Resistant Isolates Research Articles

Comparative pharmacodynamics and dose optimization of liposomal amphotericin B against Candida species in an in vitro pharmacokinetic/pharmacodynamic model.

As comparative pharmacokinetic/pharmacodynamic (PK/PD) studies of liposomal amphotericin B (L-AMB) against Candida spp. are lacking, we explored L-AMB pharmacodynamics against different Candida species in an in vitro PK/PD dilution model. Eight Candida glabrata, Candida parapsilosis, and Candida krusei isolates (EUCAST/CLSI AMB MIC 0.125-1 mg/L) were studied in the in vitro PK/PD model simulating L-AMB Cmax = 0.25-64 mg/L and t1/2 = 9 h. The model was validated with one susceptible and one resistant Candida albicans isolate. The Cmax/MIC-log10CFU/mL reduction from the initial inoculum was analyzed with the Emax model, and Monte Carlo analysis was performed for the standard (3 mg/kg with Cmax = 21.87 ± 12.47 mg/L) and higher (5 mg/kg with Cmax = 83 ± 35.2 mg/L) L-AMB dose. A ≥1.5 log10CFU/mL reduction was found at L-AMB Cmax = 8 mg/L against C. albicans, C. parapsilosis, and C. krusei isolates (MIC 0.25-0.5 mg/L) whereas L-AMB Cmax ≥ 32 mg/L was required for C. glabrata isolates. The in vitro PK/PD relationship followed a sigmoidal pattern (R2 ≥ 0.85) with a mean Cmax/MIC required for stasis of 2.1 for C. albicans (close to the in vivo stasis), 24/17 (EUCAST/CLSI) for C. glabrata, 8 for C. parapsilosis, and 10 for C. krusei. The probability of target attainment was ≥99% for C. albicans wild-type (WT) isolates with 3 mg/kg and for wild-type isolates of the other species with 5 mg/kg. L-AMB was four- to eightfold less active against the included non-C. albicans species than C. albicans. A standard 3-mg/kg dose is pharmacodynamically sufficient for C. albicans whereas our data suggest that 5 mg/kg may be recommendable for the included non-C. albicans species.

Enrichment culture evaluation and characterization of Streptococcus agalactiae among pregnant women in Japan.

Introduction. Maternal screening tests and prophylactic antibiotics are important to prevent neonatal and infant group B streptococcal (GBS) infections.Hypothesis/Gap Statement. The performance of enrichment broth media for GBS screening that are available in Japan is unclear. Whole-genome data of GBS isolates from pregnant women in Japan is lacking.Aim. The aim of this study was to compare the protocol performance of six enrichment broths and two subculture agar plates, which were all available in Japan, for GBS detection. In addition, we showed whole-genome data of GBS isolates from pregnant women in Japan.Methodology. We collected 133 vaginal-rectal swabs from pregnant women visiting clinics and hospitals in Nagasaki Prefecture, Japan, and compared the protocol performance of 6 enrichment broths and 2 subculture agar plates. All GBS isolates collected in this study were subjected to whole-genome sequencing analysis.Results. We obtained 133 vaginal-rectal swabs from pregnant women at 35-37 weeks of gestation from 8 private clinics and 2 local municipal hospitals within Nagasaki Prefecture, Japan. The detection rate of the protocol involving the six enrichment broths and subsequent subcultures varied between 95.5 and 100 %, depending on the specific choice of enrichment broth. The GBS carriage rate among pregnant women in this region was 18.8 %. All 25 isolates derived from the swabs were susceptible to penicillin, whereas 48 and 36 % of the isolates demonstrated resistance to erythromycin and clindamycin, respectively. The distribution of serotypes was highly diverse, encompassing seven distinct serotypes among the isolates, with the predominant serotype being serotype V (n = 8). Serotype V isolates displayed a tendency towards increased resistance to erythromycin and clindamycin, with all resistant isolates containing the ermB gene.Conclusion. There was no difference in performance among the culture protocols evaluated in this study. GBS strains isolated from pregnant women appeared to have greater genomic diversity than GBS strains detected in neonates/infants with invasive GBS infections. To confirm this result, further studies with larger sample sizes are needed.

Isolation, Molecular Characterization, and Determination of Antibiotic Resistance Patterns of Lactic Acid Bacteria from Regional Yogurt Samples and their Probiotic Properties

Objectives:: This investigation aims to isolate the Lactic Acid Bacteria (LAB) from yogurt samples from the Tangail district of Bangladesh and evaluate their probiotic properties. Methods:: A rigorous study was carried out from April to August, 2019. A total of 10 samples were examined by following the standard bacteriological methods. Besides the biochemical and antibiogram tests, molecular characterization of the isolated bacteria was carried out. Results:: Ten isolates were confirmed as LAB, and they exhibited excellent probiotic properties. They were able to survive in both acidic (pH 2) and alkaline (pH 8) conditions. They also survived against phenol (0.1-0.4%) and NaCl (1-10%) after 24 h incubation. Most of the isolates harboured plasmid DNA and showed good resistance patterns against the antibiotics used. During the mating experiment, no X-conjugants were found. Conclusion:: In conclusion, the mating experiment suggested that the acquired resistant genes might be chromosome mediated, and isolates showed good probiotic properties that confer health benefits.

Response of Fusarium oxysporum soil isolate to amphotericin B and fluconazole at the proteomic level.

Fusarium oxysporum is a cross-kingdom pathogen that infects humans, animals, and plants. The primary concern regarding this genus revolves around its resistance profile to multiple classes of antifungals, particularly azoles. However, the resistance mechanism employed by Fusarium spp. is not fully understood, thus necessitating further studies to enhance our understanding and to guide future research towards identifying new drug targets. Here, we employed an untargeted proteomic approach to assess the differentially expressed proteins in a soil isolate of Fusarium oxysporum URM7401 cultivated in the presence of amphotericin B and fluconazole. In response to antifungals, URM7401 activated diverse interconnected pathways, such as proteins involved in oxidative stress response, proteolysis, and lipid metabolism. Efflux proteins, antioxidative enzymes and M35 metallopeptidase were highly expressed under amphotericin B exposure. Antioxidant proteins acting on toxic lipids, along with proteins involved in lipid metabolism, were expressed during fluconazole exposure. In summary, this work describes the protein profile of a resistant Fusarium oxysporum soil isolate exposed to medical antifungals, paving the way for further targeted research and discovering new drug targets.

Sulfonamide resistance evaluation in five animal species and first report of sul4 in companion animals

Sulfonamides are one of the oldest groups of antibacterial agents with a broad-spectrum, used as first line treatment in bacterial infections. Their widespread use produced a selective pressure on bacteria, as observed by the high incidence of sulfonamides resistance mainly in Gram negative bacteria isolated from animals. In this research, the presence of sulfonamide resistance genes (sul1, sul2, sul3, and sul4) in phenotypically resistant Escherichia coli isolates has been studied. These genes were amplified in isolates recovered from five animal species, with different interactions to humans: cattle, swine, poultry as livestock, and dogs and cats as companion animals. Isolates were collected according to their phenotypic resistance, and the magnetic bead-based Luminex technology was applied to simultaneously detect sul target genes. The frequency of sul genes was highest in swine, among livestock isolates. The sul1 and sul2 were the most frequently sulfonamide resistance genes detected in all phenotypically resistant isolates. Notably, in companion animals, with a closest interaction with human, sul4 gene was detected. To our knowledge, this is the first report of the presence of sul4 gene in E. coli collected from animals, whereas previously the presence of this gene was reported in environmental, municipal wastewater and human clinical isolates. These results highlighted the importance of continuous antimicrobial resistant genes monitoring in animal species, with a special care to companion animals.

Homo and Hetero-Branched Lipopeptide Dendrimers: Synthesis and Antimicrobial Activity

Di-branched and tetra-branched versions of a previously reported analogue of the lipopeptide battacin were successfully synthesised using thiol-maleimide click and 1, 2, 3-triazole click chemistry. Antimicrobial studies against drug resistant clinical isolates of Escherichia coli (ESBL E. coli Ctx-M14), Pseudomonas aeruginosa (P. aeruginosa Q502), and Methicillin resistant Staphylococcus aureus (MRSA ATCC 33593), as well as clinically isolated Acinetobacter baumannii (A. baumannii ATCC 19606), and P. aeruginosa (ATCC 27853), revealed that the dendrimeric peptides have antimicrobial activity in the low micromolar range (0.5 –– 4 μM) which was 10 times more potent than the monomer peptides. Under high salt concentrations (150 mM NaCl, 2 mM MgCl2, and 2.5 mM CaCl2) the di-branched lipopeptides retained their antimicrobial activity while the monomer peptides were not active (>100 μM). The di-branched triazole click lipopeptide, Peptide 12, was membrane lytic, showed faster killing kinetics, and exhibited antibiofilm activity against A. baumannii and MRSA and eradicated > 85 % preformed biofilms at low micromolar concentrations. The di-branched analogues were > 30-fold potent than the monomers against Candida albicans. Peptide 12 was not haemolytic (HC10 = 932.12 μM) and showed up to 40-fold higher selectivity against bacteria and fungi than the monomer peptide. Peptide 12 exhibited strong proteolytic stability (>80 % not degraded) in rat serum over 24 h whereas > 95 % of the thiol-maleimide analogue (Peptide 10) was degraded. The tetra-branched peptides showed comparable antibacterial potency to the di-branched analogues. These findings indicate that dual branching using triazole click chemistry is a promising strategy to improve the antimicrobial activity and proteolytic stability of battacin based lipopeptides. The information gathered can be used to build effective antimicrobial dendrimeric peptides as new peptide antibiotics.

Identification of genetic markers of resistance to macrolide class antibiotics in Mannheimia haemolytica isolates from a Saskatchewan feedlot.

Mannheimia haemolytica is a major contributor to bovine respiratory disease (BRD), which causes substantial economic losses to the beef industry, and there is an urgent need for rapid and accurate diagnostic tests to provide evidence for treatment decisions and support antimicrobial stewardship. Diagnostic sequencing can provide information about antimicrobial resistance genes in M. haemolytica more rapidly than conventional diagnostics. Realizing the full potential of diagnostic sequencing requires a comprehensive understanding of the genetic markers of antimicrobial resistance. We identified genetic markers of resistance in M. haemolytica to macrolide class antibiotics commonly used for control of BRD. Genome sequences were determined for 99 M. haemolytica isolates with six different susceptibility phenotypes collected over 2 years from a feedlot in Saskatchewan, Canada. Known macrolide resistance genes estT, msr(E), and mph(E) were identified in most resistant isolates within predicted integrative and conjugative elements (ICEs). ICE sequences lacking antibiotic resistance genes were detected in 10 of 47 susceptible isolates. No resistance-associated polymorphisms were detected in ribosomal RNA genes, although previously unreported mutations in the L22 and L23 ribosomal proteins were identified in 12 and 27 resistant isolates, respectively. Pangenome analysis led to the identification of 79 genes associated with resistance to gamithromycin, of which 95% (75 of 79) had no functional annotation. Most of the observed phenotypic resistance was explained by previously identified antibiotic resistance genes, although resistance to the macrolides gamithromycin and tulathromycin was not explained in 39 of 47 isolates, demonstrating the need for continued surveillance for novel determinants of macrolide resistance.IMPORTANCEBovine respiratory disease is the costliest disease of beef cattle in North America and the most common reason for injectable antibiotic use in beef cattle. Metagenomic sequencing offers the potential to make economically significant reductions in turnaround time for diagnostic information for evidence-based selection of antibiotics for use in the feedlot. The success of diagnostic sequencing depends on a comprehensive catalog of antimicrobial resistance genes and other genome features associated with reduced susceptibility. We analyzed the genome sequences of isolates of Mannheimia haemolytica, a major bovine respiratory disease pathogen, and identified both previously known and novel genes associated with reduced susceptibility to macrolide class antimicrobials. These findings reinforce the need for ongoing surveillance for markers of antimicrobial resistance to support improved diagnostics and antimicrobial stewardship.

Virulence properties of nisin-resistant bacteria isolated from raw milk and cheese samples

AbstractNisin is a bacteriocin produced by Lactococcus lactis and it is generally recognised as safe by the U.S. Food and Drug Administration. The study aimed to determine the presence of nisin-resistant Staphylococcus, Enterococcus, and Listeria spp. in 157 raw milk and 125 cheese samples. As a result of the isolation procedure, a total of 282 bacterial strains were isolated. 83/282 strains showed resistance to 300 ppm nisin concentration and they were identified by 16S rRNA sequencing. The two most common species were Enterococcus faecalis and Staphylococcus aureus. In both raw milk and cheese samples, nisin-resistant Listeria could not be detected. Generally, enterococci (59/65) showed higher biofilm formation ability than staphylococci (13/18). 38% (25/65) of enterococci and 88% (16/18) of staphylococci were determined to have protease activity in at least one of Skim Milk Agar, Casein Agar, or Milk Agar. In addition, the most common antibiotic resistance in nisin-resistant enterococci was against chloramphenicol. This study revealed that nisin-resistant staphylococci and enterococci are present in raw milk and cheese. In addition, the presence of some virulence factors such as biofilm production, protease activity, and antibiotic resistance in resistant isolates needs to be drawn attention to. Consumption of nisin-resistant microorganisms with virulence factors through food is a food safety risk.

Dalbavancin, a Second Generation Lipoglycopeptide is a New Addition to Therapy Armamentarium

Gram-positive infections with widespread developing resistance have posed considerable challenges to the long stay of antimicrobials in the market. Also, there has been a dearth in the provision of a suitable antimicrobial to treat the evolving resistance. Dalbavancin a 2nd generation lipoglycopeptide has shown its activity against gram-positive and multidrug resistant isolates. Owing to a favorable pharmacokinetic profile and supporting evidence this drug moiety has been used as long-term therapy for various indications. These indications include infective endocarditis (IE), osteomyelitis, bloodstream infections, and prosthetic joint infections. However, it is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) only for acute bacterial skin and skin structure infections (ABSSSIs). Dalbavancin can be a valuable alternative to daily in-hospital intravenous or outpatient antimicrobial regimens in the treatment of long-term Gram-positive infections and ‘niche’ but important indications. This systematic review demonstrates comparative microbiology, chemistry, in vitro susceptibility, pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and administration of dalbavancin. Additionally, it highlights past, present, and upcoming evidence of real-world use of dalbavancin alone or in combination with different indications. Keywords: Dalbavancin, Acute bacterial skin and skin structure infections, Gram-positive, Long-term, and pharmacokinetics.

Broad synergistic antiviral efficacy between a novel elite controller-derived dipeptide and antiretrovirals against drug-resistant HIV-1.

The naturally occurring dipeptide Tryptophylglycine (WG) is enhanced in human immunodeficiency virus (HIV-1) infected Elite Controllers (EC). We have shown that this dipeptide has an anti-HIV-1 effect and evaluated now its synergistic antiretroviral activity, in combination with current antiretrovirals against multi-drug resistant HIV-1 isolates. Drug selectivity assay with WG-am and ARVs agains HIV-1 resistant isolates were carried out. Subsequently, two methods, Chou-Talalay's Combination Index (CI) and ZIP synergy score (SS), were used to quantify the synergism. WG-am had a moderate/strong synergism with the four tested antiretrovirals: raltegravir, tenofovir, efavirenz, darunavir. WG-am:TDF had strong synergism at ED50, ED75, ED90 (CI: <0.2) in isolates resistant to protease inhibitors or integrase strand inhibitors (INSTI), and a slightly less synergism in isolates resistant to non-nucleoside or nucleotide reverse transcriptase inhibitors. WG-am combined with each of the four drugs inhibited all drug-resistant isolates with over 95% reduction at maximum concentration tested. The highest selectivity indexes (CC50/ED50) were in INSTI-resistant isolates. Our data suggest that WG, identified as occurring and enhanced in Elite Controllers has a potential to become a future treatment option in patients with HIV-1 strains resistant to any of the four major categories of anti-HIV-1 compounds.

Biosorption of copper, nickel, and manganese as well as the production of metal nanoparticles by Bacillus species isolated from soils contaminated with electronic wastes.

Improper electronic waste management in the world especially in developing countries such as Iran has resulted in environmental pollution. Copper, nickel, and manganese are from the most concerned soil contaminating heavy metals which found in many electronic devices that are not properly processed. The aim of this study was to investigate the biological removal of copper, nickel, and manganese by Bacillus species isolated from a landfill of electronic waste (Zainal Pass hills located in Isfahan, Iran) which is the and to produce nanoparticles from the studied metals by the isolated bacteria. The amounts of copper, nickel, and manganese in the soil was measured as 1.9 × 104 mg/kg, 0.011 × 104 mg/kg and 0.013 × 104 mg/kg, respectively based on ICP-OES analysis, which was significantly higher than normal (0.02 mg/kg, 0.05 mg/kg, and 2 mg/kg, respectively. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of metals on the bacterial isolates was determined. The biosorption of metals by the bacteria was evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES). The metal nanoparticles were synthetized utilizing the isolates in culture media containing the heavy metals with the concentrations to which the isolates had shown resistance. X ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) were used for the evaluation of the fabrication of the produced metal nanoparticles. Based on the findings of this study, a total of 15 bacterial isolates were obtained from the soil samples. The obtained MICs of copper, nickel, and manganese on the isolates were 40-300 mM, 4-10 mM, and 60-120 mM, respectively. The most resistant isolates to copper were FM1 and FM2 which were able to bio-remove 79.81% and 68.69% of the metal, respectively. FM4 and FM5 were respectively the most resistant isolate to nickel and manganese and were able to bio-remove 86.74% and 91.96% of the metals, respectively. FM1, FM2, FM4, and FM5 was molecularly identified as Bacillus cereus, Bacillus thuringiensis, Bacillus paramycoides, and Bacillus wiedmannii, respectively. The results of XRD, SEM and EDS showed conversion of the copper and manganese into spherical and oval nanoparticles with the approximate sizes of 20-40 nm. Due to the fact that the novel strains in this study showed high resistance to copper, nickel, and manganese and high adsorption of the metals, they can be used in the future, as suitable strains for the bio-removal of these metals from electronic and other industrial wastes.

Reversion to sensitivity explains limited transmission of resistance in a hospital pathogen.

Bacterial pathogens that are successful in hospital environments must survive times of intense antibiotic exposure and times of no antibiotic exposure. When these organisms are closely associated with human hosts, they must also transmit from one patient to another for the resistance to spread. The resulting evolutionary dynamics have, in some settings, led to rising levels of resistance in hospitals. Here, we focus on an important but understudied aspect of this dynamic: the loss of resistance when the resistant organisms evolve in environments where the antibiotic pressure is removed. Based on prior data, we hypothesize that resistance arising in the context of strong selection may carry a high cost and revert to sensitivity quickly once the selective pressure is removed. Conversely, resistant isolates that persist through times of no antibiotic pressure should carry a lower cost and revert less quickly. To test this hypothesis, we utilize a genetically diverse set of patient-derived, daptomycin-resistant Enterococcus faecium isolates that include cases of both de novo emergence of resistance within patients and putatively transmitted resistance. Both of these sets of strains have survived periods of antibiotic exposure, but only putatively transmitted resistant strains have survived extended periods without antibiotic exposure. These strains were then allowed to evolve in antibiotic free laboratory conditions. We find that putatively transmitted resistant strains tended to have lower level resistance but that evolution in antibiotic-free conditions resulted in minimal loss of resistance. In contrast, resistance that arose de novo within patients was higher level but exhibited greater declines in resistance in vitro. Sequencing of the experimentally evolved isolates revealed that reversal of high level resistance resulted from evolutionary pathways that were frequently genetically associated with the unique resistance mutations of that strain. Thus, the rapid reversal of high-level resistance was associated with accessible evolutionary pathways where an increase in fitness is associated with decreased resistance. We describe how this rapid loss of resistance may limit the spread of resistance within the hospital and shape the diversity of resistance phenotypes across patients.

Impact of the COVID-19 pandemic on Haemophilus influenzae infections in pediatric patients hospitalized with community acquired pneumonia

The COVID-19 pandemic has altered the infection landscape for many pathogens. This retrospective study aimed to compare Haemophilus influenzae (H. influenzae) infections in pediatric CAP patients hospitalized before (2018–2019) and during (2020–2022) the COVID-19 pandemic. We analyzed the clinical epidemiology and antimicrobial resistance (AMR) patterns of H. influenzae from a tertiary hospital in southwest China. A total of 986 pediatric CAP patients with H. influenzae-associated infections were included. Compared to 2018, the positivity rate increased in 2019 but dropped significantly in 2020. Although it rose in the following 2 years, the rate in 2022 remained significantly lower than in 2019. Patients’ age during the pandemic was significantly higher than in 2018 and 2019, while gender composition remained similar across both periods. Notably, there were significant changes in co-infections with several respiratory pathogens during the pandemic. Resistance rates of H. influenzae isolates to antibiotics varied, with the highest resistance observed for ampicillin (85.9%) and the lowest for cefotaxime (0.0%). Resistance profiles to various antibiotics underwent dramatic changes during the COVID-19 pandemic. Resistance to amoxicillin-clavulanate, cefaclor, cefuroxime, trimethoprim-sulfamethoxazole, and the proportion of multi-drug resistant (MDR) isolates significantly decreased. Additionally, MDR isolates, alongside isolates resistant to specific drugs, were notably prevalent in ampicillin-resistant and β-lactamase-positive isolates. The number of pediatric CAP patients, H. influenzae infections, and isolates resistant to certain antibiotics exhibited seasonal patterns, peaking in the winter of 2018 and 2019. During the COVID-19 pandemic, sharp decreases were observed in February 2020, and there was no resurgence in December 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection spectrum of H. influenzae in pediatric CAP patients, as evidenced by shifts in positivity rate, demographic characteristics, respiratory co-infections, AMR patterns, and seasonal trends.

Epidemiological trends, antifungal drug susceptibility and SQLE point mutations in etiologic species of human dermatophytosis in Al-Diwaneyah, Iraq

Dermatophytes show a wide geographic distribution and are the main causative agents of skin fungal infections in many regions of the world. Recently, their resistance to antifungal drugs has led to an obstacle to effective treatment. To address the lack of dermatophytosis data in Iraq, this study was designed to investigate the distribution and prevalence of dermatophytes in the human population and single point mutations in squalene epoxidase gene (SQLE) of terbinafine resistant isolates. The identification of 102 dermatophytes isolated from clinical human dermatophytosis was performed through morphological and microscopic characteristics followed by molecular analysis based on ITS and TEF-1α sequencing. Phylogeny was achieved through RAxML analysis. CLSI M38-A2 protocol was used to assess antifungal susceptibility of the isolates to four major antifungal drugs. Additionally, the presence of point mutations in SQLE gene, which are responsible for terbinafine resistance was investigated. Tinea corporis was the most prevalent clinical manifestation accounting for 37.24% of examined cases of dermatophytosis. Based on ITS, T. indotineae (50.98%), T. mentagrophytes (19.61%), and M. canis (29.41%) was identified as an etiologic species. T. indotineae and T. mentagrophytes strains were identified as T. interdigitale based on TEF-1α. Terbinafine showed the highest efficacy among the tested antifungal drugs. T. indotineae and T. mentagrophytes showed the highest resistance to antifungal drugs with MICs of 2–4 and 4 μg/mL, while M. canis was the most susceptible species. Three of T. indotineae isolates showed mutations in SQLE gene Phe397Leu substitution. A non-previously described point mutation, Phe311Leu was identified in T. indotineae and mutations Lys276Asn, Phe397Leu and Leu419Phe were diagnosed in T. mentagrophytes XVII. The results of mutation analysis showed that Phe397Leu was a destabilizing mutation; protein stability has decreased with variations in pH, and point mutations affected the interatomic interaction, resulting in bond disruption. These results could help to control the progression of disease effectively and make decisions regarding the selection of appropriate drugs for dermatophyte infections.

Clinical differences between Raoultella spp. and Klebsiella oxytoca.

Raoultella spp. is a genus of bacteria that is known to be closely related to Klebsiella. It has been debated whether Raoultella should be reclassified as a subgroup of Klebsiella. The aim of this study is to compare clinical aspects of Raoultella and Klebsiella oxytoca, a species of Klebsiella that is known to be bacteriologically similar to Raoultella spp. Using data collected at a tertiary care hospital in the United States, we identified 43 patients with Raoultella infection and 1173 patients with Klebsiella oxytoca infection. We compared patient demographics (age and sex), hospitalization status, isolation sites and antibiotic resistance profiles between the two species. There was no significant difference in patient demographics between the two bacteria species. The proportions of intensive care unit (ICU) admission were higher among patients with Raoultella infection (p=0.008). The most common site of isolation was urine for both species (39.5% of all patients with Raoultella spp. vs. 59.3% for K. oxytoca). The second most common site of isolation was blood stream for Raoultella spp. (23.3%) and respiratory tract for K. oxytoca (10.8%). Except for the high proportion of resistant isolates of Raoultella spp. for Trimethoprim/sulfamethoxazole, the antibiotic susceptibility profiles were similar between the two bacteria species. Both were susceptible to ciprofloxacin and meropenem. While there are no significant differences in the patient demographics and antibiotic susceptibility profiles between Raoultella spp. and K. oxytoca, Raoultella may cause more serious infection requiring ICU admissions. Also, Raoultella may cause blood stream infection more frequently than K. oxytoca.

Prevalence and Antimicrobial Resistance Pattern of Uropathogenic Escherichia coli at a Tertiary Care Hospital: A Retrospective Study

Background: Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infection in humans including cystitis and pyelonephritis. Antimicrobial resistance (AMR) in UPEC is one of the global public challenges that is due to prevalent use of antibiotics in healthcare setting. Therefore, the purpose of this study is to investigate the frequency and antibiotic resistance pattern of UPEC isolated from patients admitted to Modares Hospital in Saveh, Iran. Methods: In this study, in total 633 isolates were evaluated. UPEC isolates were obtained from patients with urinary tract infection and identified using conventional microbiological protocols. Antibiotic resistance pattern of UPEC against different antibiotic were determined using disk diffusion method. SPSSTM software was used for statistical analysis Results: In this study, the most sample was related to outpatients and the lowest sample was related to the CCU wards. The highest antibiotic resistance showed against cephalothin (63.8%) and nalidixic acid (62.2%) antibiotics. The highest effective antibiotics for the tested UPEC was nitrofurantoin (90.7%) and gentamicin (77.3%). Cephalothin and nalidixic acid in hospitalized patients in ICU and emergency wards, respectively, showed the highest antibiotic resistance. Out of 633 UPEC, the rate of Multi Drug Resistant (MDR) isolates were 343 (54.2%). Conclusion: The result of this study highlighted the role of UPEC as one of the important cause of UTI in individuals. Also, nitrofurantoin then gentamicin are the most effective antibiotics against UPEC infections. Logical prescription of antibiotics and infection control strategies are needed for prevention and control of nosocomial infections especially urinary tract infection.

Emergence of Rarely Reported Extensively Drug-Resistant Salmonella Enterica Serovar Paratyphi B among Patients in East China.

In recent years, global concern over increasing multidrug resistance (MDR) among various Salmonella serotypes has grown significantly. However, reports on MDR Salmonella Paratyphi B remain scarce, let alone the extensively drug-resistant (XDR) strains. In this retrospective study, we investigated the isolates of Salmonella Paratyphi B in Jiangsu Province over the past decade and carried out antimicrobial susceptibility tests, then the strains were sequenced and bioinformatics analyses were performed. 27 Salmonella Paratyphi B strains were identified, of which the predominant STs were ST42 (11), ST86 (10), and ST2814 (5). Among these strains, we uncovered four concerning XDR Salmonella Paratyphi B ST2814 strains (4/5) which were previously unreported. These alarmingly resistant isolates showed resistance to all three major antibiotic classes for Salmonella treatment and even the last resort treatment tigecycline. Bioinformatics analysis revealed high similarity between the plasmids harbored by these XDR strains and diverse Salmonella serotypes and Escherichia coli from China and neighboring regions. Notably, these four plasmids carried the ramAp gene responsible for multiple antibiotic resistance by regulating the AcrAB-TolC pump, predominantly originating from China. Additionally, a distinct MDR ST42(1/11) strain with an ICE on chromosome was also identified. Furthermore, phylogenetic analysis of global ST42/ST2814 isolates highlighted the regional specificity of these strains, with Jiangsu isolates clustering together with domestic isolates and XDR ST2814 forming a distinct branch, suggesting adaptation to local antibiotic pressures. This research underscores the pressing need for closely monitoring the MDR/XDR Salmonella Paratyphi B, particularly the emerging ST2814 strains in Jiangsu Province, to effectively curb its spread and protect public health. Moreover, surveillance should be strengthened across different ecological niches and genera to track resistance genes and horizontal gene transfer elements under the concept of "ONE HEALTH".

Efficacy of Cefiderocol, a Novel Siderophore Cephalosporin, against Multidrug Resistant Acinetobacter baumannii Clinical Isolates in Japan.

Multidrug-resistant Acinetobacter baumannii (MDRAB) is an important pathogen that causes nosocomial infections and is resistant to almost all antibiotics, including carbapenems. Cefiderocol is a novel siderophore cephalosporin active against a broad spectrum of gram-negative bacteria. However, the susceptibility of MDRAB to cefiderocol has not yet been reported in Japan. In this study, we measured the minimum inhibitory concentrations (MICs) of antibiotics including cefiderocol against MDRAB clinical isolates collected during a nosocomial outbreak between 2009 and 2010 at the Teikyo University Hospital in Japan. We found that all 10 MDRAB clinical isolates tested were susceptible to cefiderocol, with an MIC range of 0.12 to 1 μg/mL. All the isolates also exhibited resistance to ampicillin-sulbactam and an intermediate resistance to colistin, whereas nine of them were susceptible to tigecycline. DNA sequencing revealed that all strains harbored an OXA-51-like carbapenemase, a major cause of carbapenem resistance in A. baumannii in Japan. In conclusion, this study showed that the cefiderocol susceptibility of MDRAB clinical isolates in Japan was equivalent to that to colistin or tigecycline, and thus cefiderocol is a potential treatment option for MDRAB infections.

Antimicrobial resistance of Streptococcus dysgalactiae, Streptococcus agalactiae, and Streptococcus canis in quarter milk samples from Bavaria, Southern Germany, between 2012 and 2022

The objective of this study was to analyze the in vitro antimicrobial resistance (AMR) of Streptococcus (Sc.) dysgalactiae, Sc. agalactiae, and Sc. canis over a 10-year period from 2012 to 2022 against the most commonly used antimicrobial agents. For this purpose, all quarter milk samples (QMS) submitted to the milk laboratory of the Bavarian Animal Health Service (TGD) were analyzed. Each QMS was tested using the California Mastitis Test (CMT) and categorized as negative (N), subclinical (S), or clinical (C) mastitis if the milk character was abnormal. Samples with Sc. dysgalactiae, Sc. agalactiae, or Sc. canis were included and a subset of isolates were further tested for in vitro antimicrobial resistance by breakpoint analysis with broth microdilution. Sc. dysgalactiae (61%, n = 65,750) was the most abundant pathogen among those 3 species, followed by Sc. agalactiae (28%, n = 30,486), and Sc. canis (11%, n = 11,336). All 3 species showed the highest resistance to the same 4 antimicrobial agents: erythromycin, marbofloxacin, pirlimycin, and cefalexin/kanamycin with varying degrees of resistance. Throughout the study period, Sc. dysgalactiae, Sc. agalactiae, and Sc. canis were largely susceptible to the remaining antimicrobial agents tested (penicillin, amoxicillin-clavulanate, oxacillin, cefazolin, cefoperazone, cefquinome). Only less than 14% of isolates of Sc. dysgalactiae and Sc. canis were resistant against any of the antimicrobials tested. Sc. agalactiae was the species with the highest percentage of resistant isolates. While the percentage of resistant isolates from Sc. canis and Sc. dysgalactiae decreased, the percentage of resistant Sc. agalactiae isolates increased since 2017. In summary, most isolates were not resistant to the most commonly used antimicrobial agents for mastitis therapy, including β-lactam antibiotics and penicillin should remain the first-choice therapy against streptococcal mastitis.

Comparison the effect of plant extracts and antibiotics on gram negative bacteria isolated from patients with urinary tract infection in Tikrit city

Background: With increasing bacterial resistance for antibiotic, there is an increasing interest in medicinal herbal as a new source of an antimicrobial agents and with less side effects than conventional drugs. Objective: Was to evaluate the potential of Syzygium aromaticum and rosemarinus officinalis extract on Proteus mirabilis isolates in vitro. Methods: Six pathogenic gram negative bacilli belonging to three different genus (E.coli, Proteus mirabilis, and Enterobacter aerogenes) and two isolates from each species were used in this study and four concentration (100%, 75%, 50%, 25% mg/ml ) from each plant extracts (aqueous and ethanolic of Syzygium aromaticum and rosemarinus officinalis extracts ) were prepared to be antibacterial agent. antibacterial activity was measured by using wells method and five antibiotics using to compare with the activity of antibacterial agent. Results: The result of the study shown that the ethanolic extracts of Syzygium aromaticum is a strong antibacterial agent (with diameter of inhibition zone 25 mm) against Proteus mirabilis. Enterobacter aerogenes with (15mm) of inhibition zon, E.coli did not show any inhibition zone also the aqueous and ethanolic of rosemarinus officinalis extracts and aqueous of Syzygium aromaticum extracts did not show any activity towards any gram negative bacilli also the results of the study show resistance isolates of E.coli and Proteus mirabilis toward several antibiotic while Enterobacter aerogenes is sensitive for more antibiotics that used in this study. Conclusions: Our study concluded that the extract of Syzygium aromaticum has high potential as antibacterial agent against UTI that caused by Proteus mirabilis, clove (syzygium aromaticum) can be used in pharmaceutical for the production of new synthetic agents. There is an increasing interest in phytochemicals as new sources of natural antioxidant and antimicrobial agents. The natural compounds which have biological activities are interest to pharmaceutical industries especially for treatment of human disease of microbial origin and several pathological disorders such as cancergenesis, coronary atherosclerosis, as well as in ageing processes.