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Background. Commensal streptococci are common inhabitants of the oral microbiome and regulate its structure and function in beneficial ways for human health. They can, however, also be opportunistic pathogens and act as a reservoir of resistance genes that can be passed on to other bacteria, including pathogens. Little is known about the prevalence of these commensals in parents and their children and their antimicrobial susceptibilities in the Belgian general population. Gap Statement. The macrolide susceptibility of commensal oral Streptococci in Belgium is unknown. Methods. We assessed the prevalence and azithromycin susceptibility of commensal streptococcal species in the parents ( n =38) and children ( n =50) of 35 families in Belgium. Results. The most frequently detected taxonomic grouping was Streptococcus mitis/oralis , which was detected in 78/181 (43.1%) of the children's isolates and 66/128 (51.6%) of the parents' isolates. Of the 311 isolates collected in this study, 282 isolates (90.7%) had an azithromycin MIC value greater than the breakpoint of 0.25 mg l -1 and 146 isolates (46.9%) had azithromycin MICs greater than 2 mg l -1 . There was no difference in the azithromycin MIC distribution of all streptococcal isolates between children and parents. All individuals were colonized by streptococci with azithromycin MICs greater than 0.25 mg l -1 , and 87.5% of individuals had streptococci with MICs greater than 2 mg l -1 . Interpretation. The most prevalent species identified in both age groups was S. mitis/oralis . All individuals harboured streptococci with macrolide resistance. This highlights the need for additional antimicrobial stewardship initiatives to reduce the consumption of macrolides in the general population.

Background: The emergence of ceftriaxone-resistant Neisseria gonorrhoeae poses a significant threat to existing treatment regimens. Our study aimed to assess the efficacy of antimicrobials that could be combined with ceftriaxone to reduce the probability of ceftriaxone resistance emerging and spreading in N. gonorrhoeae ., Methods and Results: Broth microdilution was used to determine the minimal inhibitory concentrations (MICs) for a panel of ceftriaxone-resistant (WHO X, Y, Z) and ceftriaxone-susceptible (WHO L, N, P) N. gonorrhoeae WHO reference strains for the following antimicrobials: ceftriaxone, doxycycline, azithromycin, zoliflodacin, fosfomycin, pristinamycin, ramoplanin, gentamicin and NAI-107. The MICs for zoliflodacin and pristinamycin for all strains were lower than or equal to the available breakpoints. A checkerboard assay was used to determine the drug-drug combination effect, which showed either an indifferent or an additive effect for all the combinations tested with ceftriaxone., Conclusions: The low MICs of zoliflodacin and pristinamycin for the three ceftriaxone-resistant strains suggest that these antimicrobials could be used as partner drugs with ceftriaxone to reduce the probability of ceftriaxone resistance spreading in areas with a high prevalence of ceftriaxone resistance., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Tolerance enables bacteria to survive intermittent antibiotic exposure without an increase in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone, azithromycin and ciprofloxacin, in clinical isolates and the WHO (World Health Organization) reference panel of Neisseria gonorrhoeae ., Methods: We used the modified tolerance disk (TD test) to assess for tolerance to ceftriaxone, azithromycin and ciprofloxacin in 14 WHO reference strains and 62 N. gonorrhoeae clinical isolates-evenly divided between anorectal and urogenital infections. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disk for 20 h of incubation (Step I), followed by the replacement of the antibiotic disk with a nutrient disk for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III)., Results: A total of 4 of the 62 clinical anorectal isolates and none of the urogenital isolates exhibited tolerance to azithromycin ( p = 0.033). Tolerance to ceftriaxone and ciprofloxacin was observed in eight and four isolates, respectively, with no difference between infection sites. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO reference strains, with varying patterns of tolerance to ceftriaxone ( n = 8), ciprofloxacin ( n = 2) and azithromycin ( n = 1)., Conclusions: This study identified ceftriaxone, azithromycin and ciprofloxacin tolerance in clinical and WHO reference N. gonorrhoeae isolates. Azithromycin tolerance was more common in anorectal than urogenital infections.

Background: The use of antimicrobials to treat food animals may result in antimicrobial residues in foodstuffs of animal origin. The European Medicines Association (EMA) and World Health Organization (WHO) define safe antimicrobial concentrations in food based on acceptable daily intakes (ADIs). It is unknown if ADI doses of antimicrobials in food could influence the antimicrobial susceptibility of human-associated bacteria., Objectives: This aim of this study was to evaluate if the consumption of ADI doses of erythromycin could select for erythromycin resistance in a Galleria mellonella model of Streptococcus pneumoniae infection., Methods: A chronic model of S. pneumoniae infection in G. mellonella larvae was used for the experiment. Inoculation of larvae with S. pneumoniae was followed by injections of erythromycin ADI doses (0.0875 and 0.012 μg/ml according to EMA and WHO, respectively). Isolation of S. pneumoniae colonies was then performed on selective agar plates. Minimum inhibitory concentrations (MICs) of resistant colonies were measured, and whole genome sequencing (WGS) was performed followed by variant calling to determine the genetic modifications., Results: Exposure to single doses of both EMA and WHO ADI doses of erythromycin resulted in the emergence of erythromycin resistance in S. pneumoniae . Emergent resistance to erythromycin was associated with a mutation in rplA , which codes for the L1 ribosomal protein and has been linked to macrolide resistance in previous studies., Conclusion: In our in vivo model, even single doses of erythromycin that are classified as acceptable by the WHO and EMA induced significant increases in erythromycin MICs in S. pneumoniae . These results suggest the need to include the induction of antimicrobial resistance (AMR) as a significant criterion for determining ADIs., Competing Interests: We have no competing interests., (© 2024 Baranchyk et al.)

The ResistAZM randomized controlled trial found that the receipt of ceftriaxone/azithromycin, compared to ceftriaxone was not associated with an increase in the proportion of oral commensal Neisseria spp. and streptococci with azithromycin resistance 14 days after treatment. We repeated the analyses by measuring the minimum inhibitory concentrations (MICs) of azithromycin and ceftriaxone for individual colonies of commensal Neisseria spp. and streptococci at day 0 and day 14 in both arms. The receipt of ceftriaxone/azithromycin but not ceftriaxone was associated with an increase in azithromycin MIC for both Neisseria spp. (P < 0.0001) and streptococci (P = 0.0076). Likewise, ceftriaxone/azithromycin but not ceftriaxone monotherapy was associated with an increase in ceftriaxone MICs in Neisseria spp. (P = 0.0035). Whereas the proportion method failed to detect an association between the receipt of azithromycin and increased macrolide resistance, the MIC distribution method detected this effect. The MIC distribution method is thus a more sensitive method to assess the effect of antimicrobials on antimicrobial susceptibility., Background: The ResistAZM randomized controlled trial found that the receipt of ceftriaxone/azithromycin, compared to ceftriaxone was not associated with an increase in the proportion of oral commensal Neisseria spp. and streptococci with azithromycin resistance 14 days after treatment., Methods: We repeated the analyses by measuring the minimum inhibitory concentrations (MICs) of azithromycin and ceftriaxone for individual colonies of commensal Neisseria spp. and streptococci at day 0 and day 14 in both arms., Results: The receipt of ceftriaxone/azithromycin but not ceftriaxone was associated with an increase in azithromycin MIC for both Neisseria spp. (P < 0.0001) and streptococci (P = 0.0076). Likewise, ceftriaxone/azithromycin but not ceftriaxone monotherapy was associated with an increase in ceftriaxone MICs in Neisseria spp. (P = 0.0035)., Conclusions: Whereas the proportion method failed to detect an association between the receipt of azithromycin and increased macrolide resistance, the MIC distribution method detected this effect. The MIC distribution method is thus a more sensitive method to assess the effect of antimicrobials on antimicrobial susceptibility., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Background: commensal Neisseria species are part of the oropharyngeal microbiome and play an important role in nitrate reduction and protecting against colonization by pathogenic bacteria. They do, however, also serve as a reservoir of antimicrobial resistance. Little is known about the prevalence of these species in the general population, how this varies by age and how antimicrobial susceptibility varies between species., Methods: we assessed the prevalence and antimicrobial susceptibility of commensal Neisseria species in the parents (n = 38) and children (n = 50) of 35 families in Belgium., Results: various commensal Neisseria (n = 5) could be isolated from the participants. Most abundant were N. subflava and N. mucosa. Neisseria subflava was detected in 77 of 88 (87.5%) individuals and N. mucosa in 64 of 88 (72.7%). Neisseria mucosa was more prevalent in children [41/50 (82%)] than parents [23/38 (60.5%); P < .05], while N. bacilliformis was more prevalent in parents [7/36 (19.4%)] than children [2/50 (4%); P < .05]. Neisseria bacilliformis had high ceftriaxone minimum inhibitory concentrations (MICs; median MIC 0.5 mg/l; IQR 0.38-0.75). The ceftriaxone MICs of all Neisseria isolates were higher in the parents than in the children. This could be explained by a higher prevalence of N. bacilliformis in the parents., Interpretation: the N. bacilliformis isolates had uniformly high ceftriaxone MICs which warrant further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Background: The prevalence of azithromycin resistance in Neisseria gonorrhoeae is increasing in numerous populations worldwide.Objectives: To characterize the genetic pathways leading to high-level azithromycin resistance.Methods: A customized morbidostat was used to subject two N. gonorrhoeae reference strains (WHO-F and WHO-X) to dynamically sustained azithromycin pressure. We tracked stepwise evolution of resistance by whole genome sequencing.Results: Within 26 days, all cultures evolved high-level azithromycin resistance. Typically, the first step towards resistance was found in transitory mutations in genes rplD, rplV and rpmH (encoding the ribosomal proteins L4, L22 and L34 respectively), followed by mutations in the MtrCDE-encoded efflux pump and the 23S rRNA gene. Low- to high-level resistance was associated with mutations in the ribosomal proteins and MtrCDE efflux pump. However, high-level resistance was consistently associated with mutations in the 23S ribosomal RNA, mainly the well-known A2059G and C2611T mutations, but also at position A2058G.Conclusions: This study enabled us to track previously reported mutations and identify novel mutations in ribosomal proteins (L4, L22 and L34) that may play a role in the genesis of azithromycin resistance in N. gonorrhoeae. [ABSTRACT FROM AUTHOR]

This study describes antimicrobial susceptibility patterns of Neisseria gonorrhoeae isolates obtained from female sex workers in Cotonou, Bénin. All isolates were susceptible to spectinomycin, ceftriaxone and ciprofloxacin, and susceptible to moderately susceptible to kanamycin; 9.8% of isolates were resistant to thiamphenicol; 9%, 87.5% and 3.5% were susceptible, moderately susceptible, resistant to trimethoprim-sulfamethoxazole, respectively; 94.4% and 99.3% were resistant to penicillin and tetracycline, respectively. All isolates with a minimal inhibitory concentration of tetracycline of >8 mg/l carried the 'American type' tetM plasmid; 94% and 6% of penicillinase-producing isolates possessed a 3.2 MDa and a 4.4MDa beta-lactamase plasmid, respectively. Surveillance of antimicrobial susceptibility of N. gonorrhoeae isolates to currently used drugs in Africa should become part of sexually transmitted diseases (STDs) control programmes. [ABSTRACT FROM AUTHOR]

Background: Plasmid-mediated and chromosomal-mediated resistance of Neisseria gonorrhoeae to penicillin, tetracycline, thiamphenicol, and trimethoprim-sulfamethoxazole has spread dramatically in Africa. Monitoring of antimicrobial susceptibility is a key element in the control of sexually transmitted diseases.Goal: To document antimicrobial susceptibilities of gonococci isolated during the past 15 years in Kigali, Rwanda.Study Design: Minimal inhibitory concentrations of recently collected gonococcal isolates of eight antimicrobials were determined. The results were compared with data collected for isolates obtained since 1986.Results: In 1986, 35% of the gonococcal isolates were penicillinase-producing N gonorrhoeae. Tetracycline-resistant N gonorrhoeae appeared in 1989. The prevalence of penicillinase-producing N gonorrhoeae and tetracycline-resistant N gonorrhoeae increased significantly to 70.5% and 89.2%, respectively. Chromosomal resistance to penicillin, tetracycline, and thiamphenicol increased temporarily, then decreased significantly. Chromosomal resistance to trimethoprim-sulfamethoxazole appeared in 1988 and increased to 21.6%. All the isolates were susceptible to ceftriaxone, ciprofloxacin, spectinomycin, and kanamycin.Conclusions: This study illustrated the rapidly increasing frequencies of penicillinase-producing N gonorrhoeae and tetracycline-resistant N gonorrhoeae. Chromosomal resistance to thiamphenicol and trimethoprim-sulfamethoxazole excludes these drugs as alternative treatment. Programs for antimicrobial susceptibility surveillance of N gonorrhoeae should urgently be established in Africa. [ABSTRACT FROM AUTHOR]