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Listeria are Gram-negative intracellular foodborne pathogens that can cause invasive infections with high mortality rates. In this work, the antibacterial activity of ten essential oils, infusion extracts, and decoction extracts of some medicinal plants was tested against Listeria monocytogenes and listeria ivanovii strains. The effects of different physical conditions including temperature, pH, sodium chloride, and some organic acids were studied. The results showed that the water extracts gave the maximum bacterial inhibition, while ethanolic extract was inactive against the tested Listeria spp. The antibiotic sensitivity of L. monocytogenes LMG10470 and L. ivanovii LMZ11352 was tested against five antibiotics including imipenem, levofloxacin, amikacin, ampicillin, and amoxicillin. Imipenem was the most effective antibiotic, resulting in inhibition zones of 40 mm and 31 mm for L. monocytogenes and L. ivanovii, respectively. When imipenem mixed with Syzygium aromaticum oil, Salvia officinalis oil, Pimpinella anisum infusion, and Mentha piperita infusion each, the water extract of Moringa oleifera leaves and seeds against LMG10470 and LMZ11352 resulted in broader antibacterial activity. The antimicrobial activity of both Pimpinella anisum and Mentha piperita plant extracts is related to a variety of bioactive compounds indicated by gas chromatography–mass spectrometry analysis of these two plant extracts. These two plant extracts seemed to contain many chemical compounds elucidated by gas chromatography–mass spectrometry (GC-MS) and infrared radiation spectra. These compounds could be classified into different chemical groups such as ethers, heterocyclic compounds, aromatic aldehydes, condensed heterocyclic compounds, ketones, alicyclic compounds, aromatics, esters, herbicides, saturated fatty acids, and unsaturated fatty acids. The use of these natural compounds seems to be a useful technological adjuvant for the control of Listeria spp. in foods. [ABSTRACT FROM AUTHOR]

Introduction: Our work aims at establishing a proof-of-concept for a method that allows the early prediction of the bactericidal and bacteriostatic effects of antibiotics on bacteria using scanning electron microscopy (SEM) as compared to traditional culture-based methods. Methods: We tested these effects using Imipenem (bactericidal) and Doxycycline (bacteriostatic) with several strains of sensitive and resistant Escherichia coli. We developed a SEM-based predictive score based on three main criteria: Bacterial Density, Morphology/Ultrastructure, and Viability. We determined the results for each of these criteria using SEM micrographs taken with the TM4000Plus II-Tabletop-SEM (Hitachi, Japan) following an optimized, rapid, and automated acquisition and analysis protocol. We compared our method with the traditional culture colony counting gold standard method and classic definitions of the two effects. Results: Our method revealed total agreement with the CFU method and classic definition by visualizing the effect of the antibiotic at 60 minutes and 120 minutes using SEM. Discussion: This early prediction allows a rapid and early identification of the bactericidal and bacteriostatic effects as compared to culture that would take a minimum of 18 hours. This has several future applications in the development of SEM-automated assays coupled to machine learning models that identify the antibiotic effect and facilitate determination of bacterial susceptibility. [ABSTRACT FROM AUTHOR]

Introduction: A chronic inflammation of the middle ear and mastoid cavity that lasts more than two weeks is known as chronic suppurative otitis media (CSOM). A common organism that causes CSOM is pseudomonas aeruginosa. Although carbapenems are among the best medicines for treating Pseudomonas infections, the development of metallo-ß-lactamases strains is frequently linked to carbapenem resistance. Finding strains that produce MBLs can help ensure that patients receive the best care possible to stop the development of resistance. Finding the imipenem-resistant Pseudomonas aeruginosa carrying the metallo-ß-lactamase (MBL) geneblaIMP-1 is the primary goal of the research. Aim and Objective: To study the Molecular Characterization of Metallo-Beta Lactamase Gene blaIMP-1 in Imipenem Resistant Pseudomonas aeruginosa isolates from Patients of Chronic Suppurative Otitis Media. Material and Methods: This was a cross sectional study carried out in the Department of Microbiology and ENT Department for a period of 1 year i.e, May 2023 to May 2024. A total of 200 patients clinically suspected cases for CSOM was studied. Swabs taken from discharging ears were sent for Gram’s staining, culture and antibiotic sensitivity test as per the latest CLSI guidelines 2023. The DNA was extracted by using Qiagen DNA Extraction kit and blaIMP-1 gene for Pseudomonas aeruginosa isolates was detected by conventional PCR. Results: In the present study the number of cases clinically diagnosed of having CSOM were 200, out of which 70 (35%) was found to be culture positive for CSOM infection. Males were 44 (62.8%) as compared to that of female 26 (37.1%), the age group of 0-10 years followed by 11-20 years were being affected the most and the least number of cases was seen in the age group above 51 years. The side of the ear affected was almost in equal distribution, with the left ear being (51.4%) and the right ear being (40%) while (8.5%) were bilateral. In our study it was observed that the maximum number of cases was found in Gram negative isolates (98.5%) as compared to the Gram positive isolates (14.2%). It was also observed that 62 isolates (88.5%) samples showed growth of single isolates while 8 (11.4%) were mixed isolates. Pseudomonas aeruginosa being the most common isolate with 42.8% followed by Klebsiella sp. with 21.4% and among gram positive isolates Staphylococcus aureus was 11.4% and Streptococcus pneumonia (2.8%) being the least observed. The sensitivity observed in P. aeruginosa for Colistin was (97.1%), Piperacillin‑tazobactam (78.5%), Amikacin (82.8%), and cefepime (78.5%) were found to be the most effective Antibiotics. The resistance to ciprofloxacin was (56.6%), Levofloxacin (50%), Piperacillin(46.6%), Gentamicin(37.1%), Imipenem (31.4%), Tobramycin(31.4%), Ceftazidime (31.4%) and Gentamycin (37.1%). The blaIMP-1 gene was detected in 14 (20%) of the isolates of Pseudomonas aeruginosa Conclusion: Pseudomonas aeruginosa was the most frequently isolated strain in the current investigation, and the most effective antibiotics were cefepime, amikacin, piperacillin-tazobactam, and colonistin, ciprofloxacin and levofloxacin were the least effective. The Kanpur region (%) is seeing an increase in P. aeruginosa isolate resistance to imipenem as a result of MBL enzymes. Understanding the CSOM etiological agents and their antibiogram is crucial for effective treatment and prevention of antimicrobial resistance as well as clinical consequences. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate literature from a 12-year period (2010–2021) on the antimicrobial resistance profile of Pseudomonas aeruginosa from the Arabian Gulf countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates). Methods: An electronic literature search was conducted for articles on antimicrobial resistance in P. aeruginosa and associated phenotypes, covering the period of 1st January 2010 to 1st December 2021. Results: Antimicrobial resistance in the Arabian Gulf was highest to meropenem (10.3–45.7%) and lowest to colistin (0.0–0.8%), among the agents tested. Annual data showed that ceftazidime resistance (Kuwait), piperacillin-tazobactam non-susceptibility (Qatar), and aztreonam, imipenem, and meropenem resistance (Saudi Arabia) increased by 12–17%. Multiple mechanisms of carbapenem resistance were identified and multiple clones were detected, including high-risk clones such as ST235. The most common carbapenemases detected were the VIM-type metallo-β-lactamases. Conclusions: Among P. aeruginosa in the Arabian Gulf countries, resistance to meropenem was higher than to the other agents tested, and meropenem resistance increased in Saudi Arabia during the study period. Resistance to colistin, a classic antibiotic used to treat Pseudomonas spp. infections, remained low. The VIM-type β-lactamase genes were dominant. We recommend local and regional antimicrobial resistance surveillance programs to detect the emergence of resistance genes and to monitor antimicrobial resistance trends in P. aeruginosa. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a life-threatening organ dysfunction caused by an excessive host response to infection, manifested by elevated levels of inflammatory cytokines. At present, the use of hemoperfusion to remove inflammatory cytokines from the bloodstream has been expanding. Meanwhile, the pharmacokinetics and pharmacodynamics characteristics of antibiotics in critically ill patients may be impacted by hemoperfusion. Case presentation: The patient was a 69-year-old male with poorly controlled type 2 diabetes. When admitted to the ICU, Multiple Organ Dysfunction Syndrome (MODS) appeared within 48 h, and he was suspected of septic shock due to acute granulocytopenia and significantly increased procalcitonin. Broad-spectrum antibiotics imipenem was administered according to Sepsis 3.0 bundle and hemoperfusion lasting 4 h with a neutron-macroporous resin device (HA-380, Jafron, China) five times was conducted to lower the extremely high value of serum inflammatory factors. Blood samples were collected to measure imipenem plasma concentration to investigate the effect of hemoperfusion quantitatively. This study showed that 4 h of hemoperfusion had a good adsorption ability on inflammatory factors and could remove about 75.2% of imipenem. Conclusions: This case demonstrated the high adsorption capacity of hemoperfusion on imipenem in critically ill patients. It implies a timely imipenem supplement is required, especially before hemoperfusion. [ABSTRACT FROM AUTHOR]

Infections caused by pathogenic Escherichia coli are a serious threat to human health, while conventional antibiotic susceptibility tests (AST) have a long turn-around time, and rapid antibiotic susceptibility methods are urgently needed to save lives in the clinic, reduce antibiotic misuse and prevent emergence of antibiotic-resistant bacteria. We optimized and validated the feasibility of a novel rapid AST based on SYBR Green I and Propidium Iodide (SGPI-AST) for E. coli drug susceptibility test. A total of 112 clinical isolates of E. coli were collected and four antibiotics (ceftriaxone, cefoxitin, imipenem, meropenem) were selected for testing. Bacterial survival rate of E. coli was remarkably linearly correlated with S value at different OD600 values. After optimizing the antibiotic concentrations, the sensitivity and specificity of SGPI-AST reached 100%/100%, 97.8%/100%, 100%/100% and 98.4%/99% for ceftriaxone, cefoxitin, imipenem and meropenem, respectively, and the corresponding concordances of the SGPI-AST with conventional AST were 1.000, 0.980, 1.000 and 0.979, respectively. The SGPI-AST can rapidly and accurately determine the susceptibility of E. coli clinical isolates to multiple antibiotics in 60 min, and has the potential to be applied to guide the precise selection of antibiotics for clinical management of infections caused by pathogenic E. coli. [ABSTRACT FROM AUTHOR]

This case report details the challenging management of a 45-year-old male construction worker who suffered severe multiple injuries after a fall and subsequent collision with cement mixers. The patient presented with extensive injuries, including amputation, fractures and internal bleeding, leading to a state known as the 'triangle of death'. Despite the initial grim prognosis, evidenced by an ISS score of 28 and a mortality risk coefficient of 89.56%, the patient was successfully resuscitated and managed through a multidisciplinary approach. This included damage control resuscitation, emergency vascular interventions and targeted temperature management for brain protection. The patient's recovery highlights the effectiveness of comprehensive trauma management and the critical role of coordinated care in severe multi-trauma cases. [ABSTRACT FROM AUTHOR]

Objectives: Antiviral therapy approaches have become significant strategies to combat antibiotic resistance. Metal ions, particularly iron, play crucial roles in metabolic activities and virulence of bacteria. Loading iron into siderophore molecules could potentially circumvent antimicrobial resistance. This study aimed to evaluate the antibiofilm and antimicrobial effects of deferoxamine (DFO), an iron chelator and natural siderophore, on antibiotic susceptibility in clinical methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. Materials and Methods: The in vitro antibacterial activity of DFO alone and in combination with vancomycin [VAN (30 μg)], amoxicillin (25 μg), colistin (10 μg), and imipenem (10 μg), was investigated against MRSA and CRAB isolates using the disk diffusion method. The spectrophotometric microplate method was used to detect the in vitro antibiofilm effect of DFO. Results: DFO exhibited a synergistic effect with VAN, amoxicillin, and colistin and significantly disrupted mature biofilm formation in MRSA and CRAB isolates. Notably, the antibiofilm effect of DFO was more pronounced in CRAB strains. Conclusion: These findings highlight the potential of DFO as an antibiofilm agent candidate and suggest that it can enhance the antibiotic susceptibility of certain microorganism species. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) caused by Escherichia coli represent a significant public health concern due to the high virulence and antimicrobial resistance exhibited by these pathogens. This study aimed to analyze the phylogenetic diversity and antibiotic resistance profiles of Uropathogenic E. coli (UPEC) strains isolated from UTI patients in Algeria, focusing on virulence factors such as extended β-lactamase (ESBL) production, biofilm formation, and hemolytic activity. Phylogenetic grouping of 86 clinical imipenem resistant E. coli isolates showed the prevalence of group B2 (48.9%), followed by groups E (22.1%), unknown (12.8%), A (8.1%), and B1 (4.7%), and Clade I, D, Clade I, or Clade II (1.2%). The highest resistance rates were observed towards amoxicillin (86.04%), ticarcillin (82.55%), piperacillin (73.25%), nitrofurantoin (84.88%), and trimethoprim-sulfamethoxazole (51.16%). Notably, 69.8% of UPEC strains were multidrug-resistant (MDR) and 23.2% were extensively drug-resistant (XDR). Additionally, 48.9%, 42%, and 71% of strains demonstrated ESBL production, hemolytic activity, and weak biofilm production, respectively. Continuous monitoring and characterization of UPEC strains are essential to track the spread of the most resistant and virulent phylogenetic groups over time, facilitating rapid therapeutic decisions to treat infections and prevent the emergence of new resistant organisms, helping choose the most effective antibiotics and reducing treatment failure. [ABSTRACT FROM AUTHOR]

Abstract Background Sepsis is a life-threatening organ dysfunction caused by an excessive host response to infection, manifested by elevated levels of inflammatory cytokines. At present, the use of hemoperfusion to remove inflammatory cytokines from the bloodstream has been expanding. Meanwhile, the pharmacokinetics and pharmacodynamics characteristics of antibiotics in critically ill patients may be impacted by hemoperfusion. Case presentation The patient was a 69-year-old male with poorly controlled type 2 diabetes. When admitted to the ICU, Multiple Organ Dysfunction Syndrome (MODS) appeared within 48 h, and he was suspected of septic shock due to acute granulocytopenia and significantly increased procalcitonin. Broad-spectrum antibiotics imipenem was administered according to Sepsis 3.0 bundle and hemoperfusion lasting 4 h with a neutron-macroporous resin device (HA-380, Jafron, China) five times was conducted to lower the extremely high value of serum inflammatory factors. Blood samples were collected to measure imipenem plasma concentration to investigate the effect of hemoperfusion quantitatively. This study showed that 4 h of hemoperfusion had a good adsorption ability on inflammatory factors and could remove about 75.2% of imipenem. Conclusions This case demonstrated the high adsorption capacity of hemoperfusion on imipenem in critically ill patients. It implies a timely imipenem supplement is required, especially before hemoperfusion.

Probiotics have emerged as agents that improve a wide range of conditions and provide essential ingredients for potential health benefits. Probiotics exhibit a diverse array of effects by engaging in [...]

ABSTRACT: Objectives: The main aim of this study was to evaluate the antibiofilm activity of cefiderocol alone and in combination with imipenem vs. sessile cells of Pseudomonas aeruginosa, assessing a potential synergistic bactericidal effect. Methods: Ten P. aeruginosa clinical isolates from infected implants and bloodstream were included in the study. Cefiderocol was tested alone and in combination with imipenem on 24-h-old P. aeruginosa biofilm formed on porous glass beads. For each antibiotic formulation, minimum bactericidal biofilm concentration (MBBC), defined as the lowest concentration that determined a reduction of at least 3 log10 CFU/mL compared with the untreated control, was evaluated. Scanning electron microscopy (SEM) was used to investigate the biofilm of P. aeruginosa treated with cefiderocol, imipenem, or their combination. Results: Cefiderocol and imipenem were tested alone on P. aeruginosa biofilm and a reasonable reduction in the number of viable cells was observed, especially at high drug concentrations tested. The synergistic effect of cefiderocol in combination with imipenem was evaluated for five selected isolates. Cotreatment with the two drugs led to a remarkable reduction of cell viability by resulting in synergistic bactericidal activity in all tested strains and in synergistic eradicating activity in only one isolate. SEM analysis revealed that, in cefiderocol-treated biofilm, bacterial cells became more elongated than in the untreated control, forming filaments in which bacterial division seems to be inhibited. Conclusions: Cefiderocol exhibited an encouraging antibiofilm activity against tested strains, representing a valid option for the treatment of P. aeruginosa biofilm-associated infections, especially when administered in combination with imipenem.

Background: The study aims to investigate the effect of combining silver nanoparticles (AGNPs) with different antibiotics on multi-drug resistant (MDR) and extensively drug resistant (XDR) isolates of Pseudomonas aeruginosa (P. aeruginosa) and to investigate the mechanism of action of AGNPs. Methods: AGNPs were prepared by reduction of silver nitrate using trisodium citrate and were characterized by transmission electron microscope (TEM) in addition to an assessment of cytotoxicity. Clinical isolates of P. aeruginosa were collected, and antimicrobial susceptibility was conducted. Multiple Antibiotic Resistance (MAR) index was calculated, and bacteria were categorized as MDR or XDR. Minimum inhibitory concentration (MIC) of gentamicin, ciprofloxacin, ceftazidime, and AGNPs were determined. The mechanism of action of AGNPs was researched by evaluating their effect on biofilm formation, swarming motility, protease, gelatinase, and pyocyanin production. Real-time PCR was performed to investigate the effect on the expression of genes encoding various virulence factors. Results: TEM revealed the spherical shape of AGNPs with an average particle size of 10.84 ± 4.64 nm. AGNPS were safe, as indicated by IC50 (42.5 µg /ml). The greatest incidence of resistance was shown against ciprofloxacin which accounted for 43% of the bacterial isolates. Heterogonous resistance patterns were shown in 63 isolates out of the tested 107. The MAR indices ranged from 0.077 to 0.84. Out of 63 P. aeruginosa isolates, 12 and 13 were MDR and XDR, respectively. The MIC values of AGNPs ranged from 2.65 to 21.25 µg /ml. Combination of AGNPs with antibiotics reduced their MIC by 5–9, 2–9, and 3-10Fold in the case of gentamicin, ceftazidime, and ciprofloxacin, respectively, with synergism being evident. AGNPs produced significant inhibition of biofilm formation and decreased swarming motility, protease, gelatinase and pyocyanin production. PCR confirmed the finding, as shown by decreased expression of genes encoding various virulence factors. Conclusion: AGNPs augment gentamicin, ceftazidime, and ciprofloxacin against MDR and XDR Pseudomonas isolates. The efficacy of AGNPs can be attributed to their effect on the virulence factors of P. aeruginosa. The combination of AGNPs with antibiotics is a promising strategy to attack resistant isolates of P. aeruginosa. [ABSTRACT FROM AUTHOR]

Carbapenemase-producing Enterobacterales are increasingly being recognized in nosocomial infections. The performance of a flow cytometry-based rapid assay for their detection and differentiation was evaluated. This is a disruptive phenotypic technology, phenotypic and growth-independent, that searches for the lesions produced by drugs acting on cells after a short incubation time. Overall, 180 Gram-negative bacteria were studied, and results were compared with those obtained molecularly by PCR and phenotypically by 'KPC, MBL and OXA-48 Confirm Kit'. This phenotypic method was used as reference for comparison purposes. Susceptibility to carbapenems (imipenem, meropenem, and ertapenem) was determined by standard broth microdilution. Overall, 112 isolates (62.2%) were carbapenemase producers, 41 KPCs, 36 MβLs, and 31 OXA-48, and 4 strains were KPC + MβL co-producers. Sixty-eight isolates were carbapenemase-negative. The percentage of agreement, sensitivity, and specificity were calculated according to ISO 20776-2:2021. The FASTinov assay showed 97.7% agreement with the reference method for carbapenemase detection. Discrepant flow cytometry results were obtained in four isolates compared with both reference and PCR results. The sensitivity and specificity of this new technology were 95.3% and 98.5%, respectively, for KPCs, 97.6% and 99.3% for MβLs, and 96.9% and 98% for OXA-48 detection. In conclusion, we describe a rapid flow cytometry assay with high accuracy for carbapenemase detection and the differentiation of various carbapenemases, which should impact clinical microbiology laboratories and patient management. [ABSTRACT FROM AUTHOR]

The phenomenon of bacterial resistance to antibiotics, the emission and spread of these bacteria, and the genes that determine antibiotic resistance in the environment are now a major health security concern. This is especially important for anthropopressed surface waters used for recreational purposes. A particular threat is the occurrence of bacteria resistant to frequently applied pharmaceuticals, especially those used to treat persistent and complicated bacterial infections. Hence, a preliminary study of the occurrence of bacteria and genes determining resistance to selected antibiotics, ciprofloxacin and imipenem, was conducted in the bathing waters of the Great Rudnickie Lake. The research showed that the resistance to ciprofloxacin was exhibited by 28% of the total mesophilic bacteria present in water, while the resistance to imipenem was detected in 3.6% of them. It was found that 17–40% of ciprofloxacin-resistant isolates contained the fluoroquinolone-resistance gene qnrS, while the β-lactam-resistance gene blaTEM was found in all the imipenem-resistant strains. The increase in the number of bacteria resistant to the tested antibiotics in the waters of the river outflowing from the lake was observed compared to the inflowing waters, suggesting the potential of the water reservoir as a site for the spreading of drug resistance against tested antibiotics. [ABSTRACT FROM AUTHOR]

Introduction: Since its discovery in 1961, methicillin-resistant Staphylococcus aureus (MRSA) has been recognized as a significant healthcare-associated pathogen (HA-MRSA) and a notorious 'superbug'. Typing is crucial for surveillance, epidemiology analysis, infection control of MRSA and sequencing of the spa gene is one of the most common methods used for determining the origin of this bacterium in humans and animals. This research aimed to determine the antibiotic resistance and spa type of S. aureus strains collected from outpatients in two hospitals in the Wasit province of Iraq. Material & Methods: The study analyzed 200 outpatient MRSA isolates by collecting nasal and sputum samples from patients. Standard biochemical and molecular methods based on the nuc gene were used to identify S. aureus bacteria and amplify the mecA and spa genes. The Kirby-Bauer disc diffusion method was employed to determine the antibiotic sensitivity of the isolates using penicillin, cefoxitin, vancomycin, gentamicin, erythromycin, tetracycline, imipenem, clindamycin, chloramphenicol and rifampicin. Results: Methods. The prevalence of MRSA was more common in women than in men. Antibiogram results showed that most of the isolates were resistant to penicillin (94.2%) and sensitive to imipenem (100%), clindamycin (100%), and chloramphenicol (100%). Of these 35 isolates, 30 (87.5%) and 26 strains (74.3%) were positive for the mecA and spa genes. Typing based on spa gene sequencing revealed four different patterns: t386, t3579, U0002 and U0234. Conclusion: Variations in the spa gene among different S. aureus isolates may he of clinical importance when treating staphylococcal infections. In this study, spa typing revealed four different patterns in Iraq, representing diagnostic and therapeutic implications. [ABSTRACT FROM AUTHOR]

OXA-244, an R214G variant of OXA-48, is silently spreading worldwide likely because of difficulties in detection using classical screening media. Here, we characterized two clinical isolates of Escherichia coli and Citrobacter youngae that displayed reduced susceptibility to carbapenems but were lacking significant carbapenemase activity as revealed by negative Carba NP test results. However, positive test results were seen for OXA-48-like enzymes by lateral flow immunoassays. WGS revealed the presence of a blaOXA-181-like gene that codes for OXA-484, an R214G variant of OXA-181. BlaOXA-484 gene was located on a 58.4-kb IncP1-like plasmid (pN-OXA-484), that upon transfer into E. coli HB4 with impaired permeability, conferred carbapenem and temocillin resistance (MICs > 32 mg/L). E. coli TOP10 (pTOPO-OXA-484) revealed reduced MICs in most substrates as compared to E. coli TOP10 (pTOPO-OXA-181), especially for imipenem (0.25 mg/L versus 0.75 mg/L) and temocillin (16 mg/L versus 1028 mg/L). Catalytic efficiencies of OXA-484 were reduced as compared to OXA-181 for most ß-lactams including imipenem and temocillin with 27.5- and 21.7-fold reduction, respectively. Molecular modeling confirmed that the salt bridges between R214, D159, and the R1 substituent's carboxylate group of temocillin were not possible with G214 in OXA-484, explaining the reduced affinity for temocillin. In addition, changes in active site's water network may explain the decrease in hydrolysis rate of carbapenems. OXA-484 has weak imipenem and temocillin hydrolytic activities, which may lead to silent spread due to underdetection using selective screening media or biochemical imipenem hydrolysis confirmatory tests. [ABSTRACT FROM AUTHOR]

Introduction: Urinary tract infection (UTI) is the most common infection of the pediatric age group. Several factors linked to higher prevalence include poor personal hygiene, improper sanitation, lower socioeconomic status, and malnourishment. In addition to having a worse quality of life, the 1.8 million children who live in Karachi's Korangi district are routinely exposed to such factors. Objectives: The study aims to evaluate the frequency of UTI and distribution of uropathogens along with their antimicrobial susceptibility pattern in patients presenting to a pediatric tertiary care center in the Korangi district of Karachi, Pakistan. Design: The study employed an observational cross-sectional design. Methods: The study was conducted at the Microbiology laboratory of Sindh Institute of Child Health and Neonatology, Karachi, Pakistan from 1st January to 15th August 2023. Urine samples of patients 1 to 16 years of age were collected via midstream clean catch method and of patients from birth up to 1 year were collected in urine collection bags. The samples were cultured on Cystine Lactose Electrolyte Deficient (CLED) agar and antibiotic susceptibility testing was performed using the Kirby-Bauer Disc Diffusion method. Results: A total of 457 urine samples were collected, of which 90 (19.7%) were positive for significant uropathogens. With a mean age of 4.6 years, majority of the culture-positive patients were female (n = 72; 80%). Enterobacterales were the most frequently isolated (n = 88; 95.6%), of which Escherichia coli was the most common (73.9%; n = 68). Citrobacter (n = 7; 7.6%), Klebsiella (n = 6; 6.5%), Serratia (n = 4; 4.3%), Proteus (n = 2; 2.2%), Salmonella (n = 2; 2.2%), and Enterobacter (n = 1; 1.1%) were among the other Enterobacterales isolated. Meropenem and imipenem were the most effective in isolates from Enterobacterales (n = 88) followed by amikacin (n = 84), ciprofloxacin (n = 75), and piperacillin-tazobactam (n = 70). Ceftriaxone and cefixime exhibited moderate susceptibility (n = 69 and 52) whereas, amoxicillin-clavulanate was the least susceptible (n = 3). Conclusion: We report high frequency of UTI in our pediatric population with uropathogens and associated antimicrobial susceptibility pattern confirming to the existing trends of pediatric UTIs in Pakistan. In addition to valuable insights for treating patients under similar conditions, our study serves as a catalyst for further multi-center research in this area. [ABSTRACT FROM AUTHOR]

Objective: Pseudomonas aeruginosa has strong drug resistance and can tolerate a variety of antibiotics, which is a major problem in the management of antibiotic-resistant infections. Direct prediction of multi-drug resistance (MDR) resistance phenotypes of P. aeruginosa isolates and clinical samples by genotype is helpful for timely antibiotic treatment. Methods: In the study, whole genome sequencing (WGS) data of 494 P. aeruginosa isolates were used to screen key anti-microbial resistance (AMR)- associated genes related to imipenem (IPM), meropenem (MEM), piperacillin/tazobactam (TZP), and levofloxacin (LVFX) resistance in P. aeruginosa by comparing genes with copy number differences between resistance and sensitive strains. Subsequently, for the direct prediction of the resistance of P. aeruginosa to four antibiotics by the AMR-associated features screened, we collected 74 P. aeruginosa positive sputum samples to sequence by metagenomics nextgeneration sequencing (mNGS), of which 1 sample with low quality was eliminated. Then, we constructed the resistance prediction model. Results: We identified 93, 88, 80, 140 AMR-associated features for IPM, MEM, TZP, and LVFX resistance in P. aeruginosa. The relative abundance of AMR-associated genes was obtained by matching mNGS and WGS data. The top 20 features with importance degree for IPM, MEM, TZP, and LVFX resistance were used to model, respectively. Then, we used the random forest algorithm to construct resistance prediction models of P. aeruginosa, in which the areas under the curves of the IPM, MEM, TZP, and LVFX resistance prediction models were all greater than 0.8, suggesting these resistance prediction models had good performance. Conclusion: In summary, mNGS can predict the resistance of P. aeruginosa by directly detecting AMR-associated genes, which provides a reference for rapid clinical detection of drug resistance of pathogenic bacteria. [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]

(1) Background: Infections caused by multidrug-resistant (MDR) bacteria represent one of the major global public health problems of the 21st century. Beta-lactam antibacterial agents are commonly used to treat infections due to Gram-negative pathogens. New β-lactam/β-lactamase inhibitor combinations are urgently needed. Combining relebactam (REL) with imipenem (IMI) and cilastatin (CS) can restore its activity against many imipenem-nonsusceptible Gram-negative pathogens. (2) Methods: we performed a systematic review of the studies reporting on the use of in vivo REAL/IPM/CS. (3) Results: A total of eight studies were included in this review. The primary diagnosis was as follows: complicated urinary tract infection (n = 234), complicated intra-abdominal infections (n = 220), hospital-acquired pneumonia (n = 276), and ventilator-associated pneumonia (n = 157). Patients with normal renal function received REL/IPM/CS (250 mg/500 mg/500 mg). The most frequently reported AEs occurring in patients treated with imipenem/cilastatin plus REL/IPM/CS were nausea (11.5%), diarrhea (9.8%), vomiting (9.8%), and infusion site disorders (4.0%). Treatment outcomes in these high-risk patients receiving REL/IPM/CS were generally favorable. A total of 70.6% of patients treated with REL/IPM/CS reported a favorable clinical response at follow-up. (4) Conclusions: this review indicates that REL/IPM/CS is active against important MDR Gram-negative organisms. [ABSTRACT FROM AUTHOR]

This research focuses on assessing the synergistic effects of Mexican oregano (Lippia graveolens) essential oil or carvacrol when combined with the antibiotic imipenem, aiming to reduce the pathogenic viability and virulence of Acinetobacter baumannii and Pseudomonas aeruginosa. The study highlighted the synergistic effect of combining L. graveolens essential oil or carvacrol with imipenem, significantly reducing the required doses for inhibiting bacterial growth. The combination treatments drastically lowered the necessary imipenem doses, highlighting a potent enhancement in efficacy against A. baumannii and P. aeruginosa. For example, the minimum inhibitory concentrations (MIC) for the essential oil/imipenem combinations were notably low, at 0.03/0.000023 mg/mL for A. baumannii and 0.0073/0.000023 mg/mL for P. aeruginosa. Similarly, the combinations significantly inhibited biofilm formation at lower concentrations than when the components were used individually, demonstrating the strategic advantage of this approach in combating antibiotic resistance. For OXA-51, imipenem showed a relatively stable interaction during 30 ns of dynamic simulation of their interaction, indicating changes (<2 nm) in ligand positioning during this period. Carvacrol exhibited similar fluctuations to imipenem, suggesting its potential inhibition efficacy, while thymol showed significant variability, particularly at >10 ns, suggesting potential instability. With IMP-1, imipenem also displayed very stable interactions during 38 ns and demonstrated notable movement and positioning changes within the active site, indicating a more dynamic interaction. In contrast, carvacrol and thymol maintained their position within the active site only ~20 and ~15 ns, respectively. These results highlight the effectiveness of combining L. graveolens essential oil and carvacrol with imipenem in tackling the difficult-to-treat pathogens A. baumannii and P. aeruginosa. [ABSTRACT FROM AUTHOR]

Abstract Therapeutic drug monitoring is an important clinical testing of the drugs to monitor their concentrations in plasma in order to guarantee their optimal impact, and to avoid any side effects resulting from drug-drug interactions. A green reversed-phase high-performance liquid chromatographic method using a photodiode array detector (RP-HPLC-PDA) was developed for the simultaneous determination of three carbapenem antibiotics (Imipenem, ertapenem, and meropenem) with the co-formulated drug (cilastatin) and contraindicated drugs (probenecid and warfarin) in spiked human plasma. The separation was achieved at 25 °C using a gradient elution of a mixture of mobile phase A: methanol and mobile phase B: phosphate buffer (pH 3.0). The photodiode array detector was adjusted at 220 nm. Bioanalytical method validation was carried out as per the FDA guidelines, and the method showed good linearity ranges for the six drugs that included their Cmax levels along with low limits of quantification. Based on the results, the method was found to be accurate and precise; with high % recovery and good % RSD, respectively. The method was successfully applied to spiked human plasma, signifying a good potential to be implemented in future TDM studies of these drugs when co-administered together.

Abstract Background In Japan, carbapenem-resistant Enterobacterales (CRE) infections were incorporated into the National Epidemiological Surveillance of Infectious Diseases (NESID) in 2014, necessitating mandatory reporting of all CRE infections cases. Subsequently, pathogen surveillance was initiated in 2017, which involved the collection and analysis of CRE isolates from reported cases to assess carbapenemase gene possession. In this surveillance, CRE is defined as (i) minimum inhibitory concentration (MIC) of meropenem ≥2 mg/L (MEPM criteria) or (ii) MIC of imipenem ≥2 mg/L and MIC of cefmetazole ≥64 mg/L (IPM criteria). This study examined whether the current definition of CRE surveillance captures cases with a clinical and public health burden. Methods CRE isolates from reported cases were collected from the public health laboratories of local governments, which are responsible for pathogen surveillance. Antimicrobial susceptibility tests were conducted on these isolates to assess compliance with the NESID CRE definition. The NESID data between April 2017 and March 2018 were obtained and analyzed using antimicrobial susceptibility test results. Results In total, 1681 CRE cases were identified during the study period, and pathogen surveillance data were available for 740 (44.0%) cases. Klebsiella aerogenes and Enterobacter cloacae complex were the dominant species, followed by Klebsiella pneumoniae and Escherichia coli. The rate of carbapenemase gene positivity was 26.5% (196/740), and 93.4% (183/196) of these isolates were of the IMP type. Meanwhile, 315 isolates were subjected to antimicrobial susceptibility testing. Among them, 169 (53.7%) fulfilled only the IPM criteria (IPM criteria-only group) which were susceptible to meropenem, while 146 (46.3%) fulfilled the MEPM criteria (MEPM criteria group). The IPM criteria-only group and MEPM criteria group significantly differed in terms of carbapenemase gene positivity (0% vs. 67.8%), multidrug resistance rates (1.2% vs. 65.8%), and mortality rates (1.8% vs 6.9%). Conclusion The identification of CRE cases based solely on imipenem resistance has had a limited impact on clinical management. Emphasizing resistance to meropenem is crucial in defining CRE, which pose both clinical and public health burden. This emphasis will enable the efficient allocation of limited health and public health resources and preservation of newly developed antimicrobials.

Yueliang Chen,1,&ast; Yun Han,2,3,&ast; Feng Guo,1 Zhenwei Yu2,3 1Intensive Care Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Research Center for Clinical Pharmacy, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Guo; Zhenwei Yu, Email 3408003@zju.edu.cn; yzw_srrsh@zju.edu.cnAbstract: Imipenem is a broad-spectrum antibiotic that has been used in treating severe infections and exhibits a time-dependent PK/PD profile. Its dose should be adjusted based on renal function. However, there is little experience with imipenem dosing in obese adolescent patients with augmented renal clearance (ARC) and history of schizophrenia. This case reported successful dosing of imipenem in an obese adolescent patient with ARC based on therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD). A 15-year-old male adolescent patient with history of schizophrenia was diagnosed with ventilator-associated pneumonia due to carbapenem-susceptible Klebsiella pneumoniae and received imipenem treatment (0.5 g every 8 hours with a 1-hour infusion). However, the exposure of imipenem was suboptimal due to ARC, and there is no available model for MIPD in this patient. Thus, we utilized prediction error to find a population pharmacokinetic model that fit this patient and ran Maximum a posteriori Bayesian estimation and Monte Carlo simulation based on screened models to predict changes in drug concentrations. The dose of imipenem was adjusted to 0.5 g every 6 hours with a 2-hour infusion, and subsequent TDM revealed that dosing adjustment was accurate and successful. Finally, the patient’s status of infection improved. This study will be beneficial to imipenem dosing in similar cases in the future, thereby improving the safety and effectiveness of imipenem or other antibiotics.Keywords: case report, imipenem, therapeutic drug monitoring, population pharmacokinetic

Background: Antibiotic resistant infections were responsible for the deaths of 1.27 million people, with an overall 4.95 million deaths associated with complications from resistant bacterial infections globally. Aim: This study determined the antibiotics; aztreonam (ATM), meropenem (MEM) and imipenem (IMP) resistant Gram negative bacteria from inpatient department in FMC, Birnin Kebbi. Methods: Thirty (30) samples from different fomites in the inpatient department were aseptically collected using swab sticks. Streak plate technique was used to characterize and identify the bacterial isolates, then disc diffusion technique was employed to check the resistance pattern of the isolates to the antibiotics as in EUCAST guidelines version 12.0. Results: The biochemical technique further confirmed the occurrence of; Escherichia coli (E. coli) (35%), Pseudomonas aeruginosa (30%), Klebseilla pneumonia (20%) and Acinetobacter baumannii (A. baumannii) (15%). On the antibiotic resistance screening, E. coli and A. baumannii were found multi-drug resistant (MDR) to the antibiotics. The remaining isolates show resistance to the antibiotics except Pseudomonas aeruginosa and Klebsiella pneumonia were found sensitive to MEM and IPM respectively. Conclusion: Bacteria isolated are highly drug resistant to the antibiotics. The need for routine environmental sanitation, proper personal hygiene among the hospital participants, drug repositioning and molecular assay for rapid detection of MDR bacteria.

Staphylococcus succinus was first described in 1998 and was isolated from 25- to 35-million-year-old Dominican amber (1). Members of this species are widespread in nature. Studies have reported the frequent [...]

Background: Infections caused by Stenotrophomonas maltophilia and related species are increasing worldwide. Unfortunately, treatment options are limited, whereas the antimicrobial resistance is increasing. Methods: We included clinical isolates identified as S. maltophilia by VITEK 2 Compact. Ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, quinolones, and tetracycline family members were evaluated by broth microdilution method and compared with first-line treatment drugs. Minimum inhibitory concentrations (MICs) were reported for all antibiotics. We sequenced the Whole Genome of cefiderocol resistant strains (CRSs) and annotated their genes associated with cefiderocol resistance (GACR). Presumptive phylogenetic identification employing the 16S marker was performed. Results: One hundred and one clinical strains were evaluated, sulfamethoxazole and trimethoprim, levofloxacin and minocycline showed susceptibilities of 99.01%, 95.04% and 100% respectively. Ceftazidime was the antibiotic with the highest percentage of resistance in all samples (77.22%). Five strains were resistant to cefiderocol exhibiting MIC values ≥ 2 μg/mL (4.95%). The β-lactamase inhibitors meropenem/vaborbactam and imipenem/relebactam, failed to inhibit S. maltophilia, preserving both MIC50 and MIC90 ≥64 μg/mL. Ceftazidime/avibactam restored the activity of ceftazidime decreasing the MIC range. Tigecycline had the lowest MIC range, MIC50 and MIC90. Phylogeny based on 16S rRNA allowed to identify to cefiderocol resistant strains as putative species clustered into Stenotrophomonas maltophilia complex (Smc). In these strains, we detected GARCs such as Mutiple Drug Resistance (MDR) efflux pumps, L1-type β-lactamases, iron transporters and type-1 fimbriae. Conclusion: Antimicrobial resistance to first-line treatment is low. The in vitro activity of new β-lactamase inhibitors against S. maltophilia is poor, but avibactam may be a potential option. Cefiderocol could be considered as a potential new option for multidrug resistant infections. Tetracyclines had the best in vitro activity of all antibiotics evaluated. [ABSTRACT FROM AUTHOR]

Introduction: Implantable medical devices continue to be vulnerable to bacterial infections. The unrelenting formation of antibiotic resistant bacterial strains not only exacerbates these infections but also renders the current treatment strategies impotent. The need is greater than ever for innovative and effective approaches to counteract drug-resistant bacteria. This study examines the innate antibacterial properties of TiO2 nanotube arrays (TNAs) and their ability to locally deliver antibiotics to inactivate gram-positive and gram-negative bacteria, in vitro. Methods: Using a two-step electrochemical anodization process, TNAs with a diameter of ~100 nm and a length of ~5 µm were grown on titanium substrates. Results and Discussion: After 24 h of incubation, as-fabricated TNAs showed 100% clearance of Escherichia coli, and 97% clearance of Staphylococcus aureus growth. The antibiotic-loaded TNAs demonstrated sustained slow-release of cefotaxime and imipenem measured over 14 days. In vitro bacterial studies revealed the capability of cefotaxime- and imipenem-loaded TNAs in completely inhibiting the growth with 100% clearance of Klebsiella pneumoniae after 24 and 48 h of incubation. Bacterial inhibition assay revealed a significantly enlarged inhibition zone difference of 18mm around the imipenem-loaded TNAs against K. pneumoniae compared to the as-fabricated TNAs which was maintained for 7 days with ~10 μgmL-1 of antibiotic released from the TNAs which was found to be lower than the dose required to completely eradicate multidrug resistant bacteria when used in conjunction with the antibacterial TNAs. The results of our study highlight the potential of TNAs as a versatile platform for addressing treatment strategies related to bacterial infections and antibiotic resistance in implantable medical devices. [ABSTRACT FROM AUTHOR]

Increased antimicrobial resistance (AMR) among bacteria underscores the need to strengthen AMR surveillance and promote data-based prescribing. To evaluate trends and associations between antimicrobial usage (AMU) and AMR, we explored a dataset of 34,672 bacterial isolates collected between 2015 and 2020 from clinical samples at the University Teaching Hospital (UTH) in Lusaka, Zambia. The most frequently isolated species were Escherichia coli (4,986/34,672; 14.4%), Staphylococcus aureus (3,941/34,672; 11.4%), and Klebsiella pneumoniae (3,796/34,672; 10.9%). Of the 16 drugs (eight classes) tested, only amikacin and imipenem showed good (> 50%) antimicrobial activity against both E. coli and K. pneumoniae, while nitrofurantoin was effective only in E. coli. Furthermore, 38.8% (1,934/4,980) of E. coli and 52.4% (2,079/3,791) of K. pneumoniae isolates displayed multidrug resistance (MDR) patterns on antimicrobial susceptibility tests. Among S. aureus isolates, 44.6% (973/2,181) were classified as methicillin-resistant (MRSA). Notably, all the MRSA exhibited MDR patterns. The annual hospital AMR rates varied over time, while there was a weak positive relationship (r = 0.38, 95% CI = 0.11–0.60) between the monthly use of third-generation cephalosporins (3GCs) and 3GC resistance among Enterobacterales. Overall, the results revealed high AMR rates that fluctuated over time, with a weak positive relationship between 3GC use and resistance. To our knowledge, this is the first report to evaluate the association between AMU and AMR in Zambia. Our results highlight the need to strengthen antimicrobial stewardship programs and optimize AMU in hospital settings. [ABSTRACT FROM AUTHOR]

The emergence and spread of multidrug-resistant pathogens like Pseudomonas aeruginosa are major concerns for public health worldwide. This study aimed to assess the prevalence of P. aeruginosa in clinical, environmental, and poultry sources in Bangladesh, along with their antibiotic susceptibility and the profiling of β-lactamase and virulence genes using standard molecular and microbiology techniques. We collected 110 samples from five different locations, viz., BAU residential area (BAURA; n = 15), BAU Healthcare Center (BAUHCC; n = 20), BAU Veterinary Teaching Hospital (BAUVTH; n = 22), Poultry Market (PM; n = 30) and Mymensingh Medical College Hospital (MCCH; n = 23). After overnight enrichment in nutrient broth, 89 probable Pseudomonas isolates (80.90%) were screened through selective culture, gram-staining and biochemical tests. Using genus- and species-specific PCR, we confirmed 22 isolates (20.0%) as P. aeruginosa from these samples. Antibiogram profiling revealed that 100.0% P. aeruginosa isolates (n = 22) were multidrug-resistant isolates, showing resistance against Doripenem, Penicillin, Ceftazidime, Cefepime, and Imipenem. Furthermore, resistance to aztreonam was observed in 95.45% isolates. However, P. aeruginosa isolates showed a varying degree of sensitivity against Amikacin, Gentamicin, and Ciprofloxacin. The blaTEM gene was detected in 86.0% isolates, while blaCMY, blaSHV and blaOXA, were detected in 27.0%, 18.0% and 5.0% of the P. aeruginosa isolates, respectively. The algD gene was detected in 32.0% isolates, whereas lasB and exoA genes were identified in 9.0% and 5.0% P. aeruginosa isolates. However, none of the P. aeruginosa isolates harbored exoS gene. Hence, this study provides valuable and novel insights on the resistance and virulence of circulating P. aeruginosa within the clinical, environmental, and poultry environments of Bangladesh. These findings are crucial for understanding the emergence of β-lactamase resistance in P. aeruginosa, highlighting its usefulness in the treatment and control of P. aeruginosa infections in both human and animal populations. [ABSTRACT FROM AUTHOR]

Background: Escherichia coli (E. coli) is a multidrug resistant opportunistic pathogen that can cause secondary bacterial infections in patients with COVID-19. This study aimed to determine the antimicrobial resistance profile of E. coli as a secondary bacterial infection in patients with COVID-19 and to assess the prevalence and characterization of genes related to efflux pumps and porin. Methods: A total of 50 nonduplicate E. coli isolates were collected as secondary bacterial infections in COVID-19 patients. The isolates were cultured from sputum samples. Confirmation and antibiotic susceptibility testing were conducted by Vitek 2. PCR was used to assess the prevalence of the efflux pump and porin-related genes in the isolates. The phenotypic and genotypic evolution of antibiotic resistance genes related to the efflux pump was evaluated. Results: The E. coli isolates demonstrated high resistance to ampicillin (100%), cefixime (62%), cefepime (62%), amoxicillin-clavulanic acid (60%), cefuroxime (60%), and ceftriaxone (58%). The susceptibility of E. coli to ertapenem was greatest (92%), followed by imipenem (88%), meropenem (86%), tigecycline (80%), and levofloxacin (76%). Regarding efflux pump gene combinations, there was a significant association between the acrA gene and increased resistance to levofloxacin, between the acrB gene and decreased resistance to meropenem and increased resistance to levofloxacin, and between the ompF and ompC genes and increased resistance to gentamicin. Conclusions: The antibiotics ertapenem, imipenem, meropenem, tigecycline, and levofloxacin were effective against E. coli in patients with COVID-19. Genes encoding efflux pumps and porins, such as acrA, acrB, and outer membrane porins, were highly distributed among all the isolates. Efflux pump inhibitors could be alternative antibiotics for restoring tetracycline activity in E. coli isolates. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring is an important clinical testing of the drugs to monitor their concentrations in plasma in order to guarantee their optimal impact, and to avoid any side effects resulting from drug-drug interactions. A green reversed-phase high-performance liquid chromatographic method using a photodiode array detector (RP-HPLC-PDA) was developed for the simultaneous determination of three carbapenem antibiotics (Imipenem, ertapenem, and meropenem) with the co-formulated drug (cilastatin) and contraindicated drugs (probenecid and warfarin) in spiked human plasma. The separation was achieved at 25 °C using a gradient elution of a mixture of mobile phase A: methanol and mobile phase B: phosphate buffer (pH 3.0). The photodiode array detector was adjusted at 220 nm. Bioanalytical method validation was carried out as per the FDA guidelines, and the method showed good linearity ranges for the six drugs that included their Cmax levels along with low limits of quantification. Based on the results, the method was found to be accurate and precise; with high % recovery and good % RSD, respectively. The method was successfully applied to spiked human plasma, signifying a good potential to be implemented in future TDM studies of these drugs when co-administered together. [ABSTRACT FROM AUTHOR]

The stability of antibiotic solutions is a critical factor influencing their efficacy during extended infusion administration. This study investigates and compares the stability of imipenem and meropenem solutions in 0.9% sodium chloride at two temperatures--25°C and 30°C--over a 6-hour period. Imipenem and meropenem solutions, each at a concentration of 10 mg/mL, were prepared and incubated, and samples were collected at various intervals. High-performance liquid chromatography (HPLC) was employed to analyze the remaining antibiotic concentrations. Statistical analyses, including t-tests, were conducted to assess stability at different time points and temperatures. Results revealed that, at 25°C, meropenem solutions maintained stability above 90% throughout the 6-hour duration, while imipenem solutions showed a significant decrease after 3 hours. At 30°C, meropenem solutions remained stable for 4 hours, whereas imipenem solutions rapidly declined below 90% within 1 hour. Comparison between the two antibiotics demonstrated that meropenem exhibited significantly higher stability at 4 and 6 hours at both temperatures (p<0.05). In conclusion, this study offers crucial insights into the stability profiles of imipenem and meropenem during extended infusion. Meropenem emerged as the preferred choice due to its superior stability, emphasizing the importance of temperature considerations in administration and the necessity for proper storage and handling to preserve antibiotic stability. [ABSTRACT FROM AUTHOR]

About 100 C. luteus were examined to determine the extent of the presence of diseasecausing bacteria in the Diwaniyah River from April 2021 to March 2022. The bacteria were isolated using the VITEK2 system, and vital tests identified the species Aeromonas hydrophila and Sphingobacterium thalpophilum. Aeromonas hydrophila and S. thalpophilum were tested in vitro, revealing noticeable antibiotic susceptibility. Levofloxacin (=0.22 µg/ml for A. hydrophila and =0.20 µg/ml for S. thalpophilum), as well as Ciprofloxacin (=0.10 µg/ml) and Imipenem (=0.23 µg/ml), demonstrated notable effectiveness. Resistance to Cefazolin was observed in A. hydrophila (=69 µg/ml) and S. thalpophilum (=70 µg/ml). The study highlights the presence of harmful bacteria in C. luteus from the river, specifically A. hydrophila and S. thalpophilum. The findings emphasize the critical importance of prudent antibiotic use and ongoing monitoring in aquaculture practices to mitigate risks and safeguard public health. [ABSTRACT FROM AUTHOR]

Objective: To investigate the frequency of exoU and exoY genes in patients with Pseudomonas aeruginosa infection. Methods: In this study, 100 clinical isolates of Pseudomonas aeruginosa were collected from patients hospitalized in educational-therapeutic hospitals and were identified using standard microbiological tests. Then, the antibiotic resistance pattern of the isolates was determined by the disk agar diffusion method. The bacterial DNAs were extracted by the alkaline lysis method. Finally, the presence of exoU and exoY genes was evaluated by the PCR test. Results: In this study, 47%, 72%, 29%, 39%, 40%, and 44% of the isolates were non-susceptible to piperacillin, aztreonam, ceftazidime, imipenem, tobramycin, and ciprofloxacin, respectively. In addition, 95% and 93% of the clinical isolates carried the exoU and exoY genes. Blood and fecal isolates had both virulence genes, while only one wound isolate had neither genes. Meanwhile, all urinary isolates contained the exoY gene and only one isolate lacked the exoU gene. Also, 88 isolates simultaneously had both exoU and exoY genes. Conclusions: High prevalence of exoU and exoY genes in this region indicates a significant role of type III secretion system in pathogenesis of Pseudomonas aeruginosa. The type III secretion system may be a suitable target to reduce the pathogenicity of this bacterium. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance poses considerable issues for current clinical care, so the modified use of antimicrobial agents and public health initiatives, coupled with new antimicrobial approaches, may help to minimize the impact of multidrug-resistant (MDR) bacteria in the future. This study aimed to evaluate the antimicrobial, antioxidant, and immunomodulatory activities of Lagenaria siceraria, Thymus vulgaris, and their chitosan nanocomposites against extensive drug-resistant (XDR) Pseudomonas aeruginosa and vancomycin-resistant Staphylococcus aureus (VRSA) using both in vitro and in vivo assays. The in vitro antimicrobial susceptibilities of P. aeruginosa and VRSA strains revealed 100% sensitivity to imipenem (100%). All P. aeruginosa strains were resistant to cefoxitin, cefepime, trimethoprim + sulfamethoxazole, and fosfomycin. However, S. aureus strains showed a full resistance to cefoxitin, amoxicillin, ampicillin, erythromycin, chloramphenicol, and fosfomycin (100% each). Interestingly, all S. aureus strains were vancomycin-resistant (MIC = 32–512 μg/mL), and 90% of P. aeruginosa and S. aureus strains were XDR. The antimicrobial potential of Lagenaria siceraria and Thymus vulgaris nanocomposites with chitosan nanoparticles demonstrated marked inhibitory activities against XDR P. aeruginosa and VRSA strains with inhibition zones' diameters up to 50 mm and MIC values ranging from 0.125 to 1 μg/mL and 1 to 8 μg/mL, respectively. The results of the in vivo approach in male Sprague Dawley rats revealed that infection with P. aeruginosa and S. aureus displayed significant changes in biochemical, hematological, and histopathological findings compared to the negative control group. These values returned to the normal range after treatment by chitosan nanoparticles, either loaded with Lagenaria siceraria or Thymus vulgaris. Real-time quantitative polymerase chain reaction (RT-qPCR) findings presented significant upregulation of the relative expression of the IL10 gene and downregulation of the IFNG gene throughout the experimental period, especially after treatment with chitosan nanoparticles loaded either with Lagenaria siceraria or Thymus vulgaris in comparison to the positive control groups. In conclusion, this is the first report suggesting the use of Lagenaria siceraria and Thymus vulgaris nanocomposites with chitosan nanoparticles as a promising contender for combating XDR P. aeruginosa and VRSA infections as well as a manager for inflammatory situations and oxidative stress-related disorders. [ABSTRACT FROM AUTHOR]