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Concept: Quinolone

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BACKGROUND:Case reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin-angiotensin-system blockers. METHODS:We formed a nested cohort of men aged 40-85 enrolled in the United States IMS LifeLink Health Plan Claims Database between 2001 and 2011. We defined cases as men admitted to hospital for acute kidney injury, and controls were admitted to hospital with a different presenting diagnosis. Using risk-set sampling, we matched 10 controls to each case based on hospital admission, calendar time (within 6 wk), cohort entrance (within 6 wk) and age (within 5 yr). We used conditional logistic regression to assess the rate ratio (RR) for acute kidney injury with current, recent and past use of fluoroquinolones, adjusted by potential confounding variables. We repeated this analysis with amoxicillin and azithromycin as controls. We used a case-time-control design for our secondary analysis. RESULTS:We identified 1292 cases and 12 651 matched controls. Current fluoroquinolone use had a 2.18-fold (95% confidence interval [CI] 1.74-2.73) higher adjusted RR of acute kidney injury compared with no use. There was no association between acute kidney injury and recent (adjusted RR 0.87, 95% CI 0.66-1.16) or past (RR 0.86, 95% CI 0.66-1.12) use. The absolute in crease in acute kidney injury was 6.5 events per 10 000 person-years. We observed 1 additional case per 1529 patients given fluoroquinolones or per 3287 prescriptions dispensed. The dual use of fluoroquinolones and renin- angiotensin-system blockers had an RR of 4.46 (95% CI 2.84-6.99) for acute kidney injury. Our case-time-control analysis confirmed an increased risk of acute kidney injury with fluoroquinolone use (RR 2.16, 95% CI 1.52-3.18). The use of amoxicillin or azithro mycin was not associated with acute kidney injury. INTERPRETATION:We found a small, but significant, increased risk of acute kidney injury among men with the use of oral fluoroquinolones, as well as a significant interaction between the concomitant use of fluoroquinolones and renin- angiotensin-system blockers.

Concepts: Logistic regression, Acute kidney injury, Confounding, Trigraph, Gh, Case, Statistical terminology, Quinolone

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There is a general lack of understanding about how communities of bacteria respond to exogenous toxins such as antibiotics. Most of our understanding of community-level stress responses comes from the study of stationary biofilm communities. Although several community behaviors and production of specific biomolecules affecting biofilm development and associated behavior have been described forPseudomonas aeruginosaand other bacteria, we have little appreciation for the production and dispersal of secreted metabolites within the 2D and 3D spaces they occupy as they colonize, spread, and grow on surfaces. Here we specifically studied the phenotypic responses and spatial variability of alkyl quinolones, including thePseudomonasquinolone signal (PQS) and members of the alkyl hydroxyquinoline (AQNO) subclass, inP. aeruginosaplate-assay swarming communities. We found that PQS production was not a universal signaling response to antibiotics as tobramycin elicited an alkyl quinolone response while carbenicillin did not. We also found that PQS and AQNO profiles in response to tobramycin were markedly distinct and influenced these swarms on different spatial scales. The distribution of alkyl quinolones varied by several orders of magnitude within the same swarm. At some tobramycin exposures,P. aeruginosaswarms produced alkyl quinolones in the range of 150 µM PQS and 400 µM AQNO that accumulated as aggregates. Our collective findings show that the distribution of alkyl quinolones can vary by several orders of magnitude within the same swarming community.  More notably, our results suggest that multiple intercellular signals acting on different spatial scales can be triggered by one common cue.

Concepts: Bacteria, Antibiotic resistance, Pseudomonas aeruginosa, Signal, Antibiotic, Behavior, Quinolone, Swarm

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The fate of chlortetracycline (CTC), sulfadiazine (SDZ) and ciprofloxacin (CIP) during composting of swine manure and their effect on composting process were investigated. Swine manure was spiked with antibiotics, mixed with saw dust (1:1 on DW basis) and composted for 56d. Antibiotics were spiked to a final concentration of 50mg/kg CTC+10mg/kg SDZ+10mg/kg CIP (High-level) or 5mg/kg CTC+1mg/kg SDZ+1mg/kg CIP (Low-level), and a control without antibiotics. Antibiotics at high concentrations delayed the initial decomposition that also affected the nitrogen mineralization. CTC and SDZ were completely removed from the composting mass within 21 and 3d, respectively; whereas, 17-31% of the spiked CIP remained in the composting mass. Therefore, composting could effectively remove the CTC and SDZ spiked even at high concentrations, but the removal of ciprofloxacin (belonging to fluoroquinolone) needs to be improved, indicating this antibiotic may get into the ecosystem through land application of livestock compost.

Concepts: Agriculture, Fertilizer, Humus, Quinolone, Compost, Composting, Vermicompost, Mulch

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Fluoroquinolone antibiotics are commonly used to treat infections and are prescribed by general practitioners, medical specialists and surgeons. Tendon injury has been associated with the use of these medications but the risk associated with newer fluoroquinolones has not been established.

Concepts: Medicine, Antibiotic resistance, Surgery, Physician, Antibiotic, Quinolone

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To evaluate the antimicrobial effectiveness of preservative-free fluoroquinolone products compared with benzalkonium chloride containing fluoroquinolones using the challenge test provided by the United States Pharmacopeia (USP) and the in-use test.

Concepts: United States, U.S. state, Caribbean, Quinolone, Chlorides, Benzalkonium chloride, United States Pharmacopeia

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In Pseudomonas aeruginosa PAO1, the pvdQ gene has been shown to have at least two functions. It encodes the acylase enzyme and hydrolyzes 3-oxo-C12-HSL, the key signaling molecule of quorum sensing system. In addition, pvdQ is involved in swarming motility. It is required and up-regulated during swarming motility, which is triggered by high cell densities. As high density bacterial populations also display elevated antibiotics resistance, studies have demonstrated swarm-cell differentiation in P. aeruginosa promotes increased resistance to various antibiotics. PvdQ acts as a signal during swarm-cell differentiation, and thus may play a role in P. aeruginosa antibiotic resistance. The aim of this study was to examine whether pvdQ was involved in modifying antibiotic susceptibility during swarming conditions and to investigate the mechanism by which this occurred. We constructed the PAO1pMEpvdQ strain, which overproduces PvdQ. PAO1pMEpvdQ promotes swarming motility, while PAO1ΔpvdQ abolishes swarming motility. In addition, both PAO1 and PAO1pMEpvdQ acquired resistance to ceftazidime, ciprofloxacin, meropenem, polymyxin B, and gentamicin, though PAO1pMEpvdQ exhibited a twofold to eightfold increase in antibiotic resistance compared to PAO1. These results indicate that pvdQ plays an important role in elevating antibiotic resistance via swarm-cell differentiation and possibly other mechanisms as well. We analyzed outer membrane permeability. Our data also suggest that pvdQ decreases P. aeruginosa outer membrane permeability, thereby elevating antibiotic resistance under swarming conditions. Our results suggest new approaches for reducing P. aeruginosa resistance.

Concepts: Bacteria, Antibiotic resistance, Pseudomonas aeruginosa, Phage therapy, Biofilm, Pseudomonas, Quorum sensing, Quinolone

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Thirty-three isolates of Proteus mirabilis and two P. vulgaris were examined for their antimicrobial resistance, the presence of integrons with regard to gene cassette content, and genetic determinants of β-lactam and low-level quinolone resistance. Integrons were detected in 23 (69.7%) P. mirabilis isolates; six (18.2%) of them had class 1 integrons, 11 (33.3%) possessed class 2 integrons and six (18.2%) carried integrons of both classes. One P. vulgaris strain possessed class 1 and class 2 integrons. The presence of integrons was associated with increased frequency of resistance to gentamicin, ciprofloxacin, sulfamethoxazole and co-trimoxazole. Moreover, integron presence was associated with increased resistance range in terms of both the number of antimicrobials and the number of classes of antimicrobials to which a strain was resistant. Class 1 integrons contained aadA1, aadB-aadA1, dfrA1-aadA1, bla(PSE-1) -aadA1 and aacA4-orfA-orfB-aadA1 gene cassette arrays, whereas all class 2 integrons had a dfrA1-sat2-aada1 array. β-lactamase genes not associated with integrons comprised bla(TEM-2) , bla(DHA-1) and bla(CMY-15) . Plasmid-mediated fluoroquinolone resistance was determined by qnrD and qnrS1 genes. This is the first report of P. vulgaris strains harbouring qnrD genes in Europe.

Concepts: Gene, Genetics, Microbiology, Horizontal gene transfer, Antibiotic resistance, Quinolone, Proteus mirabilis, Integron

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The prevalence and antimicrobial susceptibility of Ureaplasma urealyticum and Mycoplasma hominis collected during 2004-2011 were determined. A total of 9956 individuals was analyzed. Identification was performed by use of the mycoplasma IST-2 kit. Antimicrobial susceptibility against doxycycline, josamycin, ofloxacin, erythromycin, tetracycline, ciprofloxacin, azithromycin, clarithromycin, and pristinamycin was also tested by use of this commercial kit. Our results show a prevalence of 1856 positive patients for genital mycoplasmas (18.6 %). Among positive cultures, 89 and 1.1 % of isolates were Ureaplasma urealyticum and Mycoplasma hominis, respectively. For 9.8 % of isolates both urogenital mycoplasmas were grown. Doxycycline was the most active tetracycline for mycoplasma infections, and this is still the drug of first choice. Among macrolides, josamycin and clarithromycin are the most active agents against ureaplasmas; josamycin is also active against mycoplasmas and is an alternative to tetracyclines and erythromycin for mixed infections, especially for pregnant women and neonates. Fluoroquinolones had low efficacy against urogenital mycoplasmas. For Ureaplasma urealyticum, cross-resistance was found between erythromycin and macrolides (except josamycin) (40-80 %) and between erythromycin and ciprofloxacin (79 %). Antibiotic resistance over the test period did not vary significantly. Because of geographical differences among antibiotic resistance, local in-vitro susceptibility testing is recommended to avoid failure of therapy.

Concepts: Bacteria, Mycoplasma, Erythromycin, Quinolone, Mycoplasma hominis, Mollicutes, Macrolide, Mycoplasmataceae

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Laboratory-scale batch experiments were developed to investigate the main removal routes for 6 commonly found quinolones (ciprofloxacin, moxifloxacin, norfloxacin, ofloxacin, pipemidic acid, and piromidic acid), in wastewaters from a wastewater treatment plant, at μgL(-1) levels in an aerobic sludge system from a membrane bioreactor (MBR) pilot plant. It was demonstrated that sorption and biotransformation were the main removal routes for the target antibiotics over other possible pathways, as volatilization or hydrolysis, under the experimental conditions. Mass balances indicated that sorption on sludge played a dominant role in the elimination of antibiotics from waters. The sorption coefficient K(d) depended strongly on temperature and on the quinolone type and were higher at lower temperatures and for piperazinylic quinolones. K(d) values were between 516 and 3746Lkg(-1) in the temperature range of 9-38°C. Higher mixed liquor suspended solids (MLSS) increased quinolone removal efficiency mainly by sorption. Quinolone biodegradation constituted a secondary pathway, and could be described by first-order kinetics with degradation-rate constants ranging from 8.0×10(-4)h(-1) to 1.4×10(-2)h(-1) within the same temperature range and MLSS from 7000 to 15,000mgL(-1). Biodegradation depended on the MLSS and temperature, but also on the initial chemical oxygen demand (COD). Higher biodegradation rates were observed at higher MLSS and temperature, as well as at low initial COD. Ciprofloxacin and moxifloxacin registered the highest biodegradation percentages (52.8% and 47.2%, respectively, at 38°C and 15,000mgL(-1) MLSS), which is evidence that, despite the known persistence of this group of antibiotics and removal from waters mainly by sorption, it was possible to improve their removal by biodegradation, with an appropriate selection of conditions and control of process variables, as a preliminary step towards the elimination of these antibiotics from the environment. Further research is needed on the possibilities of removing sorbed antibiotics from sludge.

Concepts: Wastewater, Ciprofloxacin, Quinolone, Moxifloxacin, Ofloxacin, Levofloxacin, Quinolone antibiotics, Norfloxacin

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Microfibrous materials based on poly(l-lactide-co-d,l-lactide) (coPLA) and coPLA/poly(ethylene glycol) (PEG) containing a fluoroquinolone antibiotic: ciprofloxacin hydrochloride (Cipro), levofloxacin hemihydrate (Levo) or moxifloxacin hydrochloride (Moxi) were obtained by electrospinning. The presence of Moxi led to an increase in the conductivity of the coPLA and coPLA/PEG spinning solutions and to the preparation of membranes composed of fibers aligned with the collector rotation direction. The one-step incorporation of the antibiotics in the fibers was confirmed by infrared spectroscopy and fluorescence microscopy. The antibiotics were dispersed in the coPLA or coPLA/PEG polymer matrix and the XRD spectra revealed the presence of crystalline phase characteristic of PEG and of the respective antibiotic. It was found that the release profiles of the antibiotics did not depend on the antibiotic nature but were dependent on the fiber composition. The presence of PEG in the fibers allowed a more rapid antibiotic release within the first 2h of release. The performed microbiological tests with Staphylococcus aureus revealed that the coPLA/Cipro, coPLA/PEG/Cipro, coPLA/Levo, coPLA/PEG/Levo, coPLA/Moxi and coPLA/PEG/Moxi mats inhibited the bacterial growth. In addition, the presence of an antibiotic in the mats led to a substantial decrease in the adhesion of the pathogenic microorganism and in the case of the coPLA/PEG/antibiotic series - to prevention thereof.

Concepts: Bacteria, Microbiology, Ciprofloxacin, Quinolone, Moxifloxacin, Ofloxacin, Levofloxacin, Norfloxacin