Introduction: Neutrophilic granulocytes represent the first line of defense against microorganisms. Granulocytes phagocytose microorganisms and specifically synthesize oxygen radicals against them, which eventually kills the invaders. Methods: Neutrophilic granulocytes were isolated from peripheral blood of healthy volunteer donors. Putative interference of new-generation antibiotics with neutrophil function was tested using a collection of granulocyte-stimulating agents and Amplex™ Red-based plate assay and flow cytometry-based respiratory burst assays. In addition, phagocytosis of E. coli, IL-8 production, bactericidal activity, and CD62L expression of granulocytes were evaluated. Results: Of note, we found that the two glycopeptide antibiotics dalbavancin and teicoplanin inhibited ROS production upon granulocyte activation via different signaling pathways in a dose-dependent manner. Dalbavancin also blocked the PMA-induced shedding of CD62L. In contrast, the oxazolidinone antibiotics tedizolid and linezolid had no effect on neutrophil function, while the combination of ceftazidime/avibactam dose dependently inhibited the fMLP/Cytochalasin B-induced granulocyte burst in a dose-dependent manner. Additionally, we showed that dalbavancin and teicoplanin as well as sulfametrole/trimethoprim and ceftazidime/avibactam inhibited baseline and PMA-induced IL-8 production by neutrophilic granulocytes. Moreover, dalbavancin impaired the bactericidal activity of neutrophilic granulocytes. Conclusion: We here identified hitherto unknown inhibitory effects of several classes of antibiotics on the effector functions of neutrophilic granulocytes.

01 May 2020·Journal of Antimicrobial ChemotherapyQ2 · MEDICINE

Pharmacokinetics of trimethoprim/sulfametrole in critically ill patients on continuous renal replacement therapy

Q2 · MEDICINE

Article

Author: Eschertzhuber, Stephan ; Zaruba, Marc-Michael ; Bellmann-Weiler, Rosa ; Beyer, Rudolph ; Ranke, Paul ; Hotter, Johannes ; Broeker, Astrid ; Wicha, Sebastian G ; Lorenz, Ingo ; Joannidis, Michael ; Welte, René ; Bellmann, Romuald ; Gasperetti, Tiziana ; Ströhle, Mathias

AbstractObjectivesWe investigated the effect of continuous renal replacement therapy (CRRT) on the pharmacokinetics of trimethoprim and sulfametrole.Patients and methodsWe enrolled critically ill adults undergoing CRRT and critically ill adults with normal or slightly impaired renal function (plasma creatinine concentration <1.5 mg/dL, control group). All patients received trimethoprim/sulfametrole at standard doses. Pharmacokinetics were determined after the first dose and at steady-state. In addition, a population pharmacokinetic model using plasma data was built. We also assessed the renal clearance (CLR) and the extracorporeal clearance in patients undergoing CRRT.ResultsTwelve patients were enrolled in the CRRT group and 12 patients in the control group. There was no statistically significant difference in trimethoprim pharmacokinetics between the two groups. In patients on CRRT, total plasma clearance (CLtot) and V of sulfametrole were significantly higher than in the control group. However, sulfametrole exposure was not significantly altered during CRRT. The population pharmacokinetic analysis indicated that neither CRRT intensity nor residual diuresis were significant covariates on trimethoprim or sulfametrole CL. Median CL by continuous venovenous haemofiltration accounted for about one-third of CLtot of trimethoprim and for about one-half of CLtot of sulfametrole. In patients on CRRT, CLR of trimethoprim and sulfametrole were <5% of CLtot.ConclusionsDuring CRRT, standard doses of trimethoprim/sulfametrole appear to be adequate.

01 Apr 2014·Journal of Antimicrobial ChemotherapyQ2 · MEDICINE

Comparative in vitro activity of sulfametrole/trimethoprim and sulfamethoxazole/trimethoprim and other agents against multiresistant Gram-negative bacteria

Q2 · MEDICINE

Article

Author: Neil Woodford ; David M Livermore ; Shazad Mushtaq ; Marina Warner

OBJECTIVESSulfamethoxazole/trimethoprim is standard therapy for infections caused by opportunist non-fermenters except Pseudomonas aeruginosa and Acinetobacter. Sulfametrol(e)/trimethoprim is an alternative to sulfamethoxazole/trimethoprim available in some EU countries, with possible pharmacological advantages. We compared their activities against (i) non-fermenters, (ii) multiresistant Enterobacteriaceae and (iii) reference strains with sul1 and sul2.METHODSTest isolates were recent submissions to the reference laboratory, or were Escherichia coli previously shown to have sul1 or sul2. Identification was by MALDI-ToF, by 16S rRNA gene sequencing or with API20NE strips. MICs were determined by CLSI agar dilution. The Stenotrophomonas maltophilia and Burkholderia series were enhanced by inclusion of 25% sulfamethoxazole/trimethoprim-resistant isolates; other series were not enhanced.RESULTSMICs of sulfametrole/trimethoprim for non-fermenters tracked those of sulfamethoxazole/trimethoprim, being equal in 97/170 cases, 2-fold higher in 57/170 cases and 2-fold lower in 12/170 cases. Despite supplementing the Burkholderia and S. maltophilia collections with sulfamethoxazole/trimethoprim-resistant organisms, the antifolate combinations retained better activity against these and other non-fermenters than did piperacillin/tazobactam, moxifloxacin, ticarcillin/clavulanate, tigecycline, cefotaxime or imipenem. By contrast, few (5%-20%) of the extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacteriaceae were susceptible to the sulphonamides or their trimethoprim combinations, probably reflecting widespread co-carriage of sul1 and sul2, which both conferred resistance.CONCLUSIONSAntifolate combinations remain the most active antimicrobials against less common non-fermenters, importantly including S. maltophilia and Burkholderia spp., but resistance is prevalent among ESBL- and carbapenemase-producing Enterobacteriaceae. Sulfametrole/trimethoprim had similar activity to sulfamethoxazole/trimethoprim against non-fermenters.

100 Deals associated with Sulfametrole

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KEGG	Wiki	ATC	Drug Bank
D08541	Sulfametrole	J01	DB15975

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