Evaluation of interaction of chlorogenic acid and cefotaxime sodium based on sequential analysis / 药学学报

The joint application of traditional Chinese medicine injection containing chlorogenic acid (CA) and cefotaxime sodium (CS) is sometimes appeared in clinical practice, but the scientific basis of drug molecular compatibility is still weak. This study proposes a sequential analysis strategy based on isothermal titration calorimetry (ITC), cold-spray ionization mass spectrometry (CSI-MS) and antibacterial activity test to evaluate the molecular interactions between CA and CS. The results of ITC experiments showed that the Gibbs free energy ΔG < 0 and it was driven by enthalpy change when CA titrated CS, suggesting CA could spontaneously chemically react with CS. Subsequently, the parent ions (m/z 808.143 5) of binding molecular of CA and CS was detected by CSI-MS, indicating CA could chemically bond with CS. Furtherly, the antibacterial experiments found the antibacterial ability of CS against Klebsiella pneumonia was significantly reduced (P < 0.01) by CA in mixed solution. Finally, molecular docking technology showed CA and CS have a common target of penicillin binding protein 3 (PBP3), suggesting that the phenomenon of CA reduced the antibacterial ability of CS may be related to the competitive binding of two components with PBP3. Our studies have shown that CA could spontaneously chemically bond to CS and reduced its antibacterial ability, providing scientific data for molecular interaction evaluation of CA and CS.

Molecular characterization of multidrug-resistant Klebsiella pneumoniae isolates

Klebsiella pneumoniae is an important cause of healthcare-associated infections worldwide. Selective pressure, the extensive use of antibiotics, and the conjugational transmission of antibiotic resistance genes across bacterial species and genera facilitate the emergence of multidrug-resistant (MDR) K. pneumoniae. Here, we examined the occurrence, phenotypes and genetic features of MDR K. pneumoniae isolated from patients in intensive care units (ICUs) at the First Affiliated Hospital of Xiamen University in Xiamen, China, from January to December 2011. Thirty-eight MDR K. pneumoniae strains were collected. These MDR K. pneumoniae isolates possessed at least seven antibiotic resistance determinants, which contribute to the high-level resistance of these bacteria to aminoglycosides, macrolides, quinolones and β-lactams. Among these isolates, 24 strains were extended-spectrum β-lactamase (ESBL) producers, 2 strains were AmpC producers, and 12 strains were both ESBL and AmpC producers. The 38 MDR isolates also contained class I (28/38) and class II integrons (10/38). All 28 class I-positive isolates contained aacC1, aacC4, orfX, orfX’ and aadA1 genes. β-lactam resistance was conferred through bla_SHV (22/38), bla_TEM (10/38), and bla_CTX-M (7/38). The highly conserved bla_KPC-2 (37/38) and bla_OXA-23(1/38) alleles were responsible for carbapenem resistance, and a gyrAsite mutation (27/38) and the plasmid-mediated qnrB gene (13/38) were responsible for quinolone resistance. Repetitive-sequence-based PCR (REP-PCR) fingerprinting of these MDR strains revealed the presence of five groups and sixteen patterns. ...