Synergistic meropenem-tobramycin combination dosage regimens against clinical hypermutable Pseudomonas aeruginosa at simulated epithelial lining fluid concentrations in a dynamic biofilm model.

Synergistic meropenem-tobramycin combination dosage regimens against clinical hypermutable Pseudomonas aeruginosa at simulated epithelial lining fluid concentrations in a dynamic biofilm model. Antimicrob Agents Chemother. 2019 Aug 19;: Authors: Bilal H, Bergen PJ, Kim TH, Chung SE, Peleg AY, Oliver A, Nation RL, Landersdorfer CB Abstract Exacerbations of chronic Pseudomonas aeruginosa infections are a major treatment challenge in cystic fibrosis due to biofilm formation and hypermutation. We aimed to evaluate different dosage regimens of meropenem and tobramycin in monotherapies and combination against hypermutable carbapenem-resistant P. aeruginosa A hypermutable P. aeruginosa isolate (MICmeropenem and MICtobramycin 8 mg/L) was investigated in the dynamic CDC biofilm reactor over 120 h. Regimens were meropenem as standard (2 g 8-hourly, 30% epithelial lining fluid (ELF) penetration) and continuous infusion (CI, 6 g/day, 30% and 60% ELF penetration), and tobramycin 10 mg/kg 24-hourly (50% ELF penetration). The time-courses of total and less-susceptible bacteria and MICs were determined and antibiotic concentrations quantified by LC-MS/MS. All monotherapies failed with substantial regrowth of planktonic (>6 log10 CFU/mL) and biofilm (≥6 log10 CFU/cm2) bacteria. Except for meropenem CI (60% ELF penetration) all monotherapies amplified less-susceptible planktonic and biofilm bacteria by 120 h. The meropenem standard regimen with tobramycin caused ini...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research

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In this study, the in vitro activities of various ceragenins against Achromobacter-species biofilms were investigated comparatively with a conventional antibiotic (meropenem). Biofilm-formation inhibition and biofilm-adhesion inhibition were investigated on five strong biofilm-producing strains. The lowest MIC50 result was obtained with CSA-13. All of the tested CSAs showed significant biofilm inhibitory activity in the manner of a time- and concentration-dependent effect. To the best of our knowledge, this is the first article to evaluate the antibacterial and antibiofilm activities of tested CSAs against Achromobact...
Source: Journal of Chemotherapy - Category: Cancer & Oncology Tags: J Chemother Source Type: research
Abstract Achromobacter is a genus of non-fermenting Gram negative bacteria under order Burkholderiales Although primarily isolated from respiratory tract of people with cystic fibrosis, Achromobacter spp. can cause a broad range of infections in hosts with other underlying conditions. Their rare occurrence and ever-changing taxonomy hinder defining their clinical features, risk factors for acquisition and adverse outcomes, and optimal treatment. Achromobacter spp. are intrinsically resistant to several antibiotics (e.g. most cephalosporins, aztreonam and aminoglycosides), and are increasingly acquiring resistance ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Conclusions: This study enriches the understanding of MDR Achromobacter spp. epidemiology, confirms prevalence and chronic colonization of A. xylosoxidans in CF lungs. It presents in vitro data to support the efficacy of new combinations for use in the treatment of chronic Achromobacter infections. PMID: 32816722 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
ron G Abstract The treatment of invasive and chronic aspergillosis involves triazole drugs. Its intensive use has resulted in the selection of resistant isolates and at present, azole resistance in Aspergillus fumigatus is considered an emerging threat to public health worldwide.The aim of this work is to uncover the molecular mechanism implicated in the azole resistance phenotype of three Aspergillus fumigatus clinical strains isolated from an Argentinian cystic fibrosis patient under long-term triazole treatment.Strain susceptibilities were assessed and CYP51A gene sequences were analyzed. Two of the studied Asp...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Abstract Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOΔmutS (MICciprofloxacin 0.25 mg/L, MICmeropenem 2 mg/L) and CW44 (MICciprofloxacin 0.5 mg/L, MICmeropenem 4 mg/L), were investigated for 120h. Concentration-time profiles achievable in epithelial lining...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
ia AM Abstract Pseudomonas aeruginosa exploits intrinsic and acquired resistance mechanisms to resist almost every antibiotic used in chemotherapy. Antimicrobial resistance in P. aeruginosa isolated from cystic fibrosis (CF) patients is further enhanced by the occurrence of hypermutator strains, a hallmark of chronic CF infections. However, the within-patient genetic diversity of P. aeruginosa populations related to antibiotic resistance remains unexplored. Here, we show the evolution of the mutational resistome profile of a P. aeruginosa hypermutator lineage by performing longitudinal and transversal analyses of ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Abstract Pseudomonas aeruginosa is a major cause of respiratory biofilm-related infections in patients with cystic fibrosis. We developed an in-vitro pharmacodynamic model to study the activity of antipseudomonal antibiotics against PAO1 biofilms grown in artificial sputum medium with agar (ASM(+)) vs. trypticase soy broth supplemented with glucose and NaCl (TGN). We measured bacterial counts, metabolic activity (fluorescein diacetate [FDA] hydrolysis) and biomass (crystal violet absorbance). Biofilms grew slower in ASM(+) vs. TGN but reached the same cfu counts and metabolic activity, and slightly higher biomass ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
In conclusion, AeroVanc was well tolerated and achieved high levels in sputum with a mean systemic absorption of 49%, making it a potential therapeutic strategy for respiratory infection with MRSA. PMID: 31964790 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Conclusions: P. aeruginosa CF isolates exhibited the lowest resistance rates against ceftolozane-tazobactam, ceftazidime-avibactam and colistin. Murepavadin demonstrated the highest activity on a per weight basis and may therefore become a valuable addition to the currently available antibiotics for treatment of respiratory infection in people with CF. PMID: 31767727 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Aim: To determine the characteristics of chronic lung diseases in patients with mycobacterioses caused by slowly growing nontuberculous mycobacteria (NTM).We studied 51 patients with pulmonary mycobacterioses caused by slowly growing NTM; the average age was 54.1±0.3 yrs; disease duration was 19.5±0.5 months. In all patients the diagnosis was microbiologically verified. Out of them 25 (49%) were infected with M. avium, 21.5% – M. intracellulare, 9.8% – M. kansasii, 5.8% – M. xenopi, 3.9% – M. gordonae, 3.9% – M. lentiflavum. Four patients were co-infected with M. avium + M. intra...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Respiratory infections Source Type: research
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