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  1. Wan Nur Ismah WAK, Takebayashi Y, Findlay J, Heesom KJ, Jiménez-Castellanos JC, Zhang J, et al.
    PMID: 29263066 DOI: 10.1128/AAC.01814-17
    Fluoroquinolone resistance in Gram-negative bacteria is multifactorial, involving target site mutations, reductions in fluoroquinolone entry due to reduced porin production, increased fluoroquinolone efflux, enzymes that modify fluoroquinolones, and Qnr, a DNA mimic that protects the drug target from fluoroquinolone binding. Here we report a comprehensive analysis, using transformation and in vitro mutant selection, of the relative importance of each of these mechanisms for fluoroquinolone nonsusceptibility using Klebsiella pneumoniae as a model system. Our improved biological understanding was then used to generate 47 rules that can predict fluoroquinolone susceptibility in K. pneumoniae clinical isolates. Key to the success of this predictive process was the use of liquid chromatography-tandem mass spectrometry to measure the abundance of proteins in extracts of cultured bacteria, identifying which sequence variants seen in the whole-genome sequence data were functionally important in the context of fluoroquinolone susceptibility.
    Matched MeSH terms: Fluoroquinolones/pharmacology*
  2. Jia Y, Zhao L
    Eur J Med Chem, 2021 Nov 15;224:113741.
    PMID: 34365130 DOI: 10.1016/j.ejmech.2021.113741
    Bacterial infection is amongst the most common diseases in community and hospital settings. Fluoroquinolones, exerting the antibacterial activity through binding to type II bacterial topoisomerase enzymes, DNA gyrase and topoisomerase IV, are mainstays of chemotherapy. At present, fluoroquinolones are the most valuable antibacterial agents used popularly. However, the emergence of more virulent and resistant pathogens by the development of either mutated DNA-binding proteins or efflux pump mechanism for fluoroquinolones results in an urgent demand to develop new fluoroquinolones to withstand the drug resistance and to obtain a broader spectrum of activity. This review aims to outline the recent advances of fluoroquinolone derivatives with antibacterial potential and to summarize the structure-activity relationship (SAR) so as to provide an insight for rational design of more active candidates, covering articles published between January 2018 and June 2021.
    Matched MeSH terms: Fluoroquinolones/pharmacology
  3. Ahmad N, Javaid A, Sulaiman SA, Ming LC, Ahmad I, Khan AH
    Braz J Infect Dis, 2016;20(1):41-7.
    PMID: 26626164 DOI: 10.1016/j.bjid.2015.09.011
    BACKGROUND: Fluoroquinolones are the backbone of multidrug resistant tuberculosis treatment regimens. Despite the high burden of multidrug resistant tuberculosis in the country, little is known about drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance among multidrug resistant tuberculosis patients from Pakistan.

    OBJECTIVE: To evaluate drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients.

    METHODS: This was a cross-sectional study conducted at a programmatic management unit of drug resistant tuberculosis, Lady Reading Hospital Peshawar, Pakistan. Two hundred and forty-three newly diagnosed multidrug resistant tuberculosis patients consecutively enrolled for treatment at study site from January 1, 2012 to July 28, 2013 were included in the study. A standardized data collection form was used to collect patients' socio-demographic, microbiological, and clinical data. SPSS 16 was used for data analysis.

    RESULTS: High degree of drug resistance (median 5 drugs, range 2-8) was observed. High proportion of patients was resistant to all five first-line anti-tuberculosis drugs (62.6%), and more than half were resistant to second line drugs (55.1%). The majority of the patients were ofloxacin resistant (52.7%). Upon multivariate analysis previous tuberculosis treatment at private (OR=1.953, p=0.034) and public private mix (OR=2.824, p=0.046) sectors were predictors of ofloxacin resistance.

    CONCLUSION: The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public-private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains.

    Matched MeSH terms: Fluoroquinolones/pharmacology*
  4. Song JH, Jung SI, Ko KS, Kim NY, Son JS, Chang HH, et al.
    Antimicrob Agents Chemother, 2004 Jun;48(6):2101-7.
    PMID: 15155207
    A total of 685 clinical Streptococcus pneumoniae isolates from patients with pneumococcal diseases were collected from 14 centers in 11 Asian countries from January 2000 to June 2001. The in vitro susceptibilities of the isolates to 14 antimicrobial agents were determined by the broth microdilution test. Among the isolates tested, 483 (52.4%) were not susceptible to penicillin, 23% were intermediate, and 29.4% were penicillin resistant (MICs >/= 2 mg/liter). Isolates from Vietnam showed the highest prevalence of penicillin resistance (71.4%), followed by those from Korea (54.8%), Hong Kong (43.2%), and Taiwan (38.6%). The penicillin MICs at which 90% of isolates are inhibited (MIC(90)s) were 4 mg/liter among isolates from Vietnam, Hong Kong, Korea, and Taiwan. The prevalence of erythromycin resistance was also very high in Vietnam (92.1%), Taiwan (86%), Korea (80.6%), Hong Kong (76.8%), and China (73.9%). The MIC(90)s of erythromycin were >32 mg/liter among isolates from Korea, Vietnam, China, Taiwan, Singapore, Malaysia, and Hong Kong. Isolates from Hong Kong showed the highest rate of ciprofloxacin resistance (11.8%), followed by isolates from Sri Lanka (9.5%), the Philippines (9.1%), and Korea (6.5%). Multilocus sequence typing showed that the spread of the Taiwan(19F) clone and the Spain(23F) clone could be one of the major reasons for the rapid increases in antimicrobial resistance among S. pneumoniae isolates in Asia. Data from the multinational surveillance study clearly documented distinctive increases in the prevalence rates and the levels of antimicrobial resistance among S. pneumoniae isolates in many Asian countries, which are among the highest in the world published to date.
    Matched MeSH terms: Fluoroquinolones/pharmacology
  5. Gan IN, Tan HS
    BMC Res Notes, 2019 Feb 21;12(1):97.
    PMID: 30791948 DOI: 10.1186/s13104-019-4124-4
    OBJECTIVES: Shigella is a human pathogen that causes shigellosis, an acute invasive intestinal infection. Recent studies in the model bacterium Escherichia coli (E. coli) provided evidence that small regulatory RNAs (sRNAs) can contribute to antimicrobial resistance or susceptibility. One of the sRNAs is SdsR, which increases sensitivity of E. coli against fluoroquinolone by repressing the drug efflux pump, TolC. However, no reports exist about the effect of SdsR on fluoroquinolone resistance in Shigella sonnei (S. sonnei). In this study, we established the effect of SdsR on the sensitivity of S. sonnei to norfloxacin.

    DATA DESCRIPTION: We tested the effects of SdsR and SdsRv2 on fluoroquinolone resistance in S. sonnei in vivo. SdsRv2 is a synthetic version which promotes higher binding stability to tolC mRNA. Overexpression of either SdsR or SdsRv2 lowers the expression of tolC mRNA. Interestingly, SdsR and SdsRv2 promote the growth of S. sonnei in the presence of a sub-inhibitory concentration of norfloxacin. Mutant carrying SdsRv2 showed the highest growth advantage. This phenotype is opposite to the effect of SdsR reported in E. coli. This study is an example that demonstrates the difference in the phenotypic effect of a highly conserved sRNA in two closely related bacteria.

    Matched MeSH terms: Fluoroquinolones/pharmacology*
  6. Lindgren MM, Kotilainen P, Huovinen P, Hurme S, Lukinmaa S, Webber MA, et al.
    Emerg Infect Dis, 2009 May;15(5):809-12.
    PMID: 19402977 DOI: 10.3201/eid1505.080849
    We tested the fluoroquinolone susceptibility of 499 Salmonella enterica isolates collected from travelers returning to Finland during 2003-2007. Among isolates from travelers to Thailand and Malaysia, reduced fluoroquinolone susceptibility decreased from 65% to 22% (p = 0.002). All isolates showing nonclassical quinolone resistance were from travelers to these 2 countries.
    Matched MeSH terms: Fluoroquinolones/pharmacology*
  7. Teh X, Khosravi Y, Lee WC, Leow AH, Loke MF, Vadivelu J, et al.
    PLoS One, 2014;9(7):e101481.
    PMID: 25003707 DOI: 10.1371/journal.pone.0101481
    Helicobacter pylori is the etiological agent for diseases ranging from chronic gastritis and peptic ulcer disease to gastric adenocarcinoma and primary gastric B-cell lymphoma. Emergence of resistance to antibiotics possesses a challenge to the effort to eradicate H. pylori using conventional antibiotic-based therapies. The molecular mechanisms that contribute to the resistance of these strains have yet to be identified and are important for understanding the evolutional pattern and selective pressure imposed by the environment.
    Matched MeSH terms: Fluoroquinolones/pharmacology
  8. Mohammed AAM, Suaifan GARY, Shehadeh MB, Okechukwu PN
    Eur J Med Chem, 2020 Sep 15;202:112513.
    PMID: 32623216 DOI: 10.1016/j.ejmech.2020.112513
    Herein we report the design, synthesis and biological evaluation of structurally modified ciprofloxacin, norfloxacin and moxifloxacin standard drugs, featuring amide functional groups at C-3 of the fluoroquinolone scaffold. In vitro antimicrobial testing against various Gram-positive bacteria, Gram-negative bacteria and fungi revealed potential antibacterial and antifungal activity. Hybrid compounds 9 (MIC 0.2668 ± 0.0001 mM), 10 (MIC 0.1358 ± 00025 mM) and 13 (MIC 0.0898 ± 0.0014 mM) had potential antimicrobial activity against a fluoroquinolone-resistant Escherichia coli clinical isolate, compared to ciprofloxacin (MIC 0.5098 ± 0.0024 mM) and norfloxacin (MIC 0.2937 ± 0.0021 mM) standard drugs. Interestingly, compound 10 also exerted potential antifungal activity against Candida albicans (MIC 0.0056 ± 0.0014 mM) and Penicillium chrysogenum (MIC 0.0453 ± 0.0156 mM). Novel derivatives and standard fluoroquinolone drugs exhibited near-identical cytotoxicity levels against L6 muscle cell-line, when measured using the MTT assay.
    Matched MeSH terms: Fluoroquinolones/pharmacology*
  9. Mansouri-najand L, Saleha AA, Wai SS
    Trop Biomed, 2012 Jun;29(2):231-8.
    PMID: 22735845 MyJurnal
    The objectives of this study were to determine the occurrence of Campylobacter spp. in live chickens sold at wet markets in Selangor, Malaysia and the multidrug resistance (MDR) profiles of the isolates. Cloacal swabs were taken from the chickens before slaughter and their caecal mucosae were swabbed after slaughter. Of the 90 chickens examined, 68 (75.6%) were positive for Campylobacter. Campylobacter were recovered from caecal swabs (53/90) and cloacal swabs (34/90) and Campylobacter coli (46 isolates) were identified slightly more than Campylobacter jejuni (41 isolates), but these differences were not significant (p<0.05). The most frequently observed resistance was to cephalothin (95.5%), followed by tetracycline (80.8%), erythromycin (51.4%), enrofloxacin (42.4%) and gentamicin (24.4%). Multidrug resistance (resistant to four or more antibiotics) was detected in 35.3% isolates. Campylobacter jejuni showed nine resistance profiles and the most common was to gentamicin-eryhtromycin-enrofloxacin-cephalothin-tetracycline (32.4%) combination while C. coli showed six profiles, with cephalothin-tetracycline (32.2%) combination being most common.
    Matched MeSH terms: Fluoroquinolones/pharmacology
  10. Kumar GP, Phani AR, Prasad RG, Sanganal JS, Manali N, Gupta R, et al.
    Int J Pharm, 2014 Aug 25;471(1-2):146-52.
    PMID: 24858388 DOI: 10.1016/j.ijpharm.2014.05.033
    Enrofloxacin is a fluoroquinolone derivative used for treating urinary tract, respiratory and skin infections in animals. However, low solubility and low bioavailability prevented it from using on humans. Polyvinylpyrrolidone (PVP) is an inert, non toxic polymer with excellent hydrophilic properties, besides it can enhance bioavailability by forming drug polymer conjugates. With the aim of increasing solubility and bioavailability, enrofloxacin thin films were prepared using PVP as a polymer matrix. The obtained oral thin films exhibited excellent uniformity and mechanical properties. Swelling properties of the oral thin films revealed that the water uptake was enhanced by 21%. The surface pH has been found to be 6.8±0.1 indicating that these films will not cause any irritation to oral mucosa. FTIR data of the oral thin films indicated physical interaction between drug and polymer. SEM analysis revealed uniform distribution of drug in polymer matrix. In vitro drug release profiles showed enhanced release profiles (which are also pH dependant) for thin films compared to pure drug. Antibacterial activity was found to be dose dependent and maximum susceptibility was found on Klebsiella pneumonia making this preparation more suitable for respiratory infections.
    Matched MeSH terms: Fluoroquinolones/pharmacology
  11. Yap PSX, Ahmad Kamar A, Chong CW, Ngoi ST, Teh CSJ
    Microb Drug Resist, 2020 Mar;26(3):190-203.
    PMID: 31545116 DOI: 10.1089/mdr.2019.0199
    Background:
    Klebsiella pneumoniae is a major opportunistic pathogen frequently associated with nosocomial infections, and often poses a major threat to immunocompromised patients. In our previous study, two K. pneumoniae (K36 and B13), which displayed resistance to almost all major antibiotics, including colistin, were isolated. Both isolates were not associated with infection and isolated from the stools of two preterm neonates admitted to the neonatal intensive care unit (NICU) during their first week of life.
    Materials and Methods:
    In this study, whole genome sequencing was performed on these two clinical multidrug resistant K. pneumoniae. We aimed to determine the genetic factors that underline the antibiotic-resistance phenotypes of these isolates.
    Results:
    The strains harbored blaSHV-27, blaSHV-71, and oqxAB genes conferring resistance to cephalosporins, carbapenems, and fluoroquinolones, respectively, but not harboring any known plasmid-borne colistin resistance determinants such as mcr-1. However, genome analysis discovered interruption of mgrB gene by insertion sequences gaining insight into the development of colistin resistance.
    Conclusion:
    The observed finding that points to a scenario of potential gut-associated resistance genes to Gram negative (K. pneumoniae) host in the NICU environment warrants attention and further investigation.
    Matched MeSH terms: Fluoroquinolones/pharmacology
  12. Hart T, Tang WY, Mansoor SAB, Chio MTW, Barkham T
    BMC Infect Dis, 2020 Apr 28;20(1):314.
    PMID: 32345231 DOI: 10.1186/s12879-020-05019-1
    BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted infection, with increasing rates of resistance to fluroquinolones and macrolides, the recommended treatments. Despite this, M. genitalium is not part of routine screening for Sexually Transmitted Infections (STIs) in many countries and the prevalence of infection and patterns of disease remain to be determined in many populations. Such data is of particular importance in light of the reported rise in antibiotic resistance in M. genitalium isolates.

    METHODS: Urine and urethral swab samples were collected from the primary public sexual health clinic in Singapore and tested for C. trachomatis (CT) or N. gonorrhoeae (NG) infection and for the presence of M. genitalium. Antibiotic resistance in M. genitalium strains detected was determined by screening for genomic mutations associated with macrolide and fluroquinolone resistance.

    RESULTS: We report the results of a study into M. genitalium prevalence at the national sexual health clinic in Singapore. M. genitalium was heavily associated with CT infection (8.1% of cases), but present in only of 2.4% in CT negative cases and not independently linked to NG infection. Furthermore, we found high rates of resistance mutations to both macrolides (25%) and fluoroquinolones (37.5%) with a majority of resistant strains being dual-resistant. Resistance mutations were only found in strains from patients with CT co-infection.

    CONCLUSIONS: Our results support targeted screening of CT positive patients for M. genitalium as a cost-effective strategy to reduce the incidence of M. genitalium in the absence of comprehensive routine screening. The high rate of dual resistance also highlights the need to ensure the availability of alternative antibiotics for the treatment of multi-drug resistant M. genitalium isolates.

    Matched MeSH terms: Fluoroquinolones/pharmacology
  13. Tan SY, Khan RA, Khalid KE, Chong CW, Bakhtiar A
    Sci Rep, 2022 Feb 24;12(1):3106.
    PMID: 35210515 DOI: 10.1038/s41598-022-07142-2
    Inappropriate use of antibiotics has been shown to contribute to the occurrence of multidrug-resistant organisms (MROs). A surveillance study was performed in the largest tertiary care hospital in Kuala Lumpur, Malaysia, from 2018 to 2020 to observe the trends of broad-spectrum antibiotics (beta-lactam/beta-lactamases inhibitors (BL/BLI), extended-spectrum cephalosporins (ESC), and fluoroquinolones (FQ)) and antibiotics against MRO (carbapenems, polymyxins, and glycopeptides) usage and the correlation between antibiotic consumption and MROs. The correlation between 3-year trends of antibiotic consumption (defined daily dose (DDD)/100 admissions) with MRO infection cases (per 100 admissions) was determined using a Jonckheere-Terpstra test and a Pearson's Correlation coefficient. The antimicrobial resistance trend demonstrated a positive correlation between ESC and FQ towards the development of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp, ESBL-producing Escherichia coli (E. coli), and MRO Acinetobacter baumannii (A. baumannii). Increasing carbapenem consumption was positively correlated with the occurrence of ESBL-producing Klebsiella spp and E. coli. Polymyxin use was positively correlated with ESBL-producing Klebsiella spp, MRO A. baumannii, and carbapenem-resistant Enterobacteriaceae. The findings reinforced concerns regarding the association between MRO development, especially with a surge in ESC and FQ consumption. Stricter use of antimicrobials is thus crucial to minimise the risk of emerging resistant organisms.
    Matched MeSH terms: Fluoroquinolones/pharmacology
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