Cephalosporin MIC creep among gonococci: time for a pharmacodynamic rethink?

Chisholm, Stephanie; Mouton, Johan W.; Lewis, David A.; Nichols, Tom; Ison, Catherine; Livermore, David M.

doi:10.1093/jac/dkq289

Cited by 152 publications

(168 citation statements)

References 42 publications

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“…In 2012, the World Health Organization (WHO) released a global action plan to control the spread and impact of antimicrobialresistant N. gonorrhoeae and published new recommendations and criteria for decreased susceptibility to cephalosporins, including cefixime (a MIC of Ն0.25 g/ml) and ceftriaxone (a MIC of Ն0.125 g/ml) (http://whqlibdoc.who.int/publications/2012/97 89241503501_eng.pdf). A resistance threshold of Ͼ0.12 g/ml for cefixime in the treatment of N. gonorrhoeae has been also supported by other studies (18). The MIC for ceftriaxone in our study samples ranged from 0.004 to 0.25 g/ml, and the MIC for cefixime ranged from Ͻ0.016 to 0.12 g/ml.…”

Section: Specimens Testedsupporting

confidence: 90%

Utility of Specimens Positive for Neisseria gonorrhoeae by the Aptima Combo 2 Assay for Assessment of Strain Diversity and Antibiotic Resistance

et al. 2013

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In our jurisdiction, the Aptima Combo 2 assay (Gen-Probe, Inc.) is used to detect Neisseria gonorrhoeae from specimens collected at clinics for sexually transmitted infections (STI) and from select community patients. In addition, swabs are also collected for N. gonorrhoeae culture, susceptibility testing, and sequence typing (ST). Since only a small proportion of samples from provincial cases undergo culture, the available trends in antimicrobial susceptibility and predominant strain types may not be representative of all N. gonorrhoeae infections. Due to the limitations facing the use of N. gonorrhoeae culture to understand these trends in the general community, we performed a molecular analysis for markers of cephalosporin resistance and ST determination by using nucleic acid extracts of specimens sent for Aptima testing. Thirty-four samples submitted for both Aptima testing and N. gonorrhoeae culture from the same anatomic location (within 24 h) were included in the study. Sequence type was determined based on the sequence of the por and tbpB genes, and amino acid changes in the PBP 2 protein, encoded by the penA gene, were considered representative for the assessment of antimicrobial susceptibility. Sequence identity of 100% was observed between the sequences obtained from Aptima-analyzed samples and culture samples. Sequencing results showed an association between decreased susceptibility to extended-spectrum cephalosporins (ESC ds ), tbp allele 110, ST 1407, and amino acid changes (G545S, I312M, and V316T) in the PBP 2 protein. Our data, generated based on a few representative genes, suggest that gonococcal samples positive by Aptima testing can be used to determine single nucleotide polymorphisms associated with ESC ds and the sequence type based on molecular strain typing. Confirmation of these findings may obviate the need for gonorrhea culture in the future. N eisseria gonorrhoeae is a common sexually transmitted infection that affects mucosal surfaces and causes a spectrum of conditions, including urethritis, endocervicitis, pelvic inflammatory disease, and infertility (1). Over the years, gonococci have developed resistance to multiple classes of antibiotics, including penicillins, tetracyclines, macrolides, and quinolones (2). Of recent concern is a steady increase in the MICs to extended-spectrum cephalosporins, including cefixime and ceftriaxone, in several countries including Canada, with reported levels at 0.12 g/ml, one doubling dilution away from the Clinical and Laboratory Standards Institute (CLSI) limit of 0.25 g/ml for susceptibility (3-7; CLSI standard M100-S23, January 2013). According to a recent U.S. Centers for Disease Control and Prevention (CDC) update, untreatable gonorrhea could soon be a reality in the United States (http://www.cdc.gov/mmwr/preview /mmwrhtml/mm6131a3.htm). The agency noted that N. gonorrhoeae seems to be developing resistance to the oral antibiotic cefixime, and it no longer recommends cefixime at any dose as a firstline regimen for treatment of gonococcal infec...

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Section: Specimens Testedsupporting

confidence: 90%

Utility of Specimens Positive for Neisseria gonorrhoeae by the Aptima Combo 2 Assay for Assessment of Strain Diversity and Antibiotic Resistance

et al. 2013

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“…Many of these microorganisms most often are tested by disk diffusion or agar dilution on a variety of media (11). Like anaerobic bacteria, these microorganisms are amenable to testing by gradient endpoint susceptibility, and Etest is often used in clin-ical laboratories (4,8,14). The importance of accurate testing for monitoring the antimicrobial resistance of the microorganisms has been identified in many instances (18,19,23,29).…”

mentioning

confidence: 99%

First Comprehensive Evaluation of the M.I.C. Evaluator Device Compared to Etest and CLSI Reference Dilution Methods for Antimicrobial Susceptibility Testing of Clinical Strains of Anaerobes and Other Fastidious Bacterial Species

et al. 2012

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bThe new M.I.C. Evaluator strip uses test methodology and the recording of results that are similar to those of Etest. For this first assessment, 102 clinical strains of anaerobic bacteria from 12 genera and 155 strains from 7 genera and 8 species of fastidious bacteria were tested by M.I.C. Evaluator, Etest, and agar dilution or broth microdilution as a reference standard. Ampicillin, amoxicillin, amoxicillin-clavulanate, cefotaxime, ciprofloxacin, erythromycin, imipenem, levofloxacin, metronidazole, penicillin, and tetracycline were tested depending on the species. Agar dilution for anaerobes was performed according to CLSI document M11-A7. For the fastidious bacteria, CLSI document M45-A2 was followed. For the anaerobes, essential and categorical agreement between M.I.C. Evaluator and Etest was >90%. Compared to agar dilution, essential agreement was low for both strip tests, and many very major errors were observed for metronidazole (13 to 14%) and penicillin (8 to 9%) with isolates from the Bacteroides fragilis group and Clostridium species. For fastidious species, essential agreements for M.I.C. Evaluator and Etest plus or minus one doubling dilution were >95%. Compared to broth microdilution, essential agreements were low (40 to 90%) plus or minus one dilution and were >90% plus or minus two dilutions, with high overall category agreement (CA). Major and minor errors were within established parameters for all strains tested. The M.I.C. Evaluator strips were equivalent to Etest for anaerobes and fastidious species. These observations require further investigation to determine which methods provide the most accurate MIC for clinical utility. The further evaluation of additional M.I.C. Evaluator agents will be performed as they become available.

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“…The A8806 strain also shared the same multilocus sequence type as H041 but differed from H041 in the N. gonorrhoeae multiantigen sequence type (Table 1). Previous pharmacodynamic analyses have predicted that treatment failures are likely for strains with an MIC of 0.5 mg per liter with the use of ceftriaxone monotherapy at doses of 250 mg and 500 mg. 5 Thus, this isolate arouses new concerns over the ongoing efficacy of ceftriaxone monotherapy for treatment of gonorrhea. Data are lacking to determine the prevalence and spread of the A8806 strain in Australia and elsewhere.…”

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confidence: 99%