-
Acta Tropica May 2021Pseudomonas aeruginosa (P. aeruginosa) is an important environmental, opportunistic and nosocomial pathogen with a significant threat to public health. The objectives of...
Pseudomonas aeruginosa (P. aeruginosa) is an important environmental, opportunistic and nosocomial pathogen with a significant threat to public health. The objectives of this study were to determine the in vitro antimicrobial susceptibility patterns of, and antibiotic drug combinations with synergistic effects against P. aeruginosa isolated from drinking water and hospitalized patients in Jordan. A total of 16 P. aeruginosa isolates were obtained from hospitalized patients and 15 were isolated from bottled drinking water were used in the study. Bacterial isolation and identification was performed using routine microbiological methods and confirmed using PCR technique targeting the 16S rDNA gene. The antimicrobial susceptibility patterns were determined by measuring the minimum inhibitory concentration (MIC) using the 2-fold microdilution method. Synergy interaction between various antimicrobials was determined using the checkerboard method and fractional inhibitory concentration index (FICI). The majority of water isolates were sensitive to gentamicin (93.3%), ticarcillin (86.7%) and ciprofloxacin, levofloxacin, amikacin, colistin, piperacillin, azlocillin, aztreonam, ceftazidime and imipenem (100% each). All water isolates (100%) were resistant to amoxicillin, oxytetracycline and doxycycline (93.3% and 86.7, respectively). For the clinical isolates, all (100%) were sensitive to ceftazidime, 81.3% were sensitive to aztreonam, while 62.5% were sensitive to ciprofloxacin, levofloxacin, gentamicin, amikacin, colistin, piperacillin, ticracillin, azlocillin, and imipenem. All clinical isolates (100%) were resistant to oxytetracycline, doxycycline and amoxicillin. Analysis of the checkerboard synergy assay of multi-drug resistant isolates (n=26) showed significant synergism (P ≤ 0.05) when ciprofloxacin or gentamicin were included in the combination. There were no significant differences in synergistic activity between ciprofloxacin and levofloxacin when combined with other antimicrobial agents of the beta-lactams or aminoglycosides classes. There were no significant differences in the synergistic activities between beta lactams - aminoglycoside and beta lactams - fluoroquinolone combinations. Results of this study indicate an alarming widespread presence of multidrug-resistant P. aeruginosa associated with chronic suppurative infections in hospitalized patients and apparently clean drinking water in Jordan. Treatment of clinical suppurative lesions must be based on culture and in vitro susceptibility testing using potent antimicrobial combinations to avoid emergence of resistant strains and to improve the clinical outcome of treated patients.
Topics: Anti-Bacterial Agents; Drinking Water; Drug Resistance, Bacterial; Drug Resistance, Multiple; Drug Synergism; Hospitalization; Humans; Jordan; Microbial Sensitivity Tests; Pseudomonas aeruginosa
PubMed: 33582141
DOI: 10.1016/j.actatropica.2021.105859 -
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 -
ACS Infectious Diseases Apr 2024Effective treatment of gonorrhea is threatened by the increasing prevalence of strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we...
Effective treatment of gonorrhea is threatened by the increasing prevalence of strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we demonstrated the promise of the third-generation cephalosporin cefoperazone as an antigonococcal agent due to its rapid second-order rate of acylation against penicillin-binding protein 2 (PBP2) from the ESC-resistant strain H041 and robust antimicrobial activity against H041. Noting the presence of a ureido moiety in cefoperazone, we evaluated a subset of structurally similar ureido β-lactams, including piperacillin, azlocillin, and mezlocillin, for activity against PBP2 from H041 using biochemical and structural analyses. We found that the ureidopenicillin piperacillin has a second-order rate of acylation against PBP2 that is 12-fold higher than cefoperazone and 85-fold higher than ceftriaxone and a lower MIC against H041 than ceftriaxone. Surprisingly, the affinity of ureidopenicillins for PBP2 is minimal, indicating that their inhibitory potency is due to a higher rate of the acylation step of the reaction compared to cephalosporins. Enhanced acylation results from the combination of a penam scaffold with a 2,3-dioxopiperazine-containing R group. Crystal structures show that the ureido β-lactams overcome the effects of resistance mutations present in PBP2 from H041 by eliciting conformational changes that are hindered when PBP2 interacts with the weaker inhibitor ceftriaxone. Overall, our results support the potential of piperacillin as a treatment for gonorrhea and provide a framework for the future design of β-lactams with improved activity against ESC-resistant .
Topics: Humans; Ceftriaxone; Neisseria gonorrhoeae; Gonorrhea; Penicillin-Binding Proteins; Cefoperazone; Cephalosporins; Piperacillin; beta-Lactams
PubMed: 38446051
DOI: 10.1021/acsinfecdis.3c00713 -
Infection Control and Hospital... Dec 2020To investigate the touch-contact antimicrobial efficacy of novel cold spray surface coatings composed of copper and silver metals, regard to their rate of microbial...
OBJECTIVE
To investigate the touch-contact antimicrobial efficacy of novel cold spray surface coatings composed of copper and silver metals, regard to their rate of microbial elimination.
DESIGN
Antimicrobial time-kill assay.
SETTING
Laboratory-based study.
METHODS
An adapted time-kill assay was conducted to characterize the antimicrobial efficacy of the developed coatings. A simulated touch-contact pathogenic exposure to Gram-positive Staphylococcus aureus (ATCC 25923), Gram-negative Pseudomonas aeruginosa (ATCC 27853), and the yeast Candida albicans (ATCC 10231), as well as corresponding resistant strains of gentamicin-methicillin-resistant S. aureus (ATCC 33592), azlocillin-carbenicillin-resistant P. aeruginosa (DSM 46316), and a fluconazole-resistant C. albicans strain was undertaken. Linear regression modeling was used to deduce microbial reduction rates.
RESULTS
A >7 log reduction in microbial colony forming units was achieved within minutes on surfaces with cold spray coatings compared to a single log bacterial reduction on copper metal sheets within a 3 hour contact period. Copper-coated 3-dimensional (3D) printed acrylonitrile butadiene styrene (ABS) achieved complete microbial elimination against all tested pathogens within a 15 minute exposure period. Similarly, a copper-on-copper coating achieved microbial elimination within 10 minutes and within 5 minutes with the addition of silver powder as a 5 wt% coating constituent.
CONCLUSIONS
In response to the global need for alternative solutions for infection control and prevention, these effective antimicrobial surface coatings were proposed. A longitudinal study is the next step toward technology integration.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Humans; Laboratories; Longitudinal Studies; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests
PubMed: 32811579
DOI: 10.1017/ice.2020.335 -
Analytica Chimica Acta Mar 2020The uncontrolled usage of veterinary antibiotics has led to their widespread pollution in waterways and milk products. Potential impact of antibiotic residues on the...
The uncontrolled usage of veterinary antibiotics has led to their widespread pollution in waterways and milk products. Potential impact of antibiotic residues on the environment and human health such as increased antibiotic resistance of microorganisms and triggering allergic reactions in humans have been reported. In this work, we developed a highly selective and sensitive voltammetric aptasensor for on-step, sensitive and low cost detection of azlocillin antibiotic, one of the broad spectrum β-lactam antibiotics. The successful selection of DNA aptamers against azlocillin was accomplished using systemic evolution of ligands by exponential enrichment (SELEX) method. Fluorescence-binding assays showed dissociation constant of 55 nM for one of the selected aptamers (Az9). This aptamer was used to construct a competitive voltammetric aptasensor for azlocillin. A limit of detection of 1.2 pg/mL as well as remarkable selectivity against potential interfering agents, including amoxicillin, were achieved. This signal-off competitive sensor takes 30-50 min to complete the quantification of the target antibiotic. The sensor was challenged by detecting the target directly in complex environments such as tap and waste water where good recovery percentages were achieved.
Topics: Anti-Bacterial Agents; Aptamers, Nucleotide; Azlocillin; Base Sequence; Biosensing Techniques; DNA; Drinking Water; Electrochemical Techniques; Limit of Detection; Wastewater; Water Pollutants, Chemical
PubMed: 32029106
DOI: 10.1016/j.aca.2019.12.023 -
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 -
Clinical Pharmacokinetics Nov 2021Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex...
BACKGROUND
Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data.
OBJECTIVE
The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates.
METHODS
Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds. Individual estimates of clearance obtained from population pharmacokinetic models were used as reference clearances, and diverse machine learning methods and nested cross-validation were adopted and evaluated against these reference clearances. The predictive performance of these combined methods was compared with the performance of two other predictive methods: a covariate-based maturation model and a postmenstrual age and body weight scaling model. Relative error was used to evaluate the different methods.
RESULTS
The extra tree regressor was selected as the best-fit machine learning method. Using the combined method, more than 95% of predictions for all six drugs had a relative error of < 50% and the mean relative error was reduced by an average of 44.3% and 71.3% compared with the other two predictive methods.
CONCLUSION
A combined population pharmacokinetic and machine learning approach provided improved predictions of individual clearances of renally cleared drugs in neonates. For a new patient treated in clinical practice, individual clearance can be predicted a priori using our model code combined with demographic data.
Topics: Drug Elimination Routes; Humans; Infant, Newborn; Machine Learning; Metabolic Clearance Rate; Models, Biological; Vancomycin
PubMed: 34041714
DOI: 10.1007/s40262-021-01033-x