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.

Survey of Tetracyclines, Sulfonamides, Sulfamethazine, and Quinolones in UHT Milk in China Market

This study surveyed 180 samples of ultra high temperature （UHT） milk of four top Chinese dairy brands collected in the 25 cities in China in June 2011, and assessed their contamination with antibiotics, using the ELISA method. The percentages of tetracyclines, sulfonamides, sulfamethazine, and quinolones detected in the samples were 0, 16.7, 40.6, and 100%, respectively. The maximum concentrations of the tetracyclines, sulfonamides, sulfamethazine and quinolones in UHT milk samples were 〈1.5, 26.2, 22.6, and 58.8 μg kg-1, respectively. None of the samples exceeded the maximum residue levels （MRLs） for these four veterinary drugs, according to the regulations set by China, the European Union （EU） and the Codex Alimentarius Commission （CAC）.

Synthesis of 6,8-dichloroquinolones utilizing new method and evaluation of their antibacterial activities

Several 6,8-dichloroquinolone analogues were synthesized from the key intermediate compound of 2,3,4,5-tetrachlorobenzene carbonyl chloride, which was obtained from the starting material of tetrachlorophthalic anhydride. Their in vitro antibacterial activities were evaluated. As a result of this study, compounds 21e and 21d were twofold more potent than ciprofloxacin （CPFX） and norfloxacin （NFLX） against Staphylococcus aureus-9, and with the same potent as CPFX and NFLX while against Escherichia coli-2, but were less potent than references in against Pseudomonas aeruginosa-17.

Fourth-generation quinolones in the treatment of Helicobacter pylori infection: a meta-analysis

AIM To assess the efficacy and safety of fourth-generation quinolones for helicobacter pylori(h. pylori) eradication, we conducted this systematic review and metaanalysis of randomized clinical trials. METHODS Major literature databases(Pub Med, EMBASE and the Cochrane Central Register of Controlled Trials) were searched for relevant articles published prior to February 2018. We performed a meta-analysis of all randomized clinical trials that examined the efficacy of h. pylori eradication therapies and included fourthgeneration quinolones in the experimental arm. Subgroup analyses by regions and different types of fourth-generation quinolones were also performed.RESULTS Ten studies including a total of 2198 patients were assessed. A meta-analysis of randomized controlled trials showed that the eradication rate of therapies containing non-fourth-generation quinolones was significantly lower than that of therapies containing fourth-generation quinolones by intention-to-treat(ITT) analysis [75.4% vs 81.8%; odds ratio(OR) = 0.661; 95% confidence interval(CI): 0.447-0.977; P = 0.038]. This analysis also showed that the eradication rate of the therapies containing non-fourth-generation quinolones was inferior to that of therapies containing fourth-generation quinolones by perprotocol analysis(79.1% vs 84.7%; OR = 0.663; 95%CI: 0.433-1.016; P = 0.059). Moreover, the occurrence of side effects was significantly different between the control and experimental groups by ITT analysis(30.6% vs 19.5%; OR = 1.874; 95%CI: 1.120-3.137; P = 0.017). The sub-analyses also showed significant differences in moxifloxacin therapies vs other fourth-generation quinolone therapies(84.3% vs 71.9%) and in Asian vs European groups(76.7% vs 89.1%).CONCLUSION Therapies containing fourth-generation quinolones achieved a poor eradication rate in the treatment of h. pylori infection. Such regimens might be useful as a rescue treatment based on antimicrobial susceptibility testing. Different antibiotics should be chosen in different regions.

A Facile Synthesis of 4-Alkyl-2-Quinolones

The derivatives of 4-alkyl-2-quinolones possess a variety of biological activities. The general synthetic method of 4-alkyl-2-quinolones is the reaction of aryl amines with β-ketoesters to form β-ketoamides, which are then heated in concentrated sulfuric acid to complete the ring closure. Although a number of its 4-methyl and aryl derivatives have been obtained, other 4-alkyl-2-quinolones are rarely mentioned for lack of a convenient method to prepare the appropriate β-ketoesters used in condensation.

Rapid Determination of Residual Quinolones in Honey Samples by Fast HPLC with an On-Line Sample Pretreatment System

A method of on-line pretreatment coupled to HPLC with fluorescence detection was developed and validated for the determination of nine quinolones in honey samples. This method simplified the complicated process of sample pretreatment and reduced sample treatment time. Recovery of the quinolones was between 92% - 101% for spiked honey samples. The limit of detection was 0.22 - 3.78 ng/mL (signal/noise ratio = 3). There was good linear correlation between HPLC peak area and concentration of the quinolones, with a linear range of 1.0 - 100.0 ng/mL and correlation coefficients >0.9997. The method proposed was validated for detecting quinolones in honey samples.

Detection of Shigella gyrA mutations and correlations between gyrA mutations and quinolones resistance

118 clinical strains of Shigella were serotyped, in which 116 strains were tested to be S. flexneri. The susceptibilities of the S .flexneri strains to quinolones were measured by the disk-diffusion method. It was found that most S .flexneri strains were susceptible to norfloxacin and ciprofloxacin, but resistant to nalidixic acid. To study the correlation between gyrA mutations and quinolones resistance, a fragment within the gyrA gene was amplified by PCR. The SSCP （Single-Strand Conformation Polymorphism） analysis was applied to detect mutations in PCR products of different strains. The mutations were then confirmed by DNA sequencing. Altogether, two types of mutation were revealed, in which one type was single mutation （ C42-T）, and the other was double mutations （ C42-T and A54- G）. By statistical analysis, C42-T （encoding Ser83-keu substitution） was shown to have correlation with nalidixic-acid resistance in the clinical strains of Shigella, while A54-G （encoding Asp87-Gly substitution） was shown to have correlations with both norfloxacin resistance and ciprofloxacin resistance.

The synthesis and activity in vitro of a series of 8-difluoromethoxy quinolones: Analogues of gemifloxacin

7-[4-（Aminomethyl）-3-（methoxyimino）pyrrolidin- 1-yl]- 1-cyclopropyl-6-fluoro-8-difluoromethoxy- 1,4-dihydro-4-oxoquino- line-3-carboxylic acid and its analogues have been prepared and evaluated for antibacterial activity in vitro.

Synthesis of Quinolone Analogues: 7-[2-Aminomethylaziridin-l-yl]-quinolones

New quinolone derivatives of 7-[2-aminomethylaziridin-l-yl]quinolone-3-carboxylic acids were synthesized. The structures of these compounds were characterized by IH NMR and HRESI-MS.

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.

The Synthesis and Activity in vitro of a Series of 5-Amino-8-methoxyquinolones

A series of 1-cyclopropyl-5-amino-6-fluoro-8-methoxyquinoline-3-carboxylic acidshave been prepared and evaluated for antibacterial activity in vitro.

Synthesis of Quinolone Analogues: 7-[(2S,4R)-2-Aminomethyl-4- hydroxypyrrolidin-1-yl] Quinolones

New quinolone derivatives of 7-[(2S, 4R)-2-aminomethyl-4-hydroxypyrrolidin-1-yl] quinolone-3-carboxylic acids were synthesized by condensation of 7-halo substituted quinolone- 3-carboxylic acids with (2S, 4R)-2-aminomethyl-4-hydroxypyrrolidine. These compounds were characterized by FAB-MS and 1H NMR.

Solid Phase Synthesis of 4(1H)Quinolones from Resin-Bound Cyclic Malonic Ester

The solid phase synthesis of 4 (1H) quinolones has been reported.

Determination and Correlation of 1-Octanol/Water Partition Coefficients for Six Quinolones from 293.15 K to 323.15 K

A shake-flask method was used to determine 1-octanol/water partition coefficients of ofloxacin, norfloxacin, lomefloxacin, ciprofloxacin, pefloxacin and pipemidic acid from 293.15 K to 323.15 K. The results show that 1-octanol/water partition coefficient of each quinolone increased with the increase of temperature. Based on the fluid phase equilibrium theory, the thermodynamic relationship of 1-octanol/water partition coefficient depending on the temperature was proposed, and the changes of enthalpy, entropy, and Gibbs free energy for quinolones partitioning in 1-octanol/water were determined, respectively. Quinolones molecules partitioning in 1-octanol/water was mainly an entropy driving process, during which the order degree of system decreased. The temperature effects of 1-octanol/water partition coefficient were investigated. The results show that its magnitude is the same as the values in the literature.

C—F Bond Insertion into Indoles with CHBr_(2)F:An Efficient Method to Synthesize Fluorinated Quinolines and Quinolones

A mild and practical method for synthesizing fluorinated quinoline derivatives,which have a wide range of applications in pharmaceuticals,materials,and organic synthesis,was described through C—F bond insertion into indoles using CHBr_(2)F.The simple conditions,readily availability of CHBr_(2)F,as well as the versatility of the transformations make this strategy very powerful in synthesizing 3-fluoroquinoline and 3-fluoroquinolone.The mechanistic studies reveal that bromofluorocarbene generated in-situ under basic condition was the key intermediate.

Brucellosis: An Outpatient Non-Probability Retrospective Study of 199 Patients

Background: A descriptive study of the characteristics of brucellosis patients in Jordan and antimicrobial therapy. Methods: In an outpatient study, records were reviewed between July 2016 and April 2024 and electronically saved. Brucella diagnosis was based on epidemiological factors, risk factors, the standard tube agglutination test (STA), and blood or tissue cultures. Records were uploaded into a spreadsheet and imported into the R-Program. A 2-sample Kruskal-Wallis rank sum tested the equality of proportions between two treatment regimens for all available and spondylodiscitis, P Results: Two hundred patients with Brucellosis were analyzed;males 106 (53%) with a mean age of 46.8 years, and females 94 (47%) with a mean age of 48.1 years. Patients from Jordan were 159 (79.9%), and the Arabian Peninsula 25 (12.6%). Brucellosis was a non-focal presentation in 121 (60.50%) patients, spondylodiscitis in 64 (32.0%), and sacroiliitis in 7 (3.5%). Spondylodiscitis involved lumbar 48 (75.0%), thoracic 11 (17.20%), and cervical 5 (7.8%). STA was a common diagnostic method (188, 94%). Risk factors included cheese 80 (47.3%), cattle, small ruminants, and she-camel milk 37 (21.89%), dairy products 28 (16.57%), meat 9 (05.33%), and working with cattle 10 (05.92%). ESR was highest in spondylodiscitis (mean of 54.5). Imaging studies commonly requested were MRI and Bone scans. Doxycycline/Rifampin were mostly prescribed antimicrobials. Conclusion: There is no clear guidance on brucella treatment. In endemic areas, brucella is still a concern. Population education must be a priority. Support for randomized trials addressing antimicrobials and durations is extremely needed.

Gold nanoparticle-based paper sensor for ultrasensitive and multiple detection of 32 （fluoro）quinolones by one monoclonal antibody

For rapid and simultaneous detection of （fluoro）quinolones, a broadly specific monoclonal antibody （mAb） that recognizes 32 （fluoro）quinolone antibiotics was prepared using a mixture of a norfloxacin derivative and a sarfloxacin derivative as the hapten. An immunochromatographic strip based on gold nanoparticles （AuNPs） was then assembled with goat anti-mouse antibody and antigen （sarfloxacin coupled to ovalbumin）, used to form the C line and T line, respectively. This antigen competes with the （fluoro）quinolones in a sample incubated with mAbs labeled with AuNPs. The strip can detect 32 （fluoro）quinolones including oxolinic acid, nalidixic acid, miloxacin, pipemidic acid, piromidic acid, rosoxacin, cinoxacin, norfloxacin, pefloxacin, lomfloxacin, enofloxacin, fleroxacin, ciprofloxacin, enrofloxacin, dafloxacin, orbifloxacin, sparfloxacin, gemifloxacin, besifloxacin, balofloxacin, gatifloxacin, moxifloxacin, nadifloxacin, ofloxacin, marbofloxacin, flumequine, pazufloxacin, prulifloxacin, sarafloxacin, difloxacin, trovafloxacin, and tosufloxacin in milk within 10 min with the naked eye. The cut-off values of the strip range from 1 to 100 ng/mL and the limits of detection are 0.1- 10 ng/mL. The strip does not cross-react with antibiotics including tetracycline, sulfamethazine, ampicillin, erythromycin, aflatoxin B1, or gentamicin. In short, this immunochromatographic strip is a very useful tool for the primary screening of （fluoro）quinolones in milk.

耐药结核病的药物治疗及研究进展

近年来,耐药结核病的流行越来越严重,全球范围内的耐药结核病对各国的公共卫生已构成了严重威胁,各国的专家学者都在关注耐药结核病的产生原因,并开展大量的研究遏制耐药结核病的发展。本文检索并分析了关于耐药结核病产生以及治疗药物的相关报道,对耐药结核病的发生机制、诊断方法以及最新的治疗药物报道进行了综述。

Distribution of gyrA mutations in fluoroquinolone-resistant Helicobacter pylori strains

AIM:To investigate the resistance of Helicobacter pylori(H.pylori) to ciprofloxacin(CIP),levofloxacin(LVX) and moxifloxacin(MOX) in the Beijing area and to elucidate the resistance mechanisms.METHODS:Seventy-nine H.pylori clinical strains,isolated from patients who had undergone upper gastrointestinal endoscopy in Peking University First Hospital from 2007 to 2009,were tested for their susceptibility to CIP,LVX and MOX using the E-test method.H.pylori strain 26695 was included in the susceptibility testing as a control strain.According to the minimal inhibitory concentration(MIC) values,a strain was classified as resistant to CIP,LVX or MOX when the MIC was > 1 μg/mL.We amplified by polymerase chain reaction(PCR) and sequenced the quinolone resistance-determining regions of the gyrA and gyrB genes from 29 quinolone-resistant and 16 quinolone-susceptible H.pylori strains selected at random.RESULTS:In this study,the resistance rates of H.pylori to CIP,LVX or MOX were 55.7%(44/79),and the primary resistance rates were 26.6%(21/79).Patients with secondary resistance had received LVX in previous eradication treatments,but not MOX or CIP.Forty-five strains,including 29 CIP,LVX or MOX-resistant strains(MIC:1.5-32 μg/mL) and 16 susceptible strains,were selected randomly from the 79 strains and used in PCR analysis.Among these 45 strains,27 resistant strains had mutations in the gyrA gene,including 11 strains with mutations corresponding to Asp-91(MIC:2-32 μg/mL),one of which also had a mutation corresponding to Val-150,and 16 strains had mutations at Asn-87(MIC:4-32 μg/mL),three of which also had mutations corresponding to Arg-140 or Val-150.In addition,Arg-140,Val-150 or Ala-97 mutations were separately detected in three susceptible strains.Analysis of the gyrB gene showed that one strain of low resistance had a mutation corresponding to Ser-457 that coexisted with an Asp-91 mutation.There was a significant difference in the occurrence of mutations in the gyrA gene between CIP,LVX and MOX-resistant and-susceptible strains(P < 0.05),but 2 resistant strains were found to possess no quinolone resistance-determining region mutations.CONCLUSION:Resistance is primarily mediated through point mutations in gyrA.Whether other mechanisms are responsible for resistance in strains without mutations in the QRDR should be detected.

Antibiotic prophylaxis in patients with cirrhosis: Current evidence for clinical practice

Patients with cirrhosis show an increased susceptibility to infection due to disease-related immune-dysfunction.Bacterial infection therefore represents a common,often detrimental event in patients with advanced liver disease,since it can worsen portal hypertension and impair the function of hepatic and extrahepatic organs.Among pharmacological strategies to prevent infection,antibiotic prophylaxis remains the first-choice,especially in high-risk groups,such as patients with acute variceal bleeding,low ascitic fluid proteins,and prior episodes of spontaneous bacterial peritonitis.Nevertheless,antibiotic prophylaxis has to deal with the changing bacterial epidemiology in cirrhosis,with increased rates of gram-positive bacteria and multidrug resistant rods,warnings about quinolonesrelated side effects,and low prescription adherence.Short-term antibiotic prophylaxis is applied in many other settings during hospitalization,such as before interventional or surgical procedures,but often without knowledge of local bacterial epidemiology and without strict adherence to antimicrobial stewardship.This paper offers a detailed overview on the application of antibiotic prophylaxis in cirrhosis,according to the current evidence.