1887

Abstract

In 2018, the European Centre for Disease Prevention and Control reported the first cases of extensively drug-resistant infections in Europe. Seeking new options for antimicrobial therapy we investigated the susceptibility of to nitroxoline (NIT) and mecillinam (MCM), both of which are currently only indicated to treat uncomplicated urinary tract infections. Clinical isolates with non-susceptibility to penicillin from two German medical centres were included ( =27). Most isolates were also non-susceptible to a range of other anti-gonococcal antimicrobials (cefotaxime, ciprofloxacin, azithromycin, tetracycline). All isolates were further characterized by multi-locus sequence typing. MICs of penicillin and cefotaxime were determined by agar gradient diffusion. Production of penicillinase was tested by cefinase disk test. Susceptibility of MCM was investigated by agar dilution, NIT by agar dilution and disk diffusion. Penicillin MICs ranged from 0.125 to 64 mg l and MICs of cefotaxime ranged from < 0.016 to 1 mg l . Five isolates were penicillinase-producers. MICs of MCM ranged from 16 to > 128 mg l whereas MICs of NIT ranged from 0.125 to 2 mg l . NIT disk diffusion (median zone diameter 32 mm) correlated well with results from agar dilution. We demonstrated excellent activity of NIT against clinical isolates with non-susceptibility to standard anti-gonococcal antibiotics. MCM activity was unsatisfactory. Correlation of agar dilution and disk diffusion in NIT susceptibility testing is an important aspect with potential clinical implications.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001014
2019-07-01
2019-10-19
Loading full text...

Full text loading...

References

  1. World Health Organization WHO Guidelines for the Treatment of Neisseria gonorrhoeae Geneva: World Health Organization; 2016
    [Google Scholar]
  2. Ohnishi M, Saika T, Hoshina S, Iwasaku K, Nakayama S et al. Ceftriaxone-resistant Neisseria gonorrhoeae, Japan. Emerg Infect Dis 2011;17:148–149 [CrossRef]
    [Google Scholar]
  3. WHO Global Action Plan to Control the Spread and Impact of Antimicrobial Resistance in Neisseria gonorrhoea Geneva, Switzerland: WHO; 2012
    [Google Scholar]
  4. European Centre for Disease Prevention and Control Extensively Drug-Resistant (XDR) Neisseria gonorrhoeae in the United Kingdom and Australia Stockholm: ECDC; 2018
    [Google Scholar]
  5. Lund F, Tybring L. 6 -amidinopenicillanic acids--a new group of antibiotics. Nat New Biol 1972;236:135–137 [CrossRef]
    [Google Scholar]
  6. Petrow V, Sturgeon B. Some quinoline-5 : 8-quinones. J Chem Soc 1954;570–574 [CrossRef]
    [Google Scholar]
  7. Spratt BG. The mechanism of action of mecillinam. J Antimicrob Chemother 1977;3:13–19 [CrossRef]
    [Google Scholar]
  8. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the infectious diseases Society of America and the European Society for microbiology and infectious diseases. Clin Infect Dis 2011;52:e103–e120 [CrossRef]
    [Google Scholar]
  9. Kranz J, Schmidt S, Lebert C, Schneidewind L, Vahlensieck W et al. Epidemiology, diagnostics, therapy, prevention and management of uncomplicated bacterial outpatient acquired urinary tract infections in adult patients : Update 2017 of the interdisciplinary AWMF S3 guideline. Urologe A 2017;56:746–758
    [Google Scholar]
  10. Fraser RS, Creanor J. Rapid and selective inhibition of RNA synthesis in yeast by 8-hydroxyquinoline. Eur J Biochem 1974;46:67–73 [CrossRef]
    [Google Scholar]
  11. Pelletier C, Prognon P, Bourlioux P. Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains. Antimicrob Agents Chemother 1995;39:707–713 [CrossRef]
    [Google Scholar]
  12. Dewar S, Reed LC, Koerner RJ. Emerging clinical role of pivmecillinam in the treatment of urinary tract infection in the context of multidrug-resistant bacteria. J Antimicrob Chemother 2014;69:303–308 [CrossRef]
    [Google Scholar]
  13. Kresken M, Körber-Irrgang B. In vitro activity of nitroxoline against Escherichia coli urine isolates from outpatient departments in Germany. Antimicrob Agents Chemother 2014;58:7019–7020 [CrossRef]
    [Google Scholar]
  14. Nicolle LE. Pivmecillinam in the treatment of urinary tract infections. J Antimicrob Chemother 2000;46:35–39 [CrossRef]
    [Google Scholar]
  15. EUCAST EUCAST definitive document E.DEF 3.1, June 2000: determination of minimum inhibitory concentrations (MICs) of antibacterial agents by agar dilution. Clin Microbiol Infect 2000;6:509–515
    [Google Scholar]
  16. Matuschek E, Brown DF, Kahlmeter G. Development of the EUCAST disk diffusion antimicrobial susceptibility testing method and its implementation in routine microbiology laboratories. Clin Microbiol Infect 2014;20:O255–O266 [CrossRef]
    [Google Scholar]
  17. EUCAST Routine and extended internal quality control for MIC determination and disk diffusion as recommended by EUCAST. version 8.0. 2018
  18. Wi T, Lahra MM, Ndowa F, Bala M, Dillon JR et al. Antimicrobial resistance in Neisseria gonorrhoeae: global surveillance and a call for international collaborative action. PLoS Med 2017;14:e1002344 [CrossRef]
    [Google Scholar]
  19. Mrhar A, Kopitar Z, Kozjek F, Presl V, Karba R. Clinical pharmacokinetics of nitroxoline. Int J Clin Pharmacol Biopharm 1979;17:476–481
    [Google Scholar]
  20. Wijma RA, Huttner A, Koch BCP, Mouton JW, Muller AE. Review of the pharmacokinetic properties of nitrofurantoin and nitroxoline. J Antimicrob Chemother 2018;73:2916–2926 [CrossRef]
    [Google Scholar]
  21. Bourlioux P, Botto H, Karam D, Amgar A, Camey M. Inhibition of bacterial adherence by nitroxoline on cellular adhesion and on urinary catheter surfaces]. Pathol Biol 1989;37:451–454
    [Google Scholar]
  22. Fuchs F, Hamprecht A. Results from a Prospective In Vitro Study on the Mecillinam (Amdinocillin) Susceptibility of Enterobacterales. Antimicrob Agents Chemother 2019;02402–02418 [CrossRef]
    [Google Scholar]
  23. Kranz J, Helbig S, Mandraka F, Schmidt S, Naber KG. The revival of old antibiotics for treatment of uncomplicated urinary tract infections in the era of antibiotic stewardship. Curr Opin Urol 2017;27:127–132 [CrossRef]
    [Google Scholar]
  24. Khan MY, Siddiqui Y, Gruninger RP. Comparative in-vitro activity of selected new beta-lactam antimicrobials against Neisseria gonorrhoeae. Sex Transm Infect 1982;58:228–230 [CrossRef]
    [Google Scholar]
  25. Watts BA, Phillips I, Stoate MW. The in vitro activity of 15 penicillins and mecillinam against Neisseria gonorrhoeae. J Antimicrob Chemother 1977;3:331–337 [CrossRef]
    [Google Scholar]
  26. Lawung R, Cherdtrakulkiat R, Nabu S, Prachayasittikul S, Isarankura-Na-Ayudhya C et al. Repositioning of 8-hydroxyquinoline derivatives as a new promising candidate for combating multidrug resistant Neisseria gonorrhoeae. Excli J 2018;17:840–846 [CrossRef]
    [Google Scholar]
  27. Yahara K, Nakayama SI, Shimuta K, Lee KI, Morita M et al. Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages. Microb Genom 2018;4:
    [Google Scholar]
  28. Rice PA, Shafer WM, Ram S, Jerse AE. Neisseria gonorrhoeae: drug resistance, mouse models, and vaccine development. Annu Rev Microbiol 2017;71:665–686 [CrossRef]
    [Google Scholar]
  29. Molina JM, Charreau I, Chidiac C, Pialoux G, Cua E et al. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect Dis 2018;18:308–317 [CrossRef]
    [Google Scholar]
  30. Wagenlehner FM, Münch F, Pilatz A, Bärmann B, Weidner W et al. Urinary concentrations and antibacterial activities of nitroxoline at 250 milligrams versus trimethoprim at 200 milligrams against uropathogens in healthy volunteers. Antimicrob Agents Chemother 2014;58:713–721 [CrossRef]
    [Google Scholar]
  31. Bergogne-Berezin E, Berthelot G, Muller-Serieys C. [Present status of nitroxoline]. Pathol Biol 1987;35:873–878
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001014
Loading
/content/journal/jmm/10.1099/jmm.0.001014
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error