Beta-lactam Antibiotics Research Articles

Therapeutic Efficacy of Baicalein Green Biomolecule in Methicillin-Resistant Staphylococcus aureus Murine Mastitis Model

Methicillin-resistant Staphylococcus aureus (MRSA) mastitis poses a significant threat to dairy herds worldwide, given its resistance to methicillin and other β-lactam antibiotics, which often leads to treatment failure. Consequently, there is an urgent need for safe and effective alternative therapeutic approaches. Recent investigations have highlighted the potential of baicalein, a natural flavonoid known for its potent anti-inflammatory and antibacterial properties, especially its synergistic effects with β-lactam antibiotics against MRSA. However, the limited solubility and bioavailability of baicalein hinder its biomedical utility. The present study assessed the therapeutic efficacy of encapsulated baicalein in chitosan, forming a tricomplex with a β-lactam antibiotic, using a murine model of MRSA-induced mastitis. The experimental design comprised seven groups, each consisting of six mice. We evaluated the ability of various treatment regimens to mitigate histopathological alterations and bacterial burden induced by MRSA infection, aiming to elucidate underlying mechanisms. Our results revealed that tricomplex treatment significantly reduced bacterial load in mammary tissue and preserved tissue integrity, resulting in decreased inflammatory responses post-MRSA inoculation. In addition, tricomplex treatment markedly reduced mean leukocyte and neutrophil counts in blood and suppressed the matrix metalloproteinase-9 (MMP-9) concentration and C-reactive protein (CRP) response. Notably, the synergistic interaction between baicalein and amoxicillin was particularly pronounced. Our findings suggest that chitosan-encapsulated baicalein combined with a β-lactam antibiotic holds promise as a therapeutic option for MRSA-induced mastitis. Further investigations, particularly in target animal species, are warranted to comprehensively evaluate its clinical feasibility.

Pharmacokinetics and pharmacological target attainment of standard temocillin dosing in non-critically ill patients with complicated urinary tract infections.

Temocillin, a carbapenem-sparing β-lactam antibiotic, is commonly used at the standard 4 g/day dosage for treating complicated urinary tract infections (cUTIs). However, pharmacokinetic/pharmacodynamic (PK/PD) data supporting this regimen is limited. This study evaluated the plasma pharmacokinetics (PK) and PTA of temocillin in non-critically ill cUTI patients with varying degrees of renal insufficiency (RI). In this single-centre clinical study, 22 cUTI patients received a fixed 4 g/day (2 g q12h, intravenously) temocillin dose, irrespective of renal function (no RI: n = 5, mild RI: n = 8, moderate RI: n = 9). Plasma samples were collected post-dosing for LC-MS analysis of total and unbound temocillin levels. Monte Carlo simulations were performed based on the established PK/PD target of ≥35% fT > MIC (minimal inhibitory concentration). Among patients, the highest plasma drug exposure and PK/PD target attainment were observed in those with moderate RI (median AUC0-12h = 1143 h.mg/L and %fT > MIC = 68%), followed by mild RI patients (median AUC0-12h = 918 h.mg/L and %fT > MIC = 34%), and the lowest in those with healthy kidney function (median AUC0-12h = 692 h.mg/L and %fT > MIC = 26%). Simulations indicated that the 4 g/day temocillin dose achieves 90% PTA only for glomerular filtration rate < 60 mL/min and MIC ≤ 8 mg/L. The standard temocillin dose may need to be increased from 4 to 6 g/day to treat non-critically ill cUTI patients, in line with recent EUCAST recommendations. For patients with moderate RI, who experience higher exposure due to reduced renal drug clearance, 4 g/day temocillin remains appropriate.

Fully closed conformation of penicillin-binding protein revealed by structure of PBP2 from Acinetobacter baumannii

Penicillin-binding protein 2 (PBP2), a vital protein involved in bacterial cell-wall synthesis, serves a target for β-lactam antibiotics. Acinetobacter baumannii is a pathogen notorious for multidrug resistance; therefore, exploration of PBPs is pivotal in the development of new antimicrobial strategies. In this study, the tertiary structure of PBP2 from A. baumannii (abPBP2) was elucidated using X-ray crystallography. The structural analysis demonstrated notable movement in the head domain, potentially critical for its glycosyltransferase function, suggesting that abPBP2 assumes a fully closed conformation. Our findings offer valuable information for developing novel antimicrobial agents targeting abPBP2 that are applicable in combating multidrug-resistant infections.

Rare Presentation, Critical Diagnosis: Primary Actinomycosis of the Foot

Actinomycosis, an uncommon granulomatous infection caused by the Actinomyces species, rarely targets as primary involvement the limb and is often linked to traumatic incidents. In this report, we present the case of a 44-year-old female who developed multiple small nodules on her left foot over approximately 12 months. Some nodules exhibited firmness and a violet hue, while others discharged a yellowish fluid. The patient had no significant comorbidities. Despite thorough blood paraclinical assessments, including complete blood count, serological HIV testing, and QuantiFERON-TB Gold testing, no abnormalities were detected. Bacteriological examinations and cultures of the discharge yielded negative results. Dermatoscopic examination revealed ovoid yellowish structures, with confocal microscopy highlighting granulomas. A subsequent skin biopsy confirmed characteristic changes indicative of actinomycosis. Although systemic antibiotic therapy with penicillin derivatives was initially considered, the patient’s documented allergic history to this medication class, verified through allergological testing, prompted the initiation of doxycycline treatment. Notably, significant improvement was observed at the 3-month follow-up. This case underscores the importance of reporting rare instances of actinomycosis due to its diagnostic complexity and management challenges.

Development and validation study of compact biophotonic platform for detection of serum biomarkers

The application of advances in personalized medicine requires the support of in vitro diagnostic techniques aimed at the accurate, fast, sensitive, and precise determination of selected biomarkers. Herein, a novel optical centrifugal microfluidic device is developed for clinical analysis and point-of-care diagnostics. Based on compact disc technology, the integrated biophotonic system enables multiple immunoassays in miniaturized mode. The disposable microfluidic discs are made in cyclic olefin copolymer (COP), containing arrays of immobilized probes. In the developed approach, up to six patient samples can each be tested simultaneously. A portable instrument (<2 kg) controls the assay and the high-sensitive reproducible optical detection in transmission mode. Also, the instrument incorporates specific functionalities for personalized telemedicine.The device (analytical method, disc platform, reader, and software) has been validated to diagnose IgE-mediated drug allergies, such as amoxicillin and penicillin G. The total and specific IgE to β-lactam antibiotics were determined in human serum from patients (25 μL). The excellent analytical performances (detection limit 0.24 ng/mL, standard deviation 7–20 %) demonstrated that the developed system could have the potential for a broader impact beyond the allergy field, as it applies to other IVD tests.

Escherichia coli Strains Isolated from American Bison (Bison bison) Showed Uncommon Virulent Gene Patterns and Antimicrobial Multi-Resistance.

E. coli is considered one of the most important zoonotic pathogens worldwide. Highly virulent and antimicrobial-resistant strains of E. coli have been reported in recent years, making it essential to understand their ecological origins. In this study, we analyzed the characteristics of E. coli strains present in the natural population of American bison (Bison bison) in Mexico. We sampled 123 individuals and determined the presence of E. coli using standard bacteriological methods. The isolated strains were characterized using molecular techniques based on PCR. To evaluate the diversity of E. coli strains in this population, we analyzed 108 suggestive colonies from each fecal sample. From a total of 13,284 suggestive colonies, we isolated 33 E. coli strains that contained at least one virulence gene. The virotypes of these strains were highly varied, including strains with atypical patterns or combinations compared to classical pathotypes, such as the presence of escV, eae, bfpB, and ial genes in E. coli strain LMA-26-6-6, or stx2, eae, and ial genes in E. coli strain LMA-16-1-32. Genotype analysis of these strains revealed a previously undescribed phylogenetic group. Serotyping of all strains showed that serogroups O26 and O22 were the most abundant. Interestingly, strains belonging to these groups exhibited different patterns of virulence genes. Finally, the isolated E. coli strains demonstrated broad resistance to antimicrobials, including various beta-lactam antibiotics.

Antimicrobial Susceptibility and Molecular Epidemiology of Multidrug-resistant Pseudomonas aeruginosa in Northeast of Brazil

Introduction: This study aimed to investigate the antimicrobial susceptibility profile of nosocomial strains of Pseudomonas aeruginosa isolated from inpatients of a teaching hospital in the City of Sobral, Ceará, in Northeast of Brazil (Santa Casa de Misericórdia de Sobral - SCMS) from March/2019 to March/2020, as well as to assess the occurrence of resistance genes bla-TEM, bla-SHV, bla-CTX-M 1/2, bla-IMP-1, bla-KPC, bla-GES, bla-SPM-1, bla- NDM-1, bla-VIM. Methodology: Bacterial identification and antimicrobial susceptibility tests (AST) were performed using the automated system Vitek®2. Conventional polymerase chain reaction (PCR) was used to amplify genes of interest. Results: Thirty-eight specimens of P. aeruginosa were collected. More than half of the isolates were resistant to imipenem (55.2%), and showed different rates of resistance to the other antimicrobials tested. In addition, intermediate susceptibility was also observed to gentamicin (7.8% of the isolates) and meropenem (10.52% of the isolates). The gene bla-CTX-M 1/2 was the most prevalent (41.9%), while bla-GES was highly identified among the carbapenemase-producing strains (12.9%). Conclusion: The results demonstrated considerable resistance rates to β-lactam antibiotics, which could be attributable to the indiscriminate use of these antibiotics in the analyzed hospital, whose control relies on the improvement of antimicrobial prescription policies.

Modelling lethality and teratogenicity of zebrafish (Danio rerio) due to β-lactam antibiotics employing the QSTR approach

ABSTRACT Nowadays, β-lactam antibiotics are one of the most consumed OTC (over-the-counter) medicines in the world. Its frequent use against several infectious diseases leads to the development of antibiotic resistance. Another unavoidable risk factor of β-lactam antibiotics is environmental toxicity. Numerous terrestrial as well as aquatic species have suffered due to the excessive use of these pharmaceuticals. In this present study, we have performed a toxicity assessment employing a novel in silico technique like quantitative structure–toxicity relationships (QSTRs) to explore toxicity against zebrafish (Danio rerio). We have developed single as well as inter-endpoint QSTR models for the β-lactam compounds to explore important structural attributes responsible for their toxicity, employing median lethal (LC50) and median teratogenic concentration (TC50) as the endpoints. We have shown how an inter-endpoint model can extrapolate unavailable endpoint values with the help of other available endpoint values. To verify the models’ robustness, predictivity, and goodness-of-fit, several universally popular metrics for both internal and external validation were extensively employed in model validation (single endpoint models: r 2 = 0.631 − 0.75, Q 2 F1 = 0.607 − 0.684; inter-endpoint models: r 2 = 0.768 − 0.84, Q 2 F1 = 0.678 − 0.76). Again, these models were engaged in the prediction of these two responses for a true external set of β-lactam molecules without response values to prove the reproducibility of these models.

Use of the DMAIC Lean Six Sigma quality improvement framework to improve beta-lactam antibiotic adequacy in the critically ill.

Beta-lactam antibiotics are widely used in the intensive care unit due to their favorable effectiveness and safety profiles. Beta-lactams given to patients with sepsis must be delivered as soon as possible after infection recognition (early), treat the suspected organism (appropriate), and be administered at a dose that eradicates the infection (adequate). Early and appropriate antibiotic delivery occurs in >90% of patients, but less than half of patients with sepsis achieve adequate antibiotic exposure. This project aimed to address this quality gap and improve beta-lactam adequacy using the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework. A multidisciplinary steering committee was formed, which completed a stakeholder analysis to define the gap in practice. An Ishikawa cause and effect (Fishbone) diagram was used to identify the root causes and an impact/effort grid facilitated prioritization of interventions. An intervention that included bundled education with the use of therapeutic drug monitoring (TDM; i.e. drug-level testing) was projected to have the highest impact relative to the amount of effort and selected to address beta-lactam inadequacy in the critically ill. The education and TDM intervention were deployed through a Plan, Do, Study, Act cycle. In the 3 months after "go-live," 54 episodes of beta-lactam TDM occurred in 41 unique intensive care unit patients. The primary quality metric of beta-lactam adequacy was achieved in 94% of individuals after the intervention. Ninety-four percent of clinicians gauged the education provided as sufficient. The primary counterbalance of antimicrobial days of therapy, a core antimicrobial stewardship metric, was unchanged over time (favorable result; P = .73). Application of the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework effectively improved beta-lactam adequacy in critically ill patients. The approach taken in this quality improvement project is widely generalizable to other drugs, drug classes, or settings to increase the adequacy of drug exposure.

Prevalence and Molecular Characterization of TEM and CTX-M Beta-Lactamase Genes of Escherichia coli Isolated From Cow Milk

Objective: The study objective was to investigate the presence and antibiotic resistance of toxigenic E. coli strains in the raw milk of dairycattle and to determine the prevalence of blaTEM and blaCTX-M genes in the selected isolates. Methods: Two hundred raw milk samples were collected from 20 dairy farms located in Kafr El Sheikh City. Results: Among the samples, 60 were positive for E. coli. The sensitivity of these isolates was detected against different antibiotics. Usingthe disk diffusion test, all the isolates were resistant to at least two beta-lactam antibiotics. The resistance to beta-lactam antibiotics bythe selected E. coli was varied to be highly significant. Five percent of the tested E. coli was highly resistant with a multi-antibiotic resistant (MAR) index, of 1.0, while 8% had the lowest MAR (0.14). Both blaTEM and blaCTX-M resistant genes were detected in isolate No. 52, while, blaCTX-M was detected in isolate No. 34 and blaTEM was detected in isolates No. 9, 21, 28, and 40. The PCR products of blaTEM and blaCTX-M genes were sequenced and deposited in the GenBank of the NCBI database with the accession numbers OR450046 and OR879117, respectively. Conclusion: The macrolides group of antibiotics especially erythromycin should not be a suitable treatment of dairy herds for mastitisby E. coli in Egypt. The majority of E. coli was multiple-antibiotic resistant and co-carried many virulence genes, and it may pose a greatpotential risk to public health.

In vitro effects of the new oral β-lactamase inhibitor xeruborbactam in combination with oral β-lactams against clinical Mycobacterium abscessus isolates.

Mycobacterium abscessus subsp. abscessus (M. abscessus) disease is treated in two phases; injectable drugs for initial followed by others for continuation. There is a need to develop all-oral treatment methods for M. abscessus infection, especially in the continuation phase. However, treatment options for M. abscessus are limited owing to their natural resistance to most antibiotics. This is the first report to evaluate the in vitro effects of xeruborbactam, a cyclic boronic acid β-lactamase inhibitor capable of inhibiting the class A β-lactamase produced by M. abscessus, against 43 M. abscessus clinical isolates when combined with five β-lactam antibiotics. Xeruborbactam lowered the MIC90 values of tebipenem by five dilutions, and the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%). We showed that the tebipenem-xeruborbactam combination might be of interest to explore further as a potentially effective oral regimen for outpatient treatment of M. abscessus pulmonary disease.

Serotype distribution, antibiotic resistance, multilocus sequence typing, and virulence factors of invasive and non-invasive Streptococcus pneumoniae in Northeast China from 2000 to 2021.

Streptococcus pneumoniae infection is a major public health concern with high morbidity and mortality rates. This study aimed to evaluate the serotype distribution, antimicrobial resistance changes, clonal composition, and virulence factors of S. pneumoniae isolates causing pneumococcal disease in northeast China from 2000 to 2021. A total of 1,454 S. pneumoniae isolates were included, with 568 invasive strains and 886 non-invasive strains. The patients from whom the S. pneumoniae were isolated ranged in age from 26 days to 95 years, with those ≤ 5 years old comprising the largest group (67.19%). 19F, 19A, 23F, 14, and 6B were the most common serotypes, of which 19A and 19F were the main serotypes of invasive and non-invasive S. pneumoniae, respectively. CC271 was the most common multilocus sequence type. Serotype 14 had the lowest expression of cbpA, rrgA, and psrP genes, but expression levels of 19A and 19F genes were similar. All isolates were sensitive to ertapenem, moxifloxacin, linezolid, and vancomycin but highly resistant to macrolides, tetracyclines, and cotrimoxazole. Simultaneous resistance to erythromycin, clindamycin, tetracyclines, and trimethoprim/sulfamethoxazole was common pattern among multidrug-resistant isolates. Non-invasive S. pneumoniae had higher resistance to β-lactam antibiotics than invasive strains. 19A and 19F were the main strains of penicillin-resistant S. pneumoniae. The resistance rate of β-lactam antibiotics decreased from 2017 to 2021 compared to previous periods. Including PCV13 in the national immunization program can reduce the morbidity and mortality rates of pneumococcal disease effectively.

From Bed to Bench: Pre-analytical Stability of 29 Anti-infective Agents in Plasma and Whole Blood to Improve Accuracy of Therapeutic Drug Monitoring.

Therapeutic drug monitoring requires a validated assay and appropriate conditions for sample shipment and storage based on the stability of the compound to be analyzed. This study evaluated the stability of 29 antimicrobial compounds in whole blood (WB) and plasma samples under various storage conditions. The pre-analytical stability of 22 antibiotics (amoxicillin, aztreonam, cefazolin, cefepime, cefotaxime, cefoxitin, ceftazidime, ceftobiprole, ceftolozane, ceftriaxone, ciprofloxacin, clindamycin, cloxacillin, daptomycin, levofloxacin, linezolid, meropenem, metronidazole, moxifloxacin, piperacillin, sulfamethoxazole, and trimethoprim), 2 beta-lactamase inhibitors (avibactam, tazobactam), and 5 antituberculosis drugs (ethambutol, isoniazid, pyrazinamide, rifabutin, and rifampicin) was assessed by WB for up to 24 hours at room temperature (RT) and 72 hours at +4°C. The stability in plasma was evaluated for up to 6 hours at RT, 24 hours at +4°C, 1 month at -20°C, and 6 months at -80°C. Concerning WB stability, all investigated compounds were stable for 24 hours at RT, except meropenem and isoniazid, which were stable for 6 hours; however, for 24 hours at +4°C, all the compounds were stable. For storage durations of 48 and 72 hours at +4°C, all compounds were stable, except for ciprofloxacin, cotrimoxazole, and isoniazid. Concerning stability in plasma, all compounds were stable for 6 hours at RT, and all except isoniazid were stable for 24 hours at +4°C. All the tested compounds were stable for 7 days at -20°C, except isoniazid, for which a degradation of approximately 20% was observed. An important degradation was observed for beta-lactam antibiotics after 1 month at -20°C. All compounds were stable at -80°C for 6 months. The pre-analytical stabilities of several anti-infective compounds was described. The present results can be used to determine the appropriate conditions for shipping and storing samples dedicated to therapeutic drug monitoring of the investigated compounds.

Risk factors and molecular epidemiology of intestinal colonization by carbapenem-resistant Gram-negative bacteria in patients with hematological diseases: a multicenter case‒control study.

Patients with hematological diseases are considered to be at high risk for intestinal colonization by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the epidemiological data regarding risk factors and molecular characteristics of intestinal colonized CR-GNB isolates in this population are insufficient in China. A multicenter case‒control study involving 4,641 adult patients with hematological diseases from 92 hospitals across China was conducted. Following culture of collected rectal swabs, mass spectrometry and antimicrobial susceptibility tests were performed to identify GNB species and CR phenotype. Risk factors were assessed through retrospective clinical information. Whole-genome sequencing was used to analyze the molecular characteristics of CR-GNB isolates. This trial is registered with ClinicalTrials.gov as NCT05002582. Our results demonstrated that among 4,641 adult patients, 10.8% had intestinal colonization by CR-GNB. Of these, 8.1% were colonized by carbapenem-resistant Enterobacterales (CRE), 2.6% were colonized by carbapenem-resistant Pseudomonas aeruginosa (CRPA), and 0.3% were colonized by carbapenem-resistant Acinetobacter baumannii (CRAB). The risk factors for CR-GNB colonization include male gender, acute leukemia, hematopoietic stem cell transplantation, β-lactam antibiotic usage, and the presence of non-perianal infections within 1 week. Compared with CRPA-colonized patients, patients using carbapenems were more likely to be colonized with CRE. NDM was the predominant carbapenemase in colonized CRE. This study revealed a high CR-GNB intestinal colonization rate among adult patients with hematological diseases in China, with CRE being the predominant one. Notably, a significant proportion of CRE exhibited metallo-β-lactamase production, indicating a concerning trend. These findings emphasize the importance of active screening for CR-GNB colonization in patients with hematological diseases.IMPORTANCECarbapenem-resistant Gram-negative bacteria (CR-GNB) has emerged as a significant threat to public health. Patients with hematological diseases are at high risk of CR-GNB infections due to their immunosuppressed state. CR-GNB colonization is an independent risk factor for subsequent infection. Understanding the risk factors and molecular characteristics of CR-GNB associated with intestinal colonization in patients with hematological diseases is crucial for empirical treatment, particularly in patients with febrile neutropenia. However, the epidemiology data are still insufficient, and our study aims to determine the intestinal colonization rate of CR-GNB, identify colonization risk factors, and analyze the molecular characteristics of colonized CR-GNB isolates.

The Immediate and Delayed Maximal Nonirritating Skin Testing Concentrations of β-Lactam Antibiotics

BackgroundMaximal skin testing (ST) nonirritant concentrations (NICs) are consistent for penicillin and aminopenicillin amongst guidelines. However, there is variability amongst guidelines for maximal ST NICs of cephalosporins. ObjectiveTo determine maximal immediate and delayed ST NICs of 15 β-lactams in β-lactam-tolerant and β-lactam-naïve participants. MethodsWe performed a single-center, nonrandomized prospective study between September 2019 and January 2022 in adult participants. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at six increasing concentrations of 1 or more β-lactams. A concentration was considered irritant when more than 5% of participants had a positive test. A positive test was defined as a wheal ≥3 mm than negative control accompanied by a ≥5 mm flare for SPT/IDT and induration ≥5 mm with associated erythema at 48 hours for delayed readings (dIDT). Sensitivity analyses using 3 alternative IDT positive criteria were conducted. ResultsA total of 747 participants with a median age of 64 (IQR 54-72), 52% males, 85% White, and 92% Non-Hispanic underwent 20,858 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT/dIDT NICs (mg/ml): ampicillin (41.6/125), ampicillin-sulbactam (93.8/187.5), aztreonam (6.3/25), cefazolin (55/165), cefepime (35/140), cefoxitin (45/90), ceftaroline (7.5/15), ceftriaxone (58.3/175), cefuroxime (55/110), ertapenem (16.6/50), imipenem-cilastin (6.3/25), meropenem (8.3/25), nafcillin (31.3/62.5), oxacillin (20.9/83.5), and piperacillin-tazobactam (112.5/225). dIDTs were almost all completely non-irritant close or at undiluted concentrations. There were no differences when we applied 3 IDT positivity criteria to our raw data. ConclusionOur results suggest that SPTs with undiluted stock β-lactam antibiotic concentrations are nonirritant. Compared to previously published nonirritant concentrations, we propose a 2 to 50-fold increase to the maximal IDT and dIDT NICs of 15 β-lactam antibiotics. When performing dIDTs, a higher concentration should be used rather than the same IDT concentration.

Peroxymonosulphate activation by ultra-small Ni@NiFe2O4/ZnO magnetic nanocomposites for solar photocatalytic degradation of β-lactam antibiotic - cefadroxil

In this study, ultra-small nickel nanoparticles on NiFe2O4 (Ni@NiFe2O4) and Ni@NiFe2O4/ZnO magnetic nanocomposites were synthesized and utilized for the solar light-driven photocatalytic degradation of cefadroxil. The drug cefadroxil is widely used to treat bacterial infections and cefadroxil is a non-biodegradable pharmaceutical compound detected in the groundwater sources because of its low removal efficiency. The Raman active phonon at 540 cm−1 confirms the presence of Ni nanoparticles at the surface of NiFe2O4/ZnO. DR-UV-Vis analysis exhibited surface plasmon resonance at 350 nm for ultra-small nickel nanoparticles. The observed optical bandgap values for Ni@NiFe2O4 and NiFe2O4/ZnO are 1.2 eV and 2.43 eV, respectively. Which indicates that these magnetic nanocomposites can be utilized for the mineralization of cefadroxil (β-lactam antibiotic) under ambient environmental conditions. The efficiency was determined by the direct solar light driven photocatalytic oxidation of cefadroxil in the presence and absence of peroxymonosulphate (PMS). The experimental findings exhibits that ∼95 % of cefadroxil (CDL) was eliminated by the ultra-small Ni@NiFe2O4/ZnO within 60 min (k = 7.5 × 10−4 s−1) of direct solar light irradiation. Further, the addition of PMS enhanced the photodegradation to achieve 100 % cefadroxil oxidation within 40 min (k = 25 × 10−4 s−1) of direct sunlight. The efficiency of the nanocatalyst was compared with controlled experiments and was found to be Fe2O3 < ZnO < TiO2 (P25) < Ni@NiFe2O4 < Ni@NiFe2O4/ZnO under absence and presence of PMS. Moreover, ultra-small Ni@NiFe2O4/ZnO nanophotocatalyst were stable up to 3 consecutive cycles.

Evolving resistance landscape in gram-negative pathogens: An update on β-lactam and β-lactam-inhibitor treatment combinations for carbapenem-resistant organisms.

Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of β-lactamases diminishing the activity of classic β-lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of β-lactamase inhibitors (BLIs) with activity against extended-spectrum β-lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo-β-lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem-resistant Acinetobacter baumannii. This review aims to provide a snapshot of microbiology, pharmacology, and clinical data for currently available BL/BLI treatment options as well as agents in late stage development for CRO harboring various β-lactamases including MBL and OXA-enzymes.

Estimation of the of Beta-Lactamase Production in Staphylococcus aureus Isolates from Blepharitis Patients

In this study, 90 eyelid swabs were obtained from patients with blepharitis of both sexes and various age groups who were admitted to various hospitals, and other primary healthcare centers between September 2023 and February 2024, in Babylon governorate. It was found that blepharitis occurs in all age groups and affects both sexes without any differences between them, but it is clear that blepharitis is more prevalent in the age range of (20 to 49) years old. It was discovered that out of the 90 samples, 75 (83.3%) had positive bacterial cultures, and 15 (16.7%) had no growth at all. Also, Staphylococcus aureus was the most common bacteria 39 (52%), followed by Haemophilus influenzae 17 (22.7%), Streptococcus pneumoniae 10 (13.3%), Klebsiella pneumoniae 7 (9.3%), and only 2 isolates of Streptococcus pyogenes (2.7%). The rapid iodometric method has been employed to investigate the production of beta-lactamase enzyme by the common bacteria Staphylococcus aureus, which was isolated from the eyelid's margin of patients with blepharitis. It was found that 36 (92.3%) of the 39 Staphylococcus aureus isolates had the ability to produce β-lactamase. A number of common beta-lactam antibiotics, such as penicillin, amoxicillin, ampiclox cephalexin, and cefazolin have also been used to investigate the ability of Staphylococcus aureus to produce the β-lactamase enzyme. The results showed that all isolates of Staphylococcus aureus were 100% resistant to penicillin, cephalexin and cefazolin. whereas some isolates 30 isolates were resistant to ampiclox (77%), and only 23 isolates were resistant to amoxicillin (59%).

Differences in the prevalence and antimicrobial resistance among non-typhoidal Salmonella serovars isolated from retail chicken meat across the United States of America, 2013–2020

The emergence of antimicrobial-resistant non-typhoidal Salmonella (NTS) in retail chicken meat poses a food safety risk. Data on antimicrobial resistance (AMR) in NTS isolates collected by the National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS) from retail chicken meat across the United States of America between 2013 and 2020 were analyzed. A total of 3,067 samples tested positive for NTS. The most common NTS serovars were S. Kentucky (n = 1,088), S. Infantis (n = 587), S. Enteritidis (n = 475), and S. Typhimurium (n = 424), respectively. A significant increasing trend in the proportion of S. Infantis and a decreasing trend for S. Typhimurium has been observed. High-proportion clusters were detected in the northeast and southeast of the United States of America for S. Typhimurium and in the west coast and southeast for S. Kentucky. Multidrug resistance (resistance to at least three antimicrobial classes) was common in S. Infantis and S. Typhimurium isolates, while S. Enteritidis isolates were mainly pan-susceptible. The predicted probability of resistance to beta-lactam antibiotics (ampicillin and ceftriaxone), sulfonamides (sulfisoxazole), and quinolones (nalidixic acid) were highest in S. Infantis isolates, while S. Kentucky isolates showed the highest probability of resistance to aminoglycosides (streptomycin) and tetracyclines. Differences in the geographical distribution of NTS serovars and variations in their AMR patterns warrant serovar-specific antimicrobial stewardship programs.

The IncC and IncX1 resistance plasmids present in multi-drug resistant Escherichia coli strains isolated from poultry manure in Poland

The study describes the whole-genome sequencing of two antibiotic-resistant representative Escherichia coli strains, isolated from poultry manure in 2020. The samples were obtained from a commercial chicken meat production facility in Poland. The antibiotic resistance profile was characterized by co-resistance to β-lactam antibiotics, aminoglycosides, and fluoroquinolones. The three identified resistance plasmids (R-plasmids), pECmdr13.2, pECmdr13.3, and pECmdr14.1, harbored various genes conferring resistance to tetracyclines (tetR[A]) for, aminoglycoside (aph, aac, and aad families), β-lactam (blaCMY-2, blaTEM-176), sulfonamide (sul1, sul2), fluoroquinolone (qnrS1), and phenicol (floR). These plasmids, which have not been previously reported in Poland, were found to carry IS26 insertion elements, the intI1-integrase gene, and conjugal transfer genes, facilitating horizontal gene transfer. Plasmids pECmdr13.2 and pECmdr14.1 also possessed a mercury resistance gene operon related to transposon Tn6196; this promotes plasmid persistence even without antibiotic selection pressure due to co-selection mechanisms such as co-resistance. The chicken manure–derived plasmids belonged to the IncX1 (narrow host range) and IncC (broad host range) incompatibility groups. Similar plasmids have been identified in various environments, clinical isolates, and farm animals, including cattle, swine, and poultry. This study holds significant importance for the One Health approach, as it highlights the potential for antibiotic-resistant bacteria from livestock and food sources, particularly E. coli, to transfer through the food chain to humans and vice versa.