Concentrations Of Fluoroquinolones Research Articles

Microplastic and associated emerging contaminants in marine fish from the South China Sea: Exposure and human risks

Microplastics can act as vectors of chemical contaminants in aquatic environments, but the extent to which this phenomenon contributes to chemical exposure in marine organisms remains poorly understood. We investigated the occurrence of microplastics and emerging contaminants (ECs), including antibiotics and per- and polyfluoroalkyl substances (PFAS) in 14 marine fish species. Microplastics were detected in all marine fish species, mainly in the gastrointestinal tract. Fluoroquinolones and tetracyclines were the dominant antibiotics in fish muscles with maximum concentrations of 24.84 and 26.95 ng g−1 ww, while perfluorooctanesulfonic acid (PFOS, 0.039–0.95 ng g−1 ww) was the dominant component in the PFAS profile. Fish with more microplastics had significantly higher concentrations of fluoroquinolones and perfluoroalkyl acids than fish with less microplastics (p < 0.05), but the correlation was not observed in other chemicals. Structural equation modeling revealed the contribution of microplastics in fish on the level of ECs contamination. The health quotient value indicated the low health risk of single compounds via fish consumption to humans; however, the combined risk of microplastics and ECs still needs to be considered. This work highlights the link between microplastics with associated ECs ingested by aquatic organisms and the human health risk of consuming polluted seafood.

Варианты генов Mycobacterium tuberculosis, ассоциированные с лекарственной устойчивостью к фторхинолонам (обзор литературы)

Background: The spread of M. tuberculosis drug resistance to fluoroquinolones poses a threat to their long-term clinical efficacy. Understanding the mechanisms of formation of drug resistance to fluoroquinolones, based on information on genes associated with drug resistance of M. tuberculosis, is important for optimizing TB chemotherapy regimens. The aim of the study: To study the available literature data on the most significant variants of M. tuberculosis genes associated with drug resistance to fluoroquinolones. Materials and methods: To achieve this goal, the task was to analyze the sources of domestic and foreign literature on this priority issue over the past 5 years. The databases of scientific electronic libraries PubMed, Elibriary were used. Results: Mycobacterial resistance to fluoroquinolones is associated with mutations in the gyrA and gyrB genes, encoding the GyrA and GyrB subunits of DNA gyrase, the main target of fluoroquinolones. In the fluoroquinolone-binding pocket of the “DNA-gyrase + DNA” catalytic center, the fluoroquinolone molecule is supported by the gyrA and gyrB regions, which determine resistance to fluoroquinolones (QRDR-A and QRDR-B). Modification of any of the constituent fragments of these regions affects the level of resistance to fluoroquinolones. Small quinolone molecules (nalidixic acid) have a high MIC against Mtb and other bacteria, while larger PC molecules (sparfloxacin, sitafloxacin, gatifloxacin, levofloxacin and moxifloxacin) are tightly adjacent to the fluoroquinolone-binding pocket and have a lower MIC. Modification of the DNA structure can change the spatial structure of the pocket itself, which leads to destabilization of the fluoroquinolone inside it. Thus, the presence of heteroresistance of the tuberculosis pathogen to fluoroquinolones indicates the active development of its resistance to this group of drugs in modern conditions. Conclusion: Analysis of modern studies shows the dependence of drug resistance of mycobacteria on fluoroquinolone compounds, while most often resistance to a decrease in the concentration of fluoroquinolones is associated with substitutions in the gyrB gene, as well as mutations in the gyrA gene. It has also been established that in addition to the main studied regions of the gyrA and gyrB genes associated with phenotypic drug resistance to fluoroquinols, there are regions that have not been sufficiently studied so far. These areas cannot be diagnosed in the clinical work of bacteriological laboratories of anti-tuberculosis institutions.

A triple-channel sensor array utilizing fluorescent carbon dots for simultaneous discrimination and detection of multiple fluoroquinolones

The presence of fluoroquinolones (FQs) residues in food and the environment has prompted concerns regarding food safety and public health. Consequently, it is of great significance to analyze the types and levels of FQs present. However, the majority of studies have concentrated on the specific detection of individual FQs, with a notable absence of high-throughput and rapid analysis methods for the simultaneous detection of multiple FQs that may coexist in food and the environment. Hereon, a triple-channel sensor array was successfully constructed utilizing fluorescent carbon dots (TA-CDs), with the assistance of Cu2+ and Fe3+, for the qualitative discrimination and quantitative detection of eight types of FQs. The sensor array can distinguish between different concentrations of FQs and various mixtures of FQs, as well as 100 % accuracy in the discrimination of unknown samples. Impressively, the sensor platform can quantitatively detect FQs in animal-derived foods, such as honey, milk, eggs, and pork, as well as in water samples. This research has the potential to be extended to other analytes with similar chemical structures or properties.

Comparison of Mutant Prevention Concentrations of Fluoroquinolones Against ESBL-Positive and ESBL-Negative Klebsiella pneumoniae Isolates from Orthopedic Patients.

The majority of Klebsiella pneumonia isolates possess the extended-spectrum beta-lactamase (ESBL) enzymes. Therefore, K. pneumoniae can easily develop drug resistance. How to effectively overcome the problem of drug resistance in K. pneumoniae is still a research hotspot. This study aimed to compare the mutant prevention concentration (MPC) of ESBL-positive and ESBL-negative K. pneumoniae isolated from orthopedic patients, which may provide a basis for the effective use of drugs to control the enrichment of resistance mutants of K. pneumoniae. The MPC90 values of 55 isolates of ESBL-positive K. pneumoniae against 4 fluoroquinolones were 32 µg/mL for levofloxacin and gatifloxacin, 16 µg/mL for ciprofloxacin, and 4 µg/mL for gemifloxacin. The selection index value was 8 for levofloxacin and ciprofloxacin and 2 for gemifloxacin and gatifloxacin, respectively. For ESBL-negative K. pneumoniae isolates, the MPC90 values were 16 µg/mL for levofloxacin and ciprofloxacin, 4 µg/mL for gemifloxacin, and 32 µg/mL for gatifloxacin. The selection index value was 8 for levofloxacin and ciprofloxacin, 2 for gemifloxacin, and 4 for gatifloxacin. For the ESBL-positive K. pneumoniae, the %T>MIC90 order was gemifloxacin > levofloxacin > ciprofloxacin > gatifloxacin. For the ESBL-negative K. pneumoniae, the %T>MIC90 order was levofloxacin > gemifloxacin > ciprofloxacin > gatifloxacin. The mutant-preventing ability of gatifloxacin and gemifloxacin was the strongest among the 4 fluoroquinolones. So gemifloxacin may be the first choice of drug to treat K. pneumoniae infection.

Could traces of fluoroquinolones in food induce ciprofloxacin resistance in Escherichia coli and Klebsiella pneumoniae? An in vivo study in Galleria mellonella with important implications for maximum residue limits in food.

We hypothesized that the residual concentrations of fluoroquinolones allowed in food (acceptable daily intake-ADIs) could select for ciprofloxacin resistance in our resident microbiota. We developed models of chronic Escherichia coli and Klebsiella pneumoniae infection in Galleria mellonella larvae and exposed them to ADI doses of ciprofloxacin via single dosing and daily dosing regimens. The emergence of ciprofloxacin resistance was assessed via isolation of the target bacteria in selective agar plates. Exposure to as low as one-tenth of the ADI dose of the single and daily dosing regimens of ciprofloxacin resulted in the selection of ciprofloxacin resistance in K. pneumoniae but not E. coli. This resistance was associated with cross-resistance to doxycycline and ceftriaxone. Whole genome sequencing revealed inactivating mutations in the transcription repressors, ramR and rrf2, as well as mutations in gyrA and gyrB. We found that ciprofloxacin doses 10-fold lower than those classified as acceptable for daily intake could induce resistance to ciprofloxacin in K. pneumoniae. These results suggest that it would be prudent to include the induction of antimicrobial resistance as a significant criterion for determining ADIs and the associated maximum residue limits in food.IMPORTANCEThis study found that the concentrations of ciprofloxacin/enrofloxacin allowed in food can induce de novo ciprofloxacin resistance in Klebsiella pneumoniae. This suggests that it would be prudent to reconsider the criteria used to determine "safe" upper concentration limits in food.

Development of an in vitro biofilm model for the study of the impact of fluoroquinolones on sewer biofilm microbiota.

Sewer biofilms are likely to constitute hotspots for selecting and accumulating antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). This study aimed to optimize culture conditions to obtain in vitro biofilms, mimicking the biofilm collected in sewers, to study the impact of fluoroquinolones (FQs) on sewer biofilm microbiota. Biofilms were grown on coupons in CDC Biofilm Reactors®, continuously fed with nutrients and inoculum (1/100 diluted wastewater). Different culture conditions were tested: (i) initial inoculum: diluted wastewater with or without sewer biofilm, (ii) coupon material: concrete vs. polycarbonate, and (iii) time of culture: 7 versus 14 days. This study found that the biomass was highest when in vitro biofilms were formed on concrete coupons. The biofilm taxonomic diversity was not affected by adding sewer biofilm to the initial inoculum nor by the coupon material. Pseudomonadales, Burkholderiales and Enterobacterales dominated in the sewer biofilm composition, whereas in vitro biofilms were mainly composed of Enterobacterales. The relative abundance of qnrA, B, D and S genes was higher in in vitro biofilms than sewer biofilm. The resistome of sewer biofilm showed the highest Shannon diversity index compared to wastewater and in vitro biofilms. A PCoA analysis showed differentiation of samples according to the nature of the sample, and a Procrustes analysis showed that the ARG changes observed were linked to changes in the microbial community. The following growing conditions were selected for in vitro biofilms: concrete coupons, initial inoculation with sewer biofilm, and a culture duration of 14 days. Then, biofilms were established under high and low concentrations of FQs to validate our in vitro biofilm model. Fluoroquinolone exposure had no significant impact on the abundance of qnr genes, but high concentration exposure increased the proportion of mutations in gyrA (codons S83L and D87N) and parC (codon S80I). In conclusion, this study allowed the determination of the culture conditions to develop an in vitro model of sewer biofilm; and was successfully used to investigate the impact of FQs on sewer microbiota. In the future, this setup could be used to clarify the role of sewer biofilms in disseminating resistance to FQs in the environment.

The intracellular concentrations of fluoroquinolones determined the antibiotic resistance response of Escherichia coli

The extensive consumption of antibiotics has been reported to significantly promote the generation of antibiotic resistance (ABR), however, a quantitative causal relationship between antibiotic exposure and ABR response is absent. This study aimed to pinpoint the accurate regulatory concentration of fluoroquinolones (FQs) and to understand the biochemical mechanism of the mutual action between FQ exposure and FQ resistance response. Highly sensitive analytical methods were developed by using UPLC-MS/MS to determine the total residual, extracellular residual, total intracellular, intracellular residual and intracellular degraded concentration of three representative FQs, including ciprofloxacin (CIP), ofloxacin (OFL) and norfloxacin (NOR), with detection limits in the range of 0.002–0.057 μg/L, and recoveries in the range of 80–93%. The MICs of Escherichia coli (E. coli) were 7.0–31.4-fold of the respective MIC0 after 40-day FQ exposure, and significant negative associations were discovered between the intracellular (residual, degraded or the sum) FQ concentrations and FQ resistance. Transcriptional expression and whole-genome sequencing results indicated that reduced membrane permeability and enhanced multi-drug efflux pumps contributed to the decreasing intracellular concentration. These results unveiled the pivotal role of intracellular concentration in triggering FQ resistance, providing important information to understand the dose-response relationship between FQ exposure and FQ resistance response, and ascertain the target dose metric of FQs for eliminating FQ resistance crisis.

Fluorescent responsive membrane based on terbium coordination polymer and carbon dots with AIE effect for rapid and visual detection of fluoroquinolone

In this study, based on aggregation-induced emission (AIE) effect and antenna effect, a novel portable fluorescent responsive membrane was constructed with red carbon dots (R-CDs) as reference signal and terbium coordination polymer (Tb-AMP CPs) as response signal for visual, instrument-free, and sensitive detection of fluoroquinolones (FQs). Specifically, the fluorescent responsive membrane (R-T membrane) was prepared by physically depositing R-CDs with AIE property and Tb-AMP CPs on the surface of polyvinylidene fluoride filter membranes at ambient temperature. In the presence of FQs, Tb3+ in the Tb-AMP CPs of the prepared membrane coordinated with the β-diketone structure of FQs, which turned on the yellow-green fluorescence through the “antenna effect”. As the concentration of FQs increased, the R-T membrane achieved a fluorescent color transition from bright pink to yellow-green. Its visual detection sensitivity for three FQs, including ciprofloxacin, difloxacin, and enrofloxacin, was 0.01 μM, and the detection limits were 7.4 nM, 7.8 nM, and 9.2 nM, respectively, by analyzing the color parameter green. In the residue analysis of FQs in real samples, the constructed membrane also exhibited remarkable anti-interference and reliability, which is of great significance for ensuring the safety of animal-derived food.

Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection.

Streptococcus pneumoniae is a major pathogen responsible for severe complications in patients with prior influenza A virus (IAV) infection. We have previously demonstrated that S. pneumoniae exhibits increased intracellular survival within IAV-infected cells. Fluoroquinolones (FQs) are widely used to treat pneumococcal infections. However, our prior work has shown that S. pneumoniae can develop intracellular FQ persistence, a phenomenon triggered by oxidative stress within host cells. This persistence allows the bacteria to withstand high FQ concentrations. In this study, we show that IAV infection enhances pneumococcal FQ persistence during intracellular survival within pneumocytes, macrophages, and neutrophils. This enhancement is partly due to increased oxidative stress induced by the viral infection. We find that this phenotype is particularly pronounced in autophagy-proficient host cells, potentially resulting from IAV-induced blockage of autophagosome-lysosome fusion. Moreover, we identified several S. pneumoniae genes involved in oxidative stress response that contribute to FQ persistence, including sodA (superoxide dismutase), clpL (chaperone), nrdH (glutaredoxin), and psaB (Mn+2 transporter component). Our findings reveal a novel mechanism of antibiotic persistence promoted by viral infection within host cells. This underscores the importance of considering this phenomenon when using FQs to treat pneumococcal infections, especially in patients with concurrent influenza A infection.

An innovative probe based on aluminum ion-triggered aggregation induced emission effect for ratiometric fluorescence visual detection of fluoroquinolone

Based on the aggregation-induced emission effect triggered by Al3+, a novel probe was constructed for the ratiometric fluorescence visualization detection of fluoroquinolones (FQs) residues. In this probe, Al3+ cased the glutathione-modified copper nanoclusters (GSH-CuNCs) to aggregate by the interaction with surface carboxyl groups, restricting the intramolecular vibration and rotation of GSH-CuNCs and reducing the non-radiative relaxation of excited states. Significant enhancement of fluorescence and quantum yield were achieved. In the presence of FQs, Al3+/GSH-CuNCs coordinated with FQs to form a polymer that inhibited intramolecular proton transfer in the excited state of FQs, thereby enhancing the intrinsic fluorescence of FQs, while the fluorescence intensity of Al3+/GSH-CuNCs was not disturbed. The probe solution changed from red to blue (or green) under UV lamp as the concentration of FQs increased, providing the possibility for semi-quantitative visual analysis. It also showed sensitive spectral responses to FQs with detection limits of 7.9 (ciprofloxacin), 6.8 (gatifloxacin), and 9.5 nM (enrofloxacin), respectively. The application potential in the detection of FQs residues in poultry eggs was verified by real sample test. Additionally, the probe has been extended to the development of fluorescent test paper and the smartphone detection platform, contributing to rapid, portable, visual quantitative analysis of FQs.

Corynebacterium oculi-related bacterium may act as a pathogen and carrier of antimicrobial resistance genes in dogs: a case report

BackgroundThe genus Corynebacterium comprises well-known animal and human pathogens as well as commensals of skin and mucous membranes. Species formerly regarded as contaminants are increasingly being recognized as opportunistic pathogens. Corynebacterium oculi has recently been described as a human ocular pathogen but has so far not been reported in dogs.Case presentationHere we present two cases of infection with a novel Corynebacterium sp., a corneal ulcer and a case of bacteriuria. The two bacterial isolates could not be identified by MALDI-TOF MS. While 16 S rRNA gene (99.3% similarity) and rpoB (96.6% identity) sequencing led to the preliminary identification of the isolates as Corynebacterium (C.) oculi, whole genome sequencing revealed the strains to be closely related to, but in a separate cluster from C. oculi. Antimicrobial susceptibility testing showed high minimal inhibitory concentrations of lincosamides, macrolides, tetracycline, and fluoroquinolones for one of the isolates, which also contained an erm(X) and tet-carrying plasmid as well as a nonsynonymous mutation leading to an S84I substitution in the quinolone resistance determining region of GyrA.ConclusionsWhile the clinical signs of both dogs were alleviated by antimicrobial treatment, the clinical significance of these isolates remains to be proven. However, considering its close relation with C. oculi, a known pathogen in humans, pathogenic potential of this species is not unlikely. Furthermore, these bacteria may act as reservoir for antimicrobial resistance genes also in a One Health context since one strain carried a multidrug resistance plasmid related to pNG3 of C. diphtheriae.

Adsorptive removal of ciprofloxacin from simulated wastewater using crosslinked starch ester: Isotherms, kinetics, thermodynamics, modeling, and simulation for continuous operation

The rise in fluoroquinolone concentrations in wastewater caused significant concern due to their potential acute toxicity to living organisms. A novel eco-friendly adsorbent, crosslinked potato starch ester, was used to remove ciprofloxacin from a simulated aqueous solution by a batch adsorption process and used its obtained parameters to solve mathematical modeling. With a maximum adsorption capacity of 243.90 mg/g, the ciprofloxacin adsorption on crosslinked potato starch ester was suitable for the Langmuir isotherm model. The kinetics of ciprofloxacin adsorption showed that the pseudo-first-order kinetic model was a good fit for the adsorption process. Thermodynamic parameters exhibited that ciprofloxacin adsorption onto crosslinked potato starch ester was exothermic, achievable, and spontaneous. Finally, the process is simulated under various operating conditions using the mathematical model of a fixed bed continuous adsorption column. According to the results, under optimal operation conditions of inlet fluid velocity, particle size, bed height, and initial ciprofloxacin concentration with values 0.002 m/s, 1.2 mm, 0.2 m, and 143.4 mg/L, respectively, the highest dynamic adsorption capacity was 18.75 mg/g.

Occurrence and ecological risk assessment of antibiotics in manure and the surrounding soil from typical chicken farms in Hangzhou, China

The widespread use of antibiotics in animal and human medication has raised global concerns over environmental contamination caused by antibiotic residues. This research investigated the occurrence of 12 kinds of antibiotics belonging to three groups, sulfonamides (SAs), tetracyclines (TCs), and fluoroquinolones (FQs), in chicken manure and the surrounding soil from different chicken farms in Hangzhou, South China, were detected in the samples via ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and the contamination characteristics of each type of antibiotic and the correlations between each antibiotic and environmental factors were analyzed to identify the key influencing factors. An ecological risk assessment of antibiotics in the soil environment was conducted using the risk quotient (RQ) method to analyze the potential hazard level. The results indicated that: the total concentration of FQs was much higher than those of SAs and TCs in chicken manures and the soil samples. The mean concentration of FQs (39.17 μg·kg–1), TCs (34.37 μg·kg–1), and SAs (20.24 μg·kg–1) in chicken manure were significantly higher than those in the soil samples. Ciprofloxacin (CIP) was the main antibiotics detected in manure (19.42 μg·kg–1) and the soils samples (near soil: 18.42 μg·kg–1, far soil: 10.29 μg·kg–1), followed by enrofloxacin (ENR), tetracycline (TC), and ofloxacin (OFL). The redundancy analysis (RDA) showed that moisture content (MS), total organic carbon (TOC) and total nitrogen (TN) had a greater influence on the antibiotic concentration in the soil samples. Basis on the calculated risk quotient (RQs) values, the risk assessment indicated Sulfamerazine (SD) and Sulfamethoxazole (SMX) in soil posed a high risk, while trimethoprim (TMP), TC, CIP, and OFL in soils posed a medium or low risk. This research provides control and environmental monitoring data about chicken farms and scientific information that can be used to alleviate antibiotics pollution.

Withdrawal time of danofloxacin and difloxacin and in vitro binding phenomenon to melanin in black-boned silky fowl.

Fluoroquinolones are commonly used in poultry breeding. Few studies have evaluated the causes of serious drug residues in black-boned silky fowl until enrofloxacin has been banned in black-boned silky fowl breeding in the Chinese Veterinary Commission of Chinese Veterinary Pharmacopoeia (2020). However, similarly structured fluoroquinolones have not been studied in black-boned silky fowl. In this study, the elimination of tissue residues of danofloxacin (DAN) and difloxacin (DIF) was studied in four tissues of black-boned silky fowl. The specific administration methods were 100mg/L of DIF aqueous solution for free drinking for 5 days and 50mg/L of DAN aqueous solution for free drinking for 3 days. Based on the experiment, the withdrawal times of 44 days for muscle, 95 days for skin+fat, 3 days for liver, and 44 days for kidney of DAN were acquired, of 43 days for muscle, 61 days for skin+fat, 0 days for liver, and 38 days for kidney of DIF were acquired, which showed that DIF and DAN should be used with caution for application in black-boned silky fowl. In vitro experiments showed that black-boned silky fowl tissues had stronger adsorption capacity to DAN and DIF than yellow chicken tissues (especially in skin+fat), and melanin has a strong adsorption effect on DAN and DIF, which is an important reason for the high residual concentrations of fluoroquinolone in black-boned silky fowl.

Population pharmacokinetic analysis of enrofloxacin and its active metabolite ciprofloxacin after intravenous injection to cats with reduced kidney function.

It is unknown if enrofloxacin accumulates in plasma of cats with reduced kidney function. To determine if enrofloxacin and its active metabolite ciprofloxacin have reduced clearance in azotemic cats. Thirty-four cats hospitalized for clinical illness with variable degree of kidney function. Prospective study. After enrofloxacin (dose 5 mg/kg) administration to cats, sparse blood sampling was used to obtain 2 compartment population pharmacokinetic results using nonlinear mixed-effects modeling. Plasma enrofloxacin and ciprofloxacin concentrations were measured and summed to obtain the total fluoroquinolone concentration. A model of ciprofloxacin metabolism from enrofloxacin was created and evaluated for covariate effects on clearance, volume of distribution, and the metabolic rate of ciprofloxacin generation from enrofloxacin. Body weight was the only covariate found to affect total fluoroquinolone volume of distribution (effect 1.63, SE 0.19, P < .01) and clearance (effect 1.63, SE 0.27, P < .01). Kidney function did not have a significant effect on total fluoroquinolone clearance (median 440.8 mL/kg/h (range 191.4-538.0 mL/kg/h) in cats with normal kidney function, 365.8 mL/kg/h (range 89.49-1092.0 mL/kg/h) in cats with moderate kidney dysfunction, and 308.5 mL/kg/h (range 140.20-480.0 mL/kg/h) in cats with severe kidney dysfunction (P = .64). Blood urea nitrogen concentration influenced the metabolic generation of ciprofloxacin from enrofloxacin (effect 0.51, SE 0.08, P < .01), but other markers of kidney function did not. Adjustment of enrofloxacin dosage is not indicated for azotemic cats.

Comprehensive Investigation of Fluoroquinolone Residues in Apis mellifera and Apis cerana Honey and Potential Risks to Consumers: A Five-Year Study (2014-2018) in Zhejiang Province, China.

As a group of antibiotics largely used in China's animal husbandry, fluoroquinolone (FQ) residues in honey may pose potential threats to human health. This study performed a five-year investigation on the occurrence of FQ residues in honey in 521 Apis mellifera and 160 Apis cerana honey samples collected from Zhejiang Province, China and compared FQ residue profiles in honey with a subgroup of various factors. Deterministic and probabilistic risk assessments of exposure to FQ residues in honey were further conducted. Overall, four FQs were detected in 6.9% (47/681) of analyzed samples; banned norfloxacin with the highest level (7890 μg·kg-1) and detection frequency (4.9%) was the primary safety risk factor associated with honeybees raised in China. FQ detection frequency and concentration of rape honey was highest among four of the largest and most stable honeys (rape, acacia, chaste, and linden) in China. Processed honey from commercial sale channels had a significantly higher detection frequency of FQ residues than raw honey from apiaries. Deterministic assessment showed that the noncarcinogenic hazard quotient (HQ) value of the dietary intake of FQs by the local population was between 4.75 × 10-6 and 1.18 × 10-3, less than 1.0, indicating that FQ residues in honey posed a low risk for consumers. The order of the HQ value was ciprofloxacin > norfloxacin > enrofloxacin > ofloxacin. Probabilistic assessment showed that at P95, the HQ of FQs for the age groups of children, adolescents, adults, and older adults over 65 years ranged from 2.39 × 10-5 to 0.217, less than 1, and the exposure risk for adults was higher than for children and adolescents. Sensitivity analysis showed that FQ concentrations were the major contributors to health risks. Although a low risk was found, a strict hive management is needed for beekeepers regarding troubles of food safety, international trade, and human bacterial resistance.

Biliary excretion and pharmacokinetics of several fluoroquinolones after intravenous injection in rabbits.

The aim of this study was to measure the concentrations of enrofloxacin (ERFX) and other fluoroquinolones; orbifloxacin (OBFX), marbofloxacin (MBFX), and ofloxacin (OFLX) in the plasma and bile of rabbits after a single intravenous (IV) injection. Twenty male rabbits were divided into four groups and given each drug by IV injection into the ear vein at a dose of 5.0 mg/kg BW. The concentration of ERFX, ciprofloxacin (CPFX), OBFX, MBFX and OFLX in plasma and bile were determined by HPLC. CPFX, metabolite of ERFX, was also measured by HPLC in plasma and bile of rabbits receiving ERFX. Several pharmacokinetic parameters in plasma were calculated and biliary clearance (CLbile) was calculated from extent of biliary excretion and accumulation of AUC of each drug. After IV injection, elimination half-life (t1/2β) was 4.13, 3.68, 6.60, 5.14 hr; volume of distribution at a steady state (Vdss) was 1.24, 0.503, 0.771, 1.02 L/kg; and total body clearance (CLtot) was 1.05, 0.418, 0.271, 0.453 L/kg/hr, respectively. The values for CLbile for ERFX, OBFX, MBFX, and OFLX were 0.0048, 0.0050, 0.0057, and 0.0094 L/kg/hr, respectively. These values represent 0.48%, 1.2%, 2.1%, and 2.3% of the total body clearance (CLtot) of each drug, respectively. The biliary clearance of CPFX was also measured and found to be 0.0199 L/kg/hr with ERFX administration. The results showed that ERFX, OBFX, MBFX, and OFLX were not excreted into the bile to a significant extent, making them safe drugs to use in rabbits.

Penetration of Enrofloxacin in Aqueous Humour of Avian Eyes.

Enrofloxacin has been shown to be appropriate to treat bacterial eye infections in mammals. However, the anatomy and physiology of the avian eye substantially differ from those in mammals, and pharmacokinetic data substantiating the clinical efficacy of enrofloxacin in birds are still lacking. In total, 40 chickens (Gallus gallus, Lohman Selected Leghorn) received single intramuscular administration of enrofloxacin at a dosage of 25 mg/kg body weight (BW). Serial blood and aqueous humour samples were taken at 12 different time points after administration (0-60 min and 2-32 h) and were analysed for their fluoroquinolone concentrations using a competitive enzyme immunoassay. The metabolization of enrofloxacin to ciprofloxacin was determined using liquid chromatography-mass spectrometry. The maximum serum concentrations of fluoroquinolones were observed at the time point of 2.82 ± 0.1 h and amounted to 10.67 ± 0.5 µg/mL. Fluoroquinolones redistributed to a minor extent into the aqueous humour reaching maximum concentrations of 4.52 ± 1.2 µg/mL after 7.54 ± 1.0 h of drug administration. The mean residence time (MRT), volume of distribution (Vd), and terminal half-life (t1/2 ß) were 1.68-, 2.84-, and 2.01-fold higher in aqueous humour than in serum, indicating that fluoroquinolones were trapped in aqueous humour. Enrofloxacin was only marginally metabolized into ciprofloxacin. A single intramuscular injection of a therapeutical dose of enrofloxacin (25 mg/kg BW) thus generated sustained and therapeutically active levels of enrofloxacin in the aqueous humour of chicken eyes.

Cerebrospinal fluid concentrations of fluoroquinolones and carbapenems in tuberculosis meningitis.

Background: Tuberculosis meningitis (TBM) is the most lethal form of TB. It is difficult to treat in part due to poor or uncertain drug penetration into the central nervous system (CNS). To help fill this knowledge gap, we evaluated the cerebrospinal fluid (CSF) concentrations of fluoroquinolones and carbapenems in patients being treated for TBM. Methods: Serial serum and CSF samples were collected from hospitalized patients being treated for TBM. CSF was collected from routine lumbar punctures between alternating timepoints of 2 and 6h after drug administration to capture early and late CSF penetration. Rich serum sampling was collected after drug administration on day 28 for non-compartmental analysis. Results: Among 22 patients treated for TBM (8 with confirmed disease), there was high use of fluoroquinolones (levofloxacin, 21; moxifloxacin, 10; ofloxacin, 6) and carbapenems (imipenem, 11; meropenem, 6). Median CSF total concentrations of levofloxacin at 2 and 6h were 1.34mg/L and 3.36mg/L with adjusted CSF/serum ratios of 0.41 and 0.63, respectively. For moxifloxacin, the median CSF total concentrations at 2 and 6h were 0.78mg/L and 1.02mg/L with adjusted CSF/serum ratios of 0.44 and 0.62. Serum and CSF concentrations of moxifloxacin were not affected by rifampin use. Among the 76 CSF samples measured for carbapenem concentrations, 79% were undetectable or below the limit of detection. Conclusion: Fluoroquinolones demonstrated high CSF penetration indicating their potential usefulness for the treatment of TBM. Carbapenems had lower than expected CSF concentrations.

Transporter and metabolizer gene polymorphisms affect fluoroquinolone pharmacokinetic parameters.

Tuberculosis (TB) is an infectious disease that occurs globally. Treatment of TB has been hindered by problems with multidrug-resistant strains (MDR-TB). Fluoroquinolones are one of the main drugs used for the treatment of MDR-TB. The success of therapy can be influenced by genetic factors and their impact on pharmacokinetic parameters. This review was conducted by searching the PubMed database with keywords polymorphism and fluoroquinolones. The presence of gene polymorphisms, including UGT1A1, UGT1A9, SLCO1B1, and ABCB1, can affect fluoroquinolones pharmacokinetic parameters such as area under the curve (AUC), creatinine clearance (CCr), maximum plasma concentration (Cmax), half-life (t1/2) and peak time (tmax) of fluoroquinolones.