scholarly journals Soft-Tissue Penetration of Ceftobiprole in Healthy Volunteers Determined by In Vivo Microdialysis

2009 ◽  
Vol 53 (7) ◽  
pp. 2773-2776 ◽  
Author(s):  
April Barbour ◽  
Stephan Schmidt ◽  
Sreedharan Nair Sabarinath ◽  
Maria Grant ◽  
Christoph Seubert ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Soft Tissue ◽  
Healthy Volunteers ◽  
Free Drug ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Skin Structure ◽  
Drug Concentrations

ABSTRACT Ceftobiprole is a promising new broad-spectrum cephalosporin with activity against several multidrug-resistant gram-positive and gram-negative species, including methicillin-resistant Staphylococcus aureus. In order to make efficacy predications against these resistant bacteria in soft-tissue infections, i.e., skin and skin structure infections, ceftobiprole's ability to reach the site of action should be explored. Therefore, a microdialysis study was conducted in 12 healthy volunteers to determine the penetration of ceftobiprole into skeletal muscle and subcutaneous (s.c.) adipose tissue after a single intravenous dose of 500 mg. Plasma and tissue interstitial space fluid (ISF) drug concentrations were measured for 24 h from the start of the 2-h intravenous infusion. Pharmacokinetic parameters were determined using noncompartmental analysis. The penetration of ceftobiprole into the ISF of tissues was assessed by comparing the ratios between tissue and plasma of the free drug area under the concentration-time curve (fAUC). It was found that ceftobiprole distributes into the muscle (fAUCmuscle/fAUCplasma of 0.69 ± 0.13) and s.c. adipose tissue (fAUCs.c.adipose/fAUCplasma of 0.49 ± 0.28). The concentrations in both skeletal muscle and s.c. adipose tissue met the efficacy breakpoint (percentage of the time that free drug concentrations remained above the MIC) for at least 40% of the 8-h dosing interval for organisms with a MIC of 2 mg/liter. Therefore, ceftobiprole qualifies as a potential agent with drug penetration capabilities to treat complicated skin and skin structure infections due to both gram-negative and gram-positive pathogens with MICs equal to or below 2 mg/liter.

scholarly journals Concentrations of Gemifloxacin at the Target Site in Healthy Volunteers after a Single Oral Dose

2004 ◽  
Vol 48 (11) ◽  
pp. 4246-4249 ◽  
Author(s):  
Florian Islinger ◽  
Rene Bouw ◽  
Mathias Stahl ◽  
Edith Lackner ◽  
Petra Zeleny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Soft Tissue ◽  
Oral Dose ◽  
Healthy Volunteers ◽  
Single Oral Dose ◽  
Soft Tissues ◽  
Therapeutic Option ◽  
The Mean

ABSTRACT Free gemifloxacin concentrations in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were measured by means of in vivo microdialysis to characterize the ability of gemifloxacin to penetrate human soft tissues. Twelve healthy volunteers received a single oral dose of 320 mg of gemifloxacin. The mean areas under the concentration-time curves from 0 to 10 h (AUC0-10) were significantly higher for soft tissue than for unbound gemifloxacin in plasma (P < 0.05). The ratios of the mean AUC0-10 for tissue to the AUC0-10 for free gemifloxacin in plasma were 1.7 ± 0.7 (mean ± standard deviation) for skeletal muscle and 2.4 ± 1.0 for adipose tissue. The AUC0-24 ratios for free gemifloxacin in tissues to the MIC at which 90% of frequently isolated bacteria are inhibited were close to or higher than 100 h. Therefore, based on pharmacokinetic and pharmacodynamic calculations, we conclude that gemifloxacin might be a useful therapeutic option for the treatment of soft tissue infections.

scholarly journals In Vivo Microdialysis Study of the Penetration of Daptomycin into Soft Tissues in Diabetic versus Healthy Volunteers

2008 ◽  
Vol 52 (11) ◽  
pp. 3941-3946 ◽  
Author(s):  
Aryun Kim ◽  
Larry A. Suecof ◽  
Christina A. Sutherland ◽  
Lihong Gao ◽  
Joseph L. Kuti ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Healthy Volunteers ◽  
Healthy Subjects ◽  
Soft Tissues ◽  
In Vivo Microdialysis ◽  
Free Drug ◽  
Target Tissue ◽  
Drug Concentrations ◽  
Complicated Skin

ABSTRACT Daptomycin is approved for the treatment of complicated skin and soft tissue infections, including diabetic wounds of the lower extremities, at a dose of 4 mg/kg of body weight once daily. For such localized tissue infections, drug concentrations in the interstitial space are an important determinant of successful therapy. In the diabetic population, peripheral arterial disease may limit antibiotic penetration into the target tissue. The objective of this study was to describe and compare the pharmacokinetic profiles of daptomycin in the interstitial fluid of soft tissues in diabetic and healthy volunteers by using in vivo microdialysis. Twelve subjects (six diabetic and six healthy) received a single 4-mg/kg dose of daptomycin intravenously. Samples of plasma and tissue were simultaneously collected over 24 h. Diabetic and healthy groups were matched in mean age (±10 years), gender ratio, mean weight (±10 kg), and creatinine clearance rate (±20 ml/min/1.73 m2). Pharmacokinetic parameters for plasma were similar between groups (P > 0.05). The mean peak drug concentrations ± standard deviations in tissue were 4.3 ± 3.3 μg/ml and 3.8 ± 1.4 μg/ml for diabetic and healthy subjects, respectively. The degree of tissue penetration, defined as the ratio of the area under the free drug concentration-time curve for tissue to that for plasma, was 0.93 ± 0.61 for diabetic subjects and 0.74 ± 0.09 for healthy subjects (P = 0.46). Daptomycin at 4 mg/kg penetrated well into the soft tissue, reaching concentrations approximately 70 to 90% of those of the free drug in plasma. Moreover, these free, bioactive concentrations in tissue exceeded the MICs for staphylococci and streptococci over the 24-h dosing interval.

scholarly journals Single- and Repeated-Dose Pharmacokinetics of Ceftaroline in Plasma and Soft Tissues of Healthy Volunteers for Two Different Dosing Regimens of Ceftaroline Fosamil

2016 ◽  
Vol 60 (6) ◽  
pp. 3617-3625 ◽  
Author(s):  
Peter Matzneller ◽  
Edith Lackner ◽  
Heimo Lagler ◽  
Beatrix Wulkersdorfer ◽  
Zoe Österreicher ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Healthy Volunteers ◽  
Soft Tissues ◽  
Free Drug ◽  
Phase Iii ◽  
Ceftaroline Fosamil ◽  
Dosing Interval ◽  
Drug Concentrations ◽  
Complicated Skin ◽  
Dosing Regimens

Ceftaroline fosamil (CPT-F) is currently approved for use for the treatment of complicated skin and soft tissue infections and community-acquired pneumonia at 600 mg twice daily (q12h), but other dosing regimens are under evaluation. To date, very limited data on the soft tissue pharmacokinetics (PK) of the active compound, ceftaroline (CPT), are available. CPT concentrations in the plasma, muscle, and subcutis of 12 male healthy volunteers were measured by microdialysis after single and repeated intravenous administration of 600 mg CPT-F q12h or three times daily (q8h) in two groups of 6 subjects each. Relevant PK and PK/pharmacodynamic (PD) parameters were calculated and compared between groups. In plasma, the area under the concentration-time curve (AUC) from 0 to 24 h for total CPT and the cumulative percentage of the dosing interval during which the free drug concentrations exceeded the MIC (fTMIC) for unbound CPT for the currently established threshold of 1 mg/liter were significantly higher in the group receiving CPT-F q8h. Exposure to free drug in soft tissues was higher in the group receiving CPT-F q8h, but high interindividual variability in relevant PK parameters was observed. The mean ratios of the AUC from time zero to the end of the dosing interval (AUC0-τ) for free CPT in soft tissues and the AUC0-τfor the calculated free fraction in plasma at steady state ranged from 0.66 to 0.75. Administration of CPT-F q8h led to higher levels of drug exposure in all investigated compartments. When MIC values above 1 mg/liter were assumed, the calculatedfTMICafter dosing q12h was markedly lower than that after dosing q8h. The clinical implications of these differences are discussed in light of recently completed clinical phase III and PK/PD studies.

scholarly journals Pharmacokinetics and Tissue Penetration of Ceftolozane-Tazobactam in Diabetic Patients with Lower Limb Infections and Healthy Adult Volunteers

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Marguerite L. Monogue ◽  
Sean M. Stainton ◽  
Arlinda Baummer-Carr ◽  
Ashley K. Shepard ◽  
James F. Nugent ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Subcutaneous Tissue ◽  
Free Drug ◽  
Free Time ◽  
Pharmacokinetic Parameters ◽  
Diabetic Patients ◽  
Total Plasma ◽  
Tissue Penetration ◽  
Gram Negative ◽  
Time Zero

ABSTRACT Ceftolozane-tazobactam displays potent activity against Gram-negative bacteria that can cause diabetic foot infections (DFI), making it an attractive treatment option when few alternatives exist. The pharmacokinetics and tissue penetration of ceftolozane-tazobactam at 1.5 g every 8 h (q8h) in patients (n = 10) with DFI were compared with those in healthy volunteers (n = 6) using in vivo microdialysis. In the patient participants, the median values of the pharmacokinetic parameters for ceftolozane in total plasma were as follows: maximum concentration (C max), 55.2 μg/ml (range, 40.9 to 169.3 μg/ml); half-life (t 1/2), 3.5 h (range, 2.3 to 4.7 h); and area under the concentration-time curve (AUC) from time zero to 8 h (AUC0–8), 191.6 μg · h/ml (range, 147.1 to 286.6 μg · h/ml). The median AUC for tissue (AUCtissue; where AUCtissue was the AUC0–8 for tissue for ceftolozane)/AUC for plasma for each antibiotic corrected by the fraction of free drug (fAUCplasma) was 0.75 (range, 0.35 to 1.00), resulting in a mean free time above 4 μg/ml (the Pseudomonas aeruginosa susceptibility breakpoint) in tissue of 99.8% (range, 87.5 to 100%). In the patient participants, the median values of the pharmacokinetic parameters for tazobactam in total plasma were as follows: C max, 14.2 μg/ml (range, 7.6 to 64.2 μg/ml); t 1/2, 2.0 h (range, 0.7 to 2.4 h); and AUC0–8, 27.1 μg · h/ml (range, 15.0 to 70.0 μg · h/ml). The AUCtissue (where AUCtissue was the AUC from time zero to the time of the last measureable concentration in tissue for tazobactam)/fAUCplasma for tazobactam was 1.18 (range, 0.54 to 1.44). In the healthy volunteers, the median values of the pharmacokinetic parameters for ceftolozane in total plasma were as follows: C max, 91.5 μg/ml (range, 65.7 to 110.7 μg/ml); t 1/2, 1.9 h (range, 1.6 to 2.1 h); and AUC0–8, 191.3 μg · h/ml (range, 118.1 to 274.3 μg · h/ml). The median AUCtissue/fAUCplasma was 0.87 (range, 0.54 to 2.20), resulting in a mean free time above 4 μg/ml in tissue of 93.8% (range, 87.5 to 100%). In the healthy volunteers, the median values of the pharmacokinetic parameters for tazobactam in total plasma were as follows: C max, 17.5 μg/ml (range, 15.4 to 27.3 μg/ml); t 1/2, 0.7 h (range, 0.6 to 0.8 h); and AUC0–8, 22.2 μg · h/ml (range, 19.2 to 36.4 μg · h/ml). The AUCtissue/fAUCplasma for tazobactam was 0.85 (range, 0.63 to 2.10). Both ceftolozane and tazobactam penetrated into subcutaneous tissue with exposures similar to those of free drug in plasma in both patients with DFI and healthy volunteers. These data suggest that ceftolozane-tazobactam at 1.5 g q8h can achieve the optimal exposure with activity against susceptible Gram-negative pathogens in the tissue of patients with DFI. (This study has been registered at ClinicalTrials.gov under identifier NCT02620774.)

Microbiological pattern of prosthetic hip and knee infections: a high-volume, single-centre experience in China

2021 ◽  
Author(s):  
Yali Yu ◽  
Yiyi Kong ◽  
Jing Ye ◽  
Aiguo Wang ◽  
Wenteng Si
Keyword(s):  
Antibiotic Treatment ◽  
Prolonged Treatment ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Musculoskeletal Infection ◽  
Gram Negative ◽  
Content Type ◽  
Empirical Antibiotic Treatment ◽  
Link Type

Introduction. Prosthetic joint infection (PJI) is a serious complication after arthroplasty, which results in high morbidity, prolonged treatment and considerable healthcare expenses in the absence of accurate diagnosis. In China, microbiological data on PJIs are still scarce. Hypothesis/Gap Statement. The incidence of PJI is increasing year by year, and the proportion of drug-resistant bacteria infection is nicreasing, which brings severe challenges to the treatment of infection. Aim. This study aimed to identify the pathogens in PJIs, multi-drug resistance, and evaluate the effect of the treatment regimen in patients with PJI. Methodology. A total of 366 consecutive cases of PJI in the hip or knee joint were admitted at the Orthopedic Surgery Center in Zhengzhou, China from January 2012 to December 2018. Infections were confirmed in accordance with the Infectious Diseases Society of America and the Musculoskeletal Infection Society (MSIS) criteria. Concurrently, patient demographic data, incidence and antibiotic resistance were investigated. Statistical differences were analysed using Fisher’s exact test or chi-square test. Results. Altogether, 318 PJI cases satisfying the inclusion criteria were enrolled in this study, including 148 with hip PJIs and 170 with knee PJIs. The average age of patients with hip PJIs was lesser than that of patients with knee PJIs (56.4 vs. 68.6 years). Meanwhile, coagulase-negative staphylococcus (CNS, n=81, 25.5 %) was the predominant causative pathogen, followed by Staphylococcus aureus (n=67, 21.1 %). Methicillin-resistant Staphylococcus (MRS) was identified in 28.9 % of PJI patients. In addition, fungus accounted for 4.8 % (n=15), non-tuberculosis mycobacterium accounted for 1.6 % (n=5), polymicrobial pathogens accounted for 21.7 % (n=69), and Gram-negative bacteria accounted for 7.9 % (n=25) of the total infections. The results of antibiotic susceptibility testing showed that gentamicin and clindamycin β-lactam antibiotics were poorly susceptible to Gram-positive isolates, but they were sensitive to rifampicin, linezolid and vancomycin. While antibiotics such as amikacin and imipenem were effective against Gram-negative bacteria, there was a high resistance rate of other pathogens to gentamicin, clindamycin and some quinolone antibacterial drugs. Empirical antibiotic treatment should combine vancomycin and cephalosporin, levofloxacin or clindamycin. When the pathogen is confirmed, the treatment should be individualized. Conclusions. The prevalence of culture-negative PJIs is still very high. Gram-positive bacteria are still the main type of pathogens that cause PJIs. Attention should be paid to the high incidence of MRS, such as MRSA and MR-CNS, among PJI patients. Empirical antibiotic treatment should cover Gram-positive isolates, especially Staphylococcus .

scholarly journals Sarconesin II, a New Antimicrobial Peptide Isolated from Sarconesiopsis magellanica Excretions and Secretions

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2077 ◽  
Author(s):  
Andrea Díaz-Roa ◽  
Abraham Espinoza-Culupú ◽  
Orlando Torres-García ◽  
Monamaris M. Borges ◽  
Ivan N. Avino ◽  
...  
Keyword(s):  
Micrococcus Luteus ◽  
Multidrug Resistant ◽  
Peptide Sequence ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Antimicrobial Drugs ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Conserved Domain ◽  
Health Institutions

Antibiotic resistance is at dangerous levels and increasing worldwide. The search for new antimicrobial drugs to counteract this problem is a priority for health institutions and organizations, both globally and in individual countries. Sarconesiopsis magellanica blowfly larval excretions and secretions (ES) are an important source for isolating antimicrobial peptides (AMPs). This study aims to identify and characterize a new S. magellanica AMP. RP-HPLC was used to fractionate ES, using C18 columns, and their antimicrobial activity was evaluated. The peptide sequence of the fraction collected at 43.7 min was determined by mass spectrometry (MS). Fluorescence and electronic microscopy were used to evaluate the mechanism of action. Toxicity was tested on HeLa cells and human erythrocytes; physicochemical properties were evaluated. The molecule in the ES was characterized as sarconesin II and it showed activity against Gram-negative (Escherichia coli MG1655, Pseudomonas aeruginosa ATCC 27853, P. aeruginosa PA14) and Gram-positive (Staphylococcus aureus ATCC 29213, Micrococcus luteus A270) bacteria. The lowest minimum inhibitory concentration obtained was 1.9 μM for M. luteus A270; the AMP had no toxicity in any cells tested here and its action in bacterial membrane and DNA was confirmed. Sarconesin II was documented as a conserved domain of the ATP synthase protein belonging to the Fli-1 superfamily. The data reported here indicated that peptides could be alternative therapeutic candidates for use in infections against Gram-negative and Gram-positive bacteria and eventually as a new resource of compounds for combating multidrug-resistant bacteria.

scholarly journals Effect of Seasonality on Chemical Composition and Antibacterial and Anticandida Activities of Argentine Propolis. Design of a Topical Formulation

2012 ◽  
Vol 7 (10) ◽  
pp. 1934578X1200701 ◽  
Author(s):  
María Inés Isla ◽  
Yanina Dantur ◽  
Ana Salas ◽  
Carolina Danert ◽  
Catiana Zampini ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Candida Species ◽  
Pharmaceutical Preparation ◽  
Pharmaceutical Formulations ◽  
Resistant Bacteria ◽  
Topical Formulation ◽  
Gram Positive ◽  
Gram Negative ◽  
Propolis Extract ◽  
Phenolic And Flavonoid

The effect of seasonality on Argentine propolis collected during one year on its phenolic and flavonoid content and on the growth of Gram-positive and Gram-negative antibiotic resistant bacteria and Candida species was evaluated. Extracts of propolis samples collected in the summer and spring showed higher phenolic and flavonoid contents than the samples collected in other seasons (5.86 to 6.06 mg GAE/mL and 3.77 to 4.23 mg QE/mL, respectively). The propolis collected in summer and autumn showed higher antibacterial activity (30 μg/mL) than the other samples (MIC values between 30 and 120 μg/mL). No antibacterial activity was detected against Gram-negative bacteria. Also, these extracts were able to inhibit the development of five Candida species, with MFC values of 15-120 μg/mL. Pharmaceutical formulations containing the more active propolis extract were prepared. The hydrogel of acrylic acid polymer containing summer propolis extract as an antimicrobial agent showed microbiological, physical and functional stability during storage for 180 days. The pharmaceutical preparation, as well as the propolis extracts, was active against Candida sp. and antibiotic-multi-resistant Gram-positive bacteria. These results reveal that propolis samples collected by scraping in four seasons, especially in summer in Calingasta, San Juan, Argentina, can be used to obtain tinctures and hydrogels with antibacterial and antimycotic potential for topical use.

scholarly journals Antimicrobial Resistance Patterns of Bacterial Isolates from Blood Culture among HIV/AIDS Patients at Felege Hiwot Referral Hospital, Northwest Ethiopia

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Mohabaw Jemal ◽  
Teshiwal Deress ◽  
Teshome Belachew ◽  
Yesuf Adem
Keyword(s):  
Antimicrobial Resistance ◽  
Blood Culture ◽  
Agar Plate ◽  
Blood Cultures ◽  
Resistant Bacteria ◽  
Bacterial Isolates ◽  
Aids Patients ◽  
Gram Positive ◽  
Gram Negative ◽  
Hiv Aids

Background. The emergence and spread of antimicrobial resistance in bacteria is recognized as a global public health problem. Bloodstream infection with antimicrobial-resistant bacteria in HIV/AIDS patients makes the problem more challenging. So, regular and periodic diagnosis and use of the appropriate antimicrobial susceptibility pattern determination is the only option for decreasing the prevalence and development of drug-resistant bacteria. Methods. An institution-based cross-sectional study was conducted among 384 HIV/AIDS patients. Sociodemographic data of patients were recorded using structured questionnaires. Blood cultures were collected with BACTEC aerobic blood culture bottles. A pair of samples was collected from each patient aseptically and incubated at 37°. If samples are positive for bacterial agents, they were subcultured to solid media such as blood agar plate, chocolate agar plate, and MacConkey agar plates. Identification was performed using colony characteristics and standard biochemical techniques. The antimicrobial susceptibility test was determined by the Kirby–Bauer disc diffusion method. Data entry and analysis were performed while using SPSS version 20. Descriptive statistics were performed to calculate frequencies. Results. Altogether, 384 patients were included, and 123 blood cultures were positive, so that the yield was thus 32%. About 46 (37.4%) of Gram-negative and 77 (62.6%) of Gram-positive bacterial species were identified. Among Gram-negative bacterial isolates, K. pneumoniae was the leading pathogen, 19 (41.3%), whereas S. aureus, 38 (49.4%), was predominant among Gram-positive isolates. In his study, the majority of Gram-positive isolates showed high level of resistance to penicillin, 72 (95.5%), tetracycline, 55 (71.4%), and cotrimoxazole, 45 (58.4%). About 28 (73.6%) of S. aureus isolates were also methicillin-resistant. Gram-negative bacterial isolates also showed a high resistance to ampicillin (91.3%), tetracycline (91.3%), and gentamicin (47.8%). Overall, about 78% of multidrug resistance was observed. Conclusion. Several pathogens were resistant to greater than five antimicrobial agents, so that proper management of patients with bacteremia is needed, and a careful selection of effective antibiotics should be practiced.

scholarly journals Single-dose pharmacokinetics of temocillin in plasma and soft tissues of healthy volunteers after intravenous and subcutaneous administration: a randomized crossover microdialysis trial

2020 ◽  
Vol 75 (9) ◽  
pp. 2650-2656 ◽  
Author(s):  
Peter Matzneller ◽  
Perrin Ngougni Pokem ◽  
Arnaud Capron ◽  
Edith Lackner ◽  
Beatrix Wulkersdorfer ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Protein Binding ◽  
Healthy Volunteers ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Soft Tissues ◽  
Therapeutic Option ◽  
Subcutaneous Administration ◽  
Intravenous Route ◽  
Drug Concentrations

Abstract Background The antibiotic temocillin has recently been rediscovered as a promising therapeutic option against MDR Gram-negative bacteria. However, some aspects of the pharmacokinetic (PK) profile of the drug are still to be elucidated: subcutaneous administration of temocillin might be of interest as an alternative to the intravenous route in selected patients. Similarly, information on the penetration of temocillin into human soft tissues is lacking. Objectives To investigate the feasibility and plasma PK of subcutaneous dosing as well as soft tissue PK of temocillin after intravenous administration to healthy volunteers. Methods Eight healthy volunteers received 2 g of temocillin both as intravenous and subcutaneous infusion in a randomized two-period crossover study. Concentration–time profiles of total temocillin in plasma (after both routes) and of unbound temocillin in plasma, muscle and subcutis (only after intravenous dosing) were determined up to 12 h post-dose. Results Subcutaneous dosing caused some infusion site discomfort but resulted in sustained drug concentrations over time with only slightly decreased overall exposure compared with intravenous dosing. Plasma protein binding of temocillin showed concentration-dependent behaviour and was higher than previously reported. Still, unbound drug concentrations in muscle and subcutis determined by microdialysis markedly exceeded those in plasma, suggesting good tissue penetration of temocillin. Conclusions The subcutaneous administration of temocillin is a valid and feasible alternative to intravenous dosing. With the description of plasma protein binding and soft tissue PK of temocillin in healthy volunteers, this study provides important information that adds to the ongoing characterization of the PK profile of temocillin and might serve as input for PK/PD considerations.

scholarly journals Ceftobiprole Compared With Vancomycin Plus Aztreonam in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Results of a Phase 3, Randomized, Double-blind Trial (TARGET)

2020 ◽  
Author(s):  
J Scott Overcash ◽  
Charles Kim ◽  
Richard Keech ◽  
Illia Gumenchuk ◽  
Borislav Ninov ◽  
...  
Keyword(s):  
Clinical Response ◽  
Clinical Success ◽  
Laboratory Data ◽  
European Medicines Agency ◽  
Success Rates ◽  
Phase 3 ◽  
Gram Positive ◽  
Double Blind ◽  
Gram Negative ◽  
Skin Structure

Abstract Background The development of novel broad-spectrum antibiotics, with efficacy against both gram-positive and gram-negative bacteria, has the potential to enhance treatment options for acute bacterial skin and skin structure infections (ABSSSIs). Ceftobiprole is an advanced-generation intravenous cephalosporin with broad in vitro activity against gram-positive (including methicillin-resistant Staphylococcus aureus) and gram-negative pathogens. Methods TARGET was a randomized, double-blind, active-controlled, parallel-group, multicenter, phase 3 noninferiority study that compared ceftobiprole with vancomycin plus aztreonam. The Food and Drug Administration-defined primary efficacy endpoint was early clinical response 48–72 hours after treatment initiation in the intent-to-treat (ITT) population and the European Medicines Agency-defined primary endpoint was investigator-assessed clinical success at the test-of-cure (TOC) visit. Noninferiority was defined as the lower limit of the 95% CI for the difference in success rates (ceftobiprole minus vancomycin/aztreonam) &gt;−10%. Safety was assessed through adverse event and laboratory data collection. Results In total, 679 patients were randomized to ceftobiprole (n = 335) or vancomycin/aztreonam (n = 344). Early clinical success rates were 91.3% and 88.1% in the ceftobiprole and vancomycin/aztreonam groups, respectively, and noninferiority was demonstrated (adjusted difference: 3.3%; 95% CI: −1.2, 7.8). Investigator-assessed clinical success at the TOC visit was similar between the 2 groups, and noninferiority was demonstrated for both the ITT (90.1% vs 89.0%) and clinically evaluable (97.9% vs 95.2%) populations. Both treatment groups displayed similar microbiological success and safety profiles. Conclusions TARGET demonstrated that ceftobiprole is noninferior to vancomycin/aztreonam in the treatment of ABSSSIs, in terms of early clinical response and investigator-assessed clinical success at the TOC visit. Clinical Trials Registration NCT03137173.

Sign in / Sign up

Export Citation Format

Share Document