scholarly journals A pilot study of high-dose short duration daptomycin for the treatment of patients with complicated skin and skin structure infections caused by gram-positive bacteria

2008 ◽  
Vol 62 (9) ◽  
pp. 1455-1464 ◽  
Author(s):  
D. E. Katz ◽  
K. C. Lindfield ◽  
J. N. Steenbergen ◽  
D. P. Benziger ◽  
K. J. Blackerby ◽  
...  
Keyword(s):  
Pilot Study ◽  
Short Duration ◽  
High Dose ◽  
Gram Positive ◽  
Skin Structure ◽  
Gram Positive Bacteria ◽  
Complicated Skin

scholarly journals Results of a Double-Blind, Randomized Trial of Ceftobiprole Treatment of Complicated Skin and Skin Structure Infections Caused by Gram-Positive Bacteria

2007 ◽  
Vol 52 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Gary J. Noel ◽  
Richard S. Strauss ◽  
Karen Amsler ◽  
Markus Heep ◽  
Rienk Pypstra ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Study Drug ◽  
Primary Objective ◽  
Gram Positive ◽  
Taste Disturbance ◽  
Double Blind ◽  
Skin Structure ◽  
Gram Positive Bacteria ◽  
Complicated Skin ◽  
Cure Rates

ABSTRACT Ceftobiprole is the first broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) to be assessed in late-stage clinical trials. As a pivotal step in the clinical development of ceftobiprole, a multicenter, global, randomized, double-blind trial was conducted to compare the efficacy of ceftobiprole to that of vancomycin in patients with complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria. The primary objective was to assess noninferiority on the basis of the cure rates 7 to 14 days after the completion of therapy in patients administered ceftobiprole 500 mg every 12 h or vancomycin 1 g every 12 h. Of 784 patients randomized, 282 receiving ceftobiprole and 277 receiving vancomycin were clinically evaluable. Of these patients, 93.3% treated with ceftobiprole and 93.5% treated with vancomycin were cured (95% confidence interval of difference, −4.4%, 3.9%). The cure rates for patients with MRSA infections were 91.8% (56/61) with ceftobiprole treatment and 90.0% (54/60) with vancomycin treatment (95% confidence interval of difference, −8.4%, 12.1%). At least one adverse event (AE) was reported by 52% of the ceftobiprole-treated patients and 51% of the vancomycin-treated patients. The most common AEs reported by the ceftobiprole-treated patients were nausea (14%) and taste disturbance (8%). Discontinuation of the study drug because of treatment-emergent AEs occurred in 4% (n = 17) of the ceftobiprole-treated patients and 6% (n = 22) of the vancomycin-treated patients. The results of this trial support the use of ceftobiprole as an effective and well-tolerated treatment option for patients with cSSSIs caused by a spectrum of gram-positive bacteria.

scholarly journals Telavancin: a novel semisynthetic lipoglycopeptide agent to counter the challenge of resistant Gram-positive pathogens

2017 ◽  
Vol 4 (2) ◽  
pp. 49-73 ◽  
Author(s):  
Biswadeep Das ◽  
Chayna Sarkar ◽  
Debasmita Das ◽  
Amit Gupta ◽  
Arnav Kalra ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Phase Iii ◽  
Gram Positive ◽  
Safety And Efficacy ◽  
Skin Structure ◽  
Gram Positive Bacteria ◽  
Antibiotic Effect ◽  
Complicated Skin

Telavancin (TD-6424), a semisynthetic lipoglycopeptide vancomycin-derivative, is a novel antimicrobial agent developed by Theravance for overcoming resistant Gram-positive bacterial infections, specifically methicillin-resistant Staphylococcus aureus (MRSA). The US Food and Drug Administration (USFDA) had approved telavancin in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria, including MRSA ( S. aureus, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus anginosus group, or Enterococcus faecalis). Telavancin has two proposed mechanisms of action. In vitro, telavancin has a rapid, concentration-dependent bactericidal effect, due to disruption of cell membrane integrity. Telavancin has demonstrable in vitro activity against aerobic and anaerobic Gram-positive bacteria. Telavancin and vancomycin have similar spectra of activity. Gram-negative bacteria are usually non-susceptible to telavancin. Telavancin has been successfully tested in various animal models of bacteremia, endocarditis, meningitis, and pneumonia. Phase II Telavancin versus Standard Therapy for Treatment of Complicated Skin and Soft-Tissue Infections due to Gram-Positive Bacteria (FAST 1 and FAST 2) and phase III [Assessment of Telavancin in Complicated Skin and Skin Structure Infections 1 (ATLAS 1 and ATLAS 2)] clinical trials have been conducted for evaluating telavancin’s efficacy and safety in cSSSIs. Phase III clinical trials have been carried out for evaluating telavancin’s safety and efficacy in nosocomial pneumonia [Assessment of Telavancin for Treatment of Hospital acquired Pneumonia 1 and 2 (ATTAIN 1 and ATTAIN 2)]. A phase II randomized, double-blind, clinical trial has been carried out for evaluating telavancin’s safety and efficacy in uncomplicated S. aureus bacteremia [Telavancin for Treatment of Uncomplicated S. aureus Bacteremia (ASSURE)]. Pacemaker lead–related infective endocarditis due to a vancomycin intermediate S. aureus (VISA) strain (non-daptomycin susceptible) was successfully treated with parenteral telavancin for 8 weeks. Telavancin extensively binds to serum albumin (~93%) and has a relatively small volume of distribution. Telavancin is not biotransformed by any cytochrome P450 microsomal enzymes and excreted mainly in the urine. Though well-tolerated, worrisome adverse effects, including renal dysfunction and QTc prolongation are of potential concern. Given its extensive binding to plasma proteins, long half-life, and a long post-antibiotic effect, it represents a promising addition to the therapeutic armamentarium in combating infections caused by resistant Gram-positive pathogens, namely, MRSA.

scholarly journals A Pilot Study of Bacteriological Population Changes through Potable Water Treatment and Distribution

2000 ◽  
Vol 66 (1) ◽  
pp. 268-276 ◽  
Author(s):  
Cheryl D. Norton ◽  
Mark W. LeChevallier
Keyword(s):  
Pilot Study ◽  
Biologically Active ◽  
Plate Count ◽  
Identification System ◽  
Population Changes ◽  
Gram Positive ◽  
Pipe Surface ◽  
Treated Water ◽  
Gram Positive Bacteria ◽  
Biofilm Development

ABSTRACT This pilot study compares the compositions of bacterial biofilms in pipe networks supplied with water containing either high levels of biodegradable organic matter (BOM) or low levels of BOM (conventionally or biologically treated, respectively). The Microbial Identification System for fatty acid analysis was utilized in this study to identify a large number of organisms (>1,400) to determine population changes in both conventionally and biologically treated water and biofilms. Data generated during this study indicated that suspended bacteria have little impact on biofilms, and despite treatment (conventional or biological), suspended microbial populations were similar following disinfection. Prechlorination with free chlorine resulted not only in reduced plate count values but also in a dramatic shift in the composition of the bacterial population to predominately gram-positive bacteria. Chlorination of biologically treated water produced the same shifts toward gram-positive bacteria. Removal of assimilable organic carbon by the biologically active filters slowed the rate of biofilm accumulation, but biofilm levels were similar to those found in conventionally treated water within several weeks. Iron pipes stimulated the rate of biofilm development, and bacterial levels on disinfected iron pipes exceeded those for chlorinated polyvinyl chloride pipes. The study showed that the iron pipe surface dramatically influenced the composition, activity, and disinfection resistance of biofilm bacteria.

Daptomycin (DAP) Use in Patients with Hematologic (HEM) Cancer History; Post-Marketing Experience in a Registry.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3132-3132
Author(s):  
Gorgun Akpek ◽  
Graeme Forrest ◽  
Kenneth C. Lamp ◽  
Brian J. Donovan ◽  
Lawrence V. Friedrich
Keyword(s):  
Clinical Response ◽  
Hospital Setting ◽  
Severe Illness ◽  
Case Report Form ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Standard Case ◽  
Skin Structure ◽  
Complicated Skin ◽  
The Mean

Abstract Background: DAP is a novel lipopeptide antibiotic, approved for complicated skin and skin structure infections, with potent in vitro activity against many resistant Gram-positive organisms. Registration studies often limit or exclude patients with severe illness. Antibiotic resistant Gram-positive pathogens are frequently encountered in compromised patient populations; however, minimal information is available pre-approval in these patients. Methods: Cubicin® Outcomes Registry and Experience (CORE) is a Phase IV retrospective observational chart review (45 institutions) to quantitate characteristics and clinical outcomes of patients (pts) receiving DAP. A standard case report form including demographic, disease state, clinical, and microbiologic data was completed by each investigator. Cure, failure, and improvement were assessed using standard definitions. Nonevaluable pts had insufficient data available to determine clinical outcome. Of the 1160 pts in CORE, 56 were reported with a history of HEM cancer. Eighteen (32%) were nonevaluable; 6 of those expired. This report describes the 38 pts with an assigned outcome. Results: Fifty-five percent of pts were female, 63% were 31 to 65 years of age, and 76% of infections developed in a hospital setting. Common comorbidities included cardiovascular disease (24%), immunosuppression (18%), and transplant (11%). The most common infections were; bacteremia catheter-related (53%), skin and skin structure (34%), and bacteremia noncatheter-related (18%). Seventy-one percent (27/38) of pts were culture positive before DAP with the most common pathogens being Enterococcus sp. (52%, of which 71% were VRE), coagulase-negative staphylococci (41%), and S. aureus (19%, of which 80% were MRSA). A high percentage of pts (92%) received antibiotics (abx) prior to DAP. The most frequent initial dosing regimens were 4mg/kg QD (50%), and 6mg/kg QD (29%). The mean duration of DAP therapy was 13.6 days (range 2–44). Dose (P=0.3) and duration (P=0.58) did not vary by primary pathogen. Twenty-nine (76%) pts received concomitant abx therapy, most commonly with fluoroquinolones (31%), metronidazole (28%) or cephalosporins (24%). The mean time to clinical response was 2.4 days (n=28) and unaffected by primary pathogen (P=0.43) or the influence of concomitant abx therapy (P=0.55). All pts were reported as cured (66%) or improved (34%). Conclusion: The data from the CORE registry demonstrates that DAP shows early clinical response and clinical cure for HEM patients where catheter associated infections and VRE are prevalent. These data provide preliminary data on the use of DAP in this compromised patient population. This information should lead to further prospective studies in cancer patients with DAP.

scholarly journals Telavancin versus Standard Therapy for Treatment of Complicated Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: FAST 2 Study

2006 ◽  
Vol 50 (3) ◽  
pp. 862-867 ◽  
Author(s):  
Martin E. Stryjewski ◽  
Vivian H. Chu ◽  
William D. O'Riordan ◽  
Brian L. Warren ◽  
Lala M. Dunbar ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Clinical Success ◽  
Therapy Group ◽  
Success Rates ◽  
Standard Therapy Group ◽  
Gram Positive ◽  
Double Blind ◽  
Skin Structure ◽  
Complicated Skin ◽  
Cure Rates

ABSTRACT Telavancin is a bactericidal lipoglycopeptide with a multifunctional mechanism of action. We conducted a randomized, double blind, active-control phase II trial. Patients ≥18 years of age with complicated skin and skin structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin at 10 mg/kg intravenously every 24 h (q24h) or standard therapy (antistaphylococcal penicillin at 2 g q6h or vancomycin at 1 g q12h). A total of 195 patients were randomized and received at least one dose of study medication. Clinical success rates were similar in all analysis populations at test of cure. In microbiologically evaluable patients with Staphylococcus aureus at baseline (n = 91), 96% of the telavancin group and 90% of the standard-therapy group were cured. Among patients with methicillin-resistant S. aureus (MRSA) at baseline (n = 45), clinical cure rates were also 96% for telavancin and 90% for standard therapy. Microbiologic eradication in patients with S. aureus infection was better with telavancin compared to standard therapy (92% versus 78%, P = 0.07) and significantly better in patients with MRSA (92% versus 68%; P = 0.04). Therapy was discontinued for an adverse event (AE) in 6% and 3% of the patients receiving telavancin and standard therapy, respectively. Except for two cases of rash in the telavancin group, these AEs were similar in type and severity in the two groups. The overall incidences and severities of AEs and laboratory abnormalities were similar between the two groups. These data support the ongoing studies assessing the efficacy and safety of telavancin in the treatment of serious gram-positive infections, particularly involving MRSA.

scholarly journals Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1962
Author(s):  
Ana Gomes ◽  
Lucinda J. Bessa ◽  
Iva Fernandes ◽  
Ricardo Ferraz ◽  
Cláudia Monteiro ◽  
...  
Keyword(s):  
Antibiofilm Activity ◽  
Gram Negative Bacteria ◽  
Candida Spp ◽  
Gram Positive ◽  
Gram Negative ◽  
Wound Fluid ◽  
Skin Structure ◽  
Chimeric Peptide ◽  
Complicated Skin

Efficient antibiotics are being exhausted, which compromises the treatment of infections, including complicated skin and skin structure infections (cSSTI) often associated with multidrug resistant (MDR) bacteria, methicillin-resistant S. aureus (MRSA) being the most prevalent. Antimicrobial peptides (AMP) are being increasingly regarded as the new hope for the post-antibiotic era. Thus, future management of cSSTI may include use of peptides that, on the one hand, behave as AMP and, on the other, are able to promote fast and correct skin rebuilding. As such, we combined the well-known cosmeceutical pentapeptide-4 (PP4), devoid of antimicrobial action but possessing collagenesis-boosting properties, with the AMP 3.1, to afford the chimeric peptide PP4-3.1. We further produced its N-methyl imidazole derivative, MeIm-PP4-3.1. Both peptide-based constructs were evaluated in vitro against Gram-negative bacteria, Gram-positive bacteria, and Candida spp. fungi. Additionally, the antibiofilm activity, the toxicity to human keratinocytes, and the activity against S. aureus in simulated wound fluid (SWF) were assessed. The chimeric peptide PP4-3.1 stood out for its potent activity against Gram-positive and Gram-negative bacteria, including against MDR clinical isolates (0.8 ≤ MIC ≤ 5.7 µM), both in planktonic form and in biofilm matrix. The peptide was also active against three clinically relevant species of Candida fungi, with an overall performance superior to that of fluconazole. Altogether, data reveal that PP4-3.1 is as a promising lead for the future development of new topical treatments for severe skin infections.

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