Antimicrobial Resistance and Molecular Analysis of Staphylococcus aureus in Staphylococcal Scalded Skin Syndrome among Children in Korea.

BACKGROUND: Staphylococcal scalded skin syndrome (SSSS) is a skin disease characterized by blistering and desquamation caused by exfoliative toxins (ETs) of Staphylococcus aureus (S. aureus). Although many countries show predominance of methicillin-susceptible S. aureus (MSSA), cases of methicillin-resistant S. aureus (MRSA) have been reported. METHODS: Twenty-six children aged <15 years diagnosed with SSSS from January 2010 to December 2017 from three hospitals were included. S. aureus isolates from cases were analyzed for multilocus sequence types and ETs. Medical records were reviewed for clinical characteristics, treatment, and antimicrobial susceptibility patterns of S. aureus. RESULTS: Among the 26 cases, mean age was 2.3 years. According to skin manifestations patients were classified as generalized (n = 10, 38.5%), intermediate (n = 11, 42.3%), and abortive (n = 5, 19.2%). Among all cases, 96.2% (25/26) were due to MRSA and the macrolide-resistance rate was 92.3% (24/26). ST89 (n = 21, 80.8%) was the most prevalent clone, followed by single clones of ST1, ST5, ST72, ST121, and ST1507. The eta gene was detected in one (3.8%) isolate which was MSSA. The etb gene was detected in 14 (53.8%) isolates, all of which were ST89. Nafcillin or first-generation cephalosporin was most commonly prescribed (n=20, 76.9%). Vancomycin was administered in four patients (15.4%) and clindamycin in nine patients (34.6%). Among MRSA cases, there was no difference in duration of treatment when comparing the use of antimicrobials to which the causative bacteria were susceptible or non-susceptible (9.75 vs. 8.07 days, P > 0.05). CONCLUSION: S. aureus isolated from children with SSSS in Korea demonstrated a high prevalence of methicillin-resistant ST89 clones that harbored the etb gene. The predominance of MRSA suggests that antibiotics to which MRSA are susceptible may be considered for empirical antibiotic treatment in children with SSSS in Korea. Further studies on the role and effectiveness of systemic antibiotics in SSSS are warranted.

Increasing Numbers of Staphylococcal Scalded Skin Syndrome Cases Caused by ST121 in Houston, Texas.

BACKGROUND: The molecular epidemiology of Staphylococcus aureus strains causing staphylococcal scalded skin syndrome (SSSS) in the United States has not been described. We analyzed patient and S. aureus isolate characteristics associated with SSSS in children at Texas Children's Hospital. METHODS: Patients with SSSS were identified by ICD9/10 codes and available S. aureus isolates were identified from an ongoing S. aureus surveillance study. Medical records were reviewed for 58 patients with available S. aureus isolates. Isolate analyses included PCR for agr group, pvl (lukSF-PV), tst, eta and etb, pulsed-field gel electrophoresis, multi-locus sequence typing and antimicrobial susceptibilities. RESULTS: Cases of SSSS increased from 2.3/10,000 admissions in 2008 to 52.6/10,000 admissions in 2017 (P < 0.0001). The 58 study cases (57 methicillin-susceptible S. aureus, 1 MRSA) with isolates were from 2013 to 2017. The majority (88%) of isolates was of clonal cluster (CC) 121, agr group IV, pvl, tst and carried eta and/or etb and 26% were clindamycin resistant. Twelve ST121 isolates had high level resistance to mupirocin. Patients were treated with standard supportive care plus systemic antibiotics [clindamycin alone or in combination with another antibiotic (n = 44)]. One patient had a recurrent SSSS and one patient was transferred to a burn unit on day 3. CONCLUSIONS: Cases of SSSS are increasing at our hospital. Most S. aureus strains isolated were of one CC, CC121 and carried eta and etb. Supportive care plus clindamycin was effective treatment. We speculate that CC121 was recently introduced to our region and is responsible for the increasing numbers of SSSS cases observed at Texas Children's Hospital.

Antibiotic sensitivity and clinical outcomes in staphylococcal scalded skin syndrome.

Staphylococcal scalded skin syndrome causes widespread skin denudation primarily in infants < 1 year old. Selection of empiric therapy is complicated by rising rates of antibiotic resistance in community-acquired staphylococcal infections. Consistent with a previous study, this retrospective review found that SSSS-associated isolates were more likely to be clindamycin-resistant and less likely to be methicillin-resistant compared to overall staphylococcal infections. We favor cephalosporins and penicillinase-resistant penicillins (eg, oxacillin) for empiric management of SSSS, with consideration of adding MRSA coverage in communities with high MRSA prevalence or failure to improve following several days of treatment.

Emergence of staphylococcal scalded skin syndrome associated with a new toxinogenic, methicillin-susceptible Staphylococcus aureus clone.

A sharp increase in staphylococcal scalded skin syndrome (SSSS) cases has been recorded in our settings since 2015, with 31 cases having been documented during the period 2014-2017. The molecular investigation of strains from the above period showed the emergence of a methicillin-susceptible, mupirocin- and fusidic acid-resistant Staphyloccocus aureus clone that belongs to the ST121 complex and carries both epidermolysin (eta/etb) genes. We concluded that the SSSS caused by the newly emerged, highly virulent community-associated-methicillin sensitive S. aureus strains that have been encountered lately is more severe than impetigo. Physicians should be aware of the probability of SSSS epidemics from strains that are resistant to mupirocin and fusidic acid, which have been used irrationally and excessively.

Rapid containment of nosocomial transmission of a rare community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clone, responsible for the Staphylococcal Scalded Skin Syndrome (SSSS).

BACKGROUND: The aims of this study were to identify the source and the transmission pathway for a Staphylococcal Scalded Skin Syndrome (SSSS) outbreak in a maternity setting in Italy over 2 months, during 2014; to implement appropriate control measures in order to prevent the epidemic spread within the maternity ward; and to identify the Methicillin-Resistant Staphylococcus aureus (MRSA) epidemic clone. METHODS: Epidemiological and microbiological investigations, based on phenotyping and genotyping methods, were performed. All neonates involved in the outbreak underwent clinical and microbiological investigations to detect the cause of illness. Parents and healthcare workers were screened for Staphylococcus aureus to identify asymptomatic carriers. RESULTS: The SSSS outbreak was due to the cross-transmission of a rare clone of ST5-CA-MRSA-SCCmecV-spa type t311, exfoliative toxin A-producer, isolated from three neonates, one mother (from her nose and from dermatological lesions due to pre-existing hand eczema) and from a nurse (colonized in her nose by this microorganism). The epidemiological and microbiological investigation confirmed these as two potential carriers. CONCLUSIONS: A rapid containment of these infections was obtained only after implementation of robust swabbing of mothers and healthcare workers. The use of molecular methodologies for typing was able to identify all carriers and to trace the transmission.

[Staphylococcal Scalded Skin Syndrome in a Very Low Birth Weight Premature Infant]. / Staphylococcal Scalded Skin Syndrome bei einem sehr unreifen Frühgeborenen.

INTRODUCTION: Staphylococcal scalded skin syndrome (SSSS) was often endemic in the past but is nowadays rare. The hematogeneous spread of exfoliative toxins A (ETA) or B (ETB) produced by specific Staphylococcus aureus strains causes a scald-like eruption with disseminated bullous lesions. CASE REPORT: A perioral impetigo lesion occurred on day 14 of life in a preterm male infant (1,065 g, 30 weeks of gestational age). Empiric antibiotic therapy with cefotaxime and vancomycin was given for 6 days and led to complete resolution. A Staphylococcus aureus strain was isolated. After a symptom-free interval a relapse was noted on day 26 of life. Despite restarting the antibiotic therapy immediately the initial lesion expanded, and disseminated flaccid blisters on an erythematous base appeared within a few hours. On histological examination the cleavage was in the level of the granular layer. There was no mucosal involvement, and the Nikolsky I sign was positive. The antibiotic therapy was changed to a combination of cefotaxime, flucloxacillin and clindamycin which rapidly stopped progression of the exfoliation. Supportive therapy included adequate analgesia, parenteral rehydration, and application of local antiseptics. The preterm infant completely recovered. In the primary lesion an ETA-producing Staphylococcus aureus strain was isolated. Nasal microtrauma by a nasogastric tube was assumed to have caused the fulminant disease. At the same time, no other Staphylococcus aureus infections were seen in our Department of Neonatology. DISCUSSION: According to the literature, the incidence of SSSS is higher in premature infants and newborns than in older children. Possible causes include lower antibody levels against exfoliative toxins and renal immaturity. Rapid diagnosis and immediate appropriate antibiotic therapy are essential to prevent secondary infection, dehydration with electrolyte disturbance, death, and endemic spread.

Staphylococcal scalded skin syndrome in a premature newborn caused by methicillin-resistant Staphylococcus aureus: case report.

CONTEXT: Staphylococcal scalded skin syndrome is an exfoliative skin disease. Reports of this syndrome in newborns caused by methicillin-resistant Staphylococcus aureus are rare but, when present, rapid diagnosis and treatment is required in order to decrease morbidity and mortality. CASE REPORT: A premature newly born girl weighing 1,520 g, born with a gestational age of 29 weeks and 4 days, developed staphylococcal scalded skin syndrome on the fifth day of life. Cultures on blood samples collected on the first and fourth days were negative, but Pseudomonas aeruginosa and Enterococcus sp. (vancomycin-sensitive) developed in blood cultures performed on the day of death (seventh day), and Pseudomonas aeruginosa and Serratia marcescens were identified in cultures on nasopharyngeal, buttock and abdominal secretions. In addition to these two Gram-negative bacilli, methicillin-resistant Staphylococcus aureus was isolated in a culture on the umbilical stump (seventh day). The diagnosis of staphylococcal scalded skin syndrome was based on clinical criteria.

Staphylococcal scalded skin syndrome in a premature newborn caused by methicillin-resistant Staphylococcus aureus: case report / Síndrome da pele escaldada estafilocócica em um recém-nascido prematuro causada por Staphylococcus aureus meticilina-resistente: relato de caso

CONTEXT: Staphylococcal scalded skin syndrome is an exfoliative skin disease. Reports of this syndrome in newborns caused by methicillin-resistant Staphylococcus aureus are rare but, when present, rapid diagnosis and treatment is required in order to decrease morbidity and mortality. CASE REPORT: A premature newly born girl weighing 1,520 g, born with a gestational age of 29 weeks and 4 days, developed staphylococcal scalded skin syndrome on the fifth day of life. Cultures on blood samples collected on the first and fourth days were negative, but Pseudomonas aeruginosa and Enterococcus sp. (vancomycin-sensitive) developed in blood cultures performed on the day of death (seventh day), and Pseudomonas aeruginosa and Serratia marcescens were identified in cultures on nasopharyngeal, buttock and abdominal secretions. In addition to these two Gram-negative bacilli, methicillin-resistant Staphylococcus aureus was isolated in a culture on the umbilical stump (seventh day). The diagnosis of staphylococcal scalded skin syndrome was based on clinical criteria.

CONTEXTO: A síndrome da pele escaldada estafilocócica é uma doença esfoliativa de pele. São raros os relatos desta síndrome causada por Staphylococcus aureusresistente à meticilina em neonatos, mas, quando presentes, exigem diagnóstico e tratamento rápidos para diminuir a morbidade e mortalidade. RELATO DE CASO: Uma menina recém-nascida prematura, pesando 1.520 g ao nascimento, com idade gestacional de 29 semanas e 4 dias, desenvolveu síndrome da pele escaldada estafilocócica no quinto dia de vida. As culturas de sangue coletadas no primeiro e quarto dias foram negativas, mas houve desenvolvimento de Pseudomonas aeruginosa e Enterococcus sp. (vancomicina sensível) na hemocultura realizada no dia do óbito (sétimo dia) e Pseudomonas aeruginosa e Serratia marcescens foram identificadas nas culturas de secreção da nasofaringe, nádega e da secreção abdominal. Na cultura do coto umbilical (sétimo dia), além desses dois bacilos Gram-negativos, foi isolado o Staphylococcus aureus resistente à meticilina. O diagnóstico da síndrome da pele escaldada estafilocócica foi baseado em critério clínico.

Emergence of Staphylococcus aureus carrying multiple drug resistance genes on a plasmid encoding exfoliative toxin B.

We report the complete nucleotide sequence and analysis of pETBTY825, a Staphylococcus aureus TY825 plasmid encoding exfoliative toxin B (ETB). S. aureus TY825 is a clinical isolate obtained from an impetigo patient in 2002. The size of pETBTY825, 60.6 kbp, was unexpectedly larger than that of the archetype pETBTY4 (∼30 kbp). Genomic comparison of the plasmids shows that pETBTY825 has the archetype pETBTY4 as the backbone and has a single large extra DNA region of 22.4 kbp. The extra DNA region contains genes for resistance to aminoglycoside [aac(6')/aph(2″)], macrolide (msrA), and penicillin (blaZ). A plasmid deletion experiment indicated that these three resistance elements were functionally active. We retrospectively examined the resistance profile of the clinical ETB-producing S. aureus strains isolated in 1977 to 2007 using a MIC determination with gentamicin (GM), arbekacin (ABK), and erythromycin (EM) and by PCR analyses for aac(6')/aph(2″) and msrA using purified plasmid preparations. The ETB-producing S. aureus strains began to display high resistance to GM, which was parallel with the detection of aac(6')/aph(2″) and mecA, after 1990. Conversely, there was no significant change in the ABK MIC during the testing period, although it had a tendency to slightly increase. After 2001, isolates resistant to EM significantly increased; however, msrA was hardly detected in ETB-producing S. aureus strains, and only five isolates were positive for both aac(6')/aph(2″) and msrA. In this study, we report the emergence of a fusion plasmid carrying the toxin gene etb and drug resistance genes. Prevalence of the pETBTY825 carrier may further increase the clinical threat, since ETB-producing S. aureus is closely related to more severe impetigo or staphylococcal scalded-skin syndrome (SSSS), which requires a general antimicrobial treatment.

[Staphylococcal scalded skin syndrome associated with long-term catherter related infection in an adult].

Staphylococcal scalded skin syndrome (SSSS) is an extensive desquamative erythmatous condition caused by the Staphylococcus aureus exfoliative toxin. Although adult cases of SSSS are rare, the mortality rate is high. We report herein on a case of SSSS due to long-term catheter-related bloodstream infection caused by exfoliative toxin B, which produced methicillin-resistant Staphylococcus aureus. A 64-year-old man was admitted to our hospital with a high fever and generalized exfoliative dermatitis. He had an implanted port vascular access device in his left arm. The port was removed because it was thought to be the focus of infection. A Gram stain of the pus from the incision site revealed Gram positive coccus in clusters, and we administered intravenous vancomycin. MRSA was isolated from blood cultures and the pus, and histiology of a skin biopsy specimen from the exfoliation dermatitis showed epidermal detachment in the uppermost layer, which was consistent with SSSS. Although the patient developed infective endocarditis and septic embolisms, he eventually recovered. PCR of the MRSA was positive for exfoliative toxin B, and we finally diagnosed an adult case of SSSS due to exfoliative toxin B producing MRSA.

Skin findings of Staphylococcus aureus toxin-mediated infection in relation to toxin encoding genes.

BACKGROUND: Staphylococcal scalded skin syndrome and toxic shock syndrome are associated with exfoliatins and superantigens, respectively; and are easy to distinguish in their usual presentation. However, there is confusion about the mild forms of these 2 staphylococcal diseases. These mild forms are both designated as "staphylococcal scarlet fever" despite differences in their pathophysiology and clinical presentation. Our study aimed to distinguish between the clinical characteristics of the rash associated with exfoliatins and the rash associated with superantigens. METHODS: Patients were selected from the French National Reference Center for Staphylococci. We retrospectively compared the clinical characteristics of patients with a generalized rash during Staphylococcus aureus infection. Patients who met the criteria of staphylococcal scalded skin syndrome or toxic shock syndrome were excluded. The patients were classified into 2 groups depending on the presence of a gene coding for exfoliatin or for superantigenic toxin. RESULTS: We included 13 cases with exfoliatin and 9 with superantigens. The patients of the exfoliatin group were more likely to have facial involvement, fold involvement and a superficial focus of infection. In the second group, S. aureus was isolated from a deeper focus in 8 of 9 patients. CONCLUSION: Mild forms of S. aureus toxin-mediated infection affect the pediatric population. Examination made it possible to distinguish an exanthema associated with an exfoliatin from one associated with a superantigen. This early clinical distinction results in differences in management.

Epidemiological data of staphylococcal scalded skin syndrome in France from 1997 to 2007 and microbiological characteristics of Staphylococcus aureus associated strains.

Epidemiological data on staphylococcal scalded skin syndromes (SSSS), including bullous impetigo (BI) and generalized exfoliative syndrome (GES), are scarce. To better characterize SSSS and associated Staphylococcus aureus strains, we conducted a retrospective study of 349 cases collected in France between 1997 and 2007 by the National Reference Centre of Staphylococci. Our results showed a stationary evolution of SSSS cases, with a heterogeneous distribution of cases in France. Although notification was not exhaustive, we estimated an incidence of 0.56 cases/year/million inhabitants, in accordance with previous studies conducted in France and Europe, with a median age of 2 years old and sex ratios of 1. A seasonal effect was observed, with a higher GES/BI ratio in autumn compared with other seasons, which could be explained by the impact of viral co-infection. Genetic analysis of S. aureus strains showed that accessory gene regulator (agr) 4, exfoliative toxin A (eta) and B (etb) genes, staphylococcal and enterotoxin-like O (selo) gene and agr4 etb selo profiles were predominantly associated with GES, whereas agr2 eta and agr4 eta selo were more frequently observed with BI. Only one methicillin-resistant strain was found. Protein A (spa) typing identified two main genotypes: spa clonal complex (CC) 159/sequence-type (ST) 121 (75%) and spaCC346/ST15 (18%). spaCC159 was mainly associated with agr4 eta etb selo, agr4 eta selo and agr4 etb selo, and spaCC346 was mainly associated with agr2 eta, suggesting that French SSSS cases are caused by these two main lineages. However, in a multivariate analysis, only etb was independently associated with GES.

Staphylococcal scalded skin syndrome in an extremely low-birth-weight neonate: molecular characterization and rapid detection by multiplex and real-time PCR of methicillin-resistant Staphylococcus aureus.

BACKGROUND: Staphylococcal scalded skin syndrome (SSSS), caused by methicillin-resistant Staphylococcus aureus (MRSA) producing exfoliative toxin (ET), is a life-threatening infection for neonates in neonatal intensive care units (NICUs). SSSS in extremely low-birth-weight (ELBW) neonates is rare. A new class of MRSA (community-acquired MRSA, CA-MRSA) has been emerging in the community. The aim of this study was to characterize MRSA from an ELBW neonate with SSSS, and to develop rapid detection methods for SSSS-associated and emerging pediatric MRSA. METHODS: An ELBW infant in the NICU developed SSSS on day 16 after birth. Isolated MRSA was genetically characterized and compared with CA-MRSA from bullous impetigo (biCA-MRSA), which is positive for the ET and collagen-adhesin (CNA) genes in many cases, and the Panton-Valentine leucocidin (PVL) gene rarely. Specific primers and probes for five virulence genes (for ETA, ETB, ETD, PVL, CNA) were designed for multiplex polymerase chain reaction (PCR) and real-time PCR. RESULTS: MRSA strain H5 from SSSS exhibited the genotype (ST91, spa416[t375], agr3, SCCmecIVa, CoaI), and possessed the ETB and CNA genes, similar to ST91 biCA-MRSA (albeit with a divergence). Multiplex PCR detected the ETB and CNA genes of strain H5, and real-time PCR detected strain H5 at as low as 10(2) CFU/mL. The assays were 100% specific and 100% sensitive, for the five virulence genes. CONCLUSION: ETB-positive ST91 MRSA, which was very similar to ST91 biCA-MRSA, was isolated from an ELBW infant with SSSS. The multiplex and real-time PCR assays specifically or quantitatively detected SSSS-associated and emerging pediatric MRSA.

Neonatal staphylococcal scalded skin syndrome: clinical and outbreak containment review.

Staphylococcal scalded skin syndrome (SSSS) is a toxin-mediated exfoliating skin condition predominated by desquamation and blistering. Neonatal outbreaks have already been reported; however, our outbreak highlights the potential for SSSS following neonatal health promotion measures such as intra-muscular vitamin K administration and metabolic screening (heel prick) as well as effective case containment measures and the value of staff screening. Between February and June 2007, five confirmed cases of neonatal SSSS were identified in full-term neonates born in an Irish regional maternity hospital. All infants were treated successfully. Analysis of contact and environmental screening was undertaken, including family members and healthcare workers. Molecular typing on isolates was carried out. An outbreak control team (OCT) was assembled and took successful prospective steps to prevent further cases. All five Staphylococcus aureus isolates tested positive for exfoliative toxin A, of which two distinct strains were identified on pulsed-field gel electrophoresis analysis. Two cases followed staphylococcal inoculation during preventive measures such as intra-muscular vitamin K administration and metabolic screening (heel prick). None of the neonatal isolates were methicillin resistant. Of 259 hospital staff (70% of staff) screened, 30% were colonised with S. aureus, and 6% were positive for MRSA carriage. This is the first reported outbreak of neonatal SSSS in Ireland. Effective case containment measures and clinical value of OCT is demonstrated. Results of staff screening underlines the need for vigilance and compliance in hand disinfection strategies in maternity hospitals especially during neonatal screening and preventive procedures.

Staphylococcal scalded skin syndrome: loss of desmoglein 1 in patient skin.

Staphylococcal scalded skin syndrome (SSSS) is a blistering disease of the skin caused by an infection with certain strains of Staphylococcus aureus. In vitro studies have suggested that exfoliative toxins secreted by these bacteria cleave the desmosomal adhesion molecule desmoglein 1 leading to loss of cell-cell contact in the superficial epidermis. In this study we investigated the fate of desmoglein 1 in biopsies of patients with SSSS to see whether the ectodomain of desmoglein 1 is cleaved. Our data largely confirm previous in vitro data. The different biopsies demonstrated the loss of the ectodomain of desmoglein 1 to different degrees. The endodomain of desmoglein 1 meanwhile remained present. Most remarkably, in one of our patients, the immunofluorescent analysis demonstrated that not desmoglein1 but desmocollin 1, another desmosomal cadherin, became affected. This raises the question if other toxins and/or other bacteria than Staphylococcus aureus might also induce SSSS.