Mycoplasma genitalium urethritis in men

Mycoplasma genitalium was first isolated from two men with non-gonococcal urethritis (NGU) and thereafter shown to produce urethritis in subhuman primates, inoculated intraurethrally. This mycoplasma has been detected significantly more often in patients with acute NGU, particularly in patients with non-chlamydial NGU, than in subjects without urethritis. The prevalence of M. genitalium-positive non-chlamydial NGU ranges from 18 to 46% of all non-chlamydial NGU cases. In addition, the persistence of M. genitalium in the urethra after antimicrobial chemotherapy is associated with persistence or recurrence of NGU. The various results reported to date tend to support the proposition that M. genitalium is a pathogen of NGU. M. genitalium is highly susceptible to tetracyclines, macrolides, and some new fluoroquinolones, but the clinical data on the chemotherapy in M. genitalium-positive NGU is extremely limited. Because of the possible association between the post-treatment presence of M. genitalium in the urethra and persistent or recurrent NGU, the eradication of this mycoplasma from the urethra is essential in the management of patients with M. genitalium-positive NGU. Further studies are required to establish the optimal chemotherapy for M. genitalium-positive NGU.     

妇科患者生殖道分离培养生殖支原体和肺炎支原体的研究

目的 用病原学的方法探讨妇科感染性疾病患者生殖道是否存在生殖支原体和肺炎支原体感染，为临床诊治提供依据。方法 采集妇科感染性疾病患者宫颈管分泌物，接种到SP－4培养基作分离培养。阳性培养物用生化反应、协同凝集试验、代谢抑制试验、聚合酶链反应和DNA测序来加以鉴定。结果 从172例患者的宫颈分泌物中分离到生殖支原体4株（2．33％），肺炎支原体2株（1．16％）。而172例健康女性未分离到相应菌株。结论 本研究从病原学证实，南京地区妇科感染性疾病患者生殖道中存在生殖支原体和肺炎支原体感染，在临床诊治中应予关注。     

Molecular basis of metronidazole resistance in pathogenic bacteria and protozoa

The molecular basis of metronidazole resistance has been examined in anaerobic bacteria, such asBacteroides , Clostridium, and Helicobacter, and anaerobic parasitic protists such as Giardia,Entamoeba , and trichomonads. A variety of enzymatic and cellular alterations have been shown to correlate with metronidazole susceptibility in these pathogens; however, a common theme has been revealed. Resistant cells are typically deficient in drug activation. The frequent correlation between metronidazole resistance and ineffective drug activation suggests that drug resistance is the result of modification of proteins involved in drug activation.     

Molecular basis of branched peptides resistance to enzyme proteolysis

We found that synthetic peptides in the form of dendrimers become resistant to proteolysis. To determine the molecular basis of this resistance, different bioactive peptides were synthesized in monomeric, two-branched and tetra-branched form and incubated with human plasma and serum. Proteolytic resistance of branched multimeric sequences was compared to that of the same peptides synthesized as multimeric linear molecules. Unmodified peptides and cleaved sequences were detected by high pressure liquid chromatography and mass spectrometry. An increase in peptide copies did not increase peptide resistance in linear multimeric sequences, whereas multimericity progressively enhanced proteolytic stability of branched multimeric peptides. A structure-based hypothesis of branched peptide resistance to proteolysis by metallopeptidases is presented.     

妊娠期生殖道支原体感染的耐药监测

目的分析2011年佛山地区妊娠期妇女生殖道支原体感染情况及抗菌药物耐药情况,重点分析阿奇霉素对妊娠期生殖道支原体的耐药情况。方法以2011年1～12月本院门诊及住院收治的孕妇为监测对象,统计妊娠期生殖道支原体感染的发生情况,支原体属检测采用支原体分离培养药敏试剂盒,测试12种抗菌药物的敏感性。结果妊娠期生殖道支原体感染阳性率为33．76％,其中解脲支原体感染阳性率为33128％。人型支原体感染阳性率为4．20％,解脲支原体＋人型支原体混合感染阳性率为3．72％。12种抗菌药物的耐药率依次为：环丙沙星（58．61％）〉红霉素（24．64％）〉司巴沙星（19．14％）〉罗红霉素（12．44％）〉阿奇霉素（11.48％）=克拉霉素（11．48％）〉左旋氧氟沙星（11．24％）〉氧氟沙星（11．00％）〉四环素（6．70％）〉强力霉素（3．59％）〉美满霉素（2．87％）〉交沙霉素（0．48％）。结论妊娠期生殖道支原体感染以解脲支原体感染为主,阿奇霉素对生殖道支原体感染仍保持较高的敏感性,可为作治疗妊娠期生殖道支原体感染的首选药物。     

Tackling antimicrobial resistance

Bacteria resistant to antibiotic therapy are becoming much more common and this has led to mounting concern in the UK and worldwide. Many pathogens are now 'multiresistant', that is, they are resistant to several classes of antimicrobial drug. Infection with such organisms may be particularly difficult to treat. In this article, we briefly discuss how resistance and multiresistance occur. We consider some of the important pathogens involved and the problems they pose in hospitals and the community. We discuss strategies for slowing the accumulation of antibiotic resistance and the implications for doctors treating patients with common infections.     

Mechanisms of drug resistance in Mycoplasma pneumoniae

Mycoplasma pneumoniae is a pathogenic mycoplasma responsible for respiratory tract infections in humans, occurring worldwide in children and adults. This review briefly focuses on its antibiotic susceptibility profile and on the development of acquired resistance for this microorganism. The lack of a cell wall in mycoplasmas makes them intrinsically resistant to beta-lactams and to all antimicrobials which target the cell wall. Intrinsic resistance related to specific mycoplasma species concerns essentially the acrolide-lincosamide-streptogramin-ketolide (MLSK) antibiotic group. M. pneumoniae is susceptible to all MLSK antibiotics, except to lincomycin. Among the three antibiotic classes used for the treatment of mycoplasmal infections including tetracyclines, MLSK group, and fluoroquinolones, macrolides and related antibiotics are the drug of choice for respiratory infections caused by M. pneumoniae. Both target alterations and efflux mechanisms implicated in acquired antibiotic resistance have been described in mycoplasmas either by genetic mutation or transfer of new genes carried by transposons. At present, M. pneumoniae remains greatly susceptible to antibiotics, but as this mycoplasma is difficult to isolate, the number of clinical strains tested is limited and the occurrence of acquired resistance not well documented. However some strains having acquired resistance to MLSK have been decribed in vivo and erythromycin-resistant isolates are spreading now in Japan. To date, no clinical isolates resistant to fluoroquinolones or tetracyclines have been described in the literature, but some strains having acquired resistance to both classes have been selected in vitro. Molecular diagnosis of this acquired resistance has been related to target alterations, in ribosome for macrolides and tetracyclines, or in topoisomerase II genes for fluoroquinolones.     

Molecular basis of resistance to macrolides, lincosamides and streptogramins in Staphylococcus saprophyticus clinical isolates

The aim of this study was to evaluate the prevalence of resistance to macrolide-lincosamide-streptogramin (MLS) antibiotics as well as to assess the molecular basis of this resistance amongst 72 Staphylococcus saprophyticus urinary isolates collected from 2005 to 2009 in University Hospital of Caen (France). Of the 72 strains studied, 33 (45.8%) were resistant to at least one MLS antibiotic, including 24 (72.7%) with an M phenotype, 5 (15.2%) with an inducible MLS(B) phenotype, 3 (9.1%) with a combined M+L phenotype and 1 (3.0%) with an L phenotype. All isolates were susceptible to the combination of streptogramins A and B. The resistance genes erm(A), erm(B), erm(C), msr(A) and lnu(A) were detected alone in 0, 0, 5 (15.2%), 24 (72.7%) and 1 (3.0%) of the 33 MLS-resistant isolates, respectively, whereas 2 strains (6.1%) were positive for both msr(A) and lnu(A). All msr(A)-positive isolates exhibited an M phenotype, whereas all five erm(C)-positive and all three lnu(A)-positive strains displayed, respectively, an inducible MLS(B) phenotype and an L phenotype with a positive Hodge test. Plasmid analysis indicated that erm(C) and lnu(A) genes were borne by small-size plasmids (ca. 2.5 kb), whereas larger plasmids (30-90 kb) harboured msr(A). In conclusion, these findings show a high prevalence of MLS resistance in S. saprophyticus, which was mainly associated with the presence of the msr(A) gene. Since S. saprophyticus colonises the gastrointestinal tract, it may constitute an unexpected reservoir for MLS resistance genes, in particular msr(A), amongst coagulase-negative staphylococci.     

Molecular basis of chronopharmaceutics

Many pathophysiological circumstances vary during 24 h periods. Many physiologic processes undergo biological rhythms, including the sleep-wake rhythm and metabolism. Disruptive effect in the 24 h variations can manifest as the emergence or exacerbation of pathological conditions. So, chronotherapeutics is gaining increasing interest in experimental biology, medicine, pharmacy, and drug delivery. This science and the plethora of information should be used intelligently for optimizing the effectiveness and safety of the drug, relying on the timing of drug intake. These chronopharmacological findings are affected by not only the pharmacodynamics but also pharmacokinetics of drugs. The mammalian circadian pacemaker is located in the suprachiasmatic nucleus. The molecular mechanisms are associated with Clock genes that control the circadian rhythms in physiology, pathology, and behavior. Clock controls several diseases such as metabolic syndrome, cancer, and so on. CLOCK mutation influences the expression of both rhythmic and nonrhythmic genes in wild-type tissues. These genotypic changes lead to phenotypic changes, affecting the drug pharmacokinetic and pharmacodynamic parameters. This review is intended to elaborate system regulating biological rhythms and the applicability in pharmaceutics from viewpoints of the intraindividual and interindividual variabilities of Clock genes.     

Molecular epidemiology of antimicrobial resistance among Salmonella enterica serovar Infantis from poultry in Kagoshima, Japan

Antimicrobial susceptibility and resistance genes of 135 strains of Salmonella enterica serovar Infantis isolated from poultry in Kagoshima were examined. One strain (0.7%) was resistant to ampicillin (A), 97% to streptomycin (S), 95.6% to sulphamethoxazole (Su), 96.3% to oxytetracycline (T), 11.1% to kanamycin (Km) and 36.3% to ofloxacin (O). Multiresistant phenotypes identified were ASSuT-Km, SSuT-Km, SSuT-O and SSuT. Class 1 integrons were detected in 94.8% of isolates. Approximately 89% of oxytetracycline-resistant strains carried the tetA gene and all of the 131 streptomycin-resistant isolates carried the aadA1a gene. Forty-percent of kanamycin-resistant isolates carried the aphA1-Iab gene. All isolates were susceptible to chloramphenicol. Recognition of TEM-type beta-lactamase in a S. Infantis strain from chickens is a recent rare finding in Japan.     

Overcoming antimicrobial resistance by targeting resistance mechanisms

Three mechanisms of antimicrobial resistance predominate in bacteria: antibiotic inactivation, target site modification, and altered uptake by way of restricted entry and/or enhanced efflux. Many of these involve enzymes or transport proteins whose activity can be targeted directly in an attemptto compromise resistance and, thus, potentiate antimicrobial activity. Alternatively, novel agents unaffected by these resistance mechanisms can be developed. Given the ongoing challenge posed by antimicrobial resistance in bacteria, targeting resistance in this way may be our best hope at prolonging the antibiotic era.     

High burden of antimicrobial resistance in Asia

Pseudomonas aeruginosa is a nosocomial and community-acquired pathogen associated with considerable patient morbidity and mortality. Multidrug resistance in P. aeruginosa is a concern owing to the limited therapeutic options available to treat infections due to this organism. In this study, rates of antimicrobial resistance of P. aeruginosa isolates collected by The Surveillance Network Database-USA (Eurofins Medinet, Chantilly, VA) from 1997 to 2009 were examined. The patient population and specimens were stratified according to patient setting and age as well as specimen source. Multidrug resistance was defined as resistance to three or more of the following antimicrobial agents: aztreonam; cefepime; ciprofloxacin; imipenem; gentamicin; and piperacillin/tazobactam (TZP). A total of 924 740 P. aeruginosa isolates were examined in this study. Changes in resistance rates to individual antimicrobial agents were <5% for all agents except ciprofloxacin. There was a statistically significant decreasing rate of multidrug-resistant P. aeruginosa to four, five and six antimicrobial agents. For isolates resistant to imipenem, aztreonam and gentamicin, ciprofloxacin had the highest cross-resistance rates. The greatest coverage against P. aeruginosa was by the combination of TZP plus amikacin (94%) followed by aztreonam plus amikacin (90%). Pseudomonas aeruginosa resistance rates remained steady or minimally declined to all antimicrobials from 1997 to 2009. Amongst the β-lactams, TZP has the greatest activity against P. aeruginosa.     

Molecular basis of insulin action

Insulin is the main anabolic and anticatabolic hormone in mammals. The stimulatory effect of insulin on glucose uptake in muscle and adipose tissue is a consequence of the rapid translocation of GLUT4 glucose transporters from an intracellular site to the cell surface. The actions of insulin are initiated by hormone binding to its cell surface receptors. Insulin receptors are ligand-stimulated protein tyrosine kinases and phosphorylate a number of proteins, known as insulin receptor substrate proteins. Insulin resistance has been recognized as a main pathogenic factor in the development of type 2 diabetes, and has been associated with dyslipidemia, hypertension, endothelial dysfunction, inflammation and coagulative state. The current challenge is the study of impaired insulin signaling pathways leading to beta-cell dysfunction and its progression to type 2 diabetes, as well as control of chronic inflammation processes that may improve insulin action.     

Molecular basis and clonal nature of increasing pneumococcal macrolide resistance in South Africa, 2000-2005

The prevalence and molecular epidemiology of pneumococcal macrolide resistance in South Africa was investigated. Minimum inhibitory concentrations and serotypes of pneumococcal isolates causing invasive disease from 2000-2005 (n=15982), collected through a national laboratory-based surveillance system, were determined. Randomly selected isolates from 2005 (51%; 260/508) had resistance mechanisms determined, and clonality was investigated by pulsed-field gel electrophoresis (PFGE) (n=64) and multilocus sequence typing (n=7). Macrolide resistance increased from 9% (160/1828) in 2000 to 14% (508/3656) in 2005 (P<0.001). Serotype 14 was the most common macrolide-resistant serotype (40%; 760/1921). The majority of macrolide-resistant isolates (75%; 1437/1921) displayed the macrolide-lincosamide-streptogramin B (MLS(B)) phenotype. Of the strains screened genotypically, 57% (147/260) contained erm(B), 27% (71/260) contained mef(A) and 15% (40/260) contained erm(B) and mef(A); 1% (2/260) contained ribosomal mutations. Macrolide-resistant isolates were predominantly penicillin-non-susceptible and multidrug-resistant. Isolates clustered according to serotype by PFGE, and 22% (14/64), 11% (7/64) and 5% (3/64) of isolates were related to the Taiwan(19F)-14, England(14)-9 and Spain(9V)-3 global clones, respectively. Routine use of the 7-valent pneumococcal conjugate vaccine (PCV-7) could reduce the burden of macrolide-resistant pneumococcal disease in South Africa.