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Objectives: The aim of this study was to identify the synergistic effect and mechanisms of fosfomycin (FM) combined with colistin (COL) against KPC-producing Klebsiella pneumoniae (KPC-Kp). Methods: The bactericidal effects, induced drug resistance and cytotoxicity of FM combined with COL were evaluated by time-kill assays and mutation rate test. Time-kill assays and transcriptomics analysis were used to further clarify the mechanism of FM combined with COL. The bacteria were taken from different points in time-kill assays, reactive oxygen species (ROS), nitric oxide and redox related enzymes were detected. The mechanism of synergistic bactericidal action was analyzed by transcriptome. Results: The bactericidal effect of FM combined with COL was better than that of monotherapy. The mutation frequency of FM alone at low dose (8 mg/L) was higher than that at high dose (64 mg/L). COL induced resistant isolates resulted in FM and COL resistance, while FM alone or combined with COL only resulted in FM resistance. The survival rate of Thp-1 cells in FM combined with COL against K. pneumoniae was higher than that of monotherapy. The intracellular nitric oxide, activities of total superoxide dismutase and catalase were increased along with the increase of FM concentration against KPC-Kp. FM combined with COL induced ROS accumulation and antioxidant capacity increase. Transcriptome analysis showed FM combined with COL could regulate the levels of soxRS and oxidative phosphorylation, in order to clear ROS and repair damage. In addition, FM combined with COL could result in synergetic bactericidal efficacy by inhibiting ribosomal transcription. Conclusions: FM combined with COL mediated synergistic bactericidal effect by regulating ROS accumulation and inhibiting ribosomal protein transcription, resulting in lower resistance and cytotoxicity. [ABSTRACT FROM AUTHOR]

Objectives Performance evaluation of routine laboratory methods to determine the susceptibility of Enterobacterales urinary isolates to fosfomycin (oral administration) and mecillinam. Methods We collected 347 Enterobacterales isolates from monomicrobial midstream urine samples from women with significant bacteriuria and leukocyturia. Mostly non- Escherichia coli isolates (i.e. Klebsiella spp. Citrobacter koseri , Enterobacter cloacae complex and Proteus mirabilis) were included (n  = 298). Performance of VITEK®2, ETEST®, and disc diffusion to determine fosfomycin and mecillinam susceptibility was evaluated following International Organization for Standardization (ISO) 20776-2:2021 (or 20776-2:2007 for disc diffusion) in comparison with the agar dilution reference method. Results For fosfomycin testing, VITEK®2 and ETEST® were close to reaching ISO requirements (essential agreement  ≥ 90%; bias  ±30%) for C. koseri , E. coli and P. mirabilis. Categorical agreement (CA) and major error rates were acceptable for disc diffusion. Fosfomycin displayed lower activity against E. cloacae complex and Klebsiella spp. with MIC50 (minimum inhibitory concentration required to inhibit the growth of 50% of tested isolates) equal to the E. coli EUCAST breakpoint (8 mg/L). For these species, the three alternative techniques overestimated MICs and resistance, and did not meet performance criteria. For mecillinam testing of Enterobacterales isolates, apart from P. mirabilis , ETEST® nearly fulfilled ISO requirements, and CA rates were acceptable for disc diffusion. ISO criteria were reached for C. koseri and E. coli testing with VITEK®2, apart from too high rates of very major errors. For P. mirabilis, performances were unacceptable, whatever the routine method used. Conclusions Commercially available tests may serve as alternatives to agar dilution to assess fosfomycin (oral) and mecillinam susceptibility of Enterobacterales urinary isolates, with important interspecies variabilities. Additional studies comprising more fosfomycin- and mecillinam-resistant isolates are needed to strengthen our conclusions. [ABSTRACT FROM AUTHOR]

Treatment of patients with serious infections due to resistant Gram-negative bacteria remains highly problematic and has prompted clinicians to use existing antimicrobial agents in innovative ways. One approach gaining increased therapeutic use is combination therapy with IV fosfomycin. This article reviews the preclinical pharmacokinetic / pharmacodynamic (PK/PD) infection model and clinical data surrounding the use of combination therapy with IV fosfomycin for the treatment of serious infections caused by resistant Gram-negative bacteria. Data from dynamic in vitro and animal infection model studies of highly resistant Enterobacterales and non–lactose fermenters are positive and suggest IV fosfomycin in combination with a β-lactam, polymyxin or aminoglycoside produces a synergistic effect that rivals or surpasses that of other aminoglycoside- or polymyxin-containing regimens. Clinical studies performed to date primarily have involved patients with pneumonia and/or bacteraemia due to Klebsiella pneumoniae , Pseudomonas aeruginosa or Acinetobacter baumannii. Overall, the observed success rates with fosfomycin combination regimens were consistent with those reported for other combination regimens commonly used to treat these patients. In studies in which direct treatment comparisons can be derived, the results suggest that patients who received fosfomycin combination therapy had similar or improved outcomes compared with other therapies and combinations, especially when it was used in combination with a β-lactam that (1) targets PBP-3 and (2) has exceptional stability in the presence of β-lactamases. Collectively, the data indicate that combination therapy with IV fosfomycin should be considered as a potential alternative to aminoglycoside or polymyxin combinations for patients with antibiotic-resistant Gram-negative infections when benefits outweigh risks. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (SA) is a leading cause of bloodstream infection. The liver represents the sentinel immune organ for clearance of bloodstream pathogens and eradication of intracellular SA from liver-resident macrophages (Kupffer cells, KCs) eliminates the likely pathogenic reservoir that contributes to persistent bacteraemia. Objectives We assessed antimicrobial activity at phagolysosome-mimicking pH, intracellular penetration, and SA eradication within KCs in vitro for clinically prescribed antistaphylococcal agents alone or in combination: vancomycin, daptomycin, ceftaroline, ceftobiprole, oritavancin, oxacillin, cefazolin; rifampin and fosfomycin. Methods pH-adjusted broth microdilution assays, intracellular bioaccumulation assays, and intracellular killing assays against clinical bloodstream isolates were performed using a murine KC line with study agents. Results Rifampin and β-lactams exhibited enhanced activity [2- to 16-fold minimum inhibitory concentrations (MIC) decrease] at phagolysosomal pH while vancomycin, oritavancin, daptomycin and fosfomycin demonstrated reduced activity (2- to 32-fold MIC increase in order of least to greatest potency reduction). All agents evaluated had poor to modest intracellular to extracellular concentration ratios (0.024–7.8), with exceptions of rifampin and oritavancin (intracellular to extracellular ratios of 17.4 and 78.2, respectively). Finally, we showed that the first-line treatment for SA bacteraemia (SAB), vancomycin, performed worse than all other tested antibiotics in eradicating intracellular SA at human C max concentration (0.20 log cfu decrease), while oritavancin performed better than all other agents alone (2.05 versus 1.06–1.36 log cfu decrease). Conclusions Our findings raise concerns about the efficacy of commonly prescribed antibiotics against intracellular SA reservoirs and emphasize the need to consider targeting pathogen eradication from the liver to achieve early control of SAB. [ABSTRACT FROM AUTHOR]

Purpose: Zinc Oxide Nanoparticle (ZnO NPs) production has become more common because of the benefits of the green strategy, which include its ease of use, environmental friendliness, and cheap operating costs. In order to accomplish the goal of green chemistry, the green synthesis process also uses safe solvents like water and ethanol. ZnO NPs are among the metal oxide-NPs used in antibacterial and bioremediation applications. Materials and Methods: Energy Dispersive X-ray spectroscopy (EDX), Fourier Transform Infrared spectroscopy (FT-IR), X-Ray Diffractometer (XRD), and Field Emission Scanning Electron Microscopy (FESEM) were used to analyze the green-produced ZnO NPs. Results: ZnO nanoparticles have an average size of 22.89 nm, which is corroborated by FESEM pictures, indicating that the particles are tiny. The excellent purity of ZnO NPs has been confirmed by EDX data. The antibacterial activity of ZnO NPs was assessed against a few dangerous pathogens. Zinc oxide nanoparticles were shown to have an interesting antibacterial action against both gram-positive and gram-negative bacteria at micromolar concentrations because they exhibit the maximum diameter of inhibition zone at concentrations 100 mg/ml of S. aureus, E. coli, K. pneumonia, Acintobacret spp, S. fecalis reaching (27,19,18,17, and 14) mm, respectively while S. pneumonia were resistant. The ZnO NPs recorded at a concentration of 12.5 mg/ml lowest areas of the inhibition zone against the same isolates reaching (16, 11, 11, 12, and 10) mm while S. pneumonia were resistant, respectively, as well. Conclusion: ZnO NPs, since they have excellent antibacterial properties, and are biocompatible, they will open up a new line of inquiry for antibacterial agent research because they are stable, nontoxic, and harmless. [ABSTRACT FROM AUTHOR]

Background and objective: Hypernatremia is a possible side effect of intravenous fosfomycin. The aim of this study was to investigate the effects of changes in sodium (Na) levels on hospital stay and survival in patients hospitalized in the intensive care unit receiving fosfomycin. Subjects and methods: This study was conducted retrospectively on the files of patients over the age of 60, who were admitted to the Internal Medicine Intensive Care Unit. Plasma sodium levels were observed and documented over a period of 14 days. The patients were divided into two groups (Hypernatremia group Na > 145 mEq/L vs normonatremia group 135–145 mEq/L). In addition, daily sodium changes were noted for 14 days in patients. Results: The mean age of the patients was 75 years. Hospitalization days were longer for hypernatremia patients (31.5 days vs 41 days, p = 0.003). Patients with hypernatremia had an extended duration of stay in the intensive care unit. (21 days vs 31 days p = 0.002). The 1-month survival rate was 61.4% in patients with hypernatremia and 24.9% in patients without hypernatremia (p = 0.004). The absence of hypernatremia increases mortality by 2.09 times (95% CI 1.35–3.23). When discharge and mortality rates were analyzed according to sodium fluctuation, discharged patients exhibited a lower sodium fluctuation (4 min/max (−10/19) vs 6 min/max (−16/32) p < 0.001). Conclusion: In conclusion, the strength of our study is that it specifically focuses on the consequences of the sodium fluctuation on patient management and provides results. [ABSTRACT FROM AUTHOR]

Fosfomycin (FOS) is an effective antibiotic against multidrug-resistant Enterobacterales, but its effectiveness is reducing. Little is known on the current prevalence of FosA enzymes in low-risk pathogens, such as Citrobacter freundii. The aim of the study was the molecular characterization of a carbapenemase- and FosA-producing C. freundii collected in Italy. AK867, collected in 2023, showed an XDR profile, retaining susceptibility only to colistin. AK867 showed a FOS MIC >128 mg/L by ADM. Based on WGS, AK867 belonged to ST116 and owned a wide resistome, including fosA3, blaKPC-2, and blaVIM-1. fosA3 was carried by a conjugative pKPC-CAV1312 plasmid of 320,480 bp, on a novel composite transposon (12,907 bp). FosA3 transposon shared similarities with other fosA3-harboring pKPC-CAV1312 plasmids among Citrobacter spp. We report the first case of FosA3 production in clinical carbapenemase-producing C. freundii ST116. The incidence of FosA3 enzymes is increasing among Enterobacterales, affecting even low-virulence pathogens, as C. freundii. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of types of bacterial pathogens involved in urinary tract infections and antibiotic sensitivity patterns among diabetic patients in the medical units of Khyber Teaching Hospital Peshawar. Study Design: Cross-sectional study. Setting: Department of Medicine, Khyber Teaching Hospital, Peshawar. Period: November 9, 2022 until May 8, 2023. Methods: The study was conducted after the approval of the hospital’s ethical committee and the written informed consent of patients. Data was entered and analyzed using SPSS. Patients aged 16 to 80 years of both genders admitted to medical units with diabetes and diagnosed with urinary tract infection were enrolled using a nonprobability consecutive sampling technique. Results: In our study, a total of 184 patients were enrolled, with a mean age of 52.08±18.4 years. There were 42.4% male and 57.6% female patients. The most common organism isolated was E. coli in 37% of patients, followed by Klebsiella in 23.9% of patients, Pseudomonas in 6.3%, Enterococcus in 12%, and Proteus mirabilis in 10.9% of patients. The most sensitive drug was Fosfomycin in 89.1% of patients, followed by nitrofurantoin in 81.5%, imipenem in 77.1%, amikacin in 73.3%, Piperacillin/tazobactam in 69%, gentamycin in 67.9%, Trimethoprimsulfamethoxazole in 66.8%, Amoxicillin-clavulanic acid in 59.7%, ciprofloxacin in 54.3%, ceftriaxone in 51%, and cefixime in 46.1% of patients. Conclusion: E. coli is the most common organism isolated in urinary tract infection in diabetics and Fosfomycin is the most sensitive drug for treatment. [ABSTRACT FROM AUTHOR]

Multidrug-resistant or extended drug resistance has created havoc when it comes to patient treatment, as options are limited because of the spread of pathogens that are extensively or multidrug-resistant (MDR or XDR) and the absence of novel antibiotics that are effective against these pathogens. Physicians have therefore started using more established antibiotics such as polymyxins, tetracyclines, and aminoglycosides. Fosfomycin has just come to light as a result of the emergence of resistance to these medications since it continues to be effective against MDR and XDR bacteria that are both gram-positive and gram-negative. Fosfomycin, a bactericidal analogue of phosphoenolpyruvate that was formerly utilised as an oral medication for uncomplicated urinary tract infections, has recently attracted the interest of clinicians around the world. It may generally be a suitable therapy option for patients with highly resistant pathogenic infections, according to the advanced resistance shown by gram-negative bacteria. This review article aims to comprehensively evaluate the impact of fosfomycin on gram negative infections, highlighting its mechanism of action, pharmacokinetics, clinical efficacy, and resistance patterns. [ABSTRACT FROM AUTHOR]

Background Fosfomycin is gaining increasing attention for its activity against MDR or XDR pathogens. Currently, IV fosfomycin is a potential option for treating various infections, including urinary tract infections, pneumonia and skin infections when first-line treatments fail. Objectives To evaluate the demographic, clinical, microbiological and treatment modality of children received IV fosfomycin to treat infections caused by MDR pathogens since there are few data on the use of fosfomycin in children. Methods This study was conducted retrospectively with patients under 18 years of age who were treated with IV fosfomycin for at least 72 h due to infections caused by MDR pathogens between January 2019 and October 2023 at Marmara University Pendik Training and Research Hospital, İstanbul, Türkiye. Data on demographic and clinical features, microbiological findings, treatment modalities and side effects were evaluated. Results Twenty-five children, for a total of 32 cases of infection episodes, with a mean age of 11.4 ±   3.92 years who received IV fosfomycin were included. The most frequent comorbidity was chronic pulmonary diseases, and the most common infection needed for IV fosfomycin was MDR Pseudomonas aeruginosa pneumonia. In all cases, fosfomycin was administered in combination with other antibiotics, mainly meropenem–colistin (68.7%) or meropenem (15.6%). Twenty-two (71.9%) cases had favourable clinical responses at the end of therapy. Conclusions Our results suggest that IV fosfomycin may be an effective treatment option for MDR pathogens in the paediatric population. Nevertheless, careful stewardship is necessary to maintain efficacy and reduce antimicrobial resistance selection risk. [ABSTRACT FROM AUTHOR]

In vitro studies have suggested that acidic pH may reduce and increase the efficacy of ciprofloxacin and fosfomycin, respectively, when used to treat Escherichia coli and Klebsiella pneumoniae infections. We assessed the effects of acidic, neutral, and alkaline urine pH on the efficacy of optimized ciprofloxacin and fosfomycin dosages in UTI murine model of E. coli and K. pneumoniae. Immunocompetent and immunocompromised mice with adjusted urine pH were inoculated with E. coli and K. pneumoniae strains, and the efficacy was assessed based on the bacterial concentrations in tissues and fluids at 72 h, with respect to untreated controls. At acidic urine pH, both antimicrobials were effective, achieving similar reductions in E. coli concentrations in the kidneys in immunocompetent and immunocompromised mice and in K. pneumoniae in immunocompetent mice. At a neutral urine pH, both therapies reduced the presence of E. coli in the kidneys of immunocompetent mice. However, in immunocompromised mice, antimicrobials were ineffective at treating E. coli infection in the kidneys at a neutral urine pH and showed reduced efficacy against K. pneumoniae at both acidic and neutral urine pH. The results showed no correlation between urine pH and antimicrobial efficacy, suggesting that the reduced effectiveness is associated with the animals' immunocompetence status. [ABSTRACT FROM AUTHOR]

Abstract Objectives The aim of this study was to identify the synergistic effect and mechanisms of fosfomycin (FM) combined with colistin (COL) against KPC-producing Klebsiella pneumoniae (KPC-Kp). Methods The bactericidal effects, induced drug resistance and cytotoxicity of FM combined with COL were evaluated by time-kill assays and mutation rate test. Time-kill assays and transcriptomics analysis were used to further clarify the mechanism of FM combined with COL. The bacteria were taken from different points in time-kill assays, reactive oxygen species (ROS), nitric oxide and redox related enzymes were detected. The mechanism of synergistic bactericidal action was analyzed by transcriptome. Results The bactericidal effect of FM combined with COL was better than that of monotherapy. The mutation frequency of FM alone at low dose (8 mg/L) was higher than that at high dose (64 mg/L). COL induced resistant isolates resulted in FM and COL resistance, while FM alone or combined with COL only resulted in FM resistance. The survival rate of Thp-1 cells in FM combined with COL against K. pneumoniae was higher than that of monotherapy. The intracellular nitric oxide, activities of total superoxide dismutase and catalase were increased along with the increase of FM concentration against KPC-Kp. FM combined with COL induced ROS accumulation and antioxidant capacity increase. Transcriptome analysis showed FM combined with COL could regulate the levels of soxRS and oxidative phosphorylation, in order to clear ROS and repair damage. In addition, FM combined with COL could result in synergetic bactericidal efficacy by inhibiting ribosomal transcription. Conclusions FM combined with COL mediated synergistic bactericidal effect by regulating ROS accumulation and inhibiting ribosomal protein transcription, resulting in lower resistance and cytotoxicity.

The investigation focused on exploring the potential applications of the BN nanocage (B12N12) as both an adsorbent and a sensor for removing and detecting fosfomycin (FM) using density functional theory computations. In this respect, the interaction of FM with B12N12 was evaluated at 3 different configurations and the most stable one was determined. The results showcased the interaction between FM and B12N12, highlighting the feasibility, exothermic nature, and spontaneity of the interaction, emphasizing the effectiveness of B12N12 as an FM adsorbent. Moreover, the study scrutinized the influence of water as a solvent and different temperatures on the thermodynamic parameters. Interestingly, the results indicated that these factors had negligible impacts on the interactions. Nonetheless, it was noted that the interactions were a bit stronger in vacuum and at lower temperatures. Additionally, the Frontier Molecular Orbital (FMO) analysis exhibited a bandgap of 6.716 eV for B12N12, which increased by approximately 90 % to 13.381 eV upon FM adsorption, indicating a significant reduction in the electrochemical conductivity of BN nanocage during the FM adsorption process, thereby hinting at its potential use as an analytical signal for the electrochemical detection of FM.

Background: Urinary Tract Infection (UTI) is a prevalent infectious disease caused by Enterobacteriaceae, with Escherichia coli being the predominant etiological agent. The rise in multidrug resistance (MDR) and dearth of effective oral antibiotics have constrained the therapeutic option for UTIs. Fosfomycin, an orally administrated bactericidal broad-spectrum antibiotic exhibits activity against MDR pathogens. The aim of this study was to assess in vitro efficacy of Fosfomycin against Escherichia coli isolates. Materials and Methods: This descriptive cross-sectional study spanned a duration of 6 months. A total of 3782 samples were collected from suspected UTI patients and processed. Escherichia coli isolates were identified by conventional method and subjected to in vitro susceptibility testing to Fosfomycin and other commonly utilized antibiotics by Modified Kirby-Bauer disk diffusion method. Results: Among 3782 samples, 929 (24.56%) exhibited significant colony growth, with Escherichia coli accounting for 378 (40.6%) of the positive isolates. Higher rates of resistance were observed for Nalidixic acid (92.60%), Norfloxacin (78.58%) and Doxycycline (76.99%). Of the Escherichia coli isolates, 269 (71.76%) isolates were identified as MDR isolates. The susceptibility of Escherichia coli isolates to Fosfomycin was 95.23%, while that of MDR Escherichia coli isolates was 95.54%. Conclusion: Fosfomycin exhibits excellent in vitro susceptibility against MDR Escherichia coli isolates in UTIs, suggesting its potential as a promising alternative oral agent for outpatient therapy of UTI.

Abstract Background In 2019, the shortage of cefazolin led to the demand for cefotiam and cefmetazole exceeding the supply. The Department of Nephro-urology at Nagoya City University Hospital used fosfomycin as a substitute for perioperative prophylaxis. This retrospective preliminary study evaluated the efficacy of fosfomycin and cefotiam for preventing infections following ureterorenoscopy. Methods The study included 182 patients who underwent ureterorenoscopy between January 2018 and March 2021). Perioperative antibacterial treatment with fosfomycin (n = 108) or cefotiam (n = 74) was administered. We performed propensity score matching in both groups for age, sex, preoperative urinary catheter use, and preoperative antibiotic treatment. Results The fosfomycin and cefotiam groups (n = 69 per group) exhibited no significant differences in terms of patients’ median age, operative duration, preoperative urine white blood cell count, preoperative urine bacterial count, and the rate of preoperative antibiotic treatment. In the fosfomycin and cefotiam groups, the median duration of postoperative hospital stay was 3 and 4 days, respectively; the median maximum postoperative temperature was 37.3 °C and 37.2 °C, respectively. The fosfomycin group had lower postoperative C-reactive protein levels and white blood cell count than the cefotiam group. However, the frequency of fever > 38 °C requiring additional antibiotic administration was similar. Conclusions During cefotiam shortage, fosfomycin administration enabled surgeons to continue performing ureterorenoscopies without increasing the complication rate.

Objective: A case of post-neurosurgical ventriculitis caused by a KPC-producing Klebsiella pneumoniae (KPC-Kp) with a ceftazidime/avibactam-resistant, meropenem-susceptible phenotype is reported. Methods and results: The patient had a concomitant bloodstream infection with a wild-type KPC-Kp with a ceftazidime/avibactam-susceptible, meropenem-resistant phenotype. Prolonged treatment with intravenous fosfomycin and meropenem/vaborbactam achieved clinical success.Therapeutic drug monitoring performed during the first days of treatment showed for the first time that vaborbactam efficiently penetrates cerebrospinal fluid. In contrast, meropenem was undetectable in cerebrospinal fluid at each sampling, suggesting that additional doses of meropenem may be required to appropriately prescribe meropenem/vaborbactam for central nervous system infections. Plasma and cerebrospinal fluid levels of fosfomycin were adequate, confirming the potential of this agent possibly even in the fight against multidrug-resistant organisms. Conclusions: This case highlights the need for therapeutic drug monitoring as a crucial tool for optimizing treatment in complicated cases where the pharmacokinetic behaviour of antibiotics is difficult to predict.

Escherichia coli multi-locus sequence type ST131 is a globally distributed pandemic lineage that causes multidrug-resistant extra-intestinal infections. ST131 E. coli frequently produce extended-spectrum β-lactamases (ESBLs), which confer resistance to many β-lactam antibiotics and make infections difficult to treat. We sequenced the genomes of 154 ESBL-producing E. coli clinical isolates belonging to the ST131 lineage from patients at the University of Pittsburgh Medical Center (UPMC) between 2004 and 2018. Isolates belonged to the well described ST131 clades A (8%), B (3%), and C (89%). Time-dated phylogenetic analysis estimated that the most recent common ancestor (MRCA) for all clade C isolates emerged around 1989, consistent with previous studies. We identified multiple genes potentially under selection in clade C, including the cell wall assembly gene ftsI, the LPS biosynthesis gene arnC, and the yersiniabactin uptake receptor fyuA. Diverse ESBL-encoding genes belonging to the blaCTX-M, blaSHV, and blaTEM families were identified; these genes were found at varying numbers of loci and in variable numbers of copies across isolates. Analysis of ESBL flanking regions revealed diverse mobile elements that varied by ESBL type. Overall, our findings show that ST131 subclade C dominated among patients and uncover possible signals of ongoing adaptation within this ST131 lineage. [ABSTRACT FROM AUTHOR]

The significance of this study lies in its exploration of bioactive plant extracts as a promising avenue for combating oral bacterial pathogens, offering a novel strategy for biofilm eradication that could potentially revolutionize oral health treatments. Oral bacterial infections are common in diabetic patients; however, due to the development of resistance, treatment options are limited. Considering the excellent antimicrobial properties of phenolic compounds, we investigated them against isolated oral pathogens using in silico and in vitro models. We performed antibiogram studies and minimum inhibitory concentration (MIC), antibiofilm, and antiquorum sensing activities covering phenolic compounds. Bacterial strains were isolated from female diabetic patients and identified by using 16S rRNA sequencing as Pseudomonas aeruginosa, Bacillus chungangensis, Bacillus paramycoides, and Paenibacillus dendritiformis. Antibiogram studies confirmed that all strains were resistant to most tested antibiotics except imipenem and ciprofloxacin. Molecular docking analysis revealed the significant interaction of rutin, quercetin, gallic acid, and catechin with transcription regulator genes 1RO5, 4B2O, and 5OE3. All tested molecules followed drug-likeness rules except rutin. The MIC values of the tested compounds varied from 0.0625 to 0.5 mg/mL against clinical isolates. Significant antibiofilm activity was recorded in the case of catechin (73.5% ± 1.6% inhibition against B. paramycoides), cinnamic acid (80.9% ± 1.1% inhibition against P. aeruginosa), and vanillic acid and quercetin (65.5% ± 1.7% and 87.4% ± 1.4% inhibition, respectively, against B. chungangensis) at 0.25-0.125 mg/mL. None of the phenolic compounds presented antiquorum sensing activity. It was, therefore, concluded that polyphenolic compounds may have the potential to be used against oral bacterial biofilms, and further detailed mechanistic investigations should be performed. [ABSTRACT FROM AUTHOR]

This editorial discusses the increasing spread of foodborne pathogens and antimicrobial resistance (AMR) due to the global livestock and poultry industry, food processing industry, and international trade. It highlights the challenges posed by pathogens such as Salmonella, Campylobacter, Clostridium, and Escherichia coli, which contaminate various types of foods and contribute to the burden of AMR and foodborne diseases. The editorial emphasizes the need for more research and understanding of these pathogens, their mechanisms of resistance and virulence, and their dissemination, using multi-omics approaches. Several papers included in the editorial focus on AMR and virulence factors in Salmonella, highlighting the prevalence of resistance genes and the importance of whole genome sequencing in understanding complex patterns of AMR and virulence. The document also discusses various studies on antimicrobial resistance in different bacterial populations, the importance of a comprehensive approach combining genomics and transcriptomics, and the need for research on drug resistance mechanisms in fungi. It concludes by emphasizing the importance of technology in ensuring food safety and the need for further research to understand pathogenicity, evolution, and prevention in our food supplies. [Extracted from the article]

Background: The challenge of treating infections caused by multidrug-resistant Enterobacterales and Acinetobacter baumannii has significantly increased for medical professionals due to their resistance to conventional antibiotics. In such cases, colistin is employed as a final line of defense. This study was aimed to determine the in-vitro efficacy of colistin against multidrug-resistant gram-negative bacteria. Methods: The research was carried out in the bacteriology department of the Mohammed V Military Teaching Hospital in Rabat, Morocco. 321 isolates of multi-resistant Enterobacterales and Acinetobacter baumannii from various clinical samples were identified by standard microbiological protocols, and the Colistin minimum inhibitory concentrations value was determined using the microdilution method. Results: Of the 321 isolates included in the study, 76.3% were Enterobacterales and 23.6% were Acinetobacter baumannii. The minimum inhibitory analysis showed that 96.3% of the isolates were sensitive, while 3.7% were identified as resistant. The prevalence of resistance to colistin among multi-resistant Enterobacterales was 4.1%, and the MIC50 and MIC90 were 0.5 μg/ml and 1μg/ml respectively. Among the collected Acinetobacter baumannii isolates, the prevalence of colistin resistance was 2.6%, with the MIC50 and MIC90 of 0.5 μg/ml. Conclusion: The research indicates that colistin could be a viable treatment option for infections caused by multi-resistant Enterobacterales and Acinetobacter baumannii. [ABSTRACT FROM AUTHOR]

Background: In 2019, the shortage of cefazolin led to the demand for cefotiam and cefmetazole exceeding the supply. The Department of Nephro-urology at Nagoya City University Hospital used fosfomycin as a substitute for perioperative prophylaxis. This retrospective preliminary study evaluated the efficacy of fosfomycin and cefotiam for preventing infections following ureterorenoscopy. Methods: The study included 182 patients who underwent ureterorenoscopy between January 2018 and March 2021). Perioperative antibacterial treatment with fosfomycin (n = 108) or cefotiam (n = 74) was administered. We performed propensity score matching in both groups for age, sex, preoperative urinary catheter use, and preoperative antibiotic treatment. Results: The fosfomycin and cefotiam groups (n = 69 per group) exhibited no significant differences in terms of patients' median age, operative duration, preoperative urine white blood cell count, preoperative urine bacterial count, and the rate of preoperative antibiotic treatment. In the fosfomycin and cefotiam groups, the median duration of postoperative hospital stay was 3 and 4 days, respectively; the median maximum postoperative temperature was 37.3 °C and 37.2 °C, respectively. The fosfomycin group had lower postoperative C-reactive protein levels and white blood cell count than the cefotiam group. However, the frequency of fever > 38 °C requiring additional antibiotic administration was similar. Conclusions: During cefotiam shortage, fosfomycin administration enabled surgeons to continue performing ureterorenoscopies without increasing the complication rate. [ABSTRACT FROM AUTHOR]

Background and aim. Infections caused by pathogenic bacteria increase patient morbidity and mortality and significantly raise treatment costs. The use of silver nanoparticles as an alternative treatment for S aureus, E coli, MRSA, E faecalis, K pneumoniae and P aeruginosa indicates their antibacterial effect and prompts medical research to consider the next generation of antibacterial drugs that could change antibiotic therapy. By combining silver nanoparticles with different classes of antibiotics, the antibacterial effect is evidenced by increased values of the inhibition zone compared to the values obtained for some antibiotics commonly used in the treatment of bacterial infections. This study focuses on comparing the antibacterial activity of antibiotics versus antibiotics combined with silver nanoparticles against various bacteria, by comparing inhibition zones obtained for both. We aim to prove that the size of the inhibition zone for antibiotics combined with silver nanoparticles is greater, thus confirming the improved antibacterial effect. Metods. In this study we tested the antibacterial activity of solutions of silver nanoparticles alone or in combination with different antibiotics. We used standard bacterial strains, ATCC, both Gram positive bacteria Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, as well as Gram negative bacteria Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, but also on clinical isolates: a strain MRSA (Methicillin Resistant Staphylococcus aureus) and a PDR strain (pan drug resistant) of Klebsiella pneumoniae. Bacterial identification was performed using Vitek MS analyzer (bioMerieux). Antibiotic susceptibility determination was performed with VITEK2 COMPACT SYSTEM (bio Merieux, Inc Durham NC) with ready to use VITEK AST cards. The interpretation of the results was done in compliance with EUCAST 2023-2024 standards. Testing was performed for several classes of antibiotics, silver nanoparticle solutions in 2 concentrations (10 μg/mL and 100 μg/mL) and for combinations of antibiotics with silver nanoparticle solutions. The diameter of the inhibition zone (ZOI) for silver nanoparticles, antibiotics and silver nanoparticles combined with antibiotic against each bacterium was expressed in millimeters. The Kirby-Bauer diskdiffusion method, in accordance with current EUCAST standards, was used to analyze the antibacterial effect of antibiotics, silver nanoparticles, and antibiotics combined with silver nanoparticles at biocompatible doses of 10 and 100 μg/mL. The experiments were conducted in triplicate, and the results were almost identical. Results. The results of this study show that the silver nanoparticles displayed antibacterial activity, proven by the appearance of the inhibition zone, in various sizes, for all bacteria studied. The antibiotic classes tested were beta-lactamins, first, second, third and fourth generation cephalosporins, macrolides, fluoroquinolones, lincosamides, aminoglycosides, glycopeptides, tetracyclines, oxazolidinones, sulfonamides, rifamycins, amphenicols. Testing S aureus ATCC 29213, the highest zone of inhibition was demonstrated for cephalosporins (32.6667 ± 0.701 mm), macrolides (31.6667 ± 0.701 mm, and lincosamides (29.6667 ± 0.701 mm). Testing MRSA (internal code GR0333), the highest zone of inhibition for combination of silver nanoparticles and antibiotics was demonstrated for fluoroquinolones (36.3333 ± 0.701 mm), lincosamides (32.3333 ± 0.701 mm), Fusid acid (32.3333 ± 0.701 mm) and aminoglicosides (31.3333 ± 0.701 mm). Testing E coli ATCC 25922 the highest zone of inhibition was for Fosfomycine, 39 mm and for E faecalis ATCC 29212 for aminoglicosides was 19 mm. For K pneumoniae (internal code GQ8575) the inhibition zone for silver nanoparticles 100 µg/mL was 12.3333 ± 0.701 mm and for P aeruginosa ATCC 27253 was 16 ± 1.214 mm. Conclusions. The use of metallic nanoparticles, especially silver ones, as antimicrobial agents with definite bactericidal activity has led medical specialists to consider this new treatment which may change antibacterial therapy. Studies of in vitro combinations between silver nanoparticles and different classes of antibiotics represent a highly efficient and effective new antibacterial treatment against multidrug-resistant bacteria. To avoid the problem of antimicrobial resistance associated with conventional antibiotics, it is necessary to understand the adaptive mechanisms of bacteria under the action of metal nanoparticles, which could be exploited in future studies. Further in vitro and in vivo studies that would assess specify the biocompatibility and toxicity of silver nanoparticles will make these super nanomaterials the medicines of the future. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTIs) are a very frequent reason for consultations and antibiotic prescriptions in everyday practice. Excessive and inappropriate use of antibiotics is responsible for the emergence and spread of multidrug-resistant (MDR) uropathogenic bacteria. The aim of this study was to determine the frequency of isolation and antibiotic resistance of uropathogenic strains of Escherichia coli (UPEC) isolated in the bacteriology-virology laboratory of the University Hospital Centre (CHU) in Brazzaville, Congo. Methodology: This was a descriptive retrospective study over a 6-month period (from 1 April to 31 September 2022) that included all non-redundant uropathogenic UPEC strains isolated from urine samples of patients with UTIs referred to the bacteriology-virology laboratory of the University Hospital of Brazzaville, Congo. The strains were isolated from urine samples after inoculation onto Cystine Lactose Electrolyte Deficient agar (CLED), and incubating aerobically at 37°C for 24 hours. Identification was carried out using BioMérieux API 20 E galleries and antibiotic susceptibility testing was performed on Mueller Hinton agar medium using selected antibiotic discs. Extended spectrum β-lactamase (ESBL) production by the isolates was confirmed by double disc synergy test. Data were analysed using Microsoft Office Excel 2013. Results: Of the 187 non-repetitive uropathogenic Enterobacteriaceae isolated from urine samples of 187 patients with clinical UTIs, 81 were strains of UPEC, giving an overall frequency of UPEC isolation of 43.0%. The modal age of patients from whom UPEC strains were isolated was 57 years (age range 2 to 86 years), with 49 from females and 32 from males (F: M ratio of 1.5). The UPEC strains showed high rates of resistance to amoxicillin (94.0%), amoxicillin-clavulanic acid (84.0%), piperacillin-tazobactam (73.0%), ceftriaxone (52.0%), cefixime (54.0%), cefotaxime (55.0%), ceftazidime (58.0%), gentamicin (42.0%), ciprofloxacin (55.0%) and sulfamethoxazole-trimethoprim (90.0%) but relatively low resistance rates were observed with imipenem (4.0%), fosfomycin (8.0%) and amikacin (18.0%). The ESBL-producing strains accounted for 24.5% (46/187) of all uropathogenic Enterobacteriaceae isolates, and compared to the non-ESBL producing strains, had significantly higher resistance rates to gentamicin (p=0.018), ciprofloxacin (p=0.0003), ceftazidime (p<0.0001), ceftriaxone (p<0.0001), cefixime (p<0.0001), cefotaxime (p<0.0001), piperacillin-tazobactam (p=0.0006), and amoxicillin-clavulanate (p=0.0024). Conclusion: Our results show high rates of in vitro resistance of UPEC strains to commonly used antibiotics, which potentially limits therapeutic options and therefore a real public health challenge in Congo. [ABSTRACT FROM AUTHOR]

Background: Gram-negative bacteria (GNB) are becoming increasingly resistant to a wide variety of antibiotics. There are currently limited treatments for GNB, and the combination of antibiotics with complementary mechanisms has been reported to be a feasible strategy for treating GNB infection. The inability to cross the GNB outer membrane (OM) is an important reason that a broad spectrum of Gram-positive only class of antibiotics (GPOAs) is lacking. Polymyxins may help GPOAs to permeate by disrupting OM of GNB. Objective: To identify what kind of GPOAs can be aided to broaden their anti-GNB spectrum by polymyxins, we systematically investigated the synergy of eight GPOAs in combination with colistin (COL) and polymyxin B (PMB) against GNB in vitro. Methods: The synergistic effect of COL or PMB and GPOAs combinations against GNB reference strains and clinical isolates were determined by checkerboard tests. The killing kinetics of the combinations were assessed using time-kill assays. Results: In the checkerboard tests, polymyxins-GPOAs combinations exert synergistic effects characterized by species and strain specificity. The synergistic interactions on P. aeruginosa strains are significantly lower than those on strains of A. baumannii, K. pneumoniae and E. coli. Among all the combinations, COL has shown the best synergistic effect in combination with dalbavancin (DAL) or oritavancin (ORI) versus almost all of the strains tested, with FICIs from 0.16 to 0.50 and 0.13 to < 0.28, respectively. In addition, the time-kill assays demonstrated that COL/DAL and COL/ORI had sustained bactericidal activity. Conclusions: Our results indicated that polymyxins could help GPOAs to permeate the OM of specific GNB, thus showed synergistic effects and bactericidal effects in the in vitro assays. In vivo combination studies should be further conducted to validate the results of this study. [ABSTRACT FROM AUTHOR]

The emergence of extensively-resistant strains of Klebsiella pneumoniae (K. pneumoniae) in healthcare settings is linked to prolonged hospitalization and uncontrolled use of antibiotics. There is a paucity of data regarding the prevalence and mechanisms of colistin and fosfomycin resistance encoding genes rate and mechanisms in Iran. The objective of this study was to determine the prevalence of biofilm formation and fosfomycin and colistin resistance among K. pneumoniae strains producing ESBL and carbapenemases by detecting the mcr-1, mcr-2, and fosA genes in Tehran, Iran, during the 2020-2021 period. After collecting 73 samples, the isolates were identified using biochemical tests. Antibiotic susceptibility test was performed using the disk diffusion method. The phenotypic determination of extended-spectrum beta-lactamases (ESBLs) and carbapenemase enzymes was conducted using combined disk and CARBA-NP tests, respectively. The biofilm formation was conducted using a microtiter tissue plate assay. Polymerase chain reaction (PCR) was employed to detect the mcr-1, mcr-2 and fosA genes, which are associated with colistin and fosfomycin resistance, respectively. The highest resistance rate was observed against ampicillin (97%), chloramphenicol (90%), and ciprofloxacin (87%), respectively. In contrast, the lowest resistance rate was noted against gentamicin (4%), amikacin (10%), and cotrimoxazole (18%). Moreover, 44 and 23 isolates were identified as ESBL and carbapenemase -producing K. pneumonia), respectively. Of the fortyeight isolates that formed strong biofilms, one was a non-biofilm producer. The PCR test revealed the amplification of the fosA2 gene in four isolates and the mcr-2 genes in one isolate. However, no amplification of the fosA3 or mcr-1 genes was observed. The present study demonstrated that the frequency of K. pneumoniae isolates producing ESBL and carbapenemase, as well as mcr-1, mcr-2 and fosA genes, was relatively low. However, given the potential for these genes to be disseminated more widely, it is imperative to implement effective isolation and control measures. Moreover, these strains demonstrated the capacity to form biofilms in vitro, which can lead to persistent infections in the hospital settings. [ABSTRACT FROM AUTHOR]

Central nervous system infections are among the most severe infectious conditions in the neonatal period and are still burdened by significant mortality, especially in preterm infants and those with a low birth weight or other comorbidities. In this study, we examined the role of fosfomycin-containing antibiotic regimens in neonates with central nervous system infections. We included six neonates over a period of five years: four with meningitis and two with cerebral abscesses. All patients underwent fosfomycin therapy after failing first-line antibiotic regimens. Of the six neonates, two died; two developed neurological and psychomotor deficits and two recovered uneventfully. None of the neonates experienced adverse reactions to fosfomycin, confirming the safety of the molecule in this population. In conclusion, the deep penetration in the central nervous system, the unique mechanism of action, the synergy with other antibiotic therapies, and the excellent safety profile all make fosfomycin an attractive drug for the treatment of neonatal central nervous system infections. [ABSTRACT FROM AUTHOR]

Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07–1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14–0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting. [ABSTRACT FROM AUTHOR]

Introduction: New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae (NDM-1-KP) sequence type (ST) 147 poses a significant threat in clinical settings due to its evolution into two distinct directions: hypervirulence and carbapenem resistance. Hypervirulence results from a range of virulence factors, while carbapenem resistance stems from complex biological mechanisms. The NDM-1-KP ST147 clone has emerged as a recent addition to the family of successful clones within the species. Methods: In this study, we successfully synthesized 5-bromo-N-alkylthiophene-2-sulfonamides (3a-c) by reacting 5-bromothiophene-2-sulfonamide (1) with various alkyl bromides (2) using LiH. We also synthesized a series of compounds (4a-g) from compound (3b) using the Suzuki-Miyaura cross-coupling reaction with fair to good yields (56– 72%). Further, we screened the synthesized molecules against clinically isolated New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae ST147. Subsequently, we conducted in-silico tests on compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I. Results: The compound (3b) with favourable drug candidate status, MIC of 0.39 μg/mL, and MBC of 0.78 μg/mL. This low molecular weight compound exhibited the highest potency against the resistant bacterial strains. The in-silico tests revealed that the compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I demonstrated H-bond and hydrophobic interactions. Conclusion: The 5-bromo-N-alkylthiophene-2-sulfonamides displayed antibacterial efficacy against New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae ST147. After the in-vivo trial, this substance might offer an alternative therapeutic option. [ABSTRACT FROM AUTHOR]

Background: Carbapenemase-producing Klebsiella pneumoniae (CRKP) presents a significant challenge to antimicrobial therapy, especially when compounded by resistance to colistin. The objective of this study was to explore molecular epidemiological insights into strains of clinical K. pneumoniae that produce carbapenemases and exhibit resistance to colistin. Eighty clinical isolates of CRKP were obtained from Milad Hospital in Tehran, Iran. Antimicrobial susceptibility and colistin broth disk elution were determined. PCR assays were conducted to examine the prevalence of resistance-associated genes, including blaKPC, blaIMP, blaVIM, blaOXA−48, blaNDM and mcr-1 to -10. Molecular typing (PFGE) was used to assess their spread. Results: Colistin resistance was observed in 27 isolates (33.7%) using the Broth Disk Elution method. Among positive isolates for carbapenemase genes, the most frequent gene was blaOXA−48, identified in 36 strains (45%). The mcr-1 gene was detected in 3.7% of the obtained isolates, with none of the other of the other mcr genes detected in the studied isolates. Conclusion: To stop the spread of resistant K. pneumoniae and prevent the evolution of mcr genes, it is imperative to enhance surveillance, adhere rigorously to infection prevention protocols, and implement antibiotic stewardship practices. [ABSTRACT FROM AUTHOR]

Introduction: Antimicrobial resistance is increasingly becoming a global health concern. This study aimed to investigate and report MDR Escherichia coli (E. coli) prevalence, resistance, and virulence genes from poultry in Jos, Plateau State, Nigeria. Methods: The samples were analyzed using microbiological standard methods and polymerase chain reactions (PCRs). Results: A total of 179 cloacal swabs were collected from bothlocal and exotic poultry breeds, of which 99.4% (178/179) tested positive for E. coli. Among these culturally identified samples, 99.4% (177/178) were furtherconfirmed Escherichia coli with a molecular weight of 401 bp. Multidrugresistance of 45% (80/178) was observed from the confirmed isolates. PCR assays were conducted to detect genes associated with resistance to antibiotics, specifically, tetracycline (tetA gene), sulfonamide (sul1 gene), ampicillin (ampC gene), and quinolone (gyrA gene). Antimicrobial susceptibility test (AST) results revealed substantial antibiotic resistance, with 81.9% (145/177) of the isolates being resistant to tetracycline, 80.2% (142/177) to quinolone, 69.5% (123/177) to sulfonamide, and 66.1% (117/177) to ampicillin. Further analysis on 18 isolates that showed resistance to up to four different antibiotics was carried out using multiplex PCR to detect eae, hlyA, rfbE, fliC, and fstx virulence genes. The study found that 44.4% (15/18) of the isolates were positive for the eae gene, 27.7% (5/18) for stx, 22.2% (4/18) for rfbe gene, and 5.5% (1) for hlya gene, and none tested positive for fliC gene. Conclusion: These results showed high antibiotic resistance, virulent genes, and significant levels of MDR in E. coli from poultry. This study highlights the urgent need for antimicrobial stewardship practices within the poultry industry due to their profound implications for food safety and public health. This issue is particularly critical in Nigeria, where poultry farming constitutes a significant portion of smallholder farming practices. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) formulation in biopolymers is an attractive process for the researcher to decrease the disadvantages of NPs application alone. Bimetallic NPs are a promising formula of two NPs that usually act as synergetic phenomena. Zinc oxide and gold NPs (ZnO@AuNPs) biosynthesis as a bimetallic was prepared via the eco-friendly manner currently. Carboxymethylcellulose (CMC) was employed for the formulation of ZnO@AuNPs as a nanocomposite via a green method. Physicochemical and topographical characterization was assigned to ZnO@AuNPs and nanocomposite features. The nanostructure of bimetallic NPs and nanocomposite were affirmed with sizes around 15 and 25 nm, respectively. Indeed, the DLS measurements affirmed the more reasonable size and stability of the prepared samples as 27 and 93 nm for bimetallic NPs and nanocomposite, respectively. The inhibitory potential of nanocomposite was more than ZnO@AuNPs against Staphylococcus aureus, Escherichia coli, Salmonella typhi, Enterococcus faecalis, Mucor albicans, Aspergillus flavus, and Mucor circinelloid. ZnO@AuNPs and nanocomposite exhibited antioxidant activity via DPPH with IC50 of 71.38 and 32.4 µg/mL, correspondingly. Excellent anti-diabetic potential of nanocomposite with IC50 of 7.4 µg/mL, and ZnO@AuNPs with IC50 of 9.7 µg/mL was reported compared with the standard acarbose with the IC50 of 50.93 µg/mL for amylase inhibition (%). Photocatalytic degradation of RR195 and RB dyes was performed by ZnO@AuNPs and nanocomposite, where maximum degradation was 85.7 ± 1.53 and 88.7 ± 0.58%, respectively using ZnO@AuNPs, 90.3 ± 0.28 and 91.8 ± 0.27%, respectively using nanocomposite at 100 min. [ABSTRACT FROM AUTHOR]

Background: The objectives of the current study were to extract pyocyanin from Pseudomonas aeruginosa clinical isolates, characterize its chemical nature, and assess its biological activity against different bacteria and cancer cells. Due to its diverse bioactive properties, pyocyanin, being one of the virulence factors of P. aeruginosa, holds a promising, safe, and available therapeutic potential. Methods: 30 clinical P. aeruginosa isolates were collected from different sources of infections and identified by routine methods, the VITEK 2 compact system, and 16 S rRNA. The phenazine-modifying genes (phzM, phzS) were identified using polymerase chain reaction (PCR). Pyocyanin chemical characterization included UV-Vis spectrophotometry, Fourier Transform Infra-Red spectroscopy (FTIR), Gas Chromatography-Mass Spectrometry (GC-MS), and Liquid Chromatography-Mass Spectrometry (LC-MS). The biological activity of pyocyanin was explored by determining the MIC values against different clinical bacterial strains and assessing its anticancer activity against A549, MDA-MB-231, and Caco-2 cancer cell lines using cytotoxicity, wound healing and colony forming assays. Results: All identified isolates harboured at least one of the phzM or phzS genes. The co-presence of both genes was demonstrated in 13 isolates. The UV-VIS absorbance peaks were maxima at 215, 265, 385, and 520 nm. FTIR could identify the characteristic pyocyanin functional groups, whereas both GC-MS and LC-MS elucidated the chemical formula C11H18N2O2, with a molecular weight 210. The quadri-technical analytical approaches confirmed the chemical nature of the extracted pyocyanin. The extract showed broad-spectrum antibacterial activity, with the greatest activity against Bacillus, Staphylococcus, and Streptococcus species (MICs 31.25–125 µg/mL), followed by E. coli isolates (MICs 250–1000 µg/mL). Regarding the anticancer activity, the pyocyanin extract showed IC50 values against A549, MDA-MB-231, and Caco-2 cancer cell lines of 130, 105, and 187.9 µg/mL, respectively. Furthermore, pyocyanin has markedly suppressed colony formation and migratory abilities in these cells. Conclusions: The extracted pyocyanin has demonstrated to be a potentially effective candidate against various bacterial infections and cancers. Hence, the current findings could contribute to producing this natural compound easily through an affordable method. Nonetheless, future studies are required to investigate pyocyanin's effects in vivo and analyse the results of combining it with other traditional antibiotics or anticancer drugs. [ABSTRACT FROM AUTHOR]

Extended-spectrum beta-lactamase (ESBL) Escherichia coli (E. coli) is an emerging pathogen of high concern given its resistance to extended-spectrum cephalosporins. Broiler chicken, which is the number one consumed meat in the United States and worldwide, can be a reservoir of ESBL E. coli. Backyard poultry ownership is on the rise in the United States, yet there is little research investigating prevalence of ESBL E. coli in this setting. This study aims to identify the prevalence and antimicrobial resistance profiles (phenotypically and genotypically) of ESBL E. coli in some backyard and commercial broiler farms in the U.S. For this study ten backyard and ten commercial farms were visited at three time-points across flock production. Fecal (n = 10), litter/compost (n = 5), soil (n = 5), and swabs of feeders and waterers (n = 6) were collected at each visit and processed for E. coli. Assessment of ESBL phenotype was determined through using disk diffusion with 3rd generation cephalosporins, cefotaxime and ceftazidime, and that with clavulanic acid. Broth microdilution and whole genome sequencing were used to investigate both phenotypic and genotypic resistance profiles, respectively. ESBL E. coli was more prevalent in backyard farms with 12.95% of samples testing positive whereas 0.77% of commercial farm samples were positive. All isolates contained a blaCTX-M gene, the dominant variant being blaCTX-M-1, and its presence was entirely due to plasmids. Our study confirms concerns of growing resistance to fourth generation cephalosporin, cefepime, as roughly half (51.4%) of all isolates were found to be susceptible dose-dependent and few were resistant. Resistance to non-beta lactams, gentamicin and ciprofloxacin, was also detected in our samples. Our study identifies prevalence of blaCTX-M type ESBL E. coli in U.S. backyard broiler farms, emphasizing the need for interventions for food and production safety. [ABSTRACT FROM AUTHOR]

Background: Due to its rapid resistance development and ability to form biofilms, treatment of Pseudomonas aeruginosa infections is becoming more complicated by the day. Drug combinations may help reduce both resistance and biofilm formation. Methods: Using the microtiter plate assay, we investigated the in vitro inhibition of biofilm formation and the disruption of preformed biofilms in multidrug-resistant and extensively drug-resistant clinical isolates of P. aeruginosa in the presence of peak plasma levels of eight antipseudomonal antibiotics alone and in combination with fosfomycin: ceftazidime, piperacillin/tazobactam, cefepime, imipenem, gentamicin, amikacin, ciprofloxacin and colistin. Results: Combination therapy was significantly superior to monotherapy in its inhibition of biofilm formation. The highest inhibition rates were observed for combinations with colistin, cefepime and ceftazidime. Conclusion: Our results support fosfomycin combination therapy as an enhanced prophylactic option. Moreover, combinations with β-lactam antibiotics and colistin demonstrated a more potent inhibition effect on biofilm formation than protein synthesis inhibitors. [ABSTRACT FROM AUTHOR]

Background and Objectives: Klebsiella pneumoniae is a healthcare-associated infections agent and could be an extended spectrum ß-lactamase (ESBL) producer. Understanding the transmission of this bacterium in a hospital setting needs accurate typing methods. An antibiogram is used to detect the resistance pattern of the isolates. Random Amplified Polymorphic DNA (RAPD) and Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR are rapid, technically simple, and easy-to-interpret DNA typing methods. This study aimed to evaluate the use of antibiotyping, RAPD-, and ERIC-PCR to investigate the heterogeneity of K. pneumoniae isolated from clinical specimens. Materials and Methods: The antibiograms of 46 K. pneumoniae clinical isolates were determined by Vitek® 2 Compact. All isolates underwent RAPD-PCR using AP4 primer and ERIC-PCR using ERIC-2 primer. The dendrogram was generated using the GelJ software and analyzed to determine its similarity. The analysis of antibiogram and the molecular typing diversity index was calculated using the formula of the Simpson's diversity index. Results: About 71.7% of the isolates were ESBL-producers, and more than 80% of isolates were susceptible to amikacin, ertapenem, and meropenem. The antibiotyping produced 32 diverse types with DI = 0.964. In addition, the RAPD-PCR produced 47 different types with DI = 1, while ERIC-PCR was 46 (DI=0.999). Conclusion: Antibiotyping, RAPD- and ERIC-PCR showed powerful discrimination power among the isolates, supported the diversity of K. pneumoniae isolates in current study. These combination could be promising tools for clonal relationship determination, including in tracking the transmission of the outbreak's agent in hospital setting. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is one of the most common bacteria among all biofilm-producing as well as the beta-lactamase producing strains, which is responsible for multi-drug resistance. For better therapeutic applications, it is important to detect the biofilm production by Klebsiella pneumoniae and their antibiogram along with the ability to produce ESBL, MBL, and AmpC β-lactamases. The aim of the study was to determine the prevalence of biofilm formation and ESBL, MBL, AmpC β-lactamase phenotypes in K. pneumoniae as well as the antibiogram of all (biofilm and MBL-producing and nonproducing) isolates of K. pneumoniae. Isolates of K. pneumoniae were tested for biofilm formation by the Congo-red agar method. ESBL, MBL, and AmpC β-lactamase detection were done by both screening and confirmatory tests as per CLSI guidelines. The antibiogram was obtained by the Kirby-Bauer disc diffusion method. Among the total 100 isolates of K. pneumoniae, 40% were biofilm-producing. Most of them were from urine specimens. Out of biofilm-producing isolates, ESBL-28%, MBL- 47% and AmpC β-lactamase- 25.8% producers were observed. K. pneumoniae isolates were seen to have maximum resistance to ceftazidime and maximum sensitivity to nitrofurantoin. Study findings suggest the importance of assessment of biofilm formation for better treatment. The scenario further worsens if such biofilm-producing isolates are also MBL-positive leading to limited therapeutic options. [ABSTRACT FROM AUTHOR]

Background IV fosfomycin is used against MDR Gram-negative bacilli (GNB) but has dose-limiting side effects, especially in patients with impaired kidney function. Objectives To determine the optimal dosage of IV fosfomycin for patients with varying degrees of kidney function. Methods Adult patients receiving IV fosfomycin for treatment of GNB were eligible. Five serial blood samples were collected after at least three doses of fosfomycin; plasma was assayed by LC-MS/MS and modelled by population pharmacokinetic analysis. The PTA for AUC24/MIC of 98.9 for Escherichia coli and Klebsiella pneumoniae , and 40.8 for Pseudomonas aeruginosa were computed by Monte Carlo simulations. Cumulative fractions of response (CFR) were analysed for each pathogen using EUCAST MIC distributions. Results A total of 24 patients were included. Creatinine clearance (CLCR) and gender significantly influenced fosfomycin clearance. The kidney function-adjusted dosing regimens are proposed by using the lowest dose that can achieve ≥90% PTA for AUC24/MIC of 98.9 at an MIC of ≤32 mg/L (EUCAST v.13 susceptibility breakpoint for Enterobacterales). For patients with normal kidney function (CLCR 91–120 mL/min), a dosage of 15 g/day is suggested. This regimen achieved 97.1% CFR against E. coli , whereas CFR was 72.9% for K. pneumoniae and 76.7% for P. aeruginosa. Conclusions A fosfomycin dosage of 15 g/day with adjustment according to kidney function provided high PTA and CFR when treating E. coli. This dosage is lower than that used in current practice and may improve tolerability. Higher dosages may be needed for P. aeruginosa ; however, safety data are limited. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is an opportunistic Gram-negative bacterium that has recently emerged as a clinically important pathogen. It is the most common Acinetobacter species associated with hospital-acquired infections worldwide. This study aimed to investigate the resistance characteristics of clinical carbapenem-resistant A. baumannii isolates from Jordanian hospitals. Between May 2018 and May 2019, a total of 190 isolates of Acinetobacter were collected from patients diagnosed with upper respiratory tract infection (47.5%), sepsis (15.4%), skin infection (14.2%), bronchitis (8.6%), urinary tract infection (4.3%), meningitis (3.7%), diabetes (2.5%), necrotizing fasciitis (1.9%), and cancer, peritonitis, and pneumonia (0.6% each) from seven Jordanian hospitals. Vitek GN ID Cards were employed to identify them, and the identification was validated by the detection of Acinetobacter spp. recA gene (100%), A. baumannii intergenic spacer region (85.3%), and the A. baumannii rpoB gene (85.3%). The Vitek AST-N222 and AST-XN05 cards were utilized to determine the minimum inhibitor concentration for a variety of antibiotics including Gentamicin, Tobramycin, Piperacillin-tazobactam, Ticarcillinclavulanic acid, Ticarcillin, Imipenem, Meropenem, Cefepime, Ceftazidime, Ceftriaxone, Ciprofloxacin, Levofloxacin, Trimethoprim-sulfamethoxazole, Piperacillin, Minocycline, and Tetracycline. The E-test was performed to evaluate the effectiveness of Colistin against all A. baumannii isolates. According to the resistance profiles, the isolates had a multidrug resistance profile, with the largest resistance percentage being 98.8% for Tetracycline and the lowest being 23.5% for Minocycline. The Carbapenem-resistant isolates exhibited rates of 98.1% and 87.7% resistance to Meropenem and Imipenem, respectively. On the contrary, the isolates were 98.7% sensitive to Colistin. The most prevalent carbapenem resistance genes among the Jordanian A. baumannii isolates were blaOXA-23-like, blaOXA-51-like, blaOXA-69, and ISAba1, which were detected in all A. baumannii isolates (100%) in this study. Despite the high prevalence of multidrug resistance in the Jordanian isolates, Colistin may be a viable treatment for A. baumannii infection. [ABSTRACT FROM AUTHOR]