scholarly journals Pharmacokinetics of Single- and Multiple-Dose Oral Clarithromycin in Soft Tissues Determined by Microdialysis

2007 ◽  
Vol 51 (9) ◽  
pp. 3185-3189 ◽  
Author(s):  
Friederike Traunmüller ◽  
Markus Zeitlinger ◽  
Petra Zeleny ◽  
Markus Müller ◽  
Christian Joukhadar
Keyword(s):  
Skeletal Muscle ◽  
Single Dose ◽  
Steady State ◽  
Soft Tissue ◽  
Soft Tissues ◽  
Interstitial Space ◽  
Soft Tissue Infections ◽  
Time Curve ◽  
Dose Oral ◽  
Subcutaneous Adipose

ABSTRACT The antimicrobial spectrum of clarithromycin renders this antibiotic a frequently used option in the treatment of skin and soft-tissue infections. In most cases, these infections are caused by extracellularly proliferating microorganisms. Thus, clarithromycin concentrations achieved in the interstitial space are considered particularly important for clinical efficacy. In the present study, clarithromycin concentrations in plasma and interstitial-space fluid of subcutaneous adipose tissue and skeletal muscle of six healthy male volunteers were assessed by means of the microdialysis technique after oral single-dose administration of 250 mg and multiple doses of 500 mg of clarithromycin twice a day (b.i.d.). The ratios of the area under the concentration-time curve of free clarithromycin from 0 to 24 h calculated for a single dose of 250 mg (fAUC0-24) in interstitial-space fluid to the fAUC0-24 in plasma were 0.29 ± 0.17 and 0.42 ± 0.18 for subcutis and skeletal muscle, respectively. For 500 mg of clarithromycin at the steady state (3 to 5 days of intake twice daily), the fAUC0-24(b.i.d.) ratios at the steady state were 0.39 ± 0.04 and 0.41 ± 0.19 for subcutis and skeletal muscle, respectively. The half-life was around 2 h after a single dose but increased to approximately 4 h in plasma and tissues after repetitive clarithromycin administration. Based on subsequently performed pharmacokinetic-pharmacodynamic calculations, a dosing regimen of 500 mg b.i.d. may be ineffective in the treatment of soft-tissue infections caused by pathogens with a drug MIC higher than 0.125 mg/liter.

scholarly journals Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues

2000 ◽  
Vol 44 (10) ◽  
pp. 2728-2732 ◽  
Author(s):  
Martin Frossard ◽  
Christian Joukhadar ◽  
Boban M. Erovic ◽  
Peter Dittrich ◽  
Paulus E. Mrass ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissues ◽  
Pharmacokinetic Profile ◽  
Interstitial Space ◽  
Soft Tissue Infections ◽  
Time Curve ◽  
Tract Infections ◽  
High Degree

ABSTRACT Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. For this purpose fosfomycin concentrations in vivo in the fluid of the interstitial space of human soft tissues were measured by microdialysis following intravenous infusion of 4 or 8 g of fosfomycin (n = 6). Subsequently, bacterial isolates with relevance for soft tissue infections were exposed to concentrations according to the in vivo pharmacokinetic profile in the interstitial space fluid obtained by microdialysis. Our experiments indicated a high degree of soft tissue penetration for fosfomycin, with ratios of the area under the concentration-time curve from 0 to 8 h for muscle (AUC0–8muscle )/AUC0–8serum of 0.48 ± 0.08 and 0.53 ± 0.04 and ratios of AUC0–8adipose tissue /AUC0–8serum of 0.74 ± 0.12 and 0.71 ± 0.11 following administration of 4 and 8 g, respectively. In corresponding in vitro simulation experiments with selected isolates of Staphylococcus aureus,Enterobacter cloacae, and Serratia marcescensfor which MICs were 16 μg/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.

scholarly journals Penetration of Doripenem into Skeletal Muscle and Subcutaneous Adipose Tissue in Healthy Volunteers

2011 ◽  
Vol 56 (1) ◽  
pp. 532-535 ◽  
Author(s):  
Bernhard Burian ◽  
Markus Zeitlinger ◽  
Oliver Donath ◽  
Gottfried Reznicek ◽  
Robert Sauermann
Keyword(s):  
Skeletal Muscle ◽  
Antimicrobial Activity ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Soft Tissues ◽  
Time Curve ◽  
Bacterial Killing ◽  
Drug Concentrations ◽  
Subcutaneous Adipose

ABSTRACTSufficient antibiotic concentrations at the infection site are a prerequisite for good bacterial killing. This study was performed to determine pharmacokinetics of doripenem in soft tissues and saliva. Six healthy male volunteers received a single intravenous infusion of 500 mg doripenem over 1 h. The concentrations of doripenem were measured over 8 h in saliva, plasma, and extracellular space fluid of skeletal muscle and subcutaneous adipose tissue employingin vivomicrodialysis. Unbound drug concentrations were determined using ultra-high-performance liquid chromatography-tandem mass spectrometry. Maximum concentrations of doripenem were 15.3 ± 6.0 mg/liter in plasma, 9.9 ± 2.3 mg/liter in subcutaneous adipose tissue, 6.6 ± 2.9 mg/liter in skeletal muscle, and 0.5 ± 0.2 mg/liter in saliva. Areas under the concentration-time curve (AUC) from 0 to infinity were 26.3 ± 10.1, 20.4 ± 3.8, 12.8 ± 3.0, and 1.0 ± 0.5 mg · h/liter in plasma, adipose tissue, skeletal muscle, and saliva, respectively. Ratios of AUC in adipose tissue, skeletal muscle, and saliva to those in plasma were 0.84 ± 0.28, 0.53 ± 0.19, and 0.04 ± 0.03, respectively. In all six volunteers, a threshold of ≥40% for “time above MIC,” an index indicative of good antimicrobial activity, was exceeded in adipose tissue for MICs of ≤2 mg/liter and in skeletal muscle for MICs ≤1.5 mg/liter. Doripenem penetrates well into interstitial space fluid of skeletal muscle and adipose tissue, suggesting good antimicrobial activity in infected soft tissues, whereas it is detectable in relatively low concentrations in saliva.

scholarly journals Rhabdomyosarcoma of the Oral Cavity: A Case Report

2011 ◽  
Vol 05 (03) ◽  
pp. 340-343 ◽  
Author(s):  
Ozkan Miloglu ◽  
Sare Sipal Altas ◽  
Mustafa Cemil Buyukkurt ◽  
Burak Erdemci ◽  
Oguzhan Altun
Keyword(s):  
Skeletal Muscle ◽  
Case Report ◽  
Soft Tissue ◽  
Oral Cavity ◽  
Head And Neck ◽  
Soft Tissues ◽  
Neck Region ◽  
Childhood And Adolescence ◽  
Head And Neck Region ◽  
The Common

ABSTRACTRhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common soft tissue sarcoma encountered in childhood and adolescence. The common sites of occurrence are the head and neck region, genitourinary tract, retroperitonium, and, to a lesser extent, the extremities. In the head and neck region, the most commonly affected sites are the orbit, paranasal sinuses, soft tissues of the cheek, and the neck. RMS is relatively uncommon in the oral cavity, and the involvement of the jaws is extremely rare. Here, we report a case of oral RMS in a 13-year-old child and describe the clinical, radiological, histopathological, and immunohistochemical findings. (Eur J Dent 2011;5:340-343)

Antibiotic Resistance in Diabetic Foot Soft Tissue Infections: A Series From Greece

2017 ◽  
Vol 16 (4) ◽  
pp. 255-259 ◽  
Author(s):  
Maria Demetriou ◽  
Nikolaos Papanas ◽  
Periklis Panagopoulos ◽  
Maria Panopoulou ◽  
Efstratios Maltezos
Keyword(s):  
Antibiotic Resistance ◽  
Soft Tissue ◽  
Diabetic Foot ◽  
Soft Tissues ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Soft Tissue Infections ◽  
Diabetic Foot Infections ◽  
Initial Choice ◽  
Gram Positive Cocci

Diabetic foot infections are a common and serious problem for all health systems worldwide. The aim of this study was to examine the resistance to antibiotics of microorganisms isolated from infected soft tissues of diabetic foot ulcers, using tissue cultures. We included 113 consecutive patients (70 men, 43 women) with a mean age of 66.4 ± 11.2 years and a mean diabetes duration of 14.4 ± 7.6 years presenting with diabetic foot soft tissue infections. Generally, no high antibiotic resistance was observed. Piperacillin-tazobactam exhibited the lowest resistance in Pseudomonas, as well as in the other Gram-negative pathogens. In methicillin-resistant Staphylococcus aureus isolates, there was no resistance to anti-Staphylococcus agents. Of note, clindamycin, erythromycin, and amoxycillin/clavulanic acid exhibited high resistance in Gram-positive cocci. These results suggest that antibiotic resistance in infected diabetic foot ulcers in our area is not high and they are anticipated to prove potentially useful in the initial choice of antibiotic regimen.

scholarly journals Pharmacokinetics of Telbivudine in Healthy Subjects and Absence of Drug Interaction with Lamivudine or Adefovir Dipivoxil

2006 ◽  
Vol 50 (7) ◽  
pp. 2309-2315 ◽  
Author(s):  
Xiao-Jian Zhou ◽  
Barbara A. Fielman ◽  
Deborah M. Lloyd ◽  
George C. Chao ◽  
Nathaniel A. Brown
Keyword(s):  
Single Dose ◽  
Steady State ◽  
Plasma Concentration ◽  
Healthy Subjects ◽  
Adefovir Dipivoxil ◽  
Geometric Mean ◽  
Time Curve ◽  
Concentration Time ◽  
Plasma Pharmacokinetics ◽  
Plasma Concentration Time Curve

ABSTRACT Two phase I studies were conducted to assess the plasma pharmacokinetics of telbivudine and potential drug-drug interactions between telbivudine (200 or 600 mg/day) and lamivudine (100 mg/day) or adefovir dipivoxil (10 mg/day) in healthy subjects. Study drugs were administered orally. The pharmacokinetics of telbivudine were characterized by rapid absorption with biphasic disposition. The maximum concentrations in plasma (C max) were reached at median times ranging from 2.5 to 3.0 h after dosing. Mean single-dose C max and area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) were 1.1 and 2.9 μg/ml and 7.4 and 21.8 μg · h/ml for the 200- and 600-mg telbivudine doses, respectively. Steady state was reached after daily dosing for 5 to 7 days. The mean steady-state C max and area under the plasma concentration-time curve over the dosing interval (AUCτ) were 1.2 and 3.4 μg/ml and 8.9 and 27.5 μg · h/ml for the 200- and 600-mg telbivudine repeat doses, respectively. The steady-state AUCτ of telbivudine was 23 to 57% higher than the single-dose values. Concomitant lamivudine or adefovir dipivoxil did not appear to significantly alter the steady-state plasma pharmacokinetics of telbivudine; the geometric mean ratios and associated 90% confidence interval (CI) for the AUCτ of telbivudine alone versus in combination were 106.3% (92.0 to 122.8%) and 98.6% (86.4 to 112.5%) when coadministered with lamivudine and adefovir dipivoxil, respectively. Similarly, the steady-state plasma pharmacokinetics of lamivudine or adefovir were not markedly affected by the coadministration of telbivudine; the geometric mean ratios and associated 90% CI, alone versus in combination with telbivudine, were 99.0% (87.1 to 112.4%) and 92.2% (84.0 to 101.1%), respectively, for the lamivudine and adefovir AUCτ values. Moreover, the combination regimens studied were well tolerated in all subjects. The results from these studies provide pharmacologic support for combination therapy or therapy switching involving telbivudine, lamivudine, and adefovir dipivoxil for the treatment of chronic hepatitis B virus infection.

scholarly journals Necrotizing Soft Tissue Infections, the Challenge Remains

2021 ◽  
Vol 8 ◽  
Author(s):  
Femke Nawijn ◽  
Falco Hietbrink ◽  
Andrew B. Peitzman ◽  
Luke P. H. Leenen
Keyword(s):  
Soft Tissue ◽  
Critically Ill ◽  
Soft Tissues ◽  
Systemic Toxicity ◽  
The Other ◽  
Definitive Treatment ◽  
Critically Ill Patient ◽  
Soft Tissue Infections ◽  
Necrotizing Soft Tissue Infections ◽  
Specific Symptoms

Background: Necrotizing Soft Tissue Infections (NSTIs) are uncommon rapidly spreading infection of the soft tissues for which prompt surgical treatment is vital for survival. Currently, even with sufficient awareness and facilities available, ambiguous symptoms frequently result in treatment delay.Objectives: To illustrate the heterogeneity in presentation of NSTIs and the pitfalls entailing from this heterogeneity.Discussion: NSTI symptoms appear on a spectrum with on one side the typical critically ill patient with fast onset and progression of symptoms combined with severe systemic toxicity resulting in severe physical derangement and sepsis. In these cases, the suspicion of a NSTI rises quickly. On the other far side of the spectrum is the less evident type of presentation of the patient with gradual but slow progression of non-specific symptoms over the past couple of days without clear signs of sepsis initially. This side of the spectrum is under represented in current literature and some physicians involved in the care for NSTI patients are still unaware of this heterogeneity in presentation.Conclusion: The presentation of a critically ill patient with evident pain out of proportion, erythema, necrotic skin and bullae is the classical presentation of NSTIs. On the other hand, non-specific symptoms without systemic toxicity at presentation frequently result in a battery of diagnostics tests and imaging before the treatment strategy is determined. This may result in a delay in presentation, delay in diagnosis and delay in definitive treatment. This failure to perform an adequate exploration expeditiously can result in a preventable mortality.

The Need to Develop New Antimicrobial Molecules, as Revealed by in vitro Assessment of Drug Resistance in Staphylococcal Skin Infections Treated with Autologous Bacterial Vaccine

2020 ◽  
Vol 71 (8) ◽  
pp. 292-303
Author(s):  
Madalina Preda ◽  
Alina-Alexandra Serbanescu ◽  
Mara Madalina Mihai ◽  
Gabriela-Loredana Popa ◽  
Loredana Cornelia Sabina Manolescu ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Antimicrobial Resistance ◽  
Soft Tissues ◽  
The Body ◽  
Laboratory Research ◽  
Soft Tissue Infections ◽  
Resistance Profile ◽  
Bacterial Vaccine ◽  
Staphylococcus Spp

Staphylococcus spp. is a facultative pathogen, which can be found in the commensal microbiota of humans, most often in moist skinfolds and mucous membranes. This microorganism has the ability to cause various infections, in almost every organ of the body, with an increased frequency in the skin and soft tissues, being involved in pathologies like acne, folliculitis, furunculosis, hidradenitis suppurativa, cellulitis, abscesses, but also in secondary infections in diseases with an altered cutaneous barrier. The prolonged evolution of these diseases and severe outcome can be influenced by various factors, most importantly being the antimicrobial resistance. We have evaluated the antimicrobial susceptibility profiles, according to the Comite de l` Antibiogramme de la Societe Francaise de Microbiologie recommendations, for strains of Staphylococcus spp. isolated from acne or different types of skin and soft tissue infections in patients recommended to receive autologous bacterial vaccine. Most frequent identified species was Staphylococcus epidermidis, followed by Staphylococcus aureus. The antimicrobial resistance was higher for antibiotics usually used in the treatment of skin and soft tissue infections, with interesting differences of the resistance profile for the strains isolated from patients before receiving autologous bacterial vaccine compared with the ones from individuals already treated. Another important finding was represented by the differences in the resistance profile according to the age group of the patients. The results of this study underline the importance of antimicrobial resistance surveillance in finding new molecules and alternative therapies, the necessity of a personalized approach in medical acts and of a continuous connection between clinic and laboratory research.

scholarly journals Penetration of Linezolid into Soft Tissues of Healthy Volunteers after Single and Multiple Doses

2005 ◽  
Vol 49 (6) ◽  
pp. 2367-2371 ◽  
Author(s):  
Pejman Dehghanyar ◽  
Cornelia Bürger ◽  
Markus Zeitlinger ◽  
Florian Islinger ◽  
Florian Kovar ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Soft Tissues ◽  
In Vivo Microdialysis ◽  
Time Curve ◽  
Concentration Time ◽  
Multiple Doses ◽  
Muscle Tissues ◽  
Subcutaneous Adipose ◽  
Free Plasma

ABSTRACT The present study tested the ability of linezolid to penetrate soft tissues in healthy volunteers. Ten healthy volunteers were subjected to linezolid drug intake at a dose of 600 mg twice a day for 3 to 5 days. The first dose was administered intravenously. All following doses were self-administered orally. The tissue penetration of linezolid was assessed by use of in vivo microdialysis. In the single-dose experiments the ratios of the area under the concentration-time curve from 0 to 8 h (AUC0-8) for tissue to the AUC0-8 for free plasma were 1.4 ± 0.3 (mean ± standard deviation) and 1.3 ± 0.4 for subcutaneous adipose and muscle tissue, respectively. After multiple doses, the corresponding mean ratios were 0.9 ± 0.2 and 1.0 ± 0.5, respectively. The ratios of the AUC from 0 to 24 h (AUC0-24) for free linezolid in tissues to the MIC were between 50 and 100 for target pathogens with MICs between 2 and 4 mg/liter. In conclusion, the present study showed that linezolid penetrates rapidly into the interstitial space fluid of subcutaneous adipose and skeletal muscle tissues in healthy volunteers. On the basis of pharmacokinetic-pharmacodynamic calculations, we suggest that linezolid concentrations in soft tissues can be considered sufficient to inhibit the growth of many clinically relevant bacteria.

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