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Mortality risk factors of Acinetobacter baumannii bacteraemia.

BACKGROUND: Acinetobacter baumannii is one of the most important nosocomial pathogens, and its multiple antibiotic resistance has emerged as an obstacle in the treatment of these infections worldwide. AIMS: To identify risk factors of mortality for A. baumannii bacteraemia. METHODS: A retrospective cohort study of 72 patients with significant A. baumannii bacteraemia was conducted to evaluate risk factors for mortality. RESULTS: The median age of the 72 enrolled patients was 48 years, 96% of the cases were hospital-acquired, and the bacteraemia-related mortality rate was 29% (21 of 72 patients). Univariate analysis revealed that the risk factors for mortality included: an elevated acute physiology and chronic health evaluation (APACHE II) score, receipt of in vitro ineffective definitive antimicrobial therapy, in vitro A. baumannii resistance to cefoperazone/ sulbactam, neutropenia, and presentation with septic shock. Multivariate analysis reveals that the independent risk factors for mortality are neutropenia and elevated APACHE II scores. CONCLUSION: Risk factors such as neutropenia and elevated APACHE II scores are found to be associated with higher mortality rates of A. baumannii bacteraemia. Further study is necessary for the determination of optimal strategies for both the prevention and treatment of these infections.

Acinetobacter Infections↗

Genetic and functional analysis of the chromosome-encoded carbapenem-hydrolyzing oxacillinase OXA-40 of Acinetobacter baumannii.

Clinical isolate Acinetobacter baumannii CLA-1 was resistant to a series of antibiotic molecules, including carbapenems. Cloning and expression of the beta-lactamase gene content of this isolate in Escherichia coli DH10B identified a chromosome-encoded oxacillinase, OXA-40, that differed by one or two amino acid changes from OXA-24, -25, and -26 and an AmpC-type cephalosporinase. The OXA-40 beta-lactamase had a mainly narrow-spectrum hydrolytic profile, but it included ceftazidime and imipenem. Its activity was resistant to inhibition by clavulanic acid, tazobactam, sulbactam, and, like most of the other carbapenem-hydrolyzing oxacillinases, NaCl. OXA-40 had an FGN triad replacing a YGN motif at class D beta-lactamase (DBL) positions 144 to 146. Site-directed DNA mutagenesis leading to a Phe-to-Tyr change at DBL position 144 in OXA-40 gave a mutant enzyme with increased hydrolytic activity against most beta-lactams, including imipenem. Conversely, with a gene encoding the narrow-spectrum oxacillinase OXA-1 as the template, a nucleotide substitution leading to a Tyr-to-Phe change in the YGN motif of OXA-1 gave a mutant enzyme with decreased hydrolytic activity without an increase in carbapenem-hydrolyzing activity. Thus, the Phe residue in the FGN motif was not associated with carbapenem-hydrolyzing activity by itself but instead was associated with weak overall hydrolytic activity. Finally, this Phe residue in OXA-40 explained resistance to inhibition by NaCl whereas a Tyr residue in motif YGN was related to susceptibility to NaCl.

Acinetobacter baumannii↗

[Adherence of Acinetobacter baumannii to rat tracheal tissue].

BACKGROUND: Acinetobacter baumannii is an important nosocomial pathogen whose virulence factors have not been fully elucidated. AIM: To study the adherence and hemagglutinating capacity of several biotypes of Acinetobacter baumannii. MATERIAL AND METHODS: Thirty nine strains of Acinetobacter baumannii isolated from hospitalized patients were studied. The adherence of these strains to small pieces of rat tracheal tissue was studied. Additionally, their ability to hemagglutinate human erythrocytes and the effect of D-mannose and D-galactose on the adherence and hemagglutinating capacity was assessed. Transmission electron microscopy of strains was performed looking for the presence of fimbriae. RESULTS: All strains exhibited adherence to tissues. All strains had also D-mannose and D-galactose resistant hemagglutinating ability. Fimbriae were found in Acinetobacter baumannii and E coil cells. CONCLUSIONS: Adherence of Acinetobacter baumannii to rat tracheal tissue, apparently not related to the presence of fimbriae, may be a virulence mechanism of this bacterium.

Acinetobacter↗

In vitro double and triple synergistic activities of Polymyxin B, imipenem, and rifampin against multidrug-resistant Acinetobacter baumannii.

Eight unrelated clinical Acinetobacter baumannii isolates resistant to all commonly used antibiotics were subjected to three-dimensional checkerboard microtiter plate dilution and time-kill studies at one-fourth of their MICs of polymyxin B, imipenem, and rifampin. Synergy was demonstrated with combinations of polymyxin B and imipenem, polymyxin B and rifampin, and polymyxin B, imipenem, and rifampin. Double combinations of polymyxin B and imipenem and of polymyxin B and rifampin were bactericidal for seven of eight isolates, and triple combinations were bactericidal for all isolates within 24 h. Future clinical studies using double and triple therapy with these antibacterials may provide an effective option against potentially lethal infection due to multiresistant Acinetobacter baumannii.

Acinetobacter Infections↗

OXA-24, a novel class D beta-lactamase with carbapenemase activity in an Acinetobacter baumannii clinical strain.

Acinetobacter baumannii RYC 52763/97, a clinical isolate involved in a prolonged nosocomial outbreak at our hospital, was resistant to all beta-lactams tested, including imipenem and meropenem, which had MICs of 128 and 256 microg/ml, respectively. This strain synthesized three beta-lactamases: a plasmid-mediated TEM-1 beta-lactamase (pI 5.4), an AmpC-type chromosomal cephalosporinase (pI 9.4), and a novel, presumptively chromosomally mediated OXA-related enzyme (pI 9.0) named OXA-24. After cloning and sequencing, the deduced amino acid sequence of the OXA-24 beta-lactamase showed 40% homology with the OXA-10 (PSE-2) and OXA-7 beta-lactamases, 39% homology with the OXA-11 and OXA-5 enzymes, and 33% homology with the LCR-1 beta-lactamase. The amino acid sequence of the OXA-24 beta-lactamase contained the STFK motif found in serine beta-lactamases, but the typical class D triad KTG was replaced by KSG and the motif YGN was replaced by FGN. The OXA-24 beta-lactamase hydrolyzed benzylpenicillin and cephaloridine but lacked activity against oxacillin, cloxacillin, and methicillin. The enzymatic activity was inhibited by chloride ions and by tazobactam (50% inhibitory concentration [IC(50)], 0.5 microM), sulbactam (IC(50), 40 microM), and clavulanic acid (IC(50), 50 microM). Carbapenem MICs for an Escherichia coli transformant (pBMB-1) expressing the cloned OXA-24 enzyme had a fourfold increase. Relative V(max)/K(m) values of 13 and 6 were obtained with imipenem and meropenem, respectively, and a positive microbiological assay result with imipenem was obtained with a purified enzymatic extract of this transformant strain. Therefore, we consider this new beta-lactamase to be involved in the carbapenem resistance of A. baumannii RYC 52763/97.

Acinetobacter↗

[Evolution of antimicrobial susceptibility of Acinetobacter baumannii clinical isolates].

Acinetobacter baumannii is a microorganism frequently implicated in colonization and infection in hospitalized patients. An increase of resistance has been observed in recent years making these infections difficult to treat. The in vitro activity of 24 antibiotics, 15 betalactam agents and nine nonbetalactams, was studied in 156 A. baumannii clinical isolates. The strains were collected from different clinical samples obtained from inpatients (92%) and 8% were from outpatients. Evolution of susceptibility from January 1995 to December 1997 was studied. MIC of the following antibiotics was determined by the agar dilution method: ampicillin, ticarcillin, piperacillin, ampicillin-sulbactam, amoxicillin- clavulanic acid, ticarcillin-clavulanic acid, piperacillin-tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, clavulanic acid, sulbactam, tazobactam, amikacin, gentamicin, tobramycin, ofloxacin, doxycycline, fosfomycin, rifampin, azithromycin and colistin. Low antimicrobial susceptibility was observed in most A. baumannii strains. Colistin, imipenem, meropenem and ampicillin-sulbactam showed the greatest susceptibility (100, 88.4, 88.4 and 84.6%, respectively). A. baumannii strains from inpatients showed a lower antimicrobial susceptibility than strains from outpatients, who showed a high percentage of susceptibility to most antibiotics. Rifampin and azithromycin showed certain in vitro activity against the most susceptible A. baumannii strains. A progressive decrease in susceptibility to most antibiotics was observed during the period studied. Carbapenem-resistant A. baumannii emerged in 1996 and increased in 1997.

Acinetobacter↗

Imipenem, doxycycline and amikacin in monotherapy and in combination in Acinetobacter baumannii experimental pneumonia.

Acinetobacter baumannii is a common cause of nosocomial pneumonia and other nosocomial infections. Multiresistant A. baumannii has also a high prevalence, which can make effective treatment difficult. We designed a new model of A. baumannii experimental pneumonia using C57BL/6 immunocompetent mice. This model was used to compare the efficacy of imipenem, doxycycline and amikacin in monotherapy, and the combination of imipenem plus amikacin and doxycycline plus amikacin. Doxycycline plus amikacin were synergic in vitro after 24 h incubation, whereas imipenem plus amikacin showed no in vitro synergy. The number of sterile lungs and the lung clearance of A. baumannii were greater in the group treated with imipenem than in those treated with amikacin or doxycycline in monotherapy (P < 0.05). The combination of imipenem plus amikacin and doxycycline plus amikacin was no more effective than imipenem alone in the clearance of organisms from lungs (2.42 +/- 1.46 cfu/g versus 2.7 +/- 1.5 cfu/g versus 1.23 +/- 1.02 cfu/g). These results suggest that the addition of amikacin does not improve the results obtained by imipenem monotherapy. Doxycycline plus amikacin is an alternative to imipenem in the therapy of A. baumannii pneumonia.

Acinetobacter↗

[Ecological aspects and prophylaxis of Acinetobacter baumannii nosocomial infection].

Acinetobacter Baumannii is an aerobic strit gram negative bacteria cause of epidemic infection in intensive care units this bacteria is isolated from the patient and its environment. The detection of AB infection require the isolation of patients and decontamination of the material despite the virulence of the germ, these measures are necessary due to the rapid extension of epidemic in the absence of adequate means.

Acinetobacter Infections↗

Acinetobacter in Denmark: II. Molecular studies of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex.

The Acinetobacter calcoaceticus-Acinetobacter baumannii complex consists of four closely related "genospecies" or DNA groups: DNA group 1 (A. calcoaceticus), DNA group 2 (A. baumannii), DNA 3, and Tjernberg & Ursing's DNA group 13. Strains in this complex are so similar phenotypically that it is often impossible to identify them to the DNA group level by the use of biochemical tests. Twenty-three Danish clinical strains from 23 patients phenotypically identified to the A. calcoaceticus-A. baumannii complex were studied by ribotyping, plasmid profiling, and DNA/DNA hybridization. Multiple isolates were recovered from four patients. These were identical in each patient as judged by phenotype, ribotype and plasmic profile. Seventeen different ribotypes were observed among the 23 strains, and by using this method 19 out of the 23 strains could be identified to the DNA group level. Five strains were allocated to DNA group 2 (A. baumannii), eight to DNA group 3, and six to DNA group 13. These findings were confirmed by DNA/DNA hybridization. Two of the four unidentified strains were genotypically most closely related to but different from DNA groups 1 and 3. The last two strains were most closely related to DNA group 13. These four strains represent two new DNA groups within the A. calcoaceticus-A. baumannii-complex. One to four plasmids in the size range 2.1 kb- > kb were detected in 13 of the strains. Nine plasmid profiles were seen, indicating the usefulness of this typing method if the strains contain plasmids. The study also indicates that ribotyping is useful both for typing and for identification purposes, and that the genetic relationship in this area are more diverse than hitherto perceived. Taxonomic reconsiderations are warranted.

Acinetobacter↗

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.

Acinetobacter↗

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.

Acinetobacter↗

[Antimicrobial resistance of different Acinetobacter baumannii biotypes isolated in the northern region of Chile].

BACKGROUND: Acinetobacter baumannii nosocomial outbreaks are common and the microorganism is frequently resistant to multiple antimicrobials. There is little information about Acinetobacter baumannii antimicrobial susceptibility in the northern region of Chile. AIM: To identify different Acinetobacter baumannii biotypes isolated from clinical samples and to determine their antimicrobial susceptibility. MATERIAL AND METHODS: One hundred twenty three Acinetobacter baumannii isolates were studied. The identification and typing of Acinetobacter baumannii was based on phenotypic characteristics. Antimicrobial susceptibility was investigated using agar dilution techniques. RESULTS: Most Acinetobacter baumannii strains were isolated from wounds, urinary and respiratory infections. Seven biotypes were isolated, being biotype 9 the most frequent. Imipenem was the antimicrobial with the higher activity against the microorganism. Amikacin, cefoperazonesulbactam, ampicillinsulbactam and ceftazidime had a moderate activity. There were high resistance levels to ampicillin and older cephalosporins. CONCLUSIONS: Acinetobacter baumannii is emerging as a significant nosocomial pathogen in Chile and shows high resistance rates to multiple antibiotics.

Acinetobacter↗

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.

Acinetobacter↗

Challenges in identifying new antimicrobial agents effective for treating infections with Acinetobacter baumannii and Pseudomonas aeruginosa.

Acinetobacter baumannii and Pseudomonas aeruginosa are gram-negative pathogens that target immunocompromised patients. They express a variety of determinants that confer resistance to a broad array of antimicrobial agents. Mechanisms of resistance include impaired entry through the bacterial outer membrane, production of antibiotic-modifying enzymes, active efflux, and target mutations that reduce antimicrobial affinity. It has been a challenge to identify new agents that have activity against the more resistant variants of these species. Doripenem is a carbapenem in phase 3 trials that has excellent activity against P. aeruginosa and A. baumannii. However, it lacks activity against strains that express resistance to the currently available carbapenems. Tigecycline is a newly licensed glycylcycline that lacks activity against P. aeruginosa but has encouraging activity against many A. baumannii isolates. Resistance to tigecycline can emerge during therapy, however, and is due to expression of multidrug efflux pumps.

Acinetobacter Infections↗

Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii.

Multidrug-resistant Acinetobacter baumannii has emerged as a significant clinical problem worldwide and colistin is being used increasingly as "salvage" therapy. MICs of colistin against A. baumannii indicate its significant activity. However, resistance to colistin in A. baumannii has been reported recently. Clonotypes of 16 clinical A. baumannii isolates and ATCC 19606 were determined by pulsed-field gel electrophoresis (PFGE), and colistin MICs were measured. The time-kill kinetics of colistin against A. baumannii ATCC 19606 and clinical isolate 6 were investigated, and population analysis profiles (PAPs) were conducted. Resistance development was investigated by serial passaging with or without exposure to colistin. Five different PFGE banding patterns were found in the clinical isolates. MICs of colistin against all isolates were within 0.25 to 2 microg/ml. Colistin showed early concentration-dependent killing, but bacterial regrowth was observed at 24 h. PAPs revealed that heteroresistance to colistin occurred in 15 of the 16 clinical isolates. Subpopulations (<0.1% from inocula of 10(8) to 10(9) CFU/ml) of ATCC 19606, and most clinical isolates grew in the presence of colistin 3 to 10 microg/ml. Four successive passages of ATCC 19606 in broth containing colistin (up to 200 microg/ml) substantially increased the proportion of the resistant subpopulations able to grow in the presence of colistin at 10 microg/ml from 0.000023 to 100%; even after 16 passages in colistin-free broth, the proportion only decreased to 2.1%. This represents the first demonstration of heterogeneous colistin-resistant A. baumannii in "colistin-susceptible" clinical isolates. Our findings give a strong warning that colistin-resistant A. baumannii may be observed more frequently due to potential suboptimal dosage regimens recommended in the product information of some products of colistin methanesulfonate.

Acinetobacter Infections↗

Analysis of prognostic factors in 95 patients with Acinetobacter baumannii bacteremia.

BACKGROUND: Because Acinetobacter baumannii bacteremia is a global problem, we were motivated to characterize this disease in Taiwan. PATIENTS AND METHODS: We analyzed findings in 95 patients with documented A. baumannii bacteremia between January 1, 1998 and December 31, 2000 (47 men, 48 women; mean age 58.8 years). RESULTS: The mean length of stay in the hospital was 44.0 days. Clinically, 76 patients had fever and 35 patients developed shock. Fifty patients had respiratory tract infections; 24, urinary tract infections; 11, intra-abdominal infections; three, CNS infections; and two, catheter-related infections. Five patients had primary bacteremia. Empirical antibiotic therapy was initiated at the onset of the clinical signs of infection. Antimicrobial susceptibility test results were variable. 47 patients died and 48 survived; the mortality rate for A. baumannii bacteremia was 45.3% (43/95). CONCLUSION: Physicians should pay attention to this infection because the early identification of high-risk patients could facilitate prophylaxis and potentially reduce associated problems.

Acinetobacter Infections↗

Detection and analysis of iron uptake components expressed by Acinetobacter baumannii clinical isolates.

The Acinetobacter baumannii 19606 prototype strain produces a 78-kDa iron-regulated outer membrane protein immunologically related to FatA, which is required for iron acquisition by the fish pathogen Vibrio anguillarum via the anguibactin-mediated system. This A. baumannii strain also secretes histamine, a biosynthetic precursor of the siderophore anguibactin. In contrast, the A. baumannii 8399 clinical strain isolated in Oregon produces a siderophore and a putative 73-kDa iron-regulated outer membrane (OM73) receptor that are different from those produced by V. anguillarum and A. baumannii 19606. These observations suggest that different A. baumannii clinical isolates express unrelated iron uptake systems. This hypothesis is supported by differences in outer membrane protein profiles among A. baumannii isolates obtained from Oregon and Europe. The 19606 isolate and some European isolates expressed a FatA-like protein, while neither 19606 nor any of the European isolates expressed proteins related to OM73. Some European isolates failed to express FatA- and OM73-like proteins. All but one of the Oregon isolates expressed OM73-like proteins, while none of them contained a FatA-like protein. The presence of these proteins always correlated with the presence of the om73- and fatA-like genes in the cognate strains. While 19606 and a few European isolates produced histamine, none of the Oregon isolates had this capability. Interestingly, one strain each from the Oregon and European isolates did not express any of these products involved in iron acquisition, indicating that they could acquire iron through siderophore-mediated transport systems different from those expressed by the 19606 and 8399 clinical isolates.

Acinetobacter baumannii↗

Nosocomial infections due to Acinetobacter baumannii in a neurosurgery ICU.

Invasive infections caused by Acinetobacter baumannii in a post-operative neurosurgery ICU were studied. Sixty one patients admitted during a span of 11 months were culture positive for acinetobacter species from blood and/or CSF samples. They were followed up prospectively for evidence of infection and clinical outcome. 40 cases had clinical evidence of infection due to acinetobacter species while in 21 patients, the isolation of the organism was considered a contaminant. Acinetobacter baumannii was the most common organism associated with invasive infections. Respiratory tract was found to be the most common primary source of infection in patients with bacteraemia or meningitis. The age, sex and pre-operative hospital stay were not significantly different in the two groups (p>0.05), while post-operative hospital stay and mortality was significantly higher in patients with invasive infection (p<0.05). Acinetobacter baumannii was isolated from multiple sites (p<0.05) and repeatedly from the same site (p<0.001) in a significantly higher number of patients with invasive infections. Mortality was high in the patients infected with Acinetobacter baumannii. Even amongst the infected group, the patient shaving meningitis showed a higher mortality as compared to the patients having bacteraemia.

Acinetobacter↗