Gonorrhoea treatment failures to cefixime and azithromycin in England

Sexually Transmitted Bacteria Reference Laboratory, Health Protection Agency, London, United Kingdom.
Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin (Impact Factor: 5.72). 04/2011; 16(14).
Source: PubMed


Successful treatment of gonorrhoea is the mainstay of public health control. Cefixime and ceftriaxone, highly active third generation cephalosporins, are today the recommended first-line agents in most countries and azithromycin is a second-line agent. However, there is increasing evidence of decreasing susceptibility and emergence of therapeutic failures. In this report two cases of clinical failure to cefixime are described, one of which additionally shows failure to azithromycin and selection of a less susceptible strain during treatment.

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    • "However, its MICs are increasing over time (“MIC creep”) as observed worldwide [3,4,20], and one should be aware that CRO-resistant isolates can emerge and spread [4,7,11,12,14,17]. This possible development could also be favored by the observed decreased susceptibility to AZT, an antibiotic used together with CRO to cover Chlamydia trachomatis co-infections and more recently also implemented to prevent treatment failures of gonococcal infections [33,37]. In this overall scenario, we noted that all Ng tested were susceptible to SPE, probably because the use of this antibiotic has been abandoned after observing outbreaks of resistant isolates in the 1980s [3,4]. "
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    ABSTRACT: The spread of Neisseria gonorrhoeae (Ng) isolates resistant to the clinically implemented antibiotics is challenging the efficacy of treatments. Unfortunately, phenotypic and molecular data regarding Ng detected in Switzerland are scarce. We compared the characteristics of Ng detected during 1998-2001 (n = 26) to those detected during 2009-2012 (n = 34). MICs were obtained with the Etest and interpreted as non-susceptible (non-S) according to EUCAST. Sequence type (ST) was achieved implementing the NG-MAST. BlaTEM, ponA, penA, mtrR, penB, tet(M), gyrA, parC, mefA, ermA/B/C/F, rplD, rplV, and 23S rRNA genes were analyzed. The following susceptibility results were obtained (period:% of non-S, MIC90 in mg/L): penicillin (1998-2001: 42.3%, 3; 2009-2012: 85.3%, 16), cefixime (1998-2001: 0%, <=0.016; 2009-2012: 8.8%, 0.125), ceftriaxone (1998-2001: 0%, 0.004; 2009-2012: 0%, 0.047), ciprofloxacin (1998-2001: 7.7%, 0.006; 2009-2012: 73.5%, >=32), azithromycin (1998-2001: 11.5%, 0.25; 2009-2012: 23.6%, 0.38), tetracycline (1998-2001: 65.4%, 12; 2009-2012: 88.2%, 24), spectinomycin (1998-2001: 0%, 12; 2009-2012: 0%, 8). The prevalence of multidrug-resistant (MDR) isolates increased from 7.7% in 1998-2001 to 70.6% in 2009-2012. International STs and genogroups (G) emerged during 2009-2012 (G1407, 29.4%; G2992, 11.7%; G225, 8.8%). These isolates possessed distinctive mechanisms of resistance (e.g., G1407: PBP1 with L421, PBP2 pattern XXXIV, GyrA with S91F and D95G, ParC with S87R, PorB with G120K and A121N, mtrR promoter with A deletion). The prevalence of penicillin- ciprofloxacin- and tetracycline-resistant Ng has reached dramatic levels, whereas cefixime and ceftriaxone show MICs that tend to increase during time. International MDR clones less susceptible to cephalosporins are rapidly emerging indicating that the era of untreatable gonococcal infections is close.
    Full-text · Article · Feb 2014 · BMC Infectious Diseases
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    • "The conventional treatment of bacterial infections currently lies in administering antibiotics alone or in combination [23], or using last-generation antibiotics as the case of the multi-resistant Enterobacteriaceae with carbapenems [24]. In spite of this, strains resistant to these new antibacterials emerge continuously, making the situation critical. "
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    ABSTRACT: The emergence of antibiotic-resistant pathogenic bacteria during the last decades has become a public health concern worldwide. Aiming to explore new alternatives to treat antibiotic-resistant bacteria and given that the tellurium oxyanion tellurite is highly toxic for most microorganisms, we evaluated the ability of sub lethal tellurite concentrations to strengthen the effect of several antibiotics. Tellurite, at nM or µM concentrations, increased importantly the toxicity of defined antibacterials. This was observed with both gram negative and gram positive bacteria, irrespective of the antibiotic or tellurite tolerance of the particular microorganism. The tellurite-mediated antibiotic-potentiating effect occurs in laboratory and clinical, uropathogenic Escherichia coli, especially with antibiotics disturbing the cell wall (ampicillin, cefotaxime) or protein synthesis (tetracycline, chloramphenicol, gentamicin). In particular, the effect of tellurite on the activity of the clinically-relevant, third-generation cephalosporin (cefotaxime), was evaluated. Cell viability assays showed that tellurite and cefotaxime act synergistically against E. coli. In conclusion, using tellurite like an adjuvant could be of great help to cope with several multi-resistant pathogens.
    Full-text · Article · Apr 2012 · PLoS ONE
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    ABSTRACT: Background The development of resistance to multiple antimicrobials has limited treatment options for gonorrhoea. Potential emergence of cephalosporin resistance in Neisseria gonorrhoeae and cephalosporin allergy in some patients make it necessary to evaluate the effectiveness of other available antimicrobials. Gentamicin is widely available in the USA and is used for gonorrhoea treatment in several countries. Methods We conducted a systematic review of the medical literature to assess the effectiveness of gentamicin for treatment of uncomplicated urogenital gonococcal infections. Two reviewers assessed relevant articles and independently selected studies that met pre-specified selection criteria (including systematic enrolment and assignment to treatment and culture-confirmed diagnosis and outcome). Summary measures for selected studies were pooled using inverse variance-weighted averages with fixed effects. Heterogeneity was assessed using I-squared, which estimates proportion (from 0% to 100%) of variability attributable to heterogeneity between studies. Pooled percentage with negative follow-up culture was compared with CDC criteria for selection of recommended therapy (>95% efficacy with lower 95% CI >95%). Results 18 potentially relevant English-language studies were identified; three met inclusion criteria. Reviewer agreement for initial judgement on meeting selection criteria was substantial (κ 0.68). Two studies used 240 mg, and one study used 280 mg IM gentamicin. Percentages with negative culture after single-dose treatment were 90.7% (n=86), 91.4% (n=220), and 95.0% (n=40). Pooled percentage with negative culture after single-dose treatment was 91.5% (95% CI 88.1% to 94.0%, I-squared = 0%). Conclusions Gentamicin does not meet current CDC criteria for recommended treatment of gonorrhoea. However, if cephalosporin resistance emerges, gentamicin may be a useful alternative agent. Evaluation of additional regimens, including combination therapy, is warranted.
    Full-text · Article · Jul 2011 · Sexually Transmitted Infections
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