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Objective: To describe Neisseria gonorrhoeae treatment failure to the recommended antimicrobial regimens (azithromycin, cefixime and ceftriaxone)., Methods: Our study was a longitudinal analysis of treatment failures from an observational open cohort of gonococcal infection cases collected in Québec, Canada (n = 2547) between September 2015 and December 2019. Epidemiological and clinical data were collected using a self-administered questionnaire, direct case interviews and chart reviews. Antimicrobial susceptibility testing was performed using the agar dilution method. To be retained as a treatment failure, cases must have had (i) a laboratory-confirmed gonococcal infection; (ii) a documented treatment; (iii) a positive test of cure (TOC) performed within a defined period and (iv) no sexual contact (vaginal, oral or anal), even protected with a condom, between the beginning of treatment and the positive TOC. A broader definition, including suspected cases, was also examined., Results: Among 1593 cases where a TOC was performed, 83 had a positive TOC: 11 were retained as treatment failure, and 6 were considered suspected cases (overall = 17/1593; 1.1%). Possible explanations for retained or suspected treatment failure included resistance to the antibiotics used for treatment (n = 1), pharyngeal infection (n = 9, of which 5 had been treated with ceftriaxone and 4 with other regimens); and azithromycin monotherapy (n = 1). Some cases had more than one potential explanation., Conclusions: Treatment failure occurred in 1.1% of cases of Neisseria gonorrhoeae infection for which a TOC was performed, including some cases of pharyngeal infection treated with ceftriaxone., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) more...

Objectives: Regular quality-assured WGS with antimicrobial resistance (AMR) and epidemiological data of patients is imperative to elucidate the shifting gonorrhoea epidemiology, nationally and internationally. We describe the dynamics of the gonococcal population in 11 cities in Brazil between 2017 and 2020 and elucidate emerging and disappearing gonococcal lineages associated with AMR, compare to Brazilian WGS and AMR data from 2015 to 2016, and explain recent changes in gonococcal AMR and gonorrhoea epidemiology., Methods: WGS was performed using Illumina NextSeq 550 and genomes of 623 gonococcal isolates were used for downstream analysis. Molecular typing and AMR determinants were obtained and links between genomic lineages and AMR (determined by agar dilution/Etest) examined., Results: Azithromycin resistance (15.6%, 97/623) had substantially increased and was mainly explained by clonal expansions of strains with 23S rRNA C2611T (mostly NG-STAR CC124) and mtr mosaics (mostly NG-STAR CC63, MLST ST9363). Resistance to ceftriaxone and cefixime remained at the same levels as in 2015-16, i.e. at 0% and 0.2% (1/623), respectively. Regarding novel gonorrhoea treatments, no known zoliflodacin-resistance gyrB mutations or gepotidacin-resistance gyrA mutations were found. Genomic lineages and sublineages showed a phylogenomic shift from sublineage A5 to sublineages A1-A4, while isolates within lineage B remained diverse in Brazil., Conclusions: Azithromycin resistance, mainly caused by 23S rRNA C2611T and mtrD mosaics/semi-mosaics, had substantially increased in Brazil. This mostly low-level azithromycin resistance may threaten the recommended ceftriaxone-azithromycin therapy, but the lack of ceftriaxone resistance is encouraging. Enhanced gonococcal AMR surveillance, including WGS, is imperative in Brazil and other Latin American and Caribbean countries., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) more...

Introduction: Antimicrobial resistance in Neisseria gonorrhoeae compromises gonorrhoea treatment and rapid antimicrobial susceptibility testing (AST) would be valuable. We have developed a rapid and accurate flow cytometry method (FCM) for AST of gonococci., Methods: The 2016 WHO gonococcal reference strains, and WHO Q, R and S (n = 17) were tested against seven clinically relevant antibiotics (ceftriaxone, cefixime, azithromycin, spectinomycin, ciprofloxacin, tetracycline and gentamicin). After 4.5 h incubation of inoculated broth, the fluorescent dye Syto™ 9 was added, followed by FCM analysis. After gating, the relative remaining population of gonococci, compared with unexposed growth control samples, was plotted against antimicrobial concentration, followed by non-linear curve regression analysis. Furthermore, the response at one single concentration/tested antibiotic was evaluated with the intention to use as a screening test for detection of resistant gonococci., Results: A dose-dependent response was seen in susceptible isolates for all tested antimicrobials. There was a clear separation between susceptible/WT and resistant/non-WT isolates for ceftriaxone, cefixime, spectinomycin, ciprofloxacin and tetracycline. In contrast, for azithromycin, only high-level-resistant isolates were distinguished, while resistant isolates with MICs of 4 mg/L were indistinguishable from WT (MIC ≤ 1 mg/L) isolates. For gentamicin, all tested 17 isolates were WT and FCM analysis resulted in uniform dose-response curves. Using a single antibiotic concentration and a 50% remaining cell population cut-off, the overall sensitivity and specificity for resistance detection were 93% and 99%, respectively., Conclusions: By providing results in <5 h for gonococcal isolates, FCM-based AST can become a rapid screening method for antimicrobial resistance or antimicrobial susceptibility in gonococci., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.) more...

Objectives: Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of β-lactamases and Enterobacterales' genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs., Materials and Methods: In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates' ST and their type of β-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed., Results: All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant β-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54)., Conclusions: Despite the frequent association of ESBL genes with inhibitor-resistant β-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.) more...

Objectives: The antimicrobial susceptibility of Neisseria gonorrhoeae isolates from Saskatchewan was determined retrospectively (2003-15) to ascertain temporal trends to both current and older antimicrobials used for treatment., Method: The agar dilution method was used to test the antimicrobial susceptibilities of 685 isolates to seven antibiotics., Results: Over the period, only three (0.4%) gonococcal isolates had reduced susceptibility to cefixime and/or ceftriaxone. All isolates were susceptible to spectinomycin. Over 95% of the isolates tested were susceptible to azithromycin except in 2010 and 2013 (27.6% and 7.2% resistant, respectively). One isolate was resistant to both azithromycin and cefixime. Ciprofloxacin resistance was seen in < 5% of isolates prior to 2010, but in > 5% thereafter. From 2006 to 2012, and in 2015, penicillin resistance was detected in < 5% (0%-4.0%) of isolates, but in > 5% for the rest of the study period. Tetracycline resistance remained >5% (11.8%-89.1%) throughout the study. Plasmid-mediated resistance to tetracycline fluctuated between 0% and 17.5% of isolates tested. Four isolates were MDR and two isolates were XDR., Conclusions: N. gonorrhoeae isolates were largely susceptible (∼85%) to antibiotics no longer recommended for treatment, such as penicillin and ciprofloxacin. Gonorrhoea in Saskatchewan is primarily (>95%) diagnosed by nucleic acid amplification testing, which does not permit antimicrobial susceptibility testing. The development of molecular testing, or point-of-care tests, to evaluate antimicrobial susceptibility, would enhance knowledge of true levels of resistance and allow discretion as to whether older but still effective antibiotics could be used in individual patient care., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.) more...

Background: Tracking the spread of antimicrobial-resistant Neisseria gonorrhoeae is a major priority for national surveillance programmes., Objectives: We investigate whether WGS and simultaneous analysis of multiple resistance determinants can be used to predict antimicrobial susceptibilities to the level of MICs in N. gonorrhoeae., Methods: WGS was used to identify previously reported potential resistance determinants in 681 N. gonorrhoeae isolates, from England, the USA and Canada, with phenotypes for cefixime, penicillin, azithromycin, ciprofloxacin and tetracycline determined as part of national surveillance programmes. Multivariate linear regression models were used to identify genetic predictors of MIC. Model performance was assessed using leave-one-out cross-validation., Results: Overall 1785/3380 (53%) MIC values were predicted to the nearest doubling dilution and 3147 (93%) within ±1 doubling dilution and 3314 (98%) within ±2 doubling dilutions. MIC prediction performance was similar across the five antimicrobials tested. Prediction models included the majority of previously reported resistance determinants. Applying EUCAST breakpoints to MIC predictions, the overall very major error (VME; phenotypically resistant, WGS-prediction susceptible) rate was 21/1577 (1.3%, 95% CI 0.8%-2.0%) and the major error (ME; phenotypically susceptible, WGS-prediction resistant) rate was 20/1186 (1.7%, 1.0%-2.6%). VME rates met regulatory thresholds for all antimicrobials except cefixime and ME rates for all antimicrobials except tetracycline. Country of testing was a strongly significant predictor of MIC for all five antimicrobials., Conclusions: We demonstrate a WGS-based MIC prediction approach that allows reliable MIC prediction for five gonorrhoea antimicrobials. Our approach should allow reasonably precise prediction of MICs for a range of bacterial species., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.) more...

Objectives: Rapid, cost-effective and objective methods for antimicrobial susceptibility testing of Neisseria gonorrhoeae would greatly enhance surveillance of antimicrobial resistance. Etest, disc diffusion and agar dilution methods are subjective, mostly laborious for large-scale testing and take ∼24 h. We aimed to develop a rapid broth microdilution assay using resazurin (blue), which is converted into resorufin (pink fluorescence) in the presence of viable bacteria., Methods: The resazurin-based broth microdilution assay was established using 132 N. gonorrhoeae strains and the antimicrobials ceftriaxone, cefixime, azithromycin, spectinomycin, ciprofloxacin, tetracycline and penicillin. A regression model was used to estimate the MICs. Assay results were obtained in ∼7.5 h., Results: The EC 50 of the dose-response curves correlated well with Etest MIC values (Pearson's r  = 0.93). Minor errors resulting from misclassifications of intermediate strains were found for 9% of the samples. Major errors (susceptible strains misclassified as resistant) occurred for ceftriaxone (4.6%), cefixime (3.3%), azithromycin (0.6%) and tetracycline (0.2%). Only one very major error was found (a ceftriaxone-resistant strain misclassified as susceptible). Overall the sensitivity of the assay was 97.1% (95% CI 95.2-98.4) and the specificity 78.5% (95% CI 74.5-82.9)., Conclusions: A rapid, objective, high-throughput, quantitative and cost-effective broth microdilution assay was established for gonococci. For use in routine diagnostics without confirmatory testing, the specificity might remain suboptimal for ceftriaxone and cefixime. However, the assay is an effective low-cost method to evaluate novel antimicrobials and for high-throughput screening, and expands the currently available methodologies for surveillance of antimicrobial resistance in gonococci., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.) more...

Objectives: Antimicrobial resistance in Neisseria gonorrhoeae is a major public health concern globally. We report the first verified treatment failure of gonorrhoea with 2 g of azithromycin (extended-release formulation) in Japan and characteristics of the corresponding N. gonorrhoeae isolates., Methods: Pre- and post-treatment isolates (n = 4) were investigated by Etest for antimicrobial susceptibility. The isolates were examined for molecular epidemiology by multilocus sequence typing (MLST), N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and multiple-locus variable-number tandem repeat analysis (MLVA), and for the presence of azithromycin resistance determinants (23S rRNA gene mutations, erm genes and mtrR mutations)., Results: All isolates were resistant to azithromycin (MIC 4 mg/L) and ciprofloxacin, but remained susceptible to cefixime, ceftriaxone and spectinomycin. All isolates were assigned to MLST ST1901 and NG-MAST ST1407 and three of four isolates possessed MLVA profile 8-3-21-16-1. All isolates contained the previously described C2599T mutation (N. gonorrhoeae numbering) in all four 23S rRNA alleles and the previously described single-nucleotide (A) deletion in the mtrR promoter region., Conclusions: This verified treatment failure occurred in a patient infected with an MLST ST1901/NG-MAST ST1407 strain of N. gonorrhoeae. While this international strain commonly shows resistance or decreased susceptibility to multiple antimicrobials, including extended-spectrum cephalosporins, the strain reported here remained fully susceptible to the latter antimicrobials. Hence, two subtypes of azithromycin-resistant gonococcal MLST ST1901/NG-MAST ST1407 appear to have evolved and to be circulating in Japan. Azithromycin should not be recommended as a single antimicrobial for first-line empirical treatment of gonorrhoea., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.) more...

Objectives: To determine which mutations in penA, mtrR and porB are implicated in increasing minimum MICs of ceftriaxone and cefixime in a susceptible gonococcal population and to ascertain associations with gonococcal strain types (STs)., Methods: One hundred and forty-six Neisseria gonorrhoeae isolates formed two extended-spectrum cephalosporin susceptibility groups: group 1 isolates with cefixime and ceftriaxone MICs of 0.0005-0.016 mg/L; and group 2 isolates with cefixime MICs of 0.03-0.125 mg/L (n = 24) and ceftriaxone MICs of 0.03-0.06 mg/L (n = 23). Mutation patterns in penicillin-binding protein 2 (PBP2; penA), multiple transfer resistance repressor (MtrR; mtrR) and porin B (PorB; porB) were ascertained by DNA sequence and bioinformatic analysis. STs were determined using N. gonorrhoeae multiantigen sequence typing (NG-MAST)., Results: Most isolates carried PBP2 mutation pattern IX (D345a, F504L, A510V, A516G and P551L; 50/146, 34.2%), a G45D substitution in MtrR (37.7%) and a wild-type (WT) sequence for PorB (43.2%). Group 2 gonococcal isolates were significantly associated with: penA pattern IX; dual mutations in the promoter (A-) and DNA dimerization domain (H105Y) of MtrR; and G120K;A121D substitutions in PorB. There were 50 combined penA/mtrR/porB mutation patterns, with corresponding patterns I/WT/WT and IX/G45D/G120K;A121D predominating. Gonococci susceptible to ceftriaxone and cefixime were significantly associated with NG-MAST ST 25 (33/36; 92%) and the combined penA/mtrR/porB mutation pattern I/WT/WT. No combined mutation pattern or specific ST was associated with elevated ceftriaxone MICs. NG-MAST ST 3654 was significantly associated with the pattern IX/G45D/G120K;A121D and cefixime group 2 isolates., Conclusions: Specific single or combined mutation patterns in penA, mtrR and porB and specific STs were associated with differences in susceptibility to ceftriaxone and cefixime., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.) more...

Objectives: There is a need for new or alternative antimicrobial agents for the treatment of gonorrhoea as antimicrobial resistance emerges to current therapies. The aim was to investigate the activity of ertapenem against isolates of Neisseria gonorrhoeae with decreased susceptibility to cefixime., Methods: A panel of 52 clinical isolates and 10 control strains of N. gonorrhoeae were selected to represent a range of susceptibilities to cefixime. Susceptibility testing was performed using the methodology used for the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP). The isolates were typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST)., Results: The isolates comprised 42 different molecular types as defined by NG-MAST. The susceptibility of the clinical isolates to ertapenem was similar to that of cefixime, with a Pearson's correlation coefficient of R = 0.89. The MIC90 and MIC50 values of ertapenem were 0.25 and 0.12 mg/L, respectively, while those of cefixime were 0.12 and 0.06 mg/L, respectively. However, these isolates were more susceptible to ceftriaxone than ertapenem, with a Pearson's correlation coefficient of R = 0.65 and ceftriaxone MIC90 and MIC50 values of 0.03 and 0.016 mg/L, respectively. The isolates that were least susceptible to ertapenem were all non-producers of penicillinase. However, one isolate that was highly resistant to cefixime and ceftriaxone was more susceptible to ertapenem than either cefixime or ceftriaxone., Conclusions: This study has shown that ertapenem is not a suitable alternative for first-line treatment for gonorrhoea but that it may be useful for the treatment of highly resistant infections., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.) more...

Objectives: Antimicrobial resistance in Neisseria gonorrhoeae is an increasing problem worldwide and combinations of antimicrobial agents have been recommended to delay the onset of treatment failures. The objective of this study was to obtain in vitro data on the activity of current (ceftriaxone or cefixime plus azithromycin) and alternative (gentamicin plus azithromycin) regimens., Methods: A panel of 64 gonococcal isolates displaying various cefixime MICs was selected for inclusion in the study. Determination of the activities of the antimicrobial combinations of ceftriaxone, cefixime or gentamicin with azithromycin was performed using the agar dilution method and subsequent calculation of the fractional inhibitory concentration index (FICI) values., Results: No antagonism for any of the antimicrobial combinations was detected among the 64 gonococcal isolates. When cefixime or ceftriaxone was combined with azithromycin all isolates showed additivity/indifference with a mean FICI of 2.0. All gonococcal isolates also showed additivity/indifference with the antimicrobial combination of gentamicin with azithromycin, but with a lower mean FICI of 1.7. No significant difference in the mean FICI between isolates fully susceptible to cefixime and isolates with decreased susceptibility to cefixime was observed., Conclusions: The results obtained support the gonorrhoea treatment currently recommended in the UK national guidelines and suggest that gentamicin with azithromycin could be a future treatment option. The in vivo activity and efficacy of these combinations remain unknown and prospective clinical studies should be addressed. more...

Objectives: The third-generation cephalosporins recommended in national guidelines are amongst the last remaining effective agents for treatment of gonorrhoea. This study characterizes gonococcal isolates with decreased cefixime susceptibility from England and Wales., Methods: A total of 96 isolates of Neisseria gonorrhoeae exhibiting cefixime MICs of ≥0.125 mg/L, either collected as part of the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) between 2005 and 2008 (54 from a total of 4649 isolates) or referred to the national reference laboratory in 2008 and 2009 (42 isolates), were tested for susceptibility to a range of antimicrobial agents and were typed using N. gonorrhoeae multiantigen sequence typing (NG-MAST)., Results: All 96 isolates were also resistant to tetracycline (MIC ≥2 mg/L) and ciprofloxacin (MIC ≥16 mg/L) and 56% showed low-level chromosomal resistance to penicillin. Where data were available, the mean patient age was 31 years, and 88% (83/94) of patients were men. Isolates referred through GRASP were predominantly from men who have sex with men (MSM; 29/44, 66%) and from patients of white British ethnicity (25/43, 58%). The majority of isolates belonged either to sequence type (ST) 1407 (71/96, 74%) or to a highly related ST that shares the tpbB allele (allele 110), but with a different por allele (20/96, 21%). ST1407 was found in both MSM (22/29, 76%) and heterosexual patients (12/15, 80%) and among all eight isolates from patients reporting sex abroad., Conclusions: The emergence of a clonal group of gonococci showing decreased susceptibility to cefixime in England and Wales highlights the need for continued surveillance. more...

Objectives: Gonorrhoea remains a global public health problem and the treatment options are diminishing through the emergence of gonococci resistant to most antimicrobials. Previous in vitro studies have indicated a role for Neisseria gonorrhoeae pilQ alterations in conferring resistance to antimicrobials, including penicillin. In this study, we investigated whether pilQ polymorphisms were associated with decreased susceptibility to extended-spectrum cephalosporins (ESCs) in clinical gonococcal strains., Methods: Full-length pilQ nucleotide and PilQ amino acid sequences from geographically and temporally diverse gonococcal clinical isolates (n = 63), including the 2008 WHO reference strains, representing a range of ceftriaxone and cefixime MICs (≤0.008-0.25 and <0.016-0.5 mg/L, respectively) and 38 N. gonorrhoeae multiantigen sequence types, were examined. Previously described alterations associated with decreased ESC susceptibility (mosaic penA, mtrR and penB alterations) were also examined., Results: Fifteen different pilQ nucleotide sequence types and nine different PilQ amino acid sequence types were observed, with two PilQ types accounting for 53 (84%) of the isolates. Independent of other genetic resistance determinants (penA mosaic, mtrR promoter deletion and penB), only one pilQ alteration, a D526N substitution, provided a statistically significant association with ceftriaxone (P < 0.01) and cefixime (P < 0.05) MICs. However, the two isolates exhibiting D526N lacked all three previously described alterations associated with decreased ESC susceptibility, thereby providing an alternative basis for the low MICs (≤0.008 mg/L) observed for these strains. The previously described E666K (pilQ2) and F595L (pilQ1) mutations were absent in all 63 isolates., Conclusions: pilQ polymorphisms are unlikely contributors to decreased susceptibility to ESCs in clinical gonococcal strains. more...

Objectives: To examine mutations within the penA, mtrR, porB, ponA and pilQ genes of Neisseria gonorrhoeae to determine their contribution to cephalosporin resistance., Methods: A total of 46 N. gonorrhoeae isolates with reduced susceptibility to cefixime or ceftriaxone (MICs > or = 0.12 mg/L) and two susceptible isolates were selected. The full sequence of penA and partial sequences previously reported as hot mutation sites of the other genes were analysed. Genotyping by N. gonorrhoeae multiantigen sequence typing (NG-MAST) was also performed., Results: A mosaic penicillin-binding protein 2 (PBP 2) was found in a single isolate that exhibited the highest cefixime MIC (0.5 mg/L). The majority of the isolates with reduced susceptibility to cephalosporins contained non-mosaic PBP 2 sequences, of which PBP 2 pattern XIII was most common (28/46). All isolates with reduced susceptibility to cephalosporins also had mtrR and porB mutations. Two susceptible isolates had the PBP 2 pattern XIV and an incomplete MtrR protein, which was a new mutation. Isolates with identical PBP 2 patterns comprised multiple NG-MAST sequence types., Conclusions: Reduced susceptibility of N. gonorrhoeae to ceftriaxone and cefixime was associated with diverse penA mutations, particularly PBP 2 pattern XIII containing an Ala-501-->Val substitution, together with mtrR and porB mutations. The existence of only one strain having the mosaic penA sequence indicated that ceftriaxone and cefixime resistance in Korea is mostly not associated with a mosaic penA sequence. Highly heterogeneous NG-MAST sequence types excluded the clonal expansion of a particular subtype. more...

Aims: To test prospectively the activity of cefixime and comparators against Haemophilus influenzae from Europe and to compare the susceptibilities of isolates from 1997/1998 with isolates from 2002/2003 paying special attention to the epidemiology of amoxicillin resistance., Methods: MICs of antibiotics were determined using broth microdilution. For beta-lactamase-negative isolates with reduced susceptibility to amoxicillin, the nucleotide sequence of the penicillin-binding domain of PBP3 was determined., Results: The prevalence of beta-lactamase-positive isolates in certain countries has reached 38%. During the period 1997/1998, 8.8% of the isolates were beta-lactamase-negative and non-susceptible to amoxicillin (BLNAR). During the period 2002/2003, 9.6% of the isolates were BLNAR. The emergence of the BLNAR phenotype of H. influenzae was demonstrated in all countries with a prevalence ranging from 2% to 20%. The penicillin-binding domain of PBP3 from 30 sequenced isolates showed known amino acid substitutions, although no amino acid changes were observed in two BLNAR isolates. Clonal spread of BLNAR strains was limited or absent in our study. Both beta-lactamase-producing and BLNAR strains of H. influenzae were fully susceptible to cefixime. However, neither beta-lactamase-producing nor BLNAR isolates were fully susceptible to the other cephalosporins tested. All isolates were also fully susceptible to levofloxacin, moxifloxacin, azithromycin and telithromycin., Conclusions: The prevalence of the BLNAR phenotype in Europe is increasing, but no new amino acid substitutions were detected in the penicillin-binding domain of PBP3. Cefixime remains a useful treatment option for respiratory tract infections, including in areas with increasing resistance problems. more...

The resistance of Helicobacter pylori isolated in Israel to metronidazole, clarithromycin, tetracycline, amoxicillin and cefixime was tested in 138 isolates, including 28 from treatment failures. No resistance to tetracycline was detected. Resistance to amoxicillin was found in one isolate (MIC = 1.5 mg/L) from an untreated patient, and resistance to cefixime in two isolates from each group (P = 0.18). Resistance to metronidazole and clarithromycin was much higher in the isolates from treated than from untreated patients: 60.7% and 38.2% for metronidazole (MIC >or= 8 mg/L) (P = 0.03); 46.4% and 8.2% for clarithromycin (MIC >or= 2 mg/L) (P < 0.001). Therapeutic outcome would benefit from susceptibility testing, especially after treatment failure. more...