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The Journal of Antimicrobial... Nov 2022
Topics: Infant; Infant, Newborn; Humans; Mezlocillin; Bacterial Infections; Kinetics
PubMed: 36205004
DOI: 10.1093/jac/dkac335 -
The Journal of Antimicrobial... Jul 2022Mezlocillin is used in the treatment of neonatal infectious diseases. However, due to the absence of population pharmacokinetic studies in neonates and young infants,...
OBJECTIVES
Mezlocillin is used in the treatment of neonatal infectious diseases. However, due to the absence of population pharmacokinetic studies in neonates and young infants, dosing regimens differ considerably in clinical practice. Hence, this study aimed to describe the pharmacokinetic characteristics of mezlocillin in neonates and young infants, and propose the optimal dosing regimen based on the population pharmacokinetic model of mezlocillin.
METHODS
A prospective, open-label pharmacokinetic study of mezlocillin was carried out in newborns. Blood samples were collected using an opportunistic sampling method. HPLC was used to measure the plasma drug concentrations. A population pharmacokinetic model was developed using NONMEM software.
RESULTS
Ninety-five blood samples from 48 neonates and young infants were included. The ranges of postmenstrual age and birth weight were 29-40 weeks and 1200-4000 g, respectively, including term and preterm infants. A two-compartment model with first-order elimination was developed to describe the population pharmacokinetics of mezlocillin. Postmenstrual age, current weight and serum creatinine concentration were the most important covariates. Monte Carlo simulation results indicated that the current dose of 50 mg/kg q12h resulted in 89.2% of patients achieving the therapeutic target, when the MIC of 4 mg/L was used as the breakpoint. When increasing the dosing frequency to q8h, a dose of 20 mg/kg resulted in 74.3% of patients achieving the therapeutic target.
CONCLUSIONS
A population pharmacokinetic model of mezlocillin in neonates and young infants was established. Optimal dosing regimens based on this model were provided for use in neonatal infections.
Topics: Anti-Bacterial Agents; Creatinine; Humans; Infant; Infant, Newborn; Infant, Premature; Mezlocillin; Microbial Sensitivity Tests; Monte Carlo Method; Prospective Studies
PubMed: 35662337
DOI: 10.1093/jac/dkac176 -
The Journal of Antimicrobial... Nov 2022
Topics: Infant; Infant, Newborn; Humans; Mezlocillin; Bacterial Infections; Kinetics
PubMed: 36101504
DOI: 10.1093/jac/dkac305 -
PloS One 2022Carbapenem-resistant Escherichia coli has emerged as a major public health issue across the world. This study was aimed to determine the virulence content and...
Carbapenem-resistant Escherichia coli has emerged as a major public health issue across the world. This study was aimed to determine the virulence content and phylogenetic groups of carbapenemase-producing E. coli isolates in southwest Iran. One hundred and fifty-two non-duplicate E. coli isolates were collected from various clinical samples. Antibiotic susceptibility and minimum inhibitory concentrations (MIC) were determined according to the Clinical and Laboratory Standards Institute (CLSI) guidelines by Kirby-Bauer disc diffusion and agar dilution methods. Phenotypic screening of carbapenemase enzymes was performed by modified Hodge test (MHT). Detection of carbapenemase genes, phylogenetic groups, and virulence-associated genes were also performed by the PCR assay. The highest and lowest resistance rates were observed against mezlocillin (70.4%) and doripenem (13.1%), respectively. Out of 28 isolates that were resistant to carbapenem antibiotics, 12 (7.9%) strains were phenotypically carbapenemase producers. The blaOXA-48 was the predominant carbapenemase gene, detected in 58.3% of isolates, followed by blaIMP (41.7%) and blaNDM (8.3%). None of the isolates harbored blaVIM and blaKPC genes. Among the twelve carbapenemase-producing strains, urinary isolates were mostly classified into B2 (41.7%) and D (25%) phylogenetic groups, while other clinical isolates belonged to B1 (25%) and A (8.3%) groups. The frequency of virulence-associated genes was also investigated in all isolates and ranged from 6.6% for hly to 75% for fimA. The emergence of carbapenemase-producing strains is a growing concern to public health. Therefore, the proper implementation of monitoring programs is crucial for limiting their dissemination.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbapenem-Resistant Enterobacteriaceae; Escherichia coli; Microbial Sensitivity Tests; Phylogeny; Virulence; beta-Lactamases
PubMed: 35536848
DOI: 10.1371/journal.pone.0266787 -
Frontiers in Pharmacology 2023Acute kidney injury (AKI) is a common adverse reaction observed with the clinical use of cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium. Based upon...
Risk-factor analysis and predictive-model development of acute kidney injury in inpatients administered cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium: a single-center retrospective study.
Acute kidney injury (AKI) is a common adverse reaction observed with the clinical use of cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium. Based upon real-world data, we will herein determine the risk factors associated with AKI in inpatients after receipt of these antimicrobial drugs, and we will develop predictive models to assess the risk of AKI. Data from all adult inpatients who used cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium at the First Affiliated Hospital of Shandong First Medical University between January 2018 and December 2020 were analyzed retrospectively. The data were collected through the inpatient electronic medical record (EMR) system and included general information, clinical diagnosis, and underlying diseases, and logistic regression was exploited to develop predictive models for the risk of AKI. The training of the model strictly adopted 10-fold cross-validation to validate its accuracy, and model performance was evaluated employing receiver operating characteristic (ROC) curves and the areas under the curve (AUCs). This retrospective study comprised a total of 8767 patients using cefoperazone-sulbactam sodium, of whom 1116 developed AKI after using the drug, for an incidence of 12.73%. A total of 2887 individuals used mezlocillin-sulbactam sodium, of whom 265 developed AKI after receiving the drug, for an incidence of 9.18%. In the cohort administered cefoperazone-sulbactam sodium, 20 predictive factors ( < 0.05) were applied in constructing our logistic predictive model, and the AUC of the predictive model was 0.83 (95% CI, 0.82-0.84). In the cohort comprising mezlocillin-sulbactam sodium use, nine predictive factors were determined by multivariate analysis ( < 0.05), and the AUC of the predictive model was 0.74 (95% CI, 0.71-0.77). The incidence of AKI induced by cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium in hospitalized patients may be related to the combined treatment of multiple nephrotoxic drugs and a past history of chronic kidney disease. The AKI-predictive model based on logistic regression showed favorable performance in predicting the AKI of adult in patients who received cefoperazone-sulbactam sodium or mezlocillin-sulbactam sodium.
PubMed: 37361226
DOI: 10.3389/fphar.2023.1170987 -
The Journal of Antimicrobial... Dec 2022
PubMed: 36346101
DOI: 10.1093/jac/dkac371 -
Journal of Pharmaceutical and... Feb 2022To effectively control the polymerized impurities in mezlocillin sodium and sulbenicillin sodium, a HPSEC method with TSK-gel G2000SWxl column and a RP-HPLC method with...
To effectively control the polymerized impurities in mezlocillin sodium and sulbenicillin sodium, a HPSEC method with TSK-gel G2000SWxl column and a RP-HPLC method with C18 analytical column were established to replace the classical gel filtration chromatography with Sephadex G-10 gel as stationary phase. By studying the chromatographic behavior of polymerized impurities in both methods with different chromatographic separation mechanisms, the polymerized impurities in mezlocillin sodium and sulbenicillin sodium were separated and detected effectively. The column switching two-dimension liquid chromatography ion trap/time-of-flight mass spectrometry was applied to characterize the structures of polymerized impurities eluted from the HPSEC method and RP-HPLC method for both drugs. The structures of the polymerized impurities in mezlocillin sodium and sulbenicillin sodium were deduced based on the MS data. The results showed that the polymerized impurities detected by HPSEC method and RP-HPLC method were completely different. Therefore, two methods should be used meanwhile to control the polymerized impurities in mezlocillin sodium and sulbenicillin sodium.
Topics: Chromatography, High Pressure Liquid; Drug Contamination; Mezlocillin; Pharmaceutical Preparations; Sodium; Sulbenicillin; Tandem Mass Spectrometry
PubMed: 35026591
DOI: 10.1016/j.jpba.2022.114584 -
Jundishapur Journal of Microbiology Nov 2014Extended spectrum β-lactamase (ESBL) are gram-negative bacteria that produce the enzyme, β-lactamase, which can break down commonly used antibiotics, such as...
BACKGROUND
Extended spectrum β-lactamase (ESBL) are gram-negative bacteria that produce the enzyme, β-lactamase, which can break down commonly used antibiotics, such as penicillin and cephalosporins, making infections with ESBL producing bacteria more difficult to treat. Extended spectrum β-lactamase-producing Klebsiella pneumoniae were first reported in 1983 from Germany, and since then a steady increase in resistance against cephalosporins has been seen causing health problems.
OBJECTIVES
The aim of this study was to determine the prevalence of ESBL in strains of K. pneumoniae isolated from different clinical samples.
PATIENTS AND METHODS
One hundred and thirty isolates of K. pneumoniae were isolated from different clinical specimens from King Khalid hospital, Hafr Elbatin, Kingdom Saudi Arabia. These isolates were then characterized, tested for antimicrobial susceptibility and screened for ESBL production by the MicroScan WalkAway-96 SI System. Extended spectrum β-lactamase production was confirmed by the phenotypic confirmatory disc diffusion test (PCDDT) and the double disc synergy test (DDST).
RESULTS
Overall, 76.9% (100) of the isolates were resistant to cefuroxime, cefepime and cefazolin, 69.23% (90) were resistant to cefotaxime, and 46.15% (60) were resistant to cefoxitin. Extended spectrum β-lactamase was detected in 53.8% (70) of K. pneumoniae as detected by the MicroScan "WalkAway-96" SI System and 50.07% (66) by PCDDT and 46.15% (60) by DDST. All K. pneumoniae isolates were resistant to ampicillin followed by both piperacillin and mezlocillin 92.30% (120). K. pneumoniae isolates showed high sensitivity to imipenem (15.38%) (20), followed by ertapenem, tetracycline, tigecycline pipracilline/tazobactam and amikacin (23.07%) (30).
CONCLUSIONS
Our study showed that the prevalence of ESBL-producing K. pneumoniae at King Khalid Hospital was significantly high. Routine detection of ESBL-producing microorganisms is required by each of the laboratory standard detection methods to control the spread of these infections and allow a proper therapeutic strategy. For detection, the phenotypic confirmatory disc diffusion test is simple, sensitive and cost effective. However, there is a need for larger scale drug susceptibility surveillance.
PubMed: 25774279
DOI: 10.5812/jjm.17114 -
BMC Nephrology Nov 2020Glomerular disease patients have a high risk of infection, which contributes to the progression of disease per se and mortality, especially in those with long-term use...
BACKGROUND
Glomerular disease patients have a high risk of infection, which contributes to the progression of disease per se and mortality, especially in those with long-term use of glucocorticoids and (or) immunosuppressive agents. Cases of sporadic nocardiosis have been reported in glomerular disease patients, and this observation was conducted to comprehensively understand the manifestations of and treatments for nocardiosis, which is commonly misdiagnosed as pneumonia or tuberculosis or even as lung cancer or metastatic tumors in glomerular disease patients.
METHODS
We reviewed the demographic characteristics, laboratory abnormalities, radiological features, and treatments of 7 patients with nocardiosis and glomerular disease receiving steroids and immunosuppression therapy at the nephrology department of the Second Xiangya Hospital between 2012 and 2019.
RESULTS
It was found that all 7 patients had been receiving methylprednisolone for renal disease at a median dose of 20 mg per day and a median duration of 4 months before developing nocardiosis. There were 4 males and 3 females, and the median age was 52.14 years. All 7 patients had hypoalbuminemia at the time of admission. In addition, various cystic abscesses in the subcutaneous tissue, with or without lung and brain involvement, were observed in these patients. Encouragingly, body temperatures returned to normal, and subcutaneous abscesses diminished or disappeared with compound sulfamethoxazole treatment alone or in combination with linezolid, imipenem and mezlocillin/sulbactam.
CONCLUSIONS
It was shown that multisite abscesses, including subcutaneous, pulmonary and cerebral abscesses, were the common manifestations of nocardiosis in glomerular disease patients. Sulfonamide was the first-line antibiotic therapy for nocardiosis, and combinations of other antibiotics were also needed in some serious cases.
Topics: Abscess; Aged; Anti-Bacterial Agents; Brain; Brain Abscess; Female; Glomerulonephritis; Glucocorticoids; Humans; Immunocompromised Host; Immunosuppressive Agents; Lung; Lung Abscess; Magnetic Resonance Imaging; Male; Middle Aged; Nocardia Infections; Sulfonamides; Tomography, X-Ray Computed
PubMed: 33243202
DOI: 10.1186/s12882-020-02179-9