Supramolecular solvents based on hydrophobic natural deep eutectic solvents and primary amines for preconcentration and determination of enrofloxacin in milk.

In this work, coacervation in primary amines solutions with hydrophobic natural deep eutectic solvents based on terpenoids and carboxylic acids was demonstrated for the first time. A liquid-phase microextraction approach was developed based on supramolecular solvent formation with primary amine acting as amphiphile and hydrophobic deep eutectic solvent making up mixed vesicles and serving as coacervation agent. Such supramolecular solvents could be used to separate wide range of substances from different aqueous media, such as food products, biological liquids and wastewaters. It is important that both hydrophobic and ionic interactions with supramolecular aggregates take place ensuring synergetic effect and better extraction ability, which is significant in separating relatively polar analytes. Different primary amines and deep eutectic solvents were investigated for liquid-phase microextraction of proof-of-concept amphoteric analyte (enrofloxacin, widely used veterinary fluoroquinolone antibiotic) and its determination by high-performance liquid chromatography with fluorescence detection using Shimadzu LC-20 Prominence chromatograph and RF-20A fluorescence detector. It was found that the supramolecular solvent based on 1-nonylamine, formed after addition of a deep eutectic solvent based on menthol and hexanoic acid (molar ratio of 1:1), provided maximum extraction recovery (85 %) and maximum enrichment factor (34). To characterize the extraction system, the composition of the phases was investigated, and cryo-transmission electron microscopy images were obtained. Vesicular aggregates were observed in the supramolecular solvent. The extraction mechanism was proposed in terms of formation of mixed aggregates to capture the analyte. Limit of detection was found to be 7 µg kg-1, while linear range of 20-250 µg kg-1 was established. Relative standard deviation values were lower than 7 %. Relative bias did not exceed 12 %.

Removal of fluoroquinolone antibiotic and sulfonated dye by functionalized Persea americana seed powder: Appraisal on phase transfer kinetics, equilibrium, economics, and applications in rural settings.

The study focuses on reactive orange 16 (RO16), a sulfonated dye, and ciprofloxacin (CiP), a fluoroquinolone antibiotic treatment from aquatic surface by adsorption. The functionalized Persea americana seed powder (PASP) was developed by acid hydrolysis technique and investigated for RO16 and CiP removal in batch scale at different concentrations for CiP and RO16, pH (2-8), contact duration and temperature (303-318K). Utilizing a scanning electron microscope (SEM) with energy dispersive X-ray spectroscopy (EDAX), the generated native PASP were assessed for their morphological characteristics. Fourier transform infrared (FTIR) spectroscopy was applied to examine the performing characteristics of PASP. Experimental findings with four kinetic mathematical models allowed the estimation of the process involved in the biosorption. The most effective agreement was explained by the pseudo-second-order model and Sips isotherm (Cip = 34.603 mg/g and RO16 = 30.357 mg/g) at 303K temperature. For Cip Process economics of the biosorbent was done, and it was observed that it was less than the readily market-available activated carbon.

Single and mixture exposure to atrazine and ciprofloxacin on Clarias gariepinus antioxidant defense status, hepatic condition and immune response.

Atrazine (ATRA) and ciprofloxacin (CPRO) are widely detected, persistent and co-existing aquatic pollutants. This study investigated effects of 14-day single and joint ATRA and CPRO exposure on juvenile Clarias gariepinus. Standard bioassay methods were used to determine responses of oxidative stress, hepatic condition, and immunological biomarkers on days 7 and 14. Seven groups were used: Control, CPROEC, CPROSubl, ATRAEC, ATRASubl, CPROEC+ATRAEC, and CPROSubl+ATRASubl. The test substances caused decreased activity of superoxide dismutase, catalase, and glutathione peroxidase. Lipid peroxidation was elevated, especially in CPRO-ATRA mixtures. Serum aminotransferases (ALT, and AST), and alkaline phosphatase activity increased significantly. Total protein, albumin, total immunoglobulin, and respiratory burst decreased significantly. Therefore, single and joint exposure to CPRO and ATRA poses adverse consequences on aquatic life.

Computational simulation-assisted template selection of magnetic MOFs molecularly imprinted materials applying the adsorption and detection of multiple fluoroquinolones.

This study utilized computational simulation and surface molecular imprinting technology to develop a magnetic metal-organic framework molecularly imprinted polymer (Fe3O4@ZIF-8@SMIP) capable of selectively recognizing and detecting multiple fluoroquinolones (FQs). The Fe3O4@ZIF-8@SMIP material was synthesized using the "common" template-ofloxacin, identified by computational simulation, demonstrating notable adsorption capacity (88.61-212.93 mg g-1) and rapid mass-transfer features (equilibration time: 2-3 min) for all tested FQs, consistent with Langmuir adsorption model. Subsequently, this material was employed as a magnetic solid-phase-extraction adsorbent for adsorption and detection of multiple FQs by combining with high performance liquid chromatography. The developed method exhibited good linearity for various FQs within the concentration range of 0.1-500 µg L-1, with low limit of detection (0.0605-0.1529 µg L-1) and limit of quantitation (0.2017-0.5097 µg L-1). Satisfactory recoveries (88.38-103.44%) were obtained when applied to spiked food samples, demonstrating the substantial potential of this Fe3O4@ZIF-8@SMIP material for rapid enrichment and identification for multiple FQs residues.

LACCASE MEDIATED TRANSFORMATION OF FLUOROQUINOLONE ANTIBIOTICS: ANALYZING DEGRADATION PATHWAYS AND ASSESSING ALGAL TOXICITY.

Improper waste disposal or inadequate wastewater treatment can result in pharmaceuticals reaching water bodies, posing environmental hazards. In this study, crude extracts containing the laccase enzyme from Pleurotus florida, Pleurotus eryngii, and Pleurotus sajor caju were used to degrade the fluoroquinolone antibiotics (FQs) levofloxacin (LEV), norfloxacin (NOR), ciprofloxacin (CIP), ofloxacin (OFL), and enrofloxacin (ENR) in aqueous solutions. The results for the fungi derived laccase extracts were compared with those obtained using commercially sourced laccase. Proteomics analysis of the crude extracts confirmed the presence of laccase enzyme across all three tested species, with proteins matching those found in Trametes versicolor and Pleurotus ostreatus. In vivo studies were conducted using species pure lines of fungal whole cells. The highest degradation efficiency observed was 77.7% for LEV in the presence of P. sajor caju after 25 days of treatment. Degradation efficiencies ranged from approximately 60-72% for P. florida, 45-76% for P. eryngii, and 47-78% for P. sajor caju. A series of in vitro experiments were also conducted using crude extracts from the three species and outcomes compared with those obtained when commercial laccase was used confirmed laccase as the enzyme responsible for antibiotic removal. The degradation efficiencies in vitro surpassed those measured in vivo, ranging from approximately 91-98% for commercial laccase, 77-92% for P. florida, 76-92% for P. eryngii, and 78-88% for P. sajor caju. Liquid chromatography-high-resolution mass spectrometry (LC-MS/MS) identified the degradation products, indicating a consistent enzymatic degradation pathway targeting the piperazine moiety common to all tested FQs, irrespective of the initial antibiotic structure. Phytoplankton toxicity studies with Dunaliella tertiolecta were performed to aid in understanding the impact of emerging contaminants on ecosystems, and by-products were analysed for ecotoxicity to assess treatment efficacy. Laccase-mediated enzymatic oxidation shows promising results in reducing algal toxicity, notably with Pleurotus eryngii extract achieving a 97.7% decrease for CIP and a 90% decrease for LEV. These findings suggest the potential of these naturally sourced extracts in mitigating antibiotic contamination in aquatic ecosystems.

Fluoroquinolone resistance and clinical characteristics of acute bacterial prostatitis in Japan: A multicenter study by the Japanese Research Group for Urinary Tract Infection.

OBJECTIVE: This multicenter study aimed to analyze the risk factors for fluoroquinolone (FQ) resistance and to clarify the clinical characteristics of acute bacterial prostatitis (ABP) in Japan. METHODS: A total of 124 patients clinically diagnosed with ABP at 13 medical institutions participating in the Japanese Research Group for Urinary Tract Infection between January and December 2017 were retrospectively reviewed. RESULTS: Of the 124 patients included in this study, 37 were outpatients, and 87 were inpatients. The main underlying medical conditions before the onset of ABP were severe dysuria, urinary retention, transurethral manipulation, indwelling urinary catheter, and transrectal prostate biopsy (TRBx). The main symptoms were fever (≥ 37.5°C), prostate tenderness, dysuria, micturition pain, urinary retention, and macrohematuria. Bacteremia was observed in 14 patients. Prostatic abscess was observed in three patients. Escherichia coli was the predominant organism, accounting for 48% (51/106). FQ-resistant E. coli was detected in 33% (17/51), and extended-spectrum beta-lactamases-producing E. coli in 12% (6/51). TRBx (odds ratio [OR] = 48.60, 95% confidence interval [CI]: 5.49-430.00, p < 0.001) and inpatient status (OR = 29.00, 95% CI: 1.95-430.00, p = 0.014) were risk factors for the detection of FQ-resistant bacteria. CONCLUSIONS: The detection rate of FQ-resistant bacteria was significantly higher with TRBx ABP and inpatient status. These findings have important implications for the management of ABP and antimicrobial treatment, especially for TRBx ABP, which should be considered a separate category.

Emerging pathogens Aerococcus urinae and Aerococcus sanguinicola from a Canadian tertiary care hospital.

Background: Aerococcus urinae and Aerococcus sanguinicola are emerging pathogens linked with urinary tract infections. We present a case series of A. urinae and A. sanguinicola isolates characterizing the spectrum of clinical presentation, microbiological characteristics and antimicrobial sensitivities. Methods: Retrospective chart review was performed on patients who grew positive cultures for A. urinae and A. sanguinicola identified on MALDI-TOF in Saskatchewan from January to June 2023. Demographic and clinical variables, antimicrobial susceptibility and prescription were documented. Results: This cohort (n = 115) had a median age 82 years. A. urinae and A. sanguinicola infections spanned from urinary tract infection (n = 96) to urosepsis (n = 6). These infections were predominantly monomicrobial (73.9%) and were susceptible to ceftriaxone, penicillin G and vancomycin. Antimicrobials were seldom prescribed within the urinary tract infection cohort (31.2%). Conclusion: Untreated A. urinae and A. sanguinicola infections can precipitate into urosepsis. The reported antimicrobial susceptibility for these Aerococcus isolates should be utilized to provide appropriate antimicrobial coverage.

Aerococcus urinae and Aerococcus sanguinicola are bacteria that can cause urine infections. They are often overlooked and thought to be unable to cause serious blood infections, such as sepsis. We collected data on 87 cases of A. urinae and 28 cases of A. sanguinicola to show that these bacteria can cause urine and blood infections in elderly patients. We also looked at other studies and summarized that patients with serious blood infections from these bacteria often had a previous urine infection from these same bacteria. These bacteria can be resistant to a common antibiotic used to treat urine infections. It is important to test and report if these bacteria are resistant to this common antibiotic and doctors must be aware that they can cause serious blood infections if not treated with the correct antibiotics.

Antimicrobial susceptibility and virulence gene analysis of Shigella species causing dysentery in Iranian children: Implications for fluroquinolone resistance.

Shigella species significantly impact global health due to their role in diarrheal diseases. A 2019-2022 cross-sectional study on 432 stool samples from pediatric patients in Mashhad, Iran, identified Shigella spp. and tested their susceptibility to 12 antimicrobials by the disk diffusion method. The presence of virulence factors, namely ipaH, virA, stx1, and stx2, as well as plasmid-mediated quinolone resistance (PMQR) genes, including qnrA, qnrB, qnrC, qnrD, and qnrS, were ascertained through the utilization of polymerase chain reaction techniques. Sequencing of 15 isolates detected mutations within quinolone resistance-determining regions (QRDRs) at the gyrA and parC genes, indicating fluoroquinolone (FQ) resistance. 19.2 % (83/432) of stool samples contained Shigella, primarily S. sonnei (77.1 %), followed by S. flexneri (21.6 %) and S. boydii (1.2 %). Most isolates were from children under five (55.4 %). All strains had the ipaH gene, lacked stx1 and stx2, and 86.7 % had virA. High resistance was noted for ampicillin and tetracycline (84.3 % each), trimethoprim-sulfamethoxazole (81.9 %), and azithromycin (60.2 %). 87.1 % of isolates were multidrug-resistant (MDR). The most common PMQR genes were qnrA and qnrS (41 % each). The qnrD gene, prevalent in 36.1 % of cases, is reported in Iran for the first time. The most common PMQR profile was qnrADS (15.7 %). Resistance to nalidixic acid and ciprofloxacin was 45.8 % and 12 %, respectively. The Shigella isolates exhibited mutations in the gyrA (at codons 83, 87, and 211) and parC (at codons 80, 84, 93, 126, 128, 129, and 132) genes. The D87Y mutation in the gyrA gene was the most common in Shigella isolates, occurring in 73 % of cases. The F93S and L132T mutations in the parC gene were unique to this study. Empirical FQ therapy in patients infected with MDR Shigella, possessing PMQR determinants and/or mutations in the QRDRs of gyrA and parC, may escalate the risks of secondary diseases, extended treatment duration, therapeutic failure, and resistance spread. Consequently, the necessity for continuous surveillance and genetic testing to detect FQ-resistant Shigella strains is of paramount importance.

Role of parC Mutations at Position 84 on High-Level Delafloxacin Resistance in Methicillin-Resistant Staphylococcus aureus.

High-level delafloxacin-resistant (H-L DLX-R) Staphylococcus aureus isolates (minimum inhibitory concentration ≥1 mg/L) associated with mutations affecting position 84 of ParC have emerged. We aimed to elucidate the role of these mutations as a mechanism of H-L DLX resistance in methicillin-resistant S. aureus (MRSA) isolates recovered from blood cultures. Susceptibility to DLX was determined in 75 MRSA isolates by E-test, and an rt-PCR was developed to detect mutations affecting position 84 of ParC to screen a further 185 MRSA isolates. The genomes of 48 isolates, including all DLX-R isolates or with alterations at position 84, and also a subset of DLX-susceptible isolates were analyzed. Among the 75 isolates studied, 77.34% were DLX-susceptible and only 4 H-L DLX-R isolates were found. Seven (3.8%) isolates with alterations at position 84 of ParC were detected by rt-PCR. Genomic analysis showed that 89.9% (8/9) of isolates with the substitution E84K/G in ParC, together with other mutations in gyrA and parC, were H-L DLX-R. However, the E84K substitution in ParC alone or with other alterations was found in two isolates without H-L DLX-R. Alterations at position 84 of ParC are rare but play a key role in H-L DLX resistance in MRSA but only when other alterations in GyrA are present.

Traces of pandemic fluoroquinolone-resistant Escherichia coli clone ST131 transmitted from human society to aquatic environments and wildlife in Japan.

Transmission of antimicrobial-resistant bacteria among humans, animals, and the environment is a growing concern worldwide. The distribution of an international high-risk fluoroquinolone-resistant Escherichia coli clone, ST131, has been documented in clinical settings. However, the transmission of ST131 from humans to surrounding environments remains poorly elucidated. To comprehend the current situation and identify the source of ST131 in nature, we analyzed the genetic features of ST131 isolates from the aquatic environment (lake/river water) and wildlife (fox, raccoon, raccoon dog, and deer) and compared them with the features of isolates from humans in Japan using accessory and core genome single nucleotide polymorphism (SNP) analyses. We identified ST131 isolates belonging to the same phylotype and genome clusters (four of eight clusters were concomitant) with low SNP distance between the human isolates and those from the aquatic environment and wildlife. These findings warn of ST131 transmission between humans and the surrounding environment in Japan.

Metal-free Carbon Material Derived from Lantana Camara for the Detection and Removal of Ciprofloxacin.

This work reports the preparation of a metal-free nitrogen and sulphur functionalized graphitic carbon sheets from a unique and less expensive precursor Lantana camara, which is a common hazardous weed in India. The synthesized material NS-CN-180 was successfully tested for the adsorption and removal of fluoroquinolone antibiotics ciprofloxacin. The surface morphology and elemental composition of NS-CN-180 were investigated through FESEM and XPS analyses. The SEM data reveals the graphitic sheets stacked onto each other with cavities in between them. The presence of various functional groups was identified through FT-IR spectroscopy and the degree of graphitization was calculated from XRD pattern. The probable mechanism of interaction for ciprofloxacin molecule with NS-CN-180 was also investigated with the help of FT-IR and zeta potential analyses. The fabricated material was found to be excellent for ciprofloxacin detection with a limit of detection value 16.08 nM. Also, the prepared material efficiently removes the 66.2% ciprofloxacin drug in 1 h. Adsorption and desorption experiments were performed to demonstrate the reusability of the material.

Wearable, Biocompatible, and Dual-Emission Ocular Multisensor Patch for Continuous Profiling of Fluoroquinolone Antibiotics in Tears.

The abuse or misuse of antibiotics in clinical and agricultural settings severely endangers human health and ecosystems, which has raised profound concerns for public health worldwide. Trace detection and reliable discrimination of commonly used fluoroquinolone (FQ) antibiotics and their analogues have consequently become urgent to guide the rational use of antibiotic medicines and deliver efficient treatments for associated diseases. Herein, we report a wearable eye patch integrated with a quadruplex nanosensor chip for noninvasive detection and discrimination of primary FQ antibiotics in tears during routine eyedrop treatment. A set of dual-mode fluorescent nanoprobes of red- or green-emitting CdTe quantum dots integrated with lanthanide ions and a sensitizer, adenosine monophosphate, were constructed to provide an enhanced fluorescence up to 45-fold and nanomolar sensitivity toward major FQs owing to the aggregation-regulated antenna effect. The aggregation-driven, CdTe-Ln(III)-based microfluidic sensor chip is highly specific to FQ antibiotics against other non-FQ counterparts or biomolecular interfering species and is able to accurately discriminate nine types of FQ or non-FQ eyedrop suspensions using linear discriminant analysis. The prototyped wearable sensing detector has proven to be biocompatible and nontoxic to human tissues, which integrates the entire optical imaging modules into a miniaturized, smartphone-based platform for field use and reduces the overall assay time to ∼5 min. The practicability of the wearable eye patch was demonstrated through accurate quantification of antibiotics in a bactericidal event and the continuous profiling of FQ residues in tears after using a typical prescription antibiotic eyedrop. This technology provides a useful supplement to the toolbox for on-site and real-time examination and regulation of inappropriate daily drug use that might potentially lead to long-term antibiotic abuse and has great implications in advancing personal healthcare techniques for the regulation of daily medication therapy.

Insights into the Versatility of Using Atomic Absorption Spectrometry in Antibacterial Research.

The ongoing development of bacterial resistance to antibiotics is a global challenge. Research in that field is thus necessary. Analytical techniques are required for such a purpose. From this perspective, the focus was on atomic absorption spectrometry (AAS). Although it is old, AAS often offers unexpected potential. Of course, this should be exploited. The aim was therefore to demonstrate the versatility of the technique in antibacterial research. This is illustrated by various examples of its practical application. AAS can be used, for example, to confirm the identity of antibacterial compounds, for purity controls, or to quantify the antibiotics in pharmaceutical preparations. The latter allowed analysis without laborious sample preparation and without interference from other excipients. In addition, AAS can help elucidate the mode of action or resistance mechanisms. In this context, quantifying the accumulation of the antibiotic drug in the cell of (resistant) bacteria appears to play an important role. The general application of AAS is not limited to metal-containing drugs, but also enables the determination of some organic chemical antibiotics. Altogether, this perspective presents a range of applications for AAS in antibacterial research, intending to raise awareness of the method and may thus contribute to the fight against resistance.

Tb3+ assisted dithioerythritol stabilized copper nanocluster with AIE behavior for ratiometric fluorescent determination of fluoroquinolones.

BACKGROUND: Fluoroquinolones (FQs) are widely used in livestock and poultry industry because of their satisfactory effects in preventing and treating bacterial infection. However, due to irrational use and poor biodegradability, FQs can easily remain in food animals and further enter the human body through the food chain. Therefore, accurate and sensitive detection of FQs residues in animal-origin food is significant. The traditional methods commonly used for FQs detection have some limitations. Ratiometric fluorescence detection technology has the advantages of fast, sensitive, self-correcting, and easy visualization. However, the reports on the use of ratiometric fluorescence probes for FQs detection are limited. RESULTS: In this work, a novel probe was proposed for ratiometric fluorescent analysis of FQs. In this probe, the fluorescence of dithioerythritol stabilized copper nanoclusters (DTE-Cu NCs) was significantly enhanced due to the Tb3+ triggered aggregation-induced emission effect. FQs bound Tb3+ in Tb3+/DTE-Cu NCs through carboxyl and carbonyl groups, so that Tb3+ was effectively sensitized to emit green fluorescence. However, the red fluorescence of DTE-Cu NCs was not interfered. The fluorescence of the probe transformed from red to green with the increase of FQs concentration. Using norfloxacin (NOR), difloxacin (DIF), and enrofloxacin (ENR) as FQs simulants, this probe showed a sensitive linear response ranged from 0.025 to 22.5 µM, with the limits of detection of 9.6 nM, 9.3 nM, and 7.7 nM. The application potential for FQs detection was verified via a standard addition assay of egg samples with the recovery rate of 90.4 %-114.7 %. SIGNIFICANT: The fluorescence probe based on Tb3+/DTE-Cu NCs is expected to realize the ratiometric fluorescence sensitive detection of FQs. The establishment of this simple, effective, and rapid detection platform opens up a new way for the detection of FQs residues in animal-origin foods, and also provides a new idea for the design of rapid detection platforms for other hazard factors.

Drug metabolism of ciprofloxacin, ivacaftor, and raloxifene by Pseudomonas aeruginosa cytochrome P450 CYP107S1.

Drug metabolism is one of the main processes governing the pharmacokinetics and toxicity of drugs via their chemical biotransformation and elimination. In humans, the liver, enriched with cytochrome P450 (CYP) enzymes, plays a major metabolic and detoxification role. The gut microbiome and its complex community of microorganisms can also contribute to some extent to drug metabolism. However, during an infection when pathogenic microorganisms invade the host, our knowledge of the impact on drug metabolism by this pathobiome remains limited. The intrinsic resistance mechanisms and rapid metabolic adaptation to new environments often allow the human bacterial pathogens to persist, despite the many antibiotic therapies available. Here, we demonstrate that a bacterial CYP enzyme, CYP107S1, from Pseudomonas aeruginosa, a predominant bacterial pathogen in cystic fibrosis (CF) patients, can metabolize multiple drugs from different classes. CYP107S1 demonstrated high substrate promiscuity and allosteric properties much like human hepatic CYP3A4. Our findings demonstrated binding and metabolism by the recombinant CYP107S1 of fluoroquinolone antibiotics (ciprofloxacin and fleroxacin), a CF transmembrane conductance regulator potentiator (ivacaftor), and a SERM antimicrobial adjuvant (raloxifene). Our in vitro metabolism data were further corroborated by molecular docking of each drug to the heme active site using a CYP107S1 homology model. Our findings raise the potential for microbial pathogens modulating drug concentrations locally at the site of infection, if not systemically, via CYP-mediated biotransformation reactions. To our knowledge, this is the first report of a CYP enzyme from a known bacterial pathogen that is capable of metabolizing clinically utilized drugs.

Safety and effectiveness of three novel all-oral shortened regimens for rifampicin- or multidrug-resistant tuberculosis in Kazakhstan.

BACKGROUND: In 2019, WHO called for operational research on all-oral shortened regimens for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We report safety and effectiveness of three nine-month all-oral regimens containing bedaquiline (Bdq), linezolid (Lzd), and levofloxacin (Lfx) and reinforced with cycloserine (Cs) and clofazimine (Cfz), delamanid (Dlm) and pyrazinamide (Z), or Dlm and Cfz. METHODS: We conducted a prospective cohort study of patients initiating treatment for pulmonary MDR/RR-TB under operational research conditions at public health facilities in Kazakhstan. Participants were screened monthly for adverse events. Participants with baseline resistance were excluded from the study and treated with a longer regimen. We analyzed clinically relevant adverse events of special interest in all participants and sputum culture conversion and end-of-treatment outcomes among individuals who were not excluded. RESULTS: Of 510 participants, 41% were women, median age was 37 years (interquartile range: 28-49), 18% had a body mass index <18·5 kg/m2, and 51% had cavitary disease. Three hundred and ninety-nine (78%) initiated Bdq-Lzd-Lfx-Cs-Cfz, 83 (16%) started Bdq-Lzd-Lfx-Dlm-Z, and 28 (5%) initiated Bdq-Lzd-Lfx-Dlm-Cfz. Fifty-eight individuals (11%) were excluded from the study, most commonly due to identification of baseline drug resistance (n = 52; 90%). Among the remaining 452 participants, treatment success frequencies were 92% (95% confidence interval [CI]: 89 to 95), 89% (95%CI: 80 to 94), and 100% (95%CI: 86 to 100) for regimens with Cs/Cfz, Dlm/Z, and Dlm/Cfz respectively. Clinically-relevant adverse events of special interest were uncommon. CONCLUSION: All regimens demonstrated excellent safety and effectiveness, expanding the potential treatment options for patients, providers, and programs.

Longitudinal molecular analysis of clinical and fecal Escherichia coli isolates at a Veterans Affairs Medical Center in Minnesota, USA, 2012-2019.

Introduction: Extraintestinal Escherichia coli infections represent a growing public health threat, However, current studies often overlook important factors such as temporal patterns of infection, phylogenetic and clonal background, or the host gut E. coli population, despite their likely significance. Methods: In this study, we analyzed >7000 clinical E. coli isolates from patients at the Minneapolis Veterans Affairs Health Care System (2012-2019), and concurrent fecal E. coli from uninfected veterans. We assessed phylogenetic group distribution, membership in selected sequence types (STs), and subsets thereof-including the pandemic, resistance-associated ST131-H30R, and ST1193 lineages-and strain type, as defined by pulsed-field gel electrophoresis. We then analyzed these features alongside the temporal patterns of infection in individual hosts. Results: The H30R lineage emerged as the leading lineage, both overall and among fluoroquinolone-resistant isolates, with ST1193 following among fluoroquinolone-resistant isolates. Recurrences were common, occurring in 31% of subjects and 41% of episodes, and often multiple and delayed/prolonged (up to 23 episodes per subject; up to 2655d post-index). Remarkably, these recurrences typically involved the subject's index strain (63% of recurrences), even when affecting extra-urinary sites. ST131, H30R, ST1193, and fluoroquinolone-resistant strains generally caused significantly more recurrences than did other strains, despite similar recurrence intervals. ST131 strain types shifted significantly over the study period. Infection-causing strains were commonly detectable in host feces at times other than during an infection episode; the likelihood of detection varied with surveillance intensity and proximity to the infection. H30R and ST1193 were prominent causes of fecal-clinical clonal overlap. Discussion: These findings provide novel insights into the temporal and clonal characteristics of E. coli infections in veterans and support efforts to develop anti-colonization interventions.

Enterococcus-related vascular graft infection: A case series.

OBJECTIVES: We aimed to assess the frequency, management, and burden of enterococcal-related vascular graft infection. PATIENTS AND METHODS: From 2008 to 2021, data regarding all episodes of vascular graft infections initially managed or secondarily referred to our referral center were prospectively collected. We described the history and management of the infection, depending on the type of prosthesis used. RESULTS: The frequency of enterococcal-related vascular graft infections was 29/249 (12 %). Most of them were early infections (22/29, 76 %). Infections were polymicrobial (26/29, 90 %), mostly associated with Enterobacterales. Among patients with positive blood cultures, 7/8 (88 %) involved enterococci. Patients with enterococcal-related vascular graft infections were mainly (22/29, 76 %) treated with an association of antibiotics. Mortality and relapse occurred in 28 % and 7 % respectively of the cases. CONCLUSIONS: Enterococcal-related vascular graft infections occurred in patients with comorbidities, during the early period following surgery and were more frequent in cases of intra-cavitary prosthesis. Their potential virulence needs to be considered, especially in polymicrobial infections.

In silico degradation of fluoroquinolones by a microalgae-based constructed wetland system.

Fluoroquinolone antibiotics (FQs) have been used worldwide due to their extended antimicrobial spectrum. However, the overuse of FQs leads to frequent detection in the environment and cannot be efficiently removed. Microalgae-based constructed wetland systems have been proven to be a relatively proper method to treat FQs, mainly by microalgae, plants, microorganisms, and sediments. To improve the removal efficiency of microalgae-constructed wetland, a systematic molecular design, screening, functional, and risk evaluation method was developed using three-dimensional quantitative structure-activity relationship models, molecular dynamics simulation, molecular docking, and TOPKAT approaches. Five designed ciprofloxacin alternatives with improved bactericidal effects and lower human health risks were found to be more easily degraded by microalgae (16.11-167.88 %), plants (6.72-58.86 %), microorganisms (9.10-15.02 %), and sediments (435.83 %-1763.51 %) compared with ciprofloxacin. According to the mechanism analysis, the removal effect of the FQs can be affected via changes in the number, bond energy, and molecular descriptors of favorable and unfavorable amino acids. To the best of our knowledge, this is the first comprehensive study of improving the microalgae, plants, microorganisms, and sediment removal efficiency of FQs in constructed wetlands, which provides theoretical support for the treatment of FQ pollution.