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Wiadomosci Lekarskie (Warsaw, Poland :... 2024We reported the case of tonsillitis treatment in a 17-years-old boy with use of chemical non-antibiotic preparations, plant derived products and antibiotic benzathine...
We reported the case of tonsillitis treatment in a 17-years-old boy with use of chemical non-antibiotic preparations, plant derived products and antibiotic benzathine phenoxymethylpenicillin. The antimicrobial agents for treatment were selected on the basis of their activity against a disease agent, the group A β-hemolytic strain Streptococcus pyogenes BS1 isolated from a patient. The bacterium was susceptible in vitro to β-lactams, with largest zones conditioned by penicillin G and benzathine phenoxymethylpenicillin discs, to fluoroquinolones and to cephems, with exception of cefazolin. Lincosamide clindamycin, macrolide spiramycin, aminoglycoside gentamicin, erythromycin, tetracycline and combination of sulfamethoxazole and trimethoprim were inactive against this bacterium. The Streptococcus pyogenes BS1 demonstrated intermediate susceptibility to the cephalosporin cephalexin, fluoroquinolone lomefloxacin and glycopeptide vancomycin. Non-antibiotic preparations were evaluated against Streptococcus pyogenes BS1 also. Among them "Stomatidin", "Chlorophyllipt", and phages of "Pyofag" were more effective than "Decatylen", "Decasan" and "Furadonin" in vitro. The antimicrobial applications of "Stomatidin", "Chlorophyllipt" and phages of "Pyofag" in the patient were less effective compared to the result of antibiotic benzathine phenoxymethylpenicillin treatment. Complete recovery of the patient was achieved with use of this antibiotic and Calendula flower extract as an local anti-inflammatory agent.
Topics: Adolescent; Humans; Anti-Bacterial Agents; Anti-Infective Agents; Ethylenediamines; Penicillin V; Streptococcus pyogenes; Tonsillitis
PubMed: 38431823
DOI: 10.36740/WLek202401122 -
International Journal of Biological... Mar 2024Metallo-β-lactamases (MβLs) stand as significant resistant mechanism against β-lactam antibiotics in Gram-negative bacteria. The worldwide dissemination of New Delhi...
Metallo-β-lactamases (MβLs) stand as significant resistant mechanism against β-lactam antibiotics in Gram-negative bacteria. The worldwide dissemination of New Delhi metallo-β-lactamases (NDMs) intensifies antimicrobial resistance, posing severe threats to human health due to the absence of inhibitors available in clinical therapy. L3, a flexible β-hairpin loop flanking the active site in MβLs, has been proven to wield influence over the reaction process by assuming a crucial role in substrate recognition and intermediate stabilization. In principle, it potentially retards product release from the enzyme, consequently reducing the overall turnover rate although the details regarding this aspect remain inadequately elucidated. In this study, we crystallized NDM-1 in complex with three penicillin substrates, conducted molecular dynamics simulations, and measured the steady-state kinetic parameters. These analyses consistently unveiled substantial disparities in their interactions with loop L3. We further synthesized a penicillin V derivative with increased hydrophobicity in the R1 side chain and co-crystallized it with NDM-1. Remarkably, this compound exhibited much stronger dynamic interplay with L3 during molecular dynamics simulation, showed much lower K and k values, and demonstrated moderate inhibitory capacity to NDM-1 catalyzed meropenem hydrolysis. The data presented here may provide a strategic approach for designing mechanism-based MβL inhibitors focusing on structural elements external to the enzyme's active center.
Topics: Humans; Penicillins; beta-Lactams; Catalytic Domain; Hydrolysis; beta-Lactamases; Anti-Bacterial Agents
PubMed: 38336327
DOI: 10.1016/j.ijbiomac.2024.130041 -
Analytical Methods : Advancing Methods... Jan 2024: The optimization of antimicrobial dosing plays a crucial role in improving the likelihood of achieving therapeutic success while reducing the risks associated with...
: The optimization of antimicrobial dosing plays a crucial role in improving the likelihood of achieving therapeutic success while reducing the risks associated with toxicity and antimicrobial resistance. Probenecid has shown significant potential in enhancing the serum exposure of phenoxymethylpenicillin, thereby allowing for lower doses of phenoxymethylpenicillin to achieve similar pharmacokinetic/pharmacodynamic (PK/PD) targets. We developed a triple quadrupole liquid chromatography mass spectrometry (TQ LC/MS) analysis of, phenoxymethylpenicillin, benzylpenicillin and probenecid using benzylpenicillin-d7 and probenecid-d14 as IS in single low-volumes of human serum, with improved limit of quantification to support therapeutic drug monitoring. : Sample clean-up was performed by protein precipitation using acetonitrile. Reverse phase chromatography was performed using TQ LC/MS. The mobile phase consisted of 55% methanol in water + 0.1% formic acid, with a flow rate of 0.4 mL min. Antibiotic stability was assessed at different temperatures. : Chromatographic separation was achieved within 2 minutes, allowing simultaneous measurement of phenoxymethylpenicillin, benzylpenicillin and probenecid in a single 15 μL blood sample. Validation indicated linearity over the range 0.0015-10 mg L, with accuracy of 96-102% and a LLOQ of 0.01 mg L. All drugs demonstrated good stability under different storage conditions. : The developed method is simple, rapid, accurate and clinically applicable for the quantification of phenoxymethylpenicillin, benzylpenicillin and probenecid in tandem.
Topics: Humans; Penicillin V; Probenecid; Tandem Mass Spectrometry; Anti-Bacterial Agents; Penicillin G
PubMed: 38189092
DOI: 10.1039/d3ay01816d