RESUMO
Staphylococcus aureus is the main aetiologic agent of osteoarticular infections (OAIs) in paediatric patients. The aim of this prospective unicenter study was to describe the phenotypic and genotypic characteristics of S. aureus isolates obtained from OAIs in paediatric patients admitted to tertiary care hospital. Through a surveillance program called OsteoCode, a multidisciplinary team was created and we identified 27 patients with OAIs caused by S. aureus from 2019 to 2021. The susceptibility profile, virulence factors, biofilm formation, pulsed-field gel electrophoresis (PFGE), clonal complex (CC) and sequence type (ST) were determined. In addition, the clinical characteristics and evolution of the patients presented six months after the diagnosis of OAIs were described. Ninety-two percent of the isolates were methicillin-sensitive S. aureus (MSSA). In methicillin-resistant S. aureus (MRSA), SCCmec-II and SCCmec-V were detected. The pvl gene was only observed in MSSA (18.5%) and was associated with highest fever (p=0.015), multiple localization (p=0.017), and soft tissue sites of infection beyond the bone (pyomyositis, pulmonary abscess) (p=0.017). Biofilm formation was detected in 55.6% of isolates. The most common CC were CC5 and CC30 which represent the most common linages for bone and joint infections worldwide. The isolates were distributed in different STs, and ST672 was predominant. MRSA were associated with a longer duration of intravenous treatment and a prolonged hospital stay (p=0.023). Recurrent infection occurred in five children and orthopaedic complications in 33.3% of patients. This is the first study that reflects the epidemiology of S. aureus in OAIs in paediatric patients in Mexico; a clear predominance of MSSA distributed in different STs was observed. Our findings highlight that a multidisciplinary team is required for the diagnosis and treatment of OAIs.
Assuntos
Artrite Infecciosa , Hospitais Pediátricos , Osteomielite , Infecções Relacionadas à Prótese , Infecções Estafilocócicas , Staphylococcus aureus , Criança , Humanos , Antibacterianos/uso terapêutico , Exotoxinas/genética , Hospitais Pediátricos/estatística & dados numéricos , Leucocidinas/genética , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , México/epidemiologia , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/terapia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/epidemiologia , Artrite Infecciosa/microbiologia , Artrite Infecciosa/terapia , Osteomielite/diagnóstico , Osteomielite/epidemiologia , Osteomielite/microbiologia , Osteomielite/terapia , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/terapiaRESUMO
Resumen Staphylococcus aureus coloniza la nasofaringe en un tercio de los individuos sanos y además es causante de infecciones graves en pediatría, como endocarditis, neumonía e infecciones osteoarticulares. Posee varios mecanismos de virulencia, siendo la leucocidina de Panton Valentine (LPV) uno de ellos, una exotoxina que causa muerte celular. Su producción está comúnmente relacionada con Staphylococcus aureus resistente a meticilina (SARM) e infecciones pulmonares y musculo-esqueléticas graves. Sin embargo, la producción de LPV no es exclusiva de SARM. Se presentan dos casos clínicos de pacientes con infección por Staphylococcus aureus sensible a meticilina productora de esta exotoxina.
Abstract Staphylococcus aureus colonizes the nasopharynx in one third of healthy individuals and is also responsible for several infections in pediatrics such as endocarditis, pneumonia and osteoarticular infections. It has several virulence mechanisms, such as Panton Valentine leukocidin (PVL), which is an exotoxin that causes cell death. It is commonly related to methicillin-resistant Staphylococcus aureus (MRSA) and more serious pulmonary and musculoskeletal infections. However, PVL is not exclusive to MRSA. Two clinical cases of patients with infection by methicillin-sensitive Staphylococcus aureus producing this exotoxin are presented.
Assuntos
Humanos , Masculino , Criança , Adolescente , Osteomielite/tratamento farmacológico , Pediatria , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina , Staphylococcus aureus , Toxinas Bacterianas , Exotoxinas , Leucocidinas , Meticilina/farmacologiaRESUMO
Panton-Valentine leukocidin (PVL) is a Staphylococcus aureus virulence factor codified by lukSF-PV genes. Single-nucleotide polymorphisms (SNPs) at lukSF-PV genes can lead to two PVL sequence variants (R and H) generating different PVL isoforms. This study analyzed lukSF-PV genes SNPs among four different clonal lineages (STs/CC 1, 5, 8, and 30) of nine S. aureus isolated at Brazilian hospitals. The sequenced products showed SNPs at seven sites (positions 121, 470, 527, 663, 856, 1396, and 1729), leading to non-synonymous substitutions in all isolates investigated. Our findings showed new R and H isoforms variants in S. aureus isolated in Brazil and suggest a possible relationship between H2b isoform and the ST30/CC30 lineage.
Assuntos
Toxinas Bacterianas/genética , Exotoxinas/genética , Leucocidinas/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Fatores de Virulência/genética , Brasil , Humanos , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas , Staphylococcus aureus/isolamento & purificaçãoRESUMO
AIMS: Staphylococcus aureus is one of the most common pathogens in hospital environment and community. Panton-Valentine leukocidin (PVL) production is clinically associated with skin abscesses, soft tissues infections, bacteraemia and sepsis. This study aimed to investigate the effects of the presence of genes lukF/S-PV coding for PVL, in histological and haematological features during systemic infection, using a Swiss mice experimental model. METHODS AND RESULTS: Experiments were performed using 25 mice distributed into five experimental groups, intravenously inoculated with 50 µl suspensions at density 1·0 × 107 CFU per ml of strains: methicillin-susceptible (MSSA) and pvl-negative strains isolated from nasal colonization; MSSA pvl-positive strains isolated from nasal colonization; methicillin-resistant (MRSA) and pvl-positive strains isolated from peripheral blood of a patient with severe pulmonary infection; and a MRSA pvl-positive strains isolated from a peripheral blood culture of a patient with bacteraemia. Haematological analysis was performed at 24, 48, 72 and 96 h post-infection. Morphoanatomy and histopathological analyses were performed at 96 h post-infection. For all S. aureus strains tested, the capability of intravenous dissemination and survival into mice tissues was demonstrated. Inflammatory processes at different levels were related to the presence of pvl genes, and included alterations in the format, size and colour of the organs. Staphylococcus aureus pvl-positive strains were detected in greater numbers in the organs of the infected animals. CONCLUSIONS: The pvl-positive strains isolated from blood cultures were capable to induce the greatest modifications in both haematological and histopathological profiles, and seemed to aggravate the systemic infections. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings are valuable in characterizing infections caused by S. aureus in humans and murine.
Assuntos
Toxinas Bacterianas/metabolismo , Exotoxinas/metabolismo , Leucocidinas/metabolismo , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Animais , Bacteriemia/microbiologia , Bacteriemia/patologia , Toxinas Bacterianas/genética , Modelos Animais de Doenças , Exotoxinas/genética , Humanos , Leucocidinas/genética , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Meticilina/metabolismo , Camundongos , Staphylococcus aureus/genética , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidadeRESUMO
BACKGROUND: Staphylococcus aureus is a common nasal colonizer in 20-30% of the general population. When mucosal and cutaneous barriers are disrupted, S. aureus can cause severe infections. While MRSA nasal carriers have an increased risk of infections when compared to non-carriers, prolonged exposure to the hospital environment may cause an increase in carriage of MRSA. MATERIALS AND METHODS: A survey questionnaire was filled for analyzing risk factors of colonization. Swab isolates were identified as S. aureus by traditional microbiological assays. Antibiotic susceptibility profiles were performed following the CLSI standard guidelines. Multiplex PCR was conducted to determine the presence of genes mecA and lukS-PV/lukF-PV. Chi-squared, univariate, and multivariate logistic regressions were applied to find statistically significant associations between risk factors and the presence of S. aureus and MRSA. RESULTS: One hundred and eighty-six isolates were identified as S. aureus. The strains showed high resistance to penicillin, oxacillin, azithromycin, erythromycin, clindamycin (inducible), and tetracycline. The overall prevalence of MRSA in medical students was 45.9% [40.4-51.6] 95% CI. PCR showed a prevalence of mecA gene in MRSA isolates of 6.1% while lukS-PV/lukF-PV gene was present in 3.2% [1.2-6.9] 95% CI of the S. aureus samples. The risk factors frequency of antibiotic intake and repeated visits to hospitals demonstrated statistical significance. CONCLUSION: S. aureus and MRSA isolates have a high prevalence of colonization, and antibiotic resistance in the population studied. MRSA resistance was not related to the presence of the mecA gene. The prevalence of PVL genes was low, but it could represent a risk because they are circulating in the community.
RESUMO
Staphylococcus aureus es uno de los principales agentes etiológicos de infecciones en niños provenientes de la comunidad y del ámbito hospitalario. La gravedad de estos cuadros se asocia a factores de virulencia, entre los que se encuentra la leucocidina de Panton-Valentine. Tanto Staphylococcus aureus resistente como sensible a la meticilina producen esta leucocidina, aunque con frecuencia variable. Presentamos a dos niños con infección grave por Staphylococcus aureus sensible a la meticilina productor de leucocidina de Panton-Valentine con complicaciones osteoarticulares y endovasculares. Es fundamental la sospecha diagnóstica, el tratamiento antibiótico adecuado y el manejo quirúrgico precoz para mejorar el abordaje de estas infecciones. Se debe mantener la vigilancia epidemiológica para detectar la frecuencia de las infecciones causadas por estas bacterias.
Staphylococcus aureus is a major etiologic agent of infections in children from the community and the hospital setting. The severity of these conditions is associated with virulence factors, including the Panton-Valentine leukocidin. Both methicillin resistant and sensitive Staphylococcus aureus produce this leukocidin although with varying frequency. We present two children with severe infection by sensitive Staphylococcus aureus producer of Panton-Valentine leukocidin with musculoskeletal and endovascular complications. It is essential the suspected diagnosis, appropriate antibiotic treatment and early surgical management to improve the approach of these infections. Epidemiological surveillance should be mantained to detect the frequency of infections caused by these bacteria.
Assuntos
Humanos , Masculino , Feminino , Criança , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/terapia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Toxinas Bacterianas/biossíntese , Exotoxinas/biossíntese , Leucocidinas/biossíntese , Meticilina/farmacologia , Antibacterianos/farmacologia , Índice de Gravidade de Doença , Testes de Sensibilidade MicrobianaRESUMO
Staphylococcus aureus is a major etiologic agent of infections in children from the community and the hospital setting. The severity of these conditions is associated with virulence factors, including the Panton-Valentine leukocidin. Both methicillin resistant and sensitive Staphylococcus aureus produce this leukocidin although with varying frequency. We present two children with severe infection by sensitive Staphylococcus aureus producer of Panton-Valentine leukocidin with musculoskeletal and endovascular complications. It is essential the suspected diagnosis, appropriate antibiotic treatment and early surgical management to improve the approach of these infections. Epidemiological surveillance should be mantained to detect the frequency of infections caused by these bacteria.
Staphylococcus aureus es uno de los principales agentes etiológicos de infecciones en niños provenientes de la comunidad y del ámbito hospitalario. La gravedad de estos cuadros se asocia a factores de virulencia, entre los que se encuentra la leucocidina de Panton-Valentine. Tanto Staphylococcus aureus resistente como sensible a la meticilina producen esta leucocidina, aunque con frecuencia variable. Presentamos a dos niños con infección grave por Staphylococcus aureus sensible a la meticilina productor de leucocidina de Panton-Valentine con complicaciones osteoarticulares y endovasculares. Es fundamental la sospecha diagnóstica, el tratamiento antibiótico adecuado y el manejo quirúrgico precoz para mejorar el abordaje de estas infecciones. Se debe mantener la vigilancia epidemiológica para detectar la frecuencia de las infecciones causadas por estas bacterias.
Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/biossíntese , Exotoxinas/biossíntese , Leucocidinas/biossíntese , Meticilina/farmacologia , Infecções Estafilocócicas , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Criança , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Índice de Gravidade de Doença , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/terapiaRESUMO
Panton-Valentine leukocidin (PVL) is an exotoxin that is produced by many strains of Staphylococcus aureus, and an important virulence factor. A PVL-positive S. aureus infection leads to rapid and severe infections of soft tissue and necrotizing pneumonia in healthy adolescents, and has a high mortality. This case report included a 12-year-old male patient who admitted for fever, respiratory distress and hip pain and was identified with necrotizing pneumonia with septic pulmonary embolism, psoas abscess, cellulitis and osteomyelitis. The PVL positive methicillin-sensitive S. aureus (MSSA) was isolated in the patient blood culture.
La leucocidina de Panton-Valentine (LPV) es una exotoxina producida por muchas cepas de Staphylococcus aureus, y un importante factor de virulencia. Una infección por S. aureus positivo para LPV deriva en infecciones rápidas y graves de partes blandas y neumonía necrosante en adolescentes sanos, y la tasa de mortalidad es elevada. Presentamos el caso de un paciente de 12 años hospitalizado por fiebre, dificultad respiratoria y coxalgia en el que se identificó neumonía necrosante con embolia pulmonar séptic absceso del psoas, celulitis y osteomielitis. En el hemocultivo del paciente se aisló S. aureus sensible a la meticilina (SASM) positivo para LPV.
Assuntos
Toxinas Bacterianas/análise , Exotoxinas/análise , Leucocidinas/análise , Infecções Estafilocócicas/diagnóstico , Criança , Infecções Comunitárias Adquiridas , Humanos , Masculino , Staphylococcus aureusRESUMO
La leucocidina de Panton-Valentine (LPV) es una exotoxina producida por muchas cepas de Staphylococcus aureus, y un importante factor de virulencia. Una infección por S. aureus positivo para LPV deriva en infecciones rápidas y graves de partes blandas y neumonía necrosante en adolescentes sanos, y la tasa de mortalidad es elevada. Presentamos el caso de un paciente de 12 años hospitalizado por fiebre, dificultad respiratoria y coxalgia en el que se identificó neumonía necrosante con embolia pulmonar séptica, absceso del psoas, celulitis y osteomielitis. En el hemocultivo del paciente se aisló S. aureus sensible a la meticilina (SASM) positivo para LPV.
Panton-Valentine leukocidin (PVL) is an exotoxin that is produced by many strains of Staphylococcus aureus, and an important virulence factor. A PVL-positive S. aureus infection leads to rapid and severe infections of soft tissue and necrotizing pneumonia in healthy adolescents, and has a high mortality. This case report included a 12-year-old male patient who admitted for fever, respiratory distress and hip pain and was identified with necrotizing pneumonia with septic pulmonary embolism, psoas abscess, cellulitis and osteomyelitis. The PVL positive methicillin-sensitive S. aureus (MSSA) was isolated in the patient blood culture.
Assuntos
Humanos , Masculino , Criança , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus , Toxinas Bacterianas/análise , Infecções Comunitárias Adquiridas , Exotoxinas/análise , Leucocidinas/análiseRESUMO
The use of invasive techniques, such as intravascular catheter insertion, and the formation of biofilms in several devices by methicillin-resistant Staphylococcus aureus (MRSA) have contributed to the increased number of septic patients, morbidity and mortality. This study aimed to evaluate the virulence of strains through catheter colonization and identification of microbial biofilm, as well as pathological changes on the colonized skin. An experimental biofilm formation model utilized catheter fragments implanted subcutaneously in 25 Swiss mice. The technique consisted of inoculating a catheter fragment on the back of each animal, followed by intradermal inoculation of 50 µl of bacterial suspension at 1.0 × 107 colony forming units/ml. After 96 h, catheters were removed for macroscopic analysis and evaluated through culture. Local skin fragments were also extracted for histopathology analysis. Staphylococcus aureus can adhere to catheters, colonize and form biofilms. The high amount of viable bacterial cells colonizing catheters and virulence factors can lead to severe infections of skin and adjacent tissues. [Int Microbiol 19(4): 199-207 (2016)].