719. Cefiderocol Retains Anti-Biofilm Activity in MDR Gram-Negative Pathogens

Abstract Background Cefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens. Microorganisms forming biofilm, e.g., cUTI, utilize bacterial siderophores to access free iron. A siderophore antibiotic may have unique antimicrobial properties in the setting of biofilm. In this study, we compared antimicrobial activity of cefiderocol to comparator antibiotics in well-characterized multi-drug-resistant pathogens. We determined the activity of cefiderocol and comparator antibiotics in the biofilm setting. Methods Minimum inhibitory concentrations (MICs) in Mueller–Hinton II broth (MHII) and iron-depleted cation-adjusted MHII (ID-CAMHB) were determined for cefiderocol and seven comparator antibiotics in multidrug-resistant isolates of P. aeruginosa, Burkholderia cepacia complex (Bcc), Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. MBEC (minimum biofilm eradication concentration) assays were used to test cefiderocol’s activity in biofilms formed on pegs. Total biofilm biomass and viable cell number were measured. Results The MIC90 of cefiderocol ranged from 0.125 μg/mL (Bcc) to 1 μg/mL (P. aeruginosa) in ID-CAMHB. MIC90 values were consistently lower for cefiderocol in all strains tested compared with other agents (ceftolozane-tazobactam, ceftazidime–avibactam, ceftazidime, pipercallin-tazobactam, imipenem, tobramycin, clarithromycin). Twenty-four hour P. aeruginosa biofilms (strains ATCC 9027, MB640, MB771, MB580A, MB730) were treated every 12 hours with 4 μg/mL of cefiderocol or comparator antibiotics. Cefiderocol treatment displayed a superior reduction in biofilm based on colony counts ( >90%; P < 0.0001 vs. untreated control) compared with comparator drugs (50 to 80% reduction). Crystal violet staining revealed a dose-dependent response of cefiderocol in the reduction of biofilm. Reduction of biofilm was not significantly altered by the growth media that was used; however, P. aeruginosa strains form more biofilm in MHII. Conclusion Cefiderocol effectively reduces biofilm in multidrug-resistant strains of P. aeruginosa and is a potent inhibitor of planktonic growth across a range of Gram-negative medically important pathogens. Disclosures All authors: No reported disclosures.

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Sulfonamide-based diffusible signal factor analogs interfere with quorum sensing in Stenotrophomonas maltophilia and Burkholderia cepacia

Future Medicinal Chemistry ◽

10.4155/fmc-2019-0015 ◽

2019 ◽

Vol 11 (13) ◽

pp. 1565-1582 ◽

Cited By ~ 2

Author(s):

Pol Huedo ◽

Vydyula P Kumar ◽

Conor Horgan ◽

Daniel Yero ◽

Xavier Daura ◽

...

Keyword(s):

Multidrug Resistance ◽

Quorum Sensing ◽

Burkholderia Cepacia ◽

Stenotrophomonas Maltophilia ◽

Multidrug Resistant ◽

Burkholderia Cepacia Complex ◽

Antibiofilm Activity ◽

Gram Negative ◽

Alternative Approach ◽

Diffusible Signal Factor

Aim: Stenotrophomonas maltophilia ( Sm) and Burkholderia cepacia complex (BCC) are Gram-negative bacterial pathogens, which are typically multidrug resistant and excellent biofilm producers. These phenotypes are controlled by quorum sensing (QS) systems from the diffusible signal factor (DSF) family. We aim to interfere with this QS system as an alternative approach in combatting such difficult-to-treat infections. Materials & methods: A library of sulfonamide-based DSF bioisosteres was synthesized and tested against the major phenotypes regulated by QS. Results & conclusion: Several analogs display significant antibiofilm activity while the majority increase the action of the last-resort antibiotic colistin against Sm and BCC. Most compounds inhibit DSF synthesis in the Sm K279a strain. Our results support the strategy of interfering with QS communications to combat multidrug resistance.

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Carbapenem Resistance in Non-Fermentative Gram-Negative Bacilli Isolated from Intensive Care Unit Patients of a Referral Hospital

Journal of Nepal Health Research Council ◽

10.33314/jnhrc.v19i1.3240 ◽

2021 ◽

Vol 19 (1) ◽

pp. 55-61

Author(s):

Santosh Kumar Yadav ◽

Rajshree Bhujel ◽

Shyam Kumar Mishra ◽

Sangita Sharma ◽

Jeevan Bahadur Sherchand

Keyword(s):

Intensive Care Unit ◽

Pseudomonas Aeruginosa ◽

Intensive Care ◽

Burkholderia Cepacia ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Burkholderia Cepacia Complex ◽

Acinetobacter Species ◽

Gram Negative ◽

Carbapenem Resistant

Background: Non-fermentative Gram-negative bacilli or non-fermenters are opportunistic pathogens associated with serious infections in intensive care unit patients. Although carbapenems were considered as a backbone of treatment for life-threatening infections, these bacteria are increasingly acquiring resistance to carbapenems. Carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are prioritized as critical pathogens by the World Health Organization. The objective of the study was to document the status of carbapenem-resistant and carbapenemase-producing non-fermenters isolated from intensive care unit patients.Methods: This study was conducted at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. The clinical specimens collected from intensive care unit patients were processed for isolation and identification of non-fermenters and antibiotic susceptibility profile of bacterial isolates was determined. The multidrug-resistant isolates were identified and carbapenemase enzyme was detected in the carbapenem-resistant isolates.Results: A total of 157 non-fermenters were isolated from 1063 samples which included Acinetobacter species (n=85), Pseudomonas aeruginosa (n=55), Burkholderia cepacia complex (n=15), and Stenotrophomonas maltophilia (n=2). Carbapenem resistance was reported in 85.9%, 72.7%, and 33.3% of Acinetobacter species, Pseudomonas aeruginosa, and Burkholderia cepacia complex, respectively. Among total non-fermenters, 91.1% isolates were multidrug-resistant and 60.8% carbapenem-resistant isolates were carbapenemase producers. The carbapenem-resistant isolates demonstrated an extremely high degree of resistance than carbapenem-susceptible isolates towards other antimicrobial classes.Conclusions: This study reported high rates of carbapenem-resistant, carbapenemase-producing, and multidrug-resistant non-fermenters isolates. Therefore, preventing the spread of these superbugs among the critically ill patients in intensive care units should be a major initiative in hospitals.Keywords: Carbapenem-resistant; carbapenemase; intensive care unit; non-fermentative Gram-negative bacilli

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Application of a roller conveyor type plasma disinfection device with fungus-contaminated citrus fruits

AMB Express ◽

10.1186/s13568-020-01177-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Akikazu Sakudo ◽

Yoshihito Yagyu

Keyword(s):

Treatment Time ◽

Citrus Fruit ◽

Viable Cell ◽

Cell Number ◽

Viable Cell Number ◽

Citrus Fruits ◽

Decimal Reduction Time ◽

Gas Plasma ◽

Plasma Device ◽

Time Required

AbstractEfficient methods to achieve the safe decontamination of agricultural products are needed. Here, we investigated the decontamination of citrus fruits to test the antifungal potential of a novel non-thermal gas plasma apparatus, termed a roller conveyer plasma instrument. This instrument generates an atmospheric pressure dielectric barrier discharge (APDBP) plasma on a set of rollers. Penicillium venetum was spotted onto the surface of the fruit or pericarps, as well as an aluminium plate to act as a control, before performing the plasma treatment. The results showed that viable cell number of P. venetum decreased with a decimal reduction time (D value or estimated treatment time required to reduce viable cell number by 90%) of 0.967 min on the aluminium plate, 2.90 min and 1.88 min on the pericarps of ‘Kiyomi’ (Citrus unshiu × C. sinensis) and ‘Kawano-natsudaidai’ (C. natsudaidai) respectively, and 2.42 min on the surface of ‘Unshu-mikan’ (C. unshiu). These findings confirmed a fungicidal effect of the plasma not only on an abiotic surface (aluminium plate) but also on a biotic surface (citrus fruit). Further development of the instrument by combining sorting systems with the plasma device promises an efficient means of disinfecting citrus fruits during food processing.

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Evaluation of the electron transfer flavoprotein as an antibacterial target in Burkholderia cenocepacia

Canadian Journal of Microbiology ◽

10.1139/cjm-2017-0350 ◽

2017 ◽

Vol 63 (10) ◽

pp. 857-863 ◽

Cited By ~ 1

Author(s):

Maria S. Stietz ◽

Christina Lopez ◽

Osasumwen Osifo ◽

Marcelo E. Tolmasky ◽

Silvia T. Cardona

Keyword(s):

Electron Transfer ◽

Burkholderia Cepacia ◽

Multidrug Resistant ◽

Burkholderia Cenocepacia ◽

Burkholderia Cepacia Complex ◽

Infection Model ◽

Electron Transfer Flavoprotein ◽

C Elegans

There are hundreds of essential genes in multidrug-resistant bacterial genomes, but only a few of their products are exploited as antibacterial targets. An example is the electron transfer flavoprotein (ETF), which is required for growth and viability in Burkholderia cenocepacia. Here, we evaluated ETF as an antibiotic target for Burkholderia cepacia complex (Bcc). Depletion of the bacterial ETF during infection of Caenorhabditis elegans significantly extended survival of the nematodes, proving that ETF is essential for survival of B. cenocepacia in this host model. In spite of the arrest in respiration in ETF mutants, the inhibition of etf expression did not increase the formation of persister cells, when treated with high doses of ciprofloxacin or meropenem. To test if etf translation could be inhibited by RNA interference, antisense oligonucleotides that target the etfBA operon were synthesized. One antisense oligonucleotide was effective in inhibiting etfB translation in vitro but not in vivo, highlighting the challenge of reduced membrane permeability for the design of drugs against B. cenocepacia. This work contributes to the validation of ETF of B. cenocepacia as a target for antibacterial therapy and demonstrates the utility of a C. elegans liquid killing assay to validate gene essentiality in an in vivo infection model.

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INVESTIGATION ON QUALITY PROPERTIES OF TRADITIONAL BULK BREAD COVERED WITH PROBIOTICS AND SOYBEAN OIL EDIBLE COATING

Acta Alimentaria ◽

10.1556/066.2020.49.2.3 ◽

2020 ◽

Vol 49 (2) ◽

pp. 144-153

Author(s):

R. Amiri Qandashtant ◽

E. Ataye Salehi ◽

A. Mohamadi Sani ◽

M. Mehraban Sangatash ◽

O. Safari

Keyword(s):

Soybean Oil ◽

Whey Protein ◽

Corn Starch ◽

Lactobacillus Rhamnosus ◽

Methyl Cellulose ◽

Viable Cell ◽

Cell Number ◽

Whey Protein Concentrate ◽

Viable Cell Number ◽

Quality Properties

Probiotic food products are available at the supermarket commercially, but probiotic bakery products are much less in evidence. In the present study, methyl cellulose (2%), whey protein concentrate (2%), corn starch (1%), and soybean oil at 2, 4, and 6% were used for coating layer on the bulked bread surface, and then the quality properties were studied. The results showed that Lactobacillus rhamnosus GG, as probiotic component of the coating, immobilized in corn starch, whey protein, and methyl cellulose films had enhanced viability throughout shelf-life. The probiotics remained viable for 4 days, maintaining high viable cell number levels. Adding soybean oil at 6% concentration enhanced texture, sensory properties, and image index during storage.

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Conservation of resistance nodulation cell division efflux pump mediated antibiotic resistance in Burkholderia cepacia complex and Burkholderia pseudomallei complex species

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00920-21 ◽

2021 ◽

Author(s):

Nawarat Somprasong ◽

Jinhee Yi ◽

Carina M. Hall ◽

Jessica R. Webb ◽

Jason W. Sahl ◽

...

Keyword(s):

Cell Division ◽

Burkholderia Cepacia ◽

Burkholderia Pseudomallei ◽

Efflux Pump ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Burkholderia Cepacia Complex ◽

Complex Species ◽

Functional Studies ◽

Rnd Efflux Pump

Burkholderia cepacia complex (Bcc) and Burkholderia pseudomallei complex (Bpc) species include pathogens that are typically multidrug resistant. Dominant intrinsic and acquired multidrug resistance mechanisms are efflux mediated by pumps of the resistance nodulation cell division (RND) family. From comparative bioinformatic and, in many instances, functional studies we infer that RND pump-based resistance mechanisms are conserved in Burkholderia . We propose to use these findings as a foundation for adoption of a uniform RND efflux pump nomenclature.

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Non fermentative gram negative bacilli as nosocomial pathogens: Identification and antibiotic sensitivity in clinical samples of indoor patients

Nepal Journal of Medical Sciences ◽

10.3126/njms.v3i2.13452 ◽

2015 ◽

Vol 3 (2) ◽

pp. 101-105 ◽

Cited By ~ 1

Author(s):

D Sharma ◽

N Vyas ◽

P Sinha ◽

A Mathur

Keyword(s):

Burkholderia Cepacia ◽

Treatment Options ◽

Antibiotic Sensitivity ◽

Burkholderia Cepacia Complex ◽

Clinical Samples ◽

Sensitivity Testing ◽

Gram Negative ◽

Nosocomial Pathogens ◽

Sensitivity Pattern ◽

Medical Icus

Background: Non fermenting gram negative bacilli (NFGNB) are usually considered to be non pathogenic commensals of little significance, however, data suggest that they are remarkable because of antimicrobial resistance; propensity to cause outbreaks and complex epidemiology. This study was conducted to find out the prevalence and sensitivity pattern of NFGNB from various clinical samples.Methods: A total of 519 samples were received from patients suspected of having hospital acquired infections (HAI), admitted in Sawai Man Singh Hospital, Jaipur, India. Organisms grown on culture were subjected to phenotypic identification along with antimicrobial sensitivity testing by Kirby Bauer’s disc diffusion method.Results: Among 366 culture positive samples, 94 (25.6%) NFGNB were isolated. Maximum pevalence prevalence was found in burn ward i.e. 76.7 % followed by surgical wards 71.0%, surgical ICUs 69.6% and medical ICUs 68.0 %. Highest yield was found in pus/wound samples (95.5%) while it was only 23.7% in blood samples. Pseudomonas aeruginosa was the most common isolate (48.9%), followed by Acinetobacter baumannii (33%), Stenotrophomonas maltophilia (13.8%) and Burkholderia cepacia complex (4.3%). P.aeruginosa and A. baumanii strains were most sensitive to Meropenem. S.maltophilia showed maximum sensitivity with ticarcillin/ clavulanic acid and B. cepacia complex with Piperacillin/ Tazobactam.Conclusion: Isolation of NFGNB and their antibiotic susceptibility pattern should be regarded with all seriousness in clinical practice and epidemiology because they are emerging nosocomial pathogens and by being resistant to multiple antibiotics, their prevalence not only limits the treatment options but also act as a reservoir of drug resistance genes.Nepal Journal of Medical Sciences Vol.3(2) 2014: 101-105

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Classification of Five Uremic Solutes according to Their Effects on Renal Tubular Cells

International Journal of Nephrology ◽

10.1155/2014/512178 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Takeo Edamatsu ◽

Ayako Fujieda ◽

Atsuko Ezawa ◽

Yoshiharu Itoh

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Viable Cell ◽

Cell Number ◽

Viable Cell Number ◽

Cycle Progression ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Uremic Solutes ◽

Renal Tubular

Background/Aims. Uremic solutes, which are known to be retained in patients with chronic kidney disease, are considered to have deleterious effects on disease progression. Among these uremic solutes, indoxyl sulfate (IS) has been extensively studied, while other solutes have been studied less to state. We conducted a comparative study to examine the similarities and differences between IS,p-cresyl sulfate (PCS), phenyl sulfate (PhS), hippuric acid (HA), and indoleacetic acid (IAA).Methods. We used LLC-PK1 cells to evaluate the effects of these solutes on viable cell number, cell cycle progression, and cell death.Results. All the solutes reduced viable cell number after 48-hour incubation. N-Acetyl-L-cysteine inhibited this effect induced by all solutes except HA. At the concentration that reduced the cell number to almost 50% of vehicle control, IAA induced apoptosis but not cell cycle delay, whereas other solutes induced delay in cell cycle progression with marginal impact on apoptosis. Phosphorylation of p53 and Chk1 and expression of ATF4 and CHOP genes were detected in IS-, PCS-, and PhS-treated cells, but not in IAA-treated cells.Conclusions. Taken together, the adverse effects of PCS and PhS on renal tubular cells are similar to those of IS, while those of HA and IAA differ.

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