Economic value of Acinetobacter baumannii screening in the intensive care unit

Although Acinetobacter baumannii (A. baumannii) is an increasingly common nosocomial pathogen that can cause serious infections in the intensive care unit (ICU), most ICUs do not actively screen admissions for this pathogen. We developed an economic computer simulation model to determine the potential cost-consequences to the hospital of implementing routine A. baumannii screening of ICU admissions and isolating those patients who tested positive, comparing two screening methods, sponge and swab, with each other and no screening. Sensitivity analyses varied the colonization prevalence, percentage of colonized individuals who had active A. baumannii infections, A. baumannii reproductive rate (R), and contact isolation efficacy. Both screening methods were cost-effective for almost all scenarios tested, yielding cost-savings ranging from -$1 to -$1563. Sponge screening was not cost-saving when colonization prevalence was ≤1%, probability of infection ≤30%, R ≤ 0.25, and contact isolation efficacy ≤25%. Swab screening was not cost-saving under these same conditions when the probability of infection was ≤40%. Sponge screening tended to be more cost-saving than swab screening (additional savings ranged from $1 to $421). Routine A. baumannii screening of ICU patients may save costs for hospitals.     

医院泛耐药鲍曼不动杆菌对碳青霉烯抗生素的耐药机制

目的 探讨医院泛耐药鲍曼不动杆菌对碳青霉烯抗生素的耐药机制.方法 应用PCR方法对2010年12月至2012年3月期间本院从临床痰标本中分离的36株泛耐药鲍曼不动杆菌进行碳青霉烯酶IMP、OXA23基因和整合子基因检测;提取细菌膜蛋白行SDS-PAGE电泳分析其组成.结果 36株泛耐药鲍曼不动杆菌碳青霉烯酶OXA23基因扩增均为阳性;14株碳青霉烯酶IMP基因扩增阳性,22株阴性.12株整合子PCR产物约1200 bp,10株约3000 bp,14株整合子PCR产物约3500 bp.与碳青霉烯抗生素敏感鲍曼不动杆菌膜蛋白比较,22株泛耐药鲍曼不动杆菌存在相对分子质量为25 000、36 000的膜蛋白缺失.结论 医院泛耐药鲍曼不动杆菌耐碳青霉烯抗生素机制与产IMP、OXA23碳青霉烯酶及膜蛋白缺失有关.     

Modifications to CHROMagar Acinetobacter for improved selective growth of multi-drug resistant Acinetobacter baumannii

Performance of CHROMagar Acinetobacter was assessed for the selective isolation and identification of Acinetobacter baumannii. The medium was effective in suppressing the growth of other Gram-positive and Gram-negative species while the addition of KPC supplement ensured growth of only carbapenem resistant A baumannii.     

鲍曼不动杆菌对碳青霉烯类抗生素的耐药分析及基因型研究

目的分析20株鲍曼不动杆菌对耐碳青霉烯类抗生素的耐药性及对碳青霉烯酶基因的研究。方法用API鉴定条进行细菌鉴定及K-B法进行药敏试验,用碳青霉烯酶4种基因的特异性引物进行聚合酶链反应（PCR）扩增和基因型的测序分析,并通过网上Genbank进行比对以确定编码酶基因的类型。结果 20株鲍曼不动杆菌对左旋氧氟沙星、丁胺卡那霉素、多粘菌素B的耐药率分别为50%、25%、4%。其它抗生素的耐药率均在90%以上。携带D类碳青霉烯酶OXA-23基因有17株（85%）,携带OXA-51基因有15株（75%）,OXA-24、OXA-58基因引物PCR扩增为阴性,随机各抽取3株OXA-23基因阳性株进行测序后通过在网上Genbank比对发现与OXA-23标准株99%同源,OXA-51基因阳性株与OXA-51标准株98%同源。结论本院耐碳青霉烯类抗生素的鲍曼不动杆菌对多粘菌素B的耐药率最低,其次是丁胺卡那霉素,以携带OXA-23型碳青霉烯酶基因为主,应引起临床高度重视,防止在院内广泛传播。     

Screening for Acinetobacter baumannii colonization by use of sponges

There is currently no consensus method for the active screening of Acinetobacter baumannii. The use of swabs to culture nostrils, pharynx, and skin surface of various anatomical sites is known to yield less-than-optimal sensitivity. In the present study, we sought to determine whether the use of sterile sponges to sample large areas of the skin would improve the sensitivity of the detection of A. baumannii colonization. Forty-six patients known to be colonized with A. baumannii, defined by a positive clinical culture for this organism as defined by resistance to more than two classes of antimicrobials, participated in the study. The screening sites included the forehead, nostrils, buccal mucosa, axilla, antecubital fossa, groin, and toe webs with separate rayon swabs and the forehead, upper arm, and thigh with separate sponges. Modified Leeds Acinetobacter medium (mLAM) agar plates that contained vancomycin and either aztreonam or ceftazidime were used as the selective medium. An enrichment culture grown overnight substantially increased the sensitivity for most sites. The sensitivity ranged between 69.6 and 82.6% for individual sponge sites and 21.7 to 52.2% for individual swab sites when mLAM plates with ceftazidime were inoculated after a 24-h enrichment period. The sponge and swab sites with the best sensitivity were the leg and the buccal mucosa, respectively (82.6% and 52.2%; P = 0.003). The combined sensitivity for the upper arm and leg with a sponge was 89.1%. The novel screening method using sterile sponges was easy to perform and achieved excellent sensitivity for the detection of A. baumannii colonization.     

Colistin for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex

ObjectivesTo investigate clinical and microbiological response, and 30-day mortality of pneumonia involving multidrug-resistant (MDR) Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex treated with colistin, and identify associated factors of these outcomes.MethodsA retrospective study of 183 adult patients with colistin treatment for at least 7 days between January 2014 and October 2017.ResultsThe mean age was 76.8 years, and mean Acute Physiology and Chronic Health Evaluation II score was 17.7. Eighteen (9.8%) and 128 (69.9%) patients had intravenous (IV) colistin alone and inhaled (IH) colistin alone, respectively. Thirty-seven patients had both IV and IH colistin, including 5 (2.7%) with concurrent, and 32 (17.5%) with non-concurrent use of IV and IH colistin. The 30-day mortality rate was 19.1% and 131 (71.6%) patients had clinical response. In the 175 patients with available data, 126 (72%) had microbiological eradication. The multivariate analyses revealed that IH colistin alone was an independent predictor for 30-day survival, clinical response, and microbiological eradication, and IV colistin alone was an independent predictor for clinical failure. Patients with IV colistin alone had a significantly higher nephrotoxicity rate than IH colistin alone (37.5% vs 6.1%, P = 0.001). Sub-group analysis of 52 patients with IV colistin for ≧ 4 days revealed that 14 (26.9%) patients had inappropriate dose, and inappropriate dose was an independent predictor for 30-day mortality.ConclusionsIH colistin provided good outcomes with few side effects, and appropriate dosing of IV colistin was important to avoid excess mortality.     

Plasmid DNA fingerprinting of Acinetobacter species other than Acinetobacter baumannii.

During the last years Acinetobacter species have emerged as clinically significant pathogens. Most infections are nosocomially acquired and mainly due to Acinetobacter baumannii. Little is known about the epidemiology and clinical significance of unnamed Acinetobacter species 3 (the second most often encountered member of the genus Acinetobacter) and other Acinetobacter species such as A. johnsonii, A. junii, and A. lwoffii. Seventy-five clinical isolates of Acinetobacter species other than A. baumannii (Acinetobacter species 3, n = 37; A. johnsonii, n = 20; A. junii, n = 8; A. lwoffii, n = 10) recovered from 66 patients over a period of 12 months were analyzed by plasmid DNA fingerprinting. Plasmids were found in 84.4% of Acinetobacter species 3 isolates and in all A. johnsonii, A. junii, and A. lwoffii isolates. Strains harbored up to 15 plasmids each. Almost every isolate gave a unique plasmid pattern. With one exception, identical plasmid profiles were detected only in corresponding isolates recovered from blood cultures and intravascular catheters from a given patient. Plasmid DNA fingerprinting proved to be useful for typing Acinetobacter species other than A. baumannii. There was no evidence of patient-to-patient transmission or hospital outbreaks due to these species. This finding is in contrast to the results obtained in studies of the hospital epidemiology of A. baumannii.     

Survival of Acinetobacter baumannii on dry surfaces.

Acinetobacter spp. have frequently been reported to be the causative agents of hospital outbreaks. The circumstances of some outbreaks demonstrated the long survival of Acinetobacter in a dry, inanimate environment. In laboratory experiments, we compared the abilities of five Acinetobacter baumannii strains, three Acinetobacter sp. strains from the American Type Culture Collection (ATCC), one Escherichia coli ATCC strain, and one Enterococcus faecium ATCC strain to survive under dry conditions. Bacterial solutions of the 10 strains were inoculated onto four different material samples (ceramic, polyvinyl chloride, rubber, and stainless steel) and stored under defined conditions. We investigated the bacterial counts of the material samples immediately after inoculation, after drying, and after 4 h, 1 day, and 1, 2, 4, 8, and 16 weeks of storage. A statistical model was used to distribute the 40 resulting curves among four types of survival curves. The type of survival curve was significantly associated with the bacterial strain but not with the material. The ability of the A. baumannii strains to survive under dry conditions varied greatly and correlated well with the source of the strain. Strains isolated from dry sources survived better than those isolated from wet sources. An outbreak strain that had caused hospital-acquired respiratory tract infections survived better than the strains from wet sources, but not as well as strains from dry sources. Resistance to dry conditions may promote the transmissibility of a strain, but it is not sufficient to make a strain an epidemic one. However, in the case of an outbreak, sources of Acinetobacter must be expected in the dry environment.     

Some immunological properties of lipopolysaccharide from Acinetobacter baumannii

Acinetobacter baumannii, mainly biotype 9, is an important nosocomial opportunist pathogen in Chile and other countries. The biological basis of its virulence and prevalence is still unknown. As lipopolysaccharide (LPS) is often associated with virulence, some biological properties of purified LPS from seven nosocomial isolates, comprising four isolates of A. baumannii biotype 9, two isolates of biotype 8 and one isolate of biotype 1, were investigated. LPS was extracted and purified from each isolate by the hot phenol-water method, and its ability to elicit a mitogenic response and to induce the synthesis of a tumour necrosis factor (TNF-alpha) in mouse spleen cells was determined. Activity was evaluated in vivo by determining the splenic index in comparison with LPS from Salmonella Typhimurium. All seven LPS samples were mitogenic on the basis of cellular proliferation experiments and six induced synthesis of TNF-alpha. Similar results were obtained in in-vivo experiments in which LPS induced spleen cell growth, as shown by determination of the splenic index. These results suggest that the LPS of A. baumannii might contribute to the pathogenic properties of this species.     

Outbreak of Extensively Drug-Resistant Acinetobacter baumannii Indigo-Pigmented Strains

Acinetobacter baumannii pigmented strains are not common in clinical settings. Here, we report an outbreak caused by indigo-pigmented A. baumannii strains isolated in an acute care hospital in Argentina from March to September 2012. Pan-PCR assays exposed a unique pattern belonging to the recently described regional CC113^B/CC79^P clonal complex that confirms the relevant relationships among the indigo-pigmented A. baumannii strains. All of them were extensively drug resistant and harbored different genetic elements associated with horizontal genetic transfer, such as the transposon Tn2006, class 2 integrons, AbaR-type islands, IS125, IS26, strA, strB, florR, and the small recombinase ISCR2 associated with the sul2 gene preceded by ISAba1.     

Acinetobacter baumannii serotyping for delineation of outbreaks of nosocomial cross-infection.

A total of 152 clinical isolates of Acinetobacter baumannii from 152 patients were identified by carbon source utilization tests and examined serologically. Polyclonal rabbit immune sera against A. baumannii strains were used in checkerboard tube agglutination tests, and 20 serovars were identified. One (serovar 19) cross-reacted with genospecies 3 (serovar 3), a closely related member of the genus Acinetobacter. Several outbreaks of nosocomial cross-infection caused by serovars 4 and 10 were delineated.     

Effect of desiccation on the ultrastructural appearances of Acinetobacter baumannii and Acinetobacter lwoffii

An Acinetobacter baumannii isolate survived desiccation beyond 30 days and an Acinetobacter lwoffii isolate up to 21 days. For both species, desiccation resulted in a significant increase in the proportion of round cells (A baumannii, 40% to 80%; A lwoffii, 51% to 63%) and a significant decrease in rod shaped cells (A baumannii, 58% to 13%; A lwoffii, 46% to 34%). Electronmicroscopic examination showed that there was also a corresponding significant increase in the cell wall thickness (A baumannii, up to 53%; A lwoffii, up to 26%). Desiccated A baumannii cells became more electron-dense and had significantly thicker cell walls (x1.3) than those of A lwoffii. Cell wall structures of A baumannii strains with different abilities to resist desiccation deserve further study.     

鲍曼不动杆菌的临床分布及耐药性变迁

目的了解鲍曼不动杆菌在临床标本的分离率和病区分布及耐药性变化趋势。方法菌株鉴定采用法国梅里埃VITEK32细菌鉴定系统进行鉴定,药敏试验采用K-B法,药敏试验结果判定以CLSI/NCCLS标准进行。结果 2004-2010年共收到26670份标本,分离出阳性细菌7065株,其中鲍曼不动杆菌471株（6.67%）,分离率为1.77%（471/7065）。在471株鲍曼不动杆菌中,从痰液标本分离出最多有409株（86.83%）,分离率最高的是ICU,占49.3%。鲍曼不动杆菌对抗菌药物的耐药性普遍较高,且呈逐年升高趋势,部分表现出多重耐药特征。结论鲍曼不动杆菌的耐药状况日益严重,应重视临床鲍曼不动杆菌的感染与分离,谨防多重耐药鲍曼不动杆菌的院内感染及暴发流行。     

Ribotyping of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex.

The Acinetobacter calcoaceticus-Acinetobacter baumannii complex consists of four genotypically distinct but phenotypically very similar bacterial species or DNA groups: A. calcoaceticus (DNA group 1), A. baumannii (DNA group 2), unnamed DNA group 3 (P. J. M. Bouvet and P. A. D. Grimont, Int. J. Syst. Bacteriol. 36:228-240, 1986), and unnamed DNA group 13 (I. Tjernberg and J. Ursing, APMIS 97:595-605, 1989). Because strains in this complex cause nosocomial outbreaks, it is important to be able to identify them as completely as possible. Ribotyping could provide such identification. Therefore, ribotyping was done on 70 strains in the A. calcoaceticus-A. baumannii complex with known DNA group affiliations by use of restriction enzymes EcoRI, ClaI, and SalI. A nonradioactive digoxigenin-11-dUTP-labeled Escherichia coli rRNA-derived probe was used. With any of the three restriction enzymes, banding patterns that were specific for each DNA group were seen. All 70 strains showed banding patterns that could identify them to the correct DNA group by use of any two of the three enzymes. In addition, banding patterns that could separate strains within any one DNA group were present. The discriminatory index of P. Hunter and M. Gaston (J. Clin. Microbiol. 26:2465-2466, 1988), applied to all strains with the combined results obtained with all three enzymes, revealed a value of 0.99. For strains in each DNA group, the value varied from 0.93 to 0.98. These results indicate the high discriminatory power of the system when used for epidemiological typing.     

多重聚合酶链反应技术快速鉴定鲍曼不动杆菌

目的建立快速鉴定鲍曼不动杆菌菌株的方法。方法本研究建立多重PCR实验技术快速鉴定170株醋酸钙-鲍曼不动杆菌复合体以及对照组的其他菌属14株。结果138株菌的PCR产物扩增出2条条带,为鲍曼不动杆菌,另外32株只扩增出1条条带,为醋酸钙-鲍曼不动杆菌复合体的其他基因型,对照组的菌株没有扩增出条带。结论多重PCR技术的建立为快速鉴定鲍曼不动杆菌提供了一个快速而简便的方式。     

Acinetobacter baumannii: emergence of a successful pathogen

Acinetobacter baumannii has emerged as a highly troublesome pathogen for many institutions globally. As a consequence of its immense ability to acquire or upregulate antibiotic drug resistance determinants, it has justifiably been propelled to the forefront of scientific attention. Apart from its predilection for the seriously ill within intensive care units, A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts. This review details the significant advances that have been made in our understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.     

Predictors of mortality in Acinetobacter baumannii bacteremia.

This study retrospectively investigated 149 episodes of Acinetobacter baumannii bacteremia which occurred during a 41-month period from September 1997 to January 2001. Bacteremia was nosocomial in 139 (93%) of the episodes and community-acquired in 10 (7%). Thirty three deaths (22.1%) were attributed to these episodes of A. baumannii bacteremia. The mean age of survivors was younger than that of patients who died of bacteremia (60.4 +/- 19.9 vs 67.1 +/- 17.4) but this result was not significant on univariate analysis (p=0.084). Previous intensive care unit stay was longer among survivors than among patients who died of bacteremia (9.5 vs 18 days, p=0.048). Factors associated with mortality included immunosuppression (p=0.019), shock (p=0.002), recent surgery (p=0.008), invasive procedures such as central venous catheterization (p=0.002), urinary catheterization (p=0.012), placement of a nasogastric tube (p<0.001), pulmonary catheterization (p=0.015), and mechanical ventilation (p=0.035). The number of underlying conditions (p=0.015) and invasive procedures (p<0.001) were positively correlated with mortality. Mortality was significantly associated with lower platelet count (p=0.001) and lower serum albumin concentration (p=0.005). Patients with catheter-related bacteremia had a high survival rate (96.2%), while survival rate was low in patients with infection originating from the respiratory tract (60.8%). Susceptibility testing by agar dilution test indicated that imipenem was the most effective antibiotic, followed by cefepime and ciprofloxacin. The mortality rate was lower in patients who received 1 or more antibiotics to which the isolates were susceptible, but this difference was not significant (p=0.197). On multivariate analysis, factors that independently correlated with mortality were increased age (p=0.003), immunosuppressive status (p=0.001), recent surgery (p=0.002), acute respiratory failure (p=0.004), acute renal failure (p=0.009) and septic shock (p<0.001). These findings highlight the importance of a treatment strategy based on risk stratification among patients with A. baumannii bacteremia.     

Detection of carbapenemase-producing Acinetobacter baumannii in a hospital

Acinetobacter baumannii strains resistant to both imipenem (IPM) and ceftazidime (CAZ) were isolated from 1994 through 1996 at Gunma University Hospital. Nine isolates from different inpatients were examined for carbapenem-hydrolyzing activity and for the carbapemase gene bla(IMP) by the PCR method. All nine isolates were carbapenemase-producing strains that hydrolyzed IPM and that harbored bla(IMP). The bla(IMP) gene was transmissible by conjugation to an IPM-susceptible recipient strain of A. baumannii and conferred resistance to IPM, CAZ, cefotaxime (CTX), ampicillin (AMP), and piperacillin (PIP). Either intermediate or high-level resistance to amikacin (AMK) was transferred from two and five strains, respectively, concomitantly with bla(IMP), and gentamicin (GEN) resistance was also transferred in one instance of high-level AMK resistance. Comparative examination of clinical isolates for resistance patterns to nine drugs, IPM, CAZ, CTX, aztreonam, AMP, PIP, AMK, GEN, and norfloxacin, in addition to pulsed-field gel electrophoresis patterns with NotI-digested genomic DNA, confirmed nosocomial transmission of infections involving carbapenemase-producing A. baumannii strains.     

Inhaled Colistin for Treatment of Pneumonia due to Colistin-Only-Susceptible Acinetobacter baumannii

Purpose

Colistin is used for the treatment of pneumonia associated with multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. However, the best route of administration and dosage is not known. We report our experience with aerosolized colistin in twelve patients with pneumonia caused by colistin-only-susceptible (COS) A. baumannii.

Materials and Methods

We retrospectively reviewed patients'' medical records who were treated with aerosolized colistin for the treatment of pneumonia.

Results

Ten patients were treated only with aerosolized colistin inhalation and two patients received a 3-day course intravenous colistin, and then switched to colistin inhalation therapy. The median duration of aerosolized colistin therapy was 17 days (5-31 days). Four patients were treated only with aerosolized colistin, whereas 4 patients received concomitant glycopeptides, and 4 received concomitant levofloxacin or cefoperazone/sulbactam. At the end of the therapy, the clinical response rate and bacteriological clearance rate was 83% and 50%, respectively. Colistin-resistant strains were isolated from 3 patients after aerosolized colistin therapy; however, all of them showed favorable clinical response. The median interval between inhalation therapy and resistance was 7 days (range 5-19 days). Acute kidney injury developed in 3 patients. Two patients experienced Clostridium difficile associated diarrhea. One patient developed fever and skin rash after aerosolized colistin therapy. No patient developed neurotoxicity or bronchospasm.

Conclusion

Colistin inhalation therapy is deemed tolerable and safe, and could be beneficial as an adjuctive therapy for the management of pneumonia due to COS A. baumannii. However, the potential development of colistin resistance cannot be overlooked.