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Biomaterials May 2023Lung bacterial infections could result in acute lung inflammation/injury (ALI) that propagates to its severe form, acute respiratory distress syndrome (ADRS) leading to...
Lung bacterial infections could result in acute lung inflammation/injury (ALI) that propagates to its severe form, acute respiratory distress syndrome (ADRS) leading to the death. The molecular mechanism of ALI is associated with bacterial invasion and the host inflammation response. Here, we proposed a novel strategy to specifically target both bacteria and inflammatory pathways by co-loading of antibiotics (azlocillin, AZ) and anti-inflammatory agents (methylprednisolone sodium, MPS) in neutrophil nanovesicles. We found that cholesterol infilling in the membrane of nanovesicles can maintain a pH gradient between intra-vesicles and outer-vesicles, so we remotely loaded both AZ and MPS in single nanovesicles. The results showed that loading efficiency of both drugs can achieve more than 30% (w/w), and delivery of both drugs using nanovesicles accelerated bacterial clearance and resolved inflammation responses, thus preventing the potential lung damage due to infections. Our studies show that remote loading of multiple drugs in neutrophil nanovesicles which specifically target the infectious lung could be translational to treat ARDS.
Topics: Humans; Neutrophils; Pharmaceutical Preparations; Lung; Pneumonia; Inflammation; Respiratory Distress Syndrome; Bacterial Infections; Bacteria
PubMed: 36878092
DOI: 10.1016/j.biomaterials.2023.122071 -
Antimicrobial Agents and Chemotherapy Apr 1984The susceptibilities of 347 urine isolates of enterococci (Streptococcus faecalis, 44%; S. faecalis subsp. zymogenes, 37%; S. faecalis subsp. liquefaciens, 19%) to... (Comparative Study)
Comparative Study
The susceptibilities of 347 urine isolates of enterococci (Streptococcus faecalis, 44%; S. faecalis subsp. zymogenes, 37%; S. faecalis subsp. liquefaciens, 19%) to ampicillin, azlocillin, mezlocillin, piperacillin, vancomycin, gentamicin, erythromycin, rosaramicin, rifampin, rifampin plus trimethoprim (1:4), trimethoprim-sulfamethoxazole (1:20), and chloramphenicol were determined by the agar dilution technique. There were no significant differences in susceptibility to individual agents among the subspecies of S. faecalis. Azlocillin and mezlocillin (MIC for 90% of isolates, 0.78 micrograms/ml) and piperacillin, ampicillin, and vancomycin (MIC for 90% of isolates, 1.56 micrograms/ml) were the most active agents and were significantly more potent than the other reference antibiotics tested.
Topics: Anti-Bacterial Agents; Bacteriuria; Enterococcus faecalis; Humans; Microbial Sensitivity Tests; Streptococcal Infections
PubMed: 6428309
DOI: 10.1128/AAC.25.4.532 -
Antimicrobial Agents and Chemotherapy May 1986The single-dose pharmacokinetics of azlocillin and piperacillin were compared by using a randomized, crossover design. The concentrations of azlocillin in serum were... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The single-dose pharmacokinetics of azlocillin and piperacillin were compared by using a randomized, crossover design. The concentrations of azlocillin in serum were consistently higher than those of piperacillin throughout an 8-h study. The area under the time-concentration curve of azlocillin was significantly greater than that of piperacillin, and the total body clearance of azlocillin was significantly lower than that of piperacillin.
Topics: Adult; Azlocillin; Female; Humans; Kinetics; Male; Models, Biological; Piperacillin
PubMed: 3729353
DOI: 10.1128/AAC.29.5.938 -
Infection and Drug Resistance 2021We investigated the clonal diversity of carbapenemase-producing isolates from the Shenzhen Children's Hospital, China, and drew conclusions on the clinical and public...
AIM
We investigated the clonal diversity of carbapenemase-producing isolates from the Shenzhen Children's Hospital, China, and drew conclusions on the clinical and public health impact of these isolates as multidrug-resistant.
METHODS
From January 2014 to December 2018, a total number of 36 unique carbapenemase-producing clinical isolates of were collected out of 900 clinical isolates in paediatric patients from the Shenzhen Children's Hospital, China. After carbapenemase production confirmation, antimicrobial susceptibility, resistance determinants and phylogenetic relationship were determined.
RESULTS
The isolates showed resistance to ceftazidime, ertapenem, ampicillin, cefazolin, ceftriaxone, cefotetan, ticarcillin, cefaclor, cefpodoxime, azlocillin, cefcapene, mezlocillin and ampicillin-sulbactam. Of the 36 carbapenemase genes coding isolates, was the mostly detected 50% (n=18) followed by and 19% (n=7), 17% (n=6), 8% (n=3) and 5% (n=2), whereas extended-spectrum β-lactamase ( ) was predominantly detected 92% (n=33) followed by 53% (n=19) and 28% (n=10). Pulsed-field gel electrophoresis typing showed eight different patterns, and twenty-five distinct sequences types were observed with ST307 being predominantly identified 11% (n=4), followed by ST2407 8% (n=3). Plasmid replicon typing results indicated that IncFIS, IncHI2, IncFIC and IncFIA plasmids carry and genes.
CONCLUSION
This study reports on the occurrence and spread of carbapenemase and extended-spectrum β-lactamase encoding genes co-existence in sporadic ST307 in paediatric patients from the Shenzhen Children's Hospital, China.
PubMed: 34511949
DOI: 10.2147/IDR.S324018 -
Antimicrobial Agents and Chemotherapy Mar 1980The pharmacokinetics of azlocillin were investigated in five healthy subjects and in 16 subjects with chronic renal failure. After intravenous bolus injection of a... (Comparative Study)
Comparative Study
The pharmacokinetics of azlocillin were investigated in five healthy subjects and in 16 subjects with chronic renal failure. After intravenous bolus injection of a single dose of 30 mg/kg in normal subjects, pharmacokinetic data were calculated, using a two-compartment open body model. The mean distribution serum half-life (T(1/2alpha)) was 0.11 h, and the mean elimination serum half-life (T(1/2beta)) was 0.89 h. The volume of the central compartment (V(C)) was 7.36 liters/1.73 m(2), and the apparent volume of distribution (V(dss)) was 14.15 liters/1.73 m(2), i.e., 21.9% of body weight. The T(1/2beta) after a 30-min intravenous infusion of 80 mg/kg to the same healthy subjects was 1.11 h. Serum clearances (C(S)) for the 30- and 80-mg/kg doses were 215.0 and 152.9 ml/min per 1.73 m(2). The mean renal clearances (C(R)) were 145.2 and 94.1 ml/min per 1.73 m(2) for the respective doses. Between 61.8 and 69.6% of the injected dose was recovered in urine during the first 24 h. The elimination half-life in subjects with chronic renal impairment increased with the degree of renal insufficiency. After a 30-min intravenous infusion of 80 mg/kg the T(1/2beta) values were 2.03, 4.01, and 5.66 h with creatinine clearances (C(cr)) within 30 to 50, 10 to 30, and <10 ml/min per 1.73 m(2), respectively. Urinary elimination was inversely related to the degree of renal impairment. In four patients out of and on a 6-h hemodialysis session mean elimination half-life values were 6.53 and 2.81 h, respectively. The fraction of drug removed by dialysis was 45.8%. The linear relationships between the elimination of half-life (T(1/2beta)) and serum creatinine and the elimination rate constant (beta) and creatinine clearance (C(cr)) provided a basis for adjustment of dosage in renal failure.
Topics: Adult; Azlocillin; Creatinine; Half-Life; Humans; Kidney Failure, Chronic; Penicillins; Renal Dialysis
PubMed: 7425600
DOI: 10.1128/AAC.17.3.344 -
Biophysical Journal Mar 2006To study translocation of beta-lactam antibiotics of different size and charge across the outer bacterial membrane, we combine an analysis of ion currents through single... (Comparative Study)
Comparative Study
To study translocation of beta-lactam antibiotics of different size and charge across the outer bacterial membrane, we combine an analysis of ion currents through single trimeric outer membrane protein F (OmpF) porins in planar lipid bilayers with molecular dynamics simulations. Because the size of penicillin molecules is close to the size of the narrowest part of the OmpF pore, penicillins occlude the pore during their translocation. Favorably interacting penicillins cause time-resolvable transient blockages of the small-ion current through the channel and thereby provide information about their dynamics within the pore. Analyzing these random fluctuations, we find that ampicillin and amoxicillin have a relatively high affinity for OmpF. In contrast, no or only a weak interaction is detected for carbenicillin, azlocillin, and piperacillin. Molecular dynamics simulations suggest a possible pathway of these drugs through the OmpF channel and rationalize our experimental findings. For zwitterionic ampicillin and amoxicillin, we identify a region of binding sites near the narrowest part of the channel pore. Interactions with these sites partially compensate for the entropic cost of drug confinement by the channel. Whereas azlocillin and piperacillin are clearly too big to pass through the channel constriction, dianionic carbenicillin does not find an efficient binding region in the constriction zone. Carbenicillin's favorable interactions are limited to the extracellular vestibule. These observations confirm our earlier suggestion that a set of high-affinity sites at the narrowest part of the OmpF channel improves a drug's ability to cross the membrane via the pore.
Topics: Anti-Bacterial Agents; Computer Simulation; Escherichia coli; Ion Channel Gating; Lipid Bilayers; Membrane Fluidity; Models, Biological; Models, Chemical; Penicillins; Porins; Porosity; Static Electricity; beta-Lactams
PubMed: 16339889
DOI: 10.1529/biophysj.105.075192 -
Antimicrobial Agents and Chemotherapy Nov 1982The impacts of meningeal infection with Pseudomonas aeruginosa and route of drug administration on the penetration of azlocillin and mezlocillin into the cerebrospinal... (Comparative Study)
Comparative Study
Comparative penetration of azlocillin and mezlocillin into cerebrospinal fluid of normal rabbits and rabbits with experimentally induced Pseudomonas aeruginosa meningitis.
The impacts of meningeal infection with Pseudomonas aeruginosa and route of drug administration on the penetration of azlocillin and mezlocillin into the cerebrospinal fluid of rabbits were evaluated. The penetration of both agents was increased to a similar degree in rabbits with meningitis compared with normal rabbits. The increase in penetration was greater after intravenous administration than after intramuscular administration.
Topics: Animals; Anti-Bacterial Agents; Azlocillin; Meningitis; Mezlocillin; Penicillins; Pseudomonas Infections; Rabbits
PubMed: 6217786
DOI: 10.1128/AAC.22.5.909 -
Antimicrobial Agents and Chemotherapy Oct 1976The antimicrobial susceptibility of 492 anaerobic bacteria, the majority of which were recent clinical isolates, was determined by the agar dilution technique....
The antimicrobial susceptibility of 492 anaerobic bacteria, the majority of which were recent clinical isolates, was determined by the agar dilution technique. Penicillin G was active against most of the strains tested at 32 U or less/ml, but only 72% of Bacteroides fragilis strains were susceptible at this level and 9% required 256 U or more/ml. Ampicillin was effective against most of the strains except B. fragilis at 16 mug or less/ml. Amoxicillin was active against only 31% of B. fragilis, 76% of other Bacteroides species, and 67% of Fusobacterium species at 8 mug/ml. Two new penicillins, mezlocillin and azlocillin, were similar to ampicillin in their activity. Carbenicillin and ticarcillin inhibited all but a few strains at 128 mug or less/ml. BLP 1654 was somewhat more active than penicillin G against B. fragilis but had similar activity against other anaerobes. Cephalothin was inactive against B. fragilis, and only 65% of other Bacteroides species were inhibited by 32 mug or less/ml. It was effective against all other anaerobes at that level. Cefamandole showed somewhat greater activity than cephalothin against B. fragilis but generally less activity against gram-positive organisms. Cefazaflur (SKF 59962) was comparable to cephalothin against B. fragilis. Cefoxitin was distinctly more active than cephalothin against B. fragilis. These latter two agents were less active than cephalothin against the gram-positive anaerobes. Chloramphenicol remains active against anaerobic bacteria at 16 mug or less/ml, with rare exceptions. Thiamphenicol was similar to chloramphenicol in its activity. Clindamycin was very active against most of the anaerobes at 8 mug or less/ml. Erythromycin and josamycin were also tested, with josamycin showing greater activity against B. fragilis than either erythromycin or clindamycin. A new oligosaccharide, everninomicin B, was less active than clindamycin against B. fragilis but more active against clostridia and some of the other strains tested. Most of the groups of bacteria tested demonstrated a trend toward resistance to tetracycline. Doxycycline and minocycline were somewhat more active than was tetracycline. Metronidazole was active against the majority of the anaerobes tested; resistance ws demonstrated by some of the gram-positive cocci and gram-positive, non-sporeforming bacilli.
Topics: Anaerobiosis; Anti-Bacterial Agents; Bacteria; Cephalosporins; Chloramphenicol; Metronidazole; Penicillins; Tetracyclines
PubMed: 984809
DOI: 10.1128/AAC.10.4.736 -
British Journal of Pharmacology Aug 19991. Two in vivo models, in the rat, were used to investigate, in the presence of different substrates, the overall and net intestinal elimination of ciprofloxacin: an... (Comparative Study)
Comparative Study
1. Two in vivo models, in the rat, were used to investigate, in the presence of different substrates, the overall and net intestinal elimination of ciprofloxacin: an open-intestinal perfusion model and an intestinal loop model respectively. 2. In the presence of quinidine, verapamil and cyclosporin (substrates of the P-glycoprotein (P-gp)), plasma AUCs of ciprofloxacin were 1.5 - 2 fold increased, while biliary clearance (1.5 - 2 fold), intestinal overall and net clearances (2 - 4 fold and 1.5 - 8 fold respectively) decreased. The weak effect obtained with cyclosporin as compared to verapamil and especially quinidine, suggests, for ciprofloxacin, the existence of transport systems distinct from the P-gp, as the OCT1 transporter which could be inhibited by quinidine. 3. With cephalexin and azlocillin, two beta-lactam antibiotics, plasma AUCs of ciprofloxacin increased and biliary and intestinal overall clearances decreased in a similar fashion (1.3 - 2 fold), suggesting the involvement of organic anion and/or cation transporters. 4. In the presence of structural analogues, the effect was dependent on the compound administered: Sparfloxacin had no effect on intestinal clearance of ciprofloxacin. In contrast, with pefloxacin, overall intestinal clearance of ciprofloxacin was decreased and net intestinal clearance increased. 5. The specificity of ciprofloxacin intestinal transport appears to be different from P-gp as outlined by the lack of competition with sparfloxacin, a P-gp substrate. Ciprofloxacin intestinal elimination seems to be mediated by organic anion and/or cation transporters and a mechanism sensitive to quinidine and verapamil.
Topics: Animals; Anti-Infective Agents; Area Under Curve; Biological Transport, Active; Chemical Phenomena; Chemistry, Physical; Ciprofloxacin; Intestinal Absorption; Intestinal Mucosa; Male; Rats; Rats, Sprague-Dawley
PubMed: 10455332
DOI: 10.1038/sj.bjp.0702703 -
Antimicrobial Agents and Chemotherapy Nov 2000VIM-1 is a new group 3 metallo-beta-lactamase recently detected in carbapenem-resistant nosocomial isolates of Pseudomonas aeruginosa from the Mediterranean area. In...
VIM-1 is a new group 3 metallo-beta-lactamase recently detected in carbapenem-resistant nosocomial isolates of Pseudomonas aeruginosa from the Mediterranean area. In this work, VIM-1 was purified from an Escherichia coli strain carrying the cloned bla(VIM-1) gene by means of an anion-exchange chromatography step followed by a gel permeation chromatography step. The purified enzyme exhibited a molecular mass of 26 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and an acidic pI of 5.1 in analytical isoelectric focusing. Amino-terminal sequencing showed that mature VIM-1 results from the removal of a 26-amino-acid signal peptide from the precursor. VIM-1 hydrolyzes a broad array of beta-lactam compounds, including penicillins, narrow- to expanded-spectrum cephalosporins, carbapenems, and mechanism-based serine-beta-lactamase inactivators. Only monobactams escape hydrolysis. The highest catalytic constant/K(m) ratios (>10(6) M(-1). s(-1)) were observed with carbenicillin, azlocillin, some cephalosporins (cephaloridine, cephalothin, cefuroxime, cefepime, and cefpirome), imipenem, and biapenem. Kinetic parameters showed remarkable variability with different beta-lactams and also within the various penam, cephem, and carbapenem compounds, resulting in no clear preference of the enzyme for any of these beta-lactam subfamilies. Significant differences were observed with some substrates between the kinetic parameters of VIM-1 and those of other metallo-beta-lactamases. Inactivation assays carried out with various chelating agents (EDTA, 1,10-o-phenanthroline, and pyridine-2,6-dicarboxylic acid) indicated that formation of a ternary enzyme-metal-chelator complex precedes metal removal from the zinc center of the protein and revealed notable differences in the inactivation parameters of VIM-1 with different agents.
Topics: Anti-Bacterial Agents; Chelating Agents; Escherichia coli; Kinetics; beta-Lactamases
PubMed: 11036013
DOI: 10.1128/AAC.44.11.3003-3007.2000