Drug-resistant human immunodefiency virus

The development of antiretroviral therapy has led to a major reduction in human immunodeficiency virus (HIV)-related mortality. There are now six antiretroviral drug classes, with more than 20 unique antiretroviral drugs. However, HIV drug resistance occurs with all antiretroviral agents. Drug resistance can affect the response to antiretroviral therapy and is associated with increased mortality. The emergence of resistance in persons on antiretroviral therapy and the transmission of drug-resistant HIV strains to newly infected persons are now major public health concerns. Resistant variants that make up as little as 1% of the viral population in an HIV-infected person are clinically important, as they can rapidly grow under drug selection pressure and lead to therapy failure. However, current resistance assays used in the clinic reliably detect resistant variants only if they make up at least 20% of the circulating viral population. Recently, antiretroviral drugs have been developed that can inhibit HIV replication at new sites within the viral life cycle. These new drugs may improve clinical outcomes in persons infected with multidrug-resistant HIV. This review addresses the epidemiology and biological mechanisms of HIV drug resistance and the new approaches to detect and combat HIV drug resistance.     

产超广谱β-内酰胺酶肺炎克雷伯菌耐药基因分析

目的 了解邢台地区产超广谱β-内酰胺酶(ESBLs)肺炎克雷伯菌的分子流行病学特点,为临床感染预防和治疗提供依据.方法 采用最小抑菌浓度(MIC)法检测产ESBLs肺炎克雷伯菌的耐药性,选取13种特异性引物采用聚合酶链反应(PCR)的方法检测产ESBLs肺炎克雷伯菌的基因类型.结果 2013年1月至2014年3月从邢台人民医院分离出的125株非重复的产ESBLs肺炎克雷伯菌菌株,耐药基因以blaCTX-M的阳性率最高,为92.0％,blaSHV和blaTEM次之,为82.9％和73.2％.所有菌株均携带1种或1种以上的耐药基因.结论 产ESBLs肺炎克雷伯菌多重耐药现象严重,耐药基因以blaCTX-M、blaSHV和blaTEM为主.医院应加强对ESBLs的监测,降低ESBLs的感染率以及耐药基因的突变,提高治疗感染的效率,防止医院感染的发生.     

Drug-resistant Plasmodium falciparum infection in immigrants and non-immune travellers

Objective   To detect the incidence of drug-resistant Plasmodium falciparum malaria infection in immigrants and travellers in non-endemic Kuwait.
Methods   Over a period of 3 years, July 1995 to September 1998, 1352 malaria patients were enrolled in the study. Of these, 1293 were immigrants from countries where malaria is endemic and 59 were non-immune travellers with a recent history of travel to these countries. The in vitro drug sensitivity was determined in 892 patients.
Results   In all, 892 of 1352 (66.0%) P. falciparum isolates were successfully cultured in vitro for drug sensitivity and 419 (47.0%) isolates showed in vitro resistance to chloroquine or mefloquine. Fifty-six (13.4%) isolates were resistant to both drugs. Chloroquine resistance was observed in > 70% of the isolates from Africa and India followed by Pakistan (39.9%) and Bangladesh (35.9%). The resistance to mefloquine ranged from 26.2% in isolates from Sri Lanka to 47.5% in isolates from African countries.
Conclusion   The study highlights the important trend in drug resistance in P. falciparum malaria in immigrants from south-east Asian and African countries.     

Drug-resistant lymphocytes in man as indicators of somatic cell mutation

Direct in vivo tests of somatic mutation in man may provide realism in assessing the genetic risks of potential environmental mutagens. The autoradiographic determination of purine analogue (8-azaguanine; 6-thioguanine) resistant (AGr; TGr) peripheral blood lymphocytes (PBLs) arising in vivo in man is proposed as a candidate test. PBLs bearing the naturally occurring Lesch-Nyhan (LN) mutation are prototype mutant cells. LN PBLs are AGr and TGr, whereas normal PBLs are AG and TG sensitive. When judged by the inhibition of phytohemagglutinin (PHA) stimulated 3H-thymidine incorporation in vitro, analogue-resistant LN PBLs may be distinguished from analogue-sensitive normal PBLs by several methods. Early studies quantitating PHA stimulation by scintillation spectrometry detected down to 1% of LN PBLs in artificial mixtures with normal PBLs. Although LN heterozygous females could be identified on the basis of lymphocyte mosaicism, scintillation spectrometry was too insensitive to detect rare "LN-like" PBLs in non-LN individuals. Autoradiography, however, detected rare TGr PBLs in normal non-LN individuals. Their frequencies did not increase with age. With this method, TGr PBL frequencies in LN heterozygous females were found to range from 1 x 10(-3) to 5 x 10(-2), whereas blood samples from LN males showed from 23% to 100% TGr cells. Rare LN PBLs could be detected in artificial mixtures with normal cells. Studies in human patients undergoing various potential mutagenic therapies assessed the effects of these therapies on the TGr PBL variant frequencies (Vf) of non-LN individuals. Group TGr PBL Vf values were higher in treated patient groups than in controls. However, some untreated patient groups (cancer and psoriasis) also had elevated values, suggesting that disease itself may affect TGr PBL frequencies. Nonetheless, one patient group (vitiligo) showed elevated Vf values in treated (8-methoxypsoralen and long-range UV light = PUVA) but not in untreated patients, suggesting that treatment was responsible for the TGr PBL elevations. Longitudinal studies over time in cancer patients receiving X-irradiation therapy demonstrated that such exposures also are associated with TGr PBL frequency rises and suggested that longitudinal studies may be necessary to relate TGr PBL Vf elevations to specific environmental influences. Variant TGr PBLs were found at frequencies comparable to those in man in the peripheral blood of rats. They increased in a single study following treatment of the animals with a clinical alkylating agent. Characterization of the TGr PBLs suggests that some of these cells are mutants. Presumably the mutant cells arise in vivo by somatic cell mutation.     

Drug-resistant pneumococcal pneumonia: clinical relevance and approach to management

Community-acquired pneumonia is the most common infectious disease that causes death, with Streptococcus pneumoniae remaining the leading causative pathogen. The worldwide incidence of infections caused by pneumococci resistant to penicillin, macrolides, and other antimicrobial agents has increased at an alarming rate during the past 2 decades. Yet, these agents are still used as first-line empirical therapy in the outpatient setting. There are several reasons for this, including the infrequency of making a pathogen-specific diagnosis, the failure of studies to demonstrate the relevance of resistance, and the infrequency with which clinicians recognize clinical failures. Despite this, there is mounting evidence that supports the practice of using high doses of some antimicrobial agents, a more active antimicrobial agent within a class, or switching to another class of antimicrobial agents when a patient is identified as being at an increased risk of infection with a resistant pneumococcus. There is now information that will allow the physician to identify not only the patient at risk for infection with a resistant pneumococcus but also the antimicrobial class and, in some cases, the agent within the class to which the organism is more likely to be resistant. This will allow clinicians to better define optimal therapy for patients with community-acquired pneumonia.     

临床分离产IMP-1型金属酶非发酵菌的耐药机制研究

从临床收集耐亚胺培南的铜绿假单胞菌和鲍曼不动杆菌共50株,进行头孢他啶和2-巯基乙醇的表型协同试验(CAZ ME),然后进行金属酶IMP-1基因的PCR检测。选取IMP-1阳性株测序,用PCR方法检测有无一类整合子基因(IntI1)。表型的检测发现有28株为协同阳性,其中铜绿假单胞菌27株,鲍曼不动杆菌1株。PCR和测序检测出其中一株铜绿假单胞菌含有IMP-1基因,同时也含有IntI1基因。首次在中国西部地区发现产IMP-1型金属酶、同时也含有一类整合子的铜绿假单胞菌,对于临床上研究细菌的耐药性传播具有重要意义。     

医院感染的耐药菌分布特点与药物应用

目的 分析我院医院感染的耐药菌分布特点以及抗生素的应用情况。方法 选择2017年7月~2018年7月我院住院治疗的多重耐药菌感染者的生物标本进行细菌检测和药敏试验,并对结果进行分析。结果 检出多重耐药菌的为962株,检出率为14.70%（962/6542）;多重耐药菌株感染的发生率为21.74%（962/4425）;其中有478株（49.69%）为产超广谱β-内酰胺酶（ESBLs）大肠埃希菌;科室分布主要以普外科（186株,19.33%）最高;大肠埃希菌和肺炎克雷伯菌对于头孢西丁、头孢哌酮-舒巴坦、美罗培南、亚胺培南、哌拉西林-他唑巴坦和阿米卡星的耐药率较低;金黄色葡萄球菌对于替考拉林、阿米卡星、庆大霉素、万古霉素和利奈唑胺的耐药率均为0,对于左氧氟沙星和莫西沙星的耐药率较低。结论 细菌耐药的形势严峻,临床应用时要首选敏感度较高的抗生素,以防细菌耐药进一步发生。医院要严格加强防控举措,切实避免医院感染的发生。     

Prevalence of Multiple Drug-resistant Plasmodium falciparum Malaria Cases in Northeast India

Two numbers of Plasmodium falciparum field isolates from Gossingpara, Runikhata area in Chirang district of Assam had shown multiple mutations in Pfcrt-dhfr-dhps gene (up to seven mutations: One mutation in Pfcrt gene, three mutations in Pfdhfr gene and three mutations in Pfdhps gene). Similarly, two cases in Bat camp, Miao area under Changlang district of Arunachal Pradesh had shown a total of eight mutations, of which one mutation in Pfcrt gene, three mutations in Pfdhfr gene, three mutations in Pfdhps gene and one mutation in PfATPase6gene. One case in 3 Miles, Miao area of Changlang district has shown mutations in Pfcrt (one mutation), Pfdhfr (four mutations) and Pfdhps (three mutations) gene. These results indicated that there is an existence of multiple mutant P. falciparum malaria cases in northeastern region of India.     

Drug-resistant tuberculosis: resistance mechanisms and drug susceptibility of Mycobacterium tuberculosis

Mycobacterium (M.) tuberculosis is the most common individual causative agent of infectious disease in the world. It is responsible for 26% of preventable deaths in adulthood. Because the number of new cases grows at an annual rate of 2%, in 1993 WHO proclaimed tuberculosis a global health problem. The immediate cause for this was coinfection with causative agents of tuberculosis and human immunodeficiency virus, and spread of resistant and multiresistant strains of M. tuberculosis (MDR TB). It is estimated that 50 million people are infected with resistant strains of M. tuberculosis. Tuberculosis has emerged as a major public health problem for its high mortality (50%-80%) in the first 4-16 weeks of the disease and 100 times more expensive therapy for drug-resistant than for drug-susceptible tuberculosis. Mycobacteriologic laboratories play a fundamental role in the detection, combat and control of tuberculosis, especially in preventing the spread of drug-resistant tuberculosis. In this connection, there is an increased need of a rapid and reliable determination of the susceptibility of isolated strains of M. tuberculosis to the first- and second-line antituberculotic drugs.     

Fighting HIV with HIV

This article presents a new possibility for therapy and treatment of human immunodeficiency virus infection.     

Drug-resistant strains of Mycobacterium tuberculosis exhibit a range of virulence for mice.

A panel of clinical isolates of Mycobacterium tuberculosis, several of which were resistant to one or more antimycobacterial drugs, were tested for their capacity to give rise to active disease following aerogenic infection of normal immunocompetent mice. The panel exhibited a range of virulence in this model, which followed no clear trend in terms of geographical source, degree of drug resistance, or rate of growth in vitro. Several isolates grew very quickly over the first 20 days in mouse lungs before being contained by emerging immunity. In view of this latter observation, we hypothesize that it is possible that such so-called fast growers may be responsible for the rapid fatality sometimes seen in immunocompromised patients with tuberculosis. Moreover, the results of the study do not support the belief that increased drug resistance usually associates with loss of virulence of the isolate.