探讨不同剂量替加环素治疗泛耐药鲍曼不动杆菌重症肺炎的效果

目的探讨泛耐药鲍曼不动杆菌重症肺炎采用不同剂量替加环素治疗的效果。方法50例泛耐药鲍曼不动杆菌重症肺炎患者,依据替加环素剂量不同分为常规剂量组和增加剂量组,每组25例。常规剂量组患者给予常规剂量替加环素治疗,增加剂量组患者给予增加剂量替加环素治疗。比较两组患者的细菌清除情况、不良反应发生情况。结果增加剂量组患者细菌总清除率为88.0%(22/25),高于常规剂量组的64.0%(16/25),差异具有统计学意义(P<0.05)。增加剂量组患者不良反应发生率为12.0%(3/25),与常规剂量组的8.0%(2/25)比较差异无统计学意义(P>0.05)。结论泛耐药鲍曼不动杆菌重症肺炎采用增加剂量替加环素治疗的效果较常规剂量好。     

Colistin offers prolonged survival in experimental infection by multidrug-resistant Acinetobacter baumannii: the significance of co-administration of rifampicin

The effect of colistin on bacterial eradication and survival was tested in experimental infection by multidrug-resistant Acinetobacter baumannii. The thigh infection model was applied in 86 neutropenic Wistar rats. Six rats were used for the induction of neutropenia and for the selection of the dose regimen of colistin; the remainder was equally divided into four groups: A, controls; B, rifampicin; C, colistin; and D, both agents. Therapy was administered 5 h after bacterial challenge; 5mg/kg of rifampicin was administered intravenously and 3mg/kg of colistin intramuscularly. Survival was recorded in 10 animals of each group. The remaining 10 rats per group were killed 4h after therapy; blood and tissue samples were sampled. Median survival of animals of groups A, B, C and D was 2.00, 2.50, 4.00 and 4.00 days, respectively (P=0.0048 between A and C and P=0.0012 between A and D. Mortality rates after 6 days of follow-up were 100, 100, 100 and 70%, respectively (P=0.018 between groups). Statistically significant decreases of bacteria were found in blood, liver, lung and spleen of group B compared with A; in lung of group C compared with A; and in blood and liver of group D compared with A. Colistin was effective in prolonging survival in an experimental thigh infection by multidrug-resistant A. baumannii in neutropenic rats. Its activity was enhanced after co-administration with rifampicin. These results mandate the application of colistin in the event of infections by multidrug-resistant pathogens and the need for its co-administration with rifampicin.     

Efficacy of monotherapy and combined antibiotic therapy for carbapenem-resistant Acinetobacter baumannii pneumonia in an immunosuppressed mouse model

Acinetobacter baumannii is an important cause of nosocomial infection with increasing carbapenem resistance. The aim of this study was to compare the efficacy of colistin+rifampicin and imipenem+rifampicin combinations with that of several other antibiotic regimens against carbapenem-resistant A. baumannii pneumonia using an immunosuppressed mouse model. Three different A. baumannii strains with diverse resistance mechanisms (OXA-51-, IMP-1- and VIM-2-type beta-lactamases) were used. Among the monotherapy regimens, only rifampicin significantly reduced the bacterial load in lungs 24 h after infection with the OXA-51-producing strain. Addition of rifampicin to either imipenem or colistin yielded synergistic results after 48 h. Rifampicin was bactericidal against the IMP-1-producing strain, and only the imipenem+rifampicin combination yielded synergistic effects. In contrast, rifampicin alone was not effective against the VIM-2-producing strain, but the imipenem+rifampicin combination was bacteriostatic even at 24 h post-infection. Tigecycline and amikacin were not effective against any of the three strains. Rifampicin-based combinations were effective against A. baumannii bacteraemia and improved survival regardless of the strain type. Contrary to the similar minimum inhibitory concentration results, the antibacterial effects of rifampicin were quite different according to the strains; a tailored antibiotic strategy must be considered in treatment. Addition of rifampicin to either imipenem or colistin would be effective.     

Colistin therapy in critically ill patients with chronic renal failure and its effect on development of renal dysfunction

Recently, colistin has become a salvage therapy in the treatment of serious Intensive Care Unit infections owing to the emergence of extensively drug-resistant (XDR) bacterial isolates. This study aimed to show the effectiveness of colistin in critically ill patients with renal failure. A prospective case-control study of 94 patients admitted to medical intensive care units of a university hospital from December 2008 to June 2010 was conducted. All patients had infections with XDR Acinetobacter baumannii or Pseudomonas aeruginosa and received colistin. Cases comprised 39 patients with chronic renal failure (CRF) and controls were other patients without CRF. Apart from the male dominancy in the CRF group, there was no statistical difference between the two groups regarding demographic characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and site and type of infection. In patients who completed colistin therapy, bacteriological cure was seen in 87% of patients with CRF and 95% of patients without CRF (P=0.890). Mortality in patients with CRF was similar to that in patients without CRF (44% and 42%, respectively) (P=0.999). Nephrotoxicity developed in 23.6% of patients in the control group. Concomitant nephrotoxic agents and total defined daily dose of colistin did not affect the development of nephrotoxicity. The mortality rate was 38% in patients with nephrotoxicity, similar to the mortality rate in patients without nephrotoxicity (36%) (P=0.999). In conclusion, in critically ill patients with CRF, colistin therapy, although used at a reduced dosage, was as effective as in patients without CRF.     

Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches

Introduction: In the era of multidrug-resistant, extensively drug-resistant (XDR) and even pandrug-resistant Gram-negative microorganisms, the medical community is facing the threat of untreatable infections particularly those caused by carbapenemase-producing bacteria, that is, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Therefore, all the presently available antibiotics, as well as for the near future compounds, are presented and discussed.

Areas covered: Current knowledge concerning mechanisms of action, in vitro activity and interactions, pharmacokinetic/pharmacodynamics, clinical efficacy and toxicity issues for revived and novel antimicrobial agents overcoming current resistance mechanisms, including colistin, tigecycline, fosfomycin, temocillin, carbapenems, and antibiotics still under development for the near future such as plazomicin, eravacycline and carbapenemase inhibitors is discussed.

Expert opinion: Colistin is active in vitro and effective in vivo against XDR carbapenemase-producing microorganisms in the critically ill host, whereas tigecycline, with the exception of P. aeruginosa, has a similar spectrum of activity. The efficacy of combination therapy in bacteremias and ventilator-associated pneumonia caused by K. pneumoniae carbapenemase producers seems to be obligatory, whereas in cases of P. aeruginosa and A. baumannii its efficacy is questionable. Fosfomycin, which is active against P. aeruginosa and K. pneumoniae, although promising, shares poor experience in XDR infections. The in vivo validity of the newer potent compounds still necessitates the evaluation of Phase III clinical trials particularly in XDR infections.     

Combination carbapenem-sulbactam therapy for critically ill patients with multidrug-resistant Acinetobacter baumannii bacteremia: four case reports and an in vitro combination synergy study

Infections caused by multidrug-resistant Acinetobacter baumannii have become a therapeutic challenge for clinicians worldwide. Although colistin and tigecycline have been successful in treating patients with these infections, these agents are not available on a worldwide basis. We describe four critically ill patients in Taiwan who were diagnosed with multidrug-resistant Acinetobacter baumannii bacteremia. All bacterial isolates from these patients were resistant to commonly available antibiotics, including carbapenems and sulbactam; however, combination therapy with a carbapenem and sulbactam led to favorable clinical outcomes in all four patients. We also conducted an in vitro study using isolates from these patients that showed that this drug combination had a synergistic effect with enhanced antibacterial activity against the isolates. Thus, a carbapenem-sulbactam combination may be a therapeutic alternative for multidrug-resistant Acinetobacter baumannii bacteremia in countries where colistin and tigecycline are not available for clinical use.     

Colistin and tigecycline susceptibility among multidrug-resistant Acinetobacter baumannii isolated from ventilator-associated pneumonia

Multidrug-resistant (MDR) Acinetobacter baumannii is one of the most important pathogens in intensive care units related to morbidity and mortality, especially in ventilator-associated pneumonia (VAP). In this study, 80.5% of isolates were MDR. The antimicrobial susceptibilities for 12 different antibiotics of MDR A. baumannii isolated from VAP were tested. Among the MDR A. baumannii isolates, resistance rates were found to be 95.5%, 72.7%, 80.3%, 71.2% and 68.2% for ciprofloxacin, cefepime, imipenem, meropenem and cefoperazone/sulbactam, respectively. Netilmicin resistance was detected in 30.3% of the isolates. Resistance rates for colistin and tigecycline were 0% and 25.8%, respectively. It is obvious that new alternative drugs are needed for the treatment of MDR A. baumannii-related VAP owing to high resistance to carbapenems, quinolones, aminoglycosides and cefoperazone/sulbactam. Although colistin appears to be a good choice, adverse reactions and unavailability of colistin limit its wide usage in Turkey. Tigecycline, which will shortly be introduced commercially in Turkey, is very effective against MDR A. baumannii isolates and shows promising results to solve the problem, however resistance rates should be monitored closely.     

Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and extensively drug-resistant carbapenemase-producing Gram-negative bacteria

Fosfomycin is active in vitro against extensively drug-resistant (XDR) and pandrug-resistant (PDR) Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing strains; however, the in vivo effectiveness against such pathogens is almost unknown. A multicentre, observational, prospective case-series study was performed in 11 ICUs. All consecutive fosfomycin-treated patients suffering from XDR or PDR fosfomycin-susceptible, microbiologically documented infections were recorded. Clinical and microbiological outcomes were assessed. A safety analysis was performed. In total, 68 patients received fosfomycin during the study period, 48 of whom were considered suitable for effectiveness analysis based on predefined criteria. Bacteraemia and ventilator-associated pneumonia were the main infections. Carbapenemase-producing K. pneumoniae and P. aeruginosa were isolated in 41 and 17 cases, respectively. All isolates exhibited an XDR or PDR profile, being fosfomycin-susceptible by definition. Fosfomycin was administered intravenously at a median dose of 24 g/day for a median of 14 days, mainly in combination with colistin or tigecycline. Clinical outcome at Day 14 was successful in 54.2% of patients, whilst failure, indeterminate outcome and superinfection were documented in 33.3%, 6.3% and 6.3%, respectively. All-cause mortality at Day 28 was 37.5%. Bacterial eradication was observed in 56.3% of cases. Fosfomycin resistance developed in three cases. The main adverse event was reversible hypokalaemia. In conclusion, fosfomycin could have a place in the armamentarium against XDR and PDR Gram-negative infections in the critically ill. Resistance development during therapy, which has been a matter of concern in previous studies, did not occur frequently. The necessity of combination with other antibiotics requires further investigation.     

替加环素不同治疗方案对ICU泛耐药鲍曼不动杆菌肺部感染的临床效果对比观察#br#

目的 对不同替加环素治疗方案对重症监护室(ICU)泛耐药鲍曼不动杆菌肺部感染的临床疗效和安全性进行对比分析,为替加环素的合理用药提供临床依据。方法 回顾性分析我院ICU 2014年1月-2017年6月使用替加环素治疗的62例泛耐药鲍曼不动杆菌肺部感染的临床资料,其中29例患者单独使用替加环素治疗,33例患者使用替加环素联合头孢哌酮/舒巴坦治疗,其疗程均超过7d,采用t检验或χ²检验对两组患者的临床特征、炎症指标、临床疗效、微生物清除率及不良反应等指标进行比较。结果 替加环素单独用药组和联合用药组在性别、年龄、疾病严重程度及加倍剂量应用替加环素病例数均无统计学差异(P＞ 0.05),联合用药组的临床有效率(21/33, 63.6%)高于单独用药组(11/29, 37.9%)(χ²=4.084, P＜0.05)。其中,患者APACHEⅡ评分≤15分的临床有效率70%(14/20)高于APACHEⅡ评分＞15分的42.9%(18/42)(χ²=3.997, P＜0.05);接受替加环素加倍剂量的临床有效率69.6%(16/23)高于常规剂量的41.0%(16/39)(χ²=4.719, P＜0.05)。替加环素单独用药组和联合用药组患者治疗后PCT、WBC和CRP水平与治疗前相比均显著降低(P＜0.05),且联合用药组的PCT水平下降更为明显(P＜0.05)。两组微生物学清除率(31.0% vs 38.7%)、不良反应发生率(13.8% vs 15.2%)均无统计学差异(P＞0.05)。临床疗效相关影响因素的logistic回归分析,也表明联合用药组疗效优于单独用药组,且用药前患者APACHE评分,CRP值,剂量加倍对临床疗效均存在影响。结论 替加环素联合头孢哌酮/舒巴坦治疗ICU泛耐药鲍曼不动杆菌肺部感染有较好的临床疗效,替加环素是否加倍剂量以及患者APACHEⅡ评分的高低可能影响其治疗效果,且不增加不良反应的发生率,值得在临床进一步推广。     

Pharmacokinetic and pharmacodynamic evaluation of tigecycline

INTRODUCTION: As the spread of multidrug-resistant (MDR) and extensive drug-resistant (XDR) organisms constitutes a real threat for patients, new antimicrobials are needed. Tigecycline, the first-in-class glycylcycline, possesses an extended spectrum of antimicrobial activity including MDR and XDR organisms, which holds promise as a treatment option beyond currently approved indications and deserves expanded evaluation of its pharmacokinetics/pharmacodynamics (PK/PD). AREAS COVERED: This review highlights the areas where our knowledge on PK/PD of tigecycline has been both strengthened and questioned during the recent years. New information has become available on the PK of tigecycline in patients with complicated skin and skin structure infections, complicated intra-abdominal infection, community- and nosocomial-acquired pneumonia. Human PD data from clinical trials linking tigecycline drug exposure to clinical, microbiological and toxicological outcomes are also of great interest. EXPERT OPINION: Tigecycline remains one of our last resorts against MDR pathogens; its clear role has to be re-defined through intense PK/PD applications; dose escalation and exploration of combinations with other antibiotics seem to be the first step towards an expansion of its currently approved indications. The lung remains the most controversial and challenging site regarding the PK/PD standpoint due to the predominance of Acinetobacter baumannii and carbapenemase-producing Klebsiella pneumoniae among ventilator-associated pneumonia infections, for which tigecycline is mostly used off-label.     

Current review of antimicrobial treatment of nosocomial pneumonia caused by multidrug-resistant pathogens

Nosocomial pneumonia (including ventilator-associated pneumonia; VAP), a consistently difficult-to-treat entity, is frequently caused by multidrug-resistant (MDR) or pandrug-resistant (PDR) bacteria. Given the high mortality rates caused by drug-resistant bacteria and the difficulty of developing new potent antibiotics to target the problematic pathogens, combination regimens are under ardent evaluation as new strategies to overcome increasing drug resistance. Adjustment of the administration method of certain β-lactams (meropenem, or imipenem/cilastatin), or combination of tigecycline with some agents, may show promise with regard to successful management of MDR or PDR Acinetobacter baumannii pneumonia. Additionally, vancomycin plus rifampicin is an effective regimen against nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) responding poorly to vancomycin monotherapy. The clinical appropriateness of parenteral colistin against pneumonia caused by MDR A. baumannii has been established in a clinical trial. Facing the decline of clinical vancomycin efficacy after initial use, linezolid might be the drug of choice with regard to the treatment of MRSA-VAP. The role of tigecycline monotherapy for the management of nosocomial pneumonia caused by MRSA and extended-spectrum β-lactamase-producing Enterobacteriaceae needs to be cautiously evaluated.     

Efficacies of colistin and tigecycline in mice with experimental pneumonia due to NDM-1-producing strains of Klebsiella pneumoniae and Escherichia coli

New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an experimental model of pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella pneumoniae. The susceptibilities of K. pneumoniae NDM, E. coli NDM and K. pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an experimental model of pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 (K. pneumoniae NDM) and 37 (K. pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. pneumoniae NDM and K. pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 logCFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. pneumoniae NDM and K. pneumoniae ATCC 29665 load by 2.67 logCFU/g and 4.62 logCFU/g (P<0.05). Colistin and tigecycline decreased lung concentrations of E. coli NDM by 2.27 logCFU/g and 4.15 logCFU/g (P<0.05), respectively, compared with controls, and was more active than colistin (P<0.05). In conclusion, these results suggest that colistin is inappropriate for treating pneumonia due to NDM-1-producing K. pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli. A high tigecycline dose was efficacious for treating experimental pneumonia due to NDM-1-producing E. coli and K. pneumoniae.     

Efficacy of ceftolozane/tazobactam,alone and in combination with colistin,against multidrug-resistant Pseudomonas aeruginosa in an in vitro biofilm pharmacodynamic model

Objectives

Ceftolozane/tazobactam is a potential tool for infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa), but its efficacy against some difficult-to-treat infections has not been well defined.

氯己定擦浴联合阿米卡星滴鼻对ICU鲍曼不动杆菌呼吸机相关性肺炎的防治作用

目的:探讨氯己定擦浴联合阿米卡星滴鼻对重症监护室(ICU)防治鲍曼不动杆菌呼吸机相关性肺炎的防治作用。方法:将2010年10月-2011年10月入住ICU气管插管呼吸机辅助通气患者120名随机分为3组。空白对照组仅予清水擦浴,bid;氯己定擦浴组予氯己定擦浴(2%醋酸氯己定),bid;联合处理组在氯已定擦浴(用法用量同氯己定组)基础上同时给予阿米卡星滴鼻,0.02g,tid。观察3组患者鲍曼不动杆菌的感染率和耐药情况。空白对照组感染鲍曼不动杆菌的病例再随机分成2组,2组在抗菌药物(包括药品、用法、用量)应用相同的情况下分别予氯己定擦浴和联合处理,观察2组抗鲍曼不动杆菌的治疗效果、鲍曼不动杆菌耐药情况。结果:氯己定擦浴组和联合处理组鲍曼不动杆菌感染率明显低于空白对照组(P<0.05),氯己定擦浴组和联合处理组鲍曼不动杆菌感染率无显著性差异(P>0.05),3组鲍曼不动杆菌耐药率无显著性差异(P>0.05);空白对照组感染鲍曼不动杆菌病例再随机分组处理后,2组鲍曼不动杆菌耐药率及抗感染治疗效果无显著性差异(P>0.05)。结论:氯己定擦浴在ICU病房可有效减少鲍曼不动杆菌呼吸机相关性肺炎的发生,联合阿米卡星滴鼻未能明显提高抗鲍曼不动杆菌治疗效果。     

Rapid development of Acinetobacter baumannii resistance to tigecycline

A 53-year-old woman experienced a multidrug-resistant (MDR) Acinetobacter baumannii urinary tract infection 5 months after undergoing kidney and liver transplantation. The tigecycline minimum inhibitory concentration (MIC) for her A. baumannii isolate was 1.5 microg/ml; the patient received 2 weeks of therapy with intravenous tigecycline as a 100-mg loading dose followed by 50 mg every 12 hours, with no lapses in treatment and with resolution of the infection. Three weeks later, MDR A. baumannii was isolated from her sputum in the setting of clinical evidence of pneumonia, and tigecycline was restarted; the tigecycline MIC for the A. baumannii isolate was 2 microg/ml. At approximately the same time, the patient was found to have a paraspinal abscess and spinal osteomyelitis. Cultures of the abscess fluid grew A. baumannii with a tigecycline MIC of 24 microg/ml. A follow-up sputum culture again yielded A. baumannii, but with a tigecycline MIC of 24 microg/ml. Urine culture at that time also grew A. baumannii with a tigecycline MIC of 24 microg/ml. Clinicians should be aware that tigecycline MICs for A. baumannii isolates may increase during therapy with tigecycline after only brief exposure to the drug. Patients receiving tigecycline for Acinetobacter should be monitored for the development of clinical resistance, and isolates should be monitored for evidence of microbiologic resistance.     

静脉联合鞘内或脑室内注射多黏菌素对多重耐药鲍曼不动杆菌#br# 颅内感染疗效及安全性Meta分析

目的 系统评价多黏菌素静脉联合鞘内或脑室内注射对多重耐药鲍曼不动杆菌的疗效及安全性。方法 计算机检索PubMed、Embase、CNKI、VIP、万方数据库等数据库,检索时间为建库至2019年6月,筛选有关多黏菌素静脉联合鞘内或脑室内给药治疗多重耐药鲍曼不动杆菌感染的文献,采用RevMan 5.3软件对提取的数据进行Meta分析。结果 纳入7篇文献、178例患者。Meta分析结果显示,静脉联合鞘内或脑室内组的临床死亡率(OR=0.18, 95%CI：0.09~0.37, P＜0.00001)低于静脉组、细菌清除率(OR=20.40, 95%CI：5.94~70.12, P＜0.00001)高于静脉组;两组不良反应发生率无统计学差异(OR=0.60, 95%CI: 0.16~2.23, P=0.44)。结论 多黏菌素静脉联合鞘内或脑室内给药治疗多重耐药鲍曼不动杆菌颅内感染疗效优于静脉滴注,安全性无显著差异。     

Potentially multidrug-resistant non-fermentative Gram-negative pathogens causing nosocomial pneumonia

Owing to its high morbidity and mortality, nosocomial pneumonia represents a particularly serious illness and one of the most frequent complications in ventilated patients admitted to the Intensive Care Unit. Gram-negative microorganisms, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia, are the most relevant pathogens responsible for particularly difficult-to-treat nosocomial pneumonia. The intrinsic resistance of these bacteria to many antimicrobial agents and, in addition, the variety of their increasingly recognised acquired resistance mechanisms make their management in the hospital setting problematic. Antimicrobials that retain the best activity against P. aeruginosa include carbapenems, piperacillin, cefepime, ceftazidime, ciprofloxacin and certain aminoglycosides, whilst carbapenems and sulphamethoxazole/trimethoprim remain the most active agents against A. baumannii and S. maltophilia, respectively. However, the growing emergence among these microorganisms of multidrug-resistant (MDR) isolates and the severity of associated infections call for potential alternative drugs. Sulbactam alone or in combination with ampicillin may represent an acceptable option for MDR A. baumannii as well as colistin, which also covers MDR P. aeruginosa. Newer fluoroquinolones and some tetracyclines may be alternative drugs both for MDR S. maltophilia and A. baumannii. However, large-scale controlled clinical trials are needed to confirm these promising therapeutic options.     

抗替加环素鲍曼不动杆菌耐药机制的研究进展

鲍曼不动杆菌是临床常见的条件致病菌,广泛分布于医院环境中,常导致患者出现血流、呼吸道、泌尿生殖道及中枢神经系统感染。作为一种新型的四环素类抗菌药物,替加环素对鲍曼不动杆菌尤其是泛耐药鲍曼不动杆菌具有很好的疗效,但其耐药性也日趋严重。流行病学研究发现,鲍曼不动杆菌对替加环素的耐药性呈现出显著的地区性差异。相关基础研究表明,其耐药机制主要与AdeABC外排泵系统的过表达有关。结合近期的研究结果,本文就耐替加环素鲍曼不动杆菌的流行病学现状和耐药机制进行简要综述。     

多黏菌素联合替加环素对多重耐药鲍曼不动杆菌的作用

目的 探讨多黏菌素联合替加环素（tigecyclin）对多重耐药鲍曼不动杆菌体外抗菌的效果。方法 收集临床分离的50株多重耐药鲍曼不动杆菌,采用微量肉汤稀释法、棋盘法分别检测替加环素、多黏菌素单独及联合使用的最低抑菌浓度（MIC）,并计算药物联合使用抑菌浓度（FIC）指数,利用FIC指数判定替加环素和多黏菌素联用时对多重耐药鲍曼不动杆菌体外抗菌的效果。荧光定量PCR检测外排泵基因表达水平。结果 替加环素联合多黏菌素能显著降低各自MIC值,表现为协同作用的菌株占70%,表现为相加作用的占14%,表现为无关作用的占6%,拮抗作用则为10%。对联合用药不敏感的菌株,其外排泵基因（abeB,abeJ,abeG,abeM）表达水平显著高于敏感型（P<0.05）。结论 替加环素联合多黏菌素可对多重耐药鲍曼不动杆菌的感染进行治疗。     

Therapeutic options for Acinetobacter baumannii infections

Acinetobacter baumannii is an important cause of nosocomial infections, mainly in patients in intensive care units. This microorganism, although with slight differences depending on the country, presents resistance to multiple antimicrobial agents, occasionally including resistance to colistin: hence, it can be considered the paradigm of nosocomial multiresistant bacteria. This review analyzes the evolution of antimicrobial resistance and the molecular bases associated with the increase in antimicrobial resistance, as well as the current treatment of Acinetobacter infections. Although controversy remains, the pooled data suggest that infections by A. baumannii may be associated with considerable attributable mortality. Moreover, in cases of pneumonia and bacteraemia, inappropriate treatment is associated with, among other factors, mortality. Therefore, treatment should be carefully considered.