Limits to compensatory adaptation and the persistence of antibiotic resistance in pathogenic bacteria

Antibiotic resistance carries a fitness cost that could potentially limit the spread of resistance in bacterial pathogens. In spite of this cost, a large number of experimental evolution studies have found that resistance is stably maintained in the absence of antibiotics as a result of compensatory evolution. Clinical studies, on the other hand, have found that resistance in pathogen populations usually declines after antibiotic use is stopped, suggesting that compensatory adaptation is not effective in vivo. In this article, we argue that this disagreement arises because there are limits to compensatory adaptation in nature that are not captured by the design of current laboratory selection experiments. First, clinical treatment fails to eradicate antibiotic-sensitive strains, and competition between sensitive and resistant strains leads to the rapid loss of resistance following treatment. Second, laboratory studies overestimate the efficacy of compensatory adaptation in nature by failing to capture costs associated with compensatory mutations. Taken together, these ideas can potentially reconcile evolutionary theory with the clinical dynamics of antibiotic resistance and guide the development of strategies for containing resistance in clinical pathogens.     

Antibiotic Resistance of Acinetobacter baumannii in Iran: A Systemic Review of the Published Literature

Objectives

Acinetobacter baumannii is a bacterium responsible for health care-associated infections, and it frequently develops multiple drug resistance (MDR). The prevalence of antibiotic-resistant A. baumannii in Iran has increased, and this may cause significant clinical problems. Therefore, in order to elucidate the development of antibiotic resistance, we performed a systematic review of the literature published on antibiotic-resistant A. baumannii reported in Iran.

Methods

Thirty-six publications that met the criteria for inclusion were reviewed from an initial 87 papers. Selected papers published between 2008 and September 2014, were categorized on the basis of the sample collecting year been between 2001 and 2013.

Results

Analysis of data revealed that, in general, there was an increase in antimicrobial resistance. During the initial time point of these studies (2001–2007) there was a high rate of resistance to all antibiotics, with the exception of carbapenems, lipopeptides, and aminoglycosides that had a low resistance rate in comparison with the others. Also, the resistance rate was increased in one group of these three antimicrobial groups from 2010 to 2013. In particular, there was an increase in resistance to carbapenems (imipenem and meropenem) from 2010–2011 and 2012–2013, whereas no significant change in the resistance rate of the other two antimicrobial groups (lipopeptides and aminoglycosides) during the study time was observed, although we did observe certain trends in amikacin (aminoglycoside group antibiotic) between 2011–2012 and 2012–2013.

Conclusion

These findings indicate that antimicrobial resistance of A. baumannii in Iran has increased, which may very well affect the antimicrobial resistance of this organism worldwide. Based on these results, novel prevention and treatment strategies against A. baumannii infections are warranted. Furthermore, these data may assist in revising treatment guidelines and regional policies in care units to slow the emergence of antimicrobial resistance.     

Pneumonia in a traveller coming back from Asia

A case of Salmonella paratyphi A infection was diagnosed late in a patient treated for febrile pneumonia after his returning from India. This case was remarkable in two aspects: first, it illustrated the reemergence of S.paratyphi A infections in people having traveled to India, with increasing fluoroquinolone resistance, and second the difficulty of diagnosing this disease, since the patient was initially treated for pneumonia and flu-like syndrome. Salmonella typhi or paratyphi infections should be evoked in case of persistent fever in patients having traveled to endemic areas, even if digestive signs are absent. Furthermore, choosing an empiric antibiotic treatment with fluoroquinolones could lead to treatment failure if the patient traveled in a country where fluoroquinolone resistance is high, as in Asia and especially in India.     

肺炎克雷伯菌主要耐药机制研究进展

肺炎克雷伯菌(Klebsiella pneumoniae, KP)是导致医院内感染的常见病原菌之一,可引起呼吸道、消化道和泌尿系统感染,曾在新生儿病房、泌尿科病房和监护病房暴发流行。多重耐药肺炎克雷伯菌给临床抗生素的治疗带来极大的困难,本文从肺炎克雷伯菌β-内酰胺耐药机制;外膜蛋白的缺失和靶位的改变;生物膜的耐药机制;外排泵机制耐药作用;整合子等五个方面对肺炎克雷伯菌主要耐药机制研究进展进行阐述,通过全面了解肺炎克雷伯菌的主要耐药机制,合理使用抗菌药物,从而有效预防和监测耐药菌的播散。     

新生儿肺炎克雷伯菌脓毒血症细菌的耐药性分析

目的 探讨新生儿肺炎克雷伯菌脓毒血症的耐药特性,为药物治疗提供新依据.方法 对本院近五年确诊新生儿肺炎克雷伯菌脓毒血症临床病例及药敏结果进行回顾性分析.结果 50例肺炎克雷伯菌脓毒血症多为医院内感染,其中检出产ESBLs菌株13株（占26%）,非产ESBLs菌株37株（占74%）,均为多重耐药菌株,药敏试验证明：对常用广谱β-内酰胺类抗生素均有超强耐药;但对亚胺培南及阿米卡星等药敏感,敏感率高达100%.结论 亚胺培南和阿米卡星均可作为新生儿肺炎克雷伯菌感染首选治疗药物.     

Effects of Knowledge,Attitudes, and Practices of Primary Care Providers on Antibiotic Selection,United States

Appropriate selection of antibiotic drugs is critical to optimize treatment of infections and limit the spread of antibiotic resistance. To better inform public health efforts to improve prescribing of antibiotic drugs, we conducted in-depth interviews with 36 primary care providers in the United States (physicians, nurse practitioners, and physician assistants) to explore knowledge, attitudes, and self-reported practices regarding antibiotic drug resistance and antibiotic drug selection for common infections. Participants were generally familiar with guideline recommendations for antibiotic drug selection for common infections, but did not always comply with them. Reasons for nonadherence included the belief that nonrecommended agents are more likely to cure an infection, concern for patient or parent satisfaction, and fear of infectious complications. Providers inconsistently defined broad- and narrow-spectrum antibiotic agents. There was widespread concern for antibiotic resistance; however, it was not commonly considered when selecting therapy. Strategies to encourage use of first-line agents are needed in addition to limiting unnecessary prescribing of antibiotic drugs.     

重症监护病房铜绿假单胞菌感染调查及耐药性分析

目的调查重症监护病房(1CU)铜绿假单胞菌的感染及耐药情况,指导临床合理用药。方法取ICU标本进行常规细菌培养鉴定,以K-B法进行药物敏感性试验。结果从850份标本中分离出铜绿假单胞菌108株,总分离率为12.7%,在10种抗生素中,亚胺培南的体外抗菌活性最好,耐药率最低为15.7%,其次为阿米卡星30.6%。结论亚胺培南是治疗铜绿假单胞菌的首选药物。ICU中铜绿假单胞菌的耐药性应引起高度重视。     

Prevalence of Antibiotic Resistance in Escherichia coli Fecal Isolates From Healthy Persons and Patients With Diarrhea

Objectives

This study aimed to investigate the prevalence of antibiotic resistance in fecal Escherichia coli isolates from healthy persons and patients with diarrhea.

Methods

E. coli isolates (n = 428) were obtained from fecal samples of apparently healthy volunteers and hospitalized patients with diarrhea. Susceptibility patterns of isolates to 16 antimicrobial agents were determined by agar disc diffusion.

Results

Most E. coli isolates exhibited less than 10% resistance against imipenem, cefotetan, aztreonam, cefepime, cefoxitin, amikacin and netilamicin, although greater than 65% were resistant to ampicillin and tetracycline. No significant difference in resistance rates for all tested antibiotics was found between isolates from the healthy-and diarrheal-patient groups, including for multi-drug resistance (p = 0.22). The highest number of resistant antibiotics was 12 antibiotics. No significant differences in antibiotic resistance were found among the sex and age strata for isolates from healthy individuals. However, antibiotic resistance rates to cefoxitin, cefotaxime, amikacin, and netilamicin were significantly higher in the isolates of men than those of women (p < 0.05) in isolates from patients with diarrhea. Furthermore, isolates from patients with diarrhea older than 40-years of age showed higher resistance to cefepime and aztreonam (p < 0.05).

Conclusion

High resistance to the antibiotics most frequently prescribed for diarrhea was found in isolates from patients with diarrhea and apparently healthy individuals without any significant difference.     

Comparison of Antimicrobial Resistance in Escherichia coli Strains Isolated From Healthy Poultry and Swine Farm Workers Using Antibiotics in Korea

ObjectivesThe aim of this study is to compare the antibiotic resistance of Escherichia coli isolates from faecal samples of workers who often use antibiotics.MethodsA total of 163E coli strains isolated from faecal samples of livestock workers (poultry and swine farm workers) and restaurant workers in the same regions as a control group were analyzed by agar disc diffusion to determine their susceptibility patterns to 16 antimicrobial agents.ResultsMost of the tested isolates showed high antimicrobial resistance to ampicillin and tetracycline. The isolates showed higher resistance to cephalothin than other antibiotics among the cephems. Among the aminoglycosides, the resistance to gentamicin and tobramycin occurred at higher frequencies compared with resistance to amikacin and netilmicin. Our data indicated that faecal E coli isolates of livestock workers showed higher antibiotic resistances than nonlivestock workers (restaurant workers), especially cephalothin, gentamicin, and tobramycin (p < 0.05). Moreover, the rates of the livestock workers in the association of multidrug resistance were also higher than the rates of the restaurant workers.ConclusionThis study implies that usage of antibiotics may contribute to the prevalence of antibiotic resistance in commensal E coli strains of humans.     

抗生素耐药性全球治理的发展历程及对中国的启示

目的:归纳总结抗生素耐药性全球治理的发展历程和每个阶段的特点,并为中国参与抗生素耐药性的全球治理提供启示。方法:采用范围综述的方法在ISI Web of Science、Pubmed、Medline等外文期刊数据库中搜索并筛选有关抗生素耐药性全球治理的相关文献,同时收集世界卫生组织、联合国、联合国粮农组织以及世界动物卫生组织等发布的相关资料。结果:抗生素耐药性全球治理的发展历程大致可分为三个阶段:以临床监测为主要策略、由发达国家主导的萌芽阶段;从卫生领域到卫生、农业、环境等多领域共同治理的快速发展阶段;多国家参与并且多领域共同治理的全面覆盖阶段。结论:全世界对于抗生素耐药性全球治理的关注度日益提升,我国应借鉴世界各国采取的有效行动,鼓励多领域协同治理抗生素耐药性问题,以更加积极主动的姿态参与全球治理,并逐步提高社会公众对抗生素耐药性的重视。     

Antibiotic selection pressure and resistance in Streptococcus pneumoniae and Streptococcus pyogenes

We correlated outpatient antibiotic use with prevalence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP), macrolide-resistant S. pneumoniae (MRSP), and macrolide-resistant S. pyogenes (MRGAS) in 20 countries. Total antibiotic use was correlated with PNSP (r = 0.75; p < 0.001), as was macrolide use with MRSP (r = 0.88; p < 0.001) and MRGAS (r = 0.71; p = 0.004). Streptococcal resistance is directly associated with antibiotic selection pressure on a national level.     

Life-threatening infantile diarrhea from fluoroquinolone-resistant Salmonella enterica typhimurium with mutations in both gyrA and parC

Salmonella Typhimurium DT12, isolated from a 35-day-old infant with diarrhea, was highly resistant to ampicillin, tetracycline, chloramphenicol, streptomycin, gentamycin, sulfamethoxazole/trimethoprim, nalidixic acid, and fluoroquinolones. The patient responded to antibiotic therapy with fosfomycin. Multidrug-resistance may become prevalent in Salmonella infections in Japan, as shown in this first case of a patient infected with fluoroquinolone-resistant Salmonella.     

Gallium-mediated siderophore quenching as an evolutionarily robust antibacterial treatment

Background and objectives: Conventional antibiotics select strongly for resistance and are consequently losing efficacy worldwide. Extracellular quenching of shared virulence factors could represent a more promising strategy because (i) it reduces the available routes to resistance (as extracellular action precludes any mutations blocking a drug’s entry into cells or hastening its exit) and (ii) it weakens selection for resistance, as fitness benefits to emergent mutants are diluted across all cells in a cooperative collective. Here, we tested this hypothesis empirically. Methodology: We used gallium to quench the iron-scavenging siderophores secreted and shared among pathogenic Pseudomonas aeruginosa bacteria, and quantitatively monitored its effects on growth in vitro. We assayed virulence in acute infections of caterpillar hosts (Galleria mellonella), and tracked resistance emergence over time using experimental evolution. Results: Gallium strongly inhibited bacterial growth in vitro, primarily via its siderophore quenching activity. Moreover, bacterial siderophore production peaked at intermediate gallium concentrations, indicating additional metabolic costs in this range. In vivo, gallium attenuated virulence and growth—even more so than in infections with siderophore-deficient strains. Crucially, while resistance soon evolved against conventional antibiotic treatments, gallium treatments retained their efficacy over time. Conclusions: Extracellular quenching of bacterial public goods could offer an effective and evolutionarily robust control strategy.     

HIV耐药毒株在山东省艾滋病抗病毒治疗人群中的流行及演变

目的 了解HIV耐药毒株在山东省AIDS抗病毒治疗人群中的流行及演变.方法 对山东省抗病毒治疗时间满1年的324例AIDS患者,使用荧光实时定量PCR( NucliSens EasyQ系统)进行HIV病毒载量检测,对结果大于1000拷贝/ml的样本采用基因型耐药检测白建方法(in house)进行HIV耐药检测.对耐药者既往(治疗前、治疗中)样本进行耐药检测,分析耐药株的演变状况.结果 HIV抗病毒治疗满1年人群耐药率为6.2％ (20/324),有耐药突变位点但不耐药为0.6％ (5/324);核苷类与非核苷类耐药突变位点占所测突变位点的93.1％ (94/101),蛋白酶类仅占6.9％ (7/101);M184V及Y181C位点在25份样本中出现突变频率最高,分别为48.0％( 12/25)和32.0％ (8/25).演变研究发现,20.0％( 2/10)的耐药者属于原发耐药;最早在治疗6个月后检测到了耐药;病毒株存在从无耐药突变位点向有耐药突变位点、从仅有耐药突变位点而不耐药向耐药、从对少种类药物低水平耐受向对多种类药物高水平耐受的演变现象,也存在突变位点相互影响使得对某种药物耐受程度降低的演变现象.结论 HIV耐药毒株在山东省AIDS抗病毒治疗人群中处于较低流行水平,耐药株的演变现象复杂.     

Ciprofloxacin treatment failure in typhoid fever case, Pakistan

We report a case of ciprofloxacin treatment failure in a typhoid fever patient at a tertiary care hospital in Rawalpindi, Pakistan. This case shows not only the emergence of fluoroquinolone resistance in typhoid salmonellae but also the inadequacy of the current laboratory guidelines for detection of this resistance.     

Absence of nucleotide polymorphism in a Plasmodium vivax multidrug resistance gene after failure of mefloquine prophylaxis in French Guyana

Vivax malaria is widespread and resistance has been described for chloroquine and sulfadoxine-pyrimethamine. We report on evidence of failure of mefloquine prophylaxis in a French soldier who contracted Plasmodium vivax in French Guyana, South America. Despite regular weekly mefloquine prophylaxis (250 mg/d), the patient presented with a first episode of vivax malaria, which was treated by chloroquine alone, then experienced a second crisis in France. The reappearance of the parasites occurred one day after the end of prophylaxis, confirming parasitological and clinical resistance in a non-immune patient. Mefloquine was detected by a liquid chromatography assay in plasma at a level of 1062 ng/ml, which was higher than the expected concentration after five months of weekly prophylaxis. This isolate had no single nucleotide polymorphisms of the pvmdr1 gene at seven allele positions: pvmdr1 N91, Y189, Y976, S1071, F1076, N1079 and D1291, corresponding to codons 86, 184, 939, 1034, 1039, 1042 and 1246 in P. falciparum. This observation of failure of mefloquine prophylaxis against P. vivax, when added to previously reported chloroquine and atovaquone-proguanil failure, strengthens the case for re-evaluating drug policies for vivax malaria and the need for continuous research on molecular markers of drug resistance.     

Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae,Canada

Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010–2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines.