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  1. Yasin RM, Suan KA, Meng CY
    Sex Transm Dis, 1997 May;24(5):257-60.
    PMID: 9153733
    BACKGROUND AND OBJECTIVES: The antimicrobial susceptibility pattern of Neisseria gonorrhoeae varies from one country to another and may also change with time. To monitor these variations and changes, it is desirable to have a method that is simple and reproducible. This study was undertaken to determine the in vitro susceptibility of N. gonorrhoeae to azithromycin and to assess the reliability of results obtained using E-test methodology for determination of the minimum inhibitory concentration (MIC) of azithromycin.

    STUDY DESIGN: The MICs for 135 clinical isolates of N. gonorrhoeae were determined by a modified Kirby-Bauer method recommended by the National Committee for Clinical Laboratory Standards against penicillin, cefuroxime, ceftriaxone, norfloxacin, tetracycline, kanamycin, spectinomycin, and azithromycin. The MIC of azithromycin was determined by both the E-test and agar dilution method. All tests were done simultaneously.

    RESULTS: The MIC of azithromycin to all 135 isolates ranged from 0.078 to 0.25 microgram/ml with the agar dilution method and from 0.016 to 0.50 microgram/ml with the E-test. The MIC50 and MIC90 of azithromycin were 0.064 microgram/ml and 0.125 microgram/ml, respectively, by the agar dilution method, whereas they are slightly higher by the E-test method. Seventy-six of the isolates were beta-lactamase producers and 69 were high-level tetracycline-resistant N. gonorrhoeae. There was no difference in the MIC50 and MIC90 of azithromycin in these groups of isolates. The percentage agreement within the acceptable +/-1 log2 dilution difference between MICs obtained by E-test and those obtained by the agar dilution method was 97.8%.

    CONCLUSIONS: Azithromycin has a very good in vitro antigonococcal activity, and the E-test is a reliable method to determine the MIC of azithromycin against N. gonorrhoeae.

    Matched MeSH terms: Azithromycin/pharmacology*
  2. Jagabalan JDY, Murugaiyah V, Zainal H, Mansor SM, Ramanathan S
    J Asian Nat Prod Res, 2019 Apr;21(4):351-363.
    PMID: 29667422 DOI: 10.1080/10286020.2018.1461088
    The intestinal permeability of mitragynine was investigated in situ using a single pass intestinal perfusion (SPIP) absorption model, in small intestine of rat using mitragynine in the absence/presence of the permeability markers, P-gp and/or CYP3A4 inhibitors. Mitragynine demonstrated high intestinal permeability (Peff of 1.11 × 10-4 cm/s) that is in the range of highly permeable drugs such as propranolol (Peff of 1.27 × 10-4 cm/s) indicating that it readily crosses the intestine. The addition of azithromycin (P-glycoprotein inhibitor) and ciprofloxacin (CYP3A4 inhibitor) or combination of both has no effect on intestinal permeability of mitragynine across the rat small intestine.
    Matched MeSH terms: Azithromycin/pharmacology
  3. Amin F, Khan S, Shah SMH, Rahim H, Hussain Z, Sohail M, et al.
    Drug Des Devel Ther, 2018;12:3855-3866.
    PMID: 30510401 DOI: 10.2147/DDDT.S183534
    Background: The obnoxious bitter taste of orally taken antibiotics is one of the biggest problems in the treatment of children. The pediatric population cannot tolerate the bitter taste of drugs and vomit out which ultimately leads to suboptimal therapeutic value, grimace and mental stress so it is the challenging task for the formulation scientists to formulate a palatable formulation particularly to overcome address the issue.

    Purpose of study: The study aimed to mask and evaluate the unpleasant bitter taste of azithro-mycin (AZ) in the dry suspension dosage form by physisorption technique.

    Materials and methods: AZ was selected as an adsorbent and titanium dioxide nanoparticles as adsorbate. The AZ nanohybrids (AZN) were prepared by treating fixed amount of adsorbent with a varied amount of adsorbate, prepared separately by dispersing it in an aqueous medium. The mixture was sonicated, stirred followed by filtration and drying. The AZN produced were characterized by various techniques including scanning electron microscopy (SEM), energy dispersive X-rays (EDX), powder X-ray diffraction (PXRD), HPLC and Fourier-transformed infrared (FTIR). The optimized nanohybrid was blended with other excipients to get stable and taste masked dry suspension dosage form.

    Results: The results confirmed the adsorption of titanium dioxide nanoparticles on the surface of AZ. The fabricated optimized formulation was subjected for taste masking by panel testing and accelerated stability studies. The results showed a remarkable improvement in bitter taste masking, inhibiting throat bite without affecting the dissolution rate. The product showed an excellent stability both in dry and reconstituted suspension. The optimized formulation of AZN and was found stable when subjected to physical and chemical stability studies, this is because of short and single step process which interns limits the exposure of the product to various environmental factors that could potentially affect the stability of the product. The dissolution rate of the optimized formulation of AZN was compared with its marketed counterpart, showing the same dissolution rate compared to its marketed formulation.

    Conclusion: The current study concludes that, by fabricating AZ-titanium nanohybrids using physisorption can effectively mask the bitter taste of the drug. The palatability and stability of azithromycin formulation was potentially enhanced without affecting its dissolution rate.

    Matched MeSH terms: Azithromycin/pharmacology*
  4. Jamaludin N, Gedye K, Collins-Emerson J, Benschop J, Nulsen M
    Microb Drug Resist, 2019 Sep;25(7):1003-1011.
    PMID: 31021281 DOI: 10.1089/mdr.2018.0111
    Aim:
    To characterize mutations in penA, mtrR, ponA, and porBIB, considered target genes for antimicrobial resistance, in Neisseria gonorrhoeae isolates with elevated minimum inhibitory concentrations (MICs) of ceftriaxone cultured from patients in New Zealand.
    Results:
    Out of 28 isolates supplied by the Institute of Environmental Science and Research Limited (ESR), Porirua, New Zealand, 14 were found to show reduced susceptibility to ceftriaxone (MIC of 0.06 mg/L) according to criteria used by the ESR and the Australian Gonococcal Surveillance Programme (AGSP) when tested in our laboratory. Rates of resistance to ciprofloxacin, azithromycin, penicillin, and tetracycline were 100% (28/28), 7% (2/28), 36% (10/28), and 25% (7/28), respectively. Ten different penA (Penicillin binding protein 2 [PBP2]) sequences were observed. The most common mosaic penA M-1 resembled mosaic penA XXXIV, which has been associated with ceftriaxone treatment failures in other countries. Four semimosaic PBP2 sequences were observed and may be novel PBP sequences, while four out of five nonmosaic PBP2 sequences were similar to PBP2 sequences reported in Australia. Twenty-one isolates harbored mutations in all 4 genes (penA, mtrR, porBIB, and ponA), and 13 of these exhibited reduced susceptibility to ceftriaxone.
    Conclusion:
    Mutations in penA, mtrR, porBIB, and ponA observed in this study may have contributed to reduced susceptibility to ceftriaxone among New Zealand gonococcal isolates. Over half (16/22) of mosaic penA sequences from the gonococcal isolates resembled penA XXXIV.
    Matched MeSH terms: Azithromycin/pharmacology
  5. George CRR, Enriquez RP, Gatus BJ, Whiley DM, Lo YR, Ishikawa N, et al.
    PLoS One, 2019;14(4):e0213312.
    PMID: 30943199 DOI: 10.1371/journal.pone.0213312
    BACKGROUND: Antimicrobial resistance in Neisseria gonorrhoeae is a global concern, with the ongoing emergence of ceftriaxone and azithromycin resistance threatening current treatment paradigms. To monitor the emergence of antimicrobial resistance in N. gonorrhoeae, the World Health Organization (WHO) Gonococcal Antimicrobial Surveillance Programme (GASP) has operated in the Western Pacific and South East Asian regions since 1992. The true burden of antimicrobial resistance remains unknown. In response, the objective of this study was to survey ceftriaxone and azithromycin susceptibility in N. gonorrhoeae across the western Pacific and south-east Asia, and interlink this data with systematically reviewed reports of ceftriaxone and azithromycin resistance.

    METHODS AND FINDINGS: The WHO Collaborating Centre for Sexually Transmitted Infections and Antimicrobial Resistance, Sydney, coordinated annual surveys of gonococcal susceptibilities with participating laboratories, and additionally undertook a systematic review of reports detailing gonococcal ceftriaxone and azithromycin susceptibility data for locations geographically in the Asia Pacific from 2011 to 2016. It was found that surveillance of gonococcal antimicrobial resistance remains limited in the Asia Pacific, with weaker surveillance of azithromycin versus ceftriaxone. Ninety-three published reports were identified (including national reports) which documented susceptibility data for ceftriaxone and azithromycin. GASP survey data was available for 21 countries, territories or areas, and suggested MICs are increasing for ceftriaxone and azithromycin. Between 2011 and 2016, the percentage of locations reporting >5% of gonococcal isolates with MICs to ceftriaxone meeting WHO's definition of decreased susceptibility (MIC ≥ 0.125 mg/L) increased from 14.3% to 35.3% and the percentage of locations reporting >5% of gonococcal isolates with azithromycin resistance (MIC ≥ 1 mg/L) increased from 14.3% to 38.9%. Published reports were available for several countries that did not provide GASP surveillance responses for ceftriaxone (n = 5) and azithromycin (n = 3) respectively. Over the study period, there was a 183% increase in the number of countries providing surveillance data for GASP for both ceftriaxone and azithromycin, and a 30.6% increase in ceftriaxone MIC testing across the Asia Pacific facilitated by this project.

    CONCLUSION: This study provides the first comprehensive illustration of increasing MICs to ceftriaxone in the Asia Pacific. The survey and literature review additionally detail increasing resistance to azithromycin. Further surveillance system strengthening is required to monitor these trends in order to address and curb gonococcal AMR in the region.

    Matched MeSH terms: Azithromycin/pharmacology*
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