Early experience with tigecycline for ventilator-associated pneumonia and bacteremia caused by multidrug-resistant Acinetobacter baumannii

Study Objective . To evaluate early experience with tigecycline alone or in combination with other antimicrobials for treatment of ventilator-associated pneumonia (VAP) and/or bacteremia caused by multidrug-resistant Acinetobacter baumannii. Design . Retrospective case series. Setting . University-affiliated medical center. Patients . Twenty-five patients with multidrug-resistant A. baumannii who received tigecycline for VAP (19 patients), bacteremia (3), or VAP plus bacteremia (3) between September 1, 2005, and May 31, 2006. Five patients were treated with tigecycline alone. Measurements and Main Results . Primary outcomes were resolution of clinical signs and symptoms of the infection and documented microbial eradication of A. baumannii with tigecycline. Overall, 21 (84%) of the 25 patients had clinical resolution. Four had clinical failure: three with VAP and one with VAP plus bacteremia that developed resistance to tigecycline during therapy. Microbial eradication was demonstrated in 12 (80%) of 15 patients in whom repeat cultures were obtained. Three patients with VAP had a recurrence of infection: one patient had two recurrences, and two patients had one recurrence each. All four recurrent episodes led to clinical resolution and microbial eradication. No patients discontinued tigecycline because of adverse events. Conclusion . Tigecycline was effective in most of these 25 patients when used alone or in combination with other antimicrobials for VAP and/or bacteremia caused by multidrug-resistant A. baumannii. The emergence of a resistant strain while one patient was receiving therapy, however, is concerning.     

两种方法测定替加环素对鲍曼不动杆菌药敏结果的比较

目的：比较采用两种方法测定替加环素对鲍曼不动杆菌药敏结果的差异。方法：分别采用琼脂平板稀释法和微量肉汤稀释法测定替加环素对70株鲍曼不动杆菌的MIC值,比较其结果差异性。结果：应用琼脂平板稀释法测定的MIC50和MIC90为1μg·mL-1和2μg·mL-1,敏感率、中介率、耐药率分别为47.1%、48.6%、4.3%;应用微量肉汤稀释法测定的替加环素对鲍曼不动杆菌的MIC50和MIC90分别为0.25μg·mL-1和0.5μg·mL-1,敏感率为100%。两种方法测定结果的一致性和相关性均较差;以微量肉汤稀释法为基准时,应用琼脂平板稀释法测定的总误差率为52.9%。结论：应用琼脂平板稀释法和微量肉汤稀释法进行替加环素对鲍曼不动杆菌药敏测定时,其敏感率有明显的差别。     

替加环素治疗多重耐药鲍曼不动杆菌感染的疗效观察

目的回顾性分析替加环素治疗多重耐药鲍曼不动杆菌(MDRAB)的微生物学清除率及临床治疗效果。方法我院重症医学科2011年9月至2013年5月,26例确诊为MDRAB感染的患者。使用替加环素治疗,替加环素首剂100 mg,随后每12 h 50 mg静脉滴注,疗程≥5 d,收集其临床及微生物学相关资料。结果26例鲍曼不动杆菌感染患者应用替加环素治疗后17例(17/26,65.4%)临床治疗有效,22例(22/26,84.6%)微生物清除。14 d死亡率15.4%。4例(15.4%)因临床和细菌学反应差而在2周内死亡。其中血流感染9例中微生物学清除8例,临床治疗有效5例;肺部感染16例中微生物清除13例,临床治疗有效11例;1例血流感染合并肺部感染微生物和临床反应均成功。结论替加环素治疗MDRAB感染具有良好疗效。     

Colistin/daptomycin: an unconventional antimicrobial combination synergistic in vitro against multidrug-resistant Acinetobacter baumannii

The in vitro activity of the combination colistin/daptomycin was evaluated against multidrug-resistant Acinetobacter baumannii clinical isolates. Clonal relationships were assessed by pulsed-field gel electrophoresis. The following synergy studies were undertaken: (i) daptomycin MICs were determined by E-test on Mueller–Hinton agar plates supplemented with a subinhibitory concentration of colistin; and (ii) time–kill methodology using tubes containing an inoculum of 5 × 10⁵ CFU/mL and subinhibitory concentrations of each antibiotic alone or in combination subcultured at 0, 5 and 24 h for colony counting. Synergy was defined as ≥2 log₁₀ CFU/mL decrease of viable colonies compared with colistin alone. Ten colistin-susceptible and four colistin-resistant A. baumannii isolates were tested. Isolates were assigned to nine different clonal types. Enhanced in vitro activity of the combination was detected only against colistin-susceptible isolates; using plates supplemented with colistin, the daptomycin MIC was reduced by 4- to 128-fold. From a total of 30 isolate–concentration combinations in time–kill studies, a synergistic interaction was detected in 16 (53.3%). The combination exhibited synergy against 8 and 12 of these combinations at 5 h and 24 h, respectively. No antagonism was detected. Colistin alone was bactericidal against two colistin-susceptible isolates at 24 h, whereas the combination was bactericidal against 9 colistin-susceptible isolates at 24 h. Against all colistin-resistant isolates, the combination exhibited a static effect and indifference in time–kill studies. Potent in vitro synergistic interactions between colistin and daptomycin provide evidence that this unorthodox combination may be beneficial in the treatment of colistin-susceptible multidrug-resistant A. baumannii.     

不同MH琼脂对于替加环素对鲍曼不动杆菌药敏结果的影响

目的:观察不同厂家生产的MH琼脂(MHA)对于替加环素对鲍曼不动杆菌琼脂平板稀释法药敏结果的影响.方法:采用琼脂平板稀释法分别测定应用Difco MHA、Oxoid MHA、美坛MHA和奥博星MHA时,替加环素对50株鲍曼不动杆菌的MIC值.结果:应用Difco MHA、Oxoid MHA、美坛MHA和奥博星MHA时的MIC90分别为2、4、4、16 μg·mL-1.替加环素的敏感率分别为100％、6％、6％和0.结论:应用不同厂家的MHA进行琼脂稀释法药敏测定时,替加环素对鲍曼不动杆菌的敏感率具有明显的差别.     

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。     

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.     

Confronting multidrug-resistant Acinetobacter baumannii: a review

Multidrug-resistant Acinetobacter baumannii (MDR-AB) infections are difficult to treat owing to the extremely limited armamentarium. The present review reports all available treatment options against MDR-AB, including single molecules, combination schemes, and alternative modes of antimicrobial administration. Additionally, a group of recently reported peptides with anti-MDR-AB activity is described.     

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 tigecycline/colistin combination in a pneumonia model caused by extensively drug-resistant Acinetobacter baumannii

Due to increasing drug resistance, available antimicrobial options are limited in the treatment of Acinetobacter baumannii infections. Particularly in cases caused by extensively drug-resistant (XDR) A. baumannii, combination regimens must also be taken into consideration. In this study, the efficacies of tigecycline, colistin and tigecycline/colistin combination on bacterial counts in lung tissue were investigated in a rat pneumonia model. One A. baumannii strain resistant to all antimicrobial agents except tigecycline and colistin was selected for the study. In vivo studies revealed a >3log reduction in bacterial counts in the tigecycline, colistin and combination groups at 24h and 48h compared with the control group. No significant differences were determined between colistin, tigecycline and combination groups (P>0.05). On the other hand, differences between treatment groups and the control group were statistically significant (P=0.01). A greater reduction in bacterial counts was observed at 48h compared with 24h in the tigecycline group than in the colistin group (P=0.038 and P=0.139, respectively); the most significant decrease between 24h and 48h was observed in the combination group (P=0.014). Despite detection of in vitro synergistic activity in this study, no statistically significant differences were found between colistin, tigecycline and combination treatments in terms of efficacy on bacterial counts in lung tissue. In the treatment of infections with a high mortality rate such as pneumonia caused by XDR A. baumannii, combining tigecycline with colistin during the first 48h and continuing treatment with one of these agents seems a rational approach.     

多重耐药鲍曼不动杆菌颅内感染的药学监护

目的:探讨临床药师参与多重耐药鲍曼不动杆菌(Multidrug-resistant Acinetobacter baumannii,MDRAB)颅内感染的药学监护模式.方法:通过2例MDRAB颅内感染成功治疗案例,结合相关指南和文献报道,综述MDRAB颅内感染的治疗策略,并介绍临床药师协助医师完善治疗方案的过程.结果:MDRAB引起的颅内感染应选择敏感、易透过血脑屏障的抗菌药物联合治疗方案,并尽早去除植入的异物和脑脊液引流管.临床药师可从抗菌药物选择、抗感染治疗疗程等方面作为切入点,为患者开展药学监护.结论:对MDRAB颅内感染患者实施药学监护,可优化抗菌药物治疗方案,并督促医师用足疗程、尽早去除植入的异物和脑脊液引流管,提高MDRAB颅内感染药物治疗的有效性和安全性.     

Nontraditional dosing of ampicillin-sulbactam for multidrug-resistant Acinetobacter baumannii meningitis

A 52-year-old man was admitted to a local hospital with headache, nausea, vomiting, dizziness, photophobia, and confusion after a sudden fall. Progressive changes in neurologic function were noted despite neurosurgical intervention and broad-spectrum antimicrobial coverage. Cerebral spinal fluid (CSF) culture identified Acinetobacter baumannii that was resistant to traditionally recommended therapies of amikacin and imipenem-cilastatin. The organism demonstrated minimum inhibitory concentrations of greater than 32 microg/ml and 8 microg/ml, respectively, for these two agents. Ampicillin 2 g-sulbactam 1 g every 3 hours was administered based on history of therapeutic failure of traditional dosing in our thermal injury population. Repeat CSF cultures after 12 days of ampicillin-sulbactam therapy were negative. After 35 days, the patient's A. baumannii infection was completely resolved. The patient experienced no adverse drug events or toxicity with this high-dosage regimen.     

三联药物方案对多重耐药鲍曼不动杆菌肺炎的疗效分析

目的:分析替加环素、头孢哌酮钠/舒巴坦、多黏菌素E三联药物方案对多重耐药鲍曼不动杆菌肺炎患者的病原菌清除率、病程以及实验室指标的影响。方法:选取2015年10月至2017年10月黄石市鄂东医疗集团中心医院治疗的86例重耐药鲍曼不动杆菌肺炎患者,随机分为观察组(n=43)及对照组(n=43)。对照组给予替加环素联合头孢哌酮钠/舒巴坦进行药物治疗,观察组给予替加环素、头孢哌酮钠/舒巴坦、多黏菌素E三联药物治疗,治疗时间为2周。所有患者治疗前、后痰培养,观察其病原菌清除率、实验室指标不良反应发生情况以及生活质量情况。结果:从314例痰培养中培养出86株多重耐药鲍曼不动杆菌。观察组细菌清除率为86.05%,远高于对照组的67.44%,差异有统计学意义(P<0. 05)。观察组在白细胞恢复正常、体温降低、肺啰音消失以及胸片阴影消退方面的时间均低于对照组(P<0. 05),体征症状改善更为明显。治疗2周后,观察组患者在降钙素原、血清C反应蛋白以及体温水平均低于对照组,在WBC水平略高于对照组(P <0.05)。观察组患者不良反应发生率为11.73%,对照组为13.95%,差异无统计学意义(P>0. 05)。观察组生活质量情况显著优于对照组,差异有统计学意义(P<0. 05)。结论:头孢哌酮钠/舒巴坦、替加环素、多黏菌素E三药联用治疗多重耐药鲍曼不动杆菌肺炎患者能够提高鲍曼不动杆菌的细菌清除率,改善患者症状体征。     

ICU痰标本分离鲍曼氏不动杆菌的药敏分析

目的通过对重症监护室（ICU）送检的痰标本中分离培养出的鲍曼氏不动杆菌的药敏结果进行分析,指导临床用药。方法对2007年1月至2008年12月间从ICU送检的痰标本分离培养出112株鲍曼氏不动杆菌的药敏结果进行分析。结果ICU病区的鲍曼氏不动杆菌的耐药性很高,它的耐药性比同期全院感染的鲍曼氏不动杆菌明显增高。从ICU痰标本分离出的鲍曼氏不动杆菌比较敏感的抗生素是美洛配能（85．7％）和亚胺培南（83．9％）,比较耐药是复方新诺明（91．3％）。结论鲍曼氏不动杆菌是ICU痰标本中分离率最高的一种细菌,它的耐药性较为严重,应引起重视。     

Colistin-based treatment for extensively drug-resistant Acinetobacter baumannii pneumonia

Data for treatment and outcomes of extensively drug-resistant Acinetobacter baumannii (XDR-AB) pneumonia are limited. A retrospective cohort study of 236 adult patients with XDR-AB pneumonia was conducted between January 2009 and December 2012. The median age of subjects was 70 years (range 17–95 years), 53% were male, 55% had ventilator-associated pneumonia and 42% had been admitted to the intensive care unit. All XDR-AB isolates were susceptible only to tigecycline and colistin; 52 (22%) of the 236 subjects did not receive an agent active against XDR-AB, with an associated 28-day survival of 0%. Colistin-based two-drug combination treatment was prescribed to 166 subjects (70%); regimens included (i) colistin and high-dose sulbactam (n = 93); (ii) colistin and tigecycline (n = 43); and (iii) colistin and high-dose prolonged infusion of a carbapenem (n = 30). The 28-day survival rate and mean length of hospital stay were not statistically different between these three regimens (65%, 53% and 60% and 39, 39 and 38 days, respectively). Predictors of mortality included Acute Physiology and Chronic Health Evaluation (APACHE) II score [adjusted odds ratio (aOR) = 1.11; P < 0.001 for each point increase], duration from infection onset to receipt of active regimen (aOR = 1.01; P = 0.002 for each hour delay), underlying malignancy (aOR = 3.46; P = 0.01) and chronic kidney disease (aOR = 2.85; P = 0.03). These findings suggest that the three colistin-based two-drug combination regimens may be treatment options for XDR-AB pneumonia.     

替加环素治疗泛耐药鲍曼不动杆菌的1例病例分析

目的探讨替加环素对肺部多耐药鲍曼不动杆菌感染疗效。方法对1例使用替加环素的病例的疗效进行分析。结果与结论替加环素是治疗肺部多耐药鲍曼不动杆菌感染的一种选择。     

粘菌素等抗菌药物对临床分离鲍曼不动杆菌的抗菌活性

目的：评价粘菌素对临床分离多药耐药鲍曼不动杆菌的抗菌活性。方法：收集解放军总医院、北京医院、北京协和医院3家医院分离的非重复分离鲍曼不动杆菌70株,采用琼脂稀释法测定粘菌素与其他12种抗菌药物的最低抑菌浓度（MIC）,以CLSI标准判断其敏感率。结果：70株鲍曼不动杆菌,对青霉素类和头孢菌素类的耐药率为71．4％～82．9％,对碳青霉烯类（关罗培南、亚胺培南／西司他丁）的耐药率为75．7％～77．1％,对氨基糖苷类（奈替米星、阿米卡星）的耐药率为71．4％～75．7％,对氟喹酮类的耐药率（环丙沙星、左氧氟沙星）为32．9％～82．9％。共筛选出多药耐药鲍曼不动杆菌55株,对粘菌素全部敏感,MIC50和MIC90均为1μg／mL。结论：鲍曼不动杆菌对本研究的大多数抗菌药物耐药率较高,粘菌素对于鲍曼不动杆菌有很高的抗菌活性。     

Molecular detection of OXA carbapenemase genes in multidrug-resistant Acinetobacter baumannii isolates from Iraq and Georgia

The aim of this study was to determine the susceptibility to imipenem (IPM) of Acinetobacter baumannii isolates from different countries and to characterise the carbapenemase-encoding genes in IPM-resistant isolates. A total of 12 A. baumannii strains collected in Belgium (n = 2), Iraq (n = 8) and Georgia (n = 2) were included in the study. Identification of the isolates was confirmed using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibility testing was performed by the disk diffusion method, and Etest was used to determine the IPM minimum inhibitory concentrations (MICs) of resistant isolates. The presence of carbapenemase-encoding genes was investigated by polymerase chain reaction (PCR). All A. baumannii isolates were eventually identified by MALDI-TOF MS with high score values. Amongst the 12 strains, 6 were found to be resistant to IPM (MICs ≥ 16 μg/mL), comprising clinical isolates from wound infections of soldiers who were injured either during the Iraq war in 2007 (5 isolates) or during the Georgian-Russian war in 2008 (1 isolate from Georgia). All isolates contained ISAba1 and bla_OXA-51-like, but isolates from Iraq contained the bla_OXA-23 gene located on a plasmid whereas the isolate from Georgia contained the bla_OXA-24 gene located on the chromosome. None of the IPM-resistant isolates contained the bla_OXA-58- or bla_NDM-1-encoding genes. In conclusion, these results re-emphasise the worldwide dissemination of OXA carbapenemase genes in multidrug-resistant clinical isolates of A. baumannii and, to the best of our knowledge, report the first IPM-resistant A. baumannii strain isolated from a patient during the Georgian-Russian war with the bla_OXA-24 gene located on the chromosome.