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1.
Clin Infect Dis ; 73(11): e4568-e4577, 2021 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-32521007

RESUMEN

BACKGROUND: A household approach to decolonization decreases skin and soft tissue infection (SSTI) incidence, though this is burdensome and costly. As prior SSTI increases risk for SSTI, we hypothesized that the effectiveness of decolonization measures to prevent SSTI when targeted to household members with prior year SSTI would be noninferior to decolonizing all household members. METHODS: Upon completion of our 12-month observational Household Observation of Methicillin-resistant Staphylococcus aureus in the Environment (HOME) study, 102 households were enrolled in HOME2, a 12-month, randomized noninferiority trial. Pediatric index patients with community-associated methicillin-resistant Staphylococcus aureus (MRSA) SSTI, their household contacts, and pets were enrolled. Households were randomized 1:1 to the personalized (decolonization performed only by household members who experienced SSTI during the HOME study) or household (decolonization performed by all household members) approaches. The 5-day regimen included hygiene education, twice-daily intranasal mupirocin, and daily bleach-water baths. At 5 follow-up visits in participants' homes, swabs to detect S. aureus were collected from participants, environmental surfaces, and pets; incident SSTIs were ascertained. RESULTS: Noninferiority of the personalized approach was established for the primary outcome 3-month cumulative SSTI: 23 of 212 (10.8%) participants reported SSTI in household approach households, while 23 of 236 (9.7%) participants reported SSTI in personalized approach households (difference in proportions, -1.1% [95% confidence interval, -6.7% to 4.5%]). In multivariable analyses, prior year SSTI and baseline MRSA colonization were associated with cumulative SSTI. CONCLUSIONS: The personalized approach was noninferior to the household approach in preventing SSTI. Future studies should interrogate longer durations of decolonization and/or decontamination of the household environment to reduce household MRSA burden. CLINICAL TRIALS REGISTRATION: NCT01814371.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones de los Tejidos Blandos , Infecciones Estafilocócicas , Infecciones Cutáneas Estafilocócicas , Antibacterianos/uso terapéutico , Niño , Humanos , Mupirocina/uso terapéutico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/prevención & control , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/prevención & control , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/prevención & control , Staphylococcus aureus
2.
Immunology ; 154(3): 510-521, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29377107

RESUMEN

Ultraviolet radiation (UVr) promotes several well-known molecular changes, which may ultimately impact on health. Some of these effects are detrimental, like inflammation, carcinogenesis and immunosuppression. On the other hand, UVr also promotes vitamin D synthesis and other beneficial effects. We recently demonstrated that exposure to very low doses of UVr on four consecutive days [repetitive low UVd (rlUVd)] does not promote an inflammatory state, nor the recruitment of neutrophils or lymphocytes, as the exposure to a single high UV dose (shUVd) does. Moreover, rlUVd reinforce the epithelium by increasing antimicrobial peptides transcription and epidermal thickness. The aim of this study was to evaluate the adaptive immune response after shUVd and rlUVd, determining T-cell and B-cell responses. Finally, we challenged animals exposed to both irradiation procedures with Staphylococcus aureus to study the overall effects of both innate and adaptive immunity during a cutaneous infection. We observed, as expected, a marked suppression of T-cell and B-cell responses after exposure to an shUVd but a novel and significant increase in both specific responses after exposure to rlUVd. However, the control of the cutaneous S. aureus infection was defective in this last group, suggesting that responses against pathogens cannot be ruled out from isolated stimuli.


Asunto(s)
Inmunidad Adaptativa/efectos de la radiación , Exposición a la Radiación , Rayos Ultravioleta , Animales , Formación de Anticuerpos/inmunología , Formación de Anticuerpos/efectos de la radiación , Linfocitos B/inmunología , Linfocitos B/metabolismo , Linfocitos B/efectos de la radiación , Biomarcadores , Citocinas/metabolismo , Dermatitis/inmunología , Dermatitis/metabolismo , Dermatitis/microbiología , Dermatitis/prevención & control , Modelos Animales de Enfermedad , Inmunización , Inmunofenotipificación , Masculino , Ratones , Dosis de Radiación , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/prevención & control , Staphylococcus aureus/inmunología , Staphylococcus aureus/efectos de la radiación , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/efectos de la radiación , Toxoide Tetánico/administración & dosificación , Toxoide Tetánico/inmunología
3.
J Pediatr ; 199: 158-165, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29759849

RESUMEN

OBJECTIVES: To assess the psychosocial effects of a methicillin-resistant Staphylococcus aureus (MRSA) diagnosis on the households of children with MRSA skin and soft tissue infection (SSTI). STUDY DESIGN: We constructed and administered an interview to the primary caregiver within the home of a child with a history of MRSA SSTI. RESULTS: Seventy-six households were enrolled. Survey responses were analyzed and grouped into 4 themes: health behavior changes, disclosure, social interactions, and knowledge/awareness. The most common theme was disclosure; 91% of participants reported sharing their child's MRSA diagnosis with someone outside of the household. Forty-two percent of respondents reported a change in the manner in which household contacts interacted as a result of the index patient's MRSA diagnosis, including isolating the index patient from other children in the household. Many households reported adopting enhanced personal hygiene behaviors and environmental cleaning routines. Thirty-eight percent of participating households reported altering how they interact with people outside of their home, largely to avoid spreading MRSA to vulnerable individuals. In addition, many participants perceived that others regarded them with caution, especially at daycare, whereas other affected households were excluded from family gatherings. CONCLUSION: Primary caregivers of children with MRSA SSTI reported changing their health behaviors, altering their interactions with people outside of their home, and feeling isolated by others in response to their child's MRSA diagnosis. The findings of our study highlight a need for community interventions and education to prevent the negative psychosocial repercussions associated with MRSA.


Asunto(s)
Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Relaciones Interpersonales , Staphylococcus aureus Resistente a Meticilina , Conducta Social , Infecciones de los Tejidos Blandos/psicología , Infecciones Cutáneas Estafilocócicas/psicología , Adolescente , Adulto , Cuidadores/psicología , Niño , Preescolar , Femenino , Encuestas Epidemiológicas , Humanos , Lactante , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Infecciones de los Tejidos Blandos/prevención & control , Infecciones de los Tejidos Blandos/transmisión , Infecciones Cutáneas Estafilocócicas/prevención & control , Infecciones Cutáneas Estafilocócicas/transmisión
4.
Vet Dermatol ; 29(1): 37-e18, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28921723

RESUMEN

BACKGROUND: Acute radiation-induced dermatitis (ARID) is a common sequela of radiation therapy and carries the risk of secondary bacterial skin infection. No standard of care exists for managing canine ARID and evidence-based guidelines are lacking; however, prophylactic use of antibiotics is common. HYPOTHESIS/OBJECTIVES: To evaluate the impact of prophylactic cefalexin on the prevalence and severity of bacterial infection in canine ARID. ANIMALS: Seventeen dogs treated with definitive-intent radiotherapy. METHODS: All dogs were treated with definitive-intent radiation therapy (48-57.5 gray) targeted to the skin surface. Dogs were randomized to receive either prophylactic cefalexin (22 mg/kg twice daily) beginning halfway through the prescribed radiotherapy course (cohort A) or to serve as controls (cohort B). Aerobic skin cultures and surface cytological evaluation were performed at first onset of moist desquamation and one week following completion of radiation therapy. Skin toxicity grading and owner quality of life (QoL) questionnaires were performed weekly. The rate of infection, multidrug resistance status, toxicity severity and QoL between cohorts were compared. RESULTS: Staphylococcus schleiferi and S. pseudintermedius were the most frequent bacterial agents isolated in both cohorts. There was no significant difference in prevalence of bacterial infection or overall QoL between cohorts at either time point; however, multidrug-resistant infections were significantly increased in cohort A versus cohort B. Clinician- and client-perceived severity of toxicity was significantly greater and median duration of moist desquamation was significantly longer in cohort A than cohort B. CONCLUSIONS AND CLINICAL IMPORTANCE: Prophylactic use of cefalexin for management of canine ARID is not recommended.


Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica/veterinaria , Cefalexina/uso terapéutico , Enfermedades de los Perros/prevención & control , Enfermedades de los Perros/radioterapia , Radiodermatitis/veterinaria , Enfermedades Cutáneas Bacterianas/veterinaria , Animales , Profilaxis Antibiótica/métodos , Perros , Femenino , Masculino , Estudios Prospectivos , Radiodermatitis/complicaciones , Radioterapia/efectos adversos , Radioterapia/veterinaria , Enfermedades Cutáneas Bacterianas/etiología , Enfermedades Cutáneas Bacterianas/prevención & control , Infecciones Cutáneas Estafilocócicas/etiología , Infecciones Cutáneas Estafilocócicas/prevención & control , Infecciones Cutáneas Estafilocócicas/veterinaria , Staphylococcus/efectos de los fármacos , Staphylococcus/aislamiento & purificación
5.
Int J Mol Sci ; 19(5)2018 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-29693635

RESUMEN

Unlike USA300, a strain of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), commensal Staphylococcus aureus (S. aureus) bacteria isolated from human skin demonstrated the ability to mediate the glycerol fermentation to produce short-chain fatty acids (SCFAs). Quantitative proteomic analysis of enzymes involved in glycerol fermentation demonstrated that the expression levels of six enzymes, including glycerol-3-phosphate dehydrogenase (GPDH) and phosphoglycerate mutase (PGM), in commensal S. aureus are more than three-fold higher than those in USA300. Western blotting validated the low expression levels of GPDH in USA300, MRSA252 (a strain of hospital-acquired MRSA), and invasive methicillin-susceptible S. aureus (MSSA). In the presence of glycerol, commensal S. aureus effectively suppressed the growth of USA300 in vitro and in vivo. Active immunization of mice with lysates or recombinant α-hemolysin of commensal S. aureus or passive immunization with neutralizing sera provided immune protection against the skin infection of USA300. Our data illustrate for the first time that commensal S. aureus elicits both innate and adaptive immunity via glycerol fermentation and systemic antibody production, respectively, to fight off the skin infection of pathogenic MRSA.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina/inmunología , Microbiota/inmunología , Infecciones Cutáneas Estafilocócicas/inmunología , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Células Cultivadas , Femenino , Glicerol/metabolismo , Glicerolfosfato Deshidrogenasa/genética , Glicerolfosfato Deshidrogenasa/metabolismo , Inmunización Pasiva , Ratones , Ratones Endogámicos ICR , Fosfoglicerato Mutasa/genética , Fosfoglicerato Mutasa/metabolismo , Piel/inmunología , Piel/microbiología , Infecciones Cutáneas Estafilocócicas/prevención & control
6.
Curr Opin Infect Dis ; 30(2): 180-191, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28118218

RESUMEN

PURPOSE OF REVIEW: Skin and soft tissue infections (SSTIs) are prevalent in the obese population, with rising trend expected. Although numerous antibiotics are available for the prevention and treatment of SSTIs, their characterization in obese patients is not a regulatory mandate. Consequently, information that carries importance for optimizing the dosing regimen in the obese population may not be readily available. This review focuses on the most recent pharmacokinetic and pharmacodynamic data on this topic with attention to cefazolin for surgical prophylaxis as well as antibiotics that are active against methicillin-resistant Staphylococcus aureus (MRSA). Moreover, the implications for optimizing SSTIs prevention and treatment in the obese population will also be discussed. RECENT FINDINGS: On the basis of pharmacokinetic/pharmacodynamic considerations, most studies found a perioperative prophylactic cefazolin regimen of 2 g to be reasonable in the case of obese patients undergoing cesarean delivery or bariatric surgery. There is general paucity of data regarding the pharmacokinetic/pharmacodynamic characteristics of antimicrobials active against MRSA in obese patients, especially for the target tissue. Therapeutic drug monitoring has been correlated with pharmacokinetic/pharmacodynamic optimization for vancomycin and teicoplanin, and should be used in these cases. There is more supportive evidence for the use of oxazolidinones (linezolid and tedizolid), daptomycin and lipoglycopeptides (telavancin, dalbavancin and oritavancin) in the management of SSTIs in this population. SUMMARY: The pharmacokinetic/pharmacodynamic approach, which can be used as a basis or supplement to clinical trials, provides valuable data and decision-making tools for optimizing regimens used for both prevention and treatment of SSTIs in the obese population. Important pharmacokinetic/pharmacodynamic characteristics of antibiotics, such as the penetration into the subcutaneous tissue and the probability of reaching the pharmacodynamic, target dictate efficacy, and thus should be taken into account and further investigated.


Asunto(s)
Antibacterianos/uso terapéutico , Obesidad/complicaciones , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/prevención & control , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/prevención & control , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Humanos , Staphylococcus aureus Resistente a Meticilina , Obesidad/metabolismo , Obesidad/cirugía , Enfermedades Cutáneas Bacterianas/metabolismo , Infecciones de los Tejidos Blandos/metabolismo , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/prevención & control
7.
J Immunol ; 194(12): 5915-25, 2015 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-25980008

RESUMEN

Infections caused by Streptococcus pyogenes (group A Streptococcus [GAS]) are highly prevalent in the tropics, in developing countries, and in the Indigenous populations of developed countries. These infections and their sequelae are responsible for almost 500,000 lives lost prematurely each year. A synthetic peptide vaccine (J8-DT) from the conserved region of the M protein has shown efficacy against disease that follows i.p. inoculation of bacteria. By developing a murine model for infection that closely mimics human skin infection, we show that the vaccine can protect against pyoderma and subsequent bacteremia caused by multiple GAS strains, including strains endemic in Aboriginal communities in the Northern Territory of Australia. However, the vaccine was ineffective against a hypervirulent cluster of virulence responder/sensor mutant GAS strain; this correlated with the strain's ability to degrade CXC chemokines, thereby preventing neutrophil chemotaxis. By combining J8-DT with an inactive form of the streptococcal CXC protease, S. pyogenes cell envelope proteinase, we developed a combination vaccine that is highly effective in blocking CXC chemokine degradation and permits opsonic Abs to kill the bacteria. Mice receiving the combination vaccine were strongly protected against pyoderma and bacteremia, as evidenced by a 100-1000-fold reduction in bacterial burden following challenge. To our knowledge, a vaccine requiring Abs to target two independent virulence factors of an organism is unique.


Asunto(s)
Bacteriemia , Piodermia/prevención & control , Vacunas Estreptocócicas/inmunología , Streptococcus/inmunología , Vacunas Sintéticas/inmunología , Animales , Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/química , Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/química , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas Portadoras/química , Proteínas Portadoras/inmunología , Modelos Animales de Enfermedad , Femenino , Inmunidad Innata , Memoria Inmunológica , Macrófagos/inmunología , Ratones , Neutrófilos/inmunología , Péptidos/inmunología , Piodermia/patología , Proteínas Recombinantes/inmunología , Infecciones Cutáneas Estafilocócicas/patología , Infecciones Cutáneas Estafilocócicas/prevención & control , Vacunas Estreptocócicas/genética , Vacunas Sintéticas/genética
9.
J Allergy Clin Immunol ; 138(4): 1098-1107.e3, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27543072

RESUMEN

BACKGROUND: Staphylococcus aureus is an opportunistic pathogen that colonizes the skin of patients with atopic dermatitis (AD) and aggravates their disease. Neutrophils and the cytokines IL-17A and IL-17F, which drive the expression of the neutrophil-attracting chemokines, are important for the clearance of S aureus infection. The cytokine IL-22 is often coproduced by IL-17-secreting cells. The levels of IL-22 are elevated in AD skin lesions. OBJECTIVE: We sought to determine the role of IL-22 in the clearance of S aureus infection of mouse skin subjected to tape stripping, a surrogate for scratching, a cardinal feature of AD. METHODS: S aureus was applied to the tape-stripped skin of wild-type and Il22-/- mice. Bacterial burden was evaluated by enumerating colony-forming units. Quantitative PCR and ELISA were performed to quantify Il22 mRNA and IL-22 protein in mouse and human skin. Flow cytometry was used to enumerate neutrophils in the skin. RESULTS: Scratching the skin of healthy adults and tape stripping of mouse skin induced local expression of Il22 mRNA and IL-22 protein. Induction of Il22 expression by tape stripping was dependent on IL-23 and γδ T cells. Clearance of S aureus from tape-stripped skin was significantly impaired in Il22-/- mice. Neutrophil infiltration and upregulation of expression of genes encoding the antimicrobial peptides antigen-6/urokinase-type plasminogen activator receptor related protein-1 and ß-DEFENSIN 14 and the chemokine (C-X-C motif) ligand following tape stripping were significantly impaired in Il22-/- mice. CONCLUSIONS: These findings show that IL-22 is important for limiting the growth of S aureus on mechanically injured skin and caution that IL-23 and IL-22 blockade in patients with AD may enhance susceptibility to staphylococcal skin infection.


Asunto(s)
Interleucinas/farmacología , Infecciones Cutáneas Estafilocócicas/prevención & control , Staphylococcus aureus/efectos de los fármacos , Linfocitos T/inmunología , Animales , Dermatitis Atópica/inmunología , Citometría de Flujo , Humanos , Interleucinas/aislamiento & purificación , Ratones , Piel/lesiones , Piel/microbiología , Linfocitos T/química , Interleucina-22
10.
Antimicrob Agents Chemother ; 60(2): 862-72, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26596945

RESUMEN

In the midst of the current antimicrobial pipeline void, alternative approaches are needed to reduce the incidence of infection and decrease reliance on last-resort antibiotics for the therapeutic intervention of bacterial pathogens. In that regard, mupirocin ointment-based decolonization and wound maintenance practices have proven effective in reducing Staphylococcus aureus transmission and mitigating invasive disease. However, the emergence of mupirocin-resistant strains has compromised the agent's efficacy, necessitating new strategies for the prevention of staphylococcal infections. Herein, we set out to improve the performance of mupirocin-based ointments. A screen of a Food and Drug Administration (FDA)-approved drug library revealed that the antibiotic neomycin sulfate potentiates the antimicrobial activity of mupirocin, whereas other library antibiotics did not. Preliminary mechanism of action studies indicate that neomycin's potentiating activity may be mediated by inhibition of the organism's RNase P function, an enzyme that is believed to participate in the tRNA processing pathway immediately upstream of the primary target of mupirocin. The improved antimicrobial activity of neomycin and mupirocin was maintained in ointment formulations and reduced S. aureus bacterial burden in murine models of nasal colonization and wound site infections. Combination therapy improved upon the effects of either agent alone and was effective in the treatment of contemporary methicillin-susceptible, methicillin-resistant, and high-level mupirocin-resistant S. aureus strains. From these perspectives, combination mupirocin-and-neomycin ointments appear to be superior to that of mupirocin alone and warrant further development.


Asunto(s)
Antibacterianos/uso terapéutico , Sinergismo Farmacológico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Mupirocina/uso terapéutico , Neomicina/uso terapéutico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Administración Intranasal , Animales , Portador Sano/tratamiento farmacológico , Portador Sano/prevención & control , Combinación de Medicamentos , Farmacorresistencia Bacteriana , Femenino , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Cavidad Nasal/microbiología , Pomadas/uso terapéutico , ARN Ribosómico 16S/genética , Ribonucleasa P/antagonistas & inhibidores , Infecciones Cutáneas Estafilocócicas/prevención & control , Estados Unidos
11.
Australas J Dermatol ; 57(2): 83-91, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-25752777

RESUMEN

This is a review of the common pathogens of surgical site infections, antibiotic coverage for particular anatomical sites, mechanisms by which surgical site infections occur and the latest data and recommendations for prophylactic antibiotics in the prevention of surgical site infections, infective endocarditis and haematogenous joint infections. Recent evidence-based guidelines on surgical prophylaxis is for restricted indications and a shorter duration of antibiotic prophylaxis in situations where no clinical benefit of prolonged therapy has been proven, in order to minimise the potential adverse ecological and clinical effects associated with antibiotic therapy. This review recommends the cautious use of prophylactic antibiotics in dermatological surgery to help prevent the growing problem of bacterial resistance as well as other morbidity and health-care costs.


Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Procedimientos Quirúrgicos Dermatologicos/efectos adversos , Infecciones Cutáneas Estafilocócicas/prevención & control , Infección de la Herida Quirúrgica/prevención & control , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Profilaxis Antibiótica/efectos adversos , Endocarditis/prevención & control , Humanos , Artropatías/microbiología , Artropatías/prevención & control , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/prevención & control , Factores de Riesgo , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/prevención & control , Infección de la Herida Quirúrgica/microbiología
12.
S D Med ; 69(12): 535-539, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28810104

RESUMEN

Methicillin resistant Staphylococcus aureus (MRSA) invasive infections can be severe in the pediatric population with high morbidity and mortality. MRSA colonization can predispose to recurrent skin and soft tissue infections and invasive MRSA disease and is a frequent challenge faced by clinicians. This article reviews the importance of MRSA as a pathogen, MRSA colonization and various MRSA decolonization strategies.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas/prevención & control , Adulto , Antibacterianos/uso terapéutico , Portador Sano , Niño , Guarderías Infantiles , Desinfectantes/uso terapéutico , Humanos , Higiene , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Mucosa Nasal/microbiología , Piel/microbiología , Infecciones Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/prevención & control , Infecciones Cutáneas Estafilocócicas/transmisión
13.
Infect Immun ; 83(5): 2168-74, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25776748

RESUMEN

SasX is a recently described surface protein of Staphylococcus aureus that is linked to the epidemic success of hospital-associated methicillin-resistant clones, in particular in Asia. It enhances nasal colonization and virulence in skin and lung infection models. Here, we evaluated the potential of SasX as a vaccine component in passive and active immunization efforts using mouse infection models. We found that SasX induced a specific immune response predominantly based on IgG1 antibodies. Active immunization with recombinant SasX or passive immunization with rabbit polyclonal anti-SasX IgG significantly decreased the size of lesions caused by S. aureus in a skin infection model. Furthermore, active immunization reduced acute lung injury in a lung infection model. Moreover, active or passive immunization significantly reduced S. aureus colonization in a nasal colonization model. Finally, anti-SasX IgG enhanced the susceptibility of S. aureus to killing by human neutrophils. We conclude that SasX is a potential target for therapeutics or vaccines designed to moderate colonization and infection by sasX-positive epidemic strains of S. aureus.


Asunto(s)
Proteínas Bacterianas/inmunología , Proteínas de la Membrana/inmunología , Infecciones Estafilocócicas/prevención & control , Vacunas Estafilocócicas/inmunología , Staphylococcus aureus/inmunología , Factores de Virulencia/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Portador Sano/prevención & control , Modelos Animales de Enfermedad , Femenino , Inmunización Pasiva/métodos , Inmunoglobulina G/sangre , Ratones Endogámicos BALB C , Mucosa Nasal/microbiología , Neumonía Bacteriana/patología , Neumonía Bacteriana/prevención & control , Infecciones Cutáneas Estafilocócicas/patología , Infecciones Cutáneas Estafilocócicas/prevención & control , Vacunas Estafilocócicas/administración & dosificación , Vacunación/métodos
14.
Antimicrob Agents Chemother ; 59(2): 943-9, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25421482

RESUMEN

In a field-based trial among military trainees, personal hygiene measures, including chlorhexidine (CHG) body wash, did not prevent overall and methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections (SSTI). We conducted a secondary analysis of anterior nares cultures obtained during the trial to evaluate the impact of hygiene measures on Staphylococcus aureus colonization. A cluster-randomized trial for SSTI prevention was conducted among U.S. Army infantry trainees from May 2010 to January 2012. There were three study groups with incrementally increasing education- and hygiene-based components: standard (S), enhanced standard (ES), and CHG. Anterior nares cultures were obtained from participants to determine the prevalence of S. aureus colonization. A total of 1,706 participants (469 S, 597 ES, and 640 CHG) without SSTI were included in the colonization analysis. Of those randomized to the CHG group, 360 (56.3%) reported frequent use of body wash. Frequent use of body wash had no effect on overall S. aureus colonization (53.3% versus 56.8% among infrequent/nonusers; P=0.25). MRSA colonization prevalence was marginally lower among frequent users (2.5% versus 4.7%; P=0.07). In multivariable analysis, the odds of MRSA colonization were lower among frequent users (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.16 to 0.77). This CHG-associated reduction was not observed when comparing colonization with USA300 to that with non-USA300 types (OR, 0.59; 95% CI, 0.06 to 5.76). Frequent use of CHG body wash was associated with a reduction in MRSA nasal colonization among high-risk military trainees. Topical chlorhexidine may contribute to MRSA SSTI prevention by reducing colonization. However, further studies evaluating the pathogenesis of SSTI are needed. (This study has been registered at ClinicalTrials.gov under registration no. NCT01105767).


Asunto(s)
Antiinfecciosos Locales/uso terapéutico , Clorhexidina/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Adolescente , Adulto , Femenino , Humanos , Masculino , Personal Militar/estadística & datos numéricos , Infecciones de los Tejidos Blandos/prevención & control , Infecciones Cutáneas Estafilocócicas/prevención & control , Adulto Joven
15.
Int J Sports Med ; 36(14): 1186-91, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26332899

RESUMEN

Among athletes, Staphylococcus aureus is thought to be transmitted by close physical contact with carriers. Nevertheless, evidence is limited with regard to both the tracking of individual strains and the role of S. aureus on the skin's surface. We investigated its transmission using molecular genotyping and the presence of S. aureus on the skin during exercise. In the first study, nasal samples were obtained from 172 athletes over a period of up to one year. The 200 strains of S. aureus collected from these athletes were genotyped, and transmission of S. aureus was detected by phage open reading frame typing (POT). In the second study, the presence of S. aureus on the skin's surface was compared between nasal carriers (n=9) and non-nasal carriers (n=9), who had participated in the first study. In the first study, 10 cases of transmission were confirmed. In the second study, exercise-induced sweating increased S. aureus isolates from the skin's surface (before vs. after exercise: 5.2±5.4 vs. 41.7±40.6 CFU/ml) in nasal carriers. In 5 of 9 nasal carriers, S. aureus isolates from the skin's surface were clonally identical to those from the nares. These results identify a major route of S. aureus transmission among athletes and provide insight into the role played by exercise-induced sweating in nasal carriers.


Asunto(s)
Portador Sano , Nariz/microbiología , Piel/microbiología , Deportes/fisiología , Infecciones Cutáneas Estafilocócicas/transmisión , Staphylococcus aureus , Genotipo , Humanos , Infecciones Cutáneas Estafilocócicas/prevención & control , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificación , Sudoración
17.
Clin Infect Dis ; 58(11): 1540-8, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24633684

RESUMEN

BACKGROUND: Effective measures are needed to prevent methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) in high-risk community settings. The study objective was to evaluate the effect of personal hygiene-based strategies on rates of overall SSTI and MRSA SSTI. METHODS: We conducted a prospective, field-based, cluster-randomized trial in US Army Infantry trainees from May 2010 through January 2012. There were 3 study groups with incrementally increased education and hygiene-based interventions: standard (S), enhanced standard (ES), and chlorhexidine (CHG). The primary endpoints were incidence of overall SSTI and MRSA SSTI. RESULTS: The study included 30 209 trainees constituting 540 platoons (168 S, 192 ES, and 180 CHG). A total of 1203 (4%) participants developed SSTI, 316 (26%) due to MRSA. The overall SSTI rate was 4.15 (95% confidence interval [CI], 3.77-4.58) per 100 person-cycles. SSTI rates by study group were 3.48 (95% CI, 2.87-4.22) for S, 4.18 (95% CI, 3.56-4.90) for ES, and 4.71 (95% CI, 4.03-5.50) for CHG. The MRSA SSTI rate per 100 person-cycles for all groups was 1.10 (95% CI, .91-1.32). MRSA SSTI rates by study group were 1.0 (95% CI, .70-1.42) for S, 1.29 (95% CI, .98-1.71) for ES, and 0.97 (95% CI, .70-1.36) for CHG. CONCLUSIONS: Personal hygiene and education measures, including once-weekly use of chlorhexidine body wash, did not prevent overall SSTI or MRSA SSTI in a high-risk population of military trainees. CLINICAL TRIALS REGISTRATION: NCT01105767.


Asunto(s)
Higiene/normas , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/prevención & control , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/prevención & control , Adolescente , Adulto , Desinfección/métodos , Educación en Salud/métodos , Humanos , Incidencia , Masculino , Personal Militar , Estudios Prospectivos , Estados Unidos , Adulto Joven
18.
Br J Dermatol ; 170 Suppl 1: 7-11, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24720588

RESUMEN

Atopic dermatitis (AD) is a common, chronic inflammatory skin disease with a highly variable clinical phenotype and heterogeneous pathophysiology. Its pathogenesis is associated with alterations to both the skin barrier and the immune system, which may in turn be influenced by genetic mutations and the patient's environment. Basic and translational research, as well as clinical trials, have helped broaden our knowledge of the molecular mechanisms underlying the development of AD and to identify potential treatment targets and approaches. These include new ways of reducing transepidermal water loss and the shedding of corneocytes, new ways of interacting with established molecular targets (such as histamine receptors and interleukins and other T-cell cytokines), and the identification of new molecular targets (such as toll-like receptors and tight junction proteins). Well-established treatment options such as emollients, corticosteroids and topical calcineurin inhibitors will clearly continue to have a role in treating AD. Among the new agents that could be joining them in the near future are sphinganin (a precursor of ceramides 1 and 3), cannabinoids, highly targeted monoclonal antibodies and subcutaneous immunotherapy.


Asunto(s)
Dermatitis Atópica/terapia , Inmunidad Adaptativa/fisiología , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Péptidos Catiónicos Antimicrobianos/inmunología , Cannabinoides/uso terapéutico , Células Dendríticas/inmunología , Dermatitis Atópica/inmunología , Dermatitis Atópica/fisiopatología , Inhibidores Enzimáticos/uso terapéutico , Epidermis/fisiología , Humanos , Inmunoglobulina E/inmunología , Inmunoterapia/métodos , Erupción Variceliforme de Kaposi/prevención & control , Mastocitos/inmunología , Receptores Histamínicos/inmunología , Esfingosina/análogos & derivados , Esfingosina/uso terapéutico , Infecciones Cutáneas Estafilocócicas/prevención & control , Vitamina D/inmunología , Pérdida Insensible de Agua/inmunología , Pérdida Insensible de Agua/fisiología
19.
BMC Nephrol ; 15: 202, 2014 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-25519998

RESUMEN

BACKGROUND: This study was performed to evaluate the effectiveness of surveillance for screening and treatment of patients with chronic kidney disease undergoing hemodialysis and colonized by Staphylococcus aureus. METHODS: A systematic review and meta-analysis were performed. The literature search involved the following databases: the Cochrane Controlled Trials Register, Embase, LILACS, CINAHL, SciELO, and PubMed/Medline. The descriptors were "Staphylococcus aureus", "MRSA", "MSSA", "treatment", "decolonization", "nasal carrier", "colonization", "chronic kidney disease", "dialysis", and "haemodialysis" or "hemodialysis". Five randomized controlled trials that exhibited agreement among reviewers as shown by a kappa value of >0.80 were included in the study; methodological quality was evaluated using the STROBE statement. Patients who received various treatments (various treatments group) or topical mupirocin (mupirocin group) were compared with those who received either no treatment or placebo (control group). The outcomes were skin infection at the central venous catheter insertion site and bacteremia. RESULTS: In total, 2374 patients were included in the analysis, 626 (26.4%) of whom were nasal carriers of S. aureus. The probability of S. aureus infection at the catheter site for hemodialysis was 87% lower in the mupirocin group than in the control group (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.05-0.34; p<0.001). The risk of bacteremia was 82% lower in the mupirocin group than in the control group (OR, 0.18; 95% CI, 0.08-0.42; p<0.001). No statistically significant difference in bacteremia was observed between the various treatments group (excluding mupirocin) and the control group (OR, 0.77; 95% CI, 0.51-1.15; p=0.20). CONCLUSIONS: Twenty-six percent of patients undergoing hemodialysis were nasal carriers of S. aureus. Of all treatments evaluated, topical mupirocin was the most effective therapy for the reduction of S. aureus catheter site infection and bacteremia in patients undergoing chronic hemodialysis.


Asunto(s)
Antibacterianos/administración & dosificación , Infecciones Relacionadas con Catéteres/diagnóstico , Infecciones Relacionadas con Catéteres/prevención & control , Diálisis Renal/efectos adversos , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/prevención & control , Administración Tópica , Bacteriemia/diagnóstico , Bacteriemia/prevención & control , Portador Sano/diagnóstico , Portador Sano/prevención & control , Cateterismo Venoso Central/efectos adversos , Humanos , Mupirocina/administración & dosificación , Insuficiencia Renal Crónica/terapia , Infecciones Cutáneas Estafilocócicas/diagnóstico , Infecciones Cutáneas Estafilocócicas/prevención & control
20.
Acta Derm Venereol ; 93(3): 294-300, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23038099

RESUMEN

Metallic copper has been shown significantly to reduce methicillin-resistant Staphylococcus aureus (MRSA) contamination of the ambient surroundings of the beds of MRSA-carrying patients in dermatology wards. The aim of this study was to determine whether a bed sheet made of copper-coated film will reduce the spread of MRSA contamination in the environment of a heavily-colonized patient. The bacterial count was highest on the bed sheet. MRSA cell counts on the surface of the non-film-coated control sheet were high (6,600-11,000 colony forming units (cfu)), but those on the copper film were considerably lower (20-130 cfu). Use of metallic copper on the bed sheets of patients who are likely to be a source of MRSA contamination may help to prevent the spread of MRSA contamination in hospital wards.


Asunto(s)
Aleaciones , Ropa de Cama y Ropa Blanca , Cobre , Infección Hospitalaria/prevención & control , Dermatología , Contaminación de Equipos/prevención & control , Unidades Hospitalarias , Control de Infecciones/métodos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Cutáneas Estafilocócicas/prevención & control , Infección Hospitalaria/microbiología , Infección Hospitalaria/transmisión , ADN Bacteriano/aislamiento & purificación , Diseño de Equipo , Femenino , Genotipo , Humanos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Persona de Mediana Edad , Fenotipo , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/transmisión , Resultado del Tratamiento
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