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Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P =.48) and 0.02% (n = 11) in patients who have no rPCNA (P =.02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P =.58), deep infections (0.3 versus 0.4%, P =.68), or C difficile infections (0.04% versus 0%, P =.99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. III. [ABSTRACT FROM AUTHOR]

Background: Cefiderocol is a siderophore-conjugated cephalosporin increasingly used in the management of Achromobacter infections. Testing for cefiderocol susceptibility is challenging with distinct recommendations depending on the pathogens. Objectives: We evaluated the performance of commercial tests for testing cefiderocol susceptibility in the Achromobacter genus and reviewed the literature. Methods: Diffusion (disks, MIC gradient test strips [MTS], Liofilchem) and broth microdilution (BMD) methods (ComASP™, Liofilchem; UMIC®, Bruker) were compared with the BMD reference method according to the EUCAST guidelines on 143 Achromobacter strains from 14 species with MIC50/90 of ≤ 0.015/0.5 mg/L. A literature search was conducted regardless of method or species. Results: None of the methods tested fulfilled an acceptable essential agreement (EA). MTS displayed the lowest EA (30.8%) after UMIC® (49%) and ComASP™ (76.9%). All methods achieved an acceptable bias, with MICs either underestimated using MTS (-1.3%) and ComASP™ (-14.2%) or overestimated with UMIC® (+ 9.1%). Inhibition zone diameters ranged from 6 to 38 mm (IZD50/90=33/30 mm). UMIC® and ComASP™ failed to categorize one or the two cefiderocol-resistant strains of this study as resistant unlike the diffusion-based methods. The literature review highlighted distinct performance of the available methods according to pathogens and testing conditions. Conclusions: The use of MTS is discouraged for Achromobacter spp. Disk diffusion can be used to screen for susceptible strains by setting a threshold diameter of 30 mm. UMIC® and ComASP™ should not be used as the sole method but have to be systematically associated with disk diffusion to detect the yet rarely described cefiderocol-resistant Achromobacter sp. strains. Highlights: Performance of commercial methods are highly diverse and species-dependent. The use of MTS is discouraged due to low essential agreement. UMIC® and ComASP™ failed to detect one or the two cefiderocol-resistant strains. UMIC® or ComASP™ should not be used as the sole method for Achromobacter cefiderocol susceptibility testing. A threshold diameter of 30 mm is proposed for susceptible strain screening. [ABSTRACT FROM AUTHOR]

Background Growing evidence indicates antimicrobial resistance disproportionately affects individuals living in socially vulnerable areas. This study evaluated the association between the CDC/ATSDR Social Vulnerability Index (SVI) and Streptococcus pneumoniae (SP) antimicrobial resistance (AMR) in the United States. Methods Adult patients ≥18 years with 30-day nonduplicate SP isolates from ambulatory/hospital settings from January 2011 to December 2022 with zip codes of residence were evaluated across 177 facilities in the BD Insights Research Database. Isolates were identified as SP AMR if they were non-susceptible to ≥1 antibiotic class (macrolide, tetracycline, extended-spectrum cephalosporins, or penicillin). Associations between SP AMR and SVI score (overall and themes) were evaluated using generalized estimating equations with repeated measurements within county to account for within-cluster correlations. Results Of 8008 unique SP isolates from 574 US counties across 39 states, the overall proportion of AMR was 49.9%. A significant association between socioeconomic status (SES) theme and SP AMR was detected with higher SES theme SVI score (indicating greater social vulnerability) associated with greater risk of AMR. On average, a decile increase of SES, indicating greater vulnerability, was associated with a 1.28% increased risk of AMR (95% confidence interval [CI],.61%, 1.95%; P =.0002). A decile increase of household characteristic score was associated with a 0.81% increased risk in SP AMR (95% CI,.13%, 1.49%; P =.0197). There was no association between racial/ethnic minority status, housing type and transportation theme, or overall SVI score and SP AMR. Conclusions SES and household characteristics were the SVI themes most associated with SP AMR. [ABSTRACT FROM AUTHOR]

CONTEXT: Sepsis is a leading cause of young infant mortality. OBJECTIVE: To evaluate the efficacy of different antibiotic regimens to treat young infant sepsis or possible serious bacterial infection (PSBI) on clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, World Health Organization Global Index Medicus, Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials (RCTs) of young infants 0 to 59 days with sepsis or PBSI (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. DATA EXTRACTION: We extracted data and assessed risk of bias in duplicate. We performed random- effects meta-analysis, and used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. RESULTS: Of 2390 publications, we included 41 RCTs (n 5 18 054). Thirty-five trials were hospital-based and 6 were nonhospital-based. Meta-analysis of 4 trials demonstrated similar rates of treatment success with intramuscular/intravenous third generation cephalosporins versus intramuscular/intravenous penicillin or ampicillin 1 gentamicin (RR 1.03, 95% CI 0.93--1.13]; n 5 1083; moderate certainty of evidence). Meta-analysis of 3 trials demonstrated similar rates of treatment failure with oral amoxicillin 1 intramuscular gentamicin versus intramuscular penicillin 1 gentamicin for nonhospital treatment of clinical severe illness (RR 0.86, 95% CI 0.72--1.02]; n 5 5054; low certainty of evidence). Other studies were heterogeneous. LIMITATIONS: RCTs evaluated heterogeneous regimens, limiting our ability to pool data. CONCLUSIONS: We found limited evidence to support any single antibiotic regimen as superior to alternate regimens to treat young infant sepsis or PSBI. [ABSTRACT FROM AUTHOR]

Modified electrodes based on gold particles, mixed-valence ruthenium oxides, and a binary system combining these components were developed for the voltammetric determination of ceftriaxone, cefotaxime, and cefoperazone. The electrode with the binary system of gold particles and mixed-valence ruthenium oxides, which exhibited the best performance, was used for the detection of cephalosporins in flow-injection analysis. Optimal conditions for the detection of cephalosporins in a flow-injection system were selected. The dependence of the analytical signal on the concentration of the compounds under consideration is linear on logarithmic coordinates over the range from 5 × 10–7 to 5 × 10–3 M. The proposed procedure was tested in the determination of cephalosporins in pharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: To reduce maternal-fetal morbidity and mortality, it is becoming increasingly important for anesthetists to understand and implement enhanced recovery after surgery (ERAS) cesarean delivery guidelines. Our aim was to reveal the knowledge of anesthesia assistants in Turkey about ERAS during cesarean delivery and to increase their awareness of ERAS. Methods: This descriptive study was conducted in the city of Isparta, Turkey in 2023. The survey, which was approved by the ethics committee, was distributed to participants across Turkey via e-mail and online messages. The survey comprises of a total of 42 questions evaluating perioperative ERAS recommendations. Results: Of the 404 participants in our survey, 59.9% were associated with university hospitals and 65.8% had completed three or more years of education. A total of 87.9% of the participants were familiar with ERAS; however, only 42.8% had received ERAS training. Although 93.8% of the participants' institutions performed a cesarean delivery, ERAS recommendations were only implemented at a rate of 48%. This may be due to the absence of an ERAS team, which was identified in our survey at a high rate of 66.6%. Conclusion: Awareness about ERAS was high among the participants, but the implementation rates of some recommendations were low. The reason for this may be the inability to form a multidisciplinary team and inadequate training of participants. For this purpose, we recommend the formation of a multidisciplinary team for ERAS protocol implementation and increased participant training opportunities. [ABSTRACT FROM AUTHOR]

Disseminated gonococcal infection is the causative agent of approximately 0.6%-1.2% of septic arthritis cases in North America and Europe. Typical presentations of this disorder include tenosynovitis, dermatitis, polyarthralgia, or oligoarticular purulent arthritis affecting the distal joints. Diagnosis is contingent on clinical presentation, with urine nucleic acid amplification testing as the preferred diagnostic modality. Synovial fluid cultures, along with imaging, can confirm diagnosis. The recommended treatment is a third-generation cephalosporin, such as intravenous ceftriaxone for 7-14 days and a dose of oral azithromycin. [ABSTRACT FROM AUTHOR]

In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). In this post-hoc analysis of randomized controlled trials (RCT) on patients hospitalized for CAP (pneumonia short treatment trial) comparing 3-day vs. 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). The choice of route and molecule was left to the physician in charge. The main outcome was a failure at 15 days after the first antibiotic intake, defined as temperature >37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to the route of administration was evaluated through logistic regression. Inverse probability treatment weighting with a propensity score model was used to adjust for non-randomization of treatment routes and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC vs. 3GC treatments, intravenous vs. oral AMC, patients with multi-lobar infection, patients aged ≥65 years old, and patients with CURB65 scores of 3–4). We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. The failure rate at Day 15 was not significantly different among patients treated with initial intravenous vs. oral treatment [25/93 (26.9%) vs. 28/107 (26.2%), adjusted odds ratios (aOR) 0.973 (95% CI 0.519–1.823), p 0.932)]. Failure rates at Day 15 were not significantly different among the subgroup populations. Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. This trial is registered with ClinicalTrials.gov , NCT01963442. [ABSTRACT FROM AUTHOR]

The article highlights the transformative impact of antibiotics introduced in the mid-20th century. Topics include the exploration of secondary metabolites from microorganisms as potential new antimicrobial drugs, the three approaches to antibiotic production—fermentation, semi-synthetic modification, and chemical synthesis—and a study on the metabolic potential of Arctic fungi, which revealed novel secondary metabolites and biosynthetic gene clusters.

Objective: This study aims to assess the outcome of challenging documented moderate, severe, or unknown beta‐lactam allergies with full dose administration of a beta‐lactam antibiotic in emergency department (ED) patients admitted for acute bacterial infection. Methods: A single‐center, retrospective, descriptive study of adult patients challenged with a full dose of beta‐lactam in the ED from January 2021 to December 2022 was conducted. Included patients had at least one documented moderate, severe, or unknown beta‐lactam allergy in the electronic medical record (EMR) without documentation of prior tolerance. Patient demographics, prior beta‐lactam antibiotic reaction, beta‐lactam administered in the ED, inpatient beta‐lactam continuation, adverse drug reactions, and updates to allergy profiles were collected. Descriptive statistics for data analysis were performed using SPSS Version 22. Results: Of the 184 ED encounters with full‐dose beta‐lactam challenges, five (2.7%) patients with documented moderate, severe, or unknown beta‐lactam allergies experienced an allergic reaction after the challenge; one (0.5%) patient had an allergic reaction in the ED, and the remaining four (2.2%) occurred after admission. No anaphylactic reactions occurred. All allergic reactions were limited to mild rash or itching. Most patients (98.9%) were challenged with a cephalosporin. A beta‐lactam was continued in 86.4% of cases, and the allergy profile was updated for future utilization in 73.4% of patients. Conclusions: This study suggests that full‐dose challenge of moderate, severe, or unknown beta‐lactam allergies can be safely accomplished in the ED. This approach avoids unnecessary penicillin allergy skin testing and reduces utilization of suboptimal alternative antibiotic regimens. [ABSTRACT FROM AUTHOR]

Cephalosporin antibiotics are widely used in clinical settings, but they can cause hypersensitivity reactions, which may be influenced by genetic factors such as the expression of Human leukocyte antigen (HLA) molecules. This study aimed to investigate whether specific HLA alleles were associated with an increased risk of adverse reactions to cephalosporins among individuals in the Taiwanese population. This retrospective case–control study analyzed data from the Taiwan Precision Medicine Initiative (TPMI) on 27,933 individuals who received cephalosporin exposure and had HLA allele genotyping information available. Using logistic regression analyses, we examined the associations between HLA genotypes, comorbidities, allergy risk, and severity. Among the study population, 278 individuals had cephalosporin allergy and 2780 were in the control group. Our results indicated that certain HLA alleles, including HLA-B*55:02 (OR = 1.76, 95% CI 1.18–2.61, p = 0.005), HLA-C*01:02 (OR = 1.36, 95% CI 1.05–1.77, p = 0.018), and HLA-DQB1*06:09 (OR = 2.58, 95% CI 1.62–4.12, p < 0.001), were significantly associated with an increased risk of cephalosporin allergy reactions. Additionally, the HLA-C*01:02 allele genotype was significantly associated with a higher risk of severe allergy (OR = 2.33, 95% CI 1.05–5.15, p = 0.04). This study identified significant associations between HLA alleles and an increased risk of cephalosporin allergy, which can aid in early detection and prediction of adverse drug reactions to cephalosporins. Furthermore, our study highlights the importance of HLA typing in drug safety and expanding our knowledge of drug hypersensitivity syndromes. [ABSTRACT FROM AUTHOR]

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]

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

Nanozymes present promising alternatives to natural enzymes, but controlling nanozymes' performance and employing them for selectively removing antibiotics are extremely challenging. Employing theoretical calculations to design the coordination environments of mental and coordination atoms for directing single‐atom nanozymes synthesis emerges as a promising strategy to enhance their efficiency and selectivity in antibiotic elimination. In this study, the peroxidase‐like specificity of iron single‐atom nanozymes (FeSA‐Nx, x = 2,3, and 4) with specific Fe–N coordination numbers is demonstrated based on theoretical calculations. These calculations guide the synthesis of corresponding ultra‐thin FeSA‐Nx, achieving a high degree of consistency between theoretical predictions and experimental results. FeSA‐N3 with a Fe─N3 coordination number proves to be the most effective. The efficient electron transfer from Fe─N3 site to H2O2 reduces the free energy required for •OH generation. Quantitative structure‐activity relationship (QSAR) analysis reveals a strong positive correlation between degradation efficiency of cephalosporins and their electron‐donating capabilities (R2 = 0.820–0.929), realizing selectively eliminating cephalosporins. Integration FeSA‐N3 into ceramic membrane (FeSA‐N3/CM) improves hydrophilicity, achieving continuous and stable removal of cephalosporin. This study provides valuable insights into coordination number regulating nanozyme properties for selective antibiotics removal and offers novel perspectives for FeSA‐N3 application in integrated systems. [ABSTRACT FROM AUTHOR]

Pharmaceutical manufacturers are globally forced to follow international guidelines on cleaning validation. Cleaning validation is related to the concept of the worst-case product; however, the worst-case product is a function of the manufacturer and the product portfolio. Consequently, manufacturers are faced repeatedly by cycles of worst-case product alteration, and repeated cycles of worst-case oriented analytical method development. Generally, this problem is hardly controlled due to the various products manufactured by the same facility. However, Analytical Quality by Design (AQbD) offers a possible solution through the development of robust and sensitive multicomponent analytical methods that span a wide spectrum of possible products. Cephalosporin antibiotics are a broadly manufactured class of antibiotics that can lead to anaphylaxis in extremely small quantities; therefore, an ultra-level of cleanness is required for facilities involved in such products. A group of the highest market share cephalosporin products was used to present the application of AQbD to introduce a reliable solution to cleaning validation that can be employed in pharmaceutical facilities. A multivariate optimization approach was utilized for the development of a sensitive multicomponent HPLC method; in addition to the proposal of a novel chemometric approach to troubleshoot the developed method. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the antibiotic resistance of microorganisms isolated in cases of culture-positive nosocomial late-onset neonatal sepsis in the neonatal intensive care unit. Materials and Methods: Infants admitted to our neonatal intensive care unit between October 2015 and June 2022 were retrospectively screened. A total of 458 different cultures from 386 sepsis incidents in 250 infants were analyzed. Results: Over an 8-year period, 407 cases of culture-positive nosocomial late-onset neonatal sepsis were reviewed in a total of 4244 infants. Twenty-one cases were excluded due to insufficient data. The incidence of culture-positive nosocomial sepsis was 6.3%. Coagulase-negative Staphylococcus and Staphylococcus aureus were the most common gram-positive bacteria found in cultures. Resistance to ampicillin and cephalosporin treatments was high, while resistance to vancomycin, teicoplanin, and linezolid was low. Klebsiella spp. were the most frequent gram-negative bacteria isolated in cultures and showed high resistance to non-carbapenembased regimens. The only fungal microorganisms isolated in cultures were Candida spp., which had a high mortality rate despite their low resistance profile. The mortality rate due to nosocomial sepsis was 19.6%. Conclusion: Our study demonstrated that microorganisms and their antibiotic resistance profiles changed over time in the newborn intensive care unit. Gram-negative pathogens exhibited high antibiotic resistance, while fungi had high mortality rates. It is essential to adjust empirical antibiotic regimens for nosocomial sepsis based on thorough surveillance. [ABSTRACT FROM AUTHOR]

Background and Objectives: The search of new effective antibacterial drugs and the development of more advanced dosage and delivery systems for existing antibiotics (AB) are actual research objectives for biomedical science. During the study emulsion microgels (EM), based on whey protein isolate, containing antibacterial drugs (cefazolin (CZ), ceftriaxone (CT)) were obtained by ultrasonic homogenization method. The effect of AB-loaded EM on E. coli strain was studied in comparison to free AB. Materials and Methods: The formation of oil-in-water microemulsions stabilized by whey protein isolate (WPI) in saline was carried out using the method of spontaneous emulsification during ultrasonic homogenization using a rod ultrasonic homogenizer. This approach is based on the denaturation of protein under ultrasonic influence on a solution of biomolecules with the subsequent formation of a microgel shell on the surface of oil droplets. Quantitative characteristics of antibiotics loading and its release from microgels were determined spectrophotometrically. Visualization and calculation of EMs particle sizes were carried out using an optical microscope. The study of AB-loaded EM antibacterial action was performed in liquid nutrient media followed by seeding onto nutrient agar. The experiment was followed with live-dead test, carried out by flow cytometry with cell visualization. Results: The rate and characteristics of AB release from the obtained carriers in various model media, as well as the antimicrobial activity of microgels, have been studied. It has been found that the release of AB from synthesized carriers on the first day of the experiment is 10% in all studied model systems. The total amount of AB released over 144 hours reaches 20% in saline solution and 30% in artificial urine. According to the results of the experiment, all samples of EM, containing CZ caused inhibition of E. coli growth within 7 days. Of these, total suppression of bacterial growth was observed within 1 day for EM 1 : 3 and 1 days for EM 1 : 5, on the remaining days – partial growth suppression. Free CZ remained active during the first day. EM, containing CT, demonstrated an antibacterial effect for 14 days. In this case, the bactericidal nature of the action was observed within 10 days for EM 1 : 3 and 13 days for EM 1 : 5. Free CT also had an antimicrobial effect for 14 days, but the duration of the period of complete growth inhibition in all control samples was significantly shorter compared to EM samples. Conclusion: The immobilization of antibacterial drugs (CZ, CT) into emulsion microgels not only does not lead to a decrease in their effectiveness, but also makes it possible to significantly increase the duration and intensity of action of these drugs. The results obtained are of interest for further study of the possibilities of using emulsion MGs based on WMB as carriers of antibacterial drugs.

Abstract 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 Background The emergence and spread of β-lactamase-producing Klebsiella spp. has been associated with a substantial healthcare burden resulting in therapeutic failures. We sought to describe the proportion of phenotypic resistance to commonly used antibiotics, characterize β-lactamase genes among isolates with antimicrobial resistance (AMR), and assess the correlates of phenotypic AMR in Klebsiella spp. isolated from stool or rectal swab samples collected from children being discharged from hospital. Methods We conducted a cross-sectional study involving 245 children aged 1–59 months who were being discharged from hospitals in western Kenya between June 2016 and November 2019. Whole stool or rectal swab samples were collected and Klebsiella spp. isolated by standard microbiological culture. β-lactamase genes were detected by PCR whilst phenotypic antimicrobial susceptibility was determined using the disc diffusion technique following standard microbiology protocols. Descriptive analyses were used to characterize phenotypic AMR and carriage of β-lactamase-producing genes. The modified Poisson regression models were used to assess correlates of phenotypic beta-lactam resistance. Results The prevalence of β-lactamase carriage among Klebsiella spp. isolates at hospital discharge was 62.9% (154/245). Antibiotic use during hospitalization (adjusted prevalence ratio [aPR] = 4.51; 95%CI: 1.79–11.4, p

The incidence of multi-resistant infections has sharply increased. One of the best strategies for developing new drugs is re-engineering existing drugs to enhance their bioavailability and antimicrobial activities. The latest systems focus on designing bioinorganic platforms to develop antimicrobial agents to target drug-resistant microbial strains. Various literature reports highlight metal-based antimicrobial agents unveiling an innovative strategy to tackle microbial agents. One of the significant mechanisms of antibiotic resistance in bacteria is the impermeability of its cell membrane towards antibiotics. Antibiotic-based Schiff base complexes are prime candidates for drug design with minor side effects in this scenario. The enhanced activity of antibiotic Schiff base complexes over their parent compound plays a key role in the emergence of innovative antimicrobials. In this review, we highlight the biological potential aspects of some selected antibiotic-based Schiff base complexes of penicillin, cephalosporins, quinolones, and sulfonamides. Some of the bacteria, especially P. aeruginosa, remain resistant to most of the commercially available antibiotics. Here, the review highlights that Schiff base complexes mediated by antibiotics demonstrate bactericidal activity against these resistant strains. Additionally, their mode of action on the bacterial cell is highlighted. The increased activity of copper, zinc, and silver complexes of different Schiff bases is attributed to their inherent redox chemistry. [ABSTRACT FROM AUTHOR]

The article discusses the growing threat of multidrug-resistant Gram-negative infections. Topics discussed include the rapid evolution of bacterial resistance mechanisms, the pharmaceutical industry's challenges in developing effective antibiotics, and a poignant case study of fatal antibiotic-resistant E. coli in a child.

Purpose Multidrug-resistant (MDR) infections are challenging to treat due to underlying patient conditions, pathogen characteristics, and high antibiotic resistance rates. As newer antibiotic therapies come to market, limited data exist about their real-world utilization. Methods This was a national retrospective cohort study of ceftazidime/avibactam (approved in 2015) utilization among inpatients from the Veterans Affairs (VA) Healthcare System, from 2015 through 2021. Joinpoint regression was used to estimate time trends in utilization. Results Ceftazidime/avibactam use increased by 52.3% each year (days of therapy per 1,000 bed days; 95% confidence interval, 12.4%-106.4%). We identified 1,048 unique predominantly male (98.3%) and white (66.2%; Black, 27.7%) patients treated with ceftazidime/avibactam, with a mean (SD) age of 71.5 (11.9) years. The most commonly isolated organisms were Pseudomonas aeruginosa (36.3%; carbapenem resistant, 80.6%; MDR, 65.0%) and Klebsiella species (34.1%; carbapenem resistant, 78.4%; extended-spectrum cephalosporin resistant, 90.7%). Common comorbid conditions included hypertension (74.8%), nervous system disorders (60.2%), diabetes mellitus (48.7%), and cancer (45.1%). Median time to ceftazidime/avibactam initiation from admission was 6 days, with a median of 3 changes in therapy before ceftazidime/avibactam initiation and a subsequent median length of inpatient stay of 14 days (median of 8 days of ceftazidime/avibactam therapy). Treatment heterogeneity was high, both before ceftazidime/avibactam initiation (89.6%) and during ceftazidime/avibactam treatment (85.6%), and common concomitant antibiotics included vancomycin (41.4%), meropenem (24.1%), cefepime (15.2%), and piperacillin/tazobactam (15.2%). The inpatient mortality rate was 23.6%, and 20.8% of patients had a subsequent admission with ceftazidime/avibactam treatment. Conclusion Utilization of ceftazidime/avibactam increased from 2015 to 2021 in the national VA Healthcare System. Ceftazidime/avibactam was utilized in complex, difficult-to-treat patients, with substantial treatment heterogeneity and variation in the causative organism and culture sites. [ABSTRACT FROM AUTHOR]

The processes of biocatalytic synthesis of cefamandole and cefazoline, as well as four "chimeric" cephalosporins carrying functional groups of these antibiotics in the C3 or C7 position of β-lactam, were carried out using immobilized cephalosporin-acid synthetase under mild standard conditions. A higher efficiency of biocatalytic acylation of β-lactams with a 1(H)-tetrazolylacetic acid residue was demonstrated compared to acylation with mandelic acid residue. The chemical structure of the obtained compounds was confirmed using the HPLC-MS method. The possibility of using directly reaction mixtures for evaluating the antibacterial activity of the compounds synthesized without isolating the target products is demonstrated. The activity of the obtained cephalosporins against twelve microorganisms belonging to the genera Enterococcus, Acinetobacter, Serratia, Pseudomonas, Staphylococcus, and Escherichia was evaluated by the method of diffusion into agar. The activity of synthesized "chimeric" cephalosporins against four microorganisms was found: Escherichia coli VKPM B-6695, Staphylococcus aureus VKPM B-6646, Staphylococcus aureus VKPM B‑8171, and Staphylococcus epidermidis VKPM B-12635. [ABSTRACT FROM AUTHOR]

Non-diphtheritic Corynebacteria (NDC), originally considered contaminants in clinical samples, have now emerged as nosocomial pathogens, emphasising the importance of their identification and prompt reporting. 120 non-diphtheritic corynebacteria isolated from pus were chosen for examination. A battery of tests identified isolates and minimum inhibitory concentration (MIC) was detected by broth microdilution and interpreted as per Clinical & Laboratory Standards Institute (CLSI) and British Society for Antimicrobial Chemotherapy (BSAC) guidelines. C. amycolatum 28 (31%), followed by C. striatum 18 (20.5%) was the predominant isolate. Cephalosporins were least effective followed by Gentamycin. However, all isolates were sensitive to Vancomycin and Linezolid. Our research highlights the necessity of implementing clinical antimicrobial therapy protocols for Corynebacterium spp. Empirical treatment with vancomycin or linezolid is recommended until in vitro susceptibility results become accessible. [ABSTRACT FROM AUTHOR]

Purpose Cefdinir and cephalexin are cephalosporin antibiotics commonly used in the treatment of urinary tract infections (UTIs). Their efficacy depends on achieving sufficient time with concentrations exceeding the minimum inhibitory concentration (MIC). Despite being frequently prescribed for UTIs, cefdinir has markedly lower urine penetration compared to cephalexin. It is possible that differences in pharmacokinetics could result in dissimilar efficacy between these agents; however, comparative studies of cephalosporins in UTIs are lacking. Methods This was a retrospective comparative study of patients discharged from emergency departments within a community health system with a diagnosis of acute cystitis who were prescribed cefdinir or cephalexin. Treatment failure rates at 7 and 14 days were compared between the 2 agents using a χ 2 or Fisher's exact test, as appropriate. Results There were no differences in overall treatment failure between the cefdinir and cephalexin groups. Treatment failure at 7 days occurred in 11.6% (n = 14) of patients in the cefdinir group and 8.3% (n = 10) of patients in the cephalexin group (P = 0.389). Treatment failure at 14 days was higher for cefdinir at 20.7% (n = 25) than for cephalexin at 11.8% (n = 14), but this difference was not statistically significant (P = 0.053). There were no differences in the rate of treatment failure in subgroup analyses of uncomplicated or complicated UTIs. Conclusion The results of this study suggest that cefdinir and cephalexin have comparable efficacy for the treatment of lower UTIs. While there was a numerically higher rate of treatment failure with cefdinir, there were no significant differences in treatment failure between the agents. [ABSTRACT FROM AUTHOR]

Acid dissociation constants of three cephalosporin antibiotics (cefapirin, ceftiofur, and cefotaxime) were calculated by a newly developed methodology. Plane-wave DFT calculations were performed to determine the pKa values, and by choosing the appropriate cell sizes, accurate values could be calculated. Some characteristic points were found which helped us to find correlations among the structural and physic-chemical parameters, and correlation factors were defined as well. This present study can be a base for further approaches to determining acid dissociation constants of cephalosporin molecules. [ABSTRACT FROM AUTHOR]

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

Background: Antimicrobial stewardship (AMS) programs are effective tools for improving antibiotic prescription quality. Their implementation requires the regular surveillance of antibiotic consumption at the patient and institutional level. Our study captured and analyzed antibiotic consumption density (ACD) for hospitalized pediatric patients. Method: We collected antibacterial drug consumption data for 2020 from hospital pharmacies at 113 pediatric departments of acute care hospitals in Germany. ACD was calculated as defined daily dose (DDD, WHO/ATC Index 2019) per 100 patient days (pd). In addition, we analyzed the trends in antibiotic use during 2013–2020. Results: In 2020, median ACD across all participating hospitals was 26.7 DDD/100 pd, (range: 10.1–79.2 DDD/100 pd). It was higher at university vs. non-university hospitals (38.6 vs. 25.2 DDD/100 pd, p < 0.0001). The highest use densities were seen on oncology wards and intensive care units at university hospitals (67.3 vs. 38.4 DDD/100 pd). During 2013–2020, overall ACD declined (− 10%) and cephalosporin prescriptions also decreased (− 36%). In 2020, cephalosporins nevertheless remained the most commonly dispensed class of antibiotics. Interhospital variability in cephalosporin/penicillin ratio was substantial. Antibiotics belonging to WHO AWaRe "Watch" and "Reserve" categories, including broad-spectrum penicillins (+ 31%), linezolid (+ 121%), and glycopeptides (+ 43%), increased over time. Conclusion: Significant heterogeneity in ACD and prescription of different antibiotic classes as well as high prescription rates for cephalosporins and an increased use of reserve antibiotics indicate improvable antibiotic prescribing quality. AMS programs should urgently prioritize these issues to reduce antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Inappropriate antimicrobial use is a global problem, especially because the use of antimicrobials in excess of appropriate doses is associated with increased antimicrobial resistance. Duplicate prescriptions are an issue contributing to inappropriate antimicrobial use. This study aimed to analyse antibiotic prescriptions during a specific month to examine the frequency of outpatients receiving duplicate antibiotic prescriptions and the associated determinants. Utilizing the Japan Medical Data Centre health insurance claim database, we retrospectively identified 527,110 insured individuals with at least one medicine prescription in October 2014. Data regarding age, gender, antibiotic drug usage, and health insurance status were extracted. Duplicate prescriptions entailed a patient receiving two or more prescriptions of systemic antibiotics from multiple facilities within one month. The risk factors for duplicate antibiotic prescriptions were evaluated using logistic regression analysis. Of the total sample, 131,709 individuals (25.0%) received antibiotics, and 24,529 of these individuals (18.6%) had duplicate prescriptions. Third-generation cephalosporins accounted for the largest proportion of prescriptions (37.4%). Duplicate prescriptions were significantly associated with sex, age, medical facilities, and health insurance status. These findings could help to identify patients at risk of duplicate antibiotic prescriptions, highlighting the need to promote proper antimicrobial use in both patients and medical professionals. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of chitosan encapsulated copper oxide nanocomposites (CuNPs) using plant extracts for the photocatalytic degradation of second-generation antibiotics, cefixime and cefuroxime, were investigated. The study revealed that the presence of diverse chemical components in the plant extract significantly influenced the size of the CuNPs, with transmission electron microscopy (TEM) showing spherical shapes and sizes ranging from 11–35 nm. The encapsulation process was confirmed by an increase in size for certain samples, indicating successful encapsulation. X-ray photoelectron spectroscopy (XPS) analysis further elucidated the chemical makeup, confirming the valency state of Cu2+ and the presence of Cu–O bonding, with no contaminants detected. Photocatalytic activity assessments demonstrated that the copper oxide nanocomposites exhibited significant degradation capabilities against both antibiotics under UV light irradiation, with encapsulated nanocomposites (EnCu30) showing up to 96.18% degradation of cefuroxime within 60 min. The study highlighted the influence of chitosan encapsulation on enhancing photocatalytic performance, attributed to its high adsorption capability. Recycling studies confirmed the sustainability of the Cu nanocomposites, maintaining over 89% degradation rate after five consecutive cycles. This research underscores the potential of green-synthesized CuNPs as efficient, stable photocatalysts for the degradation of harmful antibiotics, contributing to environmental sustainability and public health protection. [ABSTRACT FROM AUTHOR]

Objective: Infection is one of the common complications of post-prostate biopsy. Therefore, prophylaxis with fluoroquinolones and/or cephalosporins is recommended. We aimed to evaluate the prevalence of antibiotic-resistant bacteria isolated from rectal swabs in candidates for transrectal ultrasound-guided (TRUS) biopsy. The possible patient's related risk factors attributing to resistance to antibiotics were also assessed. Methods: This cross-sectional study was performed on 126 male patients who were candidates for TRUS biopsy. Rectal swabs were collected and the samples were transferred to the laboratory in Amies transport medium during 2 hours and cultured on MacConkey agar with ciprofloxacin 1 mg/L and ciprofloxacin-resistant strains were identified. Kirby-Bauer disc diffusion method was used to determine the antibiotic susceptibility of the isolates. Results: In total, 59 bacterial isolates were obtained, which were Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, respectively, in terms of frequency. They showed the lowest resistance to levofloxacin. Smoking was associated with positive culture results. Age was a factor with a significant effect on carrying ciprofloxacin-resistant strains. Conclusion: Ciprofloxacin resistance was high in almost all strains, but post-biopsy infectious complications were very low. Level of evidence: Not applicable [ABSTRACT FROM AUTHOR]

Importance: Staphylococcus aureus and Escherichia coli contribute to global health challenges by forming biofilms, a key virulence element implicated in the pathogenesis of several infections. Objective: The study examined the efficacy of various generations of cephalosporins against biofilms developed by pathogenic S. aureus and E. coli. Methods: The development of biofilms by both bacteria was assessed using petri-plate and microplate methods. Biofilm hydrolysis and inhibition were tested using first to fourth generations of cephalosporins, and the effects were analyzed by crystal violet staining and phase contrast microscopy. Results: Both bacterial strains exhibited well-developed biofilms in petri-plate and microplate assays. Cefradine (first generation) showed 76.78% hydrolysis of S. aureus biofilm, while significant hydrolysis (59.86%) of E. coli biofilm was observed by cefipime (fourth generation). Similarly, cefuroxime, cefadroxil, cefepime, and cefradine caused 78.8%, 71.63%, 70.63%, and 70.51% inhibition of the S. aureus biofilms, respectively. In the case of E. coli, maximum biofilm inhibition (66.47%) was again shown by cefepime. All generations of cephalosporins were more effective against S. aureus than E. coli, which was confirmed by phase contrast microscopy. Conclusions and Relevance: Cephalosporins exhibit dual capabilities of hydrolyzing and inhibiting S. aureus and E. coli biofilms. First-generation cephalosporins exhibited the highest inhibitory activity against S. aureus, while the third and fourth generations significantly inhibited E. coli biofilms. This study highlights the importance of tailored antibiotic strategies based on the biofilm characteristics of specific bacterial strains. [ABSTRACT FROM AUTHOR]

Background: b -Lactam antibiotics are widely used with increased utilization in hospitalized patients. Of this population, as high as 10–20% report an allergy to b -lactam antibiotics but <5% are at risk of developing clinically significant immunoglobulin E– or T-lymphocyte–mediated reactions. Most of the time, these reported allergies are present during an illness with no previous inquiry of their validity, which makes investigation and possible removal of this allergy label a challenge. Methods: We report a 16-year-old boy who presented with 1 week of night sweats, chills, headaches, and fatigue, followed by 1 day of fever and right knee swelling and who was diagnosed with septic bursitis. Due to concern of a penicillin allergy label, the patient was started on a cefepime infusion. Five minutes into the infusion, the patient reported puffy eyes and itchy throat, followed by a witnessed cascading flat nonpruritic erythematous rash from head to shoulders. This rash went away in 3 minutes after stopping the infusion and the patient being given 50 mg of intravenous diphenhydramine and 10 mg of oral dexamethasone. He was subsequently diagnosed with a cefepime allergy. Results: Allergy/immunology was the speciality consulted, and, by using a screening questionnaire, the patient’s reported penicillin allergy was determined to be low risk. Subsequent 1-step oral challenge was the key to providing the patient with the necessary antibiotic course to resolve his infection. Conclusion: Multiple reported antibiotic allergies lead to poor antibiotic stewardship that causes impactful health and financial burden on the patient and health-care system. It is thus important to have an evidence-based systematic approach to de-label penicillin antibiotic allergy labels to reduce these potential harms. [ABSTRACT FROM AUTHOR]

In an era of increasing antibiotic resistance among pathogens, the treatment options for infectious diseases are diminishing. One of the clinical groups especially vulnerable to this threat are patients who are hospitalized in intensive care units due to ventilator-associated pneumonia caused by multidrug-resistant/extensively drug-resistant Gram-negative bacteria. In order to prevent the exhaustion of therapeutic options for this life-threatening condition, there is an urgent need for new pharmaceuticals. Novel β-lactam antibiotics, including combinations of cephalosporins with β-lactamase inhibitors, are proposed as a solution to this escalating problem. The unique mechanism of action, distinctive to this new group of siderophore cephalosporins, can overcome multidrug resistance, which is raising high expectations. In this review, we present the summarized results of clinical trials, in vitro studies, and case studies on the therapeutic efficacy of cefoperazone-sulbactam, ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol in the treatment of ventilator-associated pneumonia. We demonstrate that treatment strategies based on siderophore cephalosporins and combinations of β-lactams with β-lactamases inhibitors show comparable or higher clinical efficacy than those used with classic pharmaceuticals, like carbapenems, colistin, or tigecycline, and are often associated with a lower risk of adverse events. [ABSTRACT FROM AUTHOR]

The aim of the study was two-fold: first, to collect data on the use of antibiotics in Germany for dogs and cats and, second, their owners' experiences and opinions. Using an anonymous online survey, dog and cat owners were asked about the last antibiotic administration in their pet. The inclusion criterion was any antibiotic administration within the last year. A total of 708 questionnaires from 463 dogs and 245 cats could be evaluated. Diarrhea was reported as the most common reason for antibiotic administration in dogs (18.4%). Wound infection/abscess/bite injury was the second most common reason in dogs (16.0%). In cats wound infection/abscess/bite injury was the most common reason (23.3%), followed by dental treatment (21.2%) and upper respiratory tract infections (16.7%). The most common antibiotics used systemically in both species were amoxicillin/clavulanic acid (32.5%), amoxicillin (14.8%), metronidazole (6.9%), and doxycycline (6.8%). While efficacy (99.9%) and tolerability (94.8%) were rated as most important for the choice of antibiotics, costs (51.6%) were cited as predominantly unimportant. First-line antibiotics were used significantly more often than critically important antibiotics. The majority of animal owners show awareness for avoidance of antibiotic resistance and the use of critically important antibiotics. [ABSTRACT FROM AUTHOR]

Simple Summary: The inappropriate use of antibiotics has favored the adaptation of bacteria resistant to these drugs and is a growing problem in the 21st century. It may affect not only the health of humans but also domestic and wild animals. In this study, we investigated the risk factors and the presence of one type of antibacterial resistance present in the feces of domestic animals and free-living birds in the State of Piauí, Brazil. A total of 59 samples of the 387 (15.2%) analyzed showed bacterial resistance. Resistant bacteria were found in free-living animals that had never been treated with any medication and in domestic animals raised for subsistence. We hypothesize that the lack of access to veterinary care and information regarding antimicrobial therapy, along with access to antimicrobials without medical prescription, favors the inadequate use of antimicrobials in Piauí and, thus, contamination of the environment. We recommend an educational outreach platform and the development of public health policies that support the responsible use of antimicrobials in Piauí and other Brazilian states. The use, misuse, and overuse of antimicrobials is one of the main public health threats of the 21st century. We investigated the risk factor of the presence of extended-spectrum, cephalosporin-resistant Enterobacterales in feces of non-domestic and domestic birds and other domestic animals in Piauí State, northeast Brazil. We collected a total of 387 cloacal and rectal swab samples of free-living birds, domestic birds, and domestic mammals in five municipalities: Amarante, Água Branca, Lagoa Alegre, Parnaíba, and Teresina. A total of 59/387 (15.2%) of these samples harbored extended spectrum beta-lactamase (ESBL)-producing Enterobacterales. Using the MALDI-TOF technique, we identified fifty-seven samples as Escherichia coli and two samples as Klebsiella pneumoniae. Teresina and Parnaíba had the highest prevalence of animals with resistant bacteria (32.1% and 27.1%, respectively) and highest exposure risk factor (OR of 16.06 and 8.58, respectively, and p < 0.001 for all). Multidrug-resistant, ESBL-producing Enterobacterales were observed in 72.8% of the samples (43/59). For the free-living birds, the positive samples belonged to a great kiskadee (Pitangus sulphuratus) and a semipalmated sandpiper (Calidris pusilla) in migratory and resident species, respectively. For domestic animals, the swine samples showed the highest prevalence of antimicrobial resistance. The lack of access to veterinary care and information regarding antimicrobial therapy, along with the easy access to antimicrobials without medical prescription, favors the inadequate use of antimicrobials in Piauí. [ABSTRACT FROM AUTHOR]

Background: The emergence and spread of β-lactamase-producing Klebsiella spp. has been associated with a substantial healthcare burden resulting in therapeutic failures. We sought to describe the proportion of phenotypic resistance to commonly used antibiotics, characterize β-lactamase genes among isolates with antimicrobial resistance (AMR), and assess the correlates of phenotypic AMR in Klebsiella spp. isolated from stool or rectal swab samples collected from children being discharged from hospital. Methods: We conducted a cross-sectional study involving 245 children aged 1–59 months who were being discharged from hospitals in western Kenya between June 2016 and November 2019. Whole stool or rectal swab samples were collected and Klebsiella spp. isolated by standard microbiological culture. β-lactamase genes were detected by PCR whilst phenotypic antimicrobial susceptibility was determined using the disc diffusion technique following standard microbiology protocols. Descriptive analyses were used to characterize phenotypic AMR and carriage of β-lactamase-producing genes. The modified Poisson regression models were used to assess correlates of phenotypic beta-lactam resistance. Results: The prevalence of β-lactamase carriage among Klebsiella spp. isolates at hospital discharge was 62.9% (154/245). Antibiotic use during hospitalization (adjusted prevalence ratio [aPR] = 4.51; 95%CI: 1.79–11.4, p < 0.001), longer duration of hospitalization (aPR = 1.42; 95%CI: 1.14–1.77, p < 0.002), and access to treated water (aPR = 1.38; 95%CI: 1.12–1.71, p < 0.003), were significant predictors of phenotypically determined β-lactamase. All the 154 β-lactamase-producing Klebsiella spp. isolates had at least one genetic marker of β-lactam/third-generation cephalosporin resistance. The most prevalent genes were blaCTX-M 142/154 (92.2%,) and blaSHV 142/154 (92.2%,) followed by blaTEM 88/154 (57.1%,) and blaOXA 48/154 (31.2%,) respectively. Conclusion: Carriage of β-lactamase producing Klebsiella spp. in stool is common among children discharged from hospital in western Kenya and is associated with longer duration of hospitalization, antibiotic use, and access to treated water. The findings emphasize the need for continued monitoring of antimicrobial susceptibility patterns to inform the development and implementation of appropriate treatment guidelines. In addition, we recommend measures beyond antimicrobial stewardship and infection control within hospitals, improved sanitation, and access to safe drinking water to mitigate the spread of β-lactamase-producing Klebsiella pathogens in these and similar settings. [ABSTRACT FROM AUTHOR]

Food contamination with plasmid-mediated antibiotic-resistant Escherichia coli has not been thoroughly investigated. This study aimed to clarify the prevalence of colistin-resistant AmpC/extended-spectrum β-lactamase (ESBL)-producing E. coli harbouring mcr (COL-ESBL-EC) and to determine antibiotic resistance by comparison with AmpC/ESBL-producing E. coli (ESBL-EC) and colistin-resistant E. coli harbouring mcr (COL-EC). Sixty chicken meats were tested for COL-ESBL-EC contamination. The result showed that 64 COL-ESBL-EC were isolated from 66.7% of the samples, and compared with ESBL-EC and COL-EC were isolated before. The genotypes of the COL-ESBL-EC showed blaCTX-M-55/TEM, blaCTX-M-55, blaCMY-2, and blaCTX-M-65 were predominant. The COL-ESBL-EC results showed a similar trend for blaCTX-M identification to that of ESBL-EC. The mcr was investigated, and mcr-1 was detected in COL-ESBL-EC and COL-EC. Antibiotic susceptibility testing revealed that many strains of COL-ESBL-EC and ESBL-EC were resistant to quinolones, and fosfomycin (FOS). These results suggest that COL-ESBL-EC has simultaneously acquired AmpC/ESBL-related, quinolone, and FOS resistance genes in COL-EC. [ABSTRACT FROM AUTHOR]

Objectives An Escherichia coli isolate, WGS1363, showed resistance to piperacillin/tazobactam but susceptibility to cephalosporins and contained a previously unrecognized β-lactamase, CTX-M-255, as the only acquired β-lactamase. CTX-M-255 was identical to CTX-M-27 except for a G239S substitution. Here, we characterize the hydrolytic spectrum of CTX-M-255 and a previously reported β-lactamase, CTX-M-178, also containing a G239S substitution and compare it to their respective parental enzymes, CTX-M-27 and CTX-M-15. Methods All β-lactamase genes were expressed in E. coli TOP10 and MICs to representative β-lactam-antibiotics were determined. Furthermore, bla CTX-M-15,   bla CTX-M-27, bla CTX-M-178 and bla CTX-M-255 with C-terminal His-tag fusions were affinity purified for enzyme kinetic assays determining Michaelis–Menten kinetic parameters against representative β-lactam-antibiotics and IC50s of clavulanate, sulbactam, tazobactam and avibactam. Results TOP10-transformants expressing bla CTX-M-178 and bla CTX-M-255 showed resistance to penicillin/β-lactamase combinations and susceptibility to cephalothin and cefotaxime in contrast to transformants expressing bla CTX-M-15 and bla CTX-M-27. Determination of enzyme kinetic parameters showed that CTX-M-178 and CTX-M-255 both lacked hydrolytic activity against cephalosporins and showed impaired hydrolytic efficiency against penicillin antibiotics compared to their parental enzymes. Both enzymes appeared more active against piperacillin compared to benzylpenicillin and ampicillin. Compared to their parental enzymes, IC50s of β-lactamase-inhibitors were increased more than 1000-fold for CTX-M-178 and CTX-M-255. Conclusions CTX-M-178 and CTX-M-255, both containing a G239S substitution, conferred resistance to piperacillin/tazobactam and may be characterized as inhibitor-resistant CTX-M β-lactamases. Inhibitor resistance was accompanied by loss of activity against cephalosporins and monobactams. These findings add to the necessary knowledge base for predicting antibiotic susceptibility from genotypic data. [ABSTRACT FROM AUTHOR]

Cefaclor is a bactericidal antibiotic recommended for treating diverse types of infections. This review aims to comprehensively assess the pharmacokinetic (PK) data on cefaclor in humans. Google Scholar, PubMed, Cochrane Library, and EBSCO databases were systematically performed to identify all the relevant studies containing at least one reported PK parameter of cefaclor. Cefaclor shows the linear PK profile as the area under the plasma concentration-time curve from 0 to t (AUC0-t) and maximum plasma concentration (Cmax) increase in a dose-dependent manner. The AUC0-t of cefaclor in the rice diet was found to be higher than that of bread food, i.e. 19.9 ± 2.6 ug/ml.hr vs 15.4 ± 4 ug/ml.hr. The AUC in paediatrics during the fed state was significantly higher compared to that in adults. Patients with renal impairments showed a Cmax 2.2 times higher than that of normal subjects. A significant increase in Cmax was depicted among individuals following a vegetarian diet in comparison with the non-vegetarian diet. Moreover, cefaclor exhibits time-dependent killing above the minimum inhibitory concentration (MIC < 2 ug), favouring its use in treating infections caused by specific pathogens. This systematic review summarises all the reported PK parameters of cefaclor in healthy and diseased subjects in the literature. This data can help practitioners in adjusting cefaclor doses among different diseases and populations to avoid drug interactions and adverse effects. [ABSTRACT FROM AUTHOR]