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1.
PLoS One ; 18(11): e0288016, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38033025

RESUMO

BACKGROUND: Streptoccocal A (Strep A, GAS) infections in Australia are responsible for significant morbidity and mortality through both invasive (iGAS) and post-streptococcal (postGAS) diseases as well as preceding superficial (sGAS) skin and throat infection. The burden of iGAS and postGAS are addressed in some jurisdictions by mandatory notification systems; in contrast, the burden of preceding sGAS has no reporting structure, and is less well defined. This review provides valuable, contemporaneous evidence on the epidemiology of sGAS presentations in Australia, informing preventative health projects such as a Streptococcal A vaccine and standardisation of primary care notification. METHODS AND FINDINGS: MEDLINE, Scopus, EMBASE, Web of Science, Global Health, Cochrane, CINAHL databases and the grey literature were searched for studies from an Australian setting relating to the epidemiology of sGAS infections between 1970 and 2020 inclusive. Extracted data were pooled for relevant population and subgroup analysis. From 5157 titles in the databases combined with 186 grey literature reports and following removal of duplicates, 4889 articles underwent preliminary title screening. The abstract of 519 articles were reviewed with 162 articles identified for full text review, and 38 articles identified for inclusion. The majority of data was collected for impetigo in Aboriginal and Torres Strait Islander populations, remote communities, and in the Northern Territory, Australia. A paucity of data was noted for Aboriginal and Torres Strait Islander people living in urban centres or with pharyngitis. Prevalence estimates have not significantly changed over time. Community estimates of impetigo point prevalence ranged from 5.5-66.1%, with a pooled prevalence of 27.9% [95% CI: 20.0-36.5%]. All studies excepting one included >80% Aboriginal and Torres Strait Islander people and all excepting two were in remote or very remote settings. Observed prevalence of impetigo as diagnosed in healthcare encounters was lower, with a pooled estimate of 10.6% [95% CI: 3.1-21.8%], and a range of 0.1-50.0%. Community prevalence estimates for pharyngitis ranged from 0.2-39.4%, with a pooled estimate of 12.5% [95% CI: 3.5-25.9%], higher than the prevalence of pharyngitis in healthcare encounters; ranging from 1.0-5.0%, and a pooled estimate of 2.0% [95% CI: 1.3-2.8%]. The review was limited by heterogeneity in study design and lack of comparator studies for some populations. CONCLUSIONS: Superficial Streptococcal A infections contribute to an inequitable burden of disease in Australia and persists despite public health interventions. The burden in community studies is generally higher than in health-services settings, suggesting under-recognition, possible normalisation and missed opportunities for treatment to prevent postGAS. The available, reported epidemiology is heterogeneous. Standardised nation-wide notification for sGAS disease surveillance must be considered in combination with the development of a Communicable Diseases Network of Australia (CDNA) Series of National Guideline (SoNG), to accurately define and address disease burden across populations in Australia. TRIAL REGISTRATION: This review is registered with PROSPERO. Registration number: CRD42019140440.


Assuntos
Serviços de Saúde do Indígena , Impetigo , Faringite , Humanos , Povos Aborígenes Australianos e Ilhéus do Estreito de Torres , Impetigo/epidemiologia , Impetigo/microbiologia , Northern Territory , Faringite/epidemiologia , Faringite/microbiologia , Streptococcus
2.
Eur Rev Med Pharmacol Sci ; 27(19): 9273-9278, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37843341

RESUMO

OBJECTIVE: Ozenoxacin is a new antibiotic used to treat non-bullous impetigo. The aim of this study is to evaluate the microbiological and clinical efficacy of topical ozenoxacin 1% cream after 5-day twice-daily treatment, in pediatric patients with impetigo. PATIENTS AND METHODS: This observational and prospective study included patients aged 6 months to 18 years, with non-bullous impetigo. Efficacy was measured using the Skin Infection Rating Scale (SIRS) and microbiological culture at the first visit (T0), at the second visit after 72 hours (T1) and after 5 days (T2). Safety and tolerability were also evaluated. RESULTS: A total of 50 patients was enrolled. A reduction of SIRS score >10% after 72 hours of treatment was noticed in all patients, while a complete reduction was assessed after 5 days in all the population. Microbiologic success rates for ozenoxacin at T1 was 92% (four patients had original pathogens in the specimen culture from the skin area), whereas at T2, it was 100%. CONCLUSIONS: Topical ozenoxacin has strong efficacy in treating impetigo in pediatric patients. Ozenoxacin's clinical and microbiological rapid onset of response led to consider this antibiotic a novel efficacy option for the treatment of impetigo.


Assuntos
Impetigo , Humanos , Criança , Impetigo/diagnóstico , Impetigo/tratamento farmacológico , Impetigo/microbiologia , Estudos Prospectivos , Antibacterianos , Síndrome de Resposta Inflamatória Sistêmica
3.
Expert Opin Drug Saf ; 20(6): 677-683, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33726585

RESUMO

INTRODUCTION: Impetigo is a superficial bacterial skin infection largely affecting the pediatric population. The objective of this review is to provide a comparison of mechanism of action, efficacy and safety of the available topical antibiotics for impetigo. AREAS COVERED: Randomized clinical trials that evaluated the use of topical antibiotics for treatment of impetigo were included. Two thousand eighty-nine studies were initially identified, and five randomized clinical trials met the criteria for further analysis. EXPERT OPINION: Topical antibiotics had greater resolution of impetigo in comparison to vehicle in these pivotal clinical trials. Adverse events were minimal, with the most common being pruritus at the application site. Cost or insurance coverage may be a limiting factor in choosing the best therapeutic agent, with mupirocin ointment having the lowest cost. Mupirocin has shown clinical efficacy against MRSA but a bacterial culture is recommended to rule out resistance. Ozenoxacin and retapamulin are effective alternatives but may entail higher cost. Retapamulin is indicated for lesions of impetigo that are colonized by MSSA and streptococcus S. pyogenes but not MRSA based on clinical efficacy of phase III trials. Fusidic acid, available in other countries, is a non-FDA approved medication although rising resistance rates represent a growing concern.


Assuntos
Antibacterianos/administração & dosagem , Impetigo/tratamento farmacológico , Administração Cutânea , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Criança , Custos de Medicamentos , Farmacorresistência Bacteriana , Humanos , Impetigo/microbiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
4.
J Drugs Dermatol ; 20(2): 134-142, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33538559

RESUMO

BACKGROUND: Impetigo, a highly contagious bacterial skin infection commonly occurring in young children, but adults may also be affected. The superficial skin infection is mainly caused by Staphylococcus aureus (S. aureus) and less frequently by Streptococcus pyogenes (S. pyogenes). Antimicrobial resistance has become a worldwide concern and needs to be addressed when selecting treatment for impetigo patients. An evidence-based impetigo treatment algorithm was developed to address the treatment of impetigo for pediatric and adult populations. METHODS: An international panel of pediatric dermatologists, dermatologists, pediatricians, and pediatric infectious disease specialists employed a modified Delphi technique to develop the impetigo treatment algorithm. Treatment recommendations were evidence-based, taking into account antimicrobial stewardship and the increasing resistance to oral and topical antibiotics. RESULTS: The algorithm includes education and prevention of impetigo, diagnosis and classification, treatment measures, and follow-up and distinguishes between localized and widespread or epidemic outbreaks of impetigo. The panel adopted the definition of localized impetigo of fewer than ten lesions and smaller than 36 cm2 area affected in patients of two months and up with no compromised immune status. Resistance to oral and topical antibiotics prescribed for the treatment of impetigo such as mupirocin, retapamulin, fusidic acid, have been widely reported. CONCLUSIONS: When prescribing antibiotics, it is essential to know the local trends in antibiotic resistance. Ozenoxacin cream 1% is highly effective against S. pyogenes and S. aureus, including methycyllin-susceptible and resistant strains (MRSA), and may be a suitable option for localized impetigo.J Drugs Dermatol. 2021;20(2):134-142. doi:10.36849/JDD.5475 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.


Assuntos
Antibacterianos/uso terapêutico , Procedimentos Clínicos/normas , Impetigo/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Antibacterianos/farmacologia , Gestão de Antimicrobianos/normas , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Técnica Delfos , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Farmacorresistência Bacteriana , Medicina Baseada em Evidências/normas , Ácido Fusídico/farmacologia , Ácido Fusídico/uso terapêutico , Humanos , Impetigo/diagnóstico , Impetigo/microbiologia , Testes de Sensibilidade Microbiana/normas , Mupirocina/farmacologia , Mupirocina/uso terapêutico , Guias de Prática Clínica como Assunto , Quinolonas/farmacologia , Quinolonas/uso terapêutico , Creme para a Pele/farmacologia , Creme para a Pele/uso terapêutico , Staphylococcus aureus/isolamento & purificação , Streptococcus pyogenes/isolamento & purificação , Revisões Sistemáticas como Assunto
5.
Acta Clin Belg ; 76(1): 53-57, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31210583

RESUMO

Ecthyma gangrenosum (EG) is a potentially lethal skin infection, most commonly due to Pseudomonas aeruginosa with bacteremic dissemination and affecting mostly immunocompromised patients. We present two cases of EG in two men in Belgium recently admitted to our hospital, caused by a suspected coinfection by group A Streptococcus and Staphylococcus aureus, with a cutaneous dissemination, in which multiple impetigo lesions were the portal of entry. The first patient had no risk factors nor immunodeficiency, but the second was a homeless man with drug and alcohol abuse and advanced HIV infection. Early management of the condition is crucial, with initial broad spectrum antibiotherapy, rapidly narrowed down to the germs identified and skin lesion debridement if necessary. Any immunocompromising condition must be ruled out in any patient suffering from EG.


Assuntos
Ectima/microbiologia , Gangrena/microbiologia , Pele , Staphylococcus aureus , Streptococcus pyogenes , Adulto , Bélgica , Coinfecção , Ectima/diagnóstico , Ectima/patologia , Gangrena/diagnóstico , Gangrena/patologia , Humanos , Impetigo/diagnóstico , Impetigo/microbiologia , Impetigo/patologia , Masculino , Pele/microbiologia , Pele/patologia
6.
Infect Dis Clin North Am ; 35(1): 81-105, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33303329

RESUMO

Staphylococcus aureus is the most common bacteria causing purulent skin and soft tissue infections. Many disease-causing S aureus strains are methicillin resistant; thus, empiric therapy should be given to cover methicillin-resistant S aureus. Bacterial wound cultures are important for characterizing local susceptibility patterns. Definitive antibiotic therapy is warranted, although there are no compelling data demonstrating superiority of any one antibiotic over another. Antibiotic choice is predicated by the infection severity, local susceptibility patterns, and drug-related safety, tolerability, and cost. Response to therapy is expected within the first days; 5 to 7 days of therapy is typically adequate to achieve cure.


Assuntos
Infecções dos Tecidos Moles/diagnóstico , Infecções dos Tecidos Moles/terapia , Infecções Cutâneas Estafilocócicas/diagnóstico , Infecções Cutâneas Estafilocócicas/terapia , Staphylococcus aureus/patogenicidade , Abscesso/microbiologia , Abscesso/terapia , Algoritmos , Antibacterianos/uso terapêutico , Celulite (Flegmão)/microbiologia , Celulite (Flegmão)/terapia , Drenagem/métodos , Humanos , Impetigo/microbiologia , Impetigo/terapia , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Fatores de Risco , Infecções dos Tecidos Moles/microbiologia , Infecções Cutâneas Estafilocócicas/microbiologia
7.
Adv Emerg Nurs J ; 42(4): 262-269, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33105179

RESUMO

Impetigo is a common superficial bacterial infection of the skin, with a global disease burden of greater than 140 million. Children are more affected than adults and incidence decreases with age. Principal pathogens implicated include Staphylococcus aureus and Streptococcus pyogenes. There are two common variants of impetigo: nonbullous (70%) and bullous (30%). Nonbullous impetigo is caused by S. aureus and S. pyogenes whereas bullous impetigo is caused by S. aureus. The classic appearance of distinctive honey-colored, crusted legions aids in diagnosis, which is most often based on clinical presentation. The disease is generally mild and felt to be self-limited; however, antimicrobial treatment is often initiated to reduce spread and shorten clinical course. Treatment for limited impetigo is topical whereas oral therapy is recommended for extensive cases. Rising rates of bacterial resistance to standard treatment regimens should inform treatment decisions. Complications, while rare, can occur.


Assuntos
Impetigo/diagnóstico , Impetigo/tratamento farmacológico , Impetigo/microbiologia , Diagnóstico de Enfermagem , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Diagnóstico Diferencial , Humanos , Staphylococcus aureus , Streptococcus pyogenes
8.
Euro Surveill ; 25(40)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33034283

RESUMO

We observed an increase in notifications of puerperal group A Streptococcus (GAS) infections in July and August 2018 throughout the Netherlands without evidence for common sources. General practitioners reported a simultaneous increase in impetigo. We hypothesised that the outbreak of puerperal GAS infections resulted from increased exposure via impetigo in the community.We conducted a case-control study to assess peripartum exposure to possible, non-invasive GAS infections using an online questionnaire. Confirmed cases were recruited through public health services while probable cases and controls were recruited through social media. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) with logistic regression analysis.We enrolled 22 confirmed and 23 probable cases, and 2,400 controls. Contact with persons with impetigo were reported by 8% of cases and 2% of controls (OR: 3.26, 95% CI: 0.98-10.88) and contact with possible GAS infections (impetigo, pharyngitis or scarlet fever) by 28% and 9%, respectively (OR: 4.12, 95% CI: 1.95-8.68). In multivariable analysis, contact with possible GAS infections remained an independent risk factor (aOR: 4.28, 95% CI: 2.02-9.09).We found an increased risk of puerperal fever after community contact with possible non-invasive GAS infections. Further study of this association is warranted.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Febre/etiologia , Impetigo/microbiologia , Faringite/microbiologia , Infecção Puerperal/epidemiologia , Escarlatina/microbiologia , Infecções Estreptocócicas/complicações , Streptococcus pyogenes/isolamento & purificação , Adulto , Estudos de Casos e Controles , Notificação de Doenças , Transmissão de Doença Infecciosa/estatística & dados numéricos , Feminino , Humanos , Impetigo/epidemiologia , Países Baixos/epidemiologia , Faringite/epidemiologia , Período Pós-Parto , Gravidez , Infecção Puerperal/microbiologia , Escarlatina/epidemiologia , Estações do Ano , Infecções Estreptocócicas/epidemiologia
9.
PLoS Comput Biol ; 16(10): e1007838, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33017395

RESUMO

Prevalence of impetigo (skin sores) remains high in remote Australian Aboriginal communities, Fiji, and other areas of socio-economic disadvantage. Skin sore infections, driven primarily in these settings by Group A Streptococcus (GAS) contribute substantially to the disease burden in these areas. Despite this, estimates for the force of infection, infectious period and basic reproductive ratio-all necessary for the construction of dynamic transmission models-have not been obtained. By utilising three datasets each containing longitudinal infection information on individuals, we estimate each of these epidemiologically important parameters. With an eye to future study design, we also quantify the optimal sampling intervals for obtaining information about these parameters. We verify the estimation method through a simulation estimation study, and test each dataset to ensure suitability to the estimation method. We find that the force of infection differs by population prevalence, and the infectious period is estimated to be between 12 and 20 days. We also find that optimal sampling interval depends on setting, with an optimal sampling interval between 9 and 11 days in a high prevalence setting, and 21 and 27 days for a lower prevalence setting. These estimates unlock future model-based investigations on the transmission dynamics of skin sores.


Assuntos
Impetigo , Modelos Biológicos , Austrália/epidemiologia , Biologia Computacional , Bases de Dados Factuais , Humanos , Impetigo/epidemiologia , Impetigo/microbiologia , Impetigo/transmissão , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Prevalência , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/transmissão , Streptococcus pyogenes/patogenicidade
10.
Expert Rev Anti Infect Ther ; 17(9): 681-687, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31393185

RESUMO

Introduction: Antibiotic-resistant strains of bacteria are an increasing problem in hospitals and in the community. This has resulted in bacterial infections such as impetigo becoming difficult to treat. Alternative treatment options are needed. Areas covered: In this paper, a past study that assessed the health burden of scabies in North Queensland is described and from it, the potential for formaldehyde as an alternative antimicrobial treatment is discussed. In doing so, antibiotic resistance, impetigo, permethrin, and formaldehyde are introduced and the current understanding and limitations of the effects of formaldehyde on humans are outlined. The limited cases of formaldehyde resistance in bacteria are also discussed. Expert opinion: Formaldehyde is currently used as a preservative in cosmetics and medicinal creams due to its antibacterial activity. It, therefore, has the potential to be used as an alternative antibacterial treatment for infections with antibiotic-resistant bacteria. The harmful side effects of airborne formaldehyde and exposure in allergic individuals have been extensively studied. Significantly less research has been conducted on formaldehyde skin contact in healthy individuals. If formaldehyde is safe for topical use in humans, it has the potential to assist with combating antibiotic resistance.


Assuntos
Antibacterianos/administração & dosagem , Formaldeído/administração & dosagem , Impetigo/tratamento farmacológico , Dermatopatias Infecciosas/tratamento farmacológico , Administração Tópica , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Formaldeído/efeitos adversos , Formaldeído/farmacologia , Humanos , Impetigo/microbiologia , Dermatopatias Infecciosas/microbiologia
11.
Viruses ; 11(9)2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443379

RESUMO

Impetigo is a contagious skin infection predominantly caused by Staphylococcus aureus. Decontamination of S. aureus from the skin is becoming more difficult because of the emergence of antibiotic-resistant strains. Bacteriophage endolysins are less likely to invoke resistance and can eliminate the target bacteria without disturbance of the normal microflora. In this study, we investigated the therapeutic potential of a recombinant endolysin derived from kayvirus S25-3 against staphylococcal impetigo in an experimental setting. First, the recombinant S25-3 endolysin required an incubation period of over 15 minutes to exhibit efficient bactericidal effects against S. aureus. Second, topical application of the recombinant S25-3 endolysin decreased the number of intraepidermal staphylococci and the size of pustules in an experimental mouse model of impetigo. Third, treatment with the recombinant S25-3 endolysin increased the diversity of the skin microbiota in the same mice. Finally, we revealed the genus-specific bacteriolytic effect of recombinant S25-3 endolysin against staphylococci, particularly S. aureus, among human skin commensal bacteria. Therefore, topical treatment with recombinant S25-3 endolysin can be a promising disease management procedure for staphylococcal impetigo by efficient bacteriolysis of S. aureus while improving the cutaneous bacterial microflora.


Assuntos
Caudovirales/metabolismo , Endopeptidases/farmacologia , Impetigo/tratamento farmacológico , Staphylococcus aureus , Administração Cutânea , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Bacteriólise , Caudovirales/patogenicidade , Endopeptidases/administração & dosagem , Endopeptidases/genética , Genes Bacterianos , Genes Virais , Impetigo/microbiologia , Metagenômica , Camundongos , Microbiota/genética , Pseudomonas aeruginosa/virologia , RNA Ribossômico 16S , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Pele/microbiologia , Pele/patologia , Infecções Estafilocócicas/tratamento farmacológico , Fagos de Staphylococcus/metabolismo , Fagos de Staphylococcus/patogenicidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/virologia , Staphylococcus epidermidis/virologia , Streptococcus mitis/virologia
12.
J Drugs Dermatol ; 18(7): 655-661, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31334625

RESUMO

Background: Impetigo, a bacterial infection that is highly contagious, involves the superficial skin. Topical treatment for impetigo includes amongst other bacitracin, gentamycin, mupirocin, retapamulin, and more recently, ozenoxacin 1% cream. For more severe conditions systemic antibiotics are prescribed and may be combined with a topical treatment. The current review explored the challenges in treating impetigo in pediatric and adult populations and examined the role of ozenoxacin 1% cream as a safe and effective treatment option. Methods: We performed PubMed and Google Scholar searches of the English-language literature (2010-2018) using the terms impetigo, bullous impetigo, non-bullous impetigo, antimicrobial and antibiotic resistance, mupirocin, retapamulin, and ozenoxacin. The selected publications were manually reviewed for additional resources. Results: Although guidelines were updated regularly, the recommended treatments have not changed much since 2014. Emerging antimicrobial resistance is a growing concern in dermatology and pediatrics. Impetigo therapy choices should consider the resistance pattern of S. aureus. Ozenoxacin 1% cream is a prescription medicine for topical treatment of impetigo in adults and children 2 months or older. Ozenoxacin has a low probability of selecting spontaneous resistant mutants in quinolone-susceptible or quinolone-resistant bacterial strains and has shown to be active against MRSA isolates. Ozenoxacin 1% cream has potent bactericidal activity and was shown to be effective and safe for the treatment of impetigo in two well-controlled Phase 3 trials. Conclusions: Resistance patterns in a wide range of pathogens against oral or topical antibiotics and antiseptics used for the treatment of dermatological conditions, such as impetigo have been observed. When making treatment decisions for impetigo MRSA and other antimicrobial resistance has to be taken into account. Ozenoxacin 1% cream offers a potent bactericidal activity and has demonstrated clinical efficacy and safety. Combined with its favorable features, such as a low dosing frequency and a 5 days treatment regimen, ozenoxacin 1% cream is an important option for the treatment of impetigo for pediatric and adult populations. J Drugs Dermatol. 2019;18(7):655-661.


Assuntos
Aminopiridinas/farmacologia , Antibacterianos/farmacologia , Impetigo/tratamento farmacológico , Quinolonas/farmacologia , Creme para a Pele/administração & dosagem , Staphylococcus aureus/fisiologia , Aminopiridinas/uso terapêutico , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/normas , Tomada de Decisão Clínica , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Humanos , Impetigo/microbiologia , Mutação/efeitos dos fármacos , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Quinolonas/uso terapêutico , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento
15.
J Invest Dermatol ; 139(8): 1743-1752.e5, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30807768

RESUMO

Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator generated when a cell membrane or its components are damaged by various factors. S1P regulates diverse cell activities via S1P receptors (S1PRs). Keratinocytes express S1PR1-5. Although it is known that S1PRs control keratinocyte differentiation, apoptosis, and wound healing, S1PR functions in keratinocyte infections have not been fully elucidated. We propose that the S1P-S1PR axis in keratinocytes works as a biosensor for bacterial invasion. Indeed, in human impetigo infection, we found high epidermal expression of S1PR1 and S1PR2 in the skin. Furthermore, in normal human epidermal keratinocytes in vitro, treatment with Staphylococcus aureus bacterial supernatant not only induced S1P production but also increased the transcription of S1PR2, confirming our in vivo observation, as well as increased the levels of TNFA, IL36G, IL6, and IL8 mRNAs. However, direct treatment of normal human epidermal keratinocytes with S1P increased the expressions of IL36G, TNFA, and IL8, but not IL6. In both S1P- and S. aureus bacterial supernatant-treated normal human epidermal keratinocytes, S1PR1 knockdown reduced IL36G, TNFA, and IL8 transcription, and the S1PR2 antagonist JTE013 blocked the secretion of these cytokines. Overall, we have proven that during infections, keratinocytes communicate damage by using S1P release and tight control of S1PR1 and 2.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Impetigo/imunologia , Queratinócitos/imunologia , Lisofosfolipídeos/metabolismo , Pele/imunologia , Esfingosina/análogos & derivados , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Impetigo/microbiologia , Impetigo/patologia , Queratinócitos/metabolismo , Queratinócitos/microbiologia , Cultura Primária de Células , Pirazóis/farmacologia , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Pele/citologia , Pele/patologia , Esfingosina/metabolismo , Receptores de Esfingosina-1-Fosfato/antagonistas & inibidores , Receptores de Esfingosina-1-Fosfato/genética , Receptores de Esfingosina-1-Fosfato/metabolismo , Staphylococcus aureus/imunologia
16.
J Dermatol ; 46(4): 301-307, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803017

RESUMO

Recently, the USA300 clone, which is a Panton-Valentine leukocidin (PVL)-positive clonal complex 8-staphylococcal cassette chromosome mec type IV (CC8-IV) community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strain, emerged in community and hospital settings in Japan. Hence, clonal types of CA-MRSA strains are predicted to be changing. Nonetheless, long-term surveillance of CA-MRSA has not been conducted in Japan. Here, we investigated the transition and current status of CA-MRSA strains isolated from outpatients with impetigo; the samples were collected between 2007 and 2016 in Kagawa, Japan. The detection rate (22.8%, 488/2139 strains) of MRSA slightly decreased in these 10 years. Molecular epidemiological analyses showed that the prevalence of the CC89-II clone, which is a typical CA-MRSA genotype of causative agents of impetigo, significantly decreased from 48.0% (48/100 strains) in 2007-2009 to 21.9% (16/73 strains) in 2013-2016. By contrast, a non-USA300 CC8-IV clone, which is a highly pathogenic CA-MRSA/J clone, significantly increased in prevalence from 9.0% (9/100 strains) to 32.9% (24/73 strains). The prevalence of PVL-positive CA-MRSA strains increased annually from 2012 (0%) to 2015 (6.7%), whereas only one of these strains turned out to be the USA300 clone. Antibiotic susceptibility data revealed that the rates of resistance to gentamicin and clindamycin among CA-MRSA strains decreased along with the decreased prevalence of the CC89-II clone and increased prevalence of the CA-MRSA/J clone. Our data strongly suggest that the clonal types and antibiotic susceptibility of CA-MRSA isolated from patients with impetigo dramatically changed during the last 10 years in Japan.


Assuntos
Antibacterianos/uso terapêutico , Impetigo/microbiologia , Resistência a Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Adolescente , Antibacterianos/farmacologia , Toxinas Bacterianas/metabolismo , Criança , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Exotoxinas/metabolismo , Feminino , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Humanos , Impetigo/tratamento farmacológico , Impetigo/epidemiologia , Japão/epidemiologia , Leucocidinas/metabolismo , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/metabolismo , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Prevalência , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia
17.
Expert Rev Anti Infect Ther ; 17(3): 159-168, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30686133

RESUMO

INTRODUCTION: Impetigo is the most common bacterial skin infection in children. Treatment is becoming complicated due to the development of antimicrobial resistance, especially in the main pathogen, Staphylococcus aureus. Ozenoxacin, a novel non-fluorinated topical quinolone antimicrobial, has demonstrated efficacy in impetigo. Areas covered: This article reviews the microbiology, pharmacodynamic and pharmacokinetic properties of ozenoxacin, and its clinical and microbiological efficacy in impetigo. Expert opinion: In an environment of increasing antimicrobial resistance and concurrent slowdown in antimicrobial development, the introduction of a new agent is a major event. Ozenoxacin is characterized by simultaneous affinity for DNA gyrase and topoisomerase IV, appears to be impervious to certain efflux pumps that confer bacterial resistance to other quinolones, shows low selection of resistant mutants, and has a mutant prevention concentration below its concentration in skin. These mechanisms protect ozenoxacin against development of resistance, while the absence of a fluorine atom in its structure confers a better safety profile versus fluoroquinolones. In vitro studies have demonstrated high potency of ozenoxacin against staphylococci and streptococci including resistant strains of S. aureus. Clinical trials of ozenoxacin in patients with impetigo reported high clinical and microbiological success rates. Preserving the activity and availability of ozenoxacin through antimicrobial stewardship is paramount.


Assuntos
Aminopiridinas/uso terapêutico , Antibacterianos/uso terapêutico , Impetigo/tratamento farmacológico , Quinolonas/uso terapêutico , Aminopiridinas/farmacocinética , Aminopiridinas/farmacologia , Animais , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Criança , Farmacorresistência Bacteriana , Humanos , Impetigo/microbiologia , Quinolonas/farmacocinética , Quinolonas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento
18.
J Infect Chemother ; 25(3): 233-237, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30279113

RESUMO

Community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) is a causative agent of intractable skin infections. In general, clinical symptoms of hospital outpatients with skin infections are severer than those of clinic patients. Hence, molecular epidemiological features of the CO-MRSA strains from hospital outpatients are predicted to be different from those of clinic patients. Here, we conducted a comparative analysis for CO-MRSA isolates from outpatients with impetigo in hospitals and clinics located in the same district of Tokyo, Japan. Incidence of MRSA infection was higher in hospital outpatients (21.5%, 20/93 isolates) than in clinic patients (14.5%, 121/845 isolates). The resistance rate to clindamycin, which is a common topical antimicrobial agent in dermatology, in the isolates from hospital outpatients (60.0%) was higher than those from clinic patients (31.4%). Proportion of the staphylococcal cassette chromosome (SCC) mec type II, which is a representative type of hospital-acquired MRSA in Japan, in the isolates from hospital outpatients (65.0%) was significantly higher than those from clinic patients (30.6%) (P < 0.01). Multilocus sequence typing showed that the clonal complex 89-SCCmec type II (CC89-II) clone, which exhibits clindamycin resistance, was the most predominant (55.0%) in the isolates from hospital outpatients. On the other hand, all CC8-IV, CC121-V, and CC89-V clones accounted for 60% in clinic patients were susceptible to clindamycin. Our findings suggested that the clindamycin-resistant CC89-II CO-MRSA clone might be more related to skin infections in hospital outpatients than clinic patients.


Assuntos
Infecções Comunitárias Adquiridas , Impetigo , Staphylococcus aureus Resistente à Meticilina , Instituições de Assistência Ambulatorial , Antibacterianos/farmacologia , Clindamicina/farmacologia , Estudos de Coortes , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana , Feminino , Hospitais , Humanos , Impetigo/epidemiologia , Impetigo/microbiologia , Incidência , Japão/epidemiologia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana
19.
J Drugs Dermatol ; 17(10): 1051-1057, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30365584

RESUMO

Ozenoxacin is a novel topical antibacterial agent with potent bactericidal activity against Gram-positive bacteria that has been developed as a 1% cream for treatment of impetigo. This article presents pooled results of pivotal clinical trials of ozenoxacin with the objective of evaluating the efficacy, safety, and tolerability of ozenoxacin 1% cream after twice-daily topical treatment for 5 days in patients with impetigo. A pooled analysis was performed of individual patient data from two multicenter, randomized, double-blind, vehicle-controlled phase 3 registration studies conducted in patients with impetigo. Both clinical trials followed a similar methodology. Patients were randomized 1:1 to ozenoxacin or vehicle. One trial included retapamulin as an internal control. Efficacy was measured using the Skin Infection Rating Scale and microbiological culture. Safety and tolerability were evaluated. Ozenoxacin demonstrated superior clinical success versus vehicle after 5 days of therapy, superior microbiological success versus vehicle after 2 days of therapy, and was safe and well-tolerated. Ozenoxacin showed superior clinical and microbiological response versus vehicle in children as young as 2 months of age, and adults, with impetigo. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT01397461 and NCT02090764; European Clinical Trials Database Number: 2011-003032-31 and 2014-000228-52. J Drugs Dermatol. 2018;17(10):1051-1057.


Assuntos
Aminopiridinas/uso terapêutico , Antibacterianos/uso terapêutico , Impetigo/tratamento farmacológico , Quinolonas/uso terapêutico , Administração Cutânea , Adolescente , Adulto , Idoso , Aminopiridinas/administração & dosagem , Antibacterianos/administração & dosagem , Criança , Pré-Escolar , Método Duplo-Cego , Esquema de Medicação , Europa (Continente) , Feminino , Humanos , Impetigo/microbiologia , Impetigo/patologia , Lactente , Masculino , Pessoa de Meia-Idade , Quinolonas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Federação Russa , Índice de Gravidade de Doença , África do Sul , Resultado do Tratamento , Estados Unidos , Adulto Jovem
20.
PLoS Negl Trop Dis ; 12(7): e0006668, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30044780

RESUMO

BACKGROUND: Skin sores caused by Group A streptococcus (GAS) infection are a major public health problem in remote Aboriginal communities. Skin sores are often associated with scabies, which is evident in scabies intervention programs where a significant reduction of skin sores is seen after focusing solely on scabies control. Our study quantifies the strength of association between skin sores and scabies among Aboriginal children from the East Arnhem region in the Northern Territory. METHODS AND RESULTS: Pre-existing datasets from three published studies, which were conducted as part of the East Arnhem Healthy Skin Project (EAHSP), were analysed. Aboriginal children were followed from birth up to 4.5 years of age. Self-controlled case series design was used to determine the risks, within individuals, of developing skin sores when infected with scabies versus when there was no scabies infection. Participants were 11.9 times more likely to develop skin sores when infected with scabies compared with times when no scabies infection was evident (Incidence Rate Ratio (IRR) 11.9; 95% CI 10.3-13.7; p<0.001), and this was similar across the five Aboriginal communities. Children had lower risk of developing skin sores at age ≤1 year compared to at age >1 year (IRR 0.8; 95% CI 0.7-0.9). CONCLUSION: The association between scabies and skin sores is highly significant and indicates a causal relationship. The public health importance of scabies in northern Australia is underappreciated and a concerted approach is required to recognise and eliminate scabies as an important precursor of skin sores.


Assuntos
Impetigo/epidemiologia , Sarcoptes scabiei/fisiologia , Escabiose/complicações , Infecções Estreptocócicas/epidemiologia , Animais , Estudos de Casos e Controles , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Impetigo/etiologia , Impetigo/microbiologia , Lactente , Masculino , Northern Territory/epidemiologia , Escabiose/epidemiologia , Escabiose/patologia , Pele/microbiologia , Pele/patologia , Infecções Estreptocócicas/etiologia , Infecções Estreptocócicas/microbiologia , Streptococcus/fisiologia
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