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Pharmacodynamic comparisons of antimicrobials against nosocomial isolates of escherichia coli, klebsiella pneumoniae, acinetobacter baumannii and pseudomonas aeruginosa from the MYSTIC surveillance program: the OPTAMA Program, South America 2002.

The OPTAMA (Optimizing Pharmacodynamic Target Attainment using the MYSTIC [Meropenem Yearly Susceptibility Test Information Collection] Antibiogram) Program provides insight into the appropriate antibiotic options for empiric therapy for common nosocomial pathogens. In this report, South America is represented by Brazil, Colombia, Peru, and Venezuela. A 5000-subject Monte Carlo Simulation estimated pharmacodynamic target attainment for meropenem, imipenem, ceftazidime, cefepime, piperacillin/tazobactam, and ciprofloxacin against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Pharmacokinetic parameter variability was derived from existing healthy volunteer data, and minimum inhibitory concentration (MIC) data came from the 2002 MYSTIC program. Piperacillin/tazobactam and ciprofloxacin displayed the lowest target attainment against all bacterial species (14% to 24% for A. baumannii, 26% to 37% for P. aeruginosa, and 48% to 66% for the Enterobacteriaceae). Overall, the carbapenems had the highest probabilities of attainment against the Enterobacteriaceae (98% to 100%) and A. baumannii (73% to 74%), whereas cefepime obtained the greatest target attainment against P. aeruginosa (65%). Because no single regimen had high target attainment against A. baumannii and P. aeruginosa, the use of combination therapy to treat these pathogens in South America may be justified. Because of the lack of agreement with percent susceptibility for certain antimicrobial regimens, the use of pharmacodynamic target attainment may be a more accurate predictor of microbiologic success.

Acinetobacter baumannii↗

Determination of epidemic clonality among multidrug-resistant strains of Acinetobacter spp. and Pseudomonas aeruginosa in the MYSTIC Programme (USA, 1999-2003).

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme was initiated in 1997 (1999 for the United States). This program monitors resistance in participant medical centers where carbapenems are prescribed and drug use data can be obtained. An earlier report found antimicrobial use was not a clear cause of local or aggregate changes in resistance rates. This study addresses the role of dissemination of resistant clones on susceptibility rates for nonfermentors, Acinetobacter spp. (ACB) and Pseudomonas aeruginosa (PSA). Carbapenem (CARB)-multidrug-resistant strains (MDR) from among 236 ACB and 1,111 PSA were tested by reference broth microdilution methods, automated ribotyping, and pulsed field gel electrophoresis to determine possible clonal dissemination. Each strain was also tested for metallo-beta-lactamases (MbetaL) (phenotypic and polymerase chain reaction); and then analyzed by CARB-R rate and defined daily dose (DDD)/100 days use groupings (high, moderate, and low). For the aggregate 15 sites in the MYSTIC Programme each year, the CARB-resistant rate decreased over 5 years; but other drug-resistance rates generally escalated. Changes were not related to antimicrobial use calculations. The discovered clonally spread MDR-PSA strains were more frequent in high- (1.8 clones/site) and moderate-resistance (0.6 clones/site) rate centers (21.7% to 29.5% were clonal), compared with unique strains in low-resistance hospitals. ACB clonality was extreme in one geographic area, with dissemination of 5 different clones (931.7/B, C, or D; 1090.2/A; 167.5/A) in 4 centers (02, 04, 06, and 18). Resistance rates in ACB and PSA were clearly related to clonal occurrence and spread, and one MbetaL (VIM-7) was detected. Decreased CARB resistance rates from 1999 through 2002 were directly attributed to the disappearance of resistance clones in some locations. In conclusion, ACB and PSA CARB and MDR resistance rates in MYSTIC Programme institutions have been greatly influenced by clonal dissemination and less by antimicrobial use patterns. The most serious examples of resistance were the clonality observed among ACB in New York City and the documented endemic nature of VIM-7-producing PSA (0.09% of all PSA isolates). Meropenem remained the most active antimicrobial agent tested in the program, and surveillance networks must implement epidemiologic typing to accurately assess the role of clonal spread on the study results.

Acinetobacter↗

In vitro synergy test of meropenem and sulbactam against clinical isolates of Acinetobacter baumannii.

Meropenem and imipenem are often the drugs of choice for the treatment of infections due to multidrug-resistant Acinetobacter baumannii. The present study aimed at evaluating the interaction between meropenem and sulbactam through microdilution and checkerboard methods against 48 clinical isolates of A. baumannii collected from Brazilian hospitals. All the isolates presented elevated minimum inhibitory concentration (>or=2 microg/mL) to either meropenem or sulbactam. The checkerboard method with the combination of meropenem and sulbactam demonstrated 29.2% (14/48) synergism, 47.9% (23/48) partial synergism, 10.5% (5/48) additive, 6.2% (3/48) indifference, and 6.2% (3/48) antagonism (SigmaFIC(min)=0.09 and SigmaFIC(max)=8). Thus, combinations of meropenem and sulbactam may show synergism or partial synergism for most A. baumannii isolates. Further studies may help identify treatment options for patients with infections caused by these organisms, particularly with this combination, where both drugs have time-dependent activities and might be suitable for therapy optimization studies.

Acinetobacter baumannii↗

Dissemination of 16S rRNA methylase-mediated highly amikacin-resistant isolates of Klebsiella pneumoniae and Acinetobacter baumannii in Korea.

Novel 16S rRNA methylase-mediated high-level resistance to amikacin and arbekacin has been reported recently in clinical isolates of Gram-negative bacilli only from several countries. We tested amikacin- or arbekacin-nonsusceptible Gram-negative bacilli isolated in 2003 and 2005 at a tertiary-care hospital in Korea by polymerase chain reaction to detect 16S rRNA methylase genes. armA alleles were detected in 14 isolates of Klebsiella pneumoniae, 10 other species of Enterobacteriaceae, and 16 Acinetobacter baumannii, whereas the rmtB allele was detected in 1 K. pneumoniae isolate. The resistance 1st detected in 2003 persisted in 2005. 16S rRNA methylase-producing isolates were highly resistant to arbekacin and amikacin, and were mostly coresistant to levofloxacin. Most K. pneumoniae isolates also produced extended-spectrum beta-lactamases and plasmid-mediated AmpC beta-lactamases, and most A. baumannii isolates were nonsusceptible to carbapenems.

Acinetobacter baumannii↗

In vitro postantibiotic effect of colistin on multidrug-resistant Acinetobacter baumannii.

Infections by multidrug-resistant Acinetobacter baumannii constitute an increasing threat for critically ill patients. Colistin is often the only antimicrobial retaining activity against these strains. The postantibiotic effect (PAE) of colistin was studied on 19 isolates of A. baumannii resistant to ampicillin/sulbactam, ciprofloxacin, and carbapenems with the viable count method. The mean PAEs of 1x MIC and 4x MIC concentrations of colistin on the tested isolates were 3.90 and 4.48 h, respectively, indicating that a modified dosage scheme with increased dosing intervals might retain activity whereas minimizing the incidence of adverse effects.

Acinetobacter baumannii↗

Molecular epidemiology and genomic characteristics of clinical Acinetobacter baumannii isolates from patients with hospital-acquired pneumonia in China, 2019-2020: a multicentre retrospective study.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a leading cause of hospital-acquired pneumonia (HAP) with high mortality. However, large-scale nationwide data of HAP-causing CRAB in China remain limited. METHODS: Here, we performed a nationwide multicentre retrospective study to characterise the molecular epidemiology and genomic features of 802 A. baumannii isolates from patients with HAP across 33 tertiary hospitals in China during 2019-2020. Antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS), phylogenetic and comparative genomic analysis were used to investigate molecular epidemiology of HAP-causing CRAB strain. Clinical comparative analyses were carried out on data from 500 patients with HAP stratified by distinct antimicrobial susceptibility and genomic profiles, and a Galleria mellonella infection model was utilised for in vivo virulence assessment. FINDINGS: The overall carbapenem resistance rate of A. baumannii was 82.0% (658/802), with marked regional variations. CRAB exhibited high resistance to conventional agents but remained largely susceptible to polymyxin, tigecycline, cefiderocol and sulbactam-durlobactam. Among enrolled patients, CRAB infection was linked to substantially higher mortality (39.0% vs. 17.5%), and multivariate analysis confirmed ICU admission and advanced age as independent risk factors for patients with CRAB infection. Molecular typing revealed STPas2 (96.2%) as the absolutely predominant type; STOxf208, STOxf195, STOxf540, and STOxf369 were the most prevalent Oxford sequence types with obvious geographic stratification and divergent comorbidity profiles among corresponding patients. A total of 654 CRAB isolates harboured carbapenemase genes, with blaOXA-23 dominating at 98.8%. Genomic analysis revealed lineage-specific features: STOxf208 carried more virulence genes, while STOxf540 harboured a broader antimicrobial resistance genes (ARGs). The STOxf208 clone mainly belonged to KL2 (62.1%) and KL7 (36.8%) serotypes, with KL2 strains possessing richer ARGs and virulence factors, and in vivo virulence assays further validated that KL2 strains possessed higher pathogenicity than KL7 strains. INTERPRETATION: This study demonstrates the extremely high prevalence and clonal dominance of CRAB in Chinese patients with HAP, providing critical evidence for clinical treatment, antimicrobial stewardship, and targeted infection control. FUNDING: National Key Research and Development Program of China (2024YFE0106200), National Natural Science Foundation of China (U22A20338, 82502763, W2621007), Zhejiang Provincial Natural Science Foundation of China (LQN25H190006), Zhejiang Provincial Postdoctoral Science Foundation (ZJ2025058).

Acinetobacter baumannii↗

Effect of surfactants on stability of Acinetobacter johnsonii S35 and Oligotropha carboxidovorans S23 coaggregates.

The effect of anionic (sodium dodecyl sulphate or SDS) and cationic (cetyltrimethylammonium bromide or CTAB) surfactants on the stability of binary bacterial coaggregates comprising Acinetobacter johnsonii S35 and Oligotropha carboxidovorans S23 (both sewage sludge isolates) was studied and compared with that on the complex sewage sludge flocs. Both SDS and CTAB enhanced the bacterial coaggregation at their lower concentrations of 0.2 and 0.07 mg ml(-1), respectively. However, complete deflocculation of coaggregates was observed at 1 mg ml(-1) SDS and 0.3 mg l(-1) CTAB concentrations. Further, sewage sludge flocs did not deflocculate in the presence of CTAB, although a concentration-dependent deflocculation was observed in the presence of SDS. A. johnsonii S35 and O. carboxidovorans S23 cells were separately pretreated (prior to coaggregation) with the surfactants. In spite of the partial (complete) loss of viability during SDS (CTAB) pretreatment, washed cells still retained hydrophobic character and displayed significant coaggregation (aggregation index ranging from 84% to 97% in comparison to 96% in the case of non-treated cells), demonstrating reversibility of the surfactant induced deflocculation. Further, when exposed to lower concentration of surfactants (0.2 mg ml(-1) SDS), coaggregates were more resistant (76% viability) as compared to the individual partner (S35: 52%; S23: 39% viability). Since the coaggregates are stable and provide protection from surfactants at lower concentrations (those normally expected in the sewage treatment plants), their presence as well as a sustained role in the sewage sludge bioflocculation is evident.

Acinetobacter↗

Crude oil degradation efficiency of a recombinant Acinetobacter baumannii strain and its survival in crude oil-contaminated soil microcosm.

A hydrocarbon degrading Acinetobacter baumannii S30 strain, isolated from crude oil-contaminated soil, was inserted with the lux gene from the luciferase gene cassette luxCDABE. Soil microcosms were designed to study the degradation efficacy for total petroleum hydrocarbon (TPH) of crude oil by lux-tagged A. baumannii S30 pJES. Bioaugmentation of a TPH-contaminated microcosm with A baumannii S30 pJES showed that TPH levels were reduced from 89.3 to 53.9 g/kg soil in 90 days. Biodegradation of TPH by A baumannii S30 pJES was also monitored in shake flask conditions, which showed a reduction of initial TPH levels by over 50% at the end of 120 h. A lux-PCR-based approach along with the standard dilution plating with selective antibiotics was successfully utilized to monitor the survivability of the lux-tagged strain A. baumannii S30 pJES in soil microcosms and stability of the lux insert in the host strain A. baumannii S30. The selective plating technique indicated the population of A. baumannii S30 pJES to be 6.5+/-0.13 x 10(8) CFU/g at day zero (just after bioaugmentation) and 2.09+/-0.08 x 10(8) CFU/g of soil after 90 days of incubation. lux-PCR confirmed the stability of the insert in all the randomly selected colonies of A. baumannii strains from the antibiotic plates. The lux insert was stable after 50 generations in Luria Bertini broth and storage at -70 degrees C as glycerol stocks for over a year. These results revealed that the lux insert was stable and lux-tagged A. baumannii S30 strain could survive in a TPH-contaminated soil microcosm and could degrade TPH in the soil microcosm conditions. It can be used as an effective marker to monitor the survival of augmented strains at a bioremediation site.

Acinetobacter baumannii↗

Integron-associated imipenem resistance in Acinetobacter baumannii isolated from a regional hospital in Taiwan.

We investigated the genetic properties of imipenem-resistant Acinetobacter baumannii collected from a regional hospital in Taiwan. Pulsed-field gel electrophoresis demonstrated that the isolates were genetically diverse. Polymerase chain reaction, DNA sequencing, and DNA-DNA hybridisation showed that the bla(IMP-1) gene resided as a cassette in a plasmid-borne class 1 integron in two isolates. The majority of the resistant isolates were plasmid-less and carried no bla(IMP), bla(VIM) or bla(CFI) genes, indicating that other uncharacterised metallo-beta-lactamases or mechanisms other than enzyme production are involved in carbapenem resistance in this group of A. baumannii. We conclude that multidrug resistance of A. baumannii was a combined effect of lateral gene transfer and clonal spread of multiple resistant clones. Strict measures should be implemented to control the further spread of resistance.

Acinetobacter baumannii↗

Impact of Acinetobacter infection on the mortality of burn patients.

BACKGROUND: Acinetobacter calcoaceticus-baumannii complex (Acb) is recognized as an important cause of nosocomial infections. Although Acb can be associated with multidrug resistance, its impact on mortality in burn patients has not been fully elucidated. STUDY DESIGN: In a retrospective cohort study assessing medical records and microbiology laboratory data at a US military tertiary care burn center, we evaluated all patients admitted to the burn center between January 2003 and November 2005. Data collected included age, severity of burn, comorbidities, length of stay, and survival to hospital discharge. In addition, microbiology data were reviewed to determine which patients were infected with Acb during this time frame. These data were then used to compare patients infected with Acb to patients not infected. Multivariate analysis using logistic regression was performed to determine which patient characteristics were associated with increased mortality. RESULTS: There were 802 patients included in the study. Fifty-nine patients met the case definition for infection. An additional 52 patients were found to be colonized with Acb. Patients with Acb infection had more severe burns and comorbidities, and had longer lengths of stay compared with patients without Acb or those with Acb colonization. Mortality in infected patients was higher compared with those without infection (relative risk = 2.86, p = 0.001). On multivariate analysis, infection with Acb was not statistically associated with mortality. CONCLUSIONS: Multidrug-resistant Acb is a common cause of nosocomial infection in the burn patient population. Despite this, it does not independently affect mortality.

Acinetobacter Infections↗

Diketone cleaving enzyme Dke1 production by Acinetobacter johnsonii--optimization of fermentation conditions.

The main objective of this work was the optimization of the production of the novel dioxygenase diketone cleaving enzyme (Dke1) from Acinetobacter johnsonii. Acetylacetone was used as an inducer for enzyme production. In the first step, the growth medium was optimized by using screening designs for finding the optimal carbon and nitrogen source. In the second step, a genetic algorithm was used to optimize the concentrations of all medium components. After six generations the stopping criterion was reached and a growth medium was obtained which produced sixteen times more enzyme than the starting medium. In the next step, an addition profile for the inducer acetylacetone was developed to further increase enzyme production by using a genetic algorithm. In this case, after four generations the stopping criterion was fulfilled. By using the obtained optimal addition profile Dke1 activity was enhanced from 826 to 2584Ul(-1). In comparison to the starting conditions activity could even be increased by a factor of 50.

Acinetobacter↗

Mechanisms of cefiderocol resistance in carbapenem-resistant Acinetobacter baumannii: a Swiss 2023-2025 collection.

OBJECTIVES: The numbers of infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are increasing globally and present a significant burden on healthcare systems. This study describes the CRAB isolates received at the Swiss National Reference Centre for Emerging Antibiotic Resistance (NARA) over a 3-year period, from January 2022 to December 2025, and aimed to characterize the prevalence and mechanisms of FDC resistance. METHODS: Two-hundred and thirty-four non-duplicate CRAB isolates were submitted to NARA over the study period from hospitals and laboratories across Switzerland. Susceptibility testing was performed by disk diffusion and broth microdilution, according to EUCAST methodology. Whole-genome sequencing was performed on 11 isolates. ADC alleles were cloned into vector pVRL1 and transformed into Escherichia coli Top10. RESULTS: All isolates exhibited resistance to the carbapenems, and most were resistant to cephalosporins. Most isolates harboured an acquired class D carbapenemase, most frequently OXA-23 (181/234; 77.4%). One quarter of isolates were resistant to cefiderocol (FDC), exhibiting MICs ranging from 4->32 mg/L. Whole genome sequencing analyses, performed on 11 FDC-resistant isolates, identified that FDC resistance was due a combination of mechanisms including NDM and PER-production, mutations within the iron transporters, piuA and pirA, and the overexpression of ADC variants. CONCLUSIONS: This study showed that OXA-23 was the dominant mechanism of carbapenem-resistance in CRAB in Switzerland. Almost one quarter of CRAB isolates were resistant to "last resort" antimicrobial, FDC. The mechanisms of FDC resistance identified in this study emphasise that resistance to this antimicrobial is often complex and multifactorial, requiring high-resolution methods, including WGS, to identify.

Acinetobacter baumannii↗

Hexavalent chromium reduction by Acinetobacter haemolyticus isolated from heavy-metal contaminated wastewater.

Possible application of a locally isolated environmental isolate, Acinetobacter haemolyticus to remediate Cr(VI) contamination in water system was demonstrated. Cr(VI) reduction by A. haemolyticus seems to favour the lower concentrations (10-30 mg/L). However, incomplete Cr(VI) reduction occurred at 70-100 mg/L Cr(VI). Initial specific reduction rate increased with Cr(VI) concentrations. Cr(VI) reduction was not affected by 1 or 10 mM sodium azide (metabolic inhibitor), 10 mM of PO(4)3-, SO4(2-), SO(3)2-, NO3- or 30 mg/L of Pb(II), Zn(II), Cd(II) ions. However, heat treatment caused significant dropped in Cr(VI) reduction to less than 20% only. A. haemolyticus cells loses its shape and size after exposure to 10 and 50 mg Cr(VI)/L as revealed from TEM examination. The presence of electron-dense particles in the cytoplasmic region of the bacteria suggested deposition of chromium in the cells.

Acinetobacter↗

DNA microarray-based detection of nosocomial pathogenic Pseudomonas aeruginosa and Acinetobacter baumannii.

Infection by nosocomial pathogenic bacteria is increasingly becoming a major threat to the patients in the hospital. We have developed a diagnostic DNA microarray for the detection of two important nosocomial pathogens, Pseudomonas aeruginosa and Acinetobacter baumannii. The diagnostic DNA microarray contains the species-specific probes of 15mer oligonucleotides designed based on the sequences of 23S ribosomal DNA. The performance of DNA microarray in diagnosing P. aeruginosa and A. baumannii was evaluated using reference bacteria as well as clinical specimens such as blood, stool, pus, sputum, urine and cerebrospinal fluid. Using this DNA microarray, A. baumannii could be successfully detected in 11 out of 13 clinical specimens, thus giving the sensitivity of 84.6% with the specificity of 100% and the positive predictive value of 100%. P. aeruginosa could also be detected in 25 out of 26 clinical specimens, showing the sensitivity of 96.2%, the specificity of 100%, and the positive predictive value of 100%. These results suggest that two nosocomial pathogens, P. aeruginosa and A. baumannii, can be efficiently diagnosed by using the DNA microarray developed in this study.

Acinetobacter baumannii↗

Proteomic analysis of Acinetobacter lwoffii K24 by 2-D gel electrophoresis and electrospray ionization quadrupole-time of flight mass spectrometry.

The MS/MS analysis by Electrospray ionization quadrupole-time of flight mass spectrometry (ESI-Q-TOF MS) was applied to identify proteins in proteome analysis of bacteria whose genomes are not known. The protein identification by ESI-Q-TOF MS was performed sequentially by database search and then de novo sequencing using MS/MS spectra. Soil bacteria having unanalyzed genome, Acinetobacter lwoffii K24 is an aniline degrading bacterium. In this report, we present the results of a comparison between the proteome profile of A. lwoffii K24 cultured in aniline- or succinate-containing media. Protein analysis was performed using two-dimensional gel electrophoresis (2-DE) with pH 3-10 immobilized pH gradient (IPG) strips followed by ESI-Q-TOF MS. More than 780 protein spots were detected by 2-DE from the soluble proteome. Forty-eight of these proteins were expressed exclusively in aniline cultured bacteria, and 81 proteins increased and 162 proteins decreased in aniline-cultured versus succinate cultured A. lwoffii K24. Internal amino acid sequences of 43 major protein spots were successfully determined by ESI-Q-TOF MS to try to identify the bacterial proteins responding to aniline culture condition. Since the A. lwoffii K24 genome is not yet sequenced, many proteins were found to be hypothetical. Comparative proteome analysis of the insoluble protein fractions showed that one novel protein that was strongly induced by succinate-cultured A. lwoffii K24 was repressed under aniline culture conditions. These results suggest that comprehensive analysis of bacterial proteomes by 2-DE and amino acid sequence analysis by ESI-Q-TOF MS is useful for understanding induced novel proteins of biodegrading bacteria.

Acinetobacter↗

Comparative activities of cecropin A, melittin, and cecropin A-melittin peptide CA(1-7)M(2-9)NH2 against multidrug-resistant nosocomial isolates of Acinetobacter baumannii.

The in vitro activity of three polycationic peptides, cecropin A, melittin, and cecropin A-melittin hybrid peptide CA(1-7)M(2-9)NH2, alone and in combination with various clinically used antimicrobial agents, was investigated against 32 nosocomial isolates of Acinetobacter baumannii. Antimicrobial activities were measured by MIC, MBC and bacterial killing assay. The peptides demonstrated different ranges of inhibitory values: overall, the organisms were more susceptible to CA(1-7)M(2-9)NH2 (MIC range, 0.25-16 mg/l) than to cecropin A (0.50-32 mg/l) and melittin (0.50-32 mg/l). Synergy was observed when CA(1-7)M(2-9)NH2 and melittin were combined with beta-lactam antibiotics.

Acinetobacter↗

Multidrug-resistant genes are associated with an 86-kb island in Acinetobacter baumannii.

A strain of multidrug-resistant Acinetobacter baumannii that caused a 26% mortality rate in a French epidemic was characterized and compared with an antibiotic-susceptible strain of A. baumannii. The multiresistant strain carries many of its antibiotic-resistance genes on an 86-kb region, whereas the susceptible strain lacks these genes in a homologous region. Characterization of this multidrug-resistant A. baumannii strain highlights the limited options for current therapy and raises concerns for future treatment options in an era in which few novel antibiotics are being developed.

Acinetobacter baumannii↗

Antibodies to prion and Acinetobacter peptide sequences in bovine spongiform encephalopathy.

An amino acid sequence homology has been identified between the bovine prion sequence (RPVDQ) and the Acinetobacter calcoaceticus enzyme, uridine-diphosphate-N-acetyl glucosamine-1-carboxy-vinyl-transferase which also contains (RPVDQ). Class-specific IgA, IgG and IgM antibodies against synthetic peptides containing the structurally related sequences present in bovine prion and A. calcoaceticus were measured in 189 bovine spongiform encephalopathy (BSE) positive cattle, 127 BSE negative cattle and 87 healthy control animals using an ELISA technique. Class-specific IgA, IgG and IgM antibodies against the structurally related synthetic peptides were significantly elevated in BSE positive cattle when compared to BSE negative cattle (P < 0.001) and healthy control animals (P < 0.001). These autoantibodies may have a role in the pathogenesis of BSE.

Acinetobacter calcoaceticus↗