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      Interplay of the Quality of Ciprofloxacin and Antibiotic Resistance in Developing Countries

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          Abstract

          Ciprofloxacin, a second generation broad spectrum fluoroquinolone, is active against both Gram-positive and Gram-negative bacteria. Ciprofloxacin has a high oral bioavailability and a large volume of distribution. It is used for the treatment of a wide range of infections including urinary tract infections caused by susceptible bacteria. However, the availability and use of substandard and spurious quality of oral ciprofloxacin formulations in the developing countries has been thought to have contributed toward increased risk of treatment failure and bacterial resistance. Therefore, quality control and bioequivalence studies of the commercially available oral ciprofloxacin formulations should be monitored. Appropriate actions should be taken against offending manufacturers in order to prevent the sale of substandard and spurious quality of ciprofloxacin formulations.

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          Most cited references 55

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          Mechanism of Quinolone Action and Resistance

          Quinolones are one of the most commonly prescribed classes of antibacterials in the world and are used to treat a variety of bacterial infections in humans. Because of the wide use (and overuse) of these drugs, the number of quinolone-resistant bacterial strains has been growing steadily since the 1990s. As is the case with other antibacterial agents, the rise in quinolone resistance threatens the clinical utility of this important drug class. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome. This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quinolone action against their enzyme targets. It will then discuss the following three mechanisms that decrease the sensitivity of bacterial cells to quinolones. Target-mediated resistance is the most common and clinically significant form of resistance. It is caused by specific mutations in gyrase and topoisomerase IV that weaken interactions between quinolones and these enzymes. Plasmid-mediated resistance results from extrachromosomal elements that encode proteins that disrupt quinolone–enzyme interactions, alter drug metabolism, or increase quinolone efflux. Chromosome-mediated resistance results from the underexpression of porins or the overexpression of cellular efflux pumps, both of which decrease cellular concentrations of quinolones. Finally, this review will discuss recent advancements in our understanding of how quinolones interact with gyrase and topoisomerase IV and how mutations in these enzymes cause resistance. These last findings suggest approaches to designing new drugs that display improved activity against resistant strains.
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            Combination therapy for treatment of infections with gram-negative bacteria.

            Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa, those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria.
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              Acquired Antibiotic Resistance Genes: An Overview

              In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                21 August 2017
                2017
                : 8
                Affiliations
                1Pharmacy, School of Medicine, University of Tasmania, Hobart TAS, Australia
                2Department of Pharmacy, State University of Bangladesh Dhaka, Bangladesh
                3Vector borne Diseases Research Group, Pharmaceutical and Life Sciences CoRe, Universiti Teknologi MARA Shah Alam, Malaysia
                4Faculty of Pharmacy, Universiti Teknologi MARA Bertam, Malaysia
                5School of Pharmacy, KPJ Healthcare University College Negeri Sembilan, Malaysia
                Author notes

                Edited by: Xinhua Qu, Shanghai Ninth People’s Hospital, China

                Reviewed by: Giulia Maria Camerino, Università degli Studi di Bari Aldo Moro, Italy; Leonardo Augusto Moraes, National University of Singapore, Singapore

                *Correspondence: Long C. Ming, ming.long@ 123456bath.edu Rahul P. Patel, rahul.patel@ 123456utas.edu.au

                These authors have contributed equally to this work.

                This article was submitted to Translational Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2017.00546
                5566961
                Copyright © 2017 Sharma, Patel, Zaidi, Sarker, Lean and Ming.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 67, Pages: 7, Words: 0
                Funding
                Funded by: Universiti Teknologi MARA 10.13039/501100004625
                Award ID: (RAGS/1/2014/SKK10/UITM/7
                Categories
                Pharmacology
                Mini Review

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