RESUMEN
We reviewed all cases of Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) bacteremia in Danish children between 2016 and 2021. We found 2 fatal cases with preceding viral prodrome due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the usual benign course of SARS-CoV-2 infection in children, awareness of possible superinfection with PVL-SA in a child with rapid deterioration is crucial to ensure adequate treatment, including antimicrobial drugs with antitoxin effect.
Asunto(s)
Bacteriemia , Toxinas Bacterianas/biosíntesis , COVID-19/complicaciones , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , SARS-CoV-2 , Infecciones Estafilocócicas/etiología , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus/genética , Adolescente , COVID-19/virología , Niño , Preescolar , Coinfección , Comorbilidad , Dinamarca/epidemiología , Femenino , Humanos , Lactante , Masculino , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/metabolismo , Vigilancia en Salud Pública , Índice de Severidad de la Enfermedad , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/terapia , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/metabolismoRESUMEN
INTRODUCTION: Skin and soft tissue infections (SSTI) caused by Panton-Valentine leukocidin (PVL)-producing strains of Staphylococcus aureus (PVL-SA) are associated with recurrent skin abscesses. Secondary prevention, in conjunction with primary treatment of the infection, focuses on topical decolonization. Topical decolonization is a standard procedure in cases of recurrent PVL-SA skin infections and is recommended in international guidelines. However, this outpatient treatment is often not fully reimbursed by health insurance providers, which may interfere with successful PVL-SA decolonization. AIM: Our goal was to estimate the cost effectiveness of outpatient decolonization of patients with recurrent PVL-SA skin infections. We calculated the average cost of treatment for PVL-SA per outpatient decolonization procedure as well as per in-hospital stay. METHODS: The study was conducted between 2014 and 2018 at a German tertiary care university hospital. The cohort analyzed was obtained from the hospital's microbiology laboratory database. Data on medical costs, DRG-based diagnoses, and ICD-10 patient data was obtained from the hospital's financial controlling department. We calculated the average cost of treatment for patients admitted for treatment of PVL-SA induced skin infections. The cost of outpatient treatment is based on the German regulations of drug prices for prescription drugs. RESULTS: We analyzed a total of n = 466 swabs from n = 411 patients with recurrent skin infections suspected of carrying PVL-SA. PVL-SA was detected in 61.3% of all patients included in the study. Of those isolates, 80.6% were methicillin-susceptible, 19.4% methicillin-resistant. 89.8% of all patients were treated as outpatients. In 73.0% of inpatients colonized with PVL-SA the main diagnosis was SSTI. The median length of stay was 5.5 days for inpatients colonized with PVL-SA whose main diagnosis SSTI; the average cost was 2,283. The estimated costs per decolonization procedure in outpatients ranged from 50-110, depending on the products used. CONCLUSION: Our data shows that outpatient decolonization offers a highly cost-effective secondary prevention strategy, which may prevent costly inpatient treatments. Therefore, health insurance companies should consider providing coverage of outpatient treatment of recurrent PVL-SA skin and soft tissue infections.
Asunto(s)
Atención Ambulatoria , Toxinas Bacterianas/biosíntesis , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Staphylococcus aureus Resistente a Meticilina/metabolismo , Infecciones Cutáneas Estafilocócicas/terapia , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Estudios Retrospectivos , Infecciones Cutáneas Estafilocócicas/economíaRESUMEN
Necrotizing pneumonia induced by Panton-Valentine leukocidin-secreting Staphylococcus aureus is a rare but life-threatening infection that has been described in patients after they had influenza. We report a fatal case of this superinfection in a young adult who had coronavirus disease.
Asunto(s)
Toxinas Bacterianas/biosíntesis , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/complicaciones , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Necrosis/complicaciones , Neumonía Estafilocócica/complicaciones , Neumonía Viral/complicaciones , Staphylococcus aureus/patogenicidad , Adulto , Antibacterianos/uso terapéutico , Betacoronavirus/fisiología , COVID-19 , Prueba de COVID-19 , Cefotaxima/uso terapéutico , Clindamicina/uso terapéutico , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Resultado Fatal , Humanos , Linezolid/uso terapéutico , Masculino , Metronidazol/uso terapéutico , Necrosis/diagnóstico , Necrosis/terapia , Pandemias , Neumonía Estafilocócica/diagnóstico , Neumonía Estafilocócica/terapia , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , Respiración Artificial , SARS-CoV-2 , Espiramicina/uso terapéutico , Staphylococcus aureus/efectos de los fármacos , Tomografía Computarizada por Rayos XRESUMEN
It is necessary to develop agents other than antimicrobials for the treatment of Staphylococcus aureus infections to prevent the emergence of antimicrobial-resistant strains. Particularly, anti-virulence agents against the Panton-Valentine leukocidin (PVL)-positive methicillin-resistant S. aureus (MRSA), USA300 clone, is desired due to its high pathogenicity. Here, we investigated the potential anti-virulence effect of Tokiinshi, which is a traditional Japanese medicine (Kampo) used for skin diseases, against the USA300 clone. A growth inhibition assay showed that a conventional dose (20 mg/ml) of Tokiinshi has bactericidal effects against the clinical USA300 clones. Notably, the growth inhibition effects of Tokiinshi against S. epidermidis strains, which are the major constituents of the skin microbiome, was a bacteriostatic effect. The data suggested that Tokiinshi is unlikely to affect skin flora of S. epidermidis. Furthermore, PVL production and the expression of its gene were significantly suppressed in the USA300 clone by a lower concentration (5 mg/ml) of Tokiinshi. This did not affect the number of viable bacteria. Moreover, Tokiinshi significantly suppressed the expression of the agrA gene, which regulates PVL gene expression. For the first time, our findings strongly suggest that Tokiinshi has the potential to attenuate the virulence of the USA300 clone by suppressing PVL production via agrA gene suppression.
Asunto(s)
Antibacterianos/farmacología , Toxinas Bacterianas/biosíntesis , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Medicina Kampo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/metabolismo , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Humanos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrolloRESUMEN
INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is considered a major cause of healthcare-associated (HA) and community-acquired (CA) infections. Considering non-ß-lactam susceptibility as a potential marker for mecC-MRSA and CA-MRSA, the aim of this study was to determine the frequency and the associated genetic lineages of non-beta-lactam-antibiotic susceptible MRSA (NBLS-MRSA) strains in a multicenter study in Spain. METHODS: A collection of 45 NBLS-MRSA strains recovered in the period from January to June 2016 from 12 Spanish hospitals was analyzed. Molecular typing through spa-type characterization, agr group and multi-locus-sequence typing was performed. Methicillin-resistant genes (mecA and mecC) as well as immune evasion cluster (scn-chp-sak-sea-sep, considering scn gene as the marker of IEC system) and Panton-Valentine leukocidin (PVL) genes were determined with PCR/sequencing. RESULTS: The NBLS-MRSA phenotype was uncommon in the 12 hospitals analyzed (NBLS-MRSA/MRSA frequency: 0.3%-7.7%). All strains contained the mecA gene (and none contained mecC). Twenty-two different spa-types were detected among NBLS-MRSA strains, with spa-t008/agr-I the most prevalent (27%). The main clonal complexes were (CC/%): CC8/42.2%, CC5/33.3% and CC30/4.4%, with ST8 and ST5 as the main sequence types. The PVL toxin was present in 38% of strains (with spa-types t008, t024, t019, t044, t068, t318 and t3060). The IEC genes were detected in 78% of strains: IEC type-B (n=17), type-F (n=16), type-A (n=1) and type-E (n=1); 10 MRSA isolates were scn-negative. CONCLUSION: The NBLS-MRSA phenotype is uncommon in the analyzed hospitals; although no mecC-positive strains were detected, it could be a good marker for MRSA PVL-positive isolates (38%), frequently associated with CA-MRSA infections.
Asunto(s)
Toxinas Bacterianas/biosíntesis , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Staphylococcus aureus Resistente a Meticilina/genética , Humanos , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/metabolismo , EspañaRESUMEN
OBJECTIVE: Panton-Valentine leukocidin-producing Staphylococcus aureus necrotizing pneumonia is an unusual cause of community-acquired pneumonia, although associated with a high case fatality. This infection mainly affects young individuals, without any history, and is most often preceded by flu-like symptoms. METHOD: We focused on patients presenting with Staphylococcus aureus necrotizing pneumonia in Reunion (Indian Ocean) admitted to the emergency department. We performed a retrospective study based on data collected from laboratory registers and medical files of patients presenting with Staphylococcus aureus necrotizing pneumonia in Reunion between December 2014 and December 2017. RESULTS: A total of 16 patients were recruited for this study, with a median age of 40.5 years. More than half of patients had previously been admitted to the emergency department for acute respiratory distress syndrome or severe sepsis. Fourteen patients were admitted to the intensive care unit and six patients died (five premature deaths). CONCLUSION: Physicians should be aware of this infection during the flu season and quickly adapt the specific antibiotic treatment, including a drug inhibiting toxin production. As methicillin-resistant Staphylococcus aureus is very rarely observed in Reunion, physicians can still adapt the empirical treatment, without glycopeptides.
Asunto(s)
Toxinas Bacterianas/biosíntesis , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Neumonía Necrotizante/microbiología , Neumonía Estafilocócica/microbiología , Staphylococcus aureus/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Neumonía Necrotizante/diagnóstico , Neumonía Estafilocócica/diagnóstico , Estudios Retrospectivos , Reunión , Adulto JovenRESUMEN
PURPOSE: Potent extracellular toxins including alpha-haemolysin, Panton-Valentine leukocidin (PVL) and toxic-shock syndrome toxin 1 (TSST-1) significantly contribute to Staphylococcus aureus pathogenesis, thus, toxin suppression is a primary focus in treatment of staphylococcal disease. S. aureus maintains complex strategies to regulate toxin expression and previous data have demonstrated that subinhibitory concentrations of beta-lactam antibiotics can adversely increase S. aureus exotoxin production. The current study evaluates the effects of subinhibitory concentrations of tedizolid, a second-generation oxazolidinone derivative, on expression of staphylococcal exotoxins in both methicillin-resistant and methicillin-sensitive S. aureus. METHODOLOGY: S. aureus exotoxin expression levels were compared at 12 and 24 h following treatment with tedizolid, linezolid, nafcillin or vehicle control. RESULTS: Our findings show that the level of antibiotic required to alter toxin production was strain-dependent and corresponds with the quantity of toxin produced, but both tedizolid and linezolid could effectively reduce expression of alpha-haemolysin, PVL and TSST-1 toxin at subinhibitory concentrations. In contrast, nafcillin showed less attenuation and, in some S. aureus strains, led to an increase in toxin expression. Tedizolid consistently inhibited toxin production at a lower overall drug concentration than comparator agents. CONCLUSION: Together, our data support that tedizolid has the potential to improve outcomes of infection due to its superior ability to inhibit S. aureus growth and attenuate exotoxin production.
Asunto(s)
Antibacterianos/farmacología , Toxinas Bacterianas/biosíntesis , Meticilina/farmacología , Oxazolidinonas/farmacología , Staphylococcus aureus/efectos de los fármacos , Tetrazoles/farmacología , Animales , Antibacterianos/administración & dosificación , Toxinas Bacterianas/análisis , Toxinas Bacterianas/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Enterotoxinas/análisis , Enterotoxinas/antagonistas & inhibidores , Enterotoxinas/biosíntesis , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Exotoxinas/análisis , Exotoxinas/antagonistas & inhibidores , Exotoxinas/biosíntesis , Proteínas Hemolisinas/análisis , Proteínas Hemolisinas/antagonistas & inhibidores , Proteínas Hemolisinas/biosíntesis , Humanos , Leucocidinas/análisis , Leucocidinas/antagonistas & inhibidores , Leucocidinas/biosíntesis , Linezolid/administración & dosificación , Linezolid/farmacología , Resistencia a la Meticilina , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Staphylococcus aureus Resistente a Meticilina/metabolismo , Pruebas de Sensibilidad Microbiana , Nafcilina/administración & dosificación , Nafcilina/farmacología , Oxazolidinonas/administración & dosificación , Conejos , Ovinos , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/metabolismo , Superantígenos/análisis , Superantígenos/biosíntesis , Tetrazoles/administración & dosificaciónAsunto(s)
Staphylococcus aureus Resistente a Meticilina , Neumonía Necrotizante/microbiología , Infecciones Estafilocócicas/complicaciones , Toxinas Bacterianas/biosíntesis , Niño , Exotoxinas/biosíntesis , Resultado Fatal , Femenino , Humanos , Leucocidinas/biosíntesis , Staphylococcus aureus Resistente a Meticilina/metabolismo , EspañaRESUMEN
Groin pain is a frequently occurring complaint in presentations to the Emergency Department. Muscular sprain is often a differential diagnosis, however serious conditions such as pyomyositis should not be ignored. This case report presents a child with atraumatic right groin pain, which was initially diagnosed as a muscular sprain. The patient later re-presented out of hours to the Emergency Department with what was found to be extensive pelvic abscesses. He was subsequently found to have bilateral pneumonia and later developed a pericardial effusion and osteomyelitis of the right iliac bone, sacroiliac joint and sacrum. With multiple surgical interventions and appropriate antibiotics, he made a full recovery and was discharged home after a total admission time of 41 days. The causative organism was found to be Panton-Valentine leucocidin-positive methicillin-susceptible Staphylococcus aureus.
Asunto(s)
Absceso/microbiología , Toxinas Bacterianas/biosíntesis , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Osteomielitis/microbiología , Neumonía Estafilocócica/microbiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/metabolismo , Abdomen/diagnóstico por imagen , Absceso/complicaciones , Absceso/diagnóstico por imagen , Absceso/cirugía , Adolescente , Antibacterianos/uso terapéutico , Toxinas Bacterianas/aislamiento & purificación , Exotoxinas/aislamiento & purificación , Humanos , Ilion/diagnóstico por imagen , Leucocidinas/aislamiento & purificación , Pulmón/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Resistencia a la Meticilina , Microscopía Acústica , Osteomielitis/complicaciones , Osteomielitis/diagnóstico , Neumonía Estafilocócica/complicaciones , Neumonía Estafilocócica/diagnóstico , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
The amount of Panton-Valentine leukocidin (PVL) is diverse among Staphylococcus aureus isolates from different geographical regions, and its significance in some infections is disputed. However, data concerning this information in China are limited. Fifty-one lukSF-PV+ methicillin-resistant Staphylococcus aureus (MRSA) isolates gathered from varying infections were used for PVL production using enzyme-linked immunosorbent assay, and the quantity was analyzed in correlation with PVL isoform, genetic background of the isolate, and disease category. All isolates generated PVL with a range of 0.43-360.87 µg/mL, of which 56.9% isolates (29/51) generated 51-200 µg/mL of PVL; 11.8% (6/51) yielded PVL more than 200 µg/mL, and the rest (31.4%, 16/51) produced PVL of ≤50 µg/mL. The amount of PVL was not related to its variant and infection type, although isolates from skin and soft tissue infection had relatively high mean and median. Clonal complex (CC) 22 isolates might be the producer of relatively high concentrations of PVL; however, the difference among CCs was not analyzed due to a small number of CC isolates. The relevance of PVL production with the infection type, toxin isoform, and genetic characteristic of isolates may vary by clone type and also needs to be further evaluated using a large sample size and best concentration on in vivo environment.
Asunto(s)
Toxinas Bacterianas/biosíntesis , Toxinas Bacterianas/genética , Exotoxinas/biosíntesis , Exotoxinas/genética , Leucocidinas/biosíntesis , Leucocidinas/genética , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Polimorfismo Genético , Infecciones de los Tejidos Blandos/epidemiología , Infecciones Estafilocócicas/complicaciones , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Persona de Mediana Edad , Estudios Retrospectivos , Infecciones de los Tejidos Blandos/microbiología , Infecciones Estafilocócicas/microbiología , Factores de Virulencia/genética , Adulto JovenAsunto(s)
Toxinas Bacterianas/biosíntesis , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Infecciones Estafilocócicas , Staphylococcus aureus/metabolismo , Femenino , Humanos , Unidades de Cuidados Intensivos , Italia , Masculino , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiologíaRESUMEN
Despite increasing reports of skin and soft tissue infections caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Japan, the extent to which these strains cause nosocomial infections remains unknown, and this is especially true for bloodstream infections. In this study, we molecularly characterized MRSA isolates from Japanese blood samples. Among the 151 MRSA isolates collected from 53 medical facilities in 2011, 115 (76%) and 30 (20%) were classified as staphylococcal cassette chromosome mec (SCCmec) types II and IV, respectively, while the Panton-Valentine leukocidin (PVL) gene was detected in only two isolates. Among 66 MRSA isolates collected from Tokyo Medical University Hospital between 2012 and 2015, 43 (65%) and 20 (30%) were classifiable as SCCmec types II and IV, respectively. In 2015, highly virulent strains, such as the SCCmec type IV/PVL and SCCmec type IV/ toxic shock syndrome toxin-1 clonal types, increased in number. Therefore, the SCCmec type IV clone may cause invasive infections not only in community settings but also in healthcare settings in Japan.
Asunto(s)
Bacteriemia/epidemiología , Toxinas Bacterianas/genética , Infección Hospitalaria/epidemiología , Enterotoxinas/genética , Staphylococcus aureus Resistente a Meticilina/genética , Infecciones de los Tejidos Blandos/epidemiología , Infecciones Estafilocócicas/epidemiología , Superantígenos/genética , Factores de Virulencia/genética , Aminoglicósidos/farmacología , Antibacterianos/farmacología , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Toxinas Bacterianas/biosíntesis , Cultivo de Sangre , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Enterotoxinas/biosíntesis , Exotoxinas/biosíntesis , Exotoxinas/genética , Fluoroquinolonas/farmacología , Hospitales Universitarios , Humanos , Japón/epidemiología , Leucocidinas/biosíntesis , Leucocidinas/genética , Meticilina/farmacología , Resistencia a la Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Superantígenos/biosíntesis , Factores de Virulencia/biosíntesis , beta-Lactamas/farmacologíaRESUMEN
One of the most important Staphylococcus aureus virulence factors is Panton-Valentine leukocidin (PVL). We describe an outbreak of recurrent cutaneous PVL infections in different members of three family clusters. Molecular investigations were performed to confirm the presence of the mecA and PVL genes and to assign the SCCmec type, sequence type (ST) and clonal relatedness. A strain of PVL-producing methicillin-resistant S. aureus (MRSA) was responsible for infection in two related families (A and B), and a third family (C) was infected with PVL-producing methicillin-sensitive S. aureus (MSSA). Molecular investigations revealed the same clone of community-acquired (CA)-MRSA, PVL positive ST8, and SCCmec IV in families A and B and CA-MSSA PVL positive ST15 in family C. S. aureus PVL may give rise to recurrent uncontrolled infections that are difficult to eradicate, and close family contacts are at high risk for transmission.
Asunto(s)
Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus/aislamiento & purificación , Absceso/microbiología , Adulto , Toxinas Bacterianas/biosíntesis , Niño , Infecciones Comunitarias Adquiridas/microbiología , Exotoxinas/biosíntesis , Femenino , Humanos , Lactante , Leucocidinas/biosíntesis , Masculino , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/fisiología , Factores de VirulenciaRESUMEN
OBJECTIVES: We report on an outbreak of skin and soft tissue infections (SSTI) among kindergarten families. We analyzed the transmission route and aimed to control the outbreak. METHODS: The transmission route was investigated by nasal screening for Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus (PVL-SA), subsequent microbiological investigation including whole genome sequencing and a questionnaire-based analysis of epidemiological information. The control measures included distribution of outbreak information to all individuals at risk and implementation of a Staphylococcus aureus decontamination protocol. RESULTS: Individuals from 7 of 19 families were either colonized or showed signs of SSTI such as massive abscesses or eye lid infections. We found 10 PVL-SA isolates in 9 individuals. In the WGS-analysis all isolates were found identical with a maximum of 17 allele difference. The clones were methicillin-susceptible but cotrimoxazole resistant. In comparison to PVL-SAs from an international strain collection, the outbreak clone showed close genetical relatedness to PVL-SAs from a non-European country. The questionnaire results showed frequent travels of one family to this area. The results also demonstrated likely transmission via direct contact between families. After initiation of Staphylococcus aureus decontamination no further case was detected. CONCLUSIONS: Our outbreak investigation showed the introduction of a PVL-SA strain into a kindergarten likely as a result of international travel and further transmission by direct contact. The implementation of a Staphylococcus aureus decontamination protocol was able to control the outbreak.
Asunto(s)
Toxinas Bacterianas/biosíntesis , Brotes de Enfermedades/estadística & datos numéricos , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Piodermia/epidemiología , Piodermia/microbiología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/fisiología , Alelos , Preescolar , Familia , Humanos , Funciones de Verosimilitud , Filogenia , Apoyo SocialRESUMEN
A 61-year-old male presented with community-onset pneumonia not responding to treatment despite given appropriate antibiotics. Computed tomography scan of the thorax showed large multiloculated pleural effusion with multiple cavitating foci within collapsed segments; lesions which were suggestive of necrotising pneumonia. Drainage of the effusion and culture revealed methicillin-resistant Staphylococcus aureus, which had the same antibiotic profile with the blood isolate and PVL gene positive.
Asunto(s)
Toxinas Bacterianas/efectos adversos , Toxinas Bacterianas/biosíntesis , Infecciones Comunitarias Adquiridas , Exotoxinas/efectos adversos , Exotoxinas/biosíntesis , Leucocidinas/efectos adversos , Leucocidinas/biosíntesis , Staphylococcus aureus Resistente a Meticilina/metabolismo , Neumonía Necrotizante/tratamiento farmacológico , Neumonía Necrotizante/etiología , Humanos , Masculino , Persona de Mediana Edad , Neumonía Necrotizante/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Staphylococcus aureus is a major human and animal pathogen and a common cause of mastitis in cattle. S. aureus secretes several leukocidins that target bovine neutrophils, crucial effector cells in the defence against bacterial pathogens. In this study, we investigated the role of staphylococcal leukocidins in the pathogenesis of bovine S. aureus disease. We show that LukAB, in contrast to the γ-hemolysins, LukED, and LukMF', was unable to kill bovine neutrophils, and identified CXCR2 as a bovine receptor for HlgAB and LukED. Furthermore, we assessed functional leukocidin secretion by bovine mastitis isolates and observed that, although leukocidin production was strain dependent, LukMF' was most abundantly secreted and the major toxin killing bovine neutrophils. To determine the role of LukMF' in bovine mastitis, cattle were challenged with high (S1444) or intermediate (S1449, S1463) LukMF'-producing isolates. Only animals infected with S1444 developed severe clinical symptoms. Importantly, LukM was produced in vivo during the course of infection and levels in milk were associated with the severity of mastitis. Altogether, these findings underline the importance of LukMF' as a virulence factor and support the development of therapeutic approaches targeting LukMF' to control S. aureus mastitis in cattle.
Asunto(s)
Leucocidinas/metabolismo , Mastitis Bovina/metabolismo , Staphylococcus aureus/metabolismo , Animales , Bovinos , Femenino , Leucocidinas/biosíntesis , Mastitis Bovina/microbiología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/veterinariaRESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Niño , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/terapia , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/metabolismo , Toxinas Bacterianas/biosíntesis , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Meticilina/farmacología , Antibacterianos/farmacología , Índice de Severidad de la Enfermedad , Pruebas de Sensibilidad MicrobianaRESUMEN
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.
Asunto(s)
Antibacterianos/farmacología , Toxinas Bacterianas/biosíntesis , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Meticilina/farmacología , Infecciones Estafilocócicas , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/metabolismo , Niño , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Índice de Severidad de la Enfermedad , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/terapiaRESUMEN
A 76-year-old man was admitted to a community hospital due to a persistent high fever. He became afebrile after the administration of broad-spectrum antibiotics, but developed heart failure due to progressive aortic and mitral valve insufficiency and was transferred to our hospital. Although sequential blood cultures were negative, a broad-range polymerase chain reaction targeting the bacterial 16S-rRNA gene followed by the direct sequencing of whole blood revealed spa(+), mecA(-) and Panton-Valentine leukocidin (PVL)(+). He was finally diagnosed with infective endocarditis (IE) caused by PVL-producing methicillin-susceptible Staphylococcus aureus (MSSA), and underwent cardiac surgery. This is the first reported case of IE due to MSSA producing PVL.
Asunto(s)
Toxinas Bacterianas/biosíntesis , Endocarditis Bacteriana/microbiología , Exotoxinas/biosíntesis , Leucocidinas/biosíntesis , Infecciones Estafilocócicas/metabolismo , Staphylococcus aureus/metabolismo , Anciano , Antibacterianos/uso terapéutico , Endocarditis Bacteriana/tratamiento farmacológico , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/genética , Staphylococcus aureus/genéticaRESUMEN
UNLABELLED: Staphylococcus aureus is a formidable human pathogen that uses secreted cytolytic factors to injure immune cells and promote infection of its host. Of these proteins, the bicomponent family of pore-forming leukocidins play critical roles in S. aureus pathogenesis. The regulatory mechanisms governing the expression of these toxins are incompletely defined. In this work, we performed a screen to identify transcriptional regulators involved in leukocidin expression in S. aureus strain USA300. We discovered that a metabolic sensor-regulator, RpiRc, is a potent and selective repressor of two leukocidins, LukED and LukSF-PV. Whole-genome transcriptomics, S. aureus exoprotein proteomics, and metabolomic analyses revealed that RpiRc influences the expression and production of disparate virulence factors. Additionally, RpiRc altered metabolic fluxes in the trichloroacetic acid cycle, glycolysis, and amino acid metabolism. Using mutational analyses, we confirmed and extended the observation that RpiRc signals through the accessory gene regulatory (Agr) quorum-sensing system in USA300. Specifically, RpiRc represses the rnaIII promoter, resulting in increased repressor of toxins (Rot) levels, which in turn negatively affect leukocidin expression. Inactivation of rpiRc phenocopied rot deletion and increased S. aureus killing of primary human polymorphonuclear leukocytes and the pathogenesis of bloodstream infection in vivo. Collectively, our results suggest that S. aureus senses metabolic shifts by RpiRc to differentially regulate the expression of leukocidins and to promote invasive disease. IMPORTANCE: The bicomponent pore-forming leukocidins play pivotal roles in the ability of S. aureus to kill multiple host immune cells, thus enabling this pathogen to have diverse tissue- and species-tropic effects. While the mechanisms of leukocidin-host receptor interactions have been studied in detail, the regulatory aspects of leukocidin expression are less well characterized. Moreover, the expression of the leukocidins is highly modular in vitro, suggesting the presence of regulators other than the known Agr, Rot, and S. aureus exoprotein pathways. Here, we describe how RpiRc, a metabolite-sensing transcription factor, mediates the repression of two specific leukocidin genes, lukED and pvl, which in turn has complex effects on the pathogenesis of S. aureus Our findings highlight the intricacies of leukocidin regulation by S. aureus and demonstrate the involvement of factors beyond traditional virulence factor regulators.