scholarly journals 1626. Synergistic Effect of Cefiderocol with Other Antibiotics Against PER-Producing Acinetobacter baumannii Isolates from the Multinational SIDERO-WT Studies

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S805-S805
Author(s):  
Yoshinori Yamano ◽  
Miki Takemura ◽  
Naomi Anan ◽  
Rio Nakamura ◽  
Roger Echols
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Laboratory ◽  
Synergistic Effects ◽  
Single Agent ◽  
Standard Medium ◽  
Chemostat Model ◽  
Mueller Hinton ◽  
Susceptible Isolate ◽  
Checkerboard Assay ◽  
Mueller Hinton Broth

Abstract Background Cefiderocol (CFDC), a novel siderophore cephalosporin, showed potent activity at minimum inhibitory concentrations (MICs) of ≤4 μg/mL against ≥99% of Gram-negative isolates in the multinational SIDERO-WT studies. PER-producing Acinetobacter baumannii, mainly from Russia, showed high CFDC MICs of 8– >64 μg/mL. This study evaluated the synergistic effects of CFDC combined with other antibiotics against PER-producing A. baumannii isolates with high CFDC MICs. Methods Two isolates of PER-producing A. baumannii with resistance to CFDC (MIC 16 μg/mL), meropenem (MEM; MIC 64 μg/mL), ceftazidime-avibactam (CZA; MIC 64/4 μg/mL), amikacin (AMK; MIC 32 or 64 μg/mL), and ciprofloxacin (CIP; MIC ≥64 μg/mL) were tested. Against ampicillin-sulbactam (SAM), one isolate was resistant (MIC 32/64 μg/mL) and another was susceptible (MIC 8/16 μg/mL). Effects of CFDC combined with other antibiotics were evaluated by checkerboard assay and chemostat model reproducing humanized antibiotic exposure. The checkerboard assay used a single agent (e.g. ceftazidime [CAZ], avibactam [AVI], ampicillin [AMP] or sulbactam [SUL]). Iron-depleted cation-adjusted Mueller‒Hinton broth was used as the standard medium for CFDC, as recommended by the Clinical Laboratory and Standards Institute. Results Against both isolates, synergy with CFDC was seen for two β-lactamase inhibitors, AVI and SUL, with a fractional inhibitory concentration (FIC) index of 0.026–0.033 and 0.26–0.27, respectively. A synergistic to additive effect was seen for MEM and AMK, with an FIC index of 0.53–0.75 and 0.25–0.52, respectively. In the chemostat model, regrowth during 24-h treatment was observed with single agents (CFDC 2 g, q8h, 3-h infusion; MEM 2 g, q8h, 1-h infusion; CZA 2 g, q8h, 2-h infusion; SAM 3 g, q8h, 3-h infusion; AMK 15 mg/kg, q8h, 3-h infusion) for both isolates, including the SAM-susceptible isolate. However, no regrowth was seen when CFDC was combined with CZA, MEM, SAM or AMK. Conclusion The most potent synergy was seen between CFDC and AVI against PER-producing A. baumannii with a decreased MIC to ≤1 µg/mL for all isolates, followed by SUL and MEM. Under humanized pharmacokinetic exposure, combination of CFDC and CZA, MEM, SAM or AMK is expected to be effective against PER-producing A. baumannii in spite of high CFDC MICs. Disclosures Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Naomi Anan, MSc, Shionogi & Co., Ltd. (Employee) Rio Nakamura, BSc, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant)

scholarly journals Pharmacodynamic effects of antibiotics and antibiotic combinations on growing and nongrowing Staphylococcus epidermidis cells.

1997 ◽  
Vol 41 (1) ◽  
pp. 107-111 ◽  
Author(s):  
E Svensson ◽  
H Hanberger ◽  
L E Nilsson
Keyword(s):  
Staphylococcus Epidermidis ◽  
Synergistic Effects ◽  
Strong Concentration ◽  
Pharmacodynamic Effects ◽  
Mueller Hinton ◽  
Drug Removal ◽  
Bioluminescence Assay ◽  
And Control ◽  
Phosphate Buffered Saline ◽  
Mueller Hinton Broth

The pharmacodynamic effects of amikacin, imipenem, ofloxacin, rifampin, and vancomycin were studied on the slime-producing, oxacillin-resistant strain Staphylococcus epidermidis ATCC 35984 growing in Mueller Hinton broth or, in order to inhibit growth, incubated in phosphate-buffered saline. The investigated parameters were postantibiotic effect (PAE) and control-related effective regrowth time (CERT), which were determined by bioluminescence assay of bacterial ATP. PAE describes the delayed regrowth after drug removal, and CERT describes the combined effects of initial change in bacterial density during antibiotic exposure and delayed regrowth after drug removal. In growth cultures, PAE and CERT were drug concentration dependent for all antibiotics. The length of the PAE and CERT in the growing cultures were as follows: ofloxacin > rifampin > amikacin > vancomycin > imipenem. Imipenem combined with amikacin and vancomycin, respectively, induced a synergistic effect against growing cultures. In nongrowing cultures rifampin was the only drug that induced strong concentration-dependent effects. The combination of drugs induced no synergistic effects against nongrowing bacteria.

scholarly journals Highly Reproducible Bactericidal Activity Test Results by Using a Modified National Committee for Clinical Laboratory Standards Broth Macrodilution Technique

1999 ◽  
Vol 37 (6) ◽  
pp. 1881-1884 ◽  
Author(s):  
Donna M. Hacek ◽  
Dana C. Dressel ◽  
Lance R. Peterson
Keyword(s):  
Bactericidal Activity ◽  
Minimum Bactericidal Concentration ◽  
Clinical Laboratory ◽  
National Committee ◽  
Test Results ◽  
Activity Test ◽  
Mueller Hinton ◽  
Broth Macrodilution ◽  
High Level ◽  
Mueller Hinton Broth

Bactericidal testing historically has exhibited variable reproducibility, even when prior standardized methods were employed. Several modifications to the National Committee for Clinical Laboratory Standards (NCCLS) broth macrodilution method are proposed to improve reproducibility. Recommended changes from the approved NCCLS guidelines (M21-A and M26-A) include omitting serum supplementation of Mueller-Hinton broth, incubating tubes at 35°C for 24 h with no agitation until they are sampled, running all tests in duplicate with six dilutions instead of nine, reincubating the test for an additional 24 h to resolve discrepant bactericidal activity test results, using a single 0.1-ml sample from each clear tube for subculture, and adopting an alternate method for calculating endpoint determination. In order to test these recommendations in a clinical laboratory setting, we used the modified methodology on 224 separate tests for bactericidal activity. There were 102 serum bactericidal titer (SBT) and 122 minimum bactericidal concentration (MBC) assays performed. By defining reproducibility as agreement between duplicate tests ± 1 dilution, we found 207 of 224 tests (92%) were reproducible at the 24-h subculture point (94% for the SBT assay and 91% for the MBC assay). When the 17 assays with discrepant results were incubated an additional 24 h for a second subculture, only 1 of 224 tests (0.4%) remained discrepant. The method used is practical for a clinical laboratory that chooses to perform bactericidal activity testing and assures a high level of reproducibility between duplicate assays. The total cost of a test was approximately $25.00.

scholarly journals 607. Scope and Predictive Genetic/Phenotypic Signatures of “Bicarbonate [NaHCO3]-Responsivity” and β-Lactam Sensitization among Methicillin-Resistant Staphylococcus aureus (MRSA)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S284-S284
Author(s):  
Selvi Ceren. Ersoy ◽  
Brianne Zapata-Davila ◽  
Mariam Otmishi ◽  
Vanessa Milan ◽  
Liang Li ◽  
...  
Keyword(s):  
Methicillin Resistant Staphylococcus Aureus ◽  
Clonal Complex ◽  
Broth Microdilution ◽  
Standard Medium ◽  
Mueller Hinton ◽  
Solid Foundation ◽  
Mrsa Strains ◽  
Mueller Hinton Broth

Abstract Background Selected MRSA strains become susceptible to β-lactams (e.g., oxacillin [OX]; cefazolin [CFZ]) in vitro when tested in a standard medium (cation-adjusted Mueller–Hinton Broth; CA-MHB) supplemented with NaHCO3 (“NaHCO3-responsivity”). In vivo activity of β-lactams was demonstrated for MRSA strains with this phenotype in a rabbit endocarditis model (Ersoy et al Antimicrob Agents Chemother 2019). The current study was designed to: (i) determine the prevalence of the NaHCO3-responsive phenotype in a large collection of clinical MRSA isolates; and (ii) identify genetic and phenotypic predictors of this phenotype. Methods. 58 recent MRSA bloodstream isolates representing contemporary clonal complex (CC) genotypes were screened for the NaHCO3-responsive phenotype by broth microdilution MICs in CA-MHB, with or without NaHCO3 supplementation (25–44 mM). Methods 58 recent MRSA bloodstream isolates representing contemporary clonal complex (CC) genotypes were screened for the NaHCO3-responsive phenotype by broth microdilution MICs in CA-MHB, with or without NaHCO3 supplementation (25–44 mM). Results 43/58 (74.1%) and 21/58 (36.2%) were rendered susceptible to CFZ and OX, respectively, in the presence of NaHCO3; 20 of the 21 OX-susceptible strains were also susceptible to CFZ in the presence of NaHCO3. High baseline β-lactam MICs (i.e., MICs in CA-MHB alone ≥64 µg/mL) was not predictive of NaHCO3 responsivity. The CC8 genotype was correlated with NaHCO3 responsivity for OX, but not CFZ (P < 0.05). Conclusion The NaHCO3-responsive phenotype is relatively common for both OX and especially CFZ among clinical MRSA isolates. Identification of specific genetic factors linked to this phenotype remains ongoing. Confirmation in relevant animal models that this phenotype is predictive of β-lactam efficacy in vivo could provide a solid foundation for a paradigm shift in antimicrobial susceptibility testing of MRSA. Disclosures All authors: No reported disclosures.

scholarly journals ARGONAUT-I: Activity of Cefiderocol (S-649266), a Siderophore Cephalosporin, against Gram-Negative Bacteria, Including Carbapenem-Resistant Nonfermenters and Enterobacteriaceae with Defined Extended-Spectrum β-Lactamases and Carbapenemases

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Michael R. Jacobs ◽  
Ayman M. Abdelhamed ◽  
Caryn E. Good ◽  
Daniel D. Rhoads ◽  
Kristine M. Hujer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
Mueller Hinton ◽  
Mueller Hinton Broth

ABSTRACT The activity of the siderophore cephalosporin cefiderocol is targeted against carbapenem-resistant Gram-negative bacteria. In this study, the activity of cefiderocol against characterized carbapenem-resistant Acinetobacter baumannii complex, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae strains was determined by microdilution in iron-depleted Mueller-Hinton broth. The MIC90s against A. baumannii, S. maltophilia, and P. aeruginosa were 1, 0.25, and 0.5 mg/liter, respectively. Against Enterobacteriaceae, the MIC90 was 1 mg/liter for the group harboring OXA-48-like, 2 mg/liter for the group harboring KPC-3, and 8 mg/liter for the group harboring TEM/SHV ESBL, NDM, and KPC-2.

scholarly journals 1287. Double Disk Diffusion Study to Evaluate the Synergistic Effect Between Cefiderocol and Ceftazidime-Avibactam Against Cefiderocol-Non-susceptible Acinetobacter baumannii

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S732-S733
Author(s):  
Yoshinori Yamano ◽  
Miki Takemura ◽  
Naomi Anan ◽  
Roger Echols ◽  
Christopher Longshaw
Keyword(s):  
Synergistic Effect ◽  
Acinetobacter Baumannii ◽  
Disk Diffusion ◽  
Bacterial Suspension ◽  
Gram Negative Bacteria ◽  
Surveillance Studies ◽  
Mueller Hinton ◽  
Diffusion Studies ◽  
Mueller Hinton Agar ◽  
Mueller Hinton Broth

Abstract Background Cefiderocol (CFDC), a siderophore cephalosporin, has broad coverage of Gram-negative bacteria and has been approved for clinical use in USA and Europe. The SIDERO-WT surveillance studies showed that CFDC shows &gt;95% susceptibility against Acinetobacter baumannii. Against many of CFDC non-susceptible isolates, most of which had blaPER gene, the combination use of avibactam significantly decreased the MIC by broth microdilution (BMD). In this study, we evaluated the appropriate methodology to evaluate the synergistic effect by disk diffusion studies. Methods The susceptibility testing was conducted as recommended by the CLSI using CFDC non-susceptible isolates (MIC of &gt;4 µg/mL based on CLSI breakpoint). The MIC by BMD was determined using iron-depleted cation-adjusted Mueller-Hinton broth, in the presence or absence of 4 µg/mL of avibactam. The disk diffusion was evaluated using Mueller-Hinton agar, and the synergy was evaluated by using disk stacking methods. For disk stacking methods, CFDC disk was placed on agar on which bacterial suspension of 0.5 McFarland units was spread, then the ceftazidime-avibactam (CZA) disks was stacked on the top, followed by adding a drop (30 µL) of saline on the stacked disks. As an alternative method, CZA was immersed in saline for 1 second instead of adding a drop of saline, followed by the stacking on the top. The disk zone size was determined after 24-hour incubation at 37°C. Results Against blaPER-positive A. baumannii which showed &gt;64 µg/mL MIC of CFDC and CZA, CFDC MIC decreased to 0.25 µg/mL in the presence of avibactam. The disk diffusion methods also showed isolates resistant to CFDC and CZA and showed susceptiblilty disk zone to CFDC by stacking both disks. On the other hand, against blaNDM-positive A. baumannii which showed 64 µg/mL MIC of CFDC and CZA, the disk diffusion methods showed resistance even when stacking both disks. Against multiple isolates, the MIC of CFDC without or with avibactam was correlated well with the disk zone produced by CFDC disk alone or stacked with CZA disks, respectively (Figure). Conclusion The synergistic effect between CFDC and avibactam by BMD methods could be detected by disk stacking methodology using CFDC and CZA disks. Disclosures Yoshinori Yamano, PhD, Shionogi (Employee) Miki Takemura, MS, SHIONOGI & CO., LTD. (Employee) Roger Echols, MD, Shionogi (Consultant) Christopher Longshaw, PhD, Shionogi (Employee)

scholarly journals Effect of Medium Age and Supplementation with the Biocatalytic Oxygen-Reducing Reagent Oxyrase on In Vitro Activities of Tigecycline against Recent Clinical Isolates

2005 ◽  
Vol 49 (9) ◽  
pp. 3910-3918 ◽  
Author(s):  
Peter J. Petersen ◽  
Patricia A. Bradford
Keyword(s):  
Quality Control ◽  
Clinical Laboratory ◽  
Clinical Isolates ◽  
Mueller Hinton ◽  
Control Limits ◽  
Mueller Hinton Broth

ABSTRACT In determining the quality control limits for the Clinical Laboratory Standards Institute-recommended quality control organisms with tigecycline, a number of inconsistencies in the results were encountered that appeared to be related to the age of the Mueller-Hinton broth II. This study was performed to examine the effect of medium age and supplementation with Oxyrase on the activity of tigecycline using a large number of clinical isolates.

scholarly journals In Vitro and In Vivo Activities of Tigecycline (GAR-936), Daptomycin, and Comparative Antimicrobial Agents against Glycopeptide-Intermediate Staphylococcus aureus and Other Resistant Gram-Positive Pathogens

2002 ◽  
Vol 46 (8) ◽  
pp. 2595-2601 ◽  
Author(s):  
Peter J. Petersen ◽  
Patricia A. Bradford ◽  
William J. Weiss ◽  
Timothy M. Murphy ◽  
P. E. Sum ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Clinical Laboratory ◽  
Infection Model ◽  
National Committee ◽  
Gram Positive ◽  
Mueller Hinton ◽  
Mueller Hinton Broth

ABSTRACT Tigecycline (GAR-936) and daptomycin are potent antibacterial compounds in advanced stages of clinical trials. These novel agents target multiply resistant pathogenic bacteria. Daptomycin is principally active against gram-positive bacteria, while tigecycline has broad-spectrum activity. When tested by the standard protocols of the National Committee for Clinical Laboratory Standards in Mueller-Hinton broth II, tigecycline was more active than daptomycin (MICs at which 90% of isolates tested are inhibited, 0.12 to 1 and 0.5 to 16 μg/ml, respectively) against staphylococcal, enterococcal, and streptococcal pathogens. Daptomycin demonstrated a stepwise increase in activity corresponding to an increase in the supplemental concentration of calcium. When tested in base Mueller-Hinton broth supplemented with 50 mg of calcium per liter, daptomycin demonstrated improved activity (MIC90s, 0.015 to 4 μg/ml). The activity of daptomycin, however, equaled that of tigecycline against the glycopeptide-intermediate Staphylococcus aureus (GISA) strains only when the test medium was supplemented with excess calcium (75 mg/liter). Tigecycline and daptomycin demonstrated in vivo efficacies against GISA, methicillin-resistant S. aureus, and methicillin-susceptible S. aureus strains in an intraperitoneal systemic murine infection model. These data suggest that tigecycline and daptomycin may offer therapeutic options against clinically relevant resistant pathogens for which current alternatives for treatment are limited.

The Ultrashort Peptide OW: A New Antibiotic Adjuvant

2019 ◽  
Vol 20 (9) ◽  
pp. 745-754
Author(s):  
Yara Al Tall ◽  
Ahmad Abualhaijaa ◽  
Mohammed T. Qaoud ◽  
Mohammad Alsaggar ◽  
Majed Masadeh ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Rapid Development ◽  
Single Agent ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Human Blood Cells ◽  
Checkerboard Assay ◽  
Different Strains ◽  
Different Levels ◽  
Mic Value

Background:The over use of current antibiotics and low discovery rate of the new ones are leading to rapid development of multidrug-resistant pathogens worldwide. Antimicrobial peptides have shown promising results against multidrug-resistant bacteria.Objective:To investigate the antimicrobial activity of a new ultrashort hexapeptide (OW).Methods:The OW hexapeptide was designed and tested against different strains of bacteria with different levels of sensitivity. Bacterial susceptibility assays were performed according to the guidelines of the Clinical and Laboratory Institute (CLSI). The synergistic studies were then conducted using the Checkerboard assay. This was followed by checking the hemolytic effect of the hexapeptide against human blood cells and Human Embryonic Kidney cell line (HEK293). Finally, the antibiofilm activities of the hexapeptide were studied using the Biofilm Calgary method.Results:Synergistic assays showed that OW has synergistic effects with antibiotics of different mechanisms of action. It showed an outstanding synergism with Rifampicin against methicillin resistant Staphylococcus aureus; ΣFIC value was 0.37, and the MIC value of Rifampicin was decreased by 85%. OW peptide also displayed an excellent synergism with Ampicillin against multidrug-resistant Pseudomonas aeruginosa, with ΣFIC value of less than 0.38 and a reduction of more than 96% in the MIC value of Ampicillin.Conclusion:This study introduced a new ultrashort peptide (OW) with promising antimicrobial potential in the management of drug-resistant infectious diseases as a single agent or in combination with commonly used antibiotics. Further studies are needed to investigate the exact mechanism of action of these peptides.

scholarly journals Anticancer effects of the combined Thai noni juice ethanolic extracts and 5-fluorouracil against cholangiocarcinoma cells in vitro and in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeerati Prompipak ◽  
Thanaset Senawong ◽  
Banchob Sripa ◽  
Albert J. Ketterman ◽  
Suppawit Utaiwat ◽  
...  
Keyword(s):  
Nude Mice ◽  
Combination Treatment ◽  
Synergistic Effects ◽  
Single Agent ◽  
Xenograft Model ◽  
Ethanolic Extract ◽  
Model Combination ◽  
Mouse Xenograft Model ◽  
Ethanolic Extracts

AbstractApplication of 5-fluorouracil (5-FU) in cholangiocarcinoma (CCA) is limited by adverse side effects and chemoresistance. Therefore, the combination therapy of 5-FU with other substances, especially natural products may provide a new strategy for CCA treatment. The aim of this study was to evaluate the combination effects of 5-FU and two ethanolic extracts of Thai noni juice (TNJ) products on CCA cell lines and nude mice xenografts. The results of antiproliferative assay showed the combination treatment of 5-FU and each TNJ ethanolic extract exerted more cytotoxicity on CCA cells than either single agent treatment. Synergistic effects of drug combinations can enable the dose reduction of 5-FU. The mechanism underlying a combination treatment was apoptosis induction through an activation of p53 and Bax proteins. In the nude mouse xenograft model, combination treatments of 5-FU with each TNJ ethanolic extract suppressed the growth of CCA cells implanted mice more than single agent treatments with no effects on mouse body weight, kidney, and spleen. Moreover, low doses of TNJ ethanolic extracts reduced the hepatotoxicity of 5-FU in nude mice. Taken together, these data suggested that the ethanolic extracts of TNJ products can enhance the anti-CCA effect and reduce toxicity of 5-FU.

scholarly journals Recording the Presence of Peanibacillus larvae larvae Colonies on MYPGP Substrates Using a Multi-Sensor Array Based on Solid-State Gas Sensors

Sensors ◽  
2021 ◽  
Vol 21 (14) ◽  
pp. 4917
Author(s):  
Beata Bąk ◽  
Jakub Wilk ◽  
Piotr Artiemjew ◽  
Jerzy Wilde
Keyword(s):  
Gas Sensors ◽  
Culture Media ◽  
Laboratory Diagnosis ◽  
Baseline Correction ◽  
American Foulbrood ◽  
Sensor Signal ◽  
Sodium Pyruvate ◽  
Mueller Hinton ◽  
Regeneration Phase ◽  
Mueller Hinton Broth

American foulbrood is a dangerous disease of bee broods found worldwide, caused by the Paenibacillus larvae larvae L. bacterium. In an experiment, the possibility of detecting colonies of this bacterium on MYPGP substrates (which contains yeast extract, Mueller-Hinton broth, glucose, K2HPO4, sodium pyruvate, and agar) was tested using a prototype of a multi-sensor recorder of the MCA-8 sensor signal with a matrix of six semiconductors: TGS 823, TGS 826, TGS 832, TGS 2600, TGS 2602, and TGS 2603 from Figaro. Two twin prototypes of the MCA-8 measurement device, M1 and M2, were used in the study. Each prototype was attached to two laboratory test chambers: a wooden one and a polystyrene one. For the experiment, the strain used was P. l. larvae ATCC 9545, ERIC I. On MYPGP medium, often used for laboratory diagnosis of American foulbrood, this bacterium produces small, transparent, smooth, and shiny colonies. Gas samples from over culture media of one- and two-day-old foulbrood P. l. larvae (with no colonies visible to the naked eye) and from over culture media older than 2 days (with visible bacterial colonies) were examined. In addition, the air from empty chambers was tested. The measurement time was 20 min, including a 10-min testing exposure phase and a 10-min sensor regeneration phase. The results were analyzed in two variants: without baseline correction and with baseline correction. We tested 14 classifiers and found that a prototype of a multi-sensor recorder of the MCA-8 sensor signal was capable of detecting colonies of P. l. larvae on MYPGP substrate with a 97% efficiency and could distinguish between MYPGP substrates with 1–2 days of culture, and substrates with older cultures. The efficacy of copies of the prototypes M1 and M2 was shown to differ slightly. The weighted method with Canberra metrics (Canberra.811) and kNN with Canberra and Manhattan metrics (Canberra. 1nn and manhattan.1nn) proved to be the most effective classifiers.

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