Nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis from male urethritis in Japan: Comparison with the first surveillance report

The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC₉₀) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 μg/ml (2 μg/ml), 1 μg/ml (0.5 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.125 μg/ml (0.063 μg/ml), 0.125 μg/ml (0.125 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.031 μg/ml (0.031 μg/ml), 0.25 μg/ml (0.125 μg/ml), and 0.016 μg/ml (0.008 μg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth.     

广州地区淋球菌对壮观霉素敏感性的6年动态观察

目的　了解广州地区淋球菌对壮观霉素敏感性。方法　我们对 6年来广州地区 719株淋球菌临床分离株以琼脂稀释法测定壮观霉素的最小抑菌浓度 (MIC)。结果　壮观霉素MIC范围为 2～ 12 8mg L ,MIC50 和MIC90 分别为16mg L和 32mg L ,719株淋球菌中有 718株 (99 86 % )对壮观霉素敏感 ,6年间未发现耐药菌株。结论　壮观霉素作为治疗淋病的一线药物对淋球菌临床分离株仍相当有     

广州地区淋球菌耐药性的趋势分析

目的了解广州地区13年的产青霉素酶淋球菌(PPNG)和高水平耐四环素淋球菌(TRNG)的流行状况及对5种抗菌药物的耐药趋势。方法用琼脂稀释法测定最低抑菌浓度(MIC)以及用纸片碘量法检测β-内酰胺酶。结果 1 324株淋球菌中,2000~2005年度PPNG检出率占23.5%(156/665),2008~2014年度PPNG检出率占36.4%(240/659),差异有统计学意义(P0.05)。2000~2005年度TRNG检出率占33.4%(222/665),2008~2014年度TRNG检出率占42.6%(281/659),差异有统计学意义(P0.05)。青霉素耐药率从71.1%(473/665)升高至87.1%(574/659),差异有统计学意义(P0.05);环丙沙星耐药率由88.9%(591/665)升至98.0%(646/659),差异有统计学意义(P0.05);头孢曲松中度敏感率从12.3%(82/665)提升到21.5%(142/659),差异有统计学意义(P0.05);大观霉素未发现耐药菌。结论持续进行淋球菌耐药性监测非常重要,大观霉素在临床上可以作为治疗淋病的优选药物,具有良好疗效。     

淋球菌流行株对5种抗生素敏感性分析

目的检测2008年度临床分离的淋球菌对青霉素、四环素、大观霉素、头孢曲松和环丙沙星的敏感性,分析耐药菌株的流行特点。方法采用琼脂稀释法测定菌株对5种抗生素的最小抑菌浓度（MIC）,判断其敏感性并按WHO西太平洋地区淋球菌耐药性监测统一标准。用纸片酸度法检测产β-内酰胺酶淋球菌菌株。结果107株淋球菌中,检出94株对青霉素耐药（87．9％）,产β-内酰胺酶淋球菌43株（40．2％）;四环素耐药率为88．8％,其中质粒介导高度耐四环素淋球菌（TRNG）63株（58．9％）;环丙沙星耐药率81．3％;未发现对大观霉素和头孢曲松耐药菌株。青霉素、四环素和环丙沙星的MIC50及MIC90均已超过耐药标准,尤以青霉素为甚,其MIC50及MIC90均超过耐药标准1、32倍。结论淋球菌对大观霉素和头孢曲松的敏感性较高,可作为治疗的首选药物;对青霉素、四环素和环丙沙星耐药率较高,提示对淋病的治疗作用差。     

2001～2003年上海地区淋病奈瑟菌对抗生素的敏感性测定及质粒分析

目的了解上海地区2001～2003年淋病奈瑟菌(NG)对抗生素的敏感性情况及变化趋势。方法采用琼脂稀释法测定青霉素、头孢曲松、大观霉素、环丙沙星、四环素对742株NG的最小抑菌浓度(MIC)。用纸片酸度法检测β内酰胺酶菌株。用碱裂解方法抽提质粒。结果742株NG检出产青霉素酶菌(PPNG)342株(46.09%);质粒介导高度耐四环素(TRNG)166株(22.37%);耐环丙沙星718株(96.77%);耐大观霉素1株;未发现对头孢曲松耐药菌株;超过20%的菌株同时对青霉素、四环素和环丙沙星耐药;对35株菌株作了质粒分型,含耐药质粒检出率97%,分别带有5.4和7.4kb耐药性质粒。结论淋球菌对青霉素、四环素和环丙沙星3种药物分别有较高比例的耐药率。上海地区治疗淋病应首选大观霉素和头孢曲松。     

淋球菌对六种抗生素耐药性分析

目的探讨淋球菌对青霉素、四环素、喹诺酮、阿奇霉素、头孢曲松、大观霉素六种抗生素的敏感性,为临床用药提供参考。方法通过对212例淋病患者对六种抗生素的药敏试验结果进行统计,分析淋球菌对六种抗生素的耐药性。结果 212株淋球菌菌株药物敏感试验结果显示,对青霉素的耐药性达79.7%,对四环素耐药性达75.4%,对喹诺酮耐药性达70.3%,对阿奇霉素耐药达12.3%,尚未出现对大观霉素、头孢曲松具有耐药性的菌株。结论淋球菌对青霉素、四环素、喹诺酮耐药严重,尚未出现对头孢曲松和大观霉素耐药的菌株。     

Antimicrobial susceptibility and penicillin-binding protein 1 and 2 mutations in Neisseria gonorrhoeae isolated from male urethritis in Sapporo, Japan

The spread of antimicrobial-resistant Neisseria gonorrhoeae worldwide is a critical issue in the control of sexually transmitted infections. The purpose of this study was to clarify recent trends in the susceptibility of N. gonorrhoeae to various antimicrobial agents and to compare these data with our previous data. Minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined in N. gonorrhoeae strains clinically isolated from male gonococcal urethritis. In addition, amino acid sequencing of penicillin-binding protein (PBP) 2, encoded by the penA gene, was analyzed so that genetic analysis of mosaic PBP 2 could clarify the susceptibility of the strains to cefixime and other cephalosporins. The susceptibility rate for ceftriaxone, cefodizime, and spectinomycin, agents whose use is recommended by the guideline of the Japanese Society of Sexually Transmitted Infections (JSSTI), was 100 %. The susceptibility rates of the strains to penicillin G and ciprofloxacin were lower than those in previous reports. Mosaic PBP 2 structures were detected in 51.9 % of the strains and the MICs of the strains with the mosaic PBP 2 to cefixime were much higher than those of the strains without the mosaic PBP 2. In the clinical situation, the treatment regimen recommended by the JSSTI remains appropriate; however, the susceptibility to cephalosporins should be intensively surveyed because strains with mosaic PBP 2 were commonly detected.     

女性患者淋病奈瑟球菌的耐药性分析

目的 了解女性淋病患者中分离的淋病奈瑟球菌对抗菌药物的耐药性。方法 用纸片扩散法检测淋病奈瑟球菌对7种抗菌药物的敏感性，用头孢硝噻吩检测产青霉素酶淋病奈瑟球菌（PPNG）。结果 95株淋病奈瑟球菌中PPNG检出率40.0％（38／95），95株淋病奈瑟球菌对大观霉素敏感率100％，对青霉素、四环素、喹诺酮类药物的敏感率仅0％～2．6％，对头孢呋辛、头孢曲松、头孢噻肟的敏感率均高于90％。结论 大观霉素和头孢菌素类药物可作为治疗女性淋病奈瑟球菌感染的首选药物。     

Update on antimicrobial susceptibility and genotype of Neisseria gonorrhoeae isolated in Italy

Antimicrobial susceptibilities and genotypes of Neisseria gonorrhoeae collected in 2006-2010 from 6 medical centers located in Italy were compared with those from a previous survey conducted in 2003-2005. Resistance to ciprofloxacin increased from 34.2% to 62% whereas penicillin resistance declined from 25.5% to 14%. Important change in antimicrobial resistance rates and a high genetic variability among N. gonorrhoeae from Italy were observed.     

江苏省淋病奈瑟菌对抗菌药物的敏感性分析

目的检测江苏省淋病奈瑟菌（淋菌）临床分离株对几种抗生素的药敏情况，并初步探讨耐药因素。方法采用琼脂稀释法检测淋菌对青霉素、四环素、环丙沙星、头孢曲松、头孢吡肟、头孢噻肟、大观霉素、左氧氟沙星的MIC。结果淋菌对3种头孢类药物敏感率均为100％，对大观霉素敏感率为94．7％，对四环素敏感率为1．1％，而对青霉素和环丙沙星100％耐药。结论江苏省淋菌临床分离株对青霉素、四环素、环丙沙星耐药严重，对目前的一线药物（头孢类药物和大观霉素）敏感，但应重视大观霉素耐药株的出现。     

Association between proline-requiring auxotype and fluoroquinolone resistance in Neisseria gonorrhoeae isolated in Japan

We examined the association between auxotype and fluoroquinolone resistance in Neisseria gonorrhoeae isolated in Fukuoka, Japan, and investigated whether the prevalence of fluoroquinolone-resistant N. gonorrhoeae isolates was caused by the dissemination of the same clone in the community. We examined the antimicrobial susceptibility of 294 N. gonorrhoeae, isolates obtained during three different periods in Fukuoka, Japan, and 89 isolates of N. gonorrhoeae, classified by the presence of amino-acid substitutions in the quinolone resistance-determining regions (QRDRs) of GyrA and ParC proteins, to various agents, and we examined the auxotypes of the isolates. In 22 isolates with amino-acid substitutions within QRDRs in GyrA and ParC, pulsed-field gel electrophoresis analysis was performed. The proportion of fluoroquinolone-resistant isolates (ciprofloxacin, minimum inhibitory concentration [MIC] > or = 1 microg/ml) in 1998 (23.9%) was significantly higher than that in 1992-1993 (0%). The proportion of proline-requiring isolates increased significantly, from 4.4% in 1992-1993 to 54.5% in 1998. The ciprofloxacin MIC90 for the proline-requiring isolates were 32- and 128-fold, respectively, higher than those for the prototrophic isolates and the arginine-requiring isolates. The proportion of isolates with amino-acid substitutions within the QRDRs in GyrA and ParC in the proline-requiring group (55.5%) was significantly higher than that in the prototrophic group (0%). Of the 22 isolates with amino-acid substitutions within the QRDRs in GyrA and ParC, 16 showed the same pulsed-field gel electrophoresis pattern. These results suggest that a close association exists between the increase in the proline-requiring isolates and the increase in the fluoroquinolone-resistant isolates in the gonococci isolated in Fukuoka, and that the prevalence of fluoroquinolone-resistant N. gonorrhoeae isolates with GyrA and ParC substitutions may be mainly caused by the dissemination of a single clone in the community.     

Comparison of Neisseria gonorrhoeae isolates from the genital tract and pharynx of two gonorrhea patients

Neisseria gonorrhoeae was isolated simultaneously from urethral and pharyngeal specimens of two gonorrhea patients. The pair of isolates from one of the two patients were identical in auxotype, pulsed-field gel electrophoresis pattern, and antimicrobial susceptibility, which indicated that both sites in that patient were infected with the same strain of N. gonorrhoeae. However, the two isolates from the other patient had different properties, indicating that the two sites in the second patient were infected with different strains. The gonococcal infections in these patients failed to respond to initial treatment with sparfloxacin or sulbactam/ampicillin, because the causative strains of N. gonorrhoeae were resistant to the respective antibiotics. Variable patterns and routes of gonococcal infection have recently been discovered in individual patients, suggesting that specimens for bacterial isolation should be taken not just from one site but from various sites that might be infected. This method may contribute to the successful treatment and epidemiological investigation of gonococcal infections. Received: January 12, 2001 / Accepted: April 26, 2001     

A remarkable reduction in the susceptibility of Neisseria gonorrhoeae isolates to cephems and the selection of antibiotic regimens for the single-dose treatment of gonococcal infection in Japan

We compared the susceptibilities of 100 Neisseria gonorrhoeae isolates obtained from January to June 2000 to a variety of antimicrobial agents, including various cephems, with the susceptibilities of 55 isolates obtained from May to December 1995. In 11 of the 15 cephems tested, the MIC50 (minimum inhibitory concentration for 50% of isolates) ratios, calculated by dividing the MIC50 for isolates from 2000 by that for isolates from 1995, showed 4-fold to 16-fold differences. The MIC90 ratios of cefodizime and cefditoren showed only a 1-fold and 2-fold difference, respectively. However, the MIC90 ratios of the remaining 13 cephems showed 4-fold to 64-fold differences. We selected the most favorable antibiotic regimens for the single-dose treatment of gonorrhea in Japan according to the antigonococcal activity and pharmacokinetics, based on the criterion (therapeutic time) proposed by Moran and Levine i.e., the regimen should produce a concentration in the serum or plasma at least four times that of the MIC90 value for at least 10 h. Of the 20 single-dose regimens evaluated, only ceftriaxone 1 g intravenously and cefodizime 1 g intravenously were found to have a therapeutic time of more than 10 h for the isolates from 2000. Our results indicated that the susceptibilities of the isolates from 2000 to all the cephems tested, except for cefditoren and cefodizime, decreased remarkably in comparison with the susceptibilities of the isolates from 1995, while parenteral ceftriaxone 1 g and cefodizime 1 g appeared to be the most favorable single-dose regimens for the treatment of gonococcal infections in Japan. Received: August 23, 2001 / Accepted: October 26, 2001     

淋病奈瑟菌临床分离株对抗菌药物敏感性及TEM-1基因质粒分型研究

目的 检测2010～2011年度本地区临床分离的淋病奈瑟菌流行株对青霉素、四环素、大观霉素、头孢曲松和环丙沙星的敏感性,对质粒介导的产β-内酰胺酶淋球菌(PPNG)进行耐药质粒 TEM-1基因分型.方法 采用琼脂稀释法测定菌株对5种抗菌药物的最小抑菌浓度(MIC),判断敏感性按WHO西太区淋病奈瑟菌耐药性监测统一标准.用纸片酸度法检测PPNG菌株,多重PCR方法鉴定β-内酰胺酶质粒并进行 TEM-1基因分型.结果 150株淋病奈瑟菌中检出105株对青霉素耐药(70%);四环素和环丙沙星耐药率分别为84%和 98%;未发现对大观霉素和头孢曲松耐药菌株,但头孢曲松低敏率达到48%(72/150);青霉素﹑四环素和环丙沙星的MIC50及MIC90均已超过耐药标准,尤以青霉素和四环素为甚,其MIC50及MIC90均超过耐药标准的2倍和大于32倍.检出PPNG46株,阳性率为30.7%,耐药质粒TEM-1基因分型以亚洲型为主(91.3%,42/46),只有4株携带非洲型质粒.结论 淋病奈瑟菌对青霉素、四环素和环丙沙星耐药率较高,对大观霉素和头孢曲松的敏感性较高,可作为治疗的首选药物;TEM-1基因质粒分型以亚洲型为主.     

广州地区淋病奈瑟菌耐药性分析

目的监测广州地区2005年分离的淋病奈瑟菌对青霉素、四环素、大观霉素、头孢曲松和环丙沙星的耐药性,分析耐药菌株的流行特点。方法采用琼脂稀释法测定菌株对5种抗生素的MIC,按WHO标准判定四环素MIC≥16mg/L为质粒介导的高度耐四环素淋病奈瑟菌(TRNG);纸片酸度法检测产β内酰胺酶淋病奈瑟菌菌株;碱裂解法提取质粒。结果104株淋病奈瑟菌中检出质粒介导对青霉素(PRNG)和四环素(TRNG)耐药菌株分别为14株(13.5%)和15株(14.4%),环丙沙星耐药率为76.9%(80/104);未发现对大观霉素和头孢曲松耐药菌株。青霉素、四环素和环丙沙星的MIC50及MIC90分别为8mg/L、>32mg/L,2mg/L、32mg/L和4mg/L、32mg/L;其MIC50及MIC90均已超过耐药标准。结论淋病奈瑟菌对大观霉素和头孢曲松的敏感性较高,可作为治疗的首选药物,对青霉素、四环素和环丙沙星高水平耐药,提示对淋病的治疗作用差。     

The seventh nationwide surveillance of six otorhinolaryngological infectious diseases and the antimicrobial susceptibility patterns of the isolated pathogens in Japan

The Japanese Three Academic Societies Joint Antimicrobial Susceptibility Surveillance Committee conducted a nationwide surveillance on six otorhinolaryngological diseases and investigated the antimicrobial susceptibility patterns and isolation rates of the causative pathogens. The surveillance program was conducted in the otorhinolaryngological departments of 12 universities, and 36 affiliated hospitals and clinics. Patients with acute otitis media (children under six years old), chronic otitis media, acute nasal sinusitis, chronic nasal sinusitis, acute tonsillitis, and peritonsillar abscess (over 20 years old) between December 2015 and June 2017 were investigated. The collected swab or incision samples were cultivated for microbial identification, and the antimicrobial susceptibility of the detected bacteria was measured at the Kitasato University Research Center for Infections and Antimicrobials. The surveillance focused on three gram-positive bacteria (Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus), three gram-negative bacteria (Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa), and three anaerobic bacteria (anaerobic gram-positive cocci, Prevotella spp., Porphyromonas spp., and Fusobacterium spp.). Bacterial susceptibility to 40 antimicrobial agents was investigated. We were unable to completely mitigate the rise in the occurrence of resistant bacteria, such as methicillin-resistant S. aureus, penicillin-resistant S. pneumoniae, penicillin-intermediate resistant S. pneumoniae, beta-lactamase non-producing ampicillin-resistant H. influenzae, and beta-lactamase producing ampicillin-resistant H. influenzae. We suggest promoting the proper usage of antimicrobial agents to prevent the spread of these bacteria. We also suggested that immunization with pneumococcal vaccines is useful for decreasing the occurrence of otorhinolaryngological infectious diseases caused by pneumococci.     

淋球菌流行株对5种抗生素敏感性分析

目的 检测2008年度临床分离的淋球菌对青霉素、四环素、大观霉素、头孢曲松和环丙沙星的敏感性,分析耐药菌株的流行特点.方法 采用琼脂稀释法测定菌株对5种抗生素的最小抑菌浓度(MIC),判断其敏感性并按WHO西太平洋地区淋球菌耐药性监测统一标准.用纸片酸度法检测产β-内酰胺酶淋球菌菌株.结果 107株淋球菌中,检出94株对青霉素耐药(87.9%),产β-内酰胺酶淋球菌43株(40.2%);四环素耐药率为88.8%,其中质粒介导高度耐四环素淋球菌(TRNG)63株(58.9%);环丙沙星耐药率81.3%;未发现对大观霉素和头孢曲松耐药菌株.青霉索、四环素和环丙沙星的MIC50及MIC90均已超过耐药标准,尤以青霉素为甚,其MIC50及MIC90均超过耐药标准1、32倍.结论 淋球菌对大观霉素和头孢曲松的敏感性较高,可作为治疗的首选药物;对青霉素、四环素和环丙沙星耐药率较高,提示对淋病的治疗作用差.     

淋球菌流行株对5种抗生素敏感性分析

目的 检测2008年度临床分离的淋球菌对青霉素、四环素、大观霉素、头孢曲松和环丙沙星的敏感性,分析耐药菌株的流行特点.方法 采用琼脂稀释法测定菌株对5种抗生素的最小抑菌浓度(MIC),判断其敏感性并按WHO西太平洋地区淋球菌耐药性监测统一标准.用纸片酸度法检测产β-内酰胺酶淋球菌菌株.结果 107株淋球菌中,检出94株对青霉素耐药(87.9%),产β-内酰胺酶淋球菌43株(40.2%);四环素耐药率为88.8%,其中质粒介导高度耐四环素淋球菌(TRNG)63株(58.9%);环丙沙星耐药率81.3%;未发现对大观霉素和头孢曲松耐药菌株.青霉索、四环素和环丙沙星的MIC50及MIC90均已超过耐药标准,尤以青霉素为甚,其MIC50及MIC90均超过耐药标准1、32倍.结论 淋球菌对大观霉素和头孢曲松的敏感性较高,可作为治疗的首选药物;对青霉素、四环素和环丙沙星耐药率较高,提示对淋病的治疗作用差.     

淋球菌流行株对5种抗生素敏感性分析

目的 检测2008年度临床分离的淋球菌对青霉素、四环素、大观霉素、头孢曲松和环丙沙星的敏感性,分析耐药菌株的流行特点.方法 采用琼脂稀释法测定菌株对5种抗生素的最小抑菌浓度(MIC),判断其敏感性并按WHO西太平洋地区淋球菌耐药性监测统一标准.用纸片酸度法检测产β-内酰胺酶淋球菌菌株.结果 107株淋球菌中,检出94株对青霉素耐药(87.9%),产β-内酰胺酶淋球菌43株(40.2%);四环素耐药率为88.8%,其中质粒介导高度耐四环素淋球菌(TRNG)63株(58.9%);环丙沙星耐药率81.3%;未发现对大观霉素和头孢曲松耐药菌株.青霉索、四环素和环丙沙星的MIC50及MIC90均已超过耐药标准,尤以青霉素为甚,其MIC50及MIC90均超过耐药标准1、32倍.结论 淋球菌对大观霉素和头孢曲松的敏感性较高,可作为治疗的首选药物;对青霉素、四环素和环丙沙星耐药率较高,提示对淋病的治疗作用差.     

淋球菌流行株对5种抗生素敏感性分析

目的 检测2008年度临床分离的淋球菌对青霉素、四环素、大观霉素、头孢曲松和环丙沙星的敏感性,分析耐药菌株的流行特点.方法 采用琼脂稀释法测定菌株对5种抗生素的最小抑菌浓度(MIC),判断其敏感性并按WHO西太平洋地区淋球菌耐药性监测统一标准.用纸片酸度法检测产β-内酰胺酶淋球菌菌株.结果 107株淋球菌中,检出94株对青霉素耐药(87.9%),产β-内酰胺酶淋球菌43株(40.2%);四环素耐药率为88.8%,其中质粒介导高度耐四环素淋球菌(TRNG)63株(58.9%);环丙沙星耐药率81.3%;未发现对大观霉素和头孢曲松耐药菌株.青霉索、四环素和环丙沙星的MIC50及MIC90均已超过耐药标准,尤以青霉素为甚,其MIC50及MIC90均超过耐药标准1、32倍.结论 淋球菌对大观霉素和头孢曲松的敏感性较高,可作为治疗的首选药物;对青霉素、四环素和环丙沙星耐药率较高,提示对淋病的治疗作用差.