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Abstract
Objectives Disseminated gonococcal infections (DGIs) are rare. We describe the characteristics of DGIs in France.
Methods This is a 3-year retrospective analysis of DGI cases collected through two networks of microbiologists and infectious disease specialists in France between 2009 and 2011. DGI was defined either by the isolation of Neisseria gonorrhoeae from blood and synovial fluid or by the existence of a clinical syndrome consistent with DGI and the isolation of N gonorrhoeae from any site. We describe the epidemiological, clinical and microbiological characteristics and outcomes of DGIs.
Results 21 patients (9 women, 12 men; 18–62 years old) were diagnosed with DGI. The number of DGI cases increased between 2009 and 2011. Two men who had sex with men were coinfected with HIV. We found 28 extragenital locations, including arthritis (14 cases), tenosynovitis (7), skin lesions (4), endocarditis (1), prostatitis (1) and pelvic inflammatory disease (1). Genital signs were present in five patients. The diagnosis was confirmed by cultures in 20 patients—blood (4), synovial fluid (11), genital (3), throat (1), urine (1)—and by molecular biology on a pharyngeal swab in 1 patient. Seven cases were resistant to fluoroquinolones. The patients were treated with ceftriaxone, associated with corticosteroids (two cases) and surgery (six cases). Four patients had joint sequelae.
Conclusions DGIs are increasing. Men seem to be at higher risk than women. Joint involvement was common. Microbiological diagnosis was based on culture, however molecular biology using pharyngeal swabs was helpful when cultures were negative.
- NEISSERIA GONORRHOEA
- GONOCOCCI
- DERMATOLOGY
- EPIDEMIOLOGY (CLINICAL)
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Introduction
Neisseria gonorrhoea infection was the second most commonly declared sexually transmitted infection (STI) in France in 2010.1 Moreover, according to the monitoring networks RENAGO (Réseau National des gonocoques) and ResIST (Réseau de surveillance des Infections Sexuellement Transmissibles),2 gonococcal infections are increasing in France and in other countries such as the USA3 and in Europe.4
Disseminated gonococcal infection (DGI) has been estimated to account for 0.5–3% of gonococcal infections.5 DGI is usually referred to as a clinical triad with skin lesions, arthritis and tenosynovitis.6 ,7 Before the era of antibiotics, DGI and gonococcal endocarditis were observed.
The last two major reports on DGIs were published in 1983 and 1994, and included 49 and 41 patients, respectively.6 ,7 Therefore the question of modifications of DGI presentation during the last two decades can be raised. We evaluated the epidemiological, clinical and microbiological features of DGI and the associated treatment and outcome.
Materials and methods
We retrospectively studied cases of DGI observed in France from 1 January 2009 to 31 December 2011. We asked the microbiologists of the ‘Collège de bacteriologie, virologie et d'hygiène hospitalière de Paris’ (COL.BVH) and all the infectious disease (ID) specialists in France to report their cases. A single anonymous questionnaire, filled out by one of the authors for patients hospitalised in the Paris area or by the treating physician for patients in other areas, enabled data collection. DGI was defined either by the isolation of N gonorrhoeae from blood and synovial fluid or by the existence of a clinical syndrome consistent with DGI and isolation of N gonorrhoea from a genital, oral, anal or any other site. The diagnosis always relied on culture or molecular biology based on the different infection site samples. Gonococcal isolates were obtained after inoculation onto non-selective chocolate agar and selective agar containing antimicrobial agents that inhibit the growth of commensal bacteria and fungi and incubating them at 35–37°C in a moist atmosphere enriched with CO2 for 18–24 h.
We evaluated the epidemiological, clinical and microbiological features, and the treatment administered and the related outcome. The socio-demographic information included age, sex, area of residence in France and sexual orientation, such as being a man having sex with a man (MSM). History of STIs and antibiotics received during the previous 6 months were also evaluated. HIV infection was systematically investigated. Behavioural evaluation included the existence of a stable partner or casual sex practices and recent travels.
We evaluated the following clinical items: body temperature, skin manifestations, arthralgia, arthritis, tenosynovotis, meningeal signs, dysuria, heart involvement and any other signs.
Microbiological diagnosis was based on sample cultures taken at different sites of infection or by molecular biology (PCR). The susceptibility of N gonorrhoeae strains to different antibiotics (penicillin, ceftriaxone, fluoroquinolones, spectinomycin, chloramphenicol and tetracycline) was evaluated with disc diffusion, as recommended by the national guidelines.8 Molecular strains typing by N gonorrhoeae multiantigen sequence typing could not be done. We assessed the antibiotic, need for surgery, use of analgesics and anti-inflammatory drugs, treatment for coexisting STIs and outcomes distinguishing clinical cure, relapse and sequelae.
Results
Twenty-one cases of DGI were evaluated. There were 9 women and 12 men, including 5 MSM (table 1). The number of DGIs increased from 2 in 2009 to 9 in 2010 and 10 in 2011.
Epidemiological, clinical, and microbiological characteristics of 21 French patients with DGI
The median age was 30 years overall, 20 years in women (18–62 years) and 37 years in men (19–55 years). Ten patients lived in the Paris area and 11 elsewhere. Seven patients had a history of STIs (genital herpes, genital warts, Chlamydia trachomatis, N gonorrhoeae and hepatitis B in two patients). One MSM was HIV positive and efficiently treated with an undetectable viral load. In addition, among the 20 remaining patients, one was found to be infected with HIV.
Fourteen patients reported unprotected sex, including five with a steady partner and nine with casual partners, whereas the other seven patients did not specify this. Two patients had sexual intercourse during recent travel abroad.
Clinically, 28 extra genital locations were found: arthritis (14 cases), tenosynovitis (7), skin pustules or papules (4), aortic endocarditis (1), prostatitis (1) and pelvic inflammatory disease with septicaemia (1 case). Genital signs were observed in five patients, four men having urethritis and one woman with cervicitis. Among the five MSM, four had no genital symptoms. None were found with symptomatic pharyngitis.
Microbiological diagnosis relied on culture in 20 patients and molecular biology in 1 patient. DGI diagnosis was based on 21 positive cultures from articular sites (11 cases), urethra (3), throat (1), uterus (1), blood (4) and urine (1) as one patient had a positive culture from a urethral swab and articular sample. One MSM patient was diagnosed with molecular biology based on a throat swab.
Antibiograms revealed eight cases of resistance to penicillin (38%), including three β-lactamase-producing strains. Five strains were resistant to tetracycline and seven to fluoroquinolones (33%). All strains were susceptible to ceftriaxone, chloramphenicol and spectinomycin.
Nineteen patients were initially treated with ceftriaxone, either prescribed alone with daily doses of 1 g (4 cases), 2 g (11 cases) or 4 g (aortic endocarditis), or in combination with gentamicin (3 mg/kg/day for 5–7 days) in three patients (endocarditis, knee arthritis and temporo mandibular arthritis). Two patients received treatment with amoxicillin (8 g/day for 7 days) and amoxicillin clavulanate (3 g/day). In two cases, ceftriaxone was stopped due to fever with elevated liver enzyme rate, or neutropaenia. The median treatment duration was 14 days and ranged from 1 week to 2 months (endocarditis). Six patients underwent surgery—there was one valve replacement and five cases of joint lavage. Analgesics and corticosteroids were prescribed to two patients with severe inflammatory synovitis while morphinics were prescribed in three other cases.
Nine other STIs were treated, including eight, proven or probable, infections due to Chlamydia trachomatis and treated with a single dose of azithromycin or a 7-day course of doxycycline. A patient with early latent syphilis received benzathine benzyl penicillin.
The overall outcome was good except for four patients with articular sequelae (stiffness, oedema or residual pain) after a 1-month follow-up.
Discussion
This retrospective series points out a recent increase in DGI cases and highlights changes in the DGI presentation, such as male predominance, coinfection with HIV, the pharyngeal reservoir and the high frequency of sequelae.
Obviously the number of DGI cases increased between 2009 and 2011. This increasing trend is consistent with data from the Institut de Veille Sanitaire, showing that the number of declared cases of gonococcal infections went up from 397 in 2009 to 534 in 2010 and 735 in 2011 in the ResIST network, and from 1521 in 2009 to 1870 in 2010 and 1875 in 2011 in the RENAGO network.2 This is similar to trends seen in the USA where the rate of gonorrhoeae for a population of 100 000 increased by 6% between 2009 and 2011,3 and in Europe (especially in Finland, Portugal, Sweden, the UK) with an overall rate of 10.4 per 100 000 population.4
The male predominance with a M:F sex ratio of 1:3 contrasts with other large series of DGI cases. Indeed, in the two largest series, M:F sex ratios were estimated at 0.4 for patients included between 1975 and 1982 and at 0.2 between 1985 and 1991.6 ,7 Such a change is probably linked to modifications of sexual behaviour, with increasing MSM corresponding to more than 50% of male patients, and fellatio as an important risk factor for gonorrhoea as shown in other studies.9 In this study, DGI diagnosis was confirmed in two cases by throat swab, indicating the pharynx to be the forgotten reservoir for gonorrhoeae.9
Regarding the typical triad of arthritis, tenosynovitis and cutaneous lesions, 4 patients had two of the triad signs and 14 had one of the triad signs. Only one patient had all the triad signs whereas the corresponding figure was not described in the two previous studies.6 ,7 Of our 21 patients, 66% presented with arthritis whereas joint involvement was diagnosed in 39% of 49 patients in Boston6 and 100% of 41 patients in North Carolina,7 but these were the inclusion criteria in this latter study. Overall the most commonly involved joint was the knee. In contrast, cutaneous eruption was observed in 71% of the 49 patients in Boston and in a significant minority of the patients in North Carolina, whereas the corresponding figure was 19% in our study. The prevalence of tenosynovitis varied from 33% in our series to 61% in the North Carolina study. Two patients had DGI without any signs of the triad but had prostatitis and pelvic inflammatory disease, which are well known complications of gonorrhoea.10 One female patient was diagnosed with endocarditis, an unusual but well known and life-threatening complication of gonorrhoea.11
We only included patients with microbial confirmation of the diagnosis. Indeed, this pathogen is difficult to obtain by culture due to its fragility.10 Given the better sensitivity of molecular biology testing for diagnosing urethritis,12 the diagnosis of DGI could benefit from such a technique applied on different samples—urogenital, rectum, synovial fluids, skin lesions and throat—when the diagnosis cannot be made by culture.10
In this series 33% of the isolated strains were resistant to fluoroquinolones and 38% to penicillin. These results are consistent with the resistance pattern of N gonorrhoeae to antimicrobial agents in France as elsewhere more strains resistant are to fluoroquinolones.10 No strain exhibited resistance to ceftriaxone.
Some prescriptions did not follow the recommendations.13 Two patients were treated with penicillins instead of ceftriaxone. However, both strains were susceptible to penicillins.
The daily dose of ceftriaxone varied from one patient to another given the different habits of treating physicians and the range of severe complications (arthritis, endocarditis). Similarly, the severity of these complications explains the need for adjuvant treatment such as corticosteroids and surgery. Our patients were cured with antibiotics but six underwent surgery and four had sequelae after a month.
In conclusion, DGI is a re-emerging disease which now mainly affects men. A diagnosis of DGI should be systematically considered in cases of arthritis in patients taking sexual risks. The diagnosis could benefit from the molecular biology technique applied to samples taken from all potential infection sites if cultures are negative, including the pharynx, which can be considered as a reservoir.
Acknowledgments
We wish to thank the ‘Collège de bacteriologie, virologie et d'hygiène hospitalière de Paris’ (ColBVH) for assistance in identifying cases, and Maxime Romano for assistance in manuscript preparation.
Footnotes
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Handling editor Jackie A Cassell
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Handling editor Jackie A Cassell
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Collaborators Working Group FRA-DGI: Stéphane Jaureguiberry and Loic Epelboin (GH Pitié-Salpêtrière, Paris), Jean Luc Schmit (Amiens), Michèle Texereau (Niort), Mickaël Meynard (Rennes), Valérie Zeller (Hopital de la Croix Saint Simon), Jean Beytout (Clermont Ferrand), Claudine Barbuat and Nicole Bouzigues (Nimes), Pierre Delobel and Lydie Porte (Toulouse), Eric Auxenfants (Roubaix).
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Contributors We guarantee that all authors have seen and approved the manuscript.
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Provenance and peer review Not commissioned; externally peer reviewed.
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Competing interests None.
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Provenance and peer review Not commissioned; externally peer reviewed.