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Biomedicines Jun 2024Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and...
Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; = 0.002) and use of meropenem (B = 1237.220; = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; = 0.040) and longer prothrombin times (B = 0.412; = 0.043), and higher IL-6 (B = 0.137; = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = -0.306; = 0.017) were predictive of higher aPTT values. Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient's level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters.
PubMed: 38927488
DOI: 10.3390/biomedicines12061281 -
Antibiotics (Basel, Switzerland) Jun 2024We evaluated the activities of aztreonam/avibactam and recently approved β-lactamase inhibitor combinations (BLICs) to compare the antimicrobial susceptibility patterns...
Activity of Aztreonam/Avibactam and Recently Approved β-Lactamase Inhibitor Combinations against Enterobacterales and from Intensive Care Unit and Non-Intensive Care Unit Patients.
We evaluated the activities of aztreonam/avibactam and recently approved β-lactamase inhibitor combinations (BLICs) to compare the antimicrobial susceptibility patterns of Enterobacterales and isolated from intensive care unit (ICU) and non-ICU patients. Clinical isolates (1/patient) were consecutively collected from 72 United States medical centres in 2020-2022 and susceptibility tested by broth microdilution. The results for 5421 isolates from ICU patients were analysed and compared to those for 20,649 isolates from non-ICU patients. Isolates from ventilator-associated pneumonia patients were analysed separately. Aztreonam/avibactam inhibited 100.0%/>99.9% Enterobacterales and 100.0%/98.3% of carbapenem-resistant Enterobacterales (CRE) from ICU/non-ICU patients at ≤8 mg/L, respectively. The CRE susceptibility rates were 88.5%/82.9% for ceftazidime/avibactam, 82.1%/81.2% for meropenem/vaborbactam, and 78.2%/72.6% for imipenem/relebactam among ICU/non-ICU isolates. Among the isolates from ICU/non-ICU patients, the susceptibility rates were 96.3%/97.6% for ceftazidime/avibactam, 97.2/98.4% for ceftolozane/tazobactam, 97.1%/98.0% for imipenem/relebactam, 77.8%/84.6% for piperacillin/tazobactam, and 76.9%/85.8% for meropenem; aztreonam/avibactam inhibited 78.0%/81.9% of at ≤8 mg/L. In summary, lower susceptibility rates were observed among ICU than non-ICU isolates. Aztreonam/avibactam exhibited potent in vitro activity and broad-spectrum activity against Enterobacterales from ICU and non-ICU patients, including CRE and isolates non-susceptible to newer BLICs. Against , aztreonam/avibactam showed a spectrum of activity comparable to that of piperacillin/tazobactam, meropenem, and ceftazidime.
PubMed: 38927230
DOI: 10.3390/antibiotics13060564 -
Antibiotics (Basel, Switzerland) May 2024Improving local antibiotic delivery is a promising approach to improve infection control and potentially shorten systemic treatment in periprosthetic joint infection...
BACKGROUND
Improving local antibiotic delivery is a promising approach to improve infection control and potentially shorten systemic treatment in periprosthetic joint infection (PJI). This study investigates the use of an antibiotic-loaded, mouldable collagen-tricalciumphosphate composite in treatment of hip PJI.
METHODS
124 application cases in 79 patients were included from a referral centre; systemic adverse infects, local complications, and infection control were analysed.
RESULTS
In most cases, either vancomycin or meropenem were used. Pathogens were previously known in 82 (66%) cases with polymicrobial infection in 20 (25%) patients. There were no cases of hypercalcaemia. Acute kidney injure was present in 14 (11%) cases. Chronic kidney failure persisted in two cases. During a mean follow-up of 12 (SD 9.3; range 3-35) months, implant survival was achieved in 73 (92%) patients; revision due to PJI was performed in 19 cases.
CONCLUSION
Mouldable collagen-tricalciumphosphate composite bone substitute as a local antibiotic carrier in revision hip arthroplasty appears to be a valid option for local antibiotic delivery without systemic complications. Implant survival of 92% supports the hypothesis that local antibiotic therapy is an important component in the treatment of PJI.
PubMed: 38927177
DOI: 10.3390/antibiotics13060510 -
Antibiotics (Basel, Switzerland) May 2024Carbapenemase-producing (CP-KP) represents a global threat to public health, with limited antimicrobial therapeutic options. In this study, we analyzed a...
BACKGROUND
Carbapenemase-producing (CP-KP) represents a global threat to public health, with limited antimicrobial therapeutic options. In this study, we analyzed a ceftazidime/avibactam (CAZ-AVI)-resistant isolate obtained from a patient previously exposed to CAZ-AVI expressing a novel carbapenemase (KPC)-3 variant.
METHODS
Antimicrobial susceptibility testing was performed using reference broth microdilution. Whole-genome sequencing (WGS) was performed using Illumina and Nanopore Technologies. Short- and long-reads were combined with Unicycler. Assemblies were investigated for multilocus sequence typing (MLST), antimicrobial resistance genes, porins, and plasmids.
RESULTS
The . isolate (KP_RM_1) was resistant to CAZ-AVI, expanded-spectrum cephalosporins, amikacin, ertapenem, and cefiderocol (FDC) but was susceptible to tigecycline, colistin, trimethoprim/sulfamethoxazole, meropenem-vaborbactam, and imipenem-relebactam. WGS revealed that the KP_RM_1 genome is composed of a single chromosome of 5 Mbp and five circular plasmids. Further analysis showed the presence of novel located on a 72 kb plasmid. KPC-216 differs from KPC-3 by a Lysin (K) insertion at position 168 (+K168).
CONCLUSIONS
We report the identification of a new KPC-3 variant associated with CAZ-AVI resistance. The KPC variants associated with CAZ-AVI resistance should be determined to promptly inform clinicians and start the appropriate antimicrobial therapy.
PubMed: 38927174
DOI: 10.3390/antibiotics13060507 -
Antibiotics (Basel, Switzerland) May 2024Beta-lactam antibiotics have been a major climacteric in medicine for being the first bactericidal compound available for clinical use. They have continually been... (Review)
Review
Beta-lactam antibiotics have been a major climacteric in medicine for being the first bactericidal compound available for clinical use. They have continually been prescribed since their development in the 1940s, and their application has saved an immeasurable number of lives. With such immense use, the rise in antibiotic resistance has truncated the clinical efficacy of these compounds. Nevertheless, the synergism of combinational antibiotic therapy has allowed these drugs to burgeon once again. Here, the development of meropenem with vaborbactam-a recently FDA-approved beta-lactam combinational therapy-is reviewed in terms of structure rationale, activity gamut, pharmacodynamic/pharmacokinetic properties, and toxicity to provide insight into the future development of analogous therapies.
PubMed: 38927139
DOI: 10.3390/antibiotics13060472 -
British Journal of Clinical Pharmacology Jun 2024Meropenem/vaborbactam combination is approved in adults by FDA and EMA for complicated urinary tract infections and by EMA also for other Gram-negative infections. We...
AIMS
Meropenem/vaborbactam combination is approved in adults by FDA and EMA for complicated urinary tract infections and by EMA also for other Gram-negative infections. We aimed to characterise the pharmacokinetics of both moieties in an ongoing study in children and use a model-based approach to inform adequate dosing regimens in paediatric patients.
METHODS
Over 4196 blood samples of meropenem and vaborbactam (n = 414 subjects) in adults, together with 114 blood samples (n = 39) in paediatric patients aged 3 months to 18 years were available for this analysis. Data were analysed using a population with prior information from a pharmacokinetic model in adults to inform parameter estimation in children. Simulations were performed to assess the suitability of different dosing regimens to achieve adequate probability of target attainment (PTA).
RESULTS
Meropenem/vaborbactam PK was described with two-compartment models with first-order elimination. Body weight and CLcr were significant covariates on the disposition of both drugs. A maturation function was evaluated to explore changes in clearance in neonates. PTA ≥90% was derived for children aged ≥3 months after 3.5-h IV infusion of 40 mg/kg Q8h of both meropenem and vaborbactam and 2 g/2 g for those ≥50 kg. Extrapolation of disposition parameters suggest that adequate PTA is achieved after a 3.5-h IV infusion of 20 mg/kg for neonates and infants (3 months).
CONCLUSIONS
An integrated analysis of adult and paediatric data allowed accurate description of sparsely sampled meropenem/vaborbactam PK in paediatric patients and provided recommendations for the dosing in neonates and infants (3 months).
PubMed: 38925918
DOI: 10.1111/bcp.16145 -
Pathogens (Basel, Switzerland) Jun 2024is an important zoonotic pathogen capable of causing foodborne illness and bovine mastitis. Bacteriophages have been increasingly considered a promising tool to control...
is an important zoonotic pathogen capable of causing foodborne illness and bovine mastitis. Bacteriophages have been increasingly considered a promising tool to control unwanted bacteria. The aim of this study is to determine the antibiotic resistance profile of isolated from raw milk and the efficacy of phage in controlling multidrug-resistant in raw milk. Antibiotic susceptibility testing showed the highest resistance rates of isolates to co-trime (27.34%) and ampicillin (27.34%), followed by streptomycin (25.18%), tetracycline (23.02%), and the lowest resistance rates to ciprofloxacin, gentamycin, and ceftazidime, all at a rate of 2.16%. All isolates were susceptible to meropenem. Of the 139 isolates, 57 (41.01%) were resistant to at least one antibiotic, and 35 (25.18%) were classified as MDR strains. Molecular characterization indicated that 5 (3.6%) out of the 139 isolates were STEC strains carrying gene. Seven (5.04%) isolates were phenotypically identified as ESBLEC, and four isolates (2.88%) were resistant to colistin. The results of the genotypic test revealed that four out of seven ESBLEC strains carried both and , two harbored , and one possessed , while was detected in all four colistin-resistant isolates. In particular, one isolated strain (EM148) was determined to be a multidrug-resistant strain simultaneously carrying , , and . A total of eight phages were successfully recovered from raw milk. The application of phage PEM3 significantly reduced viable counts of multidrug-resistant host EM148 in raw milk by at least 2.31 log CFU/mL at both 24 °C and 4 °C.
PubMed: 38921792
DOI: 10.3390/pathogens13060494 -
Iranian Journal of Public Health Mar 2024Uropathogenic is a major cause of urinary tract infections (UTIs). This systematic review and meta-analysis was conducted to determine the prevalence of... (Review)
Review
BACKGROUND
Uropathogenic is a major cause of urinary tract infections (UTIs). This systematic review and meta-analysis was conducted to determine the prevalence of antibiotic-resistant uropathogenic among Iranian children with confirmed bacterial UTIs from 2012 to 2022.
METHODS
A systematic review was performed by searching PubMed, Scopus, Google Scholar, Web of Science, MagIran, Iranian Scientific Information Database, IranMedex, and Iranian Research Institute for Information Science and Technology. The antibiotic-specific pooled prevalence estimates were calculated by applying a random-effects model. Freeman-Tukey Double Arcsine transformation was applied. I-squared statistic, and Cochran's Q test were computed and meta-regression was conducted on latitude of sampling location.
RESULTS
The literature search retrieved 2159 articles, among which 19 articles were included. The highest antibiotic resistance was related to doxycycline, ticarcillin-clavulanic acid, cefazolin, cefuroxime, and amoxycillin-clavulanic acid, 59%, 57%, 54%, 53%, and 52%, respectively. Meta-regression on the latitude was statistically significant for nitrofurantoin (=0.05).
CONCLUSION
Resistant uropathogenic Escherichia coli strains were observed in the majority of confirmed bacterial UTIs among Iranian children. The most effective antibiotics for uropathogens were colistin, meropenem, and imipenem.
PubMed: 38919304
DOI: 10.18502/ijph.v53i3.15133 -
BMC Veterinary Research Jun 2024Acinetobacter lwoffii (A. lwoffii) is a Gram-negative bacteria common in the environment, and it is the normal flora in human respiratory and digestive tracts. The...
BACKGROUND
Acinetobacter lwoffii (A. lwoffii) is a Gram-negative bacteria common in the environment, and it is the normal flora in human respiratory and digestive tracts. The bacteria is a zoonotic and opportunistic pathogen that causes various infections, including nosocomial infections. The aim of this study was to identify A. lwoffii strains isolated from bovine milk with subclinical mastitis in China and get a better understanding of its antimicrobial susceptibility and resistance profile. This is the first study to analyze the drug resistance spectrum and corresponding mechanisms of A. lwoffii isolated in raw milk.
RESULTS
Four A. lwoffii strains were isolated by PCR method. Genetic evolution analysis using the neighbor-joining method showed that the four strains had a high homology with Acinetobacter lwoffii. The strains were resistant to several antibiotics and carried 17 drug-resistance genes across them. Specifically, among 23 antibiotics, the strains were completely susceptible to 6 antibiotics, including doxycycline, erythromycin, polymyxin, clindamycin, imipenem, and meropenem. In addition, the strains showed variable resistance patterns. A total of 17 resistance genes, including plasmid-mediated resistance genes, were detected across the four strains. These genes mediated resistance to 5 classes of antimicrobials, including beta-lactam, aminoglycosides, fluoroquinolones, tetracycline, sulfonamides, and chloramphenicol.
CONCLUSION
These findings indicated that multi-drug resistant Acinetobacter lwoffii strains exist in raw milk of bovine with subclinical mastitis. Acinetobacter lwoffii are widespread in natural environmental samples, including water, soil, bathtub, soap box, skin, pharynx, conjunctiva, saliva, gastrointestinal tract, and vaginal secretions. The strains carry resistance genes in mobile genetic elements to enhance the spread of these genes. Therefore, more attention should be paid to epidemiological surveillance and drug resistant A. lwoffii.
Topics: Animals; Cattle; Mastitis, Bovine; Female; Acinetobacter; Milk; China; Anti-Bacterial Agents; Microbial Sensitivity Tests; Acinetobacter Infections; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial
PubMed: 38918815
DOI: 10.1186/s12917-024-04119-3 -
EBioMedicine Jun 2024Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support...
BACKGROUND
Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections.
METHODS
Five β-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected. The CDSS was constructed by incorporating the drug, patient, dosage, pharmacodynamic, and microbiological factors. The CatBoost ML algorithm was used to build the CDSS. Real-world studies were used to evaluate the CDSS performance. Virtual trials were used to compare the CDSS-optimized doses with guideline-recommended doses.
FINDINGS
For a specific drug, by entering the patient characteristics and pharmacodynamic (PD) target (50%/70%/100% fraction of time that the free drug concentration is above the minimal inhibitory concentration [fT > MIC]), the CDSS can determine whether the planned dosing regimen will achieve the PD target and suggest an optimal dose. The prediction accuracy of all five drugs was >80.0% in the real-world validation. Compared with the PopPK model, the overall accuracy, precision, recall, and F1-Score improved by 10.7%, 22.1%, 64.2%, and 43.1%, respectively. Using the CDSS-optimized doses, the average probability of target concentration attainment increased by 58.2% compared to the guideline-recommended doses.
INTERPRETATION
An ML-based CDSS was successfully constructed to assist clinicians in selecting optimal β-lactam antibiotic doses.
FUNDING
This work was supported by the National Natural Science Foundation of China; Distinguished Young and Middle-aged Scholar of Shandong University; National Key Research and Development Program of China.
PubMed: 38917512
DOI: 10.1016/j.ebiom.2024.105221