Local Epidemiology of Nosocomial Staphylococcus aureus Infection in a Nigerian University Teaching Hospital.

Population-based studies of Staphylococcus aureus contribute to understanding the epidemiology of S. aureus infection. We enrolled surgical inpatients admitted to an African tertiary-care hospital in order to prospectively analyze the nosocomial impact of S. aureus. Data collection included an active sampling of the anterior nares and infectious foci within 48 h after admission and subsequently when clinically indicated. All S. aureus isolates were spa and agr genotyped. Possession of Panton-Valentine leukocidin (PVL) and other toxin genes was determined. We analyzed antibiotic susceptibility profiles by VITEK 2 systems and verified methicillin-resistant S. aureus (MRSA) by mecA/C PCR. Among 325 patients, 15.4% carried methicillin-susceptible S. aureus (MSSA) at admission, while 3.7% carried MRSA. The incidence densities of nosocomial infections due to MSSA and MRSA were 35.4 and 6.2 infections per 10,000 patient-days, respectively. Among all 47 nosocomial infections, skin and soft-tissue (40.4%) and bones or joints' (25.5%) infections predominated. Six (12.7%) infection-related S. aureus isolates harbored PVL genes including two (4.2%) MRSA: overall, seventeen (36.2%) isolates carried pyrogenic toxin superantigens or other toxin genes. This study illustrates the considerable nosocomial impact of S. aureus in a Nigerian University hospital. Furthermore, they indicate a need for effective approaches to curtail nosocomial acquisition of multidrug-resistant S. aureus.

Three-Dimensional Structure Characterization and Inhibition Study of Exfoliative Toxin D From Staphylococcus aureus.

The Staphylococcus aureus exfoliative toxins (ETs) are the main toxins that produce staphylococcal scalded skin syndrome (SSSS), an abscess skin disorder. The victims of the disease are usually newborns and kids, as well as grown-up people. Five ETs namely, exfoliative toxins A, B, C, D, and E have been identified in S. aureus. The three-dimensional (3D) structure of exfoliative toxins A, B, C and E is known, while that of exfoliative toxin D (ETD) is still unknown. In this work, we have predicted the 3D structure of ETD using protein modeling techniques (software used for 3D structure modeling comprising the MODELLER 9v19 program, SWISS-Model, and I-TESSER). The validation of the build model was done using PROCHECK (Ramachandran plot), ERRAT2, and Verify 3D programs. The results from 3D modeling show that the build model was of good quality as indicated by a GMQE score of 0.88 and by 91.1% amino acid residues in the most favored region of the Ramachandran plot, the ERRAT2 quality factor of 90.1%, and a verify3D score of >0.2 for 99.59% of amino acid residues. The 3D structure analysis indicates that the overall structure of ETD is similar to the chymotrypsin-like serine protease fold. The structure is composed of 13 ß-strands and seven α-helices that fold into two well-defined six-strand ß-barrels whose axes are roughly perpendicular to each other. The active site residues include histidine-97, aspartic acid-147, and serine-221. This represents the first structure report of ETD. Structural comparison with the other ETs shows some differences, particularly in the loop region, which also change the overall surface charge of these toxins. This may convey variable substrate specificity to these toxins. The inhibition of these toxins by natural (2S albumin and flocculating proteins from Moringa oleifera seeds) and synthetic inhibitors (suramin) was also carried out in this study. The results from docking indicate that the inhibitors bind near the C-terminal domain which may restrict the movement of this domain and may halt the access of the substrate to the active site of this enzyme. Molecular dynamic simulation was performed to see the effect of inhibitor binding to the enzyme. This work will further elucidate the structure-function relationship of this enzyme. The inhibition of this enzyme will lead to a new treatment for SSSS.

An unusual outbreak in the Netherlands: community-onset impetigo caused by a meticillin-resistant Staphylococcus aureus with additional resistance to fusidic acid, June 2018 to January 2020.

In this retrospective observational study, we analysed a community outbreak of impetigo with meticillin-resistant Staphylococcus aureus (MRSA), with additional resistance to fusidic acid (first-line treatment). The outbreak occurred between June 2018 and January 2020 in the eastern part of the Netherlands with an epidemiological link to three cases from the north-western part. Forty nine impetigo cases and eight carrier cases were identified, including 47 children. All but one impetigo case had community-onset of symptoms. Pharmacy prescription data for topical mupirocin and fusidic acid and GP questionnaires suggested an underestimated outbreak size. The 57 outbreak isolates were identified by the Dutch MRSA surveillance as MLVA-type MT4627 and sequence type 121, previously reported only once in 2014. Next-generation sequencing revealed they contained a fusidic acid resistance gene, exfoliative toxin genes and an epidermal cell differentiation inhibitor gene. Whole-genome multilocus sequence typing revealed genetic clustering of all 19 sequenced isolates from the outbreak region and isolates from the three north-western cases. The allelic distances between these Dutch isolates and international isolates were high. This outbreak shows the appearance of community-onset MRSA strains with additional drug resistance and virulence factors in a country with a low prevalence of antimicrobial resistance.

Research progress in infection-associated virulence factors of Staphylococcus aureus / 中华临床感染病杂志

Staphylococcus aureus is an important pathogen of human infectious diseases, which can cause skin and soft tissue infections, endocarditis, necrotizing pneumonia, myelitis and other serious infectious diseases. With the use of antibiotics, Staphylococcus aureus is evolving to develop drug resistance; at the same time it produces a variety of virulence factors to attack the host. This article will review the recent advances of Staphylococcus aureus virulence factors associated with the three stages of infection and introduce the detection methods of virulence factors briefly.

Exudative Epidermitis in Combination with Staphylococcal Pyoderma in Suckling Piglets.

A case of generalized exudative epidermitis (EE) is described, which occurred in a very small piglet producing farm in Austria. The antimicrobial treatment prescribed by the herd veterinarian did not improve the clinical problem. Therefore, the University Clinic for Swine intervened in the case. Lab investigations were initiated in which Staphylococcus hyicus (SH) and Staphylococcus aureus (SA), both methicillin-resistant and susceptible strains, could be isolated from the skin of affected piglets. Poor hygiene and management practices were identified as predisposing factors on site. Adaptation of antimicrobial treatment according to results of the in vitro susceptibility testing and the implementation of proper hygiene measures resolved the clinical problem. Here, we describe a fatal coinfection of SH and SA in suckling piglets.

Emergence of a mupirocin-resistant, methicillin-susceptible Staphylococcus aureus clone associated with skin and soft tissue infections in Greece.

BACKGROUND: Staphylococcus aureus causes various infections, including skin and soft tissue infections (SSTIs). In this study, methicillin-susceptible S. aureus (MSSA) from SSTIs among patients in three tertiary-care hospitals in Greece were studied in terms of antimicrobial resistance, clonal distribution, toxin and adhesin genes carriage. RESULTS: During a five-year period (2014-2018), 6145 S. aureus were recovered from 13,244 patients with SSTIs and tested for antimicrobial susceptibility. MSSA were 4806 (78.21 %) including 1484 isolates with mupirocin minimum inhibitory concentration (MIC) > 64 mg/L (30.88 %). Two hundred and sixty representative mupirocin-resistant MSSA were analyzed for genes encoding Panton-Valentine leukocidin (PVL, lukS/lukF-PV), exfoliative toxins (eta, etb), adhesin FnbA (fnbA) and resistance genes mupA (high-level resistance to mupirocin), fusB (fusidic acid), aminoglycosides' modifying enzymes, ermA, ermC and msrA (macrolides/lincosamides) by PCRs. Strains were classified into clones by PFGE and MLST. All mupirocin-resistant MSSA were penicillin-resistant; 92.7 % expressed resistance to fusidic acid and 88.9 % to tobramycin. All 260 molecularly analyzed isolates were mupA-positive; all fusidic acid-resistant (241/260) carried fusB whereas, the tobramycin-resistant ones (230), ant(4')-Ia. The majority carried eta (93.85 %), etb (98.08 %) and fnbA (88.85 %). PFGE typing revealed a mostly unvarying population; 260 MSSA were grouped into three types. One major eta/etb-positive clone comprising of 258/260 strains (99.2 %), PFGE type 1, was classified as ST121, including nine strains co-carrying PVL. Another PVL-positive strain was identified as ST1, and one toxins-negative as ST21. CONCLUSIONS: A mupirocin-resistant MSSA clone, ST121, carrying resistance, exfoliative toxins and adhesin genes, was spread and predominated in SSTIs from patients in Greece during the five-year studied period.

Staphylococcus aureus Toxins and Their Molecular Activity in Infectious Diseases.

Staphylococcus aureus is a microorganism resident in the skin and nasal membranes with a dreadful pathogenic potential to cause a variety of community and hospital-acquired infections. The frequency of these infections is increasing and their treatment is becoming more difficult. The ability of S. aureus to form biofilms and the emergence of multidrug-resistant strains are the main reasons determining the challenge in dealing with these infections. S. aureus' infectious capacity and its success as a pathogen is related to the expression of virulence factors, among which the production of a wide variety of toxins is highlighted. For this reason, a better understanding of S. aureus toxins is needed to enable the development of new strategies to reduce their production and consequently improve therapeutic approaches. This review focuses on understanding the toxin-based pathogenesis of S. aureus and their role on infectious diseases.

Staphylococcal-scalded skin syndrome: evaluation, diagnosis, and management.

BACKGROUND: Staphylococcal-scalded skin syndrome (SSSS), also known as Ritter disease, is a potentially life-threatening disorder and a pediatric emergency. Early diagnosis and treatment is imperative to reduce the morbidity and mortality of this condition. The purpose of this article is to familiarize physicians with the evaluation, diagnosis, and treatment of SSSS. DATA SOURCES: A PubMed search was completed in Clinical Queries using the key terms "Staphylococcal scalded skin syndrome" and "Ritter disease". RESULTS: SSSS is caused by toxigenic strains of Staphylococcus aureus. Hydrolysis of the amino-terminal extracellular domain of desmoglein 1 by staphylococcal exfoliative toxins results in disruption of keratinocytes adhesion and cleavage within the stratum granulosum which leads to bulla formation. The diagnosis is mainly clinical, based on the findings of tender erythroderma, bullae, and desquamation with a scalded appearance especially in friction zones, periorificial scabs/crusting, positive Nikolsky sign, and absence of mucosal involvement. Prompt empiric treatment with intravenous anti-staphylococcal antibiotic such as nafcillin, oxacillin, or flucloxacillin is essential until cultures are available to guide therapy. Clarithromycin or cefuroxime may be used should the patient have penicillin allergy. If the patient is not improving, critically ill, or in communities where the prevalence of methicillin-resistant S. aureus is high, vancomycin should be used. CONCLUSION: A high index of suspicion is essential for an accurate diagnosis to be made and treatment promptly initiated.

Virulence Factors of Staphylococcus aureus Isolates in an Iranian Referral Children's Hospital.

OBJECTIVES: The clinical importance of Staphylococcus aureus (S. aureus) is attributed to notable virulence factors, surface proteins, toxins, and enzymes as well as the rapid development of drug resistance. The aim of this study was to compare the occurrence of virulence factors produced by S. aureus strains isolated from children in an Iranian referral children's hospital. METHODS: The presence of genes encoding for the enterotoxins A (sea), B (seb), C (sec), D (sed), TSST-1 (tsst), exfoliative toxin A (eta), and exfoliative toxin B (etb) were detected by Multiplex polymerase chain reaction (PCR) using specific primers. In addition, the standardized Kirby-Bauer disc-diffusion method was performed on Mueller-Hinton agar. RESULTS: In total, 133 S. aureus isolates were obtained from different patients. Of these S. aureus isolates, 64 (48%) were methicillin-resistant S. aureus (MRSA), and all of these tested positive for the mecA gene. Regarding the classical enterotoxin genes, sea gene (40.6%) was the most prevalent followed by seb (19.6%), tsst (12.8%), eta (11.3%), etb (9%), sed (4.5%), and sec (3%). Among methicillin-susceptible S. aureus (MSSA) isolates, seb and tsst were the more prevalent toxins in comparison with MRSA isolates (p < 0.05), while the frequency of sea, sed, eta, and etb genes were higher among MRSA isolates (p > 0.05). CONCLUSION: In our study enterotoxin A was produced by 40.6% of the isolates (48% from MRSA and 33% from MSSA isolates) which was higher than in previous reports. According to our results, strict hygiene and preventative measures during food processing are highly recommended.

Staphylococcus aureus toxins--their functions and genetics.

The outcome of encounters between Staphylococcus (S.) aureus and its human host ranges from life-threatening infection through allergic reactions to symptom-free colonization. The pan-genome of this bacterial species encodes numerous toxins, known or strongly suspected to cause specific diseases or symptoms. Three toxin families are in the focus of this review, namely (i) pore-forming toxins, (ii) exfoliative toxins and (iii) superantigens. The majority of toxin-encoding genes are located on mobile genetic elements (MGEs), resulting in a pronounced heterogeneity in the endowment with toxin genes of individual S. aureus strains. Recent population genomic analysis have provided a framework for an improved understanding of the temporal and spatial scales of the motility of MGEs and their associated toxin genes. The distribution of toxin genes among clonal lineages within the species S. aureus is not random, and phylogenetic (sub-)lineages within clonal complexes feature characteristic toxin signatures. When studying pathogenesis, this lineage association, which is caused by the clonal nature of S. aureus makes it difficult to discriminate effects of specific toxins from contributions of the genetic background and/or other associated genetic factors.

High Prevalence of Exfoliative Toxins Among Carrier Isolates of Staphylococcus aureus from Healthy Individuals from Various Communities in Chennai, South India.

Staphylococcus aureus causes infections both in community and hospital settings, nasal carriage is the important source of these infections. A total of 103 carrier isolates of S. aureus from 352 asymptomatic individuals were screened for methicillin-resistant S. aureus (MRSA) and exfoliative toxins (A, B and D) by two sets of multiplex PCRs. The overall nasal carriage of MRSA was found to be 13/352 (3.7 %), of which 4 were found to be positive for Panton valentine leucocidin (PVL). Twelve (11.65 %) strains were found to carry exfoliative toxins and belonged to one of the following spa types t159, t209 and t1515. High prevalence of exfoliative toxins, pvl and MRSA pose a major threat to public health, since the isolates were from the healthy in various community settings.

Staphylococcal scalded skin syndrome due to burn wound infection.

UNLABELLED: Introduction. The staphylococcal scalded skin syndrome is an acute exfoliation of the skin caused by exfoliative toxins A and B. Although Staphylococcus aureus is a common cause of burn wound infection, SSSS following burn wound infection is rare. Method. A retrospective review of all SSSS cases admitted to a regional burns service between January 2008 and January 2012 was undertaken. Results. Two cases of SSSS were reported during this time period as occurring following burns injury. The first case was a 17-month-old boy who had been hospitalized for a conservative treatment of 6% total body surface area (TBSA) mixed depth scald burns. On day four he developed exfoliation of 85% TBSA. The second case was a ten-month-old boy who sustained a 1% TBSA scald burn and was managed conservatively in the community by his general practitioner. On day five, he developed exfoliation of 80% TBSA. Staphylococcus aureus was isolated from the burn wounds in both cases. CONCLUSION: These two cases show that it is vital for burns surgeons and intensive care specialists to be aware of the possibility of SSSS occurring in patients with burn injuries with its potential devastating effects.

Introduction. Le syndrome de la peau ébouillantée staphylococcique (sigle anglais conventionnel, SSSS) est une exfoliation aiguë de la peau causée par des toxines A et B. Bien que le Staphylococcus aureus soit une cause fréquente d'infection des brûlures, la SSSS suite à une infection brûlure est rare. Méthode. Les Auteurs ont effectué une revue rétrospective de tous les cas de patients atteints de SSSS hospitalises admis dans un service régional des brûlures entre janvier 2008 et janvier 2012. Résultats. Deux cas de SSSS ont été signalés au cours de cette période qui se sont produits suite à une brûlure. Le premier cas était un garçon de 17 mois qui avait été hospitalisé pour un traitement conservateur pour ébouillantement dans 6% de la surface corporelle totale de profondeur variable. Le quatrième jour, il a développé une exfoliation dans 85% de la surface corporelle. Quant au deuxième cas, il s'agissait d'un garçon de dix mois qui a subi une brûlure de 1% de la surface corporelle et qui a été traité en manière conservatrice dans la communauté par son médecin généraliste. Le cinquième jour, il a développé une exfoliation dans 80% de la surface corporelle. Le Staphylococcus aureus a été isolé qui provenait des brûlures dans les deux cas. Conclusion. Ces deux cas montrent qu'il est essentiel que les brûlologues et les spécialistes des soins intensifs soient au courant de la possibilité de la présence de SSSS chez des patients souffrant de brûlures, avec tous ses potentiels effets dévastateurs.

Síndrome estafilocócico de la piel escaldada. Nuestra experiencia en 10 años / Staphylococcal scalded skin syndrome (SSSS). Our 10-year experience

El síndrome estafilocócico de la piel escaldada (SEPE) es una enfermedad cutánea aguda infrecuente, causada por toxinas exfoliativas del Staphylococcus aureus. El objetivo de este estudio es describir las características epidemiológicas, clínicas y terapéuticas de los pacientes con diagnóstico de SEPE en nuestro medio.Material y métodos.Se realizó un estudio retrospectivo, descriptivo y observacional, en el que se revisaron las historias clínicas de los pacientes con diagnóstico de SEPE vistos entre mayo de 2000 y mayo de 2010, atendidos en la Sección de Dermatología Pediátrica del Hospital Ramos Mejía, y entre mayo de 2005 y mayo de 2010 en el Servicio de Dermatología del Hospital Alemán.Resultados.Se incluyó un total de 62 pacientes, cuya edad media al momento del diagnóstico fue de 22 meses. No se observó predilección por sexo ni estación del año. El 13% de los pacientes recibió corticoides sistémicos previo al diagnóstico de SEPE. Todos los pacientes excepto uno, realizaron tratamiento antibiótico luego del diagnóstico de esta entidad. El 92% recibió cefalosporinas de primera generación. El 23% de los pacientes requirió internación y el 100% evolucionó satisfactoriamente.Conclusiones.El SEPE es una entidad poco frecuente. Si bien en nuestro medio no hallamos datos epidemiológicos sobre esta entidad, los datos demográficos encontrados en este estudio difieren de los publicados en la literatura mundial. Debe sospecharse en recién nacidos y niños pequeños con eritrodermia aguda y afectación peribucal o conjuntival.

Staphylococcal scalded skin syndrome (SSSS) is a rare cutaneous disease caused by exfoliativetoxins of Staphylococcus aureus. The aim of this study is to describe the epidemiology, clinicalmanifestations and treatment of patients with the diagnosis of SSSS in our community.Methods. We conducted a retrospective, descriptive and observational study, reviewing the clinicalrecords of patients with a diagnosis of SSSS, as seen between May 2000 and May 2010 atthe Pediatric Dermatology Section of the Hospital Ramos Mejía, and between May 2005 and May2010 at the Dermatology Unit of the Hospital Alemán.Results. A total of 62 patients were included, whose average age at the time of diagnosis was22 months. No predilection for sex or season of the year was observed. Thirteen percent of thepatients received systemic steroids prior to SSSS diagnosis. All but one of the patients received antibiotictreatment after the diagnosis of this entity. First generation cephaloporins were given to92% of patients; 23% of them required hospitalization and all of them had a satisfactory outcome.Discussion. SSSS is an infrequent entity. Even though there are no epidemiological studies inour country concerning SSSS, the data we gathered differs with world-wide published literature.SSSS must be suspected in new-borns and in young children with an acute onset of erythroderma,perioral affectation and conjunctivitis.

Staphylococcal scalded skin syndrome in a newborn.

A six-day-old newborn was admitted with exfoliating erythematous lesions over the face, of two days duration. The lesions spread to the rest of the body during the next two days. A diagnosis of Staphylococcal Scalded Skin Syndrome (SSSS) was made clinically and confirmed by isolation of Staphylococcus aureus from a blood sample. The child responded to Injection vancomycin and no fresh lesions were seen after the next 48 hours. However the child developed severe pneumonia and left against medical advice.

Distribution of the putative virulence factor encoding gene sheta in Staphylococcus hyicus strains of various origins

In the present study, Staphylococcus (S.) hyicus strains isolated in Russia (n = 23) and Germany (n = 17) were investigated for the prevalence of the previously described genes sheta and shetb. Sheta was detected in 16 S. hyicus strains. Sheta-positive strains were mainly found among strains isolated from exudative epidermitis, and frequently together with the exfoliative toxin-encoding genes exhD and exhC. Partial sequencing of sheta in a single S. hyicus strain revealed an almost complete match with the sheta sequence obtained from GenBank. None of the S. hyicus strains displayed a positive reaction with the shetb-specific oligonucleotide primer used in the present study. According to the present results, the exotoxin encoding gene sheta seems to be distributed among S. hyicus strains in Russia and Germany. The toxigenic potential of this exotoxin, which does not have the classical structure of a staphylococcal exfoliative toxin, remains to be elucidated.

Action of Staphylococcal Exfoliative Toxin A on Pemphigus Antigens Expressed on Human Keratinocytes / 中华皮肤科杂志

Objective To study the action and mechanism of staphylococcal exfoliative toxin A(E-TA)on pemphigus foliaceus antigen(PFA)and pemphigus vulgaris antigen(PVA)expressed on cultured human keratinocytes.Methods Stratified human keratinocytes were incubated with ETA and then stained with sera from patients with pemphigus foliaceus or pemphigus vulgaris as the first antibodies and FITC-la-beled sheep anti-human IgG as the second antibody.Total protein was harvested from the cells pretreated with ETA and run on SDS-PAGE for Western blot with the same antibodies.Simultaneously,supernatants of the keratinocytes before and after ETA treatment were collected for detection of the levels of IL-1?,IL-6with ELISA kits.The caseinolytic activities of the supernatants were tested by spectrometry in which casein was used as a non-specific substrate.Results Down-expression of PFA was shown after ETA treatment while no change of PVA expression was found.The high intensity and continuous linear appearance of fluo-rescent staining before ETA treatment became weak and discontinuous after ETA treatment,which were re-covered gradually in24hours.The degradation of proteins recognized by PF sera after ETV treatment was revealed by Western blot.The decreasing tendency of IL-1?concentration was found in the supernatants of cell culture after ETA treatment,but IL-6level was too low to be detected.Increased caseinolytic activities were found in the supernatants,and declined36hours after ETA treatment.Conclusions ETA acts on PFA expressed on keratinocytes in vitro,which is reversible along with withdrawal of ETA.The mechanism of E-TA act on PFA may be related to proteolytic action instead of promoting cytokine secretion.