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Objectives: We examined four clinical strains of Neisseria gonorrhoeae (GU030113, GU110095, GU110332 and GU110362) isolated between 2000 and 2014 in Japan, exhibiting ceftriaxone MICs of 0.5 mg/L, for mutations of the genes associated with penicillin resistance.Methods: The penA, mtrR, porB1b (penB), ponA and pilQ genes of the strains were sequenced. PBP2s of the strains were aligned to the PBP2s associated with decreased susceptibility to oral cephalosporins, and PBP2s of previously reported strains with decreased susceptibility to ceftriaxone.Results: GU030113 had PBP2 pattern X with an additional substitution of A502T. GU110095 had PBP2 pattern XXVII. GU110332 had PBP2 pattern XXXIV with an additional substitution of P552S. GU110362 had PBP2 composed of pattern X (amino acid positions 1-291) and pattern V (amino acid positions 292-576). GU030113, GU110095 and GU110332 had deletion of A in the mtrR promoter, G120K and A121D or A121N in PorB1b and L421P in PBP1. GU110362 had A40D in the repressor of MtrR and L421P in PBP1. The strains did not have mutations of pilQ1 and pilQ2.Conclusions: Addition of A502T to PBP2 pattern X in GU030113 and of P552S to PBP2 pattern XXXIV in GU110332 would possibly contribute to decreased susceptibility to ceftriaxone. In GU110095 and GU110362, it was suggested that, in addition to their altered PBP2s, the enhanced efflux pump, reduced permeability in the outer membrane, another altered target of β-lactams and/or other mechanisms not identified in the present study might contribute to decreased susceptibility. [ABSTRACT FROM AUTHOR]

Background: There have been few comprehensive studies on Haemophilus influenza-positive urethritis.Methods: In this retrospective study, we enrolled 68 men with H. influenzae-positive urethritis, including coinfections with Neisseria gonorrhoeae, Chlamydia trachomatis, and/or genital mycoplasmas: 2, 3, 20, and 43 treated with ceftriaxone, levofloxacin, sitafloxacin, and extended-release azithromycin (azithromycin-SR), respectively. We assessed microbiological outcomes in 54 men and clinical outcomes in 46 with H. influenzae-positive monomicrobial nongonococcal urethritis. We determined minimum inhibitory concentrations (MICs) of 6 antimicrobial agents for 59 pretreatment isolates.Results: H. influenzae was eradicated from the men treated with ceftriaxone, levofloxacin, or sitafloxacin. The eradication rate with azithromycin-SR was 85.3%. The disappearance or alleviation of urethritis symptoms and the decreases in leukocyte counts in first-voided urine were significantly associated with the eradication of H. influenzae after treatment. For the isolates, ceftriaxone, levofloxacin, sitafloxacin, azithromycin, tetracycline, and doxycycline MICs were ≤0.008-0.25, 0.008-0.5, 0.001-0.008, 0.12-1, 0.25-16, and 0.25-2 μg/mL, respectively. The azithromycin MICs for 3 of 4 strains persisting after azithromycin-SR administration were 1 μg/mL. H. influenzae with an azithromycin MIC of 1 μg/mL increased chronologically.Conclusions: H. influenzae showed good responses to the chemotherapies for urethritis. The significant associations of the clinical outcomes of the chemotherapies with their microbiological outcomes suggested that H. influenzae could play pathogenic roles in urethritis. All isolates, except for one with decreased susceptibility to tetracyclines, were susceptible to the examined agents. However, the increase in H. influenzae with an azithromycin MIC of 1 μg/mL might threaten efficacies of azithromycin regimens on H. influenzae-positive urethritis. [ABSTRACT FROM AUTHOR]