High levels of susceptibility to new and older antibiotics in Neisseria gonorrhoeae isolates from Saskatchewan (2003–15): time to consider point-of-care or molecular testing for precision treatment?—authors’ response

High levels of susceptibility to new and older antibiotics in Neisseria gonorrhoeae isolates from... Sir, In response to our article, ‘High levels of susceptibility to new and older antibiotics in Neisseria gonorrhoeae isolates from Saskatchewan (2003–15): time to consider point-of-care or molecular testing for precision treatment?’,1 Davido et al.2 have made an interesting suggestion regarding the re-evaluation of aztreonam as a treatment option for infections caused by N. gonorrhoeae. Aztreonam, a monobactam, has been used, in the past, as single-dose therapy to treat gonorrhoea.3–5 Since aztreonam is stable to β-lactamases, and does not induce the production of chromosomally mediated enzymes, the antibiotic can be used effectively against penicillinase-producing N. gonorrhoeae (PPNG).6 Aztreonam has been used against PPNG in the past with 100% efficacy, with no side effects in patients.4 In a study conducted in Thailand, in 1992, aztreonam was 100% effective against N. gonorrhoeae (n =  331), including β-lactamase-producing isolates (94 of 331 isolates).7 However, two studies from Japan reported high (8 mg/L, n = 2) MICs of aztreonam for N. gonorrhoeae isolates and treatment failures using a 1 g intramuscular dose (n = 3).8,9 Another study showed that aztreonam (1 g) is not 100% effective in treating pharyngeal (2 of 3 cases) and rectal (1 of 2 cases) gonorrhoea.3 In contrast, a later study reported >96% cure rates for treating uncomplicated gonorrhoea with 1 g of aztreonam, and 100% efficacy for patients with rectal (n = 14), pharyngeal (n = 8) and PPNG (n = 40) infections.10 Gottlieb and Mills11 also reported 100% cure rates for genital (n = 29) and rectal (n = 3) gonorrhoea. Evans et al.12 also reported 100% (n = 91) treatment of gonorrhoea with 1 g of aztreonam, including rectal (2 of 91 cases), pharyngeal (1 of 91 cases), PPNG (5 of 91 cases) and penicillin-resistant (non-PPNG, 5 of 91 cases) infections. Although studies testing the susceptibility of gonococci to aztreonam were conducted during the 1980s, a recent study in Canada determined that N. gonorrhoeae isolates, with different resistance phenotypes, were susceptible to aztreonam alone, or in combination with azithromycin.13 Furthermore, Davido et al.14 reported that, with either intramuscular or intravenous administration of aztreonam (1 g), all patients with gonorrhoea (n = 5) were successfully treated, including MSM (n = 3). More studies are required to determine the efficacy of aztreonam in treating pharyngeal and rectal gonococcal infections, since few studies have been conducted in the past.3,10–12 Aztreonam has also been suggested, in the past, for the treatment of acute cases of pelvic inflammatory disease (PID), caused by N. gonorrhoeae, because of its low toxicity and higher blood levels, as compared with aminoglycosides.15 Clindamycin with gentamicin are recommended in current Canadian treatment regimens for PID.16 Aztreonam is a parenteral antibiotic, and, for gonorrhoea, oral treatments are preferred. However, treatment options for infections caused by N. gonorrhoeae are becoming increasingly limited because N. gonorrhoeae has become resistant to all classes of antimicrobial agents and treatment failure with dual therapy comprising azithromycin and ceftriaxone had been reported.17,18 Thus aztreonam may be a viable treatment option to reconsider. However, the use of this antibiotic would require active antimicrobial susceptibility testing of gonococcal isolates globally and regionally to ascertain its current susceptibility status. Also, as suggested by Davido et al.,2 there is a need to develop susceptibility breakpoints for aztreonam and basic research should be completed to ascertain gonococcal mechanisms of resistance to this antibiotic. However, if N. gonorrhoeae isolates prove to be susceptible to this antibiotic, aztreonam might supplement spectinomycin (introduced initially to treat PPNG), or other treatment options, in gonococcal treatment guidelines. Transparency declarations None to declare. References 1 Thakur SD, Levett PN, Horsman GB et al.   High levels of susceptibility to new and older antibiotics in Neisseria gonorrhoeae isolates from Saskatchewan (2003–15): time to consider point-of-care or molecular testing for precision treatment? J Antimicrob Chemother  2018; 73: 118– 25. Google Scholar CrossRef Search ADS PubMed  2 Davido B, Dinh A, Matt M et al.   Comment on: High levels of susceptibility to new and older antibiotics in Neisseria gonorrhoeae isolates from Saskatchewan (2003–15): time to consider point-of-care or molecular testing for precision treatment? J Antimicrobial Chemother  2018; 73: 828– 9. 3 Tait IB, Winning J, Sleigh JD. Single dose aztreonam in treating gonorrhoea. Genitourin Med  1987; 63: 13– 5. Google Scholar PubMed  4 Miller LK, Sanchez PL, Berg SW et al.   Effectiveness of aztreonam, a new monobactam antibiotic, against penicillin-resistant gonococci. J Infect Dis  1983; 148: 612. Google Scholar CrossRef Search ADS PubMed  5 Stöberl C, Poitschek C, Söltz-Szöts J. Aztreonam, a new approach in the therapy of gonorrhea. Wien Klin Wochenschr  1991; 103: 271– 3. Google Scholar PubMed  6 Sykes RB, Bonner DP. Monobactam antibiotics: history and development. In: Williams JD, Woods P, eds. Aztreonam: The Antibiotic Discovery for Gram-Negative Infections . London, UK: Royal Society of Medicine, 1985; 3– 24. 7 Clendennen TE, Echeverria P, Saengeur S et al.   Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand. Antimicrob Agents Chemother  1992; 36: 1682– 7. Google Scholar CrossRef Search ADS PubMed  8 Muratani T, Akasaka S, Kobayashi T et al.   Outbreak of cefozopran (penicillin, oral cephems, and aztreonam)-resistant Neisseria gonorrhoeae in Japan. Antimicrob Agents Chemother  2001; 45: 3603– 6. Google Scholar CrossRef Search ADS PubMed  9 Akasaka S, Muratani T, Yamada Y et al.   Emergence of cephem- and aztreonam-high-resistant Neisseria gonorrhoeae that does not produce β-lactamase. J Infect Chemother  2001; 7: 49– 50. Google Scholar CrossRef Search ADS PubMed  10 Spencer RC, Talbot MD. The use of aztreonam in the treatment of uncomplicated gonorrhoea. Curr Med Res Opin  1985; 9: 591– 3. Google Scholar CrossRef Search ADS PubMed  11 Gottlieb A, Mills J. Effectiveness of aztreonam for the treatment of gonorrhea. Antimicrob Agents Chemother  1985; 27: 270– 1. Google Scholar CrossRef Search ADS PubMed  12 Evans DT, Crooks AJ, Jones C et al.   Treatment of uncomplicated gonorrhoea with single dose aztreonam. Genitourin Med  1986; 62: 318– 20. Google Scholar PubMed  13 Bharat A, Martin I, Zhanel GG et al.   In vitro potency and combination testing of antimicrobial agents against Neisseria gonorrhoeae. J Infect Chemother  2016; 22: 194– 7. Google Scholar CrossRef Search ADS PubMed  14 Davido B, Dinh A, Senard O et al.   Repurposing an old drug: aztreonam as a new treatment strategy for gonorrhoea. J Antimicrob Chemother  2017; 72: 1466– 8. Google Scholar PubMed  15 Dodson MG. Optimum therapy for acute pelvic inflammatory disease. Drugs  1990; 39: 511– 22. Google Scholar CrossRef Search ADS PubMed  16 Public Health Agency of Canada. Canadian Guidelines on Sexually Transmitted Infections. Section 4. Management and Treatment of Specific Syndromes. Pelvic Inflammatory Disease . Ottawa, Canada: Public Health Agency of Canada, 2013. https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/sexually-transmitted-infections/canadian-guidelines-sexually-transmitted-infections-22.html. 17 Dillon JR, Parti R, Thakur SD. Antibiotic resistance in Neisseria gonorrhoeae isolates: will infections be untreatable in the future? Culture (Oxoid)  2015; 35: 1– 8. 18 Fifer H, Natarajan U, Jones L et al.   Failure of dual antimicrobial therapy in treatment of gonorrhea. N Engl J Med  2016; 374: 2504– 6. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Antimicrobial Chemotherapy Oxford University Press

High levels of susceptibility to new and older antibiotics in Neisseria gonorrhoeae isolates from Saskatchewan (2003–15): time to consider point-of-care or molecular testing for precision treatment?—authors’ response

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Abstract

Sir, In response to our article, ‘High levels of susceptibility to new and older antibiotics in Neisseria gonorrhoeae isolates from Saskatchewan (2003–15): time to consider point-of-care or molecular testing for precision treatment?’,1 Davido et al.2 have made an interesting suggestion regarding the re-evaluation of aztreonam as a treatment option for infections caused by N. gonorrhoeae. Aztreonam, a monobactam, has been used, in the past, as single-dose therapy to treat gonorrhoea.3–5 Since aztreonam is stable to β-lactamases, and does not induce the production of chromosomally mediated enzymes, the antibiotic can be used effectively against penicillinase-producing N. gonorrhoeae (PPNG).6 Aztreonam has been used against PPNG in the past with 100% efficacy, with no side effects in patients.4 In a study conducted in Thailand, in 1992, aztreonam was 100% effective against N. gonorrhoeae (n =  331), including β-lactamase-producing isolates (94 of 331 isolates).7 However, two studies from Japan reported high (8 mg/L, n = 2) MICs of aztreonam for N. gonorrhoeae isolates and treatment failures using a 1 g intramuscular dose (n = 3).8,9 Another study showed that aztreonam (1 g) is not 100% effective in treating pharyngeal (2 of 3 cases) and rectal (1 of 2 cases) gonorrhoea.3 In contrast, a later study reported >96% cure rates for treating uncomplicated gonorrhoea with 1 g of aztreonam, and 100% efficacy for patients with rectal (n = 14), pharyngeal (n = 8) and PPNG (n = 40) infections.10 Gottlieb and Mills11 also reported 100% cure rates for genital (n = 29) and rectal (n = 3) gonorrhoea. Evans et al.12 also reported 100% (n = 91) treatment of gonorrhoea with 1 g of aztreonam, including rectal (2 of 91 cases), pharyngeal (1 of 91 cases), PPNG (5 of 91 cases) and penicillin-resistant (non-PPNG, 5 of 91 cases) infections. Although studies testing the susceptibility of gonococci to aztreonam were conducted during the 1980s, a recent study in Canada determined that N. gonorrhoeae isolates, with different resistance phenotypes, were susceptible to aztreonam alone, or in combination with azithromycin.13 Furthermore, Davido et al.14 reported that, with either intramuscular or intravenous administration of aztreonam (1 g), all patients with gonorrhoea (n = 5) were successfully treated, including MSM (n = 3). More studies are required to determine the efficacy of aztreonam in treating pharyngeal and rectal gonococcal infections, since few studies have been conducted in the past.3,10–12 Aztreonam has also been suggested, in the past, for the treatment of acute cases of pelvic inflammatory disease (PID), caused by N. gonorrhoeae, because of its low toxicity and higher blood levels, as compared with aminoglycosides.15 Clindamycin with gentamicin are recommended in current Canadian treatment regimens for PID.16 Aztreonam is a parenteral antibiotic, and, for gonorrhoea, oral treatments are preferred. However, treatment options for infections caused by N. gonorrhoeae are becoming increasingly limited because N. gonorrhoeae has become resistant to all classes of antimicrobial agents and treatment failure with dual therapy comprising azithromycin and ceftriaxone had been reported.17,18 Thus aztreonam may be a viable treatment option to reconsider. However, the use of this antibiotic would require active antimicrobial susceptibility testing of gonococcal isolates globally and regionally to ascertain its current susceptibility status. Also, as suggested by Davido et al.,2 there is a need to develop susceptibility breakpoints for aztreonam and basic research should be completed to ascertain gonococcal mechanisms of resistance to this antibiotic. However, if N. gonorrhoeae isolates prove to be susceptible to this antibiotic, aztreonam might supplement spectinomycin (introduced initially to treat PPNG), or other treatment options, in gonococcal treatment guidelines. Transparency declarations None to declare. References 1 Thakur SD, Levett PN, Horsman GB et al.   High levels of susceptibility to new and older antibiotics in Neisseria gonorrhoeae isolates from Saskatchewan (2003–15): time to consider point-of-care or molecular testing for precision treatment? J Antimicrob Chemother  2018; 73: 118– 25. Google Scholar CrossRef Search ADS PubMed  2 Davido B, Dinh A, Matt M et al.   Comment on: High levels of susceptibility to new and older antibiotics in Neisseria gonorrhoeae isolates from Saskatchewan (2003–15): time to consider point-of-care or molecular testing for precision treatment? J Antimicrobial Chemother  2018; 73: 828– 9. 3 Tait IB, Winning J, Sleigh JD. Single dose aztreonam in treating gonorrhoea. Genitourin Med  1987; 63: 13– 5. Google Scholar PubMed  4 Miller LK, Sanchez PL, Berg SW et al.   Effectiveness of aztreonam, a new monobactam antibiotic, against penicillin-resistant gonococci. J Infect Dis  1983; 148: 612. Google Scholar CrossRef Search ADS PubMed  5 Stöberl C, Poitschek C, Söltz-Szöts J. Aztreonam, a new approach in the therapy of gonorrhea. Wien Klin Wochenschr  1991; 103: 271– 3. Google Scholar PubMed  6 Sykes RB, Bonner DP. Monobactam antibiotics: history and development. In: Williams JD, Woods P, eds. Aztreonam: The Antibiotic Discovery for Gram-Negative Infections . London, UK: Royal Society of Medicine, 1985; 3– 24. 7 Clendennen TE, Echeverria P, Saengeur S et al.   Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand. Antimicrob Agents Chemother  1992; 36: 1682– 7. Google Scholar CrossRef Search ADS PubMed  8 Muratani T, Akasaka S, Kobayashi T et al.   Outbreak of cefozopran (penicillin, oral cephems, and aztreonam)-resistant Neisseria gonorrhoeae in Japan. Antimicrob Agents Chemother  2001; 45: 3603– 6. Google Scholar CrossRef Search ADS PubMed  9 Akasaka S, Muratani T, Yamada Y et al.   Emergence of cephem- and aztreonam-high-resistant Neisseria gonorrhoeae that does not produce β-lactamase. J Infect Chemother  2001; 7: 49– 50. Google Scholar CrossRef Search ADS PubMed  10 Spencer RC, Talbot MD. The use of aztreonam in the treatment of uncomplicated gonorrhoea. Curr Med Res Opin  1985; 9: 591– 3. Google Scholar CrossRef Search ADS PubMed  11 Gottlieb A, Mills J. Effectiveness of aztreonam for the treatment of gonorrhea. Antimicrob Agents Chemother  1985; 27: 270– 1. Google Scholar CrossRef Search ADS PubMed  12 Evans DT, Crooks AJ, Jones C et al.   Treatment of uncomplicated gonorrhoea with single dose aztreonam. Genitourin Med  1986; 62: 318– 20. Google Scholar PubMed  13 Bharat A, Martin I, Zhanel GG et al.   In vitro potency and combination testing of antimicrobial agents against Neisseria gonorrhoeae. J Infect Chemother  2016; 22: 194– 7. Google Scholar CrossRef Search ADS PubMed  14 Davido B, Dinh A, Senard O et al.   Repurposing an old drug: aztreonam as a new treatment strategy for gonorrhoea. J Antimicrob Chemother  2017; 72: 1466– 8. Google Scholar PubMed  15 Dodson MG. Optimum therapy for acute pelvic inflammatory disease. Drugs  1990; 39: 511– 22. Google Scholar CrossRef Search ADS PubMed  16 Public Health Agency of Canada. Canadian Guidelines on Sexually Transmitted Infections. Section 4. Management and Treatment of Specific Syndromes. Pelvic Inflammatory Disease . Ottawa, Canada: Public Health Agency of Canada, 2013. https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/sexually-transmitted-infections/canadian-guidelines-sexually-transmitted-infections-22.html. 17 Dillon JR, Parti R, Thakur SD. Antibiotic resistance in Neisseria gonorrhoeae isolates: will infections be untreatable in the future? Culture (Oxoid)  2015; 35: 1– 8. 18 Fifer H, Natarajan U, Jones L et al.   Failure of dual antimicrobial therapy in treatment of gonorrhea. N Engl J Med  2016; 374: 2504– 6. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Journal

Journal of Antimicrobial ChemotherapyOxford University Press

Published: Mar 1, 2018

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