scholarly journals Blood, Tissue, and Intracellular Concentrations of Azithromycin during and after End of Therapy

2013 ◽  
Vol 57 (4) ◽  
pp. 1736-1742 ◽  
Author(s):  
P. Matzneller ◽  
S. Krasniqi ◽  
M. Kinzig ◽  
F. Sörgel ◽  
S. Hüttner ◽  
...  
Keyword(s):  
Blood Cells ◽  
Extracellular Space ◽  
Bacterial Resistance ◽  
Soft Tissues ◽  
White Blood Cells ◽  
Time Points ◽  
Concentration Time ◽  
Antibiotic Drug ◽  
Intracellular Concentrations ◽  
Tract Infections

ABSTRACTAlthough azithromycin is extensively used in the treatment of respiratory tract infections as well as skin and skin-related infections, pharmacokinetics of azithromycin in extracellular space fluid of soft tissues, i.e., one of its therapeutic target sites, are not yet fully elucidated. In this study, azithromycin concentration-time profiles in extracellular space of muscle and subcutaneous adipose tissue, but also in plasma and white blood cells, were determined at days 1 and 3 of treatment as well as 2 and 7 days after the end of treatment. Of all compartments, azithromycin concentrations were highest in white blood cells, attesting for intracellular accumulation. However, azithromycin concentrations in both soft tissues were markedly lower than in plasma both during and after treatment. Calculation of the area under the concentration-time curve from 0 to 24 h (AUC0–24)/MIC90ratios for selected pathogens suggests that azithromycin concentrations measured in the present study are subinhibitory at all time points in both soft tissues and at the large majority of observed time points in plasma. Hence, it might be speculated that azithromycin's clinical efficacy relies not only on elevated intracellular concentrations but possibly also on its known pleotropic effects, including immunomodulation and influence on bacterial virulence factors. However, prolonged subinhibitory azithromycin concentrations at the target site, as observed in the present study, might favor the emergence of bacterial resistance and should therefore be considered with concern. In conclusion, this study has added important information to the pharmacokinetic profile of the widely used antibiotic drug azithromycin and evidentiates the need for further research on its potential for induction of bacterial resistance.

scholarly journals Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK140944)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrea Nuzzo ◽  
Stephanie Van Horn ◽  
Christopher Traini ◽  
Caroline R. Perry ◽  
Etienne F. Dumont ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Human Microbiome ◽  
Time Points ◽  
Pharyngeal Cavity ◽  
Adult Females ◽  
Microbiome Diversity ◽  
Antibiotic Drug ◽  
Tract Infections

Abstract Background With increasing concerns about the impact of frequent antibiotic usage on the human microbiome, it is important to characterize the potential for such effects in early antibiotic drug development clinical trials. In a randomised Phase 2a clinical trial study that evaluated the pharmacokinetics of repeated oral doses of gepotidacin, a first-in-chemical-class triazaacenaphthylene antibiotic with a distinct mechanism of action, in adult females with uncomplicated urinary tract infections for gepotidacin (GSK2140944) we evaluated the potential changes in microbiome composition across multiple time points and body-sites (ClinicalTrials.gov: NCT03568942). Results Samples of gastrointestinal tract (GIT), pharyngeal cavity and vaginal microbiota were collected with consent from 22 patients at three time points relative to the gepotidacin dosing regimen; Day 1 (pre-dose), Day 5 (end of dosing) and Follow-up (Day 28 ± 3 days). Microbiota composition was determined by DNA sequencing of 16S rRNA gene variable region 4 amplicons. By Day 5, significant changes were observed in the microbiome diversity relative to pre-dose across the tested body-sites. However, by the Follow-up visit, microbiome diversity changes were reverted to compositions comparable to Day 1. The greatest range of microbiome changes by body-site were GIT followed by the pharyngeal cavity then vagina. In Follow-up visit samples we found no statistically significant occurrences of pathogenic taxa. Conclusion Our findings suggest that gepotidacin alteration of the human microbiome after 5 days of dosing is temporary and rebound to pre-dosing states is evident within the first month post-treatment. We recommend that future antibiotic drug trials include similar exploratory investigations into the duration and context of microbiome modification and recovery. Trial registration NCT03568942. Registered 26 June 2018.

scholarly journals In-vivo Antiplasmodial Effect of Dihydroartemisinin-Piperaquine-Nitrofurantoin on Plasmodium berghei- Infected Mice

2021 ◽  
pp. 12-20
Author(s):  
Udeme O. Georgewill ◽  
Festus Azibanigha Joseph ◽  
Elias Adikwu
Keyword(s):  
Plasmodium Berghei ◽  
Blood Cells ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Positive Control ◽  
Negative Control ◽  
Antiplasmodial Activity ◽  
Significant Difference ◽  
Tract Infections

Nitrofurantoin (NT) used for the treatment of urinary tract infections may have antiplasmodial activity. Dihydroartemisinin-piperaquine (DP) is an artemisinin based combination therapy used for the treatment of malaria. This study evaluated the antiplasmodial effect of dihydroartemisinin-piperaquine-nitrofurantoin (DP-NT) on mice infected with Plasmodium berghei. Adult Swiss albino mice (30-35 g) of both sexes were used. The mice were randomly grouped, inoculated with Plasmodium berghei, and treated orally with DP (1.7/13.7 mg/kg), NT (57.1 mg/kg) and DP-NT (1.71/13.7/ 57.1 mg/kg), respectively using curative, prophylactic and suppressive tests. The negative control was orally treated with normal saline (0.3 mL), while the positive control was orally treated with chloroquine CQ (10mg/kg). After treatment, blood samples were collected and evaluated for percentage parasitemia, inhibitions and hematological parameters. Liver samples were evaluated for histological changes. The mice were observed for mean survival time (MST). Treatment with DP-NT decreased parasitemia levels when compared to individual doses of DP and NT with significant difference observed at p<0.05. DP-NT prolonged MST when compared to individual doses of DP and NT with significant difference observed at p<0.05. The decrease in packed cell volume, red blood cells, hemoglobin and increase in white blood cells in parasitized mice were significantly restored by DP-NT  when compared to individual doses of DP and NT with difference observed at p<0.05. DP-NT eradicated liver Plasmodium parasite.  NT remarkably increased the antiplasmodial activity of DP. DP-NT may be used for the treatment of malaria.

Isolated Hematuria and Sterile Pyuria May Indicate Systemic Lupus Erythematosus Activity

2015 ◽  
Vol 42 (3) ◽  
pp. 437-440 ◽  
Author(s):  
Jonathan Y.C. Ding ◽  
Dominique Ibañez ◽  
Dafna D. Gladman ◽  
Murray B. Urowitz
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
High Power ◽  
Lupus Erythematosus ◽  
Blood Cells ◽  
White Blood Cells ◽  
Systemic Lupus ◽  
High Power Field ◽  
Renal Manifestation ◽  
Tract Infections

Objective.To identify patients presenting with isolated hematuria and/or pyuria in the absence of other systemic lupus erythematosus (SLE) disease activity, describe their demographics, and determine whether they present with evidence of SLE flare in a period adjacent to the presentation.Methods.We studied patients followed at the University of Toronto Lupus Clinic between 1970 and 2012. An episode of isolated hematuria (> 5 red blood cells per high power field) and/or pyuria (> 5 white blood cells per high power field) was defined as 2 consecutive visits with these findings in the absence of other concurrent SLE manifestations such as proteinuria, casts, or azotemia. We then excluded patients whose findings might be explained by urinary tract infections, menstruation, urolithiasis, and/or anticoagulation. Only patients presenting with no other SLE disease activity were included.Results.Isolated hematuria and/or pyuria were identified in 49 patients, of whom 17 were excluded according to the criteria above, leaving 32. Twenty-four patients had another renal manifestation 1 year before and/or after the occurrence; 27 had a non-renal manifestation 1 year before and/or after the occurrence; 3 patients had a biopsy in the same time frame, all with evidence of active lupus nephritis. Therefore the majority of patients with an occurrence of isolated hematuria and/or pyuria had evidence of renal or other non-renal SLE disease activity at a time adjacent to this presentation.Conclusion.Although not proven, our results suggest that these manifestations were associated with SLE activity, either before or after the episode, and therefore may represent a phase of active disease.

Neutrophil Gelatinase-associated Lipocalin Value in Patients' Urine with Gram Positive Cocci Infection in the Urinary Tract

2019 ◽  
Author(s):  
Somayeh Saadi ◽  
Seyed Mahdi Tabatabaei ◽  
Zahra Hooshmandi ◽  
Somayeh Salehizadeh
Keyword(s):  
Urinary Tract ◽  
Patient Group ◽  
Blood Cells ◽  
White Blood Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Microbial Culture ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
The Mean ◽  
Tract Infections ◽  
Neutrophil Gelatinase

Background and Aims: This study aimed to investigate the amount of Neutrophil gelatinase-associated lipocalin (NGAL) in patients' urine with Grampositive cocci infections  Materials and Methods: The microbial culture was prepared from 100 urine samples and the results were recorded. The genus and bacterial were species identified and an antibiogram test was conducted to investigate their resistance. Human Lipocalin /NGAL enzyme-linked immunosorbent assay test was used. To analyze the data, Tukey and One Way ANOVA tests were used. Results: The highest mean of NGAL in the patient group was related to the men's category with 8.77, and the gender had a significant impact on the mean of NGAL. White blood cells has a significant impact on the mean of NGAL (p<0.05). The negative significance of the mean value also indicates the amount of NGAL being higher in the patient group.  Conclusions: These data suggest a relationship between the amount of NGAL with white blood cells value in patients who present urinary infection of Grampositive cocci. NGAL value plays an important role as an adjuvant and surrogate marker in early diagnosis of urinary tract infections and acute renal damage in line with microbiological investigations. 

Detection of Occult Urinary Tract Infections in Dogs With Diabetes Mellitus

2002 ◽  
Vol 38 (6) ◽  
pp. 541-544 ◽  
Author(s):  
Nancy C. McGuire ◽  
Rhonda Schulman ◽  
Marcella D. Ridgway ◽  
German Bollero
Keyword(s):  
Diabetes Mellitus ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Blood Cells ◽  
White Blood Cells ◽  
Urine Specific Gravity ◽  
Consistent Finding ◽  
Diabetic Dogs ◽  
Tract Infections ◽  
The University

Dogs with diabetes mellitus may develop occult urinary tract infections. In this study, diabetic dogs with negative and positive bacterial urine cultures were compared. Records from 51 dogs with diabetes mellitus were reviewed at the University of Illinois. No difference was identified between the groups in urine specific gravity, pH, glucose, ketones, protein, red blood cells, white blood cells, or epithelial cells. Dogs with occult urinary tract infection did have an increased incidence of bacteriuria, but this was not a consistent finding. Therefore, the urine on all diabetic dogs should be cultured to accurately identify the presence or absence of bacterial urinary tract infections.

Urinary Tract Infections in Infants and Children

1989 ◽  
Vol 11 (3) ◽  
pp. 71-77
Author(s):  
Leonard G. Feld ◽  
Saul P. Greenfield ◽  
Pearay L. Ogra
Keyword(s):  
Urinary Tract ◽  
High Power ◽  
Blood Cells ◽  
Urine Culture ◽  
White Blood Cells ◽  
Laboratory Evaluation ◽  
Low Grade ◽  
Viral Gastroenteritis ◽  
High Power Field ◽  
Tract Infections

CASE HISTORY AND OFFICE DIAGNOSIS A 7-month-old uncircumcised male infant had vomiting, diarrhea, and low grade fever (38.4°C) 2 days before coming to the pediatrician's office. One day before seeing the baby, the physician prescribed Pedialyte and acetaminophen elixir. The child appeared active to the pediatrician. Mucous membranes were slightly dry and tears were present. His blood pressure was 98/62 mm Hg, pulse rate 92 beats per minute, and temperature 38°C. Laboratory evaluation included an analysis and culture of catheterized urine sample: specific gravity, 1.025; pH, 6.0; protein, trace; blood, negative; sugar and ketones, negative; sediment—0 to 1 red blood cells per high-power field; 6 to 8 white blood cells per high-power-field and no bacteria. Based on the differential diagnosis of viral gastroenteritis vs urinary tract infection, the patient was sent home with a prescription for Pedialyte and acetaminophen and the parents were told to call the office in 24 hours for test results. The urine culture was positive for greater than 100 000 colonies per milliliter of a single organism which was later identified as Escherichia coli and sensitive to all antibiotics. The child was started on a regimen of amoxicillin. Two weeks later, a repeat urine culture was negative for bacteria.

scholarly journals Blood, Tissue, and Intracellular Concentrations of Erythromycin and Its Metabolite Anhydroerythromycin during and after Therapy

2011 ◽  
Vol 56 (2) ◽  
pp. 1059-1064 ◽  
Author(s):  
S. Krasniqi ◽  
P. Matzneller ◽  
M. Kinzig ◽  
F. Sörgel ◽  
S. Hüttner ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Soft Tissues ◽  
Parent Compound ◽  
White Blood Cells ◽  
Interstitial Space ◽  
Clinical Activity ◽  
End Of Treatment ◽  
Short Period ◽  
Subinhibitory Concentrations ◽  
Subcutaneous Adipose

ABSTRACTFor macrolides, clinical activity but also the development of bacterial resistance has been attributed to prolonged therapeutic and subtherapeutic concentrations. Although erythromycin is a long-established antimicrobial, concomitant determination of the pharmacokinetics of erythromycin and its metabolites in different compartments is limited. To better characterize the pharmacokinetics of erythromycin and its anhydrometabolite (anhydroerythromycin [AHE]) in different compartments during and after the end of treatment with 500 mg of erythromycin four times daily, concentration-time profiles were determined in plasma, interstitial space of muscle and subcutaneous adipose tissue, and white blood cells (WBCs) at days 1 and 3 of treatment and 2 and 7 days after end of therapy. In WBCs, concentrations of erythromycin exceeded those in plasma approximately 40-fold, while free concentrations in plasma and tissue were comparable. The observed delay of peak concentrations in tissue might be caused by fast initial cellular uptake. Two days after the end of treatment, subinhibitory concentrations were observed in plasma and interstitial space of both soft tissues, while 7 days after the end of treatment, erythromycin was not detectable in any compartment. This relatively short period of subinhibitory concentrations may be advantageous compared to other macrolides. The ratio of erythromycin over AHE on day 1 was highest in plasma (2.81 ± 3.45) and lowest in WBCs (0.27 ± 0.22). While the ratio remained constant between single dose and steady state, after the end of treatment the concentration of AHE declined more slowly than that of the parent compound, indicating the importance of the metabolite for the prolonged drug interaction of erythromycin.

Ultrastructural changes in murine lymphoma cells exposed to ultraviolet-A radiation

1991 ◽  
Vol 49 ◽  
pp. 104-105
Author(s):  
Delma P. Thomas ◽  
Dianne E. Godar
Keyword(s):  
Medical Devices ◽  
Blood Cells ◽  
White Blood Cells ◽  
Consumer Products ◽  
Ultrastructural Changes ◽  
Ultraviolet A ◽  
Uv Spectrum ◽  
Lymphoma Cells ◽  
Murine Lymphoma ◽  
Transmission Electron

Ultraviolet radiation (UVR) from all three waveband regions of the UV spectrum, UVA (320-400 nm), UVB (290-320 nm), and UVC (200-290 nm), can be emitted by some medical devices and consumer products. Sunlamps can expose the blood to a considerable amount of UVR, particularly UVA and/or UVB. The percent transmission of each waveband through the epidermis to the dermis, which contains blood, increases in the order of increasing wavelength: UVC (10%) < UVB (20%) < UVA (30%). To investigate the effects of UVR on white blood cells, we chose transmission electron microscopy to examine the ultrastructure changes in L5178Y-R murine lymphoma cells.

The Effect of Red Blood Cells on the ADP-induced Aggregation of Human Platelets in Flow Through Tubes

1990 ◽  
Vol 63 (01) ◽  
pp. 112-121 ◽  
Author(s):  
David N Bell ◽  
Samira Spain ◽  
Harry L Goldsmith
Keyword(s):  
Platelet Aggregation ◽  
Shear Rate ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Platelet Rich Plasma ◽  
Mean Transit Time ◽  
White Blood Cells ◽  
Aggregate Size ◽  
Human Platelets ◽  
Induced Aggregation

SummaryThe effect of red blood cells, rbc, and shear rate on the ADPinduced aggregation of platelets in whole blood, WB, flowing through polyethylene tubing was studied using a previously described technique (1). Effluent WB was collected into 0.5% glutaraldehyde and the red blood cells removed by centrifugation through Percoll. At 23°C the rate of single platelet aggregtion was upt to 9× greater in WB than previously found in platelet-rich plasma (2) at mean tube shear rates Ḡ = 41.9,335, and 1,920 s−1, and at both 0.2 and 1.0 µM ADP. At 0.2 pM ADP, the rate of aggregation was greatest at Ḡ = 41.9 s−1 over the first 1.7 s mean transit time through the flow tube, t, but decreased steadily with time. At Ḡ ≥335 s−1 the rate of aggregation increased between t = 1.7 and 8.6 s; however, aggregate size decreased with increasing shear rate. At 1.0 µM ADP, the initial rate of single platelet aggregation was still highest at Ḡ = 41.9 s1 where large aggregates up to several millimeters in diameter containing rbc formed by t = 43 s. At this ADP concentration, aggregate size was still limited at Ḡ ≥335 s−1 but the rate of single platelet aggregation was markedly greater than at 0.2 pM ADP. By t = 43 s, no single platelets remained and rbc were not incorporated into aggregates. Although aggregate size increased slowly, large aggregates eventually formed. White blood cells were not significantly incorporated into aggregates at any shear rate or ADP concentration. Since the present technique did not induce platelet thromboxane A2 formation or cause cell lysis, these experiments provide evidence for a purely mechanical effect of rbc in augmenting platelet aggregation in WB.

White blood cells levels and PCOS: direct and indirect relationship with insulin resistance, but not with hyperandogenemia

2013 ◽  
Author(s):  
Olga Papalou ◽  
Sarantis Livadas ◽  
Athanasios Karachalios ◽  
Nektarios Benetatos ◽  
George Boutzios ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Cells ◽  
White Blood Cells ◽  
Indirect Relationship
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