15 results on '"Kyoko Hatazaki"'
Search Results
2. Antimicrobial susceptibility of Haemophilus influenzae strains isolated from the urethra of men with acute urethritis and/or epididymitis
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Kosuke Mizutani, Masahiro Nakano, Ken Shimuta, Shin Ito, Kyoko Hatazaki, Mitsuru Yasuda, Takashi Deguchi, Keita Nakane, Tetsuro Muratani, Tomohiro Tsuchiya, Shigeaki Yokoi, Makoto Ohnishi, Nozomu Hanaoka, and Kengo Horie
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Male ,0301 basic medicine ,Microbiology (medical) ,Haemophilus Infections ,medicine.drug_class ,030106 microbiology ,Antibiotics ,Microbial Sensitivity Tests ,medicine.disease_cause ,Azithromycin ,beta-Lactamases ,Microbiology ,Haemophilus influenzae ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Urethra ,Ampicillin ,Drug Resistance, Bacterial ,medicine ,Humans ,Pharmacology (medical) ,Urethritis ,Treatment Failure ,030212 general & internal medicine ,Respiratory Tract Infections ,Retrospective Studies ,Epididymitis ,Respiratory tract infections ,business.industry ,medicine.disease ,Antimicrobial ,Anti-Bacterial Agents ,Infectious Diseases ,Immunology ,Ceftriaxone ,business ,Moraxella catarrhalis ,medicine.drug - Abstract
We determined minimum inhibitory concentrations (MICs) of 41 antimicrobial agents for 73 clinical strains of Haemophilus influenzae isolated from the urethra of men with acute urethritis and/or epididymitis and examined the strains for the production of β-lactamase. We also compared their antimicrobial susceptibilities with those of H. influenzae strains from respiratory tract or otorhinolaryngological infections that were reported in Japan. The proportion of β-lactamase-nonproducing ampicillin-resistant strains from acute urethritis and/or epididymitis appeared to be lower, but that of β-lactamase-producing ampicillin-resistant strains appeared to be higher, compared with those from respiratory tract or otorhinolaryngological infections. However, their antimicrobial susceptibilities to a variety of other antimicrobial agents would be similar to those from respiratory tract or otorhinolaryngological infections. Almost all of the strains of H. influenzae from acute urethritis and/or epididymitis were susceptible to the agents, including ceftriaxone, quinolones, macrolides, and tetracyclines, commonly prescribed for treatment of acute urethritis based on the MIC breakpoints recommended by the Clinical and Laboratory Standards Institute. Ceftriaxone and quinolones could be effective on H. influenzae-induced urethritis. However, azithromycin treatment failures were reported in acute urethritis caused by H. influenzae strains considered susceptible to azithromycin. Further studies will be needed to determine MIC breakpoints of antimicrobial agents, which are recommended for treatment of urogenital infections, for H. influenzae strains causing these infections. Nevertheless, this study provides useful data regarding antimicrobial susceptibilities of H. influenzae strains isolated from the urogenital tract, which have rarely been studied.
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- 2017
3. Haemophilus influenzae Isolated From Men With Acute Urethritis: Its Pathogenic Roles, Responses to Antimicrobial Chemotherapies, and Antimicrobial Susceptibilities
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Hiromi Kondo, Kosuke Mizutani, Shin Ito, Masahiro Nakano, Ken Shimuta, Kyoko Hatazaki, Keita Nakane, Shigeaki Yokoi, Mitsuru Yasuda, Takashi Deguchi, Tomohiro Tsuchiya, and Makoto Ohinishi
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Male ,0301 basic medicine ,Non-gonococcal urethritis ,Chlamydia trachomatis ,Levofloxacin ,Drug resistance ,Azithromycin ,urologic and male genital diseases ,medicine.disease_cause ,Haemophilus influenzae ,Gonorrhea ,Leukocyte Count ,0302 clinical medicine ,Medicine ,030212 general & internal medicine ,biology ,Coinfection ,Ceftriaxone ,virus diseases ,Antimicrobial ,female genital diseases and pregnancy complications ,Anti-Bacterial Agents ,Infectious Diseases ,Doxycycline ,Acute Disease ,psychological phenomena and processes ,Fluoroquinolones ,Microbiology (medical) ,030106 microbiology ,Microbial Sensitivity Tests ,Dermatology ,Microbiology ,03 medical and health sciences ,Drug Resistance, Bacterial ,mental disorders ,Haemophilus ,Humans ,Urethritis ,Retrospective Studies ,business.industry ,Public Health, Environmental and Occupational Health ,Chlamydia Infections ,biology.organism_classification ,medicine.disease ,Neisseria gonorrhoeae ,business - Abstract
There have been few comprehensive studies on Haemophilus influenza-positive urethritis.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.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.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.
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- 2017
4. Antimicrobial Susceptibility of Neisseria gonorrhoeae in Japan from 2000 to 2015
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Harunori Narita, Akira Kido, Munekado Kojima, Takashi Deguch, Kazutoyo Miyata, Mutsumasa Yoh, Mitsuru Yasuda, Kyoko Hatazaki, Shin Ito, and Masataka Kitanohara
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Adult ,0301 basic medicine ,Microbiology (medical) ,030106 microbiology ,Antimicrobial susceptibility ,Microbial Sensitivity Tests ,Dermatology ,Drug resistance ,medicine.disease_cause ,Article ,Microbiology ,Gonorrhea ,03 medical and health sciences ,0302 clinical medicine ,Antibiotic resistance ,Japan ,Drug Resistance, Bacterial ,Humans ,Medicine ,030212 general & internal medicine ,business.industry ,Public Health, Environmental and Occupational Health ,Outbreak ,Antimicrobial ,Neisseria gonorrhoeae ,Anti-Bacterial Agents ,Infectious Diseases ,Population Surveillance ,business - Abstract
Gonococcal infections are difficult to treat because of their multidrug antimicrobial resistance. The outbreak of antimicrobial-resistant Neisseria gonorrhoeae has begun in Asia and particularly in Japan. Therefore, it is very important that we understand the trend of antimicrobial resistance of N. gonorrhoeae in Asia including Japan. Our surveillance of the antimicrobial susceptibility of N. gonorrhoeae began in 2000 under the guidance of the Department of Urology, Gifu University. We report our surveillance data from 2000 to 2015.We collected N. gonorrhoeae strains isolated from patients with gonococcal infections who visited our cooperating medical institutions in Japan from 2000 to 2015. MICs of penicillin G, cefixime, ceftriaxone, tetracycline, spectinomycin, azithromycin, and levofloxacin were determined by the agar dilution method approved by the Clinical and Laboratory Standards Institute.From 2000 to 2015, 2471 isolates of N. gonorrhoeae were collected in Japan. High rates of nonsusceptibility to penicillin, tetracycline, levofloxacin, cefixime, and azithromycin were shown. Around 5% to 10% of the strains isolated had a 0.25-mg/L MIC of ceftriaxone in each year, and 6 strains (0.24%) with a 0.5-mg/L MIC of ceftriaxone were isolated throughout the study period. Approximately 5% to 10% of the strains were resistant to each of ceftriaxone, azithromycin, and levofloxacin according to European Committee on Antimicrobial Susceptibility Testing breakpoints, and the rate has not increased significantly.From this study and previous pharmacodynamic analyses, a single 1-g dose of ceftriaxone is recommended to treat gonorrhea. As strains with high-level ceftriaxone resistance continue to spread, higher doses of ceftriaxone in monotherapy or multiple doses of ceftriaxone should be considered.
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- 2017
5. Microbiological efficacy and tolerability of a single-dose regimen of 1 g of ceftriaxone in men with gonococcal urethritis
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Mitsuru Yasuda, Shigeaki Yokoi, Kosuke Mizutani, Takashi Deguchi, Tomohiro Tsuchiya, Kyoko Hatazaki, Shin Ito, and Masahiro Nakano
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Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,030106 microbiology ,Microbial Sensitivity Tests ,medicine.disease_cause ,Gonorrhea ,03 medical and health sciences ,Japan ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Adverse effect ,Pharmacology ,business.industry ,Genitourinary system ,Urethritis ,Ceftriaxone ,Antimicrobial ,Neisseria gonorrhoeae ,Anti-Bacterial Agents ,Surgery ,Regimen ,Treatment Outcome ,Infectious Diseases ,Clinical research ,Tolerability ,business ,medicine.drug - Abstract
OBJECTIVES We treated men with gonococcal urethritis with a single-dose regimen of 1 g of ceftriaxone, which is recommended as the first-line treatment for gonorrhoea in Japan, to determine its microbiological outcomes and tolerability. METHODS We enrolled 255 men with gonococcal urethritis and treated them with a single-dose regimen of 1 g of ceftriaxone. We evaluated its microbiological outcomes and tolerability. We also determined ceftriaxone MICs for pretreatment isolates of Neisseria gonorrhoeae collected from the patients. RESULTS The microbiological efficacy of the ceftriaxone regimen, which was determined between 5 and 9 days after treatment in 111 men based on the Japanese guideline for clinical research on antimicrobial agents in urogenital infections, was 100%. In the 194 men who returned to the clinic between 2 and 41 days after treatment, 191 (98.5%; 95% CI 96.8%-100%) were negative for N. gonorrhoeae after treatment. Ceftriaxone MICs determined for 136 pretreatment isolates obtained from these 194 men ranged from 0.001 to 0.25 mg/L. One isolate persisting after treatment exhibited a ceftriaxone MIC of 0.008 mg/L. For two isolates persisting after treatment, ceftriaxone MICs were not determined. Seven adverse events were observed in 7 (3.2%) of the 220 men treated with the ceftriaxone regimen. Four men had diarrhoea classified as grade 1. Three had urticaria during ceftriaxone administration, with one event classified as grade 1 and two events classified as grade 3. CONCLUSIONS A single-dose regimen of 1 g of ceftriaxone was microbiologically effective against gonococcal urethritis and was safe and tolerable.
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- 2016
6. Macrolide and fluoroquinolone resistance is uncommon in clinical strains of Chlamydia trachomatis
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Shin Ito, Kengo Horie, Masahiro Nakano, Takashi Deguchi, Keita Nakane, Shigeaki Yokoi, Kosuke Mizutani, Tomohiro Tsuchiya, Kyoko Hatazaki, Mitsuru Yasuda, and Hiromi Kondo
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0301 basic medicine ,Microbiology (medical) ,Sitafloxacin ,DNA Topoisomerase IV ,DNA, Bacterial ,Male ,medicine.drug_class ,030106 microbiology ,DNA Mutational Analysis ,Chlamydia trachomatis ,Drug resistance ,Azithromycin ,medicine.disease_cause ,Macrolide Antibiotics ,Microbiology ,03 medical and health sciences ,23S ribosomal RNA ,Drug Resistance, Bacterial ,Medicine ,Humans ,Pharmacology (medical) ,Urethritis ,business.industry ,Chlamydia Infections ,bacterial infections and mycoses ,medicine.disease ,Anti-Bacterial Agents ,Regimen ,RNA, Ribosomal, 23S ,Infectious Diseases ,Treatment Outcome ,DNA Gyrase ,Acute Disease ,business ,medicine.drug ,Fluoroquinolones - Abstract
We analyzed the 23S rRNA, gyrA and parC genes of Chlamydia trachomatis DNAs from men with urethritis and determined microbiological outcomes of an extended-release azithromycin (azithromycin-SR) regimen (2 g once daily for 1 day) and a sitafloxacin regimen (100 mg twice daily for 7 days) for chlamydial urethritis to clarify the macrolide and fluoroquinolone resistance status of clinical strains of C. trachomatis. We amplified the portions of 2 alleles of the 23S rRNA gene and the gyrA and parC genes from C. trachomatis DNAs in 284 first-voided urine specimens from men with chlamydial urethritis by PCR and sequenced their PCR products. We enrolled 369 men with chlamydial urethritis, comprising 314 and 55 treated with the azithromycin-SR regimen and the sitafloxacin regimen, respectively. Alleles 1 and/or 2 of the 23S rRNA gene were analyzed in 162 specimens. No mutations were found in the sequenced regions, including the central portion of domain V. The gyrA and parC genes were analyzed in 118 and 113 specimens, respectively. No amino acid changes were found within the quinolone resistance-determining region of the gyrA gene and in the sequenced region of the parC gene. The microbiological outcomes of the azithromycin-SR and sitafloxacin regimens were assessed in 176 and 30 men, respectively. The eradication rates were 96.0% (95% CI 93.1%–98.9%) for the azithromycin-SR regimen and 100% for the sitafloxacin regimen. Clinical strains of C. trachomatis with macrolide and/or fluoroquinolone resistance would be uncommon, and azithromycin or fluoroquinolone regimens could be recommended as treatments for chlamydial infections.
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- 2017
7. New Clinical Strain ofNeisseria gonorrhoeaewith Decreased Susceptibility to Ceftriaxone, Japan
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Taku Kato, Takashi Deguchi, Tomohiro Tsuchiya, Koji Kameyama, Kengo Horie, Kohsuke Mizutani, Mutsumasa Yoh, Kensaku Seike, Mitsuru Yasuda, Shigeaki Yokoi, Masahiro Nakano, and Kyoko Hatazaki
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pharyngeal gonorrhea ,0301 basic medicine ,Microbiology (medical) ,Letter ,Epidemiology ,030106 microbiology ,Agar Dilution Method ,lcsh:Medicine ,Class (philosophy) ,medicine.disease_cause ,Multiple dose ,lcsh:Infectious and parasitic diseases ,Microbiology ,acute urethritis ,03 medical and health sciences ,Japan ,medicine ,lcsh:RC109-216 ,antimicrobial resistance ,Urethral swab ,Letters to the Editor ,bacteria ,New Clinical Strain of Neisseria gonorrhoeae with Decreased Susceptibility to Ceftriaxone, Japan ,sexually transmitted infections ,gonorrhea ,business.industry ,lcsh:R ,Genital gonorrhea ,Neisseria gonorrhoeae ,ceftriaxone ,Infectious Diseases ,Ceftriaxone ,business ,Urine sample ,Humanities ,medicine.drug - Abstract
To the Editor: In 2009, 2010, and 2013, Neisseria gonorrhoeae strains H041 (ceftriaxone MIC of 2 mg/L), F89 (ceftriaxone MIC of 1 mg/L), and A8806 (ceftriaxone MIC of 0.5 mg/L) were isolated from samples from patients in Japan (1), France (2) and Australia (3), respectively. In Japan, no other clinical N. gonorrhoeae strains with decreased susceptibility to ceftriaxone were reported until 2014, when clinical strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 (ceftriaxone MIC of 0.5 mg/L) was isolated from a man in in Nagoya, Japan. We report details of this case and sequencing results of the penA gene for the strain. The study was approved by the Institutional Review Board of the Graduate School of Medicine, Gifu University, Japan. N. gonorrhoeae strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 was isolated from a urethral swab sample from a man with acute urethritis. The man had received fellatio, without condom use, from a female sex worker in Nagoya in December 2013. He visited our clinic in January 2014 for urethral discharge. Culture of a urethral swab sample was positive for N. gonorrhoeae. We used the Cobas 4800 CT/NG Test (Roche Molecular Systems Inc., Pleasanton, CA, USA) to test a first-voided urine sample; results were positive for N. gonorrhoeae but negative for Chlamydia trachomatis. The infection was treated with a single-dose regimen of ceftriaxone (1 g) administered by intravenous drip infusion. Two weeks later, the man reported no symptoms, and his first-voided urine sample was negative for leukocytes. The test-of-cure for N. gonorrhoeae was not performed. The female sex worker could not be examined for the presence of N. gonorrhoeae strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 in her pharynx. The strain was confirmed to be a gonococcal species by testing with Gonochek-II (TCS Biosciences Ltd, Buckingham, UK), the HN-20 Rapid system identification test (Nissui, Tokyo, Japan), and the Aptima Combo 2 assay for CT/NG (Hologic, Inc., Bedford, MA, USA) and by 16S rRNA gene sequencing and porA pseudogene PCR (4). MICs of antimicrobial drugs for {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 were as follows, as determined by using the agar dilution method: 2.0 mg/L for penicillin G, 1.0 mg/L for tetracycline, 2.0 mg/L for cefixime, 0.5 mg/L for ceftriaxone, 8.0 mg/L for levofloxacin, 0.5 mg/L for azithromycin, and 32.0 mg/L spectinomycin. The strain was determined to be resistant to penicillin G, tetracycline, cefixime, ceftriaxone, and levofloxacin, according to criteria of the European Committee on Antimicrobial Susceptibility Testing (5) The penA gene of strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 was sequenced as previously described (6); results showed the presence of a novel mosaic penicillin-binding protein 2 (PBP2; GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"LC056026","term_id":"965690016","term_text":"LC056026"}}LC056026) (Figure). Multilocus sequence typing (MLST) and N. gonorrhoeae multiantigen sequence typing (NG-MAST) of {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 were performed as previously reported (8,9). MLST assigned strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 to sequence type 7363, the same as strains H041 and A8806 (1,2). NG-MAST assigned strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 to sequence type 6543. MLST and NG-MAST results for {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 differed from those for F89 (3). Figure Sequences of altered amino acids in penicillin-binding protein 2 (PBP2) of Neisseria gonorrhoeae strains with decreased susceptibility to oral cephalosporins and strains with resistance to ceftriaxone. Strain {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}} ... Since the naming of the mosaic PBP2 associated with decreased susceptibilities to oral cephalosporins as pattern X (6), various PBP2 mosaic structures have been discovered. Mosaic PBP2 structures are basically composed of fragments analogous to PBP2s in Neisseria species. Before strain H041 emerged, strains harboring mosaic PBP2s had been resistant to oral cephalosporins but susceptible to ceftriaxone. H041 (ceftriaxone MIC of 2 mg/L) had additional novel amino acid changes, including A311V, V316P, and T483S, in its mosaic PBP2. The presence of substitutions A311V, V316P, and T483S was reported to be responsible for resistance to ceftriaxone (7). Like strain H041, strains {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 and A8806 (ceftriaxone MICs of 0.5 mg/L) had substitutions A311V and T483S, but instead of substitution V316P, they had substitution V316T. In addition, {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 had several changes in positions 227–281 that were not present in other strains. These alterations might also contribute to the decreased susceptibility to ceftriaxone. On the basis of pharmacodynamic analyses (10), a 1-g dose of ceftriaxone (the recommended first-line treatment for gonorrhea in Japan) would be effective against genital gonorrhea caused by strains exhibiting decreased susceptibility to ceftriaxone (e.g., strains {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 and A8806). However, such strains could be resistant to lower-dose regimens, including 250-mg and 500-mg doses of ceftriaxone. This N. gonorrhoeae strain, {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106, was isolated from the urethra of a man who received fellatio from a female sex worker; thus, the bacteria could have derived from her pharynx. N. gonorrhoeae strain H041 was previously isolated from the pharynx of a female sex worker (1). To prevent the emergence and spread of ceftriaxone-resistant N. gonorrhoeae, pharyngeal gonorrhea must be treated. It is uncertain whether a 1-g dose of ceftriaxone would be effective against pharyngeal gonorrhea caused by strains with decreased susceptibility to ceftriaxone, and this regimen might facilitate the selection of such strains from oral cephalosporin-resistant strains in the pharynx. The emergence of N. gonorrhoeae {"type":"entrez-nucleotide","attrs":{"text":"GU140106","term_id":"268370439","term_text":"GU140106"}}GU140106 in Japan suggests that new strategies (not just increased ceftriaxone doses), including combination treatment with ceftriaxone and another class of antimicrobial drugs and multiple dose regimens of ceftriaxone, might be required to treat pharyngeal gonorrhea.
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- 2016
8. GyrA and/or ParC alterations of Haemophilus influenzae strains isolated from the urethra of men with acute urethritis
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Shin Ito, Kyoko Hatazaki, Kosuke Mizutani, Hiromi Kondo, Shigeaki Yokoi, Masahiro Nakano, Takashi Deguchi, Tomohiro Tsuchiya, Mitsuru Yasuda, Kengo Horie, and Keita Nakane
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0301 basic medicine ,Microbiology (medical) ,Adult ,DNA Topoisomerase IV ,Male ,Haemophilus Infections ,medicine.drug_class ,030106 microbiology ,Antibiotics ,Non-gonococcal urethritis ,Drug resistance ,Levofloxacin ,Microbial Sensitivity Tests ,Biology ,medicine.disease_cause ,Microbiology ,Haemophilus influenzae ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Urethra ,Drug Resistance, Bacterial ,medicine ,Humans ,heterocyclic compounds ,Pharmacology (medical) ,Urethritis ,030212 general & internal medicine ,Amino Acids ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,medicine.disease ,Quinolone ,Virology ,Anti-Bacterial Agents ,Infectious Diseases ,DNA Gyrase ,bacteria ,Multilocus sequence typing ,sense organs ,medicine.drug ,Fluoroquinolones - Abstract
Of 73 clinical strains of Haemophilus influenzae isolated from the urethra of men with urogenital infections, we enrolled 6 strains (8.2%) with levofloxacin (LVFX) minimum inhibitory concentrations (MICs) of ≥0.03 μg/ml in this study. All the strains were isolated from non-gonococcal urethritis (NGU). We amplified the quinolone resistance-determining region of the gyrA gene and the analogous region of the parC gene from bacterial DNAs by PCR and sequenced the PCR products. Two strains with a LVFX MIC of 0.03 μg/ml had an amino acid change of Asp88 to Gly in GyrA. One with a LVFX MIC of 0.06 μg/ml had a change of Asp88 to Tyr in GyrA. Two with respective LVFX MICs of 0.12 and 0.25 μg/ml had a change of Ser84 to Leu in GyrA. One with a LVFX MIC of 1 μg/ml had changes of Ser84 to Leu in GyrA and of Ser84 to Ile in ParC. Multilocus sequence typing showed two strains with a change of Asp88 to Gly in GyrA had the same sequence type, but the others had sequence types different from each other. Single amino acid changes in GyrA alone or single changes in both GyrA and ParC could contribute to decreased susceptibility to fluoroquinolones in H. influenzae isolates from NGU. Most of the isolates with GyrA and/or ParC alterations would be multiclonal. The prevalence of such isolates would be relatively low, and they would still be susceptible to fluoroquinolones commonly prescribed for treatment of NGU.
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- 2017
9. 'Haemophilus quentini' in the urethra of men complaining of urethritis symptoms
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Kengo Horie, Kyojiro Kawakami, Takashi Deguchi, Takayuki Ezaki, Shin Ito, Yasunori Fujita, Kyoko Hatazaki, Masafumi Ito, Masahiro Nakano, and Mitsuru Yasuda
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0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,Haemophilus Infections ,030106 microbiology ,Non-gonococcal urethritis ,medicine.disease_cause ,Haemophilus influenzae ,Microbiology ,03 medical and health sciences ,Ampicillin ,RNA, Ribosomal, 16S ,Haemophilus ,medicine ,Humans ,Pharmacology (medical) ,Urethritis ,Demography ,Retrospective Studies ,Antiinfective agent ,biology ,Base Sequence ,Condyloma Acuminatum ,biology.organism_classification ,medicine.disease ,Anti-Bacterial Agents ,030104 developmental biology ,Infectious Diseases ,Urethra ,medicine.anatomical_structure ,Urinary Tract Infections ,medicine.drug - Abstract
We isolated a cryptic genospecies of Haemophilus influenzae referred to as ‘Haemophilus quentini’ in the urethra of 3 men complaining of urethritis symptoms. H. influenzae strains, which had been isolated from the urethra in 77 of 1518 men complaining of urethritis symptoms, identified by the conventional test, and stored, were re-cultured for this study. Sixty-seven strains surviving storage were screened by a PCR-based assay specific for the cryptic genital Haemophilus genospecies. Three strains (HI09003, HI11006, and HI14016) were screened by PCR and identified as ‘H. quentini’ by 16S rRNA sequencing. The men positive for HI09003 and HI11006 were diagnosed as having non-chlamydial non-gonococcal urethritis (NGU), and their demographic and clinical features were similar to those of NGU caused by other pathogens. The man positive for HI14016 was ultimately diagnosed as having condyloma acuminatum on the glans. The 3 strains of ‘H. quentini’ produced no β-lactamase and were susceptible to ampicillin and other antimicrobial agents, including cephalosporins, fluoroquinolones, tetracyclines, and macrolides, recommended for treatment for urethritis. ‘H. quentini’ would be an uncommon pathogen in men with urogenital infections. Based on the clinical features of the two patients with ‘H. quentini’-positive NGU, it would be difficult to predict the presence of ‘H. quentini’ in the urethra. The 3 strains of ‘H. quentini’ were susceptible to a variety of antimicrobial agents. Further accumulation of data regarding ‘H. quentini’ infections is needed to characterize the pathogenic roles of this genospecies in urogenital infections and to establish appropriate management of ‘H. quentini’ infections.
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- 2017
10. Remarkable increase of Neisseria gonorrhoeae with decreased susceptibility of azithromycin and increase in the failure of azithromycin therapy in male gonococcal urethritis in Sendai in 2015
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Shin Ito, Takashi Deguchi, Kyoko Hatazaki, and Mitsuru Yasuda
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0301 basic medicine ,Microbiology (medical) ,Male ,030106 microbiology ,Azithromycin ,medicine.disease_cause ,Gonococcal infection ,Microbiology ,03 medical and health sciences ,Gonorrhea ,0302 clinical medicine ,Antibiotic resistance ,Drug Resistance, Bacterial ,Medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Clinical efficacy ,Treatment Failure ,Retrospective Studies ,business.industry ,Urethritis ,Virology ,Neisseria gonorrhoeae ,Anti-Bacterial Agents ,Infectious Diseases ,Treatment success ,Treatment Outcome ,Ceftriaxone ,business ,medicine.drug ,Gonococcal Urethritis - Abstract
The antimicrobial resistance of Neisseria gonorrhoeae is a serious problem worldwide. In this study, we examined the susceptibility of N. gonorrhoeae isolated from male gonococcal urethritis in Sendai in 2014 and 2015. Furthermore, of all cases, we investigated the clinical efficacy of a single 2-g dose of extended-release azithromycin (AZM-SR) in the treatment of male gonococcal urethritis retrospectively. Sixty N. gonorrhoeae strains in 2014 and 54 strains in 2015 were isolated from male gonococcal urethritis and stored each year. The MIC of AZM was ≥1 mg/L in 4 strains (6.7%) in 2014 and in 13 strains (24.1%) in 2015 and the number of strains having ≥1 mg/L MIC increased significantly (P = 0.016). Microbiological efficacy was evaluated in 32 and 29 of these patients, and the rates of treatment success were 93.8% and 79.3%, respectively. All of the treatment failures were caused by strains having a MIC of AZM of ≥0.5 mg/L. In particular, the increase in the isolates having a MIC of AZM of ≥1 mg/L was remarkable. Therefore, it was thought that the increase in these strains was the reason for the increase in treatment failures in 2015. Because no other drug is effective, it is currently necessary to use AZM-SR to treat gonococcal infections caused by ceftriaxone-resistant strains or patients allergic to ceftriaxone. To prevent a further increase in resistance to AZM, we should not use AZM-SR to treat normal cases of gonococcal infection.
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- 2016
11. Novel penA mutations identified in Neisseria gonorrhoeae with decreased susceptibility to ceftriaxone isolated between 2000 and 2014 in Japan
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Mitsuru Yasuda, Kosuke Mizutani, Ito Y, Shigeaki Yokoi, Yoshinori Fujimoto, Shin Ito, Takashi Deguchi, Kyoko Hatazaki, Tomohiro Tsuchiya, Kazuya Yuhara, Masahiro Nakano, and Kensaku Seike
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0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,030106 microbiology ,DNA Mutational Analysis ,Repressor ,Drug resistance ,Microbial Sensitivity Tests ,Biology ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,Gonorrhea ,Young Adult ,Bacterial Proteins ,Japan ,Drug Resistance, Bacterial ,polycyclic compounds ,medicine ,Humans ,Pharmacology (medical) ,Gene ,Pharmacology ,Mutation ,Ceftriaxone ,biochemical phenomena, metabolism, and nutrition ,MTRR ,Neisseria gonorrhoeae ,Anti-Bacterial Agents ,Infectious Diseases ,Female ,Efflux ,medicine.drug - Abstract
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.
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- 2016
12. Haemophilus influenzae Isolated From Men With Acute Urethritis: Its Pathogenic Roles, Responses to Antimicrobial Chemotherapies, and Antimicrobial Susceptibilities.
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Shin Ito, Kyoko Hatazaki, Ken Shimuta, Hiromi Kondo, Kosuke Mizutani, Mitsuru Yasuda, Keita Nakane, Tomohiro Tsuchiya, Shigeaki Yokoi, Masahiro Nakano, Makoto Ohinishi, Takashi Deguchi, Ito, Shin, Hatazaki, Kyoko, Shimuta, Ken, Kondo, Hiromi, Mizutani, Kosuke, Yasuda, Mitsuru, Nakane, Keita, and Tsuchiya, Tomohiro
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ANTIBIOTICS , *CHLAMYDIA infections , *CHLAMYDIA trachomatis , *DRUG resistance in microorganisms , *GONORRHEA , *HAEMOPHILUS influenzae , *MICROBIAL sensitivity tests , *NEISSERIA , *QUINOLONE antibacterial agents , *URETHRITIS , *AZITHROMYCIN , *RETROSPECTIVE studies , *ACUTE diseases , *CEFTRIAXONE , *DOXYCYCLINE , *LEUKOCYTE count , *MIXED infections , *PHARMACODYNAMICS - Abstract
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]- Published
- 2017
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13. Antimicrobial Susceptibility of Neisseria gonorrhoeae in Japan from 2000 to 2015.
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Mitsuru Yasuda, Kyoko Hatazaki, Shin Ito, Masataka Kitanohara, Mutsumasa Yoh, Munekado Kojima, Harunori Narita, Akira Kido, Kazutoyo Miyata, Takashi Deguch, Yasuda, Mitsuru, Hatazaki, Kyoko, Ito, Shin, Kitanohara, Masataka, Yoh, Mutsumasa, Kojima, Munekado, Narita, Harunori, Kido, Akira, Miyata, Kazutoyo, and Deguch, Takashi
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ANTIBIOTICS , *DRUG resistance in microorganisms , *GONORRHEA , *MICROBIAL sensitivity tests , *NEISSERIA , *PUBLIC health surveillance , *PHARMACODYNAMICS - Abstract
Background: Gonococcal infections are difficult to treat because of their multidrug antimicrobial resistance. The outbreak of antimicrobial-resistant Neisseria gonorrhoeae has begun in Asia and particularly in Japan. Therefore, it is very important that we understand the trend of antimicrobial resistance of N. gonorrhoeae in Asia including Japan. Our surveillance of the antimicrobial susceptibility of N. gonorrhoeae began in 2000 under the guidance of the Department of Urology, Gifu University. We report our surveillance data from 2000 to 2015.Methods: We collected N. gonorrhoeae strains isolated from patients with gonococcal infections who visited our cooperating medical institutions in Japan from 2000 to 2015. MICs of penicillin G, cefixime, ceftriaxone, tetracycline, spectinomycin, azithromycin, and levofloxacin were determined by the agar dilution method approved by the Clinical and Laboratory Standards Institute.Results: From 2000 to 2015, 2471 isolates of N. gonorrhoeae were collected in Japan. High rates of nonsusceptibility to penicillin, tetracycline, levofloxacin, cefixime, and azithromycin were shown. Around 5% to 10% of the strains isolated had a 0.25-mg/L MIC of ceftriaxone in each year, and 6 strains (0.24%) with a 0.5-mg/L MIC of ceftriaxone were isolated throughout the study period. Approximately 5% to 10% of the strains were resistant to each of ceftriaxone, azithromycin, and levofloxacin according to European Committee on Antimicrobial Susceptibility Testing breakpoints, and the rate has not increased significantly.Conclusions: From this study and previous pharmacodynamic analyses, a single 1-g dose of ceftriaxone is recommended to treat gonorrhea. As strains with high-level ceftriaxone resistance continue to spread, higher doses of ceftriaxone in monotherapy or multiple doses of ceftriaxone should be considered. [ABSTRACT FROM AUTHOR]- Published
- 2017
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14. Novel penA mutations identified in Neisseria gonorrhoeae with decreased susceptibility to ceftriaxone isolated between 2000 and 2014 in Japan.
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Kensaku Seike, Mitsuru Yasuda, Kyoko Hatazaki, Kosuke Mizutani, Kazuya Yuhara, Yasuhisa Ito, Yoshinori Fujimoto, Shin Ito, Tomohiro Tsuchiya, Shigeaki Yokoi, Masahiro Nakano, Takashi Deguchi, Seike, Kensaku, Yasuda, Mitsuru, Hatazaki, Kyoko, Mizutani, Kosuke, Yuhara, Kazuya, Ito, Yasuhisa, Fujimoto, Yoshinori, and Ito, Shin
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NEISSERIA gonorrhoeae ,CEFTRIAXONE ,GENETIC mutation ,DRUG resistance ,CEPHALOSPORINS ,DISEASE susceptibility ,BACTERIAL protein metabolism ,ANTIBIOTICS ,DRUG resistance in microorganisms ,GONORRHEA ,MICROBIAL sensitivity tests ,NEISSERIA ,SEQUENCE analysis ,PHARMACODYNAMICS - Abstract
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]- Published
- 2016
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15. Microbiological efficacy and tolerability of a single-dose regimen of 1 g of ceftriaxone in men with gonococcal urethritis.
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Shin Ito, Mitsuru Yasuda, Kyoko Hatazaki, Kosuke Mizutani, Tomohiro Tsuchiya, Shigeaki Yokoi, Masahiro Nakano, Takashi Deguchi, Ito, Shin, Yasuda, Mitsuru, Hatazaki, Kyoko, Mizutani, Kosuke, Tsuchiya, Tomohiro, Yokoi, Shigeaki, Nakano, Masahiro, and Deguchi, Takashi
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GONORRHEA treatment ,CEFTRIAXONE ,URETHRITIS ,ANTI-infective agents ,MICROBIOLOGY ,ANTIBIOTICS ,DRUG side effects ,GONORRHEA ,MICROBIAL sensitivity tests ,NEISSERIA ,TREATMENT effectiveness - Abstract
Objectives: We treated men with gonococcal urethritis with a single-dose regimen of 1 g of ceftriaxone, which is recommended as the first-line treatment for gonorrhoea in Japan, to determine its microbiological outcomes and tolerability.Methods: We enrolled 255 men with gonococcal urethritis and treated them with a single-dose regimen of 1 g of ceftriaxone. We evaluated its microbiological outcomes and tolerability. We also determined ceftriaxone MICs for pretreatment isolates of Neisseria gonorrhoeae collected from the patients.Results: The microbiological efficacy of the ceftriaxone regimen, which was determined between 5 and 9 days after treatment in 111 men based on the Japanese guideline for clinical research on antimicrobial agents in urogenital infections, was 100%. In the 194 men who returned to the clinic between 2 and 41 days after treatment, 191 (98.5%; 95% CI 96.8%-100%) were negative for N. gonorrhoeae after treatment. Ceftriaxone MICs determined for 136 pretreatment isolates obtained from these 194 men ranged from 0.001 to 0.25 mg/L. One isolate persisting after treatment exhibited a ceftriaxone MIC of 0.008 mg/L. For two isolates persisting after treatment, ceftriaxone MICs were not determined. Seven adverse events were observed in 7 (3.2%) of the 220 men treated with the ceftriaxone regimen. Four men had diarrhoea classified as grade 1. Three had urticaria during ceftriaxone administration, with one event classified as grade 1 and two events classified as grade 3.Conclusions: A single-dose regimen of 1 g of ceftriaxone was microbiologically effective against gonococcal urethritis and was safe and tolerable. [ABSTRACT FROM AUTHOR]- Published
- 2016
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