STREPTOMY.CIN IN THE TRFATMF,NT OF EXUDATIVE TUBERCULOUS PLEURISY A~lD PERITONITIS

Since 1944 streptomycin has made its advent and proved its efficacy in the treatment of certain forms of human tuberculosis (1, 2). Accumulated experiences with this drug however disclosed its limitations aruong which may be mentioned the drug resistance and toxicity deve- loped on prolonged administration* In China, streptomycin is still con- sidere as an expensive drug and economic burden to the patient adds another d.ifficulty in recomruending its use. In those cases of tuberculosis which do not require prolonged strepto''mycin therapy, these shortcomings would be minimized. .Streptomycin is moxe effective in acute forms of tuberculosis and in cases in which the number of tubercle bacilli is relatively small. Under these conditions the therapeutic effect of streptomycin usually precedes the development of toxicity or drug resistance.     

Fusidic acid: new opportunities with an old antibiotic.

The extensive foreign experience with fusidic acid prior to its belated introduction to Canada is reviewed. Fusidic acid is a steroid antibiotic with minimal toxic and hormonal effects that is mainly excreted through the liver. It has a predominantly bactericidal action and does not shown cross-resistance with other antibiotics. Since organisms resistant to this drug form easily in vitro when exposed to low concentrations, complementary treatment with another antibiotic may be required in some clinical situations. Although fusidic acid is active in vitro against a number of organisms, to date it has mainly been used to treat serious infections due to Staphylococcus aureus. The agent appears to be particularly valuable in the treatment of bone and joint infections and in pediatric practice. Fusidic acid will soon be available in Canada for both oral and intravenous administration. Attainable antibiotic levels in many tissues and body fluids greatly exceed the minimum inhibitory concentrations.     

Emergence of multidrug resistant enterococci at a tertiary care centre

Background

Enterococci have assumed great clinical importance because of their increasing resistance to various antimicrobial agents. Thus, knowledge about the antibiogram of these multidrug resistant isolates is of utmost importance in formulating an effective antibiotic policy to treat these infections and reducing the morbidity and mortality. Aim of this study was to assess the antimicrobial resistance pattern of enterococci and determine the prevalence of multidrug resistance among them.

Methods

This cross sectional study was carried out from August 2011 to February 2014, in which 200 non-repetitive clinical isolates of enterococci were included. Antimicrobial susceptibility testing was done by disc diffusion method. Minimum inhibitory concentration (MIC) of gentamicin, streptomycin, vancomycin, teicoplanin and linezolid was determined by E-test method.

Results

The prevalence of multidrug resistance among enterococcal isolates was found to be 63%. Varying levels of resistance was seen to various antibiotics. Most of the isolates were resistant to penicillin (95%), ampicillin (95%) and cotrimoxazole (90%). High level aminoglycoside resistance (HLAR) and glycopeptide resistance was seen in 39% and 14% isolates respectively. Only 4 isolates (2%) were found to be resistant to linezolid.

Conclusion

The prevalence of multidrug resistance among enterococci was found to be 63%, the resistance being more common in Enterococcus faecium as compared to Enterococcus faecalis. The study highlights the emergence and increased prevalence of multidrug resistant enterococci which pose a serious therapeutic challenge.     

Selection of antibiotic resistance at very low antibiotic concentrations

Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.     

A new look at erythromycin.

This article reviews the current place of erythromycin in antibiotic therapy. Overall, erythromycin is thought to be underused because: (1) the fear of resistance has been exaggerated; (2) significant toxicity has been associated with only one derivative (the estolate); (3) newer antibiotics have very rarely been demonstrated to be superior to erythromycin. Erythromycin has an important place in treating acute upper and lower respiratory tract infections, acute otitis media, sinusitis, skin and soft tissue, osteomyelitis, prostatitis, infections due to Mycoplasma spp. and Chlamydia organisms, and infections due to anaerobes.     

Extended spectrum beta-lactamase producing organisms at the University Hospital of the West Indies

Extended spectrum beta-lactamases (ESBL) represent a major group of beta-lactamases that have the ability to inactivate beta-lactam antibiotics containing an oxyimino group such as third generation cephalosporins and monobactams. These enzymes are produced by gram negative organisms, especially members of the Enterobacteriaceae family such as Klebsiella pneumoniae and Escherichia coli. The prevalence of these organisms varies widely internationally, as well as within the same country. This is the first study on ESBL production in K pneumoniae and E coli at the University Hospital of the West Indies, a tertiary care hospital in Jamaica. Two-hundred and sixty-four isolates of K pneumoniae and 300 isolates of E coli were collected over the study period January 2002 to December 2002. Forty-eight (18.2%) K pneumoniae isolates were confirmed to be ESBL producers, while there was no ESBL producing E coli. Infections with ESBL producing organisms can pose a therapeutic challenge, leading to treatment failure if the wrong class of antibiotics is used. With increasing resistance to all classes of antibiotics, there is a narrowing of available treatment options. It is very important that these organisms be monitored and antibiotic policies as well as infection control policies be in place to curtail their spread.     

儿童哮喘舌下特异性免疫治疗的研究进展

支气管哮喘是儿童呼吸道常见的慢性炎症,而特异性免疫治疗(SIT)作为唯一能改变其自然进程的治疗方法,不仅可以减少临床症状,还可以预防新变应原的产生。现舌下特异性免疫治疗因其良好的安全性及有效性,而且操作简单,也逐渐在我国广泛开展。随着对其作用机制的不断深入研究,以及新变应原制剂逐步优化,SIT的应用范围将会进一步扩大。而本文主要是针对儿童哮喘的特异性免疫治疗方案的最近研究进展予以综述,明确其治疗机制、适用范围及疗效评价等,以便规范临床治疗方案的选择,使儿童哮喘达到更好的治疗效果。     

Febrile neutropenia. Etiology of infection,empirical treatment and prophylaxis

Much has changed in the treatment of patients with fever and neutropenia, including the patterns of microbial flora and drug resistance, and the drugs used. Gram-positive organisms have overshadowed the gram-negative ones as causes of bacteremia. Changes in therapy may include antimicrobials directed against gram-positive bacteria, resistant gram-negative bacteria, or fungi. Due to the high risk for colonization by vancomycin resistant Enterococci, vancomycin use is restricted as first line empiric therapy unless the patient is at high-risk for serious gram-positive infection. Prophylactic antibiotic therapy may increase the selection of resistant strains and should be avoided. Therapy with colony stimulating factor is only considered for patients who remain severely neutropenic and have documented infections that do not respond to appropriate antibacterial therapy. Patients stratification for risk of infection-associated morbidity and mortality is essential to facilitate treatment decision.     

Rifampin

Rifampin is a potent antituberculous drug. In the treatment of drug-resistant tuberculosis it is highly effective provided it is given in combination with other drugs to which the patient's organisms are sensitive. Rifampin and ethambutol is a particularly powerful combination and will achieve almost 100% sputum conversion. It seems likely that rifampin will replace streptomycin, and ethambutol will replace PAS in first-treatment cases. Optimum first-line treatment will thus consist of rifampin, INH and ethambutol, with the probability of almost 100% success and the possibility also that the total duration of treatment may be considerably reduced. Rifampin is well tolerated but it may give rise to liver dysfunction and thrombocytopenia in a small proportion of patients. Patients treated with rifampin must be kept under close supervision because of the risk of side effects and, more important, because irregular treatment may lead to the development of rifampin-resistant organisms.     

Antibiotic resistance—consequences for animal health,welfare, and food production

Most of the literature on the consequences of emergence and spread of bacteria resistant to antibiotics among animals relate to the potential impact on public health. But antibiotics are used to treat sick animals, and resistance in animal pathogens may lead to therapy failure. This has received little scientific attention, and therefore, in this article, we discuss examples that illustrate the possible impact of resistance on animal health and consequences thereof. For all animals, there may be a negative effect on health and welfare when diseases cannot be treated. Other consequences will vary depending on why and how different animal species are kept. Animals kept as companions or for sports often receive advanced care, and antibiotic resistance can lead to negative social and economic consequences for the owners. Further, spread of hospital-acquired infections can have an economic impact on the affected premises. As to animals kept for food production, antibiotics are not needed to promote growth, but, if infectious diseases cannot be treated when they occur, this can have a negative effect on the productivity and economy of affected businesses. Antibiotic resistance in animal bacteria can also have positive consequences by creating incentives for adoption of alternative regimes for treatment and prevention. It is probable that new antibiotic classes placed on the market in the future will not reach veterinary medicine, which further emphasizes the need to preserve the efficacy of currently available antibiotics through antibiotic stewardship. A cornerstone in this work is prevention, as healthy animals do not need antibiotics.     

Treatment of complicated intra-abdominal infections in the era of multi-drug resistant bacteria

The management of severe intra-abdominal infections remains a major challenge facing surgeons and intensive care physicians, because of its association with high morbidity and mortality. Surgical management and intensive care medicine have constantly improved, but in the recent years a rapidly continuing emergence of resistant pathogens led to treatment failure secondary to infections with multi-drug resistant bacteria. In secondary peritonitis the rate of resistant germs at the initial operation is already 30 %. The lack of effective antibiotics against these pathogens resulted in the development of new broad-spectrum compounds and antibiotics directed against resistant germs. But so far no "super-drug" with efficacy against all resistant bacteria exists. Even more, soon after their approval, reports on resistance against these novel drugs have been reported, or the drugs were withdrawn from the market due to severe side effects. Since pharmaceutical companies reduced their investigations on antibiotic research, only few new antimicrobial derivates are available. - In abdominal surgery you may be in fear that in the future more and more patients with tertiary peritonitis secondary to multi-drug resistant species are seen with an increase of mortality after secondary peritonitis. - This article reviews the current treatment modalities for complicated intra-abdominal infections with special reference to the antibiotic treatment of complicated intra-abdominal infections with multi-drug resistant species.     

辅料对四环素吸收影响的研究

本文应用紫外分光光度法研究了体外三硅酸镁吸附四环素的能力及其与介质 pH 的关系;并应用尿药法研究了三硅酸镁及其在表面活性剂和枸橼酸的存在下对四环素吸收的影响;测定了三种不同处方的四环素混悬剂的相对生物利用度并进行了有关参数的统计比较。实验结果表明:三硅酸镁的吸附能力随介质 pH 的高低而增减。月桂醇硫酸钠和枸橼酸在体外对三硅酸镁有明显的解吸作用,而 Brij-35的解吸作用不明显。四环素与三硅酸镁同服时,前者吸收明显减少(P<0.05)。015g月桂醇硫酸钠与0.3g 三硅酸镁同服使三硅酸镁对四环素的吸附作用有一定程度的抑制,且此抑制作用不随月桂醇硫酸钠剂量继续增大而加强。枸橼酸和 Brij-35在体内均无此作用。三种四环素混悬剂的生物利用度无显著差异(P<0.05)。     

THE PRESENT PROBLEM AND ORGANIZATION OF LEPROSY- RESEARCH*

The topic:assigned to me for this discussiori is so broad that it necessitates wandering widely over the field of leprosy. There is so much that is not known definitely about this disease that practically any phase of it is a matter for research. One would not go as far as did one person who; in discussing a suggestion that there should be, somewhere, a center for graduate traimng in leprosy, was inclined to discourage the idea because there is so much that is not definitely; krWwn. But it may be agreed that any serious work on the subject may''affwd new knowledge,     

Persistence of transferable drug resistance in the lactose-fermenting enteric flora of swine following antimicrobial feeding.

Six groups of swine (85 animals) were fed a combination of antimicrobial drugs (sulfamethazine 100 g/ton, chlortetracycline 100 g/ton and penicillin 50 g/ton). After two weeks the antimicronial drugs were removed from the diet of two groups (28 animals). These swine were compared to four groups fed the medicated diet to determine the effect of duration of treatment and degree of animal isolation on the persistence of resistance in lactose-fermenting enteric organisms. The degree of resistance to penicillin, oxytetracycline, dihydrostreptomycin and neomycin as determined by minimum inhibitory concentrations and the incidence of resistant organisms were examined during and after antibiotic feedings. Ninety-two percent or greater of all isolates tested during and after treatment had minimum inhibitory concentrations for oxytetracycline of greater than 100 mug/ml. Thirty-two weeks after cessation of dietary antibiotic, resistance to oxytetracycline and dihydrostreptomycin remained at 100% and 89% respectively. Variation in degree of contact between swine receiving medicated feed and those receiving nonmedicated feed was not sufficient to reduce the incidence of resistance to oxytetracycline or dihydrostreptomycin in all animals. Factors influencing persistence of resistant enteric organisms are discussed. Addition of the antimicrobials to the ration resulted in significantly greater weight gains for treated animals than for the controls but did not alter feed conversion.     

Susceptibility profile of Enterococcus faecalis isolated at the Lagos University Teaching Hospital,Nigeria

Enterococcus faecalis is the most common of the Enterococcus genus causing infection, particularly urinary tract infections, worldwide. It is also a common cause of nosocomial infections and resistance to various antibiotics is on the increase worldwide. Thirty-five strains of E. Faecalis isolated from various clinical specimens (blood, wound swabs endocervical swabs but mostly urine) were screened for high-level aminoglycoside resistance. Their susceptibility nine antibiotics (ampicillin, gentamicin, streptomycin, vancomycin, tetracycline cotrimoxazole and chloramphenicol, ciprofloxacin and erthromycin) was also determined. All isolates were susceptible to Ampicillin and Vancomycin with MIC90 of 4microg/ml but resistant to Nalidixic acid with an MIC90>256microg/ml. Four (11%) of the isolates showed high-level resistance to Gentamicin while 11(32%) exhibited high-level resistance streptomycin after 24 hours incubation. It will appear that Ampicillin in combination with gentamicin but not streptomycin, can still be used empirically for the treatment of Enterococcal infections.     

Old and new targets of antibacterial therapy

Currently available antibiotics target bacterial cell wall synthesis, protein synthesis, or DNA replication. Antibiotics that are structurally unrelated sometimes have common targets. Mutations in these common targets frequently give rise to bacteria that are resistant to multiple antibiotics. The impact of these bacteria in clinical situations is increasing whereas development of effective antibiotics for their treatment is not keeping pace. This emerging crisis in clinical care has led to intense efforts in new antibiotic development. Both improvements in currently available classes of antibiotics as well as discovery of completely novel ones are being aggressively sought. In this review, the mechanisms of action of available antibiotics will be discussed with emphasis on newly developed drugs. Also, some of the potential new targets of antibiotic therapy in the future will be highlighted.     

An 11-year analysis of the prevalent uropathogens and the changing pattern of Escherichia coli antibiotic resistance in 38,530 community urinary tract infections, Dublin 1999–2009

Background

Knowledge of local antimicrobial resistance patterns is essential for evidence-based empirical antibiotic prescribing, and a cutoff point of 20 % has been suggested as the level of resistance at which an agent should no longer be used empirically. We sought to identify the changing incidence of causative uropathogens over an 11-year period. We also examined the trends in antibiotic resistance encountered in both the pooled urine samples and those where the causative organism was Escherichia coli.

Patient and methods

A retrospective analysis of the antimicrobial resistance within the positive community urine isolates over the 11-year period, 1999 to 2009, in a single Dublin teaching hospital was performed.

Results

In total 38,530 positive urine samples processed at our laboratory originated in the community of which 23,838 (56.7 %) had E. coli as the infecting organism. The prevalence of E. coli has been increasing in recent years in community UTIs with 70.4 % of UTIs in the community caused by E.coli in 2009. Ampicillin and trimethoprim were the least-active agents against E. coli with mean 11-year resistance rates of 60.8 and 31.5 %, respectively. Significant trends of increasing resistance over the 11-year period were identified for trimethoprim, co-amoxyclav, cefuroxime and gentamicin. Ciprofloxacin remains a reasonable empirical antibiotic choice in this community with an 11-year resistance rate of 10.6 %. Higher antibiotic resistance rates were identified in the male population and in children.

Conclusion

Resistance rates to commonly prescribed antibiotics are increasing significantly. This data will enable evidence-based empirical prescribing which will ensure more effective treatment and lessen the emergence of resistant uropathogens in the community.     

我国淋病奈瑟菌耐药趋势系统分析

目的收集近期国内外发表的关于我国淋病奈瑟菌耐药监测文献,分析淋病奈瑟菌的耐药趋势。方法检索中国期刊全文数据库、PubMed、Cochrane数据库,筛选合格文献进行系统评价。结果在1996~2007年,最终有6篇文献入选。我国部分地区NG耐药率对青霉素（57.2%~96.3%）、环丙沙星（17.6%~99.5%）均较高;头孢曲松虽然未检测到耐药株,但中敏率高（10.8~61.0%）;壮观霉素敏感率、中敏率和耐药率分别在97.8%~100%、0~2.2%、0~1.0%之间。结论在我国,青霉素、环丙沙星已不适合用于治疗淋病。头孢曲松、壮观霉素是推荐治疗淋病的一线药物,但头孢曲松中敏率偏高,必须引起高度关注。     

结核分枝杆菌痰培养阳性肺结核患者对一线抗结核药耐多药情况分析

目的:分析初治和复治结核分枝杆菌痰培养阳性的肺结核患者对4种一线抗结核药的耐多药(MDR)情况,了解抗结核药耐药现状和形势。方法:选取结核分枝杆菌痰培养阳性患者395例,按中国防痨协会《结核病诊断细菌学检验规程》的要求进行菌种鉴别试验。采用WHO推荐比例法对阳性分离菌株进行药物敏感性检测,计算每种一线药的耐药率及4种一线药的MDR情况。计算初、复治患者的MDR率。结果:4种一线抗结核药物耐药率顺位依次为链霉素(93/395,23.5%),异烟肼(88/395,22.3%),利福平(58/395,14.7%),乙胺丁醇(23/395,5.8%)。初治和复治组患者耐药均以耐链霉素和异烟肼为主,且耐药顺位一致,复治组患者利福平耐药率(17.4%)高于初治组(6.9%)(χ²=6.714,P=0.010)。至少同时对异烟肼和利福平耐药者33例,总MDR率为8.4%,复治患者MDR率(10.2%)高于初治患者MDR率(2.9%)(χ²=5.263,P=0.022)。初、复治组患者MDR形式均以同时耐异烟肼、利福平和链霉素为主,分别为2例(2.0%)和13例(4.4%)。结论:结核分枝菌痰培养阳性肺结核患者耐药频度顺位依次为链霉素、异烟肼、利福平和乙胺丁醇。复治组患者利福平耐药率、MDR率均高于初治组。初、复治组耐多药形式均以同时耐异烟肼、利福平和链霉素为主。