Cepacia Species Research Articles

2761. Activity of Cefiderocol and Comparator Agents Against Achromobacter and Burkholderia Isolates, Collected During 2020-2022 as Part of SENTRY Antimicrobial Surveillance Program

Abstract Background Achromobacter and Burkholderia species are opportunistic pathogens in individuals with an immunodeficiency, most notably cystic fibrosis. Cefiderocol (CFDC) is a siderophore-conjugated cephalosporin with broad activity against Gram-negative bacteria. In this study, the activity of CFDC and comparator agents was determined against isolates of Achromobacter and Burkholderia cepacia species complex, collected in 2020–2022 in Europe and the USA as part of the SENTRY antimicrobial surveillance program. Activity of cefiderocol and comparator agents against Achromobacter and Burkholderia Isolates Methods Minimum inhibitory concentrations (MICs) were determined according to CLSI guidelines against 167 Achromobacter and 160 Burkholderia cepacia species complex isolates, using broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparator agents and iron-depleted CAMHB for CFDC. Comparator agents included β-lactam/β-lactamase inhibitor combinations ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, meropenem-vaborbactam, piperacillin-tazobactam, as well as meropenem, ceftazidime, levofloxacin, amikacin, trimethoprim-sulfamethoxazole, and minocycline. Susceptibility was assessed for agents with CLSI breakpoints. For agents without established CLSI breakpoints, only MIC50, MIC90 and MIC ranges were reported. Results CFDC was the most potent agent tested against Achromobacter, showing MIC50 and MIC90 values of 0.03 and 0.25 µg/mL and all isolates were inhibited at ≤4 µg/mL (Table). Isolates from cystic fibrosis patients (n=15) showed higher MIC50 and MIC90 values for most agents, but CFDC MIC50 and MIC90 values remained low (0.06 and 0.25 µg/mL, respectively). Against Burkholderia cepacia species complex, CFDC was the most potent agent tested, with MIC50 and MIC90 values of 0.06 and 0.5 µg/mL, and 156 out of 160 isolates inhibited at ≤4 µg/mL. None of the comparator agents showed >90% susceptibility against these isolates (Table). Conclusion CFDC showed potent activity against a set of contemporary clinical Achromobacter and Burkholderia cepacia species complex isolates. These in vitro data suggest that CFDC could be an important treatment option for infections caused by these opportunistic pathogens. Disclosures Boudewijn L. DeJonge, PhD, Shionogi Inc.: Employee Sean T. Nguyen, PharmD, Shionogi: Employee|Shionogi, Inc: Employee Jason J. Bryowsky, PharmD, MS, Shionogi Inc.: Employee Christopher M. Longshaw, PhD, Shionogi BV: Employee Joshua Maher, PhD, AbbVie: Grant/Research Support|Affinity Biosensors: Grant/Research Support|AimMax Therapeutics, Inc: Grant/Research Support|Alterity Therapeutics: Grant/Research Support|Amicrobe, Inc: Grant/Research Support|Arietis Pharma: Grant/Research Support|Armata Pharmaceuticals, Inc: Grant/Research Support|Astrellas Pharma, Inc.: Grant/Research Support|Basilea Pharmaceutica AG: Grant/Research Support|Becton Dickinson And Company: Grant/Research Support|bioMerieux, Inc: Grant/Research Support|Boost Biomes: Grant/Research Support|Diamond V: Grant/Research Support|Fedora Pharmaceuticals, Inc: Grant/Research Support|Iterum Therapeutics plc: Grant/Research Support|Johnson & Johnson: Grant/Research Support|Kaleido Biosciences, Inc.: Grant/Research Support|Meiji Seika Pharma Co. Ltd.: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer Inc.: Grant/Research Support|Roche Holding AG: Grant/Research Support|Shionogi Inc.: Grant/Research Support|Summmit Therapeutics, Inc.: Grant/Research Support|Zoetis Inc: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Miki Takemura, n/a, Shionogi & Co., Ltd.: Stocks/Bonds Yoshinori Yamano, PhD, Shionogi HQ: Employee

1620. Minocycline Activity Against Unusual Clinically Significant Gram-Negative Pathogens

BackgroundUnusual non-glucose fermenting Gram-negative (NFGN) pathogens, including Burkholderia cepacia species complex, Achromobacter spp, Alcaligenes spp, Aeromonas spp, and other genera, can cause serious hospital-acquired infections in immunocompromised patients. Some genera are inherently resistant to common drug classes and can acquire other resistance mechanisms, making them difficult to treat. In this study, we analyzed the susceptibility of NFGN isolates to minocycline (MIN). Isolates were collected as part of the SENTRY Antimicrobial Surveillance Program from 2014-2019.MethodsFrom 2014-2019, unusual NFGN isolates were collected from hospitalized patients in 102 hospitals in 35 countries on 4 continents. Hospitals submitted 1 isolate per patient per infection episode that met local criteria for being the likely causative pathogen. Identification was performed by the submitting laboratory and confirmed by JMI Laboratories with matrix-assisted laser desorption ionization-time of flight mass spectrometry or other molecular methods as required. Isolates were tested for MIN susceptibility using the CLSI broth microdilution method at JMI Laboratories. All infection types were included in the susceptibility analysis.ResultsThe most common infection from which the NFGN were isolated was pneumonia. The top 5 NFGN species were Achromobacter xylosoxidans (n=202), Burkholderia cepacia species complex (n=199), unspeciated Achromobacter (n=190), Aeromonas spp (n=127), including Aeromonas hydrophila (n=35), Chryseobacterium spp (n=59), and Alcaligenes faecalis (n=42). The % susceptible and MIC50/90 values of MIN for these species are shown in the table.ConclusionMIN had > 85% susceptible for the most frequently isolated unusual NFGN, including 92% susceptible for Achromobacter spp. and 85.9% for B. cepacia. These data suggest that MIN remains a useful treatment option for infections caused by unusual NFGN.Activities of MIN when tested against NFGN isolates DisclosuresS. J. Ryan Arends, PhD, Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)

Minocycline activity tested against Acinetobacter baumannii complex, Stenotrophomonas maltophilia, and Burkholderia cepacia species complex isolates from a global surveillance program (2013)

Clinical isolates of Acinetobacter baumannii complex (1312), Stenotrophomonas maltophilia (464), and Burkholderia cepacia species complex (30) were selected from medical centers in the United States (USA), Europe and the Mediterranean (EU-M) region, Latin America, and Asia Pacific. Only one isolate per infected patient episode was included and local identifications were confirmed by the monitoring laboratory. Susceptibility testing was performed at the monitoring laboratory using the reference broth microdilution method as described by Clinical and Laboratory Standards Institute (CLSI). A. baumannii complex were classified as MDR (multi-drug resistant [MDR]; nonsusceptible to ≥1 agent in ≥3 antimicrobial classes) and extensively drug-resistant (XDR; nonsusceptible to ≥1 agent in all but ≤2 antimicrobial classes). A total of 81.6% of A. baumannii complex were MDR. Colistin was the most active agent against MDR A. baumannii complex. Minocycline was the most active “tetracycline” against these organisms based on susceptibility. Against B. cepacia, trimethoprim-sulfamethoxazole (MIC90, 2 μg/mL; 100.0% susceptible) was the most active agent tested. Overall, minocycline was the most active tetracycline tested against A. baumannii complex and S. maltophilia isolates collected from patients throughout EU-M, USA, Latin America, and the Asia-Pacific. Minocycline, particularly the intravenous formulation, has activity against several ESKAPE pathogens and merits consideration in seriously ill patients where treatment options may be limited due to the presence of MDR bacteria.

Genome survey sequencing of the wine spoilage yeast Dekkera (Brettanomyces) bruxellensis.

The hemiascomycete yeast Dekkera bruxellensis, also known as Brettanomyces bruxellensis, is a major cause of wine spoilage worldwide. Wines infected with D. bruxellensis develop distinctive, unpleasant aromas due to volatile phenols produced by this species, which is highly ethanol tolerant and facultatively anaerobic. Despite its importance, however, D. bruxellensis has been poorly genetically characterized until now. We performed genome survey sequencing of a wine strain of D. bruxellensis to obtain 0.4x coverage of the genome. We identified approximately 3,000 genes, whose products averaged 49% amino acid identity to their Saccharomyces cerevisiae orthologs, with similar intron contents. Maximum likelihood phylogenetic analyses suggest that the relationship between D. bruxellensis, S. cerevisiae, and Candida albicans is close to a trichotomy. The estimated rate of chromosomal rearrangement in D. bruxellensis is slower than that calculated for C. albicans, while its rate of amino acid evolution is somewhat higher. The proteome of D. bruxellensis is enriched for transporters and genes involved in nitrogen and lipid metabolism, among other functions, which may reflect adaptations to its low-nutrient, high-ethanol niche. We also identified an adenyl deaminase gene that has high similarity to a gene in bacteria of the Burkholderia cepacia species complex and appears to be the result of horizontal gene transfer. These data provide a resource for further analyses of the population genetics and evolution of D. bruxellensis and of the genetic bases of its physiological capabilities.

Physiological and cellular responses of the 2,4-D degrading bacterium, Burkholderia cepacia YK-2, to the phenoxyherbicides 2,4-D and 2,4,5-T.

Our previous research has demonstrated that novel 43-kDa DnaK and 41-kDa GroEL proteins are synthesized in Burkholderia sp. YK-2 in response to sublethal concentrations of 2,4-D stress [Cho et al. (2000) Curr Microbiol 41:33-38]. In this study, we have extended this work to examine the cellular responses of strain YK-2 to stresses induced in response to the phenoxyherbicides 2,4-D or 2,4,5-T. Strain YK-2 exhibited a more sensitive response to 2,4,5-T stress than to 2,4-D stress, as shown in physiological and morphological changes, suggesting a greater cytotoxic effect of 2,4,5-T. SEM analyses revealed the presence of perforations and irregular rod forms with wrinkled surfaces for cells treated with either herbicide. These irregularities were found more frequently for 2,4,5-T-treated cells than for 2,4-D-treated cells. Analysis of cellular fatty acids showed similar effects in the shifts of total cellular fatty acid composition in response to 2,4-D and 2,4,5-T. Strain YK-2 could degrade 2.25 m M 2,4-D completely during 28 h of incubation with transient production of 2,4-dichlorophenol as a metabolite; however, 2,4,5-T was not catabolized at any of the concentrations tested. BIOLOG and 16S rDNA analyses revealed that strain YK-2 was 98% similar to the Burkholderia cepacia species cluster; therefore, we have designated this strain as B. cepacia YK-2.

Bias Caused by Using Different Isolation Media for Assessing the Genetic Diversity of a Natural Microbial Population.

The influence of isolation medium on the biodiversity of Burkholderia cepacia strains recovered from the rhizosphere of Zea mays was evaluated by comparing the genetic diversity of isolates obtained by plating serial dilutions of root macerates on the two selective media TB-T and PCAT. From each medium, 50 randomly chosen colonies were isolated. On the basis of the restriction patterns of DNA coding for 16S rRNA (16S rDNA) amplified by means of PCR (ARDRA), all strains isolated from TB-T medium were assigned to the B. cepacia species, whereas among PCAT isolates only 74% were assigned to the B. cepacia species. Genetic diversity among the PCAT and TB-T isolates was evaluated by the random amplified polymorphic DNA (RAPD) technique. The analysis of molecular variance (AMOVA) method was applied to determine the variance component for RAPD patterns. Most of the genetic diversity (90.59%) was found within the two groups of isolates, but an appreciable amount (9.41%) still separated the two groups (P < 0.001). Mean genetic distances among PCAT isolates (10.39) and TB-T isolates (9.36) were significantly different (P < 0.0001). The results indicate that the two different isolation media select for B. cepacia populations with a different degree of genetic diversity. Moreover, a higher degree of genetic diversity was observed among strains isolated from PCAT medium than among those isolated from TB-T medium.

Exopolysaccharide production by mucoid and non-mucoid strains of Burkholderia cepacia

Thirteen strains of Burkholderia cepacia from various origins with mucoid and non-mucoid phenotypes were assayed for exopolysaccharide (EPS) production. The EPS were characterized by glycosyl composition analysis and examination of the products resulting from lithium–ethylenediamine and Smith degradations. The results showed that all strains, including the non-mucoid strains, were able to produce EPS exhibiting the same structural features, i.e. presence of one rhamnosyl, three galactosyl, one mannosyl, one glucosyl and one glucuronosyl residues, suggesting that this EPS is representative of the B. cepacia species.

Exopolysaccharide production by mucoid and non-mucoid strains of Burkholderia cepacia.

Thirteen strains of Burkholderia cepacia from various origins with mucoid and non-mucoid phenotypes were assayed for exopolysaccharide (EPS) production. The EPS were characterized by glycosyl composition analysis and examination of the products resulting from lithium-ethylenediamine and Smith degradations. The results showed that all strains, including the non-mucoid strains, were able to produce EPS exhibiting the same structural features, i.e. presence of one rhamnosyl, three galactosyl, one mannosyl, one glucosyl and one glucuronosyl residues, suggesting that this EPS is representative of the B. cepacia species.