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Recommended antimicrobial treatment of uncomplicated gonorrhoea in 2009 in 11 East European countries: implementation of a Neisseria gonorrhoeae antimicrobial susceptibility programme in this region is crucial
  1. M Unemo1,
  2. E Shipitsyna2,
  3. M Domeika3 on behalf of the Eastern European Sexual and Reproductive Health (EE SRH) Network Antimicrobial Resistance Group
  1. 1National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden
  2. 2Laboratory of Microbiology, the DO Ott Research Institute of Obstetrics and Gynaecology, St Petersburg, Russia
  3. 3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  1. Correspondence to Dr Magnus Unemo, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro SE-701 85, Sweden; magnus.unemo{at}orebroll.se

Abstract

Background Antimicrobial resistance (AMR) in Neisseria gonorrhoeae (gonococcus) is a major problem worldwide. Quality-assured and quality-controlled AMR surveillance data on gonococci globally are crucial for public health purposes. In East European countries, knowledge regarding gonococcal AMR and its prevalence is limited.

Objectives To ascertain the recommendations for antimicrobial treatment of uncomplicated gonorrhoea in 11 East European countries, valuable information for introducing an international gonococcal AMR surveillance programme.

Methods A questionnaire was used to collect information regarding the types, doses and manufacturers of the antimicrobials recommended for gonorrhoea treatment in all countries.

Results Ceftriaxone (250–1000 mg, intramuscularly (IM)×1) was reported as a first-line antimicrobial in all countries (n=11). Many of the second-line and alternative treatments seemed suboptimal for empirical treatment. Regionally manufactured antimicrobials were predominantly used and easily available, and some may be of suboptimal quality. This generates effective prerequisites for emergence, and rapid spread of gonococcal AMR and gonorrhoea.

Conclusion Ceftriaxone was first-line antimicrobial in all the 11 East European countries, which is an appropriate choice also in a global perspective. However, the adherence, especially among private physicians, to these public sector recommendations is questionable. Implementation of national and international gonococcal AMR surveillance in this region is crucial; to provide evidence-based data for regular and timely updating of treatment guidelines, to identify emerging resistance, and to assist in the prevention, control and containment of gonococcal AMR and gonorrhoea.

  • Neisseria gonorrhoeae
  • gonorrhoea
  • antimicrobial resistance (AMR)
  • treatment
  • WHO
  • EE SRH Network
  • Eastern Europe
  • surveillance
  • treatment
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Gonorrhoea remains a major public health problem.1 In East European countries, the incidence of gonorrhoea has generally been declining but still remains high.2

Effective antimicrobial treatment is essential in gonorrhoea control.3–6 However, the resistance in Neisseria gonorrhoeae (gonococcus) to all traditional gonorrhoea antimicrobials (penicillins, tetracycline, ciprofloxacin) is high, and azithromycin resistance, including high-level, has spread rapidly.3 Extended-spectrum cephalosporins (ESCs) are currently the ideal treatment options. Nevertheless, the susceptibility to ESCs is decreasing worldwide, with treatment failures using oral ESCs such as cefixime occurring, especially in Japan.3 7 Confirmed treatment failures of urogenital gonorrhoea using ceftriaxone (injectable), in an effective dose and of appropriate quality, are still lacking. However, two cases have been reported for pharyngeal gonorrhoea.3 This is a serious concern globally, and gonorrhoea may become untreatable in certain circumstances.

The WHO recently published initiatives to enhance global, quality-assured and quality-controlled, gonococcal antimicrobial resistance (AMR) surveillance.3 8 Several gonococcal AMR programmes are operating at the national and/or international level.3 For example, the European Union/European Centre for Disease Prevention and Control (EU/ECDC)-funded European gonococcal antimicrobial susceptibility programme (EURO-GASP) is operating in EU/EFTA countries.5 However, valid AMR data are exceedingly scarce in many regions, including Eastern Europe. In this entire region, only Russia has a national gonococcal AMR programme (RU-GASP).9

The aims were to ascertain the recommendations for antimicrobial treatment of uncomplicated gonorrhoea in 11 East European countries, valuable information for introducing an international gonococcal AMR surveillance programme, based on WHO protocols.3 8 10

Methods

Eleven countries from the EE SRH Network11 (table 1) participated. In April–June 2009, STI head specialists of their Health Ministries provided, through a questionnaire, information regarding the types, doses and manufacturers of the antimicrobials recommended for the gonorrhoea treatment.

Table 1

Recommendations for treatment of uncomplicated gonorrhoea in 11 East European countries*

Results

First-line gonorrhoea treatment in all countries (n=11) was ceftriaxone (injected intramuscularly (IM)); 250 mg (n=8), 1 g (n=2) and 500 mg (n=1). Second-line was predominantly spectinomycin (n=6), but cefixime (n=1), azithromycin (n=1), ciprofloxacin (n=1), ofloxacin (n=1) or roxithromycin (n=1) was recommended in some countries. As alternative treatments, antimicrobials such as kanamycin, erythromycin and doxycycline were also recommended. Some antimicrobials were used to cover both gonorrhoea and chlamydial infection.

High numbers of trademarks/manufacturers were reported for several antimicrobials—for example, 24 different (from 13 countries) ones for ceftriaxone. It was impossible to trace some of the trademarks and/or to determine how widely used each of them was. However, in most countries, predominantly antimicrobials manufactured nationally, regionally or, for example, in India were used (table 1).

Discussion

This is the first study describing the antimicrobials recommended for gonorrhoea treatment in 11 East European countries. In all countries, ceftriaxone (250–1000 mg, IM×1) was recommended as first-line, which is appropriate also in a global perspective.3 However, certainly not all, especially not private physicians, strictly adhere to these public sector recommendations. Accordingly, the present survey cannot inform on the antimicrobials actually administered to all gonorrhoea patients in clinical practice. Further studies are in progress to determine what is actually being used in both public and private clinics. In general, it would be valuable to monitor and regulate the type of antimicrobials used, the amount of the different antimicrobials, the manufacturers of the antimicrobials and the quality of the antimicrobials in all these countries. As second-line, spectinomycin was predominantly recommended. Spectinomycin is effective, and resistance is rare worldwide.3 However, resistance may emerge rapidly and has recently been reported in Russia.3 9 Five countries reported using Trobicin; however, in 2005, Pfizer discontinued this production. In many countries, the recommendations of second-line and alternative treatments were suboptimal. Based on AMR data from Russia,9 and worldwide,3 many of these antimicrobials should not be used in empirical gonorrhoea treatment.

In most countries, antimicrobials manufactured nationally, regionally or in India, for example, were predominantly used, because of the higher costs of antimicrobials from internationally recognised companies. Some countries even mentioned treatment failures using regionally manufactured ceftriaxone, which presumably reflects suboptimal quality of the antimicrobial; however, this is crucial to confirm. In settings, such as most East European countries, where antimicrobials are easily available, and the quality of antimicrobials may be suboptimal, there is a substantially increased risk for emergence and rapid spread of gonococcal AMR and gonorrhoea.3

As the WHO has stated, to avoid making gonorrhoea untreatable under certain circumstances, global initiatives integrating disease control and AMR containment are urgently needed.3 The overuse and misuse of antimicrobials, including using antimicrobials of suboptimal quality, especially in settings where the disease control is insufficient, rapidly increase the AMR.3 The WHO initiatives include enhanced global, quality-assured and quality-controlled, AMR surveillance, which is crucial for public health.3 8 Valid AMR data are exceedingly scarce in many regions, including Eastern Europe beyond Russia.9 Accordingly, implementation of local, national and international gonococcal AMR surveillance in the other East European countries is crucial; to provide evidence-based data, regarding antimicrobials used for treatment, for regular and timely updating of STI management and treatment guidelines, to identify emerging resistance and to assist in the prevention, control and containment of gonococcal AMR and gonorrhoea.3 4

In conclusion, this study ascertained the recommendations for antimicrobial treatment of gonorrhoea in 11 East European countries. Ceftriaxone (250–1000 mg) was a first-line antimicrobial in all the countries, which is an appropriate choice also in a global perspective. However, the adherence, especially among private physicians, to these public sector recommendations is questionable. This is valuable information for implementing an international gonococcal AMR surveillance programme in this region, based on WHO protocols,3 8 10 which is crucial for informing STI management and treatment guidelines for gonorrhoea and, accordingly, for public health.

Key messages

  • Antimicrobial resistance (AMR) in gonococci is an emergent problem. AMR surveillance globally is crucial for public health, but is mainly lacking in Eastern Europe.

  • Ceftriaxone (250–1000 mg) was reported as a first-line treatment in all 11 surveyed East European countries, which is an appropriate choice also in a global perspective.

  • Many of the second-line and alternative treatments seemed suboptimal. Antimicrobials were easily available, and in most countries antimicrobials manufactured regionally were predominantly used.

  • Implementation of gonococcal AMR surveillance in Eastern Europe is crucial; for appropriate updating of treatment guidelines, and assisting in gonorrhoea control and AMR containment.

References

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Footnotes

  • Funding This study was supported by the EE SRH Network, and the WHO.

    Eastern European Sexual and Health (EE SRH) Network Antimicrobial Resistance Group: K Babayan, M Aznauryan (Armenia); A Kengerli, V Eyvazov (Azerbaijan); N Sukhobokova, N Pankratova, I Shimanskaya, S Glazkova (Belarus); S Tchiokadze, G Galdava, O Kvivlidze (Georgia); T Brilene (Estonia); A Bayduysenova (Kazakhstan); G Mamayeva (Kyrgyzstan); S Polevschikova, N Frigo, A Savicheva (Russia); Z Yunusova (Tajikistan); N Kochetova, G Mavrov (Ukraine); S Ibragimov, A Davurov (Uzbekistan)

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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