Posts filed under ‘Infecciones en piel y tej blandos’

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

Ther Adv Infect Dis. March 2017 V.4 N.2 P.49-73.    

Das B1, Sarkar C2, Das D3, Gupta A4, Kalra A1, Sahni S1.

Author information

1 Department of Pharmacology, All India Institute of Medical Sciences (AIIMS) Rishikesh, Rishikesh, India.

2 Department of Pharmacology & Clinical Pharmacology, North Eastern Indira Gandhi Regional Institute of Health & Medical Sciences (NEIGRIHMS) Shillong, Shillong, India.

3 Department of Computer Science & Engineering, Faculty of Engineering, Manipal University Jaipur, Dehmi Kalan, Jaipur Ajmer Expressway, Rajasthan, India.

4 Department of Surgery, All India Institute of Medical Sciences (AIIMS) Rishikesh, Rishikesh, India.

Abstract

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.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467880/pdf/10.1177_2049936117690501.pdf

July 11, 2017 at 4:04 pm

Daptomicina: características farmacológicas y aporte en el tratamiento de infecciones por cocos gram positivos

Revista Chilena de Infectología Abril 2012 V.29 N.2

Daptomycin: pharmacological characteristics and its role in the treatment of gram positive infections

Rafael Araos, Patricia García, Leonardo Chanqueo y Jaime Labarca

Facultad de Medicina Clínica Alemana/Universidad del Desarrollo, Santiago, Chile. Departamento de Medicina Interna (RA).

Pontificia Universidad Católica de Chile. Departamento de Laboratorios Clínicos (PG).

Pontificia Universidad Católica de Chile. Departamento de Medicina Interna (JL).

Hospital San Juan de Dios de Santiago. Laboratorio de Microbiología (LCh).

Daptomicina es un anti-infeccioso de reciente introducción en Chile, miembro exclusivo de una nueva familia de antimicrobianos conocida como lipopéptidos cíclicos. Tiene un mecanismo de acción único que le confiere un potente efecto bactericida sobre los microorganismos susceptibles. Su especto antimicrobiano comprende cocáceas grampositivas de importancia clínica como Staphylococcus aureus y Enterococcus spp., incluyendo cepas resistentes a antimicrobianos habituales. Está aprobada para el uso clínico en infecciones de piel y tejidos blandos y bacteriemia complicada y no complicada por S. aureus, en adultos. Estudios en curso sugieren que será una alternativa útil en otras infecciones frecuentes como osteomielitis, infecciones asociadas a dispositivos ortopédicos, infecciones asociadas a biopelículas e infecciones en hospederos inmunosuprimidos, en particular en pacientes onco-hematológicos. El principal efecto adverso asociado al uso de daptomicina es la toxicidad muscular, observándose miopatía reversible, la mayoría de las veces asintomática, en aproximadamente 3% de los pacientes que utilizan el fármaco.

PDF

http://www.scielo.cl/pdf/rci/v29n2/art01.pdf

May 6, 2017 at 7:10 pm

Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections

Clinical Microbiology & Infection April 2016 V.22 Suppl.2 S27-36

Russo, E. Concia, F. Cristini, F.G. De Rosa, S. Esposito, F. Menichetti, N. Petrosillo, M. Tumbarello, M. Venditti, P. Viale, C. Viscoli, M. Bassetti

In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a β-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization.

PDF

http://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(16)30095-7/pdf

April 13, 2017 at 5:07 pm

Gram-negative prosthetic joint infections: risk factors and outcome of treatment.

Clin Infect Dis. 2009 Oct 1;49(7):1036-43

Hsieh PH, Lee MS, Hsu KY, Chang YH, Shih HN, Ueng SW.

Department of Orthopedic Surgery, Chang Gung Memorial Hospital, No. 5, Fu-Hsing St., 333 Kweishian, Taoyuan, Taiwan. hsiehph@adm.cgmh.org.tw

BACKGROUND:

Little information is available regarding the demographic characteristics and outcomes of patients with prosthetic joint infection (PJI) resulting from gram-negative (GN) organisms, compared with patients with PJI resulting from gram-positive (GP) organisms.

METHODS:

We performed a retrospective cohort analysis of all cases of PJI that were treated at our institution during the period from 2000 through 2006.

RESULTS:

GN microorganisms were involved in 53 (15%) of 346 first-time episodes of PJI, and Pseudomonas aeruginosa was the most commonly isolated pathogen (21 [40%] of the 53 episodes). Patients with GN PJI were older (median age, 68 vs. 59 years; P<.001) and developed infection earlier (median joint age, 74 vs. 109 days; P<.001) than those with GP PJI. Of the 53 episodes of GN PJI, 27 (51%) were treated with debridement, 16 (30%) with 2-stage exchange arthroplasty, and 10 (19%) with resection arthroplasty. Treating GN PJI with debridement was associated with a lower 2-year cumulative probability of success than treating GP PJI with debridement (27% vs. 47% of episodes were successfully treated; P=.002); no difference was found when a PJI was treated with 2-stage exchange or resection arthroplasty. A longer duration of symptoms before treatment with debridement was associated with treatment failure for GN PJI, compared with for GP PJI (median duration of symptoms, 11 vs. 5 days; P=.02).

CONCLUSIONS:

GN PJI represents a substantial proportion of all occurrences of PJI. Debridement alone has a high failure rate and should not be attempted when the duration of symptoms is long. Resection of the prosthesis, with or without subsequent reimplantation, as a result of GN PJI is associated with a favorable outcome rate that is comparable to that associated with PJI due to GP pathogens.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/49/7/10.1086/605593/2/49-7-1036.pdf?Expires=1491958662&Signature=IxAKWF6-WgKZaPGD72JDtgQ9EfZuwpmNFPVdR-BdK33eRJu1GUZJXyCJ7ri9ZaJ-a4T2iy6Mj1nesDu5OTWvIfp2j5XaVprK679YVFFTXrSfwHRKFO8JDumpQWlBnByaEbCEsj~ky9lFBC~~2xrpArBj31INcTvo1vLo5sICnAjdiELud-7DVPsbupIMI7ZE3HJiWJFNiP8FGIgyiCEeD2EhGUieinh7IbChHW6tjzh5v-AIB1LCiQzHPaVo8QPMbu9HH7ggA0JlS7YXjwhwJJfdjYU4pgWxeBL9p464aVUmZWotZzoN-lNM46Wyryl4U1xrPETeCZOVC1u8fGMdNQ__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

April 7, 2017 at 10:07 pm

Recurrent furunculosis – challenges and management: a review.

Clin Cosmet Investig Dermatol. 2014 Feb 18;7:59-64.

Ibler KS1, Kromann CB1.

Author information

1 Department of Dermatology, Roskilde Hospital, Copenhagen University, Denmark.

Abstract

Furunculosis is a deep infection of the hair follicle leading to abscess formation with accumulation of pus and necrotic tissue.

Furuncles appear as red, swollen, and tender nodules on hair-bearing parts of the body, and the most common infectious agent is Staphylococcus aureus, but other bacteria may also be causative.

In some countries, methicillin resistant S. aureus is the most common pathogen in skin and soft tissue infections which is problematic since treatment is difficult.

Furunculosis often tends to be recurrent and may spread among family members.

Some patients are carriers of S. aureus and eradication should be considered in recurrent cases. Solitary lesions should be incised when fluctuant, whereas patients with multiple lesions or signs of systemic disease or immunosuppression should be treated with relevant antibiotics.

The diagnostic and therapeutic approach to a patient suspected of staphylococcosis should include a thorough medical history, clinical examination, and specific microbiological and biochemical investigations.

This is particularly important in recurrent cases where culture swabs from the patient, family members, and close contacts are mandatory to identify and ultimately control the chain of infection.

Focus on personal, interpersonal, and environmental hygiene issues is crucial to reduce the risk of contamination and recurrences.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934592/pdf/ccid-7-059.pdf

March 11, 2017 at 7:53 pm

Propionibacterium acnes: Disease-Causing Agent or Common Contaminant? Detection in Diverse Patient Samples by Next-Generation Sequencing

Journal of Clinical Microbiology April 2016 V.54 N.4 P.980-987

Sarah Mollerup, Jens Friis-Nielsen, Lasse Vinner, Thomas Arn Hansen, Stine Raith Richter, Helena Fridholm, Jose Alejandro Romero Herrera, Ole Lund, Søren Brunak, Jose M. G. Izarzugaza, Tobias Mourier, Lars Peter Nielsen, and Anders Johannes Hansen

aCentre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark

bCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark

cDisease Systems Biology Program, Panum Institute, University of Copenhagen, Copenhagen, Denmark

dDepartment of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen S, and Aalborg University, Health Sciences, Aalborg, Denmark

Propionibacterium acnes is the most abundant bacterium on human skin, particularly in sebaceous areas. P. acnes is suggested to be an opportunistic pathogen involved in the development of diverse medical conditions but is also a proven contaminant of human clinical samples and surgical wounds.

Its significance as a pathogen is consequently a matter of debate. In the present study, we investigated the presence of P. acnes DNA in 250 next-generation sequencing data sets generated from 180 samples of 20 different sample types, mostly of cancerous origin.

The samples were subjected to either microbial enrichment, involving nuclease treatment to reduce the amount of host nucleic acids, or shotgun sequencing. We detected high proportions of P. acnes DNA in enriched samples, particularly skin tissue-derived and other tissue samples, with the levels being higher in enriched samples than in shotgun-sequenced samples.

P. acnes reads were detected in most samples analyzed, though the proportions in most shotgun-sequenced samples were low. Our results show that P. acnes can be detected in practically all sample types when molecular methods, such as next-generation sequencing, are employed.

The possibility of contamination from the patient or other sources, including laboratory reagents or environment, should therefore always be considered carefully when P. acnes is detected in clinical samples.

We advocate that detection of P. acnes always be accompanied by experiments validating the association between this bacterium and any clinical condition.

PDF

http://jcm.asm.org/content/54/4/980.full.pdf

March 9, 2017 at 3:35 pm

Primary cellulitis and cutaneous abscess caused by Yersinia enterocolitica in an immunocompetent host: A case report and literature review.

Medicine (Baltimore). 2016 Jun;95(26):e3988.

Kato H1, Sasaki S, Sekiya N.

Author information

1Department of Clinical Laboratory, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.

Abstract

Primary extraintestinal complications caused by Yersinia enterocolitica are extremely rare, especially in the form of skin and soft-tissue manifestations, and little is known about their clinical characteristics and treatments.

We presented our case and reviewed past cases of primary skin and soft-tissue infections caused by Y enterocolitica.

We report a case of primary cellulitis and cutaneous abscess caused by Y enterocolitica in an immunocompetent 70-year-old woman with keratodermia tylodes palmaris progressiva.

She presented to an outpatient clinic with redness, swelling, and pain of the left ring finger and left upper arm without fever or gastrointestinal symptoms 3 days before admission.

One day later, ulceration of the skin with exposed bone of the proximal interphalangeal joint of the left ring finger developed, and cefditoren pivoxil was described.

However, she was admitted to our hospital due to deterioration of symptoms involving the left finger and upper arm.

Cefazolin was initiated on admission, then changed to sulbactam/ampicillin and vancomycin with debridement of the left ring finger and drainage of the left upper arm abscess.

Wound culture grew Y enterocolitica serotype O:8 and methicillin-sensitive Staphylococcus aureus.

Blood cultures were negative and osteomyelitis was ruled out. Vancomycin was switched to ciprofloxacin, then skin and soft-tissue manifestations showed clear improvement within a few days.

The patient received 14 days of ciprofloxacin and oral amoxicillin/clavulanate and has since shown no recurrence.

We reviewed 12 cases of primary skin and soft-tissue infections caused by Y enterocolitica from the literature. In several past cases, portal entry involved failure of the skin barrier on distal body parts. Thereafter, infection might have spread to the regional lymph nodes from the ruptured skin.

Y enterocolitica is typically resistant to aminopenicillins and narrow-spectrum cephalosporins. In most cases, these inefficient antibiotic agents were initially prescribed, but patient conditions rapidly improved after implementing appropriate therapy and drainage. In addition, primary skin and soft-tissue infections occurred even in patients lacking risk factors.

Physicians should consider the rare differential diagnosis of Y enterocolitica infection when seeing patients with deteriorating skin lesions under standard treatment, even if the patient is immunocompetent.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937915/pdf/medi-95-e3988.pdf

March 2, 2017 at 3:28 pm

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