金黄色葡萄球菌感染性皮肤病的外用抗生素选择

常见由金黄色葡萄球菌引起的感染性皮肤病有脓疱疮、毛囊炎、疖、痈和葡萄球菌烫伤样皮肤综合征等。目前临床上常用的外用抗金葡菌的药物主要有莫匹罗星、夫西地酸和喹诺酮类抗生素。其他如庆大霉素、新霉素、金霉素和复方多粘菌素B等也是可供选择的外用药。鉴于金葡菌对多种抗生素的耐药性增加,应进行流行病学监测,根据耐药结果调整经验治疗。     

脓疱疮的病原菌分离及耐药性分析

目的观察脓疱疮的病原菌分布，监测耐药菌尤其是耐甲氧西林金黄色葡萄球菌的流行情况，为临床选择合理而有效的治疗方案提供依据。方法对 246例脓疱疮患者皮损进行病原菌分离，并对分离出的 212株金黄色葡萄球菌 (简称金葡菌 )进行 15种抗生素的琼脂稀释法药敏试验。结果从 246例脓疱疮患者皮损分离出病原菌 233株，单纯金葡菌占 87.0％；单纯 A组β－溶血性链球菌占 1.6％；金葡菌与 A组β－溶血性链球菌混合感染占 2.0％；表皮葡萄球菌占 4.1％。对 212株金葡菌进行的药敏试验结果显示，金葡菌对青霉素 100％耐药，对红霉素为 87.7％，对克林霉素为 75.5％，对四环素、氯霉素、优力欣、苯唑西林、环丙沙星耐药率依次为 63.2％、 54.2％、 44.8％、 30.2％和 12.8％，对头孢噻肟、夫西地酸、庆大霉素均为 0.9％耐药，对头孢唑啉、头孢呋辛、莫匹罗星、万古霉素均未发现耐药菌。从 212株金葡菌分离出 64株耐甲氧西林金葡菌，未发现耐万古霉素菌株。结论青霉素、红霉素、克林霉素、四环素、氯霉素和优力欣等种类的药物在本地区已不适于治疗金葡菌感染的脓疱疮。莫匹罗星、夫西地酸和头孢菌素可以作为治疗脓疱疮的局部或全身用药。     

夫西地酸乳膏治疗儿童脓疱疮临床观察

脓疱疮系葡萄球菌等引起的一种具有传染性的浅表皮肤感染性疾病,常见于2～5岁的儿童.绝大多数脓疱疮患儿在门诊就诊,及时获取细菌培养及药敏结果相对困难,医生凭临床经验选用抗生素.因此,选择合适的外用抗生素治疗儿童脓疱疮很重要.临床报道夫西地酸乳膏治疗脓疱疮效果显著[1-3].为了进一步证实夫西地酸乳膏治疗儿童脓疱疮的疗效和安全性,笔者应用夫西地酸乳膏治疗儿童脓疱疮60例,并与红霉素软膏治疗作对照,取得了较好的效果,现报告如下.     

2%夫西地酸乳膏治疗细菌性皮肤病疗效和安全性评价

夫西地酸（fusidic acid）是1962年丹麦利奥公司从梭链孢酸脂球（fusidium coccineum）真菌发酵液中提取的一种类甾体结构的抗生素。其抗菌机制是通过抑制核糖体的易位来干扰延长因子G，从而阻止细菌蛋白的合成。夫西地酸对葡萄球菌、链球菌、痤疮丙酸杆菌和短小棒状杆菌高度敏感。2％夫西地酸乳膏（商品名：立思丁）能够很好地渗透进感染灶内部，临床主要用来治疗毛囊炎、脓疱疮、疖、痈、甲沟炎、创伤感染、寻常痤疮等四。本研究采用多中心、随机、平行对照的临床试验，评价2％夫西地酸乳膏治疗无并发症细菌性皮肤病的疗效和安全性，并以2％莫匹罗星软膏（商品名：百多邦）进行对照。     

北京地区儿童皮肤感染金黄色葡萄球菌的耐药研究

目的 分析儿童皮肤感染金黄色葡萄球菌的耐药现状及社区获得性耐甲氧西林金黄色葡萄球菌的流行情况。方法 对600例感染性皮肤病患儿皮损分泌物进行细菌培养。应用琼脂稀释法检测抗生素及环丙沙星对培养出的金黄色葡萄球菌的最小抑菌浓度。结果 600例患儿皮损共培养出金黄色葡萄球菌451株，对13种抗生素及环丙沙星的药敏试验结果显示，对青霉素耐药率为93.8%，对红霉素耐药率为87.6%，对克林霉素为71.6%，对四环素、氯霉素、庆大霉素和环丙沙星的耐药率依次为37.3%，13.3%，6.4%和2.2%，对苯唑西林、头孢唑啉、头孢呋辛和莫匹罗星耐药率分别为1.6%，0.4%，0.2%和0.2%，未发现头孢曲松、万古霉素和夫西地酸耐药菌株。结论 儿童社区获得性耐甲氧西林金黄色葡萄球菌分离率为1.6%。治疗社区来源的皮肤金黄色葡萄球菌感染性皮肤病，全身治疗首选耐青霉素酶的半合成青霉素和头孢菌素，外用治疗可选择莫匹罗星或夫西地酸。     

夫西地酸乳膏（奥络）临床应用有奖征文通知北大核心CSCD

夫西地酸乳膏（商品名奥络）是香港澳美制药厂生产的新型外用抗生素,具有独特的四环三萜类甾体结构,有优异的类甾体抗炎活性表现,其抗菌作用靶点独特稳定,不易耐药且不易产生交叉耐药;主要治疗痤疮、湿疹、手术创面预防感染及各类原发和合并皮损感染者。为更好地服务于患者,促进皮肤科事业的发展,香港澳美制药厂有限公司与《中华皮肤科杂志》编辑部联合举办“夫西地酸乳膏（奥络）临床应用有奖征文”活动。征文范围：①奥络有效治疗痤疮（单独用药或联合用药）;②奥络单独用药治疗初期湿疹;③夫西地酸抗炎活性等的临床研究、治疗经验及基础研究等。上述应征稿件均需设对照组。     

金黄色葡萄球菌感染性皮肤病的外用抗生素选择1姬粉芝

目的 总结金黄色葡萄球菌感染性皮肤病的外用抗生素选择。方法 采用简单随机抽样法将我院2016年10月~2017年10月收治的60例金黄色葡萄球菌感染性皮肤病患儿分为莫匹罗星组、夫西地酸组以及环丙沙星组各20例,对三组临床疗效进行比较。结果 三组体温恢复时间、红斑消退时间、触痛消退时间、痊愈时间、不良反应发生率差异无统计学意义(P0.05)。结论 在金黄色葡萄球菌感染性皮肤病治疗中莫匹罗星、夫西地酸、环丙沙星均可取得理想的疗效,临床可自由选用。     

金黄色葡萄球菌感染性皮肤病的外用抗生素选择

目的总结金黄色葡萄球菌感染性皮肤病的外用抗生素选择。方法采用简单随机抽样法将我院2016年10月~2017年10月收治的60例金黄色葡萄球菌感染性皮肤病患儿分为莫匹罗星组、夫西地酸组以及环丙沙星组各20例,对三组临床疗效进行比较。结果三组体温恢复时间、红斑消退时间、触痛消退时间、痊愈时间、不良反应发生率差异无统计学意义(P0.05)。结论在金黄色葡萄球菌感染性皮肤病治疗中莫匹罗星、夫西地酸、环丙沙星均可取得理想的疗效,临床可自由选用。     

99例复杂皮肤软组织感染的病原学分析

目的 分析复杂皮肤软组织感染的病原菌及对抗生素的敏感性。方法 回顾性分析99例复杂皮肤软组织感染住院患者的临床资料和病原学检验结果。结果 复杂皮肤软组织感染共99例,共检出99株病原菌,其中革兰阳性菌51株,葡萄球菌是主要致病菌,该菌对红霉素、青霉素G、氯洁霉素、苯唑西林、左氧氟沙星有较高的耐药率,其中红霉素的耐药率达95.45%、青霉素G 72.73%;对替考拉宁、万古霉素、利拉唑胺、夫西地酸、莫西沙星敏感性较高;葡萄球菌中社区获得性感染对复方磺胺甲噁唑、四环素、环丙沙星的敏感性高于医院感染（P < 0.05）;发现耐甲氧西林金黄色葡萄球菌11株。革兰阴性菌48株,铜绿假单胞菌、肺炎克雷伯菌、大肠埃希菌、鲍曼不动杆菌等为主要的致病菌;革兰阴性菌对左氧氟沙星、复方磺胺甲噁唑、庆大霉素有较高的耐药性,医院感染尤为突出;对碳青霉烯类、妥布霉素、哌拉西林、他唑巴坦敏感性较好。结论 复杂皮肤软组织感染的病原菌种类繁多,耐药性较高,应在药物敏感试验指导下合理用药。     

葡萄球菌烫伤样皮肤综合征208例临床分析

目的回顾分析208例葡萄球菌烫伤样皮肤综合征患儿的临床资料,对部分病原菌进行表皮剥脱毒素及药敏检测,了解本地区致病菌分泌表皮剥脱毒素血清型别及药敏情况。方法记录所有病例的临床资料,并对其中30株金黄色葡萄球菌(以下简称SA)应用反向乳胶凝集法检测表皮剥脱毒素,对51株SA应用琼脂稀释法进行了14种抗生素的药敏试验。结果 30株SA中,21株表皮剥脱毒素A,B均阳性,8株单纯表皮剥脱毒素B阳性。51株SA药敏青霉素耐药率为96.08%,对红霉素耐药率为82.35%。对苯唑青霉素、头孢类抗生素、莫匹罗星、万古霉素和夫西地酸均未发现耐药菌。结论引起本病的SA以表皮剥脱毒素A,B均阳性的菌株为主。青霉素和红霉素耐药率较高,不适合治疗本病。头孢菌素、万古霉素和夫西地酸可作为可选择的抗生素。     

湿疹和特应性皮炎皮损处细菌定植情况及药物联合治疗的分析

目的 探讨湿疹和特应性皮炎(AD)皮损处金黄色葡萄球菌(金葡菌)及其他细菌的定植情况,评价抗菌药物与糖皮质激素联合用药的疗效。方法 采用多中心、随机、双盲试验,在筛选日及治疗后第7、14和28天对皮损评分,并在皮损和非皮损处分离细菌。试验组外用抗菌药物和糖皮质激素,对照组外用基质和糖皮质激素。结果 共入选患者327例,湿疹208例,AD119例。湿疹皮损处细菌的阳性率为70.19%,金葡菌占47.26%;非皮损部位细菌阳性率为32.69%,金葡菌占27.94%。AD皮损处细菌阳性率为74.79%,金葡菌占79.78%;非皮损部位细菌阳性率为34.45%,金葡菌占80.49%。湿疹和AD皮损部位金葡菌的定植量均高于非皮损部位(P<0.01,P<0.05),细菌的定植量与皮损的严重程度呈正相关。两组患者治疗后总体疗效无明显差异(P>0.05),但湿疹临床症状评分指数>8分者及AD评分指数>7分者,在治疗的第7天,试验组与对照组的症状评分指数改善率存在显著差异(P<0.05),在治疗的第14天和第28天,两组差异均无显著性(P>0.05)。结论 湿疹和AD患者皮损部位细菌的检出率和金葡菌的带菌率均明显增高,说明金葡菌与湿疹皮炎的关系密切,早期联用抗菌药物可提高疗效。     

Efficacy and safety of retapamulin ointment as treatment of impetigo: randomized double-blind multicentre placebo-controlled trial

BACKGROUND: Impetigo is a common skin infection, primarily caused by Staphylococcus aureus and mainly occurring in children. It is usually treated topically with antibiotics to achieve a quick cure and prevent spread of the infection. Worldwide, resistance rates of S. aureus against commonly used antibiotics are rising. Retapamulin belongs to a newly developed class of antibiotics for the treatment of uncomplicated skin infections. OBJECTIVES: Our aim was to compare the efficacy and safety of topical application of retapamulin ointment with topical placebo ointment in the treatment of primary impetigo. METHODS: In a randomized, double-blind, multicentre study, patients received either topical retapamulin ointment 1% twice daily for 5 days or topical placebo. Patients were enrolled into the study for 14 days and attended the clinic for three visits during which clinical and laboratory evaluations were performed. RESULTS: Two hundred and thirteen patients were randomized, with 139 evaluable patients in the retapamulin group and 71 in the placebo group. Based on the primary efficacy endpoint of clinical response after 7 days (intention to treat), retapamulin ointment was superior to placebo (success rate 85.6% vs. 52.1%; P<0.0001). Similar results were found in the per protocol analysis and in the subgroup of patients who had a pathogen isolated at baseline. The most common adverse effect, pruritus at the application site, was reported by 6% and 1% of patients in the retapamulin and placebo groups, respectively. CONCLUSIONS: This study shows that topical retapamulin is effective and safe in the treatment of primary impetigo, offering a new treatment option.     

Confocal laser scanning microscopic observation of glycocalyx production by Staphylococcus aureus in mouse skin: does S. aureus generally produce a biofilm on damaged skin?

BACKGROUND: Bacteria that adhere to damaged tissues encase themselves in a hydrated matrix of polysaccharides, forming a slimy layer known as a biofilm. This is the first report of detection of glycocalyx production by Staphylococcus aureus using confocal laser scanning microscopy (CLSM) on damaged skin tissues. OBJECTIVES: To analyse glycocalyx production by S. aureus cells on damaged skin tissues and the influence of polymorphonuclear leucocytes (PMNs) and various antimicrobial agents on its production using CLSM in cyclophosphamide (Cy)-treated (neutropenic) or non-Cy-treated (normal) mice. METHODS: S. aureus cells were inoculated on damaged skin tissues in neutropenic or normal mice with or without topical application of antimicrobial agents. S. aureus cells were stained with safranine, and positive staining with fluorescein isothiocyanate-conjugated concanavalin A was considered to indicate the presence of glycocalyx. RESULTS: All S. aureus cells tested on damaged skin tissues formed microcolonies encircled by glycocalyx. The colony counts of S. aureus cells on croton oil dermatitis in normal mice treated with 2% fusidic acid ointment were about 100 times lower than those in neutropenic mice (control). CONCLUSIONS: As S. aureus cells can generally produce a biofilm on damaged skin tissues, antimicrobial agents may not eradicate S. aureus cells without the help of PMNs. S. aureus glycocalyx may play a crucial role in colonization and adherence to damaged skin tissues.     

Noninvasive in vivo imaging to evaluate immune responses and antimicrobial therapy against Staphylococcus aureus and USA300 MRSA skin infections

Staphylococcus aureus skin infections represent a significant public health threat because of the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). As greater understanding of protective immune responses and more effective antimicrobial therapies are needed, a S. aureus skin wound infection model was developed in which full-thickness scalpel cuts on the backs of mice were infected with a bioluminescent S. aureus (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo imaging was used to noninvasively monitor the bacterial burden. In addition, the infection-induced inflammatory response was quantified using in vivo fluorescence imaging of LysEGFP mice. Using this model, we found that both IL-1α and IL-1β contributed to host defense during a wound infection, whereas IL-1β was more critical during an intradermal S. aureus infection. Furthermore, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, mupirocin ointment had minimal clinical activity against this USA300 strain, resulting in only a 2-fold reduction in bacterial burden. Taken together, this S. aureus wound infection model provides a valuable preclinical screening method to investigate cutaneous immune responses and the efficacy of topical antimicrobial therapies.     

Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial

BACKGROUND: Staphylococcus aureus has a peculiar ability to colonize the skin of patients with eczema and atopic dermatitis (AD), and is consistently found in eczematous skin lesions in these patients. A correlation between the severity of the eczema and colonization with S. aureus has been demonstrated, and it has been determined that bacterial colonization is an important factor aggravating skin lesions. Patients colonized with S. aureus have been treated with antibiotics in several open and double-blind placebo-controlled studies, with conflicting results. OBJECTIVES: To investigate the colonizing features of S. aureus in the lesional and nonlesional skin of patients with eczema and AD in China and to compare the therapeutic effect of mupirocin plus hydrocortisone butyrate with vehicle ointment plus hydrocortisone butyrate. METHODS: A multicentre, double-blind randomized trial was conducted. Eczema Area and Severity Index (EASI) scores were evaluated before the start of the trial and on the 7th, 14th and 28th day of treatment. Swabs for bacterial isolation were taken from lesional skin before the start of the trial and on the 7th, 14th and 28th day of treatment, and from nonlesional skin only before the start of the trial. A combination topical therapy with mupirocin plus hydrocortisone butyrate ointment was used in the experimental group, with vehicle ointment plus hydrocortisone butyrate ointment as a control. RESULTS: Of 327 patients enrolled in the study, 208 had eczema and 119 had AD. Bacteria were isolated from 70.2% of lesional and 32.7% of nonlesional skin samples from patients with eczema, of which S. aureus accounted for 47.3% and 27.9%, respectively. Bacteria were isolated from 74.8% of lesional and 34.5% of nonlesional skin samples from patients with AD, of which S. aureus accounted for 79.8% and 80.5%, respectively. The colonization density of S. aureus was markedly higher in lesional than in nonlesional skin, both in patients with eczema and with AD (P < 0.01, P < 0.05), and was positively correlated with lesion severity. Considering the EASI scores before and after treatment and the final effective rate, good therapeutic effects were obtained in both the combination experimental groups and the control groups (P < 0.01), and there were no differences in the global therapeutic effect between the two groups in patients with eczema and with AD (P > 0.05). However, in patients with eczema with a clinical score of > 8 or in patients with AD with a clinical score of > 7, the therapeutic effect in the experimental groups was superior to that in the control groups (P < 0.05) on the 7th day of treatment. There were no differences between the two groups on the 14th and 28th days of treatment (P > 0.05). Following the improvement of symptoms and signs of eczema and AD, the positive rates of bacteria and S. aureus were reduced on the 7th day of treatment. CONCLUSIONS: This study confirmed that lesional skin of patients with eczema and AD was more frequently colonized with S. aureus than was nonlesional skin. The more severe the eczema, the higher the colonization rate of S. aureus, and S. aureus was also more often present in lesional and nonlesional skin in patients with AD than in those with eczema. Staphylococcus aureus infection is related to the pathogenesis of eczema and AD. An antibiotic-corticosteroid combination and corticosteroid alone both gave good therapeutic effect in eczema and in AD, and both reduced colonization by S. aureus. Early combined topical therapy is beneficial to patients with moderate to severe eczema and AD, and it is unnecessary to use antibiotics at later stages of disease or in mild eczema or AD.     

Impetigo: An Overview

Abstract: This article reviews in detail the pathogenesis, clinical characteristics and management of impetigo in children. Impetigo is the most common bacterial skin infection of children. Most cases of nonbullous impetigo and all cases of bullous impetigo are caused by Staphylocaccus aureus . The remainder of cases of nonbullous impetigo are due to group A beta hemolytic streptococci (GABHS). GABHS colonize the skin directly by binding to sites on f ibronectin that are exposed by trauma. In contrast, S. aureus colonizes the nasal epithelium first; from this reservoir, colonization of the skin occurs. Patients with recurrent impetigo should be evaluated for carriage of S. aureus . Superficial, localized impetigo may be treated successfully in more than 90% of cases with topical application of mupirocin ointment. Impetigo that is widespread or involves deeper tissues should be treated with a beta-lactamase-resistant oral antibiotic. The choice of antibiotics is affected by the local prevalence of resistance to erythromycin among strains of S. aureus , antibiotic cost and availability, and issues of compliance.     

Spotlight on Retapamulin in Impetigo and Other Uncomplicated Superficial Skin Infections†

Topical retapamulin (Altabax, Altargo) is the first pleuromutilin antibacterial approved for the treatment of uncomplicated superficial skin infections caused by Staphylococcus aureus (excluding methicillin-resistant S. aureus [MRSA]) and Streptococcus pyogenes in patients aged > or = 9 months. In the EU, retapamulin is indicated for use in patients with impetigo or with infected small lacerations, abrasions, or sutured wounds (without abscesses); in the US, it is indicated for use in patients with impetigo. Retapamulin has a novel site of action on bacterial ribosomes. In clinical trials in patients with impetigo, topical retapamulin 1% ointment twice daily for 5 days (the approved regimen) was superior to placebo; treatment with retapamulin was noninferior to that with topical fusidic acid. In patients with secondarily infected traumatic lesions, treatment with retapamulin was noninferior to that with oral cephalexin, although the efficacy of retapamulin was reduced in patients with MRSA infections or superficial abscesses. Retapamulin was well tolerated in both pediatric and adult patients, and the majority of adverse events were of mild to moderate severity. Thus, the introduction of topical retapamulin 1% ointment extends the treatment options available in the management of impetigo and uncomplicated secondarily infected traumatic lesions.     

Effects of a ceramide‐containing water‐in‐oil ointment on skin barrier function and allergen penetration in an IL‐31 treated 3D model of the disrupted skin barrier

Atopic dermatitis (AD) is a chronically relapsing, pruritic inflammation of the skin with dryness and disturbed skin barrier function. Recently, we established that IL‐31 treatment of human 3D skin models resulted in a disrupted skin barrier phenotype resembling AD. In this model, we found that IL‐31 interferes with the differentiation of keratinocytes and inhibits the expression of terminal differentiation markers. In the present study, we investigated the effects of a ceramide‐containing water‐in‐oil skin care ointment on the physical skin barrier structure and function in disrupted skin barrier models, generated either by using primary normal human epidermal keratinocytes (NHEK) or HaCaT cells. We observed that the physical skin barrier of the models recovered after daily topical treatment with the ceramide‐containing ointment. Topical application of the ointment prevented downregulation of filaggrin and disorganization of other differentiation markers, such as keratin 10 and β4‐integrin, as demonstrated by immunohistological analysis. The expression of Ki67 was also upregulated in response to the ointment. Furthermore, functional studies revealed that local application of the ointment diminished the increased uptake of fluorescently labelled recombinant allergens of timothy grass (phl p1) in our model. In conclusion, our data revealed that topical application of a ceramide‐containing skin care ointment reduced IL‐31 induced impairments of the physical skin barrier and skin barrier function in an in vitro model of the disrupted skin barrier. This standardized model can be utilized in the future to monitor ex vivo effects of various topical therapies on skin morphology, physiology, and gene expression.     

Iatrogenic hypercalcemia due to vitamin D3 ointment (1,24(OH)2D3) combined with thiazide diuretics in a case of psoriasis

Tacalcitol is a synthetic vitamin D3 analogue developed for topical treatment of inflammatory skin diseases such as psoriasis. Hypercalcemia has not been previously reported during treatment with topical tacalcitol. We experienced a male patient with psoriasis and hypertension whose conditions were treated with tacalcitol ointment and thiazide, respectively, resulting in hypercalciuria and hypercalcemia. After initiation of topical vitamin D3 ointment (20 micro g/g of tacalcitol) 10 g/day for the skin lesions, both the serum level of calcium and urinary excretion of calcium increased gradually. On day 28 of the treatment, his serum calcium levels had reached 3.55 mmol/l, and his urinary calcium excretion had also increased from 0.008 g/day to 0.475 g/day. The tacalcitol treatment was terminated, seven days later, the serum calcium level had returned to the reference range without any specific treatment. The present case is the first report of hypercalcemia induced by vitamin D3 ointment and thiazide simultaneously.     

Tacrolimus ointment (Protopic) for atopic dermatitis

Tacrolimus ointment (Protopic, Fujisawa) is an effective agent in a class of topical immunomodulators. Its mechanism of action is based on calcineurin inhibition, which results in decreased T-cell activation and inflammatory cytokine release. Tacrolimus ointment is safe and effective for short- and long-term treatment of atopic dermatitis (AD) in pediatric and adult patients. The most common adverse events associated with its use are a transient burning sensation and pruritus at the site of application. Unlike topical corticosteroid agents, tacrolimus ointment does not cause a reduction in collagen synthesis or skin thickness. Because tacrolimus ointment does not cause skin atrophy, it may be safely used for months or years on all skin areas, including the face and intertriginous areas.