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Cureus Aug 2023Lyme disease and its treatment implications have become an ever-increasing area of concern within the United States related to the markedly increased prevalence of... (Review)
Review
Lyme disease and its treatment implications have become an ever-increasing area of concern within the United States related to the markedly increased prevalence of infection within the last two decades. The presentation, pathophysiology, and epidemiology of Lyme disease have been well studied, and thus treatments for this disease are widely available. While the treatment of its early and late stages is relatively simple with 10-14 day and four-week courses of doxycycline, respectively, the main problem rests in the understanding of the etiology and pathology of post-treatment Lyme disease syndrome (PTLDS). With the time of symptoms onsetting approximately six months after treatment and potentially lasting indefinitely, this syndrome's effect on patients' quality of life could be devastating. Searching on PubMed, Google Scholar, MEDLINE, and ScienceDirect using keywords including Lyme disease, PTLDS, doxycycline, erythema migrans, azlocillin, and treatment, the authors have tried to make clear the different aspects. The authors have reviewed and discussed clinical studies of Lyme disease and its treatments/potential therapeutics as well as PTLDS and its sparse treatments/potential therapeutics.
PubMed: 37692614
DOI: 10.7759/cureus.43112 -
Pathogens (Basel, Switzerland) Jun 2021Bartonellosis is caused by a Gram-negative intracellular bacterium with a zoonotic transmission. The disease, caused by any of several genospecies of can range from a...
Bartonellosis is caused by a Gram-negative intracellular bacterium with a zoonotic transmission. The disease, caused by any of several genospecies of can range from a benign, self-limited condition to a highly morbid and life-threatening illness. The current standard of care antibiotics are generally effective in acute infection; these include azithromycin or erythromycin, doxycycline, gentamicin, rifampin, and ciprofloxacin. However, treatment of chronic infection remains problematic. We tested six different antibiotics for their ability to stop the growth of sp. in the standard insect media and in an enrichment media. All antibiotics (ceftriaxone, doxycycline, gentamycin, azithromycin, ampicillin, and azlocillin) had minimum inhibitory concentrations (MICs) below 0.5 µg/mL in the BAPGM enrichment media but were ineffective at inhibiting growth when the standard insect media was used. Azlocillin was the most potent, with a MIC of 0.01 µg/mL. When was tested under intracellular growth conditions, none of the antibiotics were efficacious singly. However, growth inhibition was observed when azlocillin and azithromycin were combined. These studies illustrate the impact of growth medium and intracellular environment on antibiotic susceptibility testing and indicate that azlocillin combined with azithromycin may be an effective drug combination for the treatment of Bartonellosis.
PubMed: 34201011
DOI: 10.3390/pathogens10060718 -
Frontiers in Pediatrics 2022The antimicrobial therapy of sepsis and septic shock should be individualized based on pharmacokinetic/pharmacodynamic (PK/PD) parameters to deliver effective and timely... (Review)
Review
The antimicrobial therapy of sepsis and septic shock should be individualized based on pharmacokinetic/pharmacodynamic (PK/PD) parameters to deliver effective and timely treatment of life-threatening infections. We conducted a literature scoping review to identify therapeutic targets of beta-lactam antibiotics in septic pediatric patients and the strategies that have been applied to overcome sepsis-related altered pharmacokinetics and increase target attainment against susceptible pathogens. A systematic search was conducted in the MEDLINE, EMBASE and Web of Science databases to select studies conducted since 2010 with therapeutic monitoring data of beta-lactams in septic children. Last searches were performed on 02 September 2021. Two independent authors selected the studies and extracted the data. A narrative and qualitative approach was used to summarize the findings. Out of the 118 identified articles, 21 met the eligibility criteria. Population pharmacokinetic modeling was performed in 12 studies, while nine studies reported data from bedside monitoring of beta-lactams. Most studies were conducted in the United States of America ( = 9) and France ( = 5) and reported PK/PD data of amoxicillin, ampicillin, azlocillin, aztreonam, cefazolin, cefepime, cefotaxime, ceftaroline, ceftazidime, doripenem, meropenem and piperacillin/tazobactam. Therapeutic targets ranged from to 40% T> MIC to 100% T> 6 × MIC. Prolonging the infusion time and frequency were most described strategies to increase target attainment. Monitoring beta-lactam serum concentrations in clinical practice may potentially maximize therapeutic target attainment. Further studies are required to define the therapeutic target associated with the best clinical outcomes.
PubMed: 35359889
DOI: 10.3389/fped.2022.777854 -
Scientific Reports Mar 2020Lyme disease is one of most common vector-borne diseases, reporting more than 300,000 cases annually in the United States. Treating Lyme disease during its initial...
Lyme disease is one of most common vector-borne diseases, reporting more than 300,000 cases annually in the United States. Treating Lyme disease during its initial stages with traditional tetracycline antibiotics is effective. However, 10-20% of patients treated with antibiotic therapy still shows prolonged symptoms of fatigue, musculoskeletal pain, and perceived cognitive impairment. When these symptoms persists for more than 6 months to years after completing conventional antibiotics treatment are called post-treatment Lyme disease syndrome (PTLDS). Though the exact reason for the prolongation of post treatment symptoms are not known, the growing evidence from recent studies suggests it might be due to the existence of drug-tolerant persisters. In order to identify effective drug molecules that kill drug-tolerant borrelia we have tested two antibiotics, azlocillin and cefotaxime that were identified by us earlier. The in vitro efficacy studies of azlocillin and cefotaxime on drug-tolerant persisters were done by semisolid plating method. The results obtained were compared with one of the currently prescribed antibiotic doxycycline. We found that azlocillin completely kills late log phase and 7-10 days old stationary phase B. burgdorferi. Our results also demonstrate that azlocillin and cefotaxime can effectively kill in vitro doxycycline-tolerant B. burgdorferi. Moreover, the combination drug treatment of azlocillin and cefotaxime effectively killed doxycycline-tolerant B. burgdorferi. Furthermore, when tested in vivo, azlocillin has shown good efficacy against B. burgdorferi in mice model. These seminal findings strongly suggests that azlocillin can be effective in treating B. burgdorferi sensu stricto JLB31 infection and furthermore in depth research is necessary to evaluate its potential use for Lyme disease therapy.
Topics: Animals; Anti-Bacterial Agents; Azlocillin; Borrelia burgdorferi; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Female; Humans; Lyme Disease; Mice, Inbred C3H
PubMed: 32123189
DOI: 10.1038/s41598-020-59600-4 -
International Journal of Molecular... Oct 2022Raman spectra of oxacillin (OXN), carbenicillin (CBC), and azlocillin (AZL) are reported for the first time together with their full assignment of the normal modes, as...
Raman spectra of oxacillin (OXN), carbenicillin (CBC), and azlocillin (AZL) are reported for the first time together with their full assignment of the normal modes, as calculated using Density Functional Theory (DFT) methods with the B3LYP exchange-correlation functional coupled to the 6-31G(d) and 6-311+G(2d,p) basis sets. Molecular docking studies were performed on five penicillins, including OXN, CBC, and AZL. Subsequently, their chemical reactivity and correlated efficiency towards specific pathogenic strains were revealed by combining frontier molecular orbital (FMO) data with molecular electrostatic potential (MEP) surfaces. Their bactericidal activity was tested and confirmed on a couple of species, both Gram-positive and Gram-negative, by using the disk diffusion method. Additionally, a surface-enhanced Raman spectroscopy (SERS)-principal component analysis (PCA)-based of is proposed as a clinically relevant insight resulting from the synergistic cheminformatics and vibrational study on CBC and AZL.
Topics: Spectroscopy, Fourier Transform Infrared; Models, Molecular; Cheminformatics; beta-Lactams; Molecular Docking Simulation; Azlocillin; Spectrum Analysis, Raman; Static Electricity; Vibration; Carbenicillin; Oxacillin; Quantum Theory; Thermodynamics
PubMed: 36293563
DOI: 10.3390/ijms232012685 -
African Health Sciences Jun 2021Tuberculosis (TB) sputum culture contaminants make it difficult to obtain pure TB isolates.We aimed to study and identify persistent TB sputum culture contaminants post...
BACKGROUND
Tuberculosis (TB) sputum culture contaminants make it difficult to obtain pure TB isolates.We aimed to study and identify persistent TB sputum culture contaminants post the standard laboratory pre-culture sample decontamination techniques.
METHODS
This was a longitudinal study of TB sputum culture contamination for a cohort of TB patients on standard treatment at: baseline, during TB treatment and post TB treatment. Sputum samples were decontaminated with 1.5%NaOH and neutralized using 6.8 Phosphate buffer solution.Sputum was then inoculated into MGIT (mycobactrial growth indicator tube) supplemented with 0.8ml PANTA. A drop of each positive MGIT culture was sub cultured onto blood agar and incubated for 48 hours at 35 -37OC.Any growth was identified using growth characteristics and colony morphology.
RESULTS
From October 2017 through May 2019;we collected 8645 sputum samples of which 8624(99.8%) were eligible and inoculated into MGIT where 2444(28.3%)samples were TB culture positive and 255(10.4%)were positive for contaminants: 237 none-tuberculosis bacteria, 12 fungi and 6 mixed(none-tuberculous bacteria+fungi). There was no statistically significant difference between none tuberculosis bacteria and fungi in the treatment (OR=1.4,95%CI:0.26-7.47,p=0.690) and the post treatment TB phases(OR=2.02,95%CI:0.38-10.79,p=0.411)Vs baseline.
CONCLUSION
None-tuberculous bacteria and fungi dominate the plethora of TB sputum culture contamination and persist beyond the standard laboratory pre-culture decontamination algorithm.
Topics: Amphotericin B; Anti-Bacterial Agents; Azlocillin; Bacteria; Bacteriological Techniques; Fungi; Humans; Longitudinal Studies; Mycobacterium tuberculosis; Nalidixic Acid; Polymyxin B; Sputum; Trimethoprim; Tuberculosis
PubMed: 34795716
DOI: 10.4314/ahs.v21i2.18 -
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 -
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