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
Bibliographic record
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. None to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.029 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.017 | 0.013 |
| Insufficient payload (model declined to judge) | 0.009 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".