ICU病房鲍曼不动杆菌的耐药特点及相关感染的护理干预

目的探讨ICU病房下呼吸道感染患者鲍曼不动杆菌（AB）的耐药特点,及其相关护理干预措施对控制ICU鲍曼不动杆菌感染的作用。方法对从26例ICU住院下呼吸道感染患者痰液标本中分离的26株AB分析耐药特性,并比较耐泰能鲍曼不动杆菌（IRAB）和泰能敏感的鲍曼不动杆菌（ISAB）的耐药性差别,及其ICU病房中分离的AB与非ICU病房分离的AB耐药性差别,总结相应的护理干预措施。结果ICU分离的26株鲍曼不动杆菌对15种抗菌药物的敏感性,AB对磷霉素的敏感性最强,为88．5％,对三代头孢菌素等其他种类的抗菌药物敏感性都很低;26株AB,IRAB15株,占57．7％;ISAB11株,占42．3％。IRAB与ISAB耐药性比较,IRAB对头孢曲松、四环素、哌拉西林、氨曲南、复方磺胺、左氧氟沙星的耐药率达到100％,其他种类的抗菌药物的耐药率也很强,要强于ISAB（P〈0．01或P〈0．05）。结论ICU病房鲍曼不动杆菌耐药性强,治疗较为棘手,因此在使用敏感抗菌药物治疗同时,必须对患者采取相应护理措施,加强医院感染管理力度,做好隔离措施,避免交叉感染,保护其他易感患者。     

鲍曼不动杆菌的临床分布及耐药情况分析

目的：了解高邮市人民医院鲍曼不动杆菌的临床分布状况及耐药情况,为有效预防和控制医院感染、指导临床合理用药提供理论依据。方法对2010-2012年我院临床分离的鲍曼不动杆菌进行鉴定,采用纸片扩散法进行药敏试验,采用 WHONET 5．6软件对数据进行统计分析鲍曼不动杆菌的科室分布情况与耐药率及变化趋势。结果3年共分离出155株鲍曼不动杆菌,主要分离来自痰液（82．6％）,其次为分泌物及脓汁（12．3％）;科室分布以 ICU （34．2％）为主,其次是神经外科（18．1％）和呼吸内科（15．5％）;3年来鲍曼不动杆菌总体耐药率呈现上升趋势,尤其以亚胺培南最为明显,亚胺培南3年的耐药率分别是23．3％,44．2％和68．3％;临床常用抗菌药物中只有头孢哌酮/舒巴坦和哌拉西林/他唑巴坦的耐药率低于40％,其余均大于65％。结论鲍曼不动杆菌是医院感染中重要的条件致病菌,且耐药率较高,临床医务人员应根据药敏结果合理选择抗菌药物,控制耐药菌株的流行及医院感染。     

碳青霉烯抗生素处方限制策略对呼吸机相关性肺炎多药耐药鲍曼不动杆菌发生率的影响

目的 分析重症监护病房(ICU)内碳青霉烯抗生素的处方量与呼吸机相关性肺炎(VAP)多药耐药(MDR)鲍曼不动杆菌发生率的关系.方法 选择2007年6-12月四川大学华西医院ICU收治的行机械通气的VAP患者26例,随机分为采用碳青霉烯抗生素"处方限制策略"组(限制组,12例)和不加限制组(常规组,14例),收集两组患者治疗期的痰标本,分析MDR细菌的分布及与同期碳青霉烯抗生素处方量的相关性.结果 限制组碳青霉烯抗生素处方量以及MDR鲍曼不动杆菌的发生率均较常规组显著降低,差异有统计学意义(处方量:61 g比188 g,发生率:10.7%(7/65)比17.8%(13/73),P均<0.05].提示MDR鲍曼不动杆菌发生率的降低归因于碳青霉烯处方量的减少.结论 采取碳青霉烯"处方限制策略"可以减少VAP MDR鲍曼不动杆菌的发生率.     

Carbapenem resistance in Acinetobacter baumannii: laboratory challenges,mechanistic insights and therapeutic strategies

Unprecedented levels of antimicrobial resistance in bacterial isolates have prompted great concerns globally. In 2012 the WHO released a publication outlining the evolving threat of antimicrobial resistance in order to raise awareness and to stimulate coordinated international efforts. The carbapenem class of antibiotics is largely considered as an antibiotic of last-resort when treating infections. Now carbapenem resistance further limits treatment options. In this article the authors discuss carbapenem resistance in Acinetobacter baumannii, a bacterial isolate often implicated in nosocomial infections. Virulence factors, intrinsic and acquired resistance mechanisms, together with laboratory challenges in the detection and antibiotic susceptibility testing of A. baumannii make this a truly problematic isolate. Therapeutic options are exceedingly limited, relying on polymyxins in combinations with other antibiotics, with few, if any, new active agents in the pipeline.     

Photodynamic Therapy for Acinetobacter baumannii Burn Infections in Mice

Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 10⁸ A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections.Acinetobacter baumannii is a gram-negative pathogenic bacterium that has recently attracted much attention due to its remarkable acquisition of multidrug resistance (18, 19). It has been reported to have caused intractable infections in traumatic wounds and burns suffered by military personnel injured in recent Middle Eastern conflicts (24, 25). Photodynamic therapy (PDT) is a rapidly expanding approach to the treatment of diseases because it eliminates unwanted cells, such as malignant cancer cells and infectious microbial cells. PDT involves the combination of nontoxic photosensitizers (PSs) and harmless visible light that, in the presence of oxygen, give reactive oxygen species by energy or electron transfer from the PS excited state that are able to oxidize biomolecules and thereby kill cells (17). The use of PDT to treat localized infections generally involves the topical application of a PS into the infected tissue, followed by illumination with red or near-infrared light that is able to penetrate the tissue (2, 9). Selectivity for bacteria over host tissue can be obtained by the appropriate chemical design of the PS to ensure that the molecule will preferentially bind to bacterial cells rather than mammalian cells. It has been determined by many researchers that the most important features of this molecular design are a combination of an overall cationic charge and water solubility (11, 16). Cationic charge is even more important in the case of gram-negative bacteria that possess a double membrane structure because that structure excludes many anionic and uncharged lipophilic molecules that can effectively penetrate gram-positive bacteria and fungal cells (14).We have previously reported that a covalent conjugate between the tetrapyrrole molecule known as chlorin(e6) (c_e6) and the synthetic cationic polymer polyethylenimine (PEI) is a highly effective PS with activity against gram-negative species (27).In this report we describe the establishment of a mouse model of A. baumannii infection in full-thickness thermal burns. We used a multidrug-resistant clinical isolate from a U.S. soldier that was transformed with a plasmid that encodes the entire lux operon from Photorhabdus luminescens and that allows bioluminescence imaging of the course of the infection noninvasively in real time. The topical application of PEI-c_e6 was carried out, followed by illumination with red light after 15 min.     

Epidemiology of Bloodstream Infections Caused by Acinetobacter baumannii and Impact of Drug Resistance to both Carbapenems and Ampicillin-Sulbactam on Clinical Outcomes

Acinetobacter baumannii has become a leading cause of bloodstream infections (BSI) in health care settings. Although the incidence of infection with carbapenem- and ampicillin-sulbactam-resistant (CASR) A. baumannii has increased, there is a scarcity of studies which investigate BSI caused by CASR A. baumannii. A retrospective cohort study was conducted on adult patients with BSI caused by A. baumannii and who were admitted to the Detroit Medical Center between January 2006 and April 2009. Medical records were queried for patients'' demographics, antimicrobial exposures, comorbidities, hospital stay, and clinical outcomes. Bivariate analyses and logistic regression were employed in the study. Two hundred seventy-four patients with BSI caused by A. baumannii were included in the study: 68 (25%) caused by CASR A. baumannii and 206 (75%) caused by non-CASR A. baumannii. In multivariate analysis, factors associated with BSI caused by CASR A. baumannii included admission with a rapidly fatal condition (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.27 to 6.32, P value = 0.01) and prior use of antimicrobials (OR = 2.83, 95% CI = 1.18 to 6.78, P value = 0.02). In-hospital mortality rates for BSI caused by CASR A. baumannii were significantly higher than those for non-CASR A. baumannii-induced BSI (43% versus 20%; OR = 3.0, 95% CI = 1.60 to 5.23, P value < 0.001). However, after adjusting for potential confounders, the association between BSI caused by CASR A. baumannii and increased risk of in-hospital mortality was not significant (OR = 1.15, 95% CI = 0.51 to 2.63, P value = 0.74). This study demonstrated that CASR A. baumannii had a distinct epidemiology compared to more susceptible A. baumannii strains; however, clinical outcomes were similar for the two groups. Admission with a rapidly fatal condition was an independent predictor for both CASR A. baumannii and in-hospital mortality.     

DNA Microarray for Genotyping Antibiotic Resistance Determinants in Acinetobacter baumannii Clinical Isolates

In recent decades, Acinetobacter baumannii has emerged as an organism of great concern due to its ability to accumulate antibiotic resistance. In order to improve the diagnosis of resistance determinants in A. baumannii in terms of lead time and accuracy, we developed a microarray that can be used to detect 91 target sequences associated with antibiotic resistance within 4 h from bacterial culture to result. The array was validated with 60 multidrug-resistant strains of A. baumannii in a blinded, prospective study. The results were compared to phenotype results determined by the automated susceptibility testing system VITEK2. Antibiotics considered were piperacillin-tazobactam, ceftazidime, imipenem, meropenem, trimethoprim-sulfamethoxazole, amikacin, gentamicin, tobramycin, ciprofloxacin, and tigecycline. The average positive predictive value, negative predictive value, sensitivity, and specificity were 98, 98, 99, and 94%, respectively. For carbapenemase genes, the array results were compared to singleplex PCR results provided by the German National Reference Center for Gram-Negative Pathogens, and results were in complete concordance. The presented array is able to detect all relevant resistance determinants of A. baumannii in parallel. The short handling time of 4 h from culture to result helps to provide fast results in order to initiate adequate anti-infective therapy for critically ill patients. Another application would be data acquisition for epidemiologic surveillance.     

Therapeutic Efficacy of Lysophosphatidylcholine in Severe Infections Caused by Acinetobacter baumannii

Due to the significant increase in antimicrobial resistance of Acinetobacter baumannii, immune system stimulation to block infection progression may be a therapeutic adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC), a major component of phospholipids in eukaryotic cells, is involved in immune cell recruitment and modulation. The aim of this study was to show if LPC could be useful for treating infections caused by A. baumannii. A. baumannii ATCC 17978 was used in this study. Levels of serum LPC and levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-10 were determined by spectrophotometric assay and enzyme-linked immunosorbent assay (ELISA), respectively, using a murine peritoneal sepsis model in which mice were inoculated with 5.3 log CFU/ml of A. baumannii. The therapeutic efficacy of LPC against A. baumannii in murine peritoneal sepsis and pneumonia models was assessed for 48 h after bacterial infection. At early time points in the murine model of peritoneal sepsis caused by A. baumannii, LPC was depleted and was associated with an increase of inflammatory cytokine release. Preemptive therapy with LPC in murine peritoneal sepsis and pneumonia models markedly enhanced spleen and lung bacterial clearance and reduced the numbers of positive blood cultures and the mouse mortality rates. Moreover, treatment with LPC reduced proinflammatory cytokine production. These data demonstrate that LPC is efficacious as a preemptive treatment in experimental models of peritoneal sepsis and pneumonia caused by A. baumannii.     

Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates

Acinetobacter baumannii has emerged as an important opportunistic pathogen equipped with a growing number of antibiotic resistance genes. Our study investigated the molecular epidemiology and antibiotic resistance features of 28 consecutive carbapenem-resistant clinical isolates of A. baumannii collected throughout Sweden in 2012 and 2013. The isolates mainly belonged to clonal complexes (CCs) with an extensive international distribution, such as CC2 (n = 16) and CC25 (n = 7). Resistance to carbapenems was related to bla_OXA-23 (20 isolates), bla_{OXA-24/40-like} (6 isolates), bla_OXA-467 (1 isolate), and ISAba1-bla_OXA-69 (1 isolate). Ceftazidime resistance was associated with bla_PER-7 in the CC25 isolates. Two classical point mutations were responsible for resistance to quinolones in all the isolates. Isolates with high levels of resistance to aminoglycosides carried the 16S rRNA methylase armA gene. The isolates also carried a variety of genes encoding aminoglycoside-modifying enzymes. Several novel structures involved in aminoglycoside resistance were identified, including Tn6279, ΔTn6279, Ab-ST3-aadB, and different assemblies of Tn6020 and TnaphA6. Importantly, a number of circular forms related to the IS26 or ISAba125 composite transposons were detected. The frequent occurrence of these circular forms in the populations of several isolates indicates a potential role of these circular forms in the dissemination of antibiotic resistance genes.     

Multiple Genetic Mutations Associated with Polymyxin Resistance in Acinetobacter baumannii

We studied polymyxin B resistance in 10 pairs of clinical Acinetobacter baumannii isolates, two of which had developed polymyxin B resistance in vivo. All polymyxin B-resistant isolates had lower growth rates than and substitution mutations in the lpx or pmrB gene compared to their parent isolates. There were significant differences in terms of antibiotic susceptibility and genetic determinants of resistance in A. baumannii isolates that had developed polymyxin B resistance in vivo compared to isolates that had developed polymyxin B resistance in vitro.     

Role of OmpA in the Multidrug Resistance Phenotype of Acinetobacter baumannii

Acinetobacter baumannii has emerged as a nosocomial pathogen with an increased prevalence of multidrug-resistant strains. The role of the outer membrane protein A (OmpA) in antimicrobial resistance remains poorly understood. In this report, disruption of the ompA gene led to decreased MICs of chloramphenicol, aztreonam, and nalidixic acid. We have characterized, for the first time, the contribution of OmpA in the antimicrobial resistance phenotype of A. baumannii.     

Molecular Mechanisms of Sulbactam Antibacterial Activity and Resistance Determinants in Acinetobacter baumannii

Sulbactam is a class A β-lactamase inhibitor with intrinsic whole-cell activity against certain bacterial species, including Acinetobacter baumannii. The clinical use of sulbactam for A. baumannii infections is of interest due to increasing multidrug resistance in this pathogen. However, the molecular drivers of its antibacterial activity and resistance determinants have yet to be precisely defined. Here we show that the antibacterial activities of sulbactam vary widely across contemporary A. baumannii clinical isolates and are mediated through inhibition of the penicillin-binding proteins (PBPs) PBP1 and PBP3, with very low frequency of resistance; the rare pbp3 mutants with high levels of resistance to sulbactam are attenuated in fitness. These results support further investigation of the potential clinical utility of sulbactam.     

鲍曼不动杆菌的临床分布特征及耐药性分析

目的了解佳木斯大学附属第一医院鲍曼不动杆菌的分布特征及耐药情况。方法常规方法分离培养鉴定,K-B法做药敏分析。结果鲍曼不动杆菌最多见于痰液标本,占62.0%(98/158),其次是脓液及分泌物标本,占14.6%(23/158);鲍曼不动杆菌为院内感染,呼吸内科分布最多,占33.5%(53/158),其次是神经内科、重症监护病房和烧伤科。在18种抗菌药物中,碳青霉烯类药物亚胺培南的耐药率最低,为17.1%,美罗培南耐药率为21.5%,其他抗菌药物的耐药率均大于40.0%。结论鲍曼不动杆菌为医院感染中重要的条件致病菌,且耐药率较高,临床医务人员应根据药敏试验结果合理选择抗菌药物,定期进行耐药检测,以便及时有效地控制感染,减少鲍曼不动杆菌耐药菌株的产生。