Quinolone Antibacterials Research Articles

Insights into antibiotic resistance promoted by quinolone exposure.

Quinolone-induced antibiotic resistance (QIAR) refers to the phenomenon by which bacteria exposed to sublethal levels of quinolones acquire resistance to non-quinolone antibiotics. We have explored this in Escherichia coli MG1655 using a variety of compounds and bacteria carrying a quinolone-resistance mutation in gyrase, mutations affecting the SOS response, and mutations in error-prone polymerases. The nature of the antibiotic-resistance mutations was determined by whole-genome sequencing. Exposure to low levels of most quinolones tested led to mutations conferring resistance to chloramphenicol, ampicillin, kanamycin, and tetracycline. The mutations included point mutations and deletions and could mostly be correlated with the resistance phenotype. QIAR depended upon DNA gyrase and involved the SOS response but was not dependent on error-prone polymerases. Only moxifloxacin, among the quinolones tested, did not display a significant QIAR effect. We speculate that the lack of QIAR with moxifloxacin may be attributable to it acting via a different mechanism. In addition to the concerns about antimicrobial resistance to quinolones and other compounds, QIAR presents an additional challenge in relation to the usage of quinolone antibacterials.

Trends in Hospital Antibacterial Consumption in Belgium (2017-2021): Evaluating the Impact of the COVID-19 Pandemic

This study aimed to evaluate the impact of the COVID-19 pandemic on antimicrobial consumption (AMC) in Belgian hospitals from 2017 to 2021, using data from the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) and the Belgian Hospitals Surveillance of Antimicrobial Consumption (BeH-SAC). Antimicrobial volume was quantified in Defined Daily Doses (DDDs), and AMC was expressed in DDDs/1000 inhabitants/day (DIDs), DDDs/1000 patient days and DDDs/1000 admissions. Linear regressions were employed to analyze 5-year trends for the ATC J01 group, at the ATC-3 level and for broad-spectrum antimicrobials. Broad-spectrum antibiotics included combinations of penicillins, incl. beta-lactamase inhibitors (J01CR), second-generation cephalosporins (J01DC), third-generation cephalosporins (J01DD), macrolides, lincosamides and streptogramins (J01F, excluding erythromycin J01FA01), and fluoroquinolones (J01MA). The compound annual growth rate (CAGR) calculated for the years preceding the pandemic was used to forecast 2020 and 2021 AMC, enabling a comparison with the actual use. Hospital AMC measured as DIDs decreased by 12% from 2019 to 2020. In contrast, when expressed as DDDs/1000 patient days and DDDs/1000 admissions, a 5% and 7% increase was observed, respectively. Antibacterials for systemic use (J01) showed a significant decrease over the 5 years only when expressed in DIDs. Notable trends included a negative trend for quinolone antibacterials (J01M) when expressed in the three incidence units, as for amphenicols (J01B) when using hospital denominators only. Positive trends were observed for sulfonamides and trimethoprim (J01E) using hospital denominators and for other beta-lactam antibacterials (J01D) with the ‘patient days’ denominator. While the consumption of all J01 antimicrobial subclasses deviated negatively from predicted use both in 2020 and 2021 when expressed in DIDs, positive deviations were recorded using hospital denominators, except for macrolides (J01F). The use of broad-spectrum antimicrobials showed a notable decrease between 2017 and 2021 when expressed in DIDs. However, when using hospital denominators, the observed use of broad-spectrum antimicrobials exceeded the forecasted values in 2020, to regress below the forecasted levels in 2021 (Figure 1). Contrary to results obtained using the widely applied country’s population as the denominator, a notable surge in AMC, particularly for broad-spectrum antimicrobials, was observed in 2020 when using hospital-specific denominators. This increase coincided with the onset of the COVID-19 crisis. These findings emphasize the need for a national hospital surveillance system that uses denominators that accurately represent the specific population being monitored. Implementing robust hospital-specific surveillance mechanisms would improve the precision of evaluations and facilitate targeted interventions aimed at optimizing antimicrobial utilization.

In Vitro Evaluation of Anti-Parasitic Activities of Quinolone-Coumarin Hybrids Derived from Fluoroquinolones and Novobiocin Against Toxoplasma gondii.

Toxoplasmosis is caused by the parasite Toxoplasma gondii (T. gondii). In immunocompetent individuals, the infection is often asymptomatic; however, in expectant mothers and those with immune system deficiencies, complications may arise. Consequently, there is a need for new drugs that cause minimal damage to host cells. The purpose of this study was to investigate the in vitro antiparasitic efficacy of quinolone-coumarin hybrids QC1-QC12, derived from quinolone antibacterials and novobiocin, against T. gondii. The derivatives were compared with novobiocin and ciprofloxacin during testing, with pyrimethamine used as a positive control. We conducted the MTT assay to examine the anti-toxoplasmic effects of the test compounds and novobiocin. Evaluation included the infection and proliferation indices, as well as the size and number of plaques, based on the viability of both healthy and infected cells. The in vitro assays revealed that QC1, QC3, QC6, and novobiocin, with selectivity indices (SIs) of 7.27, 13.43, and 8.23, respectively, had the least toxic effect on healthy cells and the highest effect on infected cells compared to pyrimethamine (SI = 3.05). Compared to pyrimethamine, QC1, QC3, QC6, and novobiocin Without having a significant effect on cell viability, demonstrated a significant effect on reducing in both infection index and proliferation index, in addition to reducing the quantity and dimensions of plaques ( P < 0.05). Based on our results, QC1, QC3, QC6, and novobiocin due to their significant therapeutic effects could be considered as potential new leads in the development of novel anti-Toxoplasma agents.

Insights into solid–liquid equilibrium behavior of 2′,4′-Dichloro-5′-fluoroacetophenone

2′,4′-Dichloro-5′-fluoroacetophenone is a key intermediate in the preparation of ciprofloxacin hydrochloride, a broad-spectrum quinolone antibacterial drug. Wherein, crystallization and solid–liquid equilibrium thermodynamics play an irreplaceable role in the separation and purification of 2′,4′-Dichloro-5′-fluoroacetophenone. Therefore, in this work, the solubility of 2′,4′-Dichloro-5′-fluoroacetophenone was measured by dynamic method in eight different solvents and range from 273.15 K to 288.15 K. The results showed that the solubility of 2′,4′-Dichloro-5′-fluoroacetophenone increased with increasing temperature. Further analysis showed that the solubility of 2′,4′-Dichloro-5′-fluoroacetophenone increased with increasing carbon chain length in ester solvents. Single crystals of 2′,4′-Dichloro-5′-fluoroacetophenone were successfully prepared and the result reveals that the Cl⋯H, O⋯H, and F⋯H interactions dominated the packing and long-range order of the crystals. Then, different thermodynamic models were employed to describe the thermodynamic behavior of 2′,4′-Dichloro-5′-fluoroacetophenone. The calculated ARD% and RMSD values show that the correlation results are in good agreement with the experimental data, and the Van’t Hoff equation has the best regression performance. Finally, it is interesting to find that the contribution of entropy and enthalpy change to dissolution of 2′,4′-Dichloro-5′-fluoroacetophenone tends to be equal with increasing temperature.

A molybdenum-ciprofloxacin complex with an isopolyoxometalate having DNA binding and antibacterial activity

In this study, an antibacterial complex based on the quinolone antibacterial drug ciprofloxacin (CF) and a polyoxometalate was synthesized, Mo2O5(CF)2(CFd)2(β-Mo8O26)·5H2O (1). Complex 1 was characterized by elemental analysis and X-ray single-crystal diffraction. Single-crystal structural analysis revealed that 1 was made of β-Mo8 clusters, binuclear molybdenum clusters Mo2O5(CF)2(CFd)2, and water molecules. The antibacterial activity of 1 has been tested against three microorganisms (Staphylococcus aureus, Escherichia coli, and Bacillus subtilis strains); the antibacterial activities of 1 were higher than those of free CF at the same mass amounts. The interaction between 1 and calf thymus DNA (CT-DNA) was investigated using Uv-vis spectroscopy to determine the binding constants. The results indicated that intercalation is the probable mode of action, with 1 demonstrating higher binding constants (K b) to CT-DNA (1.8 × 105 M−1) compared to pure CF (4.9 × 104 M−1). These findings show that the implementation of molybdate for ciprofloxacin modification resulted in the formation of a metal complex with enhanced antibacterial activity over CF and significantly improving its binding affinity to DNA.

Differences in antibiotic use between COPD and non-COPD residents based on the health information system.

To compare the differences in antibiotic use between COPD and non-COPD residents, and to explore the effect of COPD on antibiotic use. Participants aged 40 years old or over from the Songjiang Adult Cohort were included. Information on prescription and baseline survey was collected based on the health information system. A logit-negative binomial Hurdle model was used to explore correlations between COPD and percentage of antibiotic use and average rate of antibiotic prescribing of different types of antibiotic. Multinomial logistic regression was used to assess the association between COPD and antimicrobial combination therapy and routes of administration. A total of 34576 individuals were included and 1594 (4.6%) were COPD patients. During the 6 years' follow-up, the percentage of antibiotic use for COPD patients was 98.4%, which was 7.88 (95%CI: 5.24-11.85) times of that for non-COPD patients after adjusting for potential confounders. The prescribing rate was 3220 prescriptions (95%CI: 3063.6-3385.2) per 1000 person-years for COPD patients, which was 1.96 (95%CI: 1.87-2.06) times of that for non-COPD patients. Other beta-lactam antibacterials, Macrolides, lincosamides and streptogramins, and quinolone antibacterials were the most commonly used types of antibiotic. Except for aminoglycoside antibacterials, both percentage of antibiotic use and rate of antibiotic prescription were increased in COPD patients. COPD patients were more likely to be prescribed a maximum of two antibiotics (OR=1.34, 95%CI: 1.20-1.50); and were more likely to use antibiotics intravenously (OR=2.77, 95%CI: 2.47-3.11). COPD patients were more likely to have increased antibiotic use in a large-scale population-based adult cohort, suggesting COPD patients are a high-priority group for the management of antibiotic use in communities.

Fabrication and Applications of Potentiometric Membrane Sensors Based on Specific Recognition Sites for the Measurement of the Quinolone Antibacterial Drug Gemifloxacin.

Supramolecular gemifloxacin (GF) sensors have been developed. Supramolecular chemistry is primarily concerned with noncovalent intermolecular and intramolecular interactions, which are far weaker than covalent connections, but they can be exploited to develop sensors with remarkable affinity for a target analyte. In order to determine the dose form of the quinolone antibacterial drug gemifloxacin, the current study's goal is to adapt three polyvinylchloride (PVC) membrane sensors into an electrochemical technique. Three new potentiometric membrane sensors with cylindric form and responsive to gemifloxacin (GF) were developed. The sensors' setup is based on the usage of o-nitrophenyl octyl ether (o-NPOE) as a plasticizer in a PVC matrix, β-cyclodextrin (β-CD) (sensor 1), γ-cyclodextrin (γ-CD) (sensor 2), and 4-tert-butylcalix[8]arene (calixarene) (sensor 3) as an ionophore, potassium tetrakis (4-chlorophenyl) borate (KTpClPB) as an ion additive for determination of GF. The developed method was verified according to IUPAC guidelines. The sensors under examination have good selectivity for GF, according to their selectivity coefficients. The constructed sensors demonstrated a significant response towards to GF over a concentration range of 2.4 × 10-6, 2.7 × 10-6, and 2.42 × 10-6 mol L-1 for sensors 1, 2, and 3, respectively. The sensors showed near-Nernstian cationic response for GF at 55 mV, 56 mV, and 60 mV per decade for sensors 1, 2, and 3, respectively. Good recovery and relative standard deviations during the day and between days are displayed by the sensors. They demonstrated good stability, quick response times, long lives, rapid recovery, and precision while also exhibiting good selectivity for GF in various matrices. To determine GF in bulk and dose form, the developed sensors have been successfully deployed. The sensors were also employed as end-point indicators for titrating GF with sodium tetraphenyl borate.

Sporadic Use of Antibiotics in Older Adults and the Risk of Dementia: A Nested Case-Control Study Based on German Health Claims Data.

Antibiotics for systemic use may increase the risk of neurodegeneration, yet antibiotic therapy may be able to halt or mitigate an episode of neurodegenerative decline. To investigate the association of sporadic use of antibiotics and subsequent dementia risk (including Alzheimer's disease). We used data from the largest public health insurance fund in Germany, the Allgemeine Ortskrankenkasse (AOK). Each of the 35,072 dementia cases aged 60 years and older with a new dementia diagnosis during the observation period from 2006 to 2018 was matched with two control-patients by age, sex, and time since 2006. We ran conditional logistic regression models for dementia risk in terms of odds ratios (OR) as a function of antibiotic use for the entire antibiotic group and for each antibiotic subgroup. We controlled for comorbidities, need for long-term care, hospitalizations, and nursing home placement. Antibiotic use was positively associated with dementia (OR = 1.18, 95% confidence interval (95% CI):1.14-1.22), which became negative after adjustment for comorbidities, at least one diagnosis of bacterial infection or disease, and covariates (OR = 0.93, 95% CI:0.90-0.96). Subgroups of antibiotics were also negatively associated with dementia after controlling for covariates: tetracyclines (OR = 0.94, 95% CI:0.90-0.98), beta-lactam antibacterials, penicillins (OR = 0.93, 95% CI:0.90-0.97), other beta-lactam antibacterials (OR = 0.92, 95% CI:0.88-0.95), macrolides, lincosamides, and streptogramins (OR = 0.88, 95% CI:0.85-0.92), and quinolone antibacterials (OR = 0.96, 95% CI:0.92-0.99). Our results suggest that there was a decreased likelihood of dementia for preceding antibiotic use. The benefits of antibiotics in reducing inflammation and thus the risk of dementia need to be carefully weighed against the increase in antibiotic resistance.

SLC54 Mitochondrial pyruvate carriers in GtoPdb v.2023.1

Pyruvate is oxidized to acetyl‐CoA by pyruvate dehydrogenase which is localized in the mitochondrial matrix. The mitochondrial pyruvate carrier (MPC) is composed of SLC54 family members (MPC1 and MPC2) [1, 5], which form functional hetero-dimers [9, 8]. The MPC is expressed in the inner mitochondrial membrane and involved in the import of pyruvate into mitochondria [1, 5]. Ubiquitous disruption of either MPC1 or MPC2 expression results in embryonic lethality [11, 12]. Clinically relevant concentrations of the insulin sensitizers, thiazolidinediones, inhibit the MPC [3]. Other clinically relevant inhibitors of the MPC complex are lonidamine [7, 8], quinolone antibacterials [6], entacapone and nitrofurantoin [8].

Conversion of antibacterial quinolone drug levofloxacin to potent cytotoxic agents.

Levofloxacin, the optical S-(-) isomer of ofloxacin, is a broad-spectrum antibacterial agent widely used to control various infections caused by Gram-positive and Gram-negative bacteria. While the COOH group is necessary for antibacterial activity, its modification can offer anticancer activity to the fluoroquinolone framework. Therefore, several levofloxacin carboxamides 11a-j and 12 containing 5-substituted-1,3,4-thiadiazole residue were synthesized and screened in vitro for their anticancer activity. The in vitro MTT viability assay revealed that the most compounds had significant activity against cancer cells MCF-7, A549, and SKOV3. In particular, the 3-chloro- and 4-fluoro- benzyl derivatives (11b and 11h), with IC50 values of 1.69-4.76 μM were as potent as or better than doxorubicin. It should be noted that the mother quinolone levofloxacin showed no activity on the tested cancer cell lines. The SAR analysis demonstrated that the 3-chloro or 4-fluoro substituent on the S-benzyl moiety had positive effect on the activity. Further in vitro evaluations of the most promising compounds 11b and 11h by flow cytometric analysis and comet test revealed the ability of compounds in the induction of apoptosis and blockage of the cell proliferation at the G1-phase by nuclear fragmentation and DNA degradation in cancer cells. The obtained results demonstrated that the alteration of 6-COOH functional group in the levofloxacin structure and conjugation with a proper heterocyclic pharmacophore is a good strategy to obtain new anticancer agents.

Safety of Quinolones in Children: A Systematic Review and Meta-Analysis.

The results of animal experiments show that quinolone antibacterial drugs may permanently damage the soft tissues of the weight-bearing joints of young animals. Out of safety concerns, using quinolones in children has always been controversial. The aim of this study was to assess the risk of using quinolones in children and provide evidence for clinicians to support decision making. The MEDLINE (Ovid), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), International Pharmaceutical Abstracts (Ovid), CINAHL, CNKI, VIP, and WanFang Data databases were searched from inception to 8 September 2021. All types of studies that reported the safety data of quinolones in children, including clinical trials and observational studies. Data extraction and cross-checking were completed by two independent reviewers using a pilot-tested standardized data extraction form. The overall incidence rate of adverse drug events (ADEs) in children using systemic quinolones was 5.39% and the most common ADEs were gastrointestinal reactions (incidence rate, 2.02%). Quinolone-induced musculoskeletal ADEs in children were uncommon (0.76%). Meta-analysis results showed that the risk of musculoskeletal ADEs in children using quinolones was higher than children in the control group (51 studies; rate ratio [RR] 2.03, 95% confidence interval [CI] 1.82-2.26; p<0.001; I2=18.6%; moderate-quality evidence). However, the subgroup analysis results showed that differences might only be observed in children who were followed up for 2 months to 1 year (2-6 months: RR 2.56, 95% CI 2.26-2.89; 7 months to 1 year: RR 1.35, 95% CI 0.98-1.86). Moreover, children (adolescents) aged between 13 and 18 years might be sensitive to the musculoskeletal toxicity of quinolones (RR 2.69, 95% CI 2.37-3.05; moderate-quality evidence) and the risk of levofloxacin-induced musculoskeletal ADEs might be higher (RR 1.33, 95% CI 1.00-1.77; low-quality evidence). Although the existing evidence shows that quinolone-induced musculoskeletal ADEs seem to be only short-term and reversible, and no serious skeletal and muscular system damage cases have been reported in children, quinolones should be avoided unless necessary in children because the incidence rate of quinolone-related ADEs is not low and they are broad-spectrum antibiotics that will induce the emergence of resistant strains if used frequently.

Thermodynamics, simulation and chiral recognition mechanism of two asymmetric center quinolone

A novel antibacterial quinolone was prepared with two chiral centers. For medicinal safety purposes, the four stereoisomers of the molecule are separated by HPLC using a Chiral (+)-Crownpack column (25 cm × 0.46 cm, 5.0 μm) with an eluent of 50 mM H2SO4. The values of the retention, separation, and resolution factors of RR-, SS-, RS-, and SR-stereoisomers were in the range of 1.15–7.55, 1.18 to 2.34, and 1.05 to 2.38 at 15, 20, 25, 30 and 35 °C temperatures. The values of the linearity, limits of detection, and limits of quantitation were in the range of 55.6–125, 1.5 to 4.0, and 14.0–37.6 μg mL−1. Chiral HPLC separation was validated properly. The thermodynamics parameters were in the range of 1.96–10.72 kJ mol−1 (ΔΔH), 0.013–0.041 kJ mol−1K−1 (ΔΔS) and −0.52 to −1.99 kJ mol−1K−1 (ΔG298). These values confirmed chiral separation as spontaneous and thermodynamically stable. The simulation study was used to understand the mechanism of the chiral separation at the supramolecular level. The binding affinities of the stereoisomers with the chiral stationary phase were in the range of −3.0 to −3.5 kcal mol−1. The hydrogen bonding was found responsible for the chiral separation. The reported HPLC conditions are inexpensive and may be used to separate the four stereoisomers successfully in any sample.

New Pharmacokinetic and Microbiological Prediction Equations to Be Used as Models for the Search of Antibacterial Drugs.

Currently, the development of resistance of Enterobacteriaceae bacteria is one of the most important health problems worldwide. Consequently, there is a growing urge for finding new compounds with antibacterial activity. Furthermore, it is very important to find antibacterial compounds with a good pharmacokinetic profile too, which will lead to more efficient and safer drugs. In this work, we have mathematically described a series of antibacterial quinolones by means of molecular topology. We have used molecular descriptors and related them to various pharmacological properties by using multilinear regression (MLR) analysis. The regression functions selected by presenting the best combination of a number of quality and validation metrics allowed for the reliable prediction of clearance (CL), and minimum inhibitory concentration 50 against Enterobacter aerogenes (MIC50Ea) and Proteus mirabilis (MIC50Pm). The obtained results clearly reveal that the combination of molecular topology methods and MLR provides an excellent tool for the prediction of pharmacokinetic properties and microbiological activities in both new and existing compounds with different pharmacological activities.

Trends and Patterns of Antibiotics Use in China's Urban Tertiary Hospitals, 2016-19.

Objectives: This study aimed to identify the trends in antibiotics utilization and patients costs, evaluating the effect of the policy and exploring factors associated with the irrational use of antibiotics. Methods: Based on the Cooperation Project Database of Hospital Prescriptions, data were collected from 89 tertiary hospitals in nine cities in China during 2016–2019. The study sample consisted of prescription records with antibiotics for 3,422,710 outpatient and emergency visits and 26, 118, 436 inpatient hospitalizations. Results: For outpatients, the proportion of treated with antibiotics declined from 14.72 to 13.92% significantly (p < 0.01). The proportion of antibiotic costs for outpatients decreased from 5.79 to 4.45% significantly (p < 0.01). For emergency patients, the proportion of treated with antibiotics increased from 39.31 to 43.45% significantly (p < 0.01). The proportion of antibiotic costs for emergency patients decreased from 36.44 to 34.69%, with no significant change (p = 0.87). For inpatients, the proportion of treated with antibiotics increased from 23.82 to 27.25% significantly (p < 0.01). The proportion of antibiotic costs for outpatients decreased from 18.09 to 17.19% with no statistical significance (p = 0.89). Other β-lactam antibacterials (1,663.03 ten thousand DDD) far exceeded other antibiotics categories. Stablely ranked first, followed by Macrolides, lincosamide and streptogramins (965.74 ten thousand DDD), Quinolone antibacterials (710.42 ten thousand DDD), and β-lactam antibacterials, penicillins (497.01 ten thousand DDD). Conclusions: The proportion of treated with antibiotics for outpatients and inpatients meet the WHO standards. The antibiotics use varied by different survey areas, clinical departments, patient gender, patient age and antibiotics categories. More efforts should focus on improving the appropriateness of antibiotics use at the individual level.

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones-Shaping the Fifth Generation.

The evolution of the class of antibacterial quinolones includes the introduction in therapy of highly successful compounds. Although many representatives were withdrawn due to severe adverse reactions, a few representatives have proven their therapeutical value over time. The classification of antibacterial quinolones into generations is a valuable tool for physicians, pharmacists, and researchers. In addition, the transition from one generation to another has brought new representatives with improved properties. In the last two decades, several representatives of antibacterial quinolones received approval for therapy. This review sets out to chronologically outline the group of approved antibacterial quinolones since 2000. Special attention is given to eight representatives: besifloxacin, delafoxacin, finafloxacin, lascufloxacin, nadifloxacin and levonadifloxacin, nemonoxacin, and zabofloxacin. These compounds have been characterized regarding physicochemical properties, formulations, antibacterial activity spectrum and advantageous structural characteristics related to antibacterial efficiency. At present these new compounds (with the exception of nadifloxacin) are reported differently, most often in the fourth generation and less frequently in a new generation (the fifth). Although these new compounds’ mechanism does not contain essential new elements, the question of shaping a new generation (the fifth) arises, based on higher potency and broad spectrum of activity, including resistant bacterial strains. The functional groups that ensured the biological activity, good pharmacokinetic properties and a safety profile were highlighted. In addition, these new representatives have a low risk of determining bacterial resistance. Several positive aspects are added to the fourth fluoroquinolones generation, characteristics that can be the basis of the fifth generation. Antibacterial quinolones class continues to acquire new compounds with antibacterial potential, among other effects. Numerous derivatives, hybrids or conjugates are currently in various stages of research.

Multi–class analysis of 30 antimicrobial residues in poultry feathers by liquid chromatography tandem mass spectrometry

ABSTRACT Poultry feathers are nowadays partially re-introduced into the animal food chain and the environment. They are valorised by their transformation into feather meal in order to be used as fertilisers in agriculture but also in animal feed (in particular, pet food and fish feed). However, unlike food producing animals for humans, feathers from poultry animals are not subject to a ban or regulatory limits on the presence of antibiotic residue after veterinary treatment. Feathers could therefore be a potential reservoir of antibiotic residues, unintentionally exposing the environment and animals through food, which might contribute to the emergence of antibiotic resistance. To this end, a multi-class liquid chromatographic method coupled with tandem mass spectrometry (LC-MS/MS) was developed for the detection and determination of residues of 30 antibiotics from eight groups of antibacterial (quinolones, lincosamides, macrolides, penicillins, phenicols, tetracyclines, sulphonamides and diaminopyrimidines) in feathers. The extraction of the analytes from the feathers was carried out by the salting out technique. The separation of the analytes employed a Kinetex C18 column. Quantification was made using internal standards. All analytes have been validated according to the performance criteria of Decision 2002/657/EC. Trueness of the method ranged from to 93% to 111% for all analytes and intermediate precision were to 1.2–18.8%. The limits of quantification (LOQ) were from 13 to 150 µg kg−1 depending on the analytes. The method is suitable for the monitoring and quantification of antibiotic residues in feathers over the range 13–600 µg kg−1 depending on the compound.

Microbiological pattern of prosthetic hip and knee infections: a high-volume, single-centre experience in China.

Introduction. Prosthetic joint infection (PJI) is a serious complication after arthroplasty, which results in high morbidity, prolonged treatment and considerable healthcare expenses in the absence of accurate diagnosis. In China, microbiological data on PJIs are still scarce.Hypothesis/Gap Statement. The incidence of PJI is increasing year by year, and the proportion of drug-resistant bacteria infection is nicreasing, which brings severe challenges to the treatment of infection.Aim. This study aimed to identify the pathogens in PJIs, multi-drug resistance, and evaluate the effect of the treatment regimen in patients with PJI.Methodology. A total of 366 consecutive cases of PJI in the hip or knee joint were admitted at the Orthopedic Surgery Center in Zhengzhou, China from January 2012 to December 2018. Infections were confirmed in accordance with the Infectious Diseases Society of America and the Musculoskeletal Infection Society (MSIS) criteria. Concurrently, patient demographic data, incidence and antibiotic resistance were investigated. Statistical differences were analysed using Fisher's exact test or chi-square test.Results. Altogether, 318 PJI cases satisfying the inclusion criteria were enrolled in this study, including 148 with hip PJIs and 170 with knee PJIs. The average age of patients with hip PJIs was lesser than that of patients with knee PJIs (56.4 vs. 68.6 years). Meanwhile, coagulase-negative staphylococcus (CNS, n=81, 25.5 %) was the predominant causative pathogen, followed by Staphylococcus aureus (n=67, 21.1 %). Methicillin-resistant Staphylococcus (MRS) was identified in 28.9 % of PJI patients. In addition, fungus accounted for 4.8 % (n=15), non-tuberculosis mycobacterium accounted for 1.6 % (n=5), polymicrobial pathogens accounted for 21.7 % (n=69), and Gram-negative bacteria accounted for 7.9 % (n=25) of the total infections. The results of antibiotic susceptibility testing showed that gentamicin and clindamycin β-lactam antibiotics were poorly susceptible to Gram-positive isolates, but they were sensitive to rifampicin, linezolid and vancomycin. While antibiotics such as amikacin and imipenem were effective against Gram-negative bacteria, there was a high resistance rate of other pathogens to gentamicin, clindamycin and some quinolone antibacterial drugs. Empirical antibiotic treatment should combine vancomycin and cephalosporin, levofloxacin or clindamycin. When the pathogen is confirmed, the treatment should be individualized.Conclusions. The prevalence of culture-negative PJIs is still very high. Gram-positive bacteria are still the main type of pathogens that cause PJIs. Attention should be paid to the high incidence of MRS, such as MRSA and MR-CNS, among PJI patients. Empirical antibiotic treatment should cover Gram-positive isolates, especially Staphylococcus.

Low concentration noroxin detection using terahertz spectroscopy combined with metamaterial.

The unreasonable use of antibiotics in poultry breeding has led to the frequent occurrence of antibiotic residues in poultry products, affecting food safety and posing a threat to human health. Accurate and rapid detection of antibiotic drug content is therefore of great significance. In this study, a new metamaterial method based on terahertz (THz) spectroscopy for the detection of the quinolone antibacterial drug noroxin in low concentrations was developed and tested. First, a new metamaterial structure was designed using a computational electromagnetics simulation tool with experimental verification. Three-dimensional full-wave electromagnetic field simulations and measured transmission spectra for the metamaterials were observed. Second, the transmission spectra of photoresists with different thicknesses (0-40µm) on the metamaterials surface were simulated, and the transmission spectra of noroxin thin films of different concentrations on the metamaterial surface were measured. Finally, using a purchased standard sample of noroxin in ethanol (100µg/mL) as the mother liquor, test samples of different concentrations were prepared, and experiments and multivariate data analysis were carried out. The noroxin detection limit for the method presented in this paper was determined as 0.01µg/mL. Thus, the new metamaterial method based on terahertz spectroscopy designed in this study was shown to effectively detect low concentrations of noroxin, providing a theoretical and experimental basis for the rapid detection of quinolone antibiotic residues in food matrices.

Impact of changes in the WHO's 2019 update of DDDs on the measurement of adult hospital antibacterial consumption in Catalonia (Spain), 2008-18.

ObjectivesIn 2019 the WHO fully adopted new DDD values. The objective of this study is to analyse their impact on the measurement of consumption of antibacterials in hospitals participating in the Catalan Infection Control and Antimicrobial Stewardship National Program (VINCat-PROA) in Catalonia (Spain) between 2008 and 2018.MethodsThe anatomical therapeutic chemical/DDD system was used to monitor adult hospital antibacterial consumption expressed in DDD/100 bed-days. Consumption from 2008 to 2018 was calculated using both pre- and post-update DDD values. Differences were calculated as the percentage variation in DDD/100 bed-days and analysed with Student’s t-test. Simple linear regressions were performed to evaluate the trends in adult antimicrobial consumption over the study period.ResultsThe overall consumption according to post-update DDD values decreased by 12.2% (P < 0.001) compared with the pre-update DDD values. Penicillins (−19.6.%; P < 0.001) and carbapenems (−19.0%; P = 0.023) showed the greatest reduction, followed by cephalosporins (−7.7%; P = 0.021) and quinolone antibacterials (−7.7%; P = 0.017). ICU services showed the greatest overall reduction (−13.1%; P < 0.001). From 2008 to 2018 there was a statistically significant decrease in consumption of penicillins and quinolone antibacterials and a statistically significant increase in cephalosporin and carbapenem consumption with both pre- and post-update DDD values. There were no variations in the ranking of consumption between the pre- and post-update DDD values.ConclusionsThe WHO’s updates of DDDs have had a significant impact on the measurement of antibacterial consumption. In our region, they have corrected an overestimation of penicillin and carbapenem consumption amounting to 19%. It is essential to bear these findings in mind for an accurate assessment of temporal trends and benchmarking.

Simultaneous determination of quinolones in livestock and marine products by high performance liquid chromatography

A high performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of nalidixic acid, flumequine, oxolinic acid, piromidic acid, danofloxacin, enrofloxacin and sarafloxacin in chicken, pork and fish. These seven quinolone antibacterials were extracted with 0.3% metaphosphoric acid: acetonitrile (1:10, v/v), followed by a Bond Elut C18 cartridge clean up procedure. The HPLC separation was achieved on a Cosmosil 5C18-AR-II column (5 μm, 4.6 mm i.d. × 250 mm) with acetonitrile: 0.05M NaH2PO4 (pH 2.5)(35:65, v/v) containing 3.5 mM sodium dodecyl sulfate as a mobile phase, and detection was performed with photodiode array and fluorescence detector (by using wavelength programming). Good linearity was observed from the calibration plot at concentrations from 0.05 to 10.0 mg/mL (0.005-2.0 μg/mL for danofloxacin). Recovery studies of the analytes were performed at 0.01, 0.1, 0.4 and 2.0 ppm (0.001, 0.01, 0.04 and 0.20 ppm for danofloxacin) spiked levels. Average recoveries of low concentration ranged from 74.3 to 85.5% and those of the rest ranged from 80.1 to 99.9% with coefficients of variation less than 5.8%. The detection limits of quinolones were 0.01-0.04 ppm with photodiode array detection and 0.0006-0.05 ppm with fluorescence detection. The coefficients of variation of intra-day and inter-day assays were lower than 3.29% and 5.23%, respectively. These results indicated that the developed method had an acceptable precision. Using this method to detect quinolones in sixty three samples purchased from various markets in Taipei, we found that nine wu ku chicken muscles contained enrofloxacin residues ranged from 0.08 to 4.04 ppm, four wu ku chicken liver muscles contained enrofloxacin residues ranged from 0.01 to 0.27 ppm, and oxolinic acid residues in three sweet fish samples ranged from 0.13 to 0.35 ppm. The results indicated that 25.4% of samples violated the regulation set by the Department of Health. The enrofloxacin residue in wu ku chicken muscle is very stable even after a long period of refrigeration at 4°C.