女性生殖道支原体感染与不孕症的关系及药敏分析

目的探讨女性生殖道支原体感染与不孕症之间的关系及对11种抗生素的敏感率,指导临床明确诊断,合理用药。方法随机选择2007年至2009年来长治市妇幼保健院就诊的女性不孕症患者360例,进行宫颈分泌物支原体培养和药敏试验。结果 360例宫颈分泌物标本中检出解脲支原体(Uu)阳性者161例、人型支原体(Mh)阳性者3例、解脲支原体(Uu)+人型支原体(Mh)混合阳性者29例;对阳性标本都做了11种抗生素的药敏试验,其中交沙霉素敏感率为93.47%、美满霉素敏感率为92.00%、强力霉素敏感率为90.21%、克拉霉素敏感率为83.69%、甲砜霉素敏感率为73.91%、环脂红霉素敏感率为61.95%和阿奇霉素敏感率为53.26%等。结论女性不孕症伴随高发的生殖道支原体感染,支原体感染与不孕症可能有关;长治地区生殖道支原体对交沙霉素、美满霉素、强力霉素、克拉霉素、甲砜霉素敏感性较高,环脂红霉素、阿奇霉素次之,对红霉素、罗红霉素敏感性较低,对环丙沙星、左氧氟沙星敏感性很低。     

支原体对抗生素的体外敏感性研究

目的研究非淋菌性尿道(宫颈)炎(NGU)患者支原体对12种抗生素敏感性,指导临床治疗。方法男性标本取尿道拭子．女性标本取宫颈拭子,采用支原体培养鉴定及药敏试剂盒进行体外药敏测定。结果126株解脲支原体(Uu)对12种抗生素敏感性从高至低依次为交沙霉素、强力霉素、美满霉素、克拉霉素、四环素、阿奇霉素、罗红霉素、司帕沙星、甲砜霉素、红霉素、可乐必妥和壮观霉素。12株人型支原体(Mh)对12种抗生素敏感性从高至低依次为交沙霉素、强力霉素、美满霉素、司帕沙星、四环素、壮观霉素、可乐必妥、甲砜霉素、红霉素、阿奇霉素、克拉霉素和罗红霉素。结论支原体耐药情况相当普遍。Uu、Mh对相同抗生素具有不同的敏感性。治疗时可依据药敏结果选择用药。     

3类抗菌药物体外抗解脲脲原体和人型支原体的作用

目的比较四环素类、大环内酯类和喹诺酮类3类抗菌药物,对临床分离株解脲脲原体(Uu)和人型支原体(Mh)的抗菌作用,为临床用药提供参考依据.方法采用直接肉汤药盘法测定了临床标本中,195株Uu和1218株Mh对3类抗菌药物中的8种抗生素的敏感性.结果 195株Uu对四环素、多西环素、米诺环素、罗红霉素、阿齐霉素、交沙霉素、氧氟沙星和司帕沙星的敏感率,分别为21.0%、48.2%、39.5%、79.0%、88.7%、74.9%、28.2%和64.6%.118株Mh对四环素、多西环素、米诺环素、罗红霉素、阿齐霉素、交沙霉素、氧氟沙星、司帕沙星的敏感率分别为5.1%、33.9%、26.3%、0.0%、0.0%、89.8%、70.3%和64.4%.960例混合感染的Uu Mh,对交沙霉素最敏感(79.2%).结论泌尿生殖道支原体的药敏监测对指导临床治疗具有重要意义.     

Treatment of Mycoplasma genitalium. Observations from a Swedish STD Clinic

Objectives

To evaluate therapy for Mycoplasma genitalium infection with doxycycline or azithromycin 1 g compared to five days of azithromycin (total dose 1.5 g).

Methods

A retrospective case study was performed among patients attending the STD-clinic in Falun, Sweden 1998–2005. All patients with a positive PCR test for M. genitalium were routinely offered a test of cure (toc). Response to doxycycline for 9 days, azithromycin 1 g single dose and extended azithromycin (500 mg on day 1 followed by 250 mg o.d. for 4 days) was determined. In patients with treatment failure after azithromycin, macrolide resistance was monitored before and after treatment. Furthermore, the rate of macrolide resistance was monitored for positive specimens available from 2006–2011.

Results

The eradication rate after doxycycline was 43% (48% for women and 38% for men), for azithromycin 1 g 91% (96% for women and 88% for men) and for extended azithromycin 99% (100% for women and 93% for men). Macrolide resistance developed in 7/7 examined (100%) of those testing positive after azithromycin 1 g, but in none of those treated with extended azithromycin. Macrolide resistance before treatment increased from 0% in 2006 and 2007 to 18% in 2011.

Conclusions

These findings confirm the results from other studies showing that doxycycline is inefficient in eradicating M. genitalium. Although azithromycin 1 g was not significantly less efficient than extended dosage, it was associated with selection of macrolide resistant M. genitalium strains and should not be used as first line therapy for M. genitalium. Monitoring of M. genitalium macrolide resistance should be encouraged.     

Inhibition of 50S Ribosomal Subunit Assembly in <Emphasis Type="Italic">Haemophilus influenzae</Emphasis> Cells by Azithromycin and Erythromycin

Azithromycin is an important antibiotic for the treatment of several different Gram-positive and Gram-negative bacterial infections. Erythromycin and clarithromycin are less useful antibiotics against Gram-negative infections. This difference in inhibitory activity was explored by comparing the effects of azithromycin and erythromycin on cellular functions in Haemophilus influenzae cells. Effects of both antibiotics on translation, cell viability, and growth rates have been measured. An IC₅₀ of 0.4 μg/ml was found for the effects of azithromycin on each of these processes. For erythromycin, an IC₅₀ of 1.5 μg/ml was observed, indicating a fourfold lower sensitivity of the organisms to this compound. The features of a second target for macrolide antibiotic inhibition in H. influenzae cells have also been examined. Inhibition of the synthesis of the large 50S ribosomal subunit was measured. Subunit formation was prevented in a concentration dependent fashion, with azithromycin showing a ninefold greater effect on this process compared with erythromycin. Synthesis of the 30S ribosomal subunit was not effected. Pulse and chase labeling kinetics confirmed the slower synthesis rate of the 50S particle in the presence of each antibiotic. The results are discussed in terms of the stronger effect of azithromycin on ribosome biosynthesis in this organism. Received: 24 July 2001 / Accepted: 25 September 2001     

4103例泌尿生殖道支原体感染及药敏分析

目的通过分析泌尿生殖道支原体感染及药敏情况,为临床提供用药指导。方法采用支原体检测试剂盒进行支原体属培养和药敏试验。结果4103例患者标本中,检出支原体属1336株,总阳性率为32．56％;其中单一解脲脲原体（Uu）感染1227例,阳性率为91．84％;单纯人型支原体（Mh）感染15例,阳性率为1．12％;Uu＋Mh混合合感染94例,阳性率为7．04％。解脲脲原体对阿奇霉素、红霉素、交沙霉素、罗红霉素、米诺环素、强力霉素敏感性高;单纯人型支原体对交沙霉素、米诺环素、强力霉素敏感。结论泌尿生殖道支原体感染以Uu为主。支原体大多具有多重耐药性,临床治疗需根据药敏结果选药物。     

Administration of antibiotics in combination. Determination of antibacterial effectivity of blood serum and urine after simultaneous administration of macrolides and tetracyclines.

The authors deal with antibacterial effectivity of blood serum and urine in simultaneous administration of macrolids and tetracyclines under in vivo conditions, using Staphylococcus aureus strains. The obtained results suggest that pharmacodynamic effect, i.e., higher effective concentration, is induced in some combinations of these preparations. It was found mainly after the administration of the combinations of erythromycin 250 mg + doxycycline 200 mg in all the chosen reference strains S. a. The results have also shown that the combination of erythromycin with tetracycline has a higher effect when an erythromycin-resistant strain is used than when using a strain resistant to tetracycline.     

解脲脲原体药物敏感性变迁研究

目的:探讨上海地区2008与2012年泌尿生殖道解脲脲原体(Ureaplasma urealyticum,UU)耐药性变化,为临床合理用药提供参考。方法:采用自制UU药物敏感检测试剂对2008年450例和2012年459例患者的标本进行检测,观察UU阳性情况及UU对交沙霉素、氧氟沙星、阿奇霉素和强力霉素的药物敏感性。结果:2008年分离到150例UU阳性标本和2012年分离到134例UU阳性标本分别对交沙霉素、强力霉素、氧氟沙星和阿奇霉素等4种抗菌素的敏感率有显著性差异;2008年46例和2012年38例男性患者阳性标本中分离的UU分别对交沙霉素和阿奇霉素敏感率有显著性差异;对强力霉素和氧氟沙星敏感率无显著性差异。2008年104例和2012年96例女性患者阳性标本中分离的UU分别对交沙霉素、强力霉素、氧氟沙星和阿奇霉素等4中抗菌素的敏感率都有显著性差异。结论:5年间UU药物敏感性发生了变迁;临床医师应该关注本地区药物敏感性变迁,合理选用抗生素。     

Effect of subinhibitory concentrations of antimicrobial agents (quinolones and macrolide) on the production of verotoxin by enterohemorrhagic Escherichia coli O157:H7.

In Japan, antimicrobial agent therapy for patients with diarrhea due to enterovirulent organisms including enterohemorrhagic Escherichia coli (EHEC) is common, and norfloxacin (NFLX), fosfomycin, and kanamycin are recommended for EHEC treatment by the Japanese Ministry of Health and Welfare. The aim of this study was to analyze the effects of antimicrobial agents which have been used or recommended for the treatment of EHEC on the production of verotoxin (VT) in vitro. Subinhibitory concentrations of quinolones, NFLX, sparofloxacin (SPFX), and grepafloxacin (GPFX) markedly stimulated the productions of VT1 and VT2. The macrolide azithromycin (AZM), erythromycin (EM), and clarithromycin (CAM) did not stimulate the production of VT at a wide range of concentrations. These in vitro results indicate that when quinolones are prescribed for a patient infected with EHEC, the concentration of antimicrobial agents used in vivo and the susceptibility of the EHEC strains against quinolones should be taken into consideration.     

Antibiotic sensitivity of plague microbe strains from foreign countries]

The method of serial dilutions on the Hottinger agar was applied to comparative assay of antibiotic sensitivity in 50 strains of the plague microbe isolated abroad and in 5 strains isolated in the plague focus in the Central Caucasus. The antibiotics used in the assay were the following: streptomycin, gentamicin, doxycycline, monomycin, kanamycin, tetracycline, erythromycin, ristomycin, lincomycin and polymyxin M. Irrespective of the origin, all the isolates were resistant to erythromycin, lincomycin and polymyxin M. The levels of the sensitivity to the other antibiotics were different. The data serve as a ground for the statement that there is no tendency to development of antibiotic resistance in the plague microbe in patients treated with high doses of the antibiotics and mainly streptomycin. Along with streptomycin, such antibiotics as gentamicin, tetracycline, doxycycline and kanamycin are useful in the therapy of plague and require further investigation.     

Susceptibility to antibiotics of Ureaplasma urealiticum strains isolated at the primorye region]

Susceptibility to antibiotics of Ureaplasma urealyticum strains isolated in Primorye Region and its changes were evaluated. Among the sexually transmited diseases urogenital ureaplasmosis has the leading position in combination with gonorrhoea, trichomoniasis and infections caused by opportunistic pathogens. The spectrum of investigated antibacterial agents included gentamycin, clarithromycin, roxythromycin, azithromycin, doxycycline, three fluoroquinolones of II generation and for cephalosporins of the I and III generations. The most potent activity against U. urealyticum was demonstrated for pefloxacin (67 per cent of susceptible strains), ofloxacin (63 per cent) and roxythmycin (54 per cent). It is concluded that at Primorye Region the drugs of first choice for the urogenital infections therapy are fluoroquinolones.     

Time-Resolved Binding of Azithromycin to Escherichia coli Ribosomes

Azithromycin is a semisynthetic derivative of erythromycin that inhibits bacterial protein synthesis by binding within the peptide exit tunnel of the 50S ribosomal subunit. Nevertheless, there is still debate over what localization is primarily responsible for azithromycin binding and as to how many molecules of the drug actually bind per ribosome. In the present study, kinetic methods and footprinting analysis are coupled together to provide time-resolved details of the azithromycin binding process. It is shown that azithromycin binds to Escherichia coli ribosomes in a two-step process: The first-step involves recognition of azithromycin by the ribosomal machinery and places the drug in a low-affinity site located in the upper part of the exit tunnel. The second step corresponds to the slow formation of a final complex that is both much tighter and more potent in hindering the progression of the nascent peptide through the exit tunnel. Substitution of uracil by cytosine at nucleoside 2609 of 23S rRNA, a base implicated in the high-affinity site, facilitates the shift of azithromycin to this site. In contrast, mutation U754A hardly affects the binding process. Binding of azithromycin to both sites is hindered by high concentrations of Mg²⁺ ions. Unlike Mg²⁺ ions, polyamines do not significantly affect drug binding to the low-affinity site but attenuate the formation of the final complex. The low- and high-affinity sites of azithromycin binding are mutually exclusive, which means that one molecule of the drug binds per E. coli ribosome at a time. In contrast, kinetic and binding data indicate that in Deinococcus radiodurans, two molecules of azithromycin bind cooperatively to the ribosome. This finding confirms previous crystallographic results and supports the notion that species-specific structural differences may primarily account for the apparent discrepancies between the antibiotic binding modes obtained for different organisms.     

Concentrations of erythromycin and azithromycin in mature Chinook salmon Oncorhynchus tshawytscha after intraperitoneal injection, and in their progeny

A single dose (40 mg kg(-1)) of erythromycin or azithromycin dihydrate was injected intraperitoneally into maturing female fall Chinook salmon 12 to 32 d before spawning to observe the distribution, retention and clearance of the drugs in plasma, kidney, coelomic fluid and egg vitellin, and their persistence in alevins derived from these fish. Salmon administered prophylactic dosages of erythromycin as subadults were also included to investigate potential interactive effects of oral and injected treatments on reproductive performance and antibiotic clearance. Erythromycin was rapidly cleared from plasma and coelomic fluid, but was detected in the kidney (3.52 to 12.40 microg g(-1)) and egg vitellin (5.32 to 8.87 microg ml(-1)) of all fish at spawning. High, stable concentrations of azithromycin were detected in plasma (14.66 to 20.33 microg ml(-1)), kidney (43.16 to 59.96 microg g(-1)), coelomic fluid (2.52 to 5.50 microg ml(-1)) and egg vitellin (12.65 to 23.51 microg ml(-1)). Oral administration of erythromycin to subadult salmon did not significantly affect tissue concentrations of either erythromycin or azithromycin administered by prespawning injection. Reductions in the percentage of eggs that yielded live embryos at the eyed stage of development occurred among eggs derived from females that had received orally administered erythromycin as subadults. Erythromycin was not detected in unfed fry derived from adults injected with the drug prespawning, but azithromycin was present for more than 2 mo after the onset of exogenous feeding.     

Mechanism and diversity of the erythromycin esterase family of enzymes

Macrolide antibiotics such as azithromycin and erythromycin are mainstays of modern antibacterial chemotherapy, and like all antibiotics, they are vulnerable to resistance. One mechanism of macrolide resistance is via drug inactivation: enzymatic hydrolysis of the macrolactone ring catalyzed by erythromycin esterases, EreA and EreB. A genomic enzymology approach was taken to gain insight into the catalytic mechanisms and origins of Ere enzymes. Our analysis reveals that erythromycin esterases comprise a separate group in the hydrolase superfamily, which includes homologues of uncharacterized function found on the chromosome of Bacillus cereus, Bcr135 and Bcr136, whose three-dimensional structures have been determined. Biochemical characterization of Bcr136 confirms that it is an esterase that is, however, unable to inactivate macrolides. Using steady-state kinetics, homology-based structure modeling, site-directed mutagenesis, solvent isotope effect studies, pH, and inhibitor profiling performed in various combinations for EreA, EreB, and Bcr136 enzymes, we identified the active site and gained insight into some catalytic features of this novel enzyme superfamily. We rule out the possibility of a Ser/Thr nucleophile and show that one histidine, H46 (EreB numbering), is essential for catalytic function. This residue is proposed to serve as a general base in activation of a water molecule as the reaction nucleophile. Furthermore, we show that EreA, EreB, and Bcr136 are distinct, with only EreA inhibited by chelating agents and hypothesized to contain a noncatalytic metal. Detailed characterization of these esterases allows for a direct comparison of the resistance determinants, EreA and EreB, with their prototype, Bcr136, and for the discussion of their potential connections.     

Temporal prevalence of antimicrobial resistance in Campylobacter spp. from beef cattle in Alberta feedlots

Antimicrobial resistance (AMR) was temporally assessed in campylobacters isolated from beef cattle (7,738 fecal samples from 2,622 animals) in four commercial feedlots in Alberta. All calves were administered chlortetracycline and oxytetracycline in feed, and a majority of the animals (93%) were injected with long-acting oxytetracycline upon arrival at the feedlot. Fecal samples from individual animals were collected upon arrival (i.e., entry sample), 69 days (standard deviation [SD] = 3 days) after arrival (i.e., interim sample), and 189 days (SD = 33 days) after arrival (i.e., exit sample) at the feedlot. In total, 1,586 Campylobacter isolates consisting of Campylobacter coli (n = 154), Campylobacter fetus (n = 994), Campylobacter jejuni (n = 431), Campylobacter hyointestinalis (n = 4), and Campylobacter lanienae (n = 3) were recovered and characterized. The administration of antimicrobials did not decrease carriage rates of campylobacters, and minimal resistance (< or =4%) to azithromycin, ciprofloxacin, enrofloxacin, gentamicin, and meropenem was observed. In contrast, substantive increases in the prevalence of isolates resistant to tetracycline and doxycycline (56 to 89%) for C. coli, C. fetus, and C. jejuni, as well as in the number of animals (7 to 42%) from which resistant isolates were recovered, were observed during the feedlot period. Increased resistance to erythromycin (total isolates and carriages rates) was also observed in isolates of C. coli over the three isolation times. The majority of C. fetus isolates recovered were resistant to nalidixic acid, but this was independent of when they were isolated. A relatively limited number of multidrug-resistant isolates were recovered and consisted primarily of C. coli resistant to tetracyclines and erythromycin (10% of isolates). Over the course of the feedlot period, considerable increases in antimicrobial resistance were observed in C. coli, C. fetus, and C. jejuni, but with the exception of erythromycin resistance in C. coli, the administration of antimicrobial agents to beef cattle was found to have a minimal impact on resistance to macrolides and fluoroquinolones, the two classes of antimicrobials used to treat campylobacteriosis in humans. However, the widespread use of antimicrobial agents in beef production and the possible horizontal transfer of mobile genetic elements with antimicrobial resistance determinants among Campylobacter and other bacterial taxa emphasize the need to monitor AMR development in bacteria from beef cattle.     

Micronucleus frequency in women with genital Chlamydia Trachomatis infection before and after therapy

The main aim of the present study was to investigate the influence of infection with the intracellular bacterium Chlamydia trachomatis, and subsequent treatments with oral doxycycline or azithromycin on the frequency of micronuclei (MN) in peripheral blood lymphocytes of adult female patients receiving standard doses of these drugs. The frequency of micronuclei was measured in the lymphocytes of 38 newly diagnosed adult women with genital C. trachomatis infection. Samples were taken before and after the therapy, and from 50 healthy control females. The therapy was taken orally during 10 days at 2 x 100 mg per day, and then for another 10 days at 1 x 100 mg per day for doxycycline, and as a single dose of 1g for azithromycin. Isolated lymphocytes from all subjects were cultured by use of the whole-blood method and blocked in metaphase with cytochalasin B (Cyt B). One thousand binucleate cells per subject were scored according to published criteria. The frequency of micronuclei was not significantly higher in samples of infected females before therapy, compared with the baseline frequency in healthy control females (p > 0.05). In patients who received doxycycline, the micronucleus frequency after the end of therapy was significantly higher than before treatment (p < 0.001). The mean frequency of micronuclei in females after the end of the therapy with azithromycin did not show an increase (p > 0.05). The application of linear regression analysis showed that the difference in micronucleus frequency before and after therapy (effect of the antibiotics) was affected by the therapy type. Age and smoking did not affect micronucleus frequency in analyzed samples of patients (p = 0.078, 0.579). We conclude that C. trachomatis infection does not induce micronuclei in peripheral blood lymphocytes of infected adult female patients. Therapy with doxycycline significantly increases the micronucleus frequency in lymphocytes of treated patients, but treatment with azithromycin does not induce micronuclei.