Journal: Antimicrobial Agents and Chemotherapy

Article Title: Exploring Cluster-Dependent Antibacterial Activities and Resistance Pathways of NOSO-502 and Colistin against Enterobacter cloacae Complex Species

doi: 10.1128/aac.00776-22

Figure Lengend Snippet: MIC 50 , MIC 90 , and MIC ranges of NOSO-502 and antimicrobial agents against a panel of recent ECC clinical isolates from the United Kingdom

Article Snippet: NOSO-502 was synthesized at Nosopharm, Nîmes, France (Biosynth, ref: AC20542), ciprofloxacin (Biosynth, ref: AC58172), meropenem (Biosynth, ref: AM32026), ceftazidime-avibactam (CAZ: Biosynth, ref: AC19871; AVI: Biosynth, ref: AA158833), tigecycline (Biosynth, ref: AT10818), and amikacin (CAZ: Biosynth, ref: AA17356) were obtained from manufacturers as standard powders.

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Aminoglycosides enhance meropenem/vaborbactam activity against KPC-producing Klebsiella pneumoniae in the hollow fiber infection model

doi: 10.1128/aac.01365-25

Figure Lengend Snippet: Comparison of the meropenem/vaborbactam activity in time-kill assays against four KPC-Kp isolates with the same meropenem/vaborbactam MICs (2/8 mg/L) but with differing mutation frequencies. The mutation frequencies were <2 × 10 −9 ( A and C ) or 2.65–3.19 × 10 −7 ( B and D ). The data are presented as the mean ± SD of the log 10 CFU/mL. Bactericidal activity: ≥3-log 10 CFU/mL reduction from baseline.

Article Snippet: Antibiotics used in this study included meropenem (Sigma-Aldrich), vaborbactam (MedChem Express), meropenem/vaborbactam (Vabomere; clinical-grade powder), gentamicin (Sigma-Aldrich), and plazomicin (ZEMDRI; clinical-grade powder).

Techniques: Comparison, Activity Assay, Mutagenesis

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Aminoglycosides enhance meropenem/vaborbactam activity against KPC-producing Klebsiella pneumoniae in the hollow fiber infection model

doi: 10.1128/aac.01365-25

Figure Lengend Snippet: Pharmacodynamic activity of meropenem/vaborbactam alone and in combination with gentamicin against KPC-Kp NU-CRE105 and NU-CRE244 in the HFIM. Antibiotic exposures simulated PKs in the plasma ( A ) and ELF ( B ) following human doses of meropenem/vaborbactam and gentamicin. Bactericidal activity: ≥3-log 10 CFU/mL reduction from baseline.

Article Snippet: Antibiotics used in this study included meropenem (Sigma-Aldrich), vaborbactam (MedChem Express), meropenem/vaborbactam (Vabomere; clinical-grade powder), gentamicin (Sigma-Aldrich), and plazomicin (ZEMDRI; clinical-grade powder).

Techniques: Activity Assay, Clinical Proteomics

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Aminoglycosides enhance meropenem/vaborbactam activity against KPC-producing Klebsiella pneumoniae in the hollow fiber infection model

doi: 10.1128/aac.01365-25

Figure Lengend Snippet: A fusion between two plasmids occurred in AR-1054 following exposure to meropenem/vaborbactam in the HFIM and emergence of resistance (AR-1054-MV). Plasmids p1 (top) and p2 (bottom) from the parental strain fused to form a single 273,529 bp plasmid p1.2 (middle), which includes two copies of bla KPC (red).

Article Snippet: Antibiotics used in this study included meropenem (Sigma-Aldrich), vaborbactam (MedChem Express), meropenem/vaborbactam (Vabomere; clinical-grade powder), gentamicin (Sigma-Aldrich), and plazomicin (ZEMDRI; clinical-grade powder).

Techniques: Plasmid Preparation

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Mass spectrometry fragmentation pattern for cefazolin (CZO), cefepime (CEP), cefotaxime (CTA), ceftazidime (CTZ), ciprofloxacin (CIP), flucloxacillin (FLU), linezolid (LIN), meropenem (MER), piperacillin (PIP) and tazobactam (TAZ).

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Mass Spectrometry

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Chromatograms for cefepime (CEP, 1), tazobactam (TAZ, 2), ceftazidime (CTZ, 3), meropenem (MER, 4), ciprofloxacin (CIP, 5), cefotaxime (CTA, 6), cefazolin (CZO, 7), linezolid (LIN, 8), piperacillin (PIP, 9) and flucloxacillin (FLU, 10) in human plasma at lower limit of quantitation.

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Clinical Proteomics, Quantitation Assay

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Intra and inter-day precision and accuracy data.

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Concentration Assay

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Recovery (%) of the spiked patient samples (n = 35). Samples from patients requested for antimicrobial monitoring were analyzed in duplicate: a) neat and b) spiked with a solution mixture containing all the analytes. The recovered concentrations were calculated by subtracting the concentration obtained for the neat sample from the spiked (b-a). The percent recovery (%) was calculated from recovered concentration divided by the concentration of the spiked solution mixture and multiplied by 100. The recovery (%) was withing 85–115 %, except for CEP (81–124 %). CZO, cefazolin; CEP, cefepime; CTA, cefotaxime; CTZ, ceftazidime; CIP, ciprofloxacin; FLU, flucloxacillin; LIN, linezolid; MER, meropenem; PIP, piperacillin; TAZ, tazobactam.

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Concentration Assay

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Summary of the stability data for all analytes in plasma and whole blood matrices. The stability of the analyte is assumed for the length of time at the specified temperature.

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Clinical Proteomics

Journal: Journal of Mass Spectrometry and Advances in the Clinical Lab

Article Title: LC–MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring

doi: 10.1016/j.jmsacl.2022.11.001

Figure Lengend Snippet: Antimicrobials concentrations of patients requested for therapeutic drug monitoring. MIC breakpoints for each agent were set based on the EUCAST PK/PD clinical breakpoints and are non-species related. The breakpoints for the susceptible (S) and resistant (R) organisms were 4 and 8 mg/L (CEP, CTZ); 1 and 2 mg/L (CZO, CTA); 0.25 and 0.5 mg/L (CIP); 2 and 4 (FLU); 2 and 8 mg/L (MER); 2 and 2 mg/L (LIN) and 8 and 16 mg/L (PIP), respectively. The target plasma concentration ranges set as 4 and 8 times the MIC breakpoint of the R organism were as per recommendation of the French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anesthesia and Intensive Care Medicine (SFAR) . The targets of the total drug concentrations for CZO, CEP, CTA, CTZ, PIP and FLU, were based on the free drug fraction (%) and the MIC of the pathogen. For CZO, for example, the target free plasma concentration of 4 to 8 times the MIC of R (2 mg/L) is 8 and 16 mg/L, respectively. As the free fraction of CZO is approximately 20 % of the total dose, the target total plasma concentration is 40–80 mg/L. The estimated free fraction (%) for CZO, CEP, CTA, CTZ, PIP and FLU were approximately 15–20, 80, 60–80, 90, 80 and 5–10 %, respectively. For CEP, the target plasma concentration (5–35 mg/L) were taken from the SEPT and SFAR guidelines where calculations were based on the MIC of 1 mg/L ( Enterobacteriaceae ) and not 8 mg/L ( P. aeruginosa ), since this would have resulted in a concentration above the defined toxic threshold. For CTA and MER, the target ranges were also from the SEPT and SFAR guidelines and were based on the MIC of 4 mg/L for S. aureus and 2 mg/L for P. aeruginosa , respectively. For LIN and FLU, the targets were based on the 2–4 times the MIC . For CIP, the target range was set as Cmax/MIC > 10. TAZ range was 2–5 mg/L at 500 mg given with PIP. MIC, minimum inhibitory concentration; EUCAST, European Committee on Antimicrobial Susceptibility Testing; PK/PD, pharmacokinetic/pharmacodynamic; Cmax, maximum concentration; CZO, cefazolin; CEP, cefepime; CTA, cefotaxime; CTZ, ceftazidime; CIP, ciprofloxacin; FLU, flucloxacillin; MER, meropenem; LIN, linezolid; PIP, piperacillin; TAZ, tazobactam; S, susceptible, wild-type organism; R, resistant organism.

Article Snippet: Cefazolin sodium (98 % purity), cefazolin 13 C 2 15 N (CZO-IS; 98.6 % isotopic purity), cefepime dihydrochloride monohydrate (98 % purity), cefepime 2 H 3 sulfate (CEP-IS; 98.6 % isotopic purity), cefotaxime 2 H 3 (CTA-IS; 99.8 % isotopic purity), ceftazidime pentahydrate (97 % purity), ceftazidime 2 H 5 (CTZ-IS; 99.4 % isotopic purity), ciprofloxacin (98 % purity), ciprofloxacin 2 H 8 (CIP-IS; 98.3 % isotopic purity), flucloxacillin sodium (97 % purity), flucloxacillin 13 C 4 (FLU-IS; 99.5 % isotopic purity), linezolid (98 % purity), linezolid 2 H 3 (LIN-IS; 98.3 % isotopic purity), meropenem trihydrate (97 % purity), meropenem 2 H 6 (MER-IS; 99.6 % isotopic purity), piperacillin 2 H 5 (PIP-IS; 98.9 % isotopic purity), tazobactam sodium (96 % purity), tazobactam sodium 13 C 2 15 N (TAZ-IS; 97.9 % isotopic purity) were purchased from Toronto Research Chemicals (PM Separations, Australia).

Techniques: Clinical Proteomics, Concentration Assay

Journal: npj Antimicrobials and Resistance

Article Title: Flash optimization of drug combinations for Acinetobacter baumannii with IDentif.AI-AMR

doi: 10.1038/s44259-025-00079-2

Figure Lengend Snippet: Selected drug concentrations for IDentif.AI analysis

Article Snippet: Nine FDA-approved drugs of meropenem (MEM), tigecycline (TGC), polymyxin B (PB), minocycline (MI), amikacin (AN), ampicillin-sulbactam (SAM), rifampicin (RA), eravacycline (ERV), and cefiderocol (FDC) were purchased from Selleckchem (MEM: S1381, PB: S1395, TGC: S1403, MI: S4226), TargetMol (ERV: T11227, RA: T0681, AMP: T0814L, SUL: T1631, AN: T1013), and BOC Sciences (FDC: B0084-475177).

Techniques: Clinical Proteomics, Concentration Assay

Journal: bioRxiv

Article Title: Pathogen genomic surveillance as a scalable framework for precision phage therapy

doi: 10.1101/2024.06.15.599013

Figure Lengend Snippet: A, Kaplan-Meier curves showing the survival of G. mellonella larvae after infection with either phage-resistant ST2-KL3 CRAB lines or with wild-type counterparts. HSFPh- and HS-resistant lines (left and middle panel) have decreased virulence compared to their wild-type counterparts, in contrast to the H-resistant line (right panel). **** indicates p < 0.0001 from two-sided Log-rank test, n = 10 larvae/group, ≥ 3 biological replicates/group, PBS means larvae injected only with PBS, inoculum size = 9*10 6 CFU. B, Antibiotic sensitivity profile of the HSFPh cocktail-resistant lines. The intensity of the orange shading indicates the median (n≥3) log 2 fold change in the minimum inhibitory concentration (MIC) of the cocktail-resistant lines in comparison to their wild-type counterparts as measured using the microbroth dilution method (see Methods and Supplementary Table 25). The darker the intensity, the higher the reduction in the MIC. The 5 antibiotics with clinical relevance are: MER-meropenem, IMI-Imipenem, COL-colistin, LEV-levofloxacin, T-S-a combination of Trimethoprim and Sulfamethoxazole (1:5 ratio). The star indicates a transition from the resistant state to the intermediate state according to EUCAST clinical breakpoint. C, Kaplan-Meier curves showing that both the cocktail HS (MOI 10:10, purple) and the cocktail HSFPh (MOI 10:1:0.1:0.1, orange) significantly improve the survival of G. mellonella larvae infected with Aci 110 ST2-KL3 isolate as compared to the untreated larvae (grey) (CFU = 9*10 6 , n = 10 larvae/group, ≥ 3 biological replicates/group, PBS – larvae injected only with PBS). **** indicates p < 0.0001 from a two-sided Log-rank test. D, Kaplan-Meier curves showing that both Highwayman phage alone (MOI 6, red) and the cocktail HSFPh (MOI 6:1:1:1, orange) saved 100% of mice infected with Aci 15 ST2-KL3 isolate as opposed to the untreated animals (grey) (CFU = 10 9 , n = 5 mice/group) *** indicates p < 0.00027 from the Log-rank test. For A, C, and D data are available in Supplementary Table 24.

Article Snippet: Minimum inhibitory concentrations (MICs) of five clinically relevant antibiotics: Colistin (Pharma), Meropenem (Bioscience), Imipenem (MedChemExpress), Levofloxacin (MedChemExpress), Trimetoprim: Sulphametoxazole (1:5 ratio) (Sigma, MedChemExpress) were determined using the standard microbroth dilution protocol and interpreted using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines.

Techniques: Infection, Injection, Concentration Assay, Comparison