken up by the breast cancer cells and delivered elacridar, in vitro. Biodistribution studies demonstrated substantial accumulation of the folate receptor-targeted PLGA/MSN hybrid nanoparticles in tumour-bearing mice. Moreover, deceleration of the tumour growth was remarkable in the animals administered with the DOX and elacridar co-loaded hybrid nanoparticles when compared to those treated with the marketed liposomal DOX (Caelyx®) or its combination with elacridar. [ABSTRACT FROM AUTHOR]

Simple Summary: Public health concerns continue about the spread of colistin resistance, especially after the discovery of the mobile colistin resistance (mcr) gene in Eschierichia coli a decade ago, which could potentially transfer resistance to other bacteria, posing risks to humans, animals and the environment. This study investigated the presence of colistin-resistant and ESBL-producing E. coli in both conventional indoor and organic outdoor Wallon meat lambs from birth to slaughter. Assessing n = 109 fecal samples in 2020 and 2021, 15% of E. coli isolates from conventional sheep showed reduced sensitivity to colistin, and 8% of these were multi-resistant. Genetic analysis showed the resistance was due to chromosomal mutations rather than the mcr-1 gene. In contrast, no resistant E. coli was isolated from the n = 32 samples from organic sheep, potentially due to different husbandry practices. The results highlight the importance of careful antimicrobial use and strict hygiene during slaughter to minimize risks to consumers, aligning with the One Health approach. Major efforts have been made to reduce the use of colistin in livestock since the discovery of the plasmid-borne mobile colistin resistance (mcr) gene in E. coli a decade ago, to curb the burden of its potential transmission to other bacterial species, spread between animals, humans and the environment. This study explored the longitudinal prevalence and characteristics of colistin-resistant and extended-spectrum beta-lactamase-producing (ESBL) E. coli via in vivo fecal and ex vivo carcass swabs from two batches of conventional indoor and organic outdoor Wallon meat sheep from birth to slaughter in 2020 and 2021. Antimicrobial susceptibility testing via broth microdilution revealed that n = 16/109 (15%) E. coli isolates from conventional meat lamb fecal samples had a reduced colistin sensitivity (MIC = 0.5 μg/mL) and thereof, n = 9/109 (8%) were multi-drug-resistant E. coli, while no resistant isolates were recovered from their carcasses. Sequencing revealed causative pmrB genes, indicating that the reduced sensitivity to colistin was not plasmid-borne. While the sample size was small (n = 32), no colistin-resistant and ESBL-producing E. coli were isolated from the organic meat sheep and their carcasses, potentially due to the different husbandry conditions. Prudent and judicious antimicrobial use and strict slaughter hygiene remain imperative for effective risk management to protect consumers in a sustainable One Health approach. [ABSTRACT FROM AUTHOR]

Alpha-helical AMPs' specific targeting on both cell wall and cytoplasmic membrane of Gram-positive S. aureus , and their obvious behaviour of inducing membrane microphase-separation in bacterial killing. [Display omitted] Multidrug resistance (MDR) is a rising threat to global health because the number of essential antibiotics used for treating MDR infections is increasingly compromised. In this work we report a group of new amphiphilic peptides (AMPs) derived from the well-studied G 3 (G(IIKK) 3 I-NH 2) to fight infections from Gram-positive bacteria including susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA), focusing on membrane interactions. Time-dependent killing experiments revealed that substitutions of II by WW (GWK), II by FF (GFK) and KK by RR (GIR) resulted in improved bactericidal efficiencies compared to G 3 (GIK) on both S. aureus and MRSA, with the order of GWK > GIR > GFK > GIK. Electronic microscopy imaging revealed structural disruptions of AMP binding to bacterial cell walls. Fluorescence assays including AMP binding to anionic lipoteichoic acids (LTA) in cell-free and cell systems indicated concentration and time-dependent membrane destabilization associated with bacterial killing. Furthermore, AMP's binding to anionic plasma membrane via similar fluorescence assays revealed a different extent of membrane depolarization and leakage. These observations were supported by the penetration of AMPs into the LTA barrier and the subsequent structural compromise to the cytoplasmic membrane as revealed from SANS (small angle neutron scattering). Both experiments and molecular dynamics (MD) simulations revealed that GWK and GIR could make the membrane more rigid but less effective in diffusive efficiency than GIK and GFK through forming intramembrane peptide nanoaggregates associated with hydrophobic mismatch and formation of fluidic and rigid patches. The reported peptide-aggregate-induced phase-separation emerged as a crucial factor in accelerated membrane disintegration and fast bacterial killing. This work has demonstrated the importance of membrane interactions to the development of more effective AMPs and the relevance of the approaches as reported in assisting this area of research. [ABSTRACT FROM AUTHOR]

After the pandemic COVID-19, global health agencies remind us that tuberculosis is the deadliest infectious disease worldwide. As per WHO reports, approximately ten million people are infected with tuberculosis every year. Only a small portion of global cases receive imperative life-saving medicines. Even in the face of enduring efforts in the discovery of effective management of tuberculosis, the disease remains to affect millions of patients worldwide, with a high rate of morbidity and mortality. Considering the low treatment success, high drug treatment failure, and resistance to existing antituberculosis drugs, there is an urgency for the development of new chemical entities as antituberculosis agents. The development of resistance in tuberculosis (TB) patients to the medications used to treat and prevent the disease presents a significant challenge worldwide. Extensive research confines the molecules to counteract this disease has led to identifying many inhibitory pharmacophores. A wide range of compounds has been screened to find a novel ideal drug candidate for curing tuberculosis. Chalcone and its derivatives are considered precursors of flavonoids and isoflavonoids and display a diverse array of reported pharmacological activities including anti-inflammatory and antituberculosis activities. As this field continues to evolve, these molecules present further opportunities for understanding the mechanism of antituberculosis action and the treatment of MDR. Here, we summarize the impact of chalcone derivatives in tuberculosis treatment. The current statuses of various synthetic chalcone-based approaches for tuberculosis treatment are systematically reviewed here. [ABSTRACT FROM AUTHOR]

The Global increase in colonization by multidrug-resistant (MDR) bacteria poses a significant concern. The precise impact of MDR colonization in solid organ transplant recipients (SOTR) remains not well established. To assess the impact of MDR colonization on SOTR's mortality, infection, or graft loss. Data from PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library, ProQuest Dissertations, Theses Global, and SCOPUS were systematically reviewed, spanning from inception until 20 March 2023. The study protocol was registered with PROSPERO (CRD42022290011) and followed the PRISMA guidelines. Cohorts and case–control studies that reported on adult SOTR colonized by Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase (ESBL) or carbapenem-resistant Enterobacteriaceae. (CRE), or MDR-pseudomonas, and compared to noncolonized, were included. Two reviewers assessed eligibility, conducted a risk of bias evaluation using the Newcastle-Ottawa Scale, and rated certainty of evidence using the GRADE approach. We employed RevMan for a meta-analysis, using random-effects models to compute pooled odds ratios (OR) and 95% confidence intervals (CI). Statistical heterogeneity was determined using the I2 statistic. 15,202 SOTR (33 cohort, six case–control studies) were included, where liver transplant and VRE colonization (25 and 14 studies) were predominant. MDR colonization significantly increased posttransplant 1-year mortality (OR, 2.35; 95% CI, 1.63–3.38) and mixed infections (OR, 10.74; 95% CI, 7.56–12.26) across transplant types (p < 0.001 and I2 = 58%), but no detected impact on graft loss (p 0.41, I2 = 0). Subgroup analysis indicated a higher association between CRE or ESBL colonization with outcomes (CRE: death OR, 3.94; mixed infections OR, 24.8; ESBL: mixed infections OR, 10.3; no mortality data) compared to MRSA (Death: OR, 2.25; mixed infection: OR, 7.75) or VRE colonization (Death: p 0.20, mixed infections: OR, 5.71). MDR colonization in SOTR, particularly CRE, is associated with increased mortality. Despite the low certainty of the evidence, actions to prevent MDR colonization in transplant candidates are warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: The emergence of the global problem of multi-drug resistant bacteria (MDR) is closely related to the improper use of antibiotics, which gives birth to an urgent need for antimicrobial innovation in the medical and health field. Silver nanoparticles (AgNPs) show significant antibacterial potential because of their unique physical and chemical properties. By accurately regulating the morphology, size and surface properties of AgNPs, the antibacterial properties of AgNPs can be effectively enhanced and become a next generation antibacterial material with great development potential. OBJECTIVE: The detection of the inhibitory effect of AgNPs on MDR provides more possibilities for the research and development of new antimicrobial agents. METHODS: Promote the formation of AgNPs by redox reaction; determine the minimum inhibitory concentration (MIC) of AgNPs to bacteria by broth microdilution method; evaluate the killing efficacy of AgNPs against multi-drug-resistant bacteria by plate counting; evaluate the inhibitory effect of AgNPs on biofilm construction by crystal violet staining; study the drug resistance of bacteria by gradually increasing the concentration of AgNPs; and detect the toxicity of AgNPs to cells by CCK-8 method. RESULTS: AgNPs has a significant bactericidal effect on a variety of drug-resistant bacteria. After exposure to AgNPs solution for 12 hours, the number of E. coli decreased sharply, and S. aureus was basically eliminated after 16 hours. In particular, AgNPs showed stronger inhibition against Gram-negative bacteria. In addition, AgNPs can effectively hinder the formation of bacterial biofilm, and its inhibitory effect increases with the increase of AgNPs solution concentration. When AgNPs is used for a long time, the development of bacterial resistance to it is slow. From the point of view of safety, AgNPs has no harmful effects on organisms and has biosafety. CONCLUSION: AgNPs can inhibit MDR, and the bacteriostatic ability of Gram-negative bacteria is higher than that of Gram-positive bacteria. It can also inhibit the formation of bacterial biofilm, avoid drug resistance and reduce cytotoxicity. [ABSTRACT FROM AUTHOR]

The urgency of multidrug-resistant (MDR) bacterial infections in wounds is a significant concern due to the high prevalence of MDR in healthcare settings. Black pigmented marine bacteria, strain PS1C, were isolated from marine sediment on Awur Beach Jepara, Central Java, Indonesia, and cultured in the laboratory. The aim of this research includes molecular identification of strain PS1C, extracting black pigment from strain PS1C, isolation of MDR bacteria from wounds, and evaluating the antibacterial activity of black pigment from strain PS1C against MDR bacteria isolates of wound infections. We examined the 16S rRNA gene sequences strain PS1C to identify the species. Then, the black pigment from PS1C was extracted using methanol: acetone (7:3) solvent. Antibacterial activity was evaluated against MDR bacteria from wounds with the microdilution method. A black-pigmented bacterium was isolated and identified as Pseudomonas aeruginosa PS1C. We found that the black pigment from P. aeruginosa PS1C can be developed as an antibacterial agent against the MDR bacterial isolate of wounds with MIC and MBC values of 6.25-12.5 mg/ml and 6.25-25 mg/ml, respectively. In conclusion, the study's findings highlight the potential of the extract of black pigment from P. aeruginosa PS1C as an antibacterial agent against wound-causing MDR bacteria and reinforce previous research into P. aeruginosa can be isolated from marine sources. Additional in vivo investigations and the identification of the antibacterial activity's mode of action are required. [ABSTRACT FROM AUTHOR]

Background In 2018 the World Health Organization recommended a switch to an all oral bedaquiline-based second-line regimen for treatment of drug-resistant tuberculosis (DR-TB). How these new second-line regimens fare in comparison to first-line regimens for treatment of drug-sensitive tuberculosis (DS-TB) is not well known. Methods In this study, we contemporaneously enrolled subjects with DS-TB (n = 31) or DR-TB (n = 23) and assessed their response to therapy with first-line (rifampin, isoniazid, ethambutol, pyrazinamide) or second-line (bedaquiline, pyrazinamide, levofloxacin, linezolid, clofazimine) regimens, respectively. Results We found that the early bactericidal activity of first- and second-line regimens was similar during the first 2 weeks of therapy as determined by BACTEC MGIT, colony-forming units, and a liquid limiting dilution assay capable of detecting differentially detectable/culturable Mycobacterium tuberculosis. Furthermore, an identical percentage (77.8%) of subjects from the DS-TB and DR-TB cohorts converted to culture negative after 2 months of therapy. Conclusions Despite presenting with more advanced disease at time of treatment, subjects with DR-TB receiving an all oral bedaquiline-based second-line treatment regimen displayed a similar microbiological response to therapy as subjects with DS-TB receiving a first-line treatment regimen. [ABSTRACT FROM AUTHOR]

AbstractOne can recognize multidrug resistance (MDR) and residue as a biggest difficulty in cancer specialist. Chemotherapy-resistant cancer may be successfully treated by combining MDR-reversing phytochemicals with anticancer drugs. Though, clinical application of phytochemicals either alone or in conjunction with chemotherapy is still in its early stages or requires more research to determine their safety and efficacy. In this review we highlighted topics related to MDR in cancer, including an introduction to subject, mechanism of action of efflux pump, specific proteins involved in drug resistance, altered drug targets, increased drug metabolism, and potential role of phytochemicals in overcoming drug resistance. [ABSTRACT FROM AUTHOR]

The current investigation explores the antibacterial properties of Quercetin, a flavonoid found in plants, and lemon peel extract, renowned for its rich bioactive content, against multiple drug resistant bacteria. The study method involved the identification of multidrug-resistant bacteria through antimicrobial susceptibility testing (AST). Nine standard bacterial strains exhibited resistance to different antibiotics, with a MAR index exceeding 0.10, including Ampicillin, Vancomycin, Polymyxin B, Nitrofurantoin, Trimethoprim, and Penicillin. In the present study bioactive compounds from lemon peel were extracted using two solvents, methanol and water, and their efficacy was assessed against drug-resistant bacteria. Minimum Inhibitory Concentration (MIC) values, determined by using the well plate method, revealed higher MIC values for the water extract (LPWE) compared to the methanol extract (LPME) and quercetin. For instance, the MIC for LPWE against E. hermanniensis ATCC 700323 was 140 mg/ml, whereas it was 50 mg/ml for quercetin & 1 mg/ml for LPME. From the results, it can be interpreted that Methanol extract was most effective against drug-resistant bacteria when compared to water extract and quercetin. Furthermore, GC-MS analysis was performed to analyze the chemical entities present in each extract. Given the activity of LPME, LPWE, and Quercetin against both Gram-negative bacteria and Gram-positive bacteria, these extracts hold promise as broadspectrum antibacterial agents applicable in various fields such as medicine, food, and cosmetics. [ABSTRACT FROM AUTHOR]

Background: Enterobacter cloacae complex (ECC) including different species are isolated from different human clinical samples. ECC is armed by many different virulence genes (VGs) and they were also classified among ESKAPE group by WHO recently. The present study was designed to find probable association between VGs and antibiotic susceptibility in different ECC species. Methods: Forty-five Enterobacter isolates that were harvested from different clinical samples were classified in four different species. Seven VGs were screened by PCR technique and antibiotic susceptibility assessment was performed by disk-diffusion assay. Result: Four Enterobacter species; Enterobacter cloacae (33.3%), Enterobacter hormaechei (55.6%), Enterobacter kobei (6.7%) and Enterobacter roggenkampii (4.4%) were detected. Minimum antibiotic resistance was against carbapenem agents and amikacin even in MDR isolates. 33.3% and 13.3% of isolates were MDR and XDR respectively. The rpoS (97.8%) and csgD (11.1%) showed maximum and minimum frequency respectively. Blood sample isolated were highly virulent but less resistant in comparison to the other sample isolates. The csgA, csgD and iutA genes were associated with cefepime sensitivity. Conclusion: The fepA showed a predictory role for differentiating of E. hormaechei from other species. More evolved iron acquisition system in E. hormaechei was hypothesized. The fepA gene introduced as a suitable target for designing novel anti-virulence/antibiotic agents against E. hormaechei. Complementary studies on other VGs and ARGs and with bigger study population is recommended. [ABSTRACT FROM AUTHOR]

This study was aimed to determine the relationship between Integron class I and multidrug resistance in Uropathogenic E. coli. A total of 302 urine samples were used in this study. 139 Uropathogenic E coli were collected from hospitalized patients. Then, using biochemical testing and the Vitek II compact system, all of the isolates were diagnosed and confirmed. All E. coli isolates were tested using a disc diffusion procedure to detect their susceptibility to 23 types of antibiotics from different classes, and the result showed that these bacteria were highly resistant to most used antibiotics especially, Cefotaxime, Ampicillin, Piperacillin, Trimethoprim- sulfamethoxazole,Cefepime and Ceftazidime, while the most effective antibiotics were Colistin and Tigecyclin. Also the results show different resistance patterns in which 111 (79.86%) isolate showed multidrug resistance MDR, Extensively drug resistance XDR 18 isolate (12.94%), while Pandrug resistance PDR 3 (2.15%). PCR was used to detect the presence of integron class I in MDR isolates,which was found in 87 of isolates with a 483 bp amplification product. The resolved PCR products were sequenced in both directions (forward and reverse), and the NCBI BLASTn engine revealed 100% sequence similarity between the sequenced samples and the planned reference1target sequences. These findings revealed that E. coli strains were highly resistant to common antibiotics; however, given the high prevalence of integron class I among these isolates, we can deduce that antibiotic resistance genes were most likely carried on mobile genetic elements (integron) in these isolates. [ABSTRACT FROM AUTHOR]

An infected wound affects the quality of life, and compromises the wound’s healing rate. This study was aimed at isolating bacteria from wounds and determining their antibiotics susceptibility patterns. A total of 100 wound swab samples were collected from wound patients attending Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. The samples were cultured and the resulting isolates identified using biochemical tests. The identified bacteria were subjected to antibiotic susceptibility test using agar disc diffusion method. Out of the 100 wound samples collected, 43 were infected with bacteria; given rise to overall prevalence of 43% bacterial wound infection. Out of the 43 isolated bacteria, 58.1% were Staphylococcus aureus, 18.6% were Klebsiella spp while 23.3% were identified to be Pseudomonas spp. Prevalence of bacterial wound infection was higher in female patients (47.3%) than their male counterpart (37.8%). Age group 21-40 years had the highest prevalence of the infections (48.3%) and the least was observed among 10-20 years (33.3%). None of the risk factors is significantly associated with the infection (p>0.05). All the isolates were 100% susceptible to ofloxacin. All the isolates showed 100% resistance to penicillin. All the Pseudomonas species were 100% MDR. Staphylococcus aureus was the most frequently encountered bacteria and ofloxacin was the first drug of choice in the treatment of wound infections. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is a pathogenic bacterium that has been linked to several illnesses acquired in both the community and hospitals. This study aimed to determine the prevalence of the clbA, K1, and K2 genes in K. pneumoniae and their relationship with antibiotic resistance. In this research, 130 clinical samples from patients in hospitals were collected from blood, urine, wounds, burns, and sputum, and only 61 of those samples were positively identified as K. pneumoniae using biochemical tests, selective media, and Vitek II. The method of disc diffusion was utilized to evaluate the 61 isolates' susceptibility to 10 antibiotics, including Imipenem, Meropenem, Cefixime, Ceftazidime, Amoxicillin-clavulanate, Gentamicin, Aztreonam, Azithromycin, Levofloxacin, and Trimethoprim-sulfamethoxazole. The results showed that the highest resistance was towards amoxicillin-clavulanate (98.36%) and the lowest towards meropenem (13.11%), and that 95.08% of the isolates were multidrug resistant (MDR). The clbA, K1, and K2 genes were detected using conventional PCR; the results showed that out of 61 isolates, only 3 were positive for K1, 52 were positive for K2, and none of the isolates were clbA+. (2/3) of the K1 and (51/52) of the K2 isolates were MDR. The finding shows a substantial association between the K1 and K2 genes and resistance to antibiotics, as the capsule is the main virulence factor in this bacteria. [ABSTRACT FROM AUTHOR]

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) expresses the Panton-Valentine leukocidin (PVL) virulence gene, which is associated with community and hospital-acquired severe MRSA infections. The objective of this study was to determine the prevalence and antibiotic susceptibility profile with a focus on the presence of the PVL gene among MRSA isolates in healthcare settings. Methodology: A total of 1,207 clinical specimens and 304 hospital environment swabs were collected in a tertiary care hospital in Nepal, and investigated following basic microbiological techniques. S. aureus was confirmed with the coagulase test. An antibiotic susceptibility test (AST) was performed by the Kirby-Bauer method and screening for MRSA was carried out by the cefoxitin disc diffusion method guided by the Clinical and Laboratory Standards Institute (CLSI), 2020. DNA was extracted and used in a polymerase chain reaction (PCR) to detect mecA and PVL genes. Results: Of the 1,511 samples, 45 (2.9%) S. aureus (23 clinical and 22 environmental) were isolated. Among them, 69.6% (16/23) and 27.3% (6/22) were MRSA in clinical and environmental isolates, respectively. Twelve (52.2%) clinical isolates and seven (31.8%) environmental isolates were multidrug resistant. The majority of isolates were susceptible to vancomycin and linezolid. The PVL gene was detected in 18.2% (n = 4/22) of the MRSA isolates, of which three were from clinical sources and one was from an environmental swab. Conclusions: The prevalence of MRSA, and PVL-producing S. aureus were higher in the hospital setting. Hence, immediate and urgent implementation of infection control and sanitation measures are needed in the hospital. [ABSTRACT FROM AUTHOR]

BACKGROUND: K.pneumoniae is a gram-negative bacterium belonging to the Enterobacteriaceae family. This microorganism is a part of the healthy microbiome of individuals and colonizes many parts of the body. The incidence of carbapenemresistant Klebsiella pneumoniae (CRKP) infections is increasing globally. In India, around 65% of K. pneumoniae isolates are resistant to carbapenem antibiotics. The blaNDM is the predominant carbapenem-resistant gene in CRKP isolates. AIM AND OBJECTIVE: To Study the Molecular Characterization of blaNDM-1 Resistant genes in Carbapenem Resistance Klebsiella Pneumonia Clinical isolates. MATERIAL AND METHODS:This was a cross sectional study carried out for a period of 1 year i.e, during 2023 to 2024at K.G.M.U, Lucknow . Samples like urine, sputum, ET tube, pleural fluid, pus, CSF, blood and Ascitic fluid were included in this study. Carbapenemase resistance was detected phenotypically by MHT, mCIM and eCIM methods and genotypically by using PCR where the DNA extraction was done and the resistant gene blaNDM-1 was confirmed by PCR assay. RESULT:A total of 350 isolates of K. pneumoniae were collected from patients, with 127(36.28%) identified as CRKP. There were 30 (57.69%) isolates obtained from male and 22(42.30%) were obtained from female, while the maximum number of patients belong to the age group <50 years and maximum patients were engaged as Student/Housewife/Retired (44.09%) followed by Clerical/Shopkeeper/Farmer (36.22%) and others. In our study,it was also observed that, in phenotypic test 81.88% were positive for M-CIM while 77.95% were positive for E-CIM and in genotypic test there were 86.61 % positive for NDM-1. CONCLUSION: The study highlighted the existence of carbapenemase-producing K. pneumoniae, particularly in blaNDM-1, in patients with comorbidities. Our findings emphasize the importance of the molecular characterization of resistance-determinant-carrying bacterial pathogens as a part of infection control and prevention in hospital settings. [ABSTRACT FROM AUTHOR]

The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that efflux various substrates across extra- and intracellular membranes. Among them, ABCB1, ABCG2, and ABCC1 are directly linked to tumor multidrug resistance (MDR). This review provides an overview of the current understanding on the novel mechanisms and functions of ABCB1, ABCG2, and ABCC1 transporters in tumor MDR, discusses the latest strategies to target these transporters, and explores further opportunities to overcome MDR. [ABSTRACT FROM AUTHOR]

The health of calves has a significant impact on the production of cows and livestock. Some desert plants have pharmacological importance, as they can be used to reduce antibiotic resistance. Our hypothesis is designed to detect Virulent- Multidrug-Resistant and Extended- spectrum Beta- lactamase Enterobacteriaceae (Virulent-MDR-ESBL Enterobacteriaceae and to determine whether Moringa oleifera has antibacterial activity against the detected isolates. A total of 39 Enterobacteriaceae isolates from 28 diarrheic samples were collected from calves aged between 20 days and 20 months from 3 different flocks in North Sinai, Sahl-Eltina region, Egypt. E.coli 46% (18/39), O157 13% (5/39), Klebsiella pneumoniae 41% (16/39). MDR members accounted for 87%, while ESBL isolates accounted for 43%. The antibacterial activity is represented by microdilution. Minimum inhibition concentration (MIC) for the methanol extract of Moringa oleifera ranged from 2.5,5,10, and 25mg/ ml among E.coli isolates, and O157 was susceptible to (2.5mg/ ml), Klebsiella pneumoniae isolates were susceptible to (5-50mg/ ml). Analysis of the methanol extract revealed that ferulic acid was the dominant phenolic compound with a concentration of 29,832 parts per million (ppm). In silico docking study expected the active site of ferulic acid to act on the tyrosine bacterial enzyme through Pi-alkyl, Pi-anion, Carbon hydrogen bonds, and extra ionic attractive interactions with copper ions which can stabilize ferulic acid inside the targeted pocket Diverse virulent gene profiles were observed in E. coli. The Shiga toxin-producing Escherichia coli (STEC) was reported in 83% of the isolated E. coli, while the DNA gyrase (gyrA) was harbored in 100% of Klebsiella pneumoniae isolates. Various profiles of antibiotic resistance genes for both E. coli and Klebsiella pneumoniae isolates were distinguished. blaTEM genes were detected in 99% of E. coli and 100% of Klebsiella pneumoniae. Sequence analysis for E. coli strain DRC-North Sinai-Eg was placed in accession numbers (OP955786) for the Shiga toxin 2 gene (Stx2A), (OP997748) and (OP997749) for the Adhesion to host cell gene (Eae). For the hemolysine gene (hylA), the accession number was (OP946183). Klebsiellapneumoniae strain DRC-North Sinai-Eg was placed in (OP946180) for (gyrA). This study has proven the broad range of Moringa oliefera's antibacterial effects in vitro against the virulent-MDR- ESBL E. coli and Klebsiella pneumoniae isolated from North Sinai calves diarrhea. These are congruent with the disability effect on bacterial tyrosinase enzyme through docking study therefore, we recommend the usage of this desert plant as a prospective feed additive, we endorse this as an antibacterial new insight natural source and for the medication of considered pathogens with zoonotic impacts. [ABSTRACT FROM AUTHOR]

Introduction: Medical devices (MDs) have a long history of use, and come with regulatory frameworks to ensure user safety. Although topically applied MDs in the form of gels and creams might be used on damaged skin, their composition is often similar to that of cosmetic products applicable to intact skin, especially in terms of preservatives and fragrances. However, unlike cosmetics, these products are not subject to compound‐specific restrictions when used in MDs. Objective: This study aimed to identify and quantify preservatives and fragrances in topically applied MDs and assess their safety towards the Cosmetic Regulation (EC) 1223/2009. Method: Sixty‐nine MDs available on the EU market were subjected to previously validated liquid chromatography tandem mass spectrometry (LC–MS/MS) and gas chromatography–mass spectrometry (GC–MS) methods to identify and quantify occurring preservatives and fragrances. Results: Findings revealed that 32% of the examined MDs did not provide comprehensive ingredient lists, leaving users uninformed about potential risks associated with product use. Furthermore, 30% of these MDs would not meet safety standards for cosmetic products and, most significantly, 13% of the analysed samples contained ingredients that are prohibited in leave‐on cosmetics. Conclusion: Results highlight the pressing demand for more stringent requirements regarding the labelling and composition of MDs to enhance patient safety. Improved regulation and transparency can mitigate potential risks associated with the use of topically applied MDs. [ABSTRACT FROM AUTHOR]

Purpose: The global increase in breast cancer cases necessitates ongoing exploration of advanced therapies. Taxol (Tx), an initial breast cancer treatment, induces mitotic arrest but faces limitations due to side effects and the development of resistance. Addressing Tx resistance involves understanding the complex molecular mechanisms, including alterations in tubulin dynamics, NF-κB signaling, and overexpression of ABC transporters (ABCB1 and ABCG2), leading to multidrug resistance (MDR). Methods: Real-time PCR and ELISA kits were used to analyze ABCB1, ABCG2 and NF-κB gene and protein expression levels, respectively. An MDR test assessed the resistance cell phenotype. Results: MCF-7/Tx cells exhibited a 24-fold higher resistance to Tx. Real-time PCR and ELISA analysis revealed the upregulation of ABCB1, ABCG2, and NF-κB. U-359 significantly downregulated both ABCB1 and ABCG2 gene and protein levels. Co-incubation with Tx and U-359 further decreased the mRNA and protein expression of these transporters. The MDR test indicated that U-359 increased MDR dye retention, suggesting its potential as an MDR inhibitor. U-359 and Tx, either individually or combined, modulated NF-κBp65 protein levels. Conclusion: The development of a Taxol-resistant MCF-7 cell line provided valuable insights. U-359 demonstrated effectiveness in reducing the expression of ABC transporters and NF-κB, suggesting a potential solution for overcoming multidrug resistance in breast cancer cells. The study recommends a strategy to enhance the sensitivity of cancer cells to chemotherapy by integrating U-359 with traditional drugs. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP), as a broad-spectrum anticancer drug, is able to bind to DNA and inhibit cell division. Despite the widespread use of cisplatin since its discovery, cisplatin resistance developed during prolonged chemotherapy, similar to other small molecule chemotherapeutic agents, severely limits its clinical application. Cisplatin resistance in cancer cells is mainly caused by three reasons: DNA repair, decreased cisplatin uptake/increased efflux, and cisplatin inactivation. In earlier combination therapies, the emergence of multidrug resistance (MDR) in cancer cells prevented the achievement of the desired therapeutic effect even with the accurate combination of two chemotherapeutic drugs. Therefore, combination therapy using nanocarriers for co-delivery of drugs is considered to be ideal for alleviating cisplatin resistance and reducing cisplatin-related toxicity in cancer cells. This article provides an overview of the design of cisplatin nano-drugs used to combat cancer cell resistance, elucidates the mechanisms of action of cisplatin and the pathways through which cancer cells develop resistance, and finally discusses the design of drugs and related carriers that can synergistically reduce cancer resistance when combined with cisplatin. [Display omitted] [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is considered as the most common pathogen of hospital-acquired pneumonia. K. pneumoniae has emerged as the superbug which had shown multidrug resistance (MDR) as well as extensively drug resistance. Carbapenem resistant K. pneumoniae (CRKP) has become a menace for the treatment with monotherapy of the patients mainly admitted in intensive care units. Hence, in the present study we collected total 187 sputum isolates of K. pneumoniae and performed the antimicrobial susceptibility testing by using the automated Vitek-2 system and broth micro-dilution method (67 CRKP). The combination study of solithromycin with meropenem, colistin, cefotaxime, piperacillin and tazobactam, nitrofurantoin, tetracycline, levofloxacin, curcumin and nalidixic acid was performed by using checkerboard assay. We observed the high rate of resistance towards ampicillin, cefotaxime, ceftriaxone, cefuroxime and aztreonam. The colistin and tigecycline were the most sensitive drugs. The CRKP were 36%, maximum were from the patients of ICUs. The best synergistic effect of solithromycin was with meropenem and cefotaxime (100%), colistin and tetracycline (80%). So, these combinations can be a choice of treatment for the infections caused by MDR CRKP and other Gram-negative bacteria where the monotherapy could not work. [ABSTRACT FROM AUTHOR]

Simple Summary: One key factor in the emergence of antimicrobial resistance (AMR) in microorganisms is antimicrobial usage in veterinary and human medicine. In dairy cattle, the prevalence of AMR E. coli is age-dependent, with a higher prevalence detected during the early stages of life. In veal calf fattening herds, the high degree of commingling calves from different farms of origin can lead to the rapid spread of infections within the farm. This can cause severe health issues, necessitating greater use of antimicrobial agents. Antimicrobial use has been reported to be higher in the veal calf fattening sector compared to the other production branches of livestock production. This represents an unquantified risk to human health, as antimicrobial-resistant bacteria and the genetic elements mediating resistance can potentially spread through foodborne transmission or environmental dissemination. This surveillance study was conducted, using data available from routine diagnostic activity, to: (i) determine the proportion of antimicrobial-resistant strains and AMR profiles of E. coli isolated from the intestinal contents of veal and dairy calves in the Veneto Region (Northeaster Italy); (ii) investigate potential variation in the AMR profiles of isolates between the two categories of calves and, (iii) identify potential AMR variations over the period considered (2017–2022). This surveillance study aimed to estimate the proportion of antimicrobial resistant strains and antimicrobial resistance (AMR) profiles of E. coli isolates detected from the intestinal contents of veal and dairy calves in the Veneto Region, Northeaster Italy. Additionally, we investigated the differences in AMR profiles between dairy and veal calves over the period 2017–2022. Overall 1150 E. coli isolates were tested from calves exhibiting enteric disease, with 868 from dairy and 282 from veal calves. The percentage of resistant isolates to nine antimicrobials was notably higher in veal calves compared to dairy calves, except for ampicillin. Throughout the study period, we observed a significant increase in the proportion of resistant isolates to florfenicol, gentamycin, paromomycin, tetracycline and trimethoprim/sulfamethoxazole in dairy calves, while we did not detect any significant increase in the proportion of resistant isolates among veal calves. A substantial proportion (75.9%) of the isolated E. coli exhibited multi-drug resistance (MDR). The proportion of multi-drug resistant isolates was significantly higher in veal calves (91.7%) compared to dairy calves (74.3%) all through the surveillance period (2017–2022), with no significant variation in MDR proportion among veal calves between 2017 and 2022 but a significant increase among dairy calves. [ABSTRACT FROM AUTHOR]

Wound infection is one of the most important factors affecting wound healing, so its effective control is critical to promote the process of wound healing. However, with the increasing prevalence of multi-drug-resistant (MDR) bacterial strains, the prevention and treatment of wound infections are now more challenging, imposing heavy medical and financial burdens on patients. Furthermore, the diminishing effectiveness of conventional antimicrobials and the declining research on new antibiotics necessitate the urgent exploration of alternative treatments for wound infections. Recently, phage therapy has been revitalized as a promising strategy to address the challenges posed by bacterial infections in the era of antibiotic resistance. The use of phage therapy in treating infectious diseases has demonstrated positive results. This review provides an overview of the mechanisms, characteristics, and delivery methods of phage therapy for combating pathogenic bacteria. Then, we focus on the clinical application of various phage therapies in managing refractory wound infections, such as diabetic foot infections, as well as traumatic, surgical, and burn wound infections. Additionally, an analysis of the potential obstacles and challenges of phage therapy in clinical practice is presented, along with corresponding strategies for addressing these issues. This review serves to enhance our understanding of phage therapy and provides innovative avenues for addressing refractory infections in wound healing. [ABSTRACT FROM AUTHOR]

Background: Findings from randomized trials (RCTs) on cervical pessary treatment to prevent spontaneous preterm birth are inconsistent. Objectives: Our hypothesis suggests that adhering to the European Medical Device Regulation (MDR) and following the instructions for use are essential prerequisites for successful therapy. Conversely, the non‐adherence to these guidelines will probably contribute to its failure. Search Strategy and Selection Criteria: Based on validated criteria from integrity assessments we performed a systematic review identifying 14 RCTs evaluating the effect of cervical pessaries. Data Collection and Analysis: We analyzed the implications of 14 criteria each accounting for 0–2 points of a score reflecting the clinical evaluation plan (CEP) as proposed by the MDR to evaluate the risk–benefit ratio of medical devices. Main Results: Seven RCTs in each singleton and twin pregnancies (5193 "cases") were included, detecting a high heterogeneity within control groups (I2 = 85% and 87%, respectively, P < 0.01). The CEP score varied from 11 to 26 points for all studies. The most common reasons for low scores and potential data compromise were poor recruitment rates, no (completed) power analysis, and no pre‐registration, but mainly non‐adherence to technical, biological, and clinical equivalence to the instructions for use as required by the MDR. All trials with score values greater than 20 had applied audit procedures. Within this group we found significantly reduced rates of spontaneous preterm birth at less than 34 weeks within the pessary group in singleton (odds ratio 0.28; 95% confidence interval 0.12–0.65) and twin pregnancies (odds ratio 0.30; 95% confidence interval 0.13–0.67). Similarly, there was a significant reduction in the composite poor neonatal outcome in singleton (odds ratio 0.25; 95% confidence interval 0.10–0.61) and twin pregnancies (odds ratio 0.54; 95% confidence interval 0.35–0.82) after a pessary as compared with controls. Conclusion: Non‐audited RCTs and meta‐analyses mixing studies of different clinical quality as pre‐defined by a CEP and the MDR pose the risk for erroneous conclusions. Synopsis: Our findings underline the importance of clinical audit procedures for randomized trials and specifically for the effect of cervical pessaries. [ABSTRACT FROM AUTHOR]

Simple Summary: Salmonella spp. of both human and animal origin have a high resistance percentage to tetracyclines. Essential oils, including cinnamon, clove, oregano, and red thyme, have demonstrated bactericidal activity against this bacterium. However, in many cases, the minimum inhibitory concentration (MIC) exceeds the cytotoxicity limits. The aim of this study was to evaluate the in vitro effectiveness of combining oxytetracycline with essential oils against multidrug-resistant Salmonella enterica strains. The results indicated a positive interaction (synergy and additivity) between oxytetracycline and the four oils that were tested. This led to a reduction in the MIC of both the oils and the antibiotic. The reduction was between 2 and 4 times the initial value for the oils and between 2 and 1024 times for the antibiotic. The best results were achieved with the combination of oxytetracycline and cinnamon, which decreased the effective concentration of this antibiotic to below the sensitivity threshold. Although differences in response were observed depending on the bacterial strain, there was no antagonistic effect in any case. The study suggests that combining oxytetracycline with cinnamon oil may be an effective alternative for controlling tetracycline-resistant strains of Salmonella, although further studies would be advisable. Tetracyclines have a high resistance percentage in Salmonella spp. of both human and animal origin. Essential oils, such as cinnamon (Cinnamomum zeylanicum), clove (Eugenia caryophyllata), oregano (Origanum vulgare), and red thyme (Thymus zygis), have shown bactericidal activity against this bacterium. However, in many cases, the minimum inhibitory concentration (MIC) exceeds the cytotoxicity limits. The objective of this study was to assess the in vitro efficacy of combining oxytetracycline with essential these oils against field multidrug-resistant (MDR) Salmonella enterica strains. The MIC of each product was determined using the broth microdilution method. The interaction was evaluated using the checkerboard method, by means of the fractional inhibitory concentration index (FICindex) determination. The results showed a positive interaction (synergy and additivity) between oxytetracycline and the four oils tested, resulting in a reduction in both products' MICs by 2 to 4 times their initial value, in the case of oils, and by 2 to 1024 times in the case of the antibiotic. The combination of oxytetracycline and cinnamon achieved the best results (FICindex 0.5), with a decrease in the antibiotic effective concentration to below the sensitivity threshold (MIC of the combined oxytetracycline 0.5 µg/mL). There was no antagonistic effect in any case, although differences in response were observed depending on the bacterial strain. The results of this study suggest that combining oxytetracycline with cinnamon oil could be an effective alternative for controlling tetracycline-resistant strains of Salmonella. However, its individual use should be further evaluated through in vitro susceptibility tests. [ABSTRACT FROM AUTHOR]

Introduction: Uropathogenic Escherichia coli (UPEC) is a leading cause of community-acquired and healthcare-associated infections, and antimicrobial resistance in UPEC poses significant challenges to managing these infections. This study aimed to investigate the molecular types of UPEC using enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and analyze their resistance patterns in a tertiary care setting. Methods: A cross-sectional study was conducted at a tertiary care hospital, where 65 consecutive E. coli isolates from urinary specimens were collected. Isolates were identified biochemically and confirmed by 16S rRNA gene PCR. Antibiotic susceptibility testing was conducted following CLSI guidelines, and molecular typing was performed using ERIC-PCR. ERIC-PCR profiles were analyzed using PAST software version 4.0, generating a dendrogram to visualize similarity among ERIC types. Fisher's exact test was used to determine if specific ERIC types were significantly associated with particular antibiotic resistance profiles. Results: The results showed that 95% of the isolates were resistant to at least two antibiotics, with 92.3% being multidrug resistant (MDR). The highest resistance was observed against ampicillin, while no resistance was seen against colistin and tigecycline. The resistant isolates displayed 36 different antibiograms, indicating a significant degree of resistance variability. ERIC-PCR typing revealed 22 unique clusters at a similarity coefficient of approximately 70%, highlighting the genetic diversity of UPEC isolates in our setting. Conclusion: This study enhances the understanding of UPEC epidemiology in healthcare by revealing the molecular characteristics and resistance profiles of prevalent strains. The high occurrence of MDR UPEC and the absence of a correlation between ERIC types and antibiograms suggest adaptability and increased resistance. These results highlight the necessity for continuous surveillance to inform infection control measures and direct targeted interventions against the spread of MDR UPEC. [ABSTRACT FROM AUTHOR]

The rapid surge in antibiotic resistance to pathogens has emerged as a grave threat to public health, globally. This multiple drug resistance (MDR) is directly linked to the high rates of morbidity and mortality worldwide due to untreated microbial infections. Therefore, it is inevitable to identify some novel, efficient, and comparatively safer antimicrobial agents to rescue the declining health index. In this regard, nanomaterials with modified structure, size, and infinity have risen as the sole source to tackle the MDR either through ameliorating the efficacy of existing drugs or by triggering entirely new bactericidal mechanisms. Out of all the nanomaterials, metals, and metal oxide nanoparticles with biopolymer-induced reduction have fetched the attention of global researchers due to their significant and promising pathogen-killing ability without any hint of resistance. The current review covers the updated molecular modes of resistance development in Gram-positive and Gram-negative bacteria, comprehensively. This review also highlighted the detailed mode of action of various metallic nanoparticles (silver, zinc, copper, titanium, and cobalt) against MDR pathogens. Moreover, this review article thoroughly discussed the correlation between the mechanisms of resistance and alternative NPs bactericidal modes for better understanding for the readers. Last but not least, toxicity analysis is also explained for safe further use. [ABSTRACT FROM AUTHOR]

Chryseobacterium demonstrates a diverse environmental presence and a significant pathogenic potential across various ecosystems. This clinical case showcases a rare instance of bacterial infection in a 75-year-old male with untreated diabetes and recurrent urinary tract infections (UTIs). The patient presented symptoms of abdominal pain, burning urination, fever, and an elevated eosinophil count. A subsequent urine culture identified a Chryseobacterium-related bacterium as the causative agent, exhibiting sensitivity to piperacillin/tazobactam, trimethoprim/sulfamethoxazole, and nitrofurantoin, which led to successful treatment using oral nitrofurantoin. Analysis of the 16S rRNA gene sequence of APV-1T revealed a close relationship of 98.2% similarity to Chryseobacterium gambrini strain 5-1St1aT (AM232810). Furthermore, comparative genome analysis, incorporating Average Nucleotide Identity (ANI), Digital DNA–DNA Hybridization (dDDH) values, and comprehensive phylogenetic assessments utilizing 16S rRNA gene sequences, core genes, and amino acid sequences of core proteins, highlighted the unique phylogenetic positioning of APV-1T within the Chryseobacterium genus. Distinct carbon utilization and assimilation patterns, along with major fatty acid content, set APV-1T apart from C. gambrini strain 5-1St1aT. These findings, encompassing phenotypic, genotypic, and chemotaxonomic characteristics, strongly support the proposal of a novel species named Chryseobacterium urinae sp. nov., with APV-1T designated as the type strain (= MCC 50690 = JCM 36476). Despite its successful treatment, the strain displayed resistance to multiple antibiotics. Genomic analysis further unveiled core-conserved genes, strain-specific clusters, and genes associated with antibiotic resistance and virulence. This report underscores the vital importance of elucidating susceptibility patterns of rare pathogens like Chryseobacterium, particularly in immunocompromised individuals. It advocates for further analyses to understand the functional significance of identified genes and their implications in treatment and pathogenesis. [ABSTRACT FROM AUTHOR]

Background and Aims: Ventilator-associated pneumonia (VAP) is a nosocomial infection associated with high morbidity and mortality. This study was undertaken to monitor the trend of the demographical details, comorbid conditions, bacterial etiological agents, and their antibiogram causing VAP in adults in the year 2008, 2013 and 2018. Material and Methods: A retrospective study conducted at the Department of Microbiology, Hospital Infection control and Quality Control at a tertiary care teaching hospital. All the adult patients with more than 48 h of the mechanical ventilator with endotracheal intubation with Clinical Pulmonary infection Score >6 with suspicion of VAP were included in the study at a difference of 5 years, i.e., 2008, 2013, and 2018. Results: A total of 338 patients were included in the study, of which males accounted for more than two-third of the patients studied. Nearly 45% of the patients belonged to geriatric (>60 years) age group. The most common comorbid conditions were chronic obstructive pulmonary disease, hypertension and diabetes mellitus. Among the gram-negative isolates, Klebsiella pneumoniae, Acinetobacter species, and Pseudomonas aeruginosa were the most common. There is an emergence of resistance to most commonly administered antimicrobial agents like aminoglycosides, levofloxacin, piperacillin/tazobactum, and carbapenems during the study period. Conclusion: This is a ten-year study on the antibiotic resistance pattern of organisms causing VAP. As far as the authors are aware, this is the first study addressing the pattern of change in drug resistance in the organisms causing VAP over a decade. The emergence of multi-drug resistant (MDR) MDR pathogens, especially in intensive care unit (ICU), is a great concern for the intensivist and infection control physicians. Preventive measures need to be undertaken to control the spread of these pathogens to the patients in the ICU. [ABSTRACT FROM AUTHOR]

Background: It has been determined that Escherichia coli is the prevailing uropathogen (50-90%) in both complicated and uncomplicated urinary tract infections. Uropathogenic Escherichia coli (UPEC) possesses an extensive array of virulence factors, which confers the potential to induce urinary tract infections and is correlated with the development of antibiotic resistance. The purpose of this research was to detect the distribution of virulence genes and their association with antibiotic resistance rates at the molecular level. Materials & Methods: This study was conducted in the microbiology laboratory at Al-Hussein Medical city teaching hospital, Laboratory of microbiology in Karbala province, Iraq. Urine samples were collected b/w October 2023 to January 2024, and transported for further analysis using standard microbiological and biochemical techniques. The sampling technique used in the study can be described as convenience sampling. The identification of E.coli isolates was confirmed using 16rRNA, resistance and sensitivity to various antibiotics were determined with Vitek2 system. Identification of genes (fimH, KpsmII, Pap, ompT) by uniplex PCR. Results: E.Coli was shown to be the most often isolated bacterium for various urine samples, with a percentage of 16(35.5%). The most virulent gene observed were Fim H, KpsMII, pap and OmpT were16 (100%), 13 (81.3%), 9(56.3%) and 8(50%) respectively. Thirteen type of antibiotics were identified sensitive to E.coli isolate the most common resistant rate was Ticarcillin, Pipraciilin had high resistance rate 14(87.5), Ciprofloxacin 9(56.3%), Minocycline, Aztreonam, Trimethoprim had rate of 8(50). Sensitivity rate of Meropenem, Imipenem, Gentamicin was 14(87.5), Cefepime 13(81.25), Amikacin 12(75.0). Conclusion: The study concluded that there is distribution of virulence gene in E.coli isolates, specially fimH, pap correlated with resistance to antibiotics specially with MDR and XDR patterns. [ABSTRACT FROM AUTHOR]

Overuse of antibiotics during coronavirus disease 2019 (COVID-19) in an attempt to reduce COVID-19 mortality in the short term may have contributed to long-term mortality from antimicrobial resistance (AMR). The aim of this study was to evaluate the impact of the COVID-19 pandemic on AMR in Egypt and map the distribution of multidrug-resistant (MDR) and extensive drug-resistant (XDR) across Egypt. Through a multicenter cross-sectional study 2430 culture results were collected in 2019 and 2022 pre and post-COVID-19 pandemic in Egypt, including 400 Klebsiella pneumoniae, 760 Escherichia coli, 650 Acinetobacter baumannii, and 620 Methicillin-resistantstaphylococcus aureus (MRSA) culture results. MDR and XDR culture results distribution across Egypt was highlighted through the geographic information system. Mixed effect logistic regression models and sub-group analysis were performed according to the type of specimens to test the impact of COVID-19 on resistance. Adjusted analysis demonstrated K. pneumoniae resistance has increased against quinolones and carbapenems (P < 0.001). Resistance of E. coli has increased significantly against imipenem and meropenem. While E.coli susceptibility has increased to cefoxitin, levofloxacin, and ciprofloxacin. A. baumannii resistance has increased more than double against ceftazidime, cefepime, and piperacillin-tazobactam (P < 0.001). MRSA reserved its susceptibility to vancomycin and linezolid. MDR K. pneumoniae and A. baumannii have increased post-COVID-19 from 67% to 94% and from 79% to 98%, respectively (P < 0.001). XDR K. pneumoniae and A. baumannii have increased from 6% to 46%, and from 47% to 69%, respectively (P < 0.001). COVID-19 has changed the profile of AMR in Egypt so that urgent action is required to mitigate this threat and preserve our capacity to face infections in future decades. [ABSTRACT FROM AUTHOR]

Background: Copper-induced gene expression in Xanthomonas campestris pv. campestris (Xcc) is typically evaluated using targeted approaches involving qPCR. The global response to copper stress in Xcc and resistance to metal induced damage is not well understood. However, homologs of heavy metal efflux genes from the related Stenotrophomonas genus are found in Xanthomonas which suggests that metal related efflux may also be present. Methods and Results: Gene expression in Xcc strain BrA1 exposed to 0.8 mM CuSO4.5H2O for 15 minutes was captured using RNA-seq analysis. Changes in expression was noted for genes related to general stress responses and oxidoreductases, biofilm formation, protein folding chaperones, heat-shock proteins, membrane lipid profile, multiple drug and efflux (MDR) transporters, and DNA repair were documented. At this timepoint only the cohL (copper homeostasis/tolerance) gene was upregulated as well as a chromosomal czcCBA efflux operon. An additional screen up to 4 hrs using qPCR was conducted using a wider range of heavy metals. Target genes included a cop-containing heavy metal resistance island and putative metal efflux genes. Several efflux pumps, including a copper resistance associated homolog from S. maltophilia, were upregulated under toxic copper stress. However, these pumps were also upregulated in response to other toxic heavy metals. Additionally, the temporal expression of the coh and cop operons was also observed, demonstrating co-expression of tolerance responses and later activation of part of the cop operon. Conclusions: Overall, initial transcriptional responses focused on combating oxidative stress, mitigating protein damage and potentially increasing resistance to heavy metals and other biocides. A putative copper responsive efflux gene and others which might play a role in broader heavy metal resistance were also identified. Furthermore, the expression patterns of the cop operon in conjunction with other copper responsive genes allowed for a better understanding of the fate of copper ions in Xanthomonas. This work provides useful evidence for further evaluating MDR and other efflux pumps in metal-specific homeostasis and tolerance phenotypes in the Xanthomonas genus. Furthermore, non-canonical copper tolerance and resistance efflux pumps were potentially identified. These findings have implications for interpreting MIC differences among strains with homologous copLAB resistance genes, understanding survival under copper stress, and resistance in disease management. [ABSTRACT FROM AUTHOR]

Acinetobacter is an important nosocomial pathogen causing health care associated infections. It is highly antibiotic resistant gram-negative bacilli. The study was done to determine the prevalence of Acinetobacter species isolated from various clinical samples with their antibiotic susceptibility pattern. To determine the antimicrobial susceptibility pattern of the isolated Acinetobacter species and also the multidrug resistant mechanisms by phenotypic characterization. The retrospective study was carried out in patients diagnosed with Acinetobacter infection in the Microbiology Department, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth, Deemed To Be University, Karad, a tertiary care hospital, including the clinical departments, during the period of two years from November 2020 till November 2022. Organism identification, biochemical test, antibiotic resistance pattern and phenotypic tests such as ESBL, MBL and Carbapenemase production were performed as per the Clinical and Laboratory Standards Institute (CLSI). The Modified Hodge test (MHT) was performed for Carbapenemase production detection in Acinetobacter species. A total of 150 Acinetobacter species were isolated from clinical samples. Acinetobacter baumannii was the most prevalent species 138 (92%), followed by Acinetobacter lwoffii 10 (7%) and Acinetobacter hemolyticus 2 (1%). The isolates showed highest resistance to Ampicillin 130 (87%) and sensitive to Colistin 113 (75.3%). Most of the isolates of of Acinetobacter baumannii showed maximum ESBL 21(14%) and MBL 75 (93%) production. Modified Hodge test showed positive results in Acinetobacter baumannii, only 11 (7%). The study showed that Acinetobacter baumannii was the most prevalent species showing drug resistance by phenotypic detection methods. At present Acinetobacter is a frequent pathogen in hospital acquired infections in critically ill patients admitted to ICU. The isolates of Acinetobacter species in our study showed resistant to most commonly used antibiotics. The study showed that ESBL production in Acinetobacter was 22 (15%) and MBL 80 (53%). Most Acinetobacter isolates were Multi Drug Resistant (MDR). MDR Acinetobacter is widely increasing due to inappropriate use of antibiotics in healthcare hospital. In our study, detection of carbapenemase by Modified Hodge test was positive in 11 (7%) isolates. [ABSTRACT FROM AUTHOR]

Escherichia coli is gram negative bacteria and represents a typical resident of the digestive systems of both humans and animals. The stability and equilibrium of the luminal microbial flora are significantly influenced by E. coli. The Escherichia coli uropathogenic-specific protein (Usp) represents type of genotoxins produced by uropathogenic E. coli rather than fecal E. coli isolates. In the current study E. coli was isolated from urine and stool and usp gene was detected in it. Sensitivity test was evaluated by using different types of antibiotics and the usp gene was detected by PCR in all bacterial isolates. Antibiotics sensitivity test showed variable degrees of sensitivity and resistance. High percentage of sensitivity was achieved against amikacin (86%) and that for ciprofloxacin, ceftazidime, gentamicin and tobramycin it was 80%. Whereas trimethoprim and aztreonam showed 64% and 60% sensitivity respectively. In this study, most isolates were resistant to amoxicillin 92%; while they showed different degrees of resistance against other types of antibiotics (from tetracycline 62% to amikacin 4%). The frequency of multi drug resistant (MDR) bacteria was about 64 % (32 isolates), 30 from urine and 2 from the stool. The results showed that usp gene was found in 26 bacterial isolates (52%), whereas other 24 (48%) isolates didn’t have this gene. It was concluded that source of bacterial isolates carry usp gene was urine, with the exception of one isolate from f stool, and E. coli recorded as multidrug resistant bacteria (MDR). [ABSTRACT FROM AUTHOR]

The emergence and spread of resistance in Enterobacteriaceae are complicating the treatment of serious nosocomial infections and threatening to create species resistant to all currently available agents. They are inhabitants of normal intestinal flora and are among the most common human pathogens, causing multiple infections . They are the source of communityand hospital-acquired infections. An observational study was conducted over a period of six months (July 2023 -- December 2023) in the microbiology laboratory of Swami Ramanand Teerth Government Medical College, Ambajogai, Maharashtra . A total of 468 bacterial isolates of Enterobacteriaceae from clinical specimens were processed for antimicrobial susceptibility testing The rate of multidrug resistance and extended spectrum beta-lactamases production was 54.2% and 23.8% respectively. Of the total ESBL producers 92.4% were multidrug resistance. The rate of multidrug resistance and extended spectrum beta-lactamases production were higher in organisms isolated from clinical samples collected from inpatients. High rate of MDR and ESBL was seen in E. coli (54.7% & 21.4%), Klebsiella spp. (68% & 16.8%) and Citrobacter spp. (41.1% & 44.1%). The antimicrobial resistance rate was highest against ampicillin (80.3%) followed by cefixime (56.4%), ceftazidime (53.6%), ceftriaxone (53.0%), cotrimoxazole (51.2%), ciprofloxacin (45%) and ofloxacin (42.3%). Multidrug resistance is common among Enterobacteriaceae. These bacteria have high rate of resistance against commonly used groups of antibiotics like cephalosporins and quinolones. Continuous monitoring, surveillance of antimicrobial resistance, proper infection control and practices are important to combat with these issues. [ABSTRACT FROM AUTHOR]

As antibiotics cannot inhibit multidrug-resistant bacteria (MDR), continuous research is mandatory to find other antibacterials from natural resources. Native legume proteins and their modified forms exhibited broad spectra of high antimicrobial activities. Sixteen bacterial isolates were mapped for antibiotic resistance, showing resistance in the range of (58–92%) and (42–92%) in the case of the Gram-negative and Gram-positive bacteria, respectively. White native Phaseolus vulgaris protein (NPP) was isolated from the seeds and methylated (MPP). The MIC range of MPP against 7 MDR bacteria was 10–25 times lower than NPP and could (1 MIC) considerably inhibit their 24 h liquid growth. MPP showed higher antibacterial effectiveness than Gentamycin, the most effective antibiotic against Gram-positive bacteria and the second most effective against Gram-negative bacteria. However, MPP recorded MICs against the seven studied MDR bacteria in the 1–20 µg/mL range, the same for Gentamycin. The combination of Gentamycin and MPP produced synergistic effects against the seven bacteria studied, as confirmed by the Transmission Electron Microscopic images. The antimicrobial activity of MPP against the seven MDR bacteria remained stable after two years of cold storage at 8–10 °C as contrasted to Gentamycin, which lost 20–72% of its antimicrobial effectiveness. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) have been increasingly used as a valid option to improve the prognosis and reduce the symptoms of end-stage heart failure. However, long-term complications, mostly infections and coagulation disorders, are frequent. We described the epidemiology and risk factors for nosocomial infections (NIs) in a cohort of adult patients who underwent continuous-flow LVAD implant between January 2010 and December 2017 in Turin, Italy. Secondary outcomes were the prevalence of multidrug-resistant (MDR) bacteria and mortality. Results: Overall, 64 LVADs were implanted. A total of 32 (50%) patients experienced at least one episode of NI, with a total of 46 infectious events. VAD-related infections occurred in 22 patients (68.8%). Non VAD-related NIs occurred in 12 patients (37.5%), mainly low respiratory tract infections. Length of intensive care unit admission was a risk factor for NI (OR 1.224, 95%CI; 1.049, 1.429). Gram-negative bacilli were responsible for 58.8% of VAD-related infections and 79.5% of non-VAD related infections. In sixteen patients (50%), at least one episode of infection was related to an MDR strain. INTERMACS class and length of MV were independent risk factors for NIs by MDR strains (respectively, OR 2.12, 95%CI: 1.08, 6.80; p = 0.02 and OR 1.46, 95%CI: 1.07, 5.52, p = 0.047). In-hospital mortality was 6.3%. No differences in mortality were observed between infected and non-infected patients (p = 0.61) even when caused by MDR strains (p = 0.143). Conclusion: the rate of nosocomial infections in LVAD patients is associated with the length of ICU admission, and the etiology of nosocomial infection after LVAD implant is mainly due to GNB, including a high rate of MDR strains, especially KPC-KP and MDR PA. [ABSTRACT FROM AUTHOR]

Salmonella Typhi, the invasive serovar of S. enterica subspecies enterica, causes typhoid fever in healthy human hosts. The emergence of antibiotic‐resistant strains has consistently challenged the successful treatment of typhoid fever with conventional antibiotics. Antimicrobial resistance (AMR) in Salmonella is acquired either by mutations in the genomic DNA or by acquiring extrachromosomal DNA via horizontal gene transfer. In addition, Salmonella can form a subpopulation of antibiotic persistent (AP) cells that can survive at high concentrations of antibiotics. These have reduced the effectiveness of the first and second lines of antibiotics used to treat Salmonella infection. The recurrent and chronic carriage of S. Typhi in human hosts further complicates the treatment process, as a remarkable shift in the immune response from pro‐inflammatory Th1 to anti‐inflammatory Th2 is observed. Recent studies have also highlighted the overlap between AP, persistent infection (PI) and AMR. These incidents have revealed several areas of research. In this review, we have put forward a timeline for the evolution of antibiotic resistance in Salmonella and discussed the different mechanisms of the same availed by the pathogen at the genotypic and phenotypic levels. Further, we have presented a detailed discussion on Salmonella antibiotic persistence (AP), PI, the host and bacterial virulence factors that can influence PI, and how both AP and PI can lead to AMR. [ABSTRACT FROM AUTHOR]

The emergence of multidrug-resistant Pseudomonas aeruginosa possesses a significant public health concern. Constitutively expressed MexAB–OprM efflux pumps in P. aeruginosa significantly contribute to its resistance to a variety of antibiotics. The development of efflux pump inhibitors (EPIs) has emerged as an attractive strategy in reversing antibiotic resistance. In this study, structure-based virtual screening techniques were used for the identification of new MexAB–OprM efflux inhibitors. The predicted poses were thoroughly filtered by induced fit docking procedures followed by in vitro microbiological assays for the validation of in silico results. Two compounds, NSC-147850 and NSC-112703, were able to restore tetracycline susceptibility in MexAB–OprM overexpressing Pseudomonas aeruginosa ATCC® 27853™ strain. This correlation observed between in silico screening and positive efflux inhibitory activity in vitro suggests that NSC-147850 and NSC-112703 have potential as EPIs and may be effective in combination therapy against drug-resistant strains of P. aeruginosa. [ABSTRACT FROM AUTHOR]

Introduction: The main objective of this study was to investigate the three-year evaluation of antibiotic resistance (AR) of multi-drug-resistant organisms and extended-spectrum beta-lactamase (ESBL)-resistant rate of gram-negative bacteria in one of the largest hospitals by the Saudi Arabia Nation Plan. Methods: This study was conducted in the Department of Laboratory Medicine, in a private hospital in Riyadh City, Saudi Arabia, from January 2019 to December 2021 in 120-bed private hospitals. A total of 4700 gram-negative isolated organisms were obtained from the various specimens of the patients, and antibiotic sensitivity tests were performed. According to the manufacturer's instructions, the inoculum prepared was applied to two test cards, one for the identification system VITEK 2 ID-GNB and another for susceptibility testing antimicrobial susceptibility testing (AST) No. 12. Result: The most common gram-negative bacteria isolated was Escherichia coli (2706/4700; 57.57%), followed by Klebsiella pneumoniae (905/4700; 19.25%) and Pseudomonas aeruginosa (395/4700; 8.40%). Escherichia coli's highest AR reduction was reported for cefotaxime (CTX) of 29% (295/1018; 29%, 172/818; 21%, 0/870; 0%) for 2019, 2020, and 2021, respectively. Except for Salmonella species, which displayed enhanced AR, the ESBL and multidrug-resistant (MDR) rates decreased significantly (p 0.05) for most bacteria. Conclusion: This study helps to understand the maximum number of gram-negative bacteria susceptible to the Saudi National Action Plan (SNAP) to decrease the prevalence of AR, ESBL, and MDR. To comprehensively understand SNAP's effectiveness, other trials involving gram-positive bacteria should be considered. [ABSTRACT FROM AUTHOR]

Background: Catheter-associated urinary tract infections (CAUTIs) due to multidrug-resistant Gram-negative bacilli (GNB) is a common concern globally. Investigating the incidence of CAUTI and associated antibiotic resistance has paramount importance from the health care associated infections perspective. This study therefore assessed the incidence of CAUTIs due to GNB and the production of extended-spectrum beta-lactamase (ESBL) and carbapenemase among inpatients in specialized hospitals of Northwest, Ethiopia. Methods: A total of 363 patients with indwelling urinary catheters who were admitted in the hospital for > 48 h were consecutively enrolled and followed from 3 to 18 days. Data were collected through interviewing and review of medical records. Patients who developed at least one of the following: fever (> 38 OC), suprapubic tenderness, or costovertebral angle pain, coupled with a GNB positive urine culture of ≥ 103 CFU/mL with no more than two bacterial species were defined as CAUTI. The ESBL and carbapenemase production were detected and identified by chromogenic medium. Logistic regression analysis was done to identify associated factors. Results: From 363 patients followed, the incidence rate of CAUTI was 27.8 per 1000 catheter days. Catheterization for ≥ 8 days (AOR = 10.6, 95%CI:1.8–62.1) and hospitalization for > 10 days (AOR = 8.1, 95%CI: 2.4–27.2) were the factors significantly associated with CAUTIs. E. coli (n = 18, 34.6%), Proteus species (n = 7, 13.5%), and P. aeruginosa (n = 6, 11.5%) were the most frequent GNB. Isolates revealed high rates of resistance to amoxicillin-clavulanic acid (100%), cefazolin (n = 51, 98%), ceftazidime (n = 47, 90%) and cefotaxime (n = 46, 88%). Most of the GNB isolates (86.5%) were multidrug-resistant. Overall, 19.2% and 5.8% of GNB isolates were ESBL and carbapenemase producers, respectively. Conclusions: Incidence of CAUTI with Gram-negative bacilli is high. As most of the GNB isolates are MDR and showed a super high rate of resistance to amoxicillin-clavulanic and third-generation cephalosporins, empirical treatment with these substances is virtually ineffective in patients with suspected GNB infection in Ethiopia. The expression of ESBL and carbapenemase among GNB isolates is also a concern. Therefore, improved infection prevention and control measures, careful use of catheters and third generation of cephalosporins are needed to improve patient outcomes and reduce the burden of CAUTIs and the spreading of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

An agent that contributes to hospital acquired illnesses is Klebsiella pneumoniae. In community-acquired infections and illnesses of the urinary tract, it is the primary and most frequent causal agent. The strains were detected by using Analytical Profile Index (Api-20 E) and 16s rRNA techniques, fifteen trains of K. pneumoniae were obtained from eighteen urine samples collected from patients in Al-Hussein Hospital, Thi-Qar Governorate, Iraq. This research sought to identify the antibiotic resistance of K. pneumoniae to Aztreonam, Ceftriaxone, Trimethoprim, Amikacin, Ciprofloxacin, Meropenem, and Piperacillin, the resistance was high and ranged between (86.6-100)%. The multidrug resistance percentage was 100%, in addition the investigation aimed to detect some virulence genes, (i.e. HtrA and MrkA gene) in K. pneumoniae. The HtrA and MrkA genes were found using the PCR method, which revealed that 6 (40%) of the isolates had the HtrA gene and that all strains under study lacked the MrkA gene. [ABSTRACT FROM AUTHOR]

This study was established to discover and determine multidrug-resistant Escherichia coli and Klebsiella pneumoniae from women suffering urinary tract infections, specifically in Mosul city. A total of 62 E. coli and 32 K. pneumoniae bacterial isolates were considered for this study. All isolates were characterized using standard bacterial culture methods, including culture on MacConkey agar, Eosin Methylene Blue agar and biochemical tests. Also antibiotic sensitivity test using standard disc method for different antibiotics and also special discs to detect ESBL activity were carried out, in addition to PCR as molecular identification tool. The results showed that most isolated E. coli and K. pneumoniae demonstrated MDR resistance pattern with highest resistance recorded for E. coli to tetracycline 62/62 (100%), trimethoprim/sulfamethoxazole 60/62 (96.8%), gentamycin 51/62 (82.3%) and azithromycin 50/62 (80.7%). While K. pneumoniae recorded high resistance to nalidixic acid 32/32 (100%) and tetracycline 26/32 (81.2%). On the other hand, imipenem was the only one that showed ultimate sensitivity for all E. coli and K. pneumoniae isolates. Furthermore, the current results revealed that 68/94 (72.3%) of the studied isolates have ESBL activity. The results for molecular studies confirmed that E. coli and K. pneumoniae have resistance genes with dominated CTX-M gene, followed by SHV and finally TEM gene. The study concluded that E. coli and K. pneumoniae with MDR feature are serious threat to women with UTIs and all necessary measures ought to be performed in order to reduce the antibiotic resistance. [ABSTRACT FROM AUTHOR]

Nanotechnology offers promising opportunities in combating infectious agents, especially multidrug-resistant bacteria (MDR), which is a major concern in modern times. Zinc oxide nanoparticles (ZnO-NPs) are effective in delivering therapeutic agents to living systems due to their biocompatibility and bioactivity, making them effective against infectious microbes and also allowing them to be applied as an effective anticancer instrument. This study aimed to investigate the antimicrobial activity of ZnO-NPs against P. aeruginosa, a multi-drug resistant (MDR) bacterium in combination with Piperacillin-Tazobactam, as well as the in vitro effect of anticancer activity on MCF-7 and HepG2 cell lines. Piperacillin-Tazobactam, are beta-lactam antibiotics highly effective against Gram-positive and Gram-negative bacteria such as Pseudomonas aeruginosa, and recommended for the empirical treatment of Febrile Neutropenia (FN) after chemotherapy. ZnO-NPs of variable size (designated as ZnO-NPs-A, ZnO-NPs-B, and ZnO-NPs-C with 35±2.5 nm, 50±2 nm, and 65±3 nm mean sizes, respectively) and Piperacillin-Tazobactam alone and in combination were used for the study. The extended-spectrum beta-lactamase (ESBLs) producing MDR P. aeruginosa strain sensitivity profiling towards different combinations of ZnO-NPs and Piperacillin-Tazobactam was measured. There was no synergistic effect observed against growth inhibition of P. aeruginosa. The combined dose of ZnO-NPs-A and Piperacillin-Tazobactam showed great antibacterial efficacy even as compared to the pure drug against P. aeruginosa. Similarly, the Piperacillin-Tazobactam with ZnO-NPs-C showed the least cell viability as compared to the drug alone. The study showed a significant decrease in cell viability with the combined application of Piperacillin-Tazobactam and ZnO-Nps in comparison to the individual treatments. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas infections are among the most common infections encountered in hospitalized patients, especially those with chronic illnesses or an immunocompromised state. Management of these infections has become challenging due to increased antibiotic resistance. Therefore, this study examines the antibiotic resistance profiles of Pseudomonas spp. and the associated factors among patients admitted to a large tertiary hospital in a developing country. Methods: This retrospective observational chart review study assessed patients admitted to a large tertiary hospital in a developing country with a positive culture growth of Pseudomonas from anybody site. Antibiotic susceptibility of the isolated Pseudomonas and patient characteristics were studied from the start of 2021 to the end of 2022. The study ground consisted of 185 patients. Results: The study included 185 patients with positive Pseudomonas isolates. Males constituted 54.6% of the sample, while 45.4% were females. The median age of the patients was 53 years. Patient comorbidities and risk factors for Pseudomonas infection and multidrug resistance were assessed. Antibiotic resistance to the Pseudomonas regimens showed the highest resistance to meropenem and ciprofloxacin (23.4%, similarly) among isolates of Pseudomonas aeruginosa. Multidrug resistance (MDR) was found in 108 (58.4%) isolates. The most commonly used antibiotic for treatment was piperacillin-tazobactam, accounting for 33.3% of cases, followed by aminoglycosides at 26.6%. Conclusions: Pseudomonas aeruginosa isolates were resistant to meropenem and ciprofloxacin. Over half of the isolates were multidrug-resistant, which was worrying. Piperacillin-tazobactam and aminoglycosides were the most often utilized antibiotics, highlighting the significance of susceptibility testing. Implementing antimicrobial stewardship programs and infection control measures can help reduce drug resistance and improve outcomes in Pseudomonas infections. [ABSTRACT FROM AUTHOR]

Many dangerous bacteria have become highly resistant to traditional antibiotics, which is a huge public health concern. This study investigated the use of silver nanoparticles biosynthesized in a culture filtrate of Lactobacillus acidophilus as antimicrobials. UV–visual spectrophotometry, Fourier-transform-infrared spectroscopy, X-ray power diffraction, and scanning electron microscopy have all validated the findings. The biosynthesized nanoparticles ranged in size from 33 to 90 nm. The cytotoxicity of the nanosilver generated was then investigated using nine 200 g BW rats separated into three groups. When compared to the control group, the treated rats showed little signs of toxicity; parameters of physiological function, including alanine transaminase, aspartate aminotransferase, albumin, creatinine, and urea were significantly different in treated and non-treated animals. Moreover, the antibacterial role of the generated silver nanoparticles was examined in multi-drug resistant (MDR) pathogenic bacteria, Proteus vulgaris, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae, revealing high antibacterial activity against the examined bacteria. For more demonstration of the effect of the nanosilver on transcription and gene regulation of treated and non-treated bacteria differential display droplet digital-PCR was used, and the results revealed that several genes were up- and down-regulated. Some genes were selected for DNA sequencing and according to the sequence analysis, these genes were mecA, beta-lactam, and unidentified protein genes, and these have been deposited in the GenBank Database with the following accession numbers: Staphylococcus MZ748472 and Klebsiella MZ748473. We conclude that silver nanoparticles biosynthesized by L. acidophilus are environmentally friendly and have antibacterial activities against MDR pathogenic bacteria. Key Points: Our gifted results established that we were right for renewed interest of AgNPs. The AgNPS, can be used to prevent treatment failure. MDR bacteria are of a great health burden and should be overcomed. [ABSTRACT FROM AUTHOR]

The antimicrobial resistance of pathogenic microorganisms against commercial drugs has become a major problem worldwide. This study is the first of its kind to be carried out in Egypt to produce antimicrobial pharmaceuticals from isolated native taxa of the fungal Chaetomium, followed by a chemical investigation of the existing bioactive metabolites. Here, of the 155 clinical specimens in total, 100 pathogenic microbial isolates were found to be multi-drug resistant (MDR) bacteria. The Chaetomium isolates were recovered from different soil samples, and wild host plants collected from Egypt showed strong inhibitory activity against MDR isolates. Chaetomium isolates displayed broad-spectrum antimicrobial activity against C. albicans, Gram-positive, and Gram-negative bacteria, with inhibition zones of 11.3 to 25.6 mm, 10.4 to 26.0 mm, and 10.5 to 26.5 mm, respectively. As a consecutive result, the minimum inhibitory concentration (MIC) values of Chaetomium isolates ranged from 3.9 to 62.5 µg/mL. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis was performed for selected Chaetomium isolates with the most promising antimicrobial potential against MDR bacteria. The LC-MS/MS analysis of Chaetomium species isolated from cultivated soil at Assuit Governate, Upper Egypt (3), and the host plant Zygophyllum album grown in Wadi El-Arbaein, Saint Katherine, South Sinai (5), revealed the presence of alkaloids as the predominant bioactive metabolites. Most detected bioactive metabolites previously displayed antimicrobial activity, confirming the antibacterial potential of selected isolates. Therefore, the Chaetomium isolates recovered from harsh habitats in Egypt are rich sources of antimicrobial metabolites, which will be a possible solution to the multi-drug resistant bacteria tragedy. [ABSTRACT FROM AUTHOR]