Identification of Quinolones/Fluoroquinolones Resistance Genes from Staphylococci Strains Isolated at the University Hospital of Brazzaville, Republic of the Congo

Staphylococci strains, like the majority of bacterial strains, have developed the resistance to several antibiotics, including Quinolones and Fluoroquin-olones In the Republic of the Congo, cases of resistance leading to treat-ment failures have been observed during the treatment of staphylococcal infections with antibiotics in hospitals. The objective of this study was to identify the Quinolone/Fluoroquinolone resistance genes from staphylo-cocci strains isolated in hospitals. A total of 51 strains of Staphylococci were isolated, including 16 (31.37%) community strains, and 35 (68.62%) clinical strains. 46 strains of Staphylococcus aureus (S. aureus) and 5 SCNs were identified. A total of 34 DNA fragments from different strains resistant to Quinolones/Fluoroquinolones, including 21 (61.67%) DNA fragments from clinical S. aureus and 13 (38.23%) from community SCN strains were analyzed by the molecular method (genotypic detection) by PCR. The genotypic results made it possible to identify the gyrA, grLA and norA genes and to show that these genes are involved in the resistance of the strains to the various antibiotics used. The grLA gene was the most identified gene with a frequency of 75%. The gyrA and grLA genes have been identified in Staphylococcus aureus and Coagulase Negative Staphy-lococci. The norA gene, on the other hand, has only been identified in Staphylococcus aureus. Two mechanisms are essentially involved in the resistance of Staphylococci to quinolones/Fluoroquinolones, the mecha-nism of resistance by efflux, which takes place thanks to a transmembrane protein coded by the norA gene and by point mutations (substitution and deletion of acids or nucleotides) observed within the protein and nucleic sequences of the chromosomal gyrA and grLA genes.

Subinhibitory Levels of Fluoroquinolones Result in Enrichment of the Membrane Proteome of Staphylococcus aureus

Staphylococcus aureus is a common marine foodborne pathogen.In this study,antibiotics ciprofloxacin and enrofloxacin were used to induce drug-resistance in S.aureus.The differentially expressed proteins(DEPs)were analyzed and compared with those in the bacteria cultured without antibiotics.The primary proteomic alterations were in the levels of cell membrane components and proteins related to lysine and folic acid biosynthesis,which were all significantly up-regulated.The minimal inhibitory concentrations(MIC)for both test drugs were elevated to 10μg m L^(-1)following serial passaging.These results indicated that,for both ciprofloxacin and enrofloxacin,drug-resistance were developed even in the subinhibitory levels and the primary response was a major alteration in the cell membrane proteome.These changes were similar to those observed in S.aureus cultured with super-MIC levels of these antibiotics.The current study provides a theoretical basis for in-depth study of the related changes of marine foodborne pathogens in subinhibitory concentrations that are commonly found in situ.

Determination of fluoroquinolones, sulfonamides, and tetracyclines multiresidues simultaneously in porcine tissue by MSPD and HPLC-DAD

An efficient method is provided to detect simultaneously some important veterinary drugs from different classes in highly complex animal tissue matrix. This method using matrix solid-phase dispersion (MSPD) and high performance liquid chromatography (HPLC) with diode array detection (DAD) is developed to effectively determine two fiuoroquinolones (enoxacin and lomefioxacin), two sulfonamides (sulfanilamide and sulfamethoxazole) and one tetracycline (tetracycline) simultaneously in porcine tissues. In the process, MSPD methodology was used to treat samples, washed by n-hexane to remove lipid, eluted the analytes with acetonitrile–dichloromethane (1:1, v/v). Solvent acetonitrile and solvent acetic acid (0.1%) were combined in a gradient. HPLC–DAD analysis of the tissue samples was performed within 15 min at a fiow rate of 1.0 mL/min. The results showed that a recovery at 0.1, 0.5 and 1.0 mg/g fortification levels ranged from 80.6% to 99.2% with satisfactory relative standard deviations (RSDs) (below 6.1%, nfi3) and the limits of quantitation (LOQ) ranged from 7 mg/kg to 34 mg/kg in porcine tissues. Utilization of the method in successfully simultaneous analysis of porcine tissue incurred with veterinary drug multiresidues is described.

Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation

Solid organ transplantation(SOT)is the best treatment option for end-stage organ disease.Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection,particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis.Active tuberculosis(TB)after SOT is a significant cause of morbidity and mortality.Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection(LTBI)due to the effects of long-term immunosuppressive therapy.Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation.Isoniazid with vitamin B6 supplementation is the treatment of choice.However,liver transplantation(LT)candidates and recipients have an increased risk of isoniazid-induced liver toxicity,leading to lower treatment completion rates than in other SOT populations.Fluoroquinolones(FQs)exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid.In the present review,we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.

Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil:A national survey

AIM To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods.METHODS The primary antibiotic resistance rates of Helicobacter pylori(H. pylori) were determined from November 2012 to March 2015 in the Southern,South-Eastern,Northern,North-Eastern,and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female,mean age 43 years(range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using Geno Type Helico DR(Hain Life Science,Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies,multiplex amplification,and reverse hybridization. RESULTS Clarithromycin resistance was found in 83(16.9%) patients,and fluoroquinolone resistance was found in 66(13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones(P = 0.55 and P = 0.06,respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3%(21/490) of patients. The A2147 G mutation was present in 90.4%(75/83),A2146 G in 16.9%(14/83) and A2146 C in 3.6%(3/83) of clarithromycin-resistant patients. In 10.8%(9/83) of clarithromycin-resistant samples,more than 01 mutation in the 23 S r RNA gene was noticed. In fluoroquinolone-resistant samples,37.9%(25/66) showed mutations not specified by the Geno Type Helico DR test. D91 N mutation was observed in 34.8%(23/66),D91 G in 18.1%(12/66),N87 K in 16.6%(11/66) and D91 Y in 13.6%(9/66) of cases. Among fluoroquinolone-resistant samples,37.9%(25/66) showed mutations not specified by the Geno Type Helico DR test. CONCLUSION The H. pylori clarithromycin resistance rate in Brazil is at the borderline(15%-20%) for applying the standard triple therapy. The fluoroquinolone resistance rate(13.5%) is equally concerning.

QSAR Studies on 7-Substituted Fluoroquinolones

The PM3 and B3LYP methods were employed to calculate the properties of 18 7-substituted fluoroquinolones. The correlation between biological activity （against gram-positive organisms or gram-negative organisms） and structural properties was obtained by using multiple linear regression （MLR） methods： The best model generated correlates the antibacterial activity with EHOMO and QF8 for gram-positive organisms, and EHOMO and dipole moment for gram-negative organisms, respectively. It suggests that the interaction mechanisms ,of fluoroquinolons with gram-positive and gram-negative organisms are different.

Effect and Mechanism Analysis of Solvent on the Electron Transition of Fluoroquinolones Based on Quantum Chemical Calculation

Ciprofloxacin（CIP）, moxifoxacin（MOX） and enrofloxacin（ENR） were selected as typical fluoroquinolones（FQs） to analyze the excitation-enhancing effect and mechanism of solvents on FQs＇ electron transition based on quantum chemical calculations. The UV spectra of three FQs in gas and five different solvents（water, cyclohexane, dimethylsulfoxide, methanol, acetone） were calculated using Gaussian 09 software. The transition mechanisms of FQs＇ main electron transitions were analyzed by natural bond orbital（NBO） theory, and the solvent effect on each electron transition was assessed qualitatively and quantitatively by sensitivity analysis and an established index system. The excitation enhancing mechanism of solvent on electron transitions of FQs was analyzed from the view of photo-induced reactions between solvent and FQs molecules. The results show that there are two main transitions located in the spectrum ranges of 300~380 and 240~300 nm for each FQ in any medium, which are assigned as n →π＊ and π→π＊ electron transitions, respectively. By comparison, the n →π＊ transition is more sensitive to solvent because of the energy transfer between solvent molecules and FQs, but the solvent effect on the π→π＊ transition is stronger than on the n →π＊ transition. The sequence of affected extent of solvent effect on electron transition was CIP 〉 MOX 〉 ENR, and the sequence of solvent effect was water 〉 DMSO 〉 methanol 〉 acetone 〉 cyclohexane（stronger solvent effect with increasing the dielectric constant of solvent）. From the view of photo-induced reactions, the reaction between FQs＊T1 and solvent＊T1 has the decisive regulatory effect on the n →π＊ transition of FQs in solvent, and the reaction between FQsS0 and solvent＊TI has an enhancing effect on the π→π＊ transition.

Study on Rapid Detection of Tetracyclines,Fluoroquinolones and Sulfonamides in Milk

Aiming at the market demand for rapid detection of tetracyclines,fluoroquinolones and sulfonamides in milk,a golloidal gold immunochromatography test strip for simultaneous detection of tetracyclines,fluoroquinolones and sulfonamides in milk was prepared based on the principle of competitive inhibition immunochromatography. The performance indicators of the test strip were verified. The results showed that the test strip can simultaneously detect 4 tetracyclines,13 fluoroquinolones and 13 sulfonamides,and the detection limits all can meet the national residue limits; the tests strip exhibited false positive rate≤5% and false negative rate = 0; and no cross-reaction with other drugs was commonly found in milk,indicating good specificity. The method is simple,rapid,and has low cost and easy popularization. It provides a means for realizing on-site rapid detection and is of important practical significance to guarantee of safety of milk and dairy products in China.

Effective extraction of fluoroquinolones from water using facile modified plant fibers

In this study,ecofriendly and economic carboxy-terminated plant fibers(PFs)were used as adsorbents for the effective in-syringe solid phase extraction(IS-SPE)of fluoroquinolone(FQ)residues from water.Based on the thermal esterification and etherification reaction of cellulose hydroxy with citric acid(CA)and sodium chloroacetate in aqueous solutions,carboxy groups grafted onto cotton,cattail,and corncob fibers were fabricated.Compared with carboxy-terminated corncob and cotton,CA-modified cattail with more carboxy groups showed excellent adsorption capacity for FQs.The modified cattail fibers were reproducible and reusable with relative standard deviations of 3.2%-4.2% within 10 cycles of adsorptiondesorption.A good extraction efficiency of 71.3%-80.9% was achieved after optimizing the extraction condition.Based on carboxylated cattail,IS-SPE coupled with ultra-performance liquid chromatography with a photodiode array detector was conducted to analyze FQs in environmental water samples.High sensitivity with limit of detections of 0.08-0.25 mg/L and good accuracy with recoveries of 83.8%-111.7% were obtained.Overall,the simple and environment-friendly modified waste PFs have potential applications in the effective extraction and detection of FQs in natural waters.

Colloidal Gold Test Strip for the Detection of Fluoroquinolones in Foods Using an Analyzer

A test strip was developed to rapidly detect fluoroquinolones in foods by colloidal gold immunochromatography method in combination with a food safety analyzer. The results showed that the test strip has the detection sensitivity of 20 μg/L for enrofloxacin, sarafloxacin, difloxacin, ofloxacin, norfloxacin, ciprofloxacin, pefloxacin, flumequine and danofloxacin, and the detection sensitivity of 40 μg/L for enoxacin and oxolinic acid. The test strip consumes only 10 min for detection, and the false positive rate and the false negative rate are both zero. The test strip can accurately, reliably and easily detect residual fluoroquinolones in foods, and is suitable for on-site detection of a large number of samples.

Sensitive Spectrofluorimetric Method for Determination of Fluoroquinolones through Charge-Transfer Complex Formation

A sensitive spectrofluorimetric method was developed for determination of ciprofloxacin (CPFX), levofloxacin (LEV), gatifloxacin (GAT) and moxifloxacin (MOX) in pure, commercial formulations, human urine and plasma. The method is based on charge-transfer (CT) complex with chloranilic acid. Fluorescence intensity of the complexes was measured at emission wavelength ranging from 445-492 nm with excitation wavelengths from 285-330 nm. At optimum experimental conditions, a linear calibration plot was obtained in the concentration range of 20-1000 ng·mL-1, 60-320 ng·mL-1, 20-800 ng·mL-1 and 20 -00 ng·mL-1 for CPFX, LEV, MOX and GAT, respectively with good correlation coefficient in the range of 0.9929-1.0 in methanolic medium. The limit of detection and limit of quantification were found to be 5 ng·mL-1 and 18 ng·mL-1 for CPFX, 12 ng·mL-1 and 40 ng·mL-1 for LEV, 8 ng·mL-1 and 19 ng·mL-1 for MOX, 6 ng·mL-1 and 19 ng·mL-1 for GAT, respectively. The method was found free of interferences from excipients used as additive in pharmaceutical preparations, some common cations and compounds present in urine and plasma as well as co-administered analgesic, vitamins and other drugs. The method was successfully applied for quantification of selected fluoroquinolones in commercial formulations and also in spiked human urine and plasma samples with percent recoveries of 100.0 ± 1.56 and 100.2 ± 1.29 respectively.

Analysis on Influential Factors for Anti-Infection Efficacy of Fluoroquinolones

Objective: To investigate factors contributed to anti-infection efficacy of fluoroquinolones (FQNS), and ultimately to provide guidelines for the application of such drugs. Methods: Clinical data of 519 infected patients who were treated with fluoroquinolones were analyzed retrospectively. According to the therapeutic efficacy of the drugs, cases were divided into 3 groups: clinical inefficient, improved and cured. 11 potential factors were investigated. The data were analyzed through logistic regression analysis to determine the main factors which influence therapeutic effects. Results: Ordinal logistic regression revealed that age (OR = 0.979, 95% CI: 0.969, 0.989), a variety of medicine (moxifloxacin-OR = 3.465, 95% CI: 1.396, 8.601;levofloxacin-OR = 4.605, 95% CI: 1.971, 10.760;ciprofloxacin-OR = 3.220, 95% CI: 1.089, 9.552;compared to lomefloxacin) (levofloxacin-OR = 2.591, 95% CI: 1.130, 5.944;compared to fleroxacin) and site of infection (respiratory system-OR = 3.016, 95% CI: 1.737, 5.236;urological system-OR = 4.077, 95% CI: 1.981, 8.391;digestive system-OR = 3.740, 95% CI: 1.849, 7.565) are main factors which influence the efficacy. Conclusion: Fluoroquinolones are more effective in the treatment of bacterial infection within drug’s indications in young population. Variety, dosage and intervals of the drugs should be adjusted according to disease condition.

Inhibitory Effects of Several Fluoroquinolones on Feline CYP1A and 3A in Hepatic Microsomes

In this study, the effects of several fluoroquinolones (FQs), such as Ciprofloxacin (CPFX);Orbifloxacin (OBFX);Norfloxacin (NFX);Ofloxacin (OFX);and Enerofloxacin (EFX) on activities of both Cytochrome P450 1A (CYP1A) and Cytochrome P450 3A (CYP3A) of feline microsomes by in vitro tests were studied. Ethoxyresorufin O-deethylation (EROD) and Midazolam 1' hydroxylation and 4-hydroxylation (MDZ1'H and MDZ4H) were analyzed by High Performance Liquid Chromatography (HPLC). All the FQs inhibited the reactions by a competitive or noncompetitive and irreversible manner. The inhibitory constants (Ki) were as followings: CYP1A;ranged from 0.12 to 1.23 mM for NFX, OBFX, EFX, CPFX, OFX and CYP3A, for MDZ1'H;ranged from 5.8 to 35 and MDZ4H;9 to 29 mM, respectively. As these values are higher by 24 to 200-times of given single clinical dose of serum levels after application of FQs. It indicates that if co-administrated with these FQs by reversible inhibitory manner, the inhibition of CYP1A and CYP3A effect on CYP1A and 3A actions is not very significant to cause drug interaction with above mentioned enzyme substrates. Out of the FQs tested, CPFX and NFX for CYP1A, and CPFX for CYP3A showed irreversible inhibitory effects (time-dependent), so it has been concluded that these drugs may cause drug-drug interaction by accumulation, when they are repeatedly administrated. Since EFX is biotransformed to CPFX by the liver, it could have the identical risk too.

Resistance to Fluoroquinolones and Other Antimicrobials in Culture-Positive <i>Salmonella typhi</i>Isolates in Gulbarga, South India

Background: Typhoid fever is a major public health concern in developing countries. The upsurge in the occurrence of bacterial isolates that are resistant to nalidixic acid;with reduced susceptibility to ciprofloxacin in typhoidal Salmonellae constitutes a challenge to the clinician. Methods: In order to better understand the epidemiology of Salmonella infections in South India, Salmonella typhi isolates were screened from various healthcare centers. Salmonella isolates were identified by using standard phenotypic, serological, antibiotic susceptibility and molecular methods. Results: Among a total of 100 S. typhi isolates 9% were found to be multidrug resistant and 30% were nalidixic acid resistant. Isolates with reduced susceptibility to ciprofloxacin displays single base mutations in the gyrA gene. A very low rate of 1% resistance was found to ciprofloxacin. The only one isolate with ciprofloxacin MIC ≥ 4 μg/ml also showed single mutation in the QRDR of the gyrA gene in S. typhi (GenBank accession no. HQ176349-HQ176368). Conclusions: A very low rate of nalidixic acid resistance with reduced susceptibility to ciprofloxacin was observed in comparison to other endemic areas in isolates of S. typhi from Gulbarga, South India, with steadily increasing NAR S. typhi but decreasing MDR isolations over the study period. This is most likely due to an increased use of ciprofloxacin as a first line drug of choice over more traditional antimicrobial agents for the treatment of typhoid fever.

GyrA and ParC Gene Mutation of Clinically Isolated Fluoroquinolones-resistant Strain of Salmonella

Nine strains resistant to five fluoroquinolones （Ciprofloxacin, Ofloxacin, Enrofloxacin, Danofloxacin, Sarafloxacin） were isolated from clinical samples and extracted the chromosomal DNA of these strains. Designed primers to amplify the Quinolone-resistance-determining region （QRDR） of gyrA and par（？,, then the PCR products were sequenced and analyzed. In comparision with NCTC5776, a single mutation was found at base 371 in gyrA of strain 38 which changed from C to T, and a single mutation was found at base 350 in gyrA of strain 60 which changed from A to C. No mutation was found in gyrA of the rest The mutation of strain 38 led to an amino acid substitution of Arg99Cys and the mutation of 60 led to an amino acid substitution of Met 92 Leu. No mutation was found in parC QRDR of all the isolates. These results indicats that the DNA gyrase will be the primary target to salmonella of fluoroquinolone.

Comparative clinical study of conjunctival toxicities of newer generation fluoroquinolones without the influence of preservatives

AIMTo compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives.METHODSIn a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a primary pterygium were enrolled, and divided randomly into three groups (levofloxacin 0.5%, gatifloxacin 0.3%, and moxifloxacin 0.5%). After pterygium surgery with the same conjunctival autograft technique, each patient maintained a regimen with a randomly assigned fluoroquinolone eye drop. Patients were examined every other day after surgery until the epithelium had completely healed. Photos were taken and used to measure the area of residual epithelial defects. Conjunctival healing time and speed (initial defect area/healing time (mm2/d) compared in each group using Kruskal-Wallis tests.RESULTSThere were no significant differences in mean age, gender, and conjunctival defect size of the donor site between these groups. However, the mean of conjunctival healing time and speed were statistically different in each group. The mean of conjunctival epithelial healing time was 8.93±2.69d (levofloxacin group), 10.31±2.96d (gatifloxacin group), and 13.50±4.10d (moxifloxacin group), P=0.006. The mean conjuctival epithelial healing speed was 6.18±1.39 mm2/d (levofloxacin group), 5.52±1.68 mm2/d (gatifloxacin group), and 4.40±1.30 mm2/d (moxifloxacin group), P=0. 003.CONCLUSIONWithout the influence of preservatives, levofloxacin and gatifloxacin might be less toxic to the regeneration of conjunctival epithelial cells and cause a faster conjunctival wound healing relative to moxifloxacin.

Spectroscopic Investigations for the Six New Synthesized Complexes of Fluoroquinolones and Quinolones Drugs With Nickel(Ⅱ) Metal Ion:Infrared and Electronic Spectroscopy

Quinolone has a broad spectrum of synthetic antibiotics with a strong therapeutic effect and quinolone is a term used for chemical treatments used to treat a powerful bacteria.Quinolones are divided into 4 generations according to the bacterial spectrum,the majority of quinolones used clinically belong to the sub fluoroquinolones group,which has a fluorine atom linked to the central ring system,usually on its carbon atom 6 or 7.Herein in this article,six new nickel(Ⅱ)complexes(Ⅰ—Ⅵ)have been synthesized in aqueous alkaline media at pH ranged 8-9,the chemical reactions take place between levofloxacin(HLEV),lomefloxacin(HLOM),nalidixic acid(HNLA),oxolonic acid(HOXO),pipemidic acid(HPIP),and pefloxacin mesylate(HPEF)with nickel(Ⅱ)nitrate hexahydrate.The microanalytical(percentage of carbon,hydrogen and nitrogen),molar conductance(Λm),Infrared(FTIR)spectra,electronic(UV-Vis)spectra,and effective magnetic moment instrumentals were used to identify the suggested structures and their surface morphology.According the analytical and spectroscopic analyses,the stoichiometry between nickel(Ⅱ)metal ion and drug ligands was found to be 1∶2 with general formula as[Ni(L)_(2)(H_(2)O)_(2)]·x H_(2)O(L=LEV(Ⅰ),LOM(Ⅱ),NAL(Ⅲ),OXO(Ⅳ),PIP(V),and PEF(Ⅵ);x=2 or 4).By the comparison between FTIR spectra of quinolone drugs and their complexes,it can be deduced that all the drug ligands act as a bidentate chelates through oxygen atoms of pyridine ring and carboxylate group.The electronic configuration of all synthesized nickel(Ⅱ)complexes were octahedral geometry which confirmed based on the values of magnetic susceptibility and the electronic transition bands.

Cloning and Sequence Analysis of gyrB Gene of Fluoroquinolones-resistant Salmonella Isolated from Chickens

Nine strains resistant to five fluoroquinolones (Ciprofloxacin, Ofloxacin, Enrofloxacin, Danofloxacin, Sarafloxacin) were isolated from clinical samples and extracted the chromosomal DNA of these strains. Designed primers to amplify the Quinolone-resistance-determining region(QRDR) of gyrB gene, then the PCR products were cloned and the sequence was analyzed. In comparison with the standarded strain NCTC5776, no mutation was found in the QRDR of gyrB gene of all resistant strains. The result indicated that the QRDR of gyrB has little relationship with fluoroquinolone resistance to salmonella.

Fluoroquinolones Reported Hepatotoxicity

Fluoroquinolones are known to be safe and well tolerated. They are said to have the widest clinical acceptability when compared with other antibiotics. Their reported side effects include gastrointestinal tract, central nervous system effect and blood disorder. Rare side effects include phototoxicity, hypersensitivity, convulsion, psychosis, tendinitis, hypoglycemia, cardiotoxicity and nephrotoxicity. Some of these side effects have led to the withdrawal of some fluoroquinolones like travofloxacin from clinical use in some countries. Of recent fluoroquinolones induce cardiotoxicity and hepatotoxicity has gain attention. Due to increasing reports on fluoroquinolones associated hepatotoxicity in experimental Animal studies and clinical experience. This study reviews reported hepatotoxicity associated with clinically used fluoroquinolones and their safety profile on liver function. It was observed that some fluoroquinolones may have hepatotoxic potential. Reported fluoroquinolones induce hepatotoxicity manifested as hepatitis, pancreatis, jaundice, liver injury and hepatic failure. Most reported cases of fluoroquinolones induced hepatotoxicity were marked by elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, direct bilirubin, total bilirubin and prolong prothrobin time. In some reported cases liver biopsy revealed hepatocellular damage, necrosis and degeneration. Mixed inflammatory infiltrates containing eosinophils, portal edema, bile ductular proliferation and lobular cholestasis were also observed in some cases. The mechanism of fluoroquinolones induce hepatotoxicity may involve generation of oxidative radicals in the liver during drug metabolism which induces DNA damage, mitochondrial damage and gene regulation leading to hepatocellular damage. This was observed in travofloxacin which enhances hepatic mitochondrial peroxynitrite stress in mice with underlying increased basal levels of super oxide leading to the disruption of critical mitochondrial enzyme and gene regulation. This mechanism could be associated with fluoroquinolones mechanism of action which includes DNA damage. In conclusion fluoroquinolones are well tolerated but some may have hepatotoxic potential. Most clinically used fluoroquinolones are relatively safe but Clinicians should consider patients liver function status before fluoroquinolones clinical recommendation. In some cases biochemical parameters associated with liver function should be monitored in patients with impaired liver function.

An insight into the removal of fluoroquinolones in activated sludge process:Sorption and biodegradation characteristics

The detailed sorption steps and biodegradation characteristics of fluoroquinolones （FQs） including ciprofloxacin, enrofloxacin, lomefloxacin, norfloxacin, and ofioxacin were investigated through batch experiments. The results indicate that FQs at a total concentration of 500 μg/L caused little inhibition of sludge bioactivity. Sorption was the primary removal pathway of FQs in the activated sludge process, followed by biodegradation, while hydrolysis and volatilization were negligible. FQ sorption on activated sludge was a reversible process governed by surface reaction, Henry and Freundlich models could describe the FQ sorption isotherms well in the concentration range of 100-300 μg/L. Thermodynamic parameters revealed that FQ sorption on activated sludge is spontaneous, exothermic, and enthalpy-driven. Hydrophobicity-independent mechanisms determined the FQ sorption affinity with activated sludge. The zwitterion of FQs had the strongest sorption affinity, followed by cation and anion, and aerobic condition facilitated FQ sorption. PQs were slowly biodegradable, with long half-lives （〉100 hr）. FQ biodegradation was enhanced with increasing temperature and under aerobic condition, and thus was possibly achieved through co-metabolism during nitrification. This study provides an insight into the removal kinetics and mechanism of FQs in the activated sludge process, but also helps assess the environmental risks of FQs resulting from sludge disposal.