First cases of Neisseria gonorrhoeae resistant to ceftriaxone in Catalonia, Spain, May 2011

Dear Editor,

We report the first 2 cases of Neisseria gonorrhoeae (NG) infection with a high minimal inhibitory concentration (MIC = 1.5 and 1 mg/L) to ceftriaxone in Catalonia, and to our knowledge in Spain, and the second in Europe.¹ Isolates were obtained from the rectum and urethra, respectively. The strain that triggered the alert came from a 21 year old man (case A) who attended the emergency department (ED) of a regional hospital on 20th April 2011 (day 15). He had received a phone call from his most recent sexual partner who had recently been diagnosed with gonococcal urethritis. On the date of arrival at the ED he was asymptomatic and the physical examination did not reveal signs of proctitis or urethritis. A rectal swab was performed and antimicrobial treatment with levofloxacin 500 mg/day for 7 days was prescribed. On 9th of May, (day 34) the microbiology laboratory reported the isolation of a strain of NG resistant to ceftriaxone and cefixime that was confirmed by a University Reference Laboratory. Susceptibility to penicillin, cefixime, ceftriaxone and ciprofloxacin was determined using E-test (bioMerieux) on a GC agar base supplemented by 1% defined growth supplement (Isovilalex, BD). Susceptibility to doxycycline and ciprofloxacin was tested by the disk diffusion method using the same medium. The interpretation was based on EUCAST breakpoints.² The MIC to penicillin was 0.094 mg/L, cefixime 1.5 mg/L and ceftriaxone 1.5 mg/L. The beta-lactamase test using the nitrocefin method (Cefinase, BD) was negative. The strain was also resistant to doxycycline and ciprofloxacin (MIC > 32 mg/L), but susceptible to azithromycin and spectinomycin. The patient was contacted on day 34, and despite being asymptomatic, based on the results of susceptibility studies, azithromycin 500 mg/day for 3 days was prescribed. On 26th of May (day 51), the patient remained asymptomatic. At that time, additional rectal and throat swabs were taken and the eradication of NG was confirmed. Epidemiological contact tracing information did not lead to further testing of the other three partners he had in previous three months.

Case B was the male sexual partner of case A for a period of 45 days prior to the onset of symptoms. He was seen by his general practitioner on day 4 of the onset of urethral discharge. Urethral swab and serological testing were performed and he was treated with doxycycline 100 mg, twice a day for seven days. Symptoms resolved on the second day of treatment. No additional swabs were taken. On day 13, microbiological results showed NG with a MIC to tetracycline 1.5 mg/L, ciprofloxacin >32 mg/L, ceftriaxone 1.5 mg/L. Testing for HIV and syphilis was negative. This patient was recalled and advised to alert his sexual partner. Apart from his current partner he had no relevant epidemiological and contact tracing information to consider.

Although there are some incongruities in the clinical development of the cases, patient B became asymptomatic despite being treated with an antibiotic for which the strain of NG was resistant, and although patient A was always asymptomatic, we think that the finding of in vitro resistance, together with the recent reports in the literature³ should trigger an alert regarding the emergence of these highly resistant strains.

Some lessons from our experience can be highlighted:

Firstly, emphasis should be placed on collecting urethral, rectal and pharyngeal swabs, especially from men having sex with men even if they are asymptomatic.⁴ Secondly, it is crucial to ensure that clinicians are aware of the latest guidelines on sexually transmitted diseases.^5,6 In our opinion, both patients received empirical treatment with suboptimal antimicrobial regimens. Finally, it is necessary to review the empirical ESC treatments, and the break-points of resistance by the sensitivity observed in each country.

Unfortunately, the spread of gonococcal isolates resistant to ceftriaxone in our country is probably only a matter of time, since public health alerts and extensive sampling of all anatomical sites are not systematically performed. Furthermore, the ability to identify, invite for testing and adequately treat all those potentially infected is quite difficult due to the high promiscuity of some of the infected subjects.

Therefore, as experts are already stressing^7,8 the use of AMR surveillance standards is a must to better understand the mechanisms of emergence and spread of AMR. Recent detection of treatment failures with cefixime in Europe^9,10 and the detection of a strain with high ceftriaxone MIC (2 mg/L) in Japan^11,12 which also caused treatment failure highlight the need for enhanced AMR and clinical failures surveillance.

Acknowledgements

Dr. Antonia Andreu, Microbiology Department of Hospital Vall d’Hebron (University Hospital Reference Laboratory), Barcelona, Spain, for her microbiological input in this letter and to Dr. M Luisa Garzo for triggering the alarm regarding the case that arrived in the emergency department of the Regional Hospital.