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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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: Extracellular protein toxins contribute to the pathogenesis of Staphylococcus aureus infections. The present study compared the effects of iclaprim and trimethoprim - two folic acid synthesis inhibitors - with nafcillin and vancomycin on production of Panton-Valentine leukocidin (PVL), alpha haemolysin (AH) and toxic-shock syndrome toxin I (TSST-1) in methicillin-resistant and vancomycin-intermediate S. aureus (MRSA and VISA, respectively)., Methodology: Northern blotting and RT-PCR were used to assess gene transcription; toxin-specific bioassays were used to measure protein toxin production., Results: As shown previously, sub-inhibitory concentrations (sub-MIC) of nafcillin increased and prolonged MRSA toxin gene transcription and enhanced PVL, TSST-1 and AH production. Sub-inhibitory doses of iclaprim and trimethoprim delayed maximal AH gene (hla) transcription and suppressed AH production; both drugs delayed, but neither reduced, maximal TSST-1 production. Trimethoprim significantly increased lukF-PV expression and PVL production compared to both untreated and iclaprim-treated cultures. Higher concentrations of iclaprim and trimethoprim markedly suppressed MRSA growth, mRNA synthesis and toxin production. In VISA, iclaprim, vancomycin and nafcillin variably increased tst and hla expression, but only nafcillin increased toxin production. Despite its ability to increase hla expression, iclaprim was the most potent inhibitor of AH production., Conclusions: We conclude that, due to its ability to suppress toxin production, iclaprim should be effective against severe staphylococcal infections caused by toxin-producing MRSA and VISA strains, especially given its ability to concentrate at sites of infection such as skin and skin structures and the lung.

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.

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 ., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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)]., (Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.)

Since late 2014, multiple cases of abscesses and boils due to methicillin-susceptible Staphylococcus aureus (MSSA) expressing the Panton-Valentine leucocidin (PVL) were observed in Eritrean asylum seekers in Lausanne, Switzerland. Strains isolated from infected Eritrean and non-Eritrean patients were compared by whole genome sequencing to determine whether these numerous cases result from an outbreak. The genome of S. aureus PVL-producing strains were sequenced and compared. Clinical and epidemiological characteristics of patients infected by PVL-producing strains were investigated. This work reports 15 cases of infections due to PVL-producing strains affecting mostly asylum seekers (n = 10), people working with refugees and/or exposed to Africans (n = 3). Most infections were due to closely related strains of CC152 (n = 8) and CC15 (n = 3), two distantly related (>34 000 core single nucleotide polymorphisms) clonal complexes. An epidemiological link between the 15 cases could be ruled out by whole genome sequencing (33 to 172 core single nucleotide polymorphisms between the different strains of a given complex). Altogether, these results reflect the probable high incidence of CC15 and CC152 PVL-producing strains in eastern Africa. Clinicians facing unusual skin infections in African refugees (or in any person returning from this region of high endemicity) should consider S. aureus PVL-producer before suspecting rare infections such as leishmaniasis or rickettsiosis. Clinicians should also remember that PVL are frequently expressed by MSSA in some regions of the world and that antibiotics that are efficient on toxin expression, such as clindamycin, represent the best therapeutic option., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (Sociedad Argentina de Pediatría.)

Staphylococcus aureus is among the most important human pathogens. It is associated with different infections and is a major cause of skin and soft tissue infections (SSTIs). The aim of our study was to compare S. aureus isolates associated with SSTIs with isolates obtained from healthy carriers in the Central Slovenia region in terms of antimicrobial susceptibility, genetic diversity by clonal complex (CC)/sequence type, spa type, and by toxin gene profiling. In total, 274 S. aureus isolates were collected prospectively by culturing wound samples from 461 SSTI patients and nasal samples from 451 healthy carriers. We have demonstrated high heterogeneity in terms of CCs and spa type in both groups of isolates. The main clone among SSTI strains was Panton-Valentine leukocidin gene (pvl) positive CC121, whereas the main clone among carrier strains was CC45 carrying a large range of toxin genes. The main spa type in both groups was t091. Pvl was more frequently present in SSTI strains (31.2% SSTI vs 3.6% carrier strains) and staphylococcal enterotoxin C was more frequently present in carrier strains (1.6% SSTI vs 17.0% carrier strains). We have also demonstrated that methicillin-resistant S. aureus was a rare cause (2.8%) of SSTIs in our region., (© 2016 APMIS. Published by John Wiley & Sons Ltd.)

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.

Objectives: We set out to investigate the impact of common antibiotics on Panton-Valentine Leucocidin (PVL) expression by methicillin-sensitive Staphylococcus aureus (MSSA). PVL expression by methicillin-resistant S. aureus (MRSA) is reportedly enhanced by β-lactams, but inhibited by protein-synthesis inhibitors, a fact that has influenced management of infections associated with PVL. Although PVL is more frequently associated with MSSA than MRSA in the UK, the effect of antibiotics on PVL expression by MSSA has not been fully addressed., Methods: MSSA was cultured in vitro with varying concentrations of flucloxacillin, clindamycin or linezolid and PVL expression measured by qRT-PCR and Western blotting. A murine MSSA abscess model was developed to measure leucocidin expression in vivo following antibiotic treatment., Results: 9% (27/314) of MSSA isolates from patients with uncomplicated community skin/soft tissue infections were positive for PVL genes (lukFS-PV). PVL expression by MSSA in broth was unaffected by varying concentrations of flucloxacillin, clindamycin or linezolid. In a murine abscess model, treatment with flucloxacillin did, however, enhance in vivo MSSA lukF-PV transcription and this was sustained even when flucloxacillin was combined with clindamycin, or clindamycin plus linezolid. Notwithstanding increased leucocidin transcription, functional leucotoxin activity was not enhanced. Treatment with flucloxacillin plus clindamycin significantly decreased leucotoxin activity, but the addition of a second protein synthesis inhibitor, linezolid, did not confer benefit., Conclusions: Our results suggest flucloxacillin in combination with a single protein-synthesis inhibitor such as clindamycin would give the best treatment outcome., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Staphylococcus aureus is an important pathogen within the context of cystic fibrosis lung disease. Case reports have identified a strong association between the toxin Panton-Valentine Leukocidin (PVL) and lethal necrotizing pneumonia in healthy immunocompetent patients. PVL+ strains of Staphylococcus aureus have also been identified in patients with cystic fibrosis. We describe a further case of pneumonia in a patient with cystic fibrosis, and outline potential transmission of the organism from healthy family members to this patient. We review the evidence regarding the pathogenicity of PVL toxin with a special reference to patients with cystic fibrosis. We outline current concerns regarding the potential transmission of the organism and possible treatment strategies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We describe three cases of community-acquired necrotizing pneumonia which were caused by Panton-Valentine leucocidin-producing strains of Staphylococcus aureus (one of them methicillin sensitive). All cases were successfully treated without any sequelae for the patients due to the prompt initiation of adequate antimicrobial therapy. High suspicion toward this fatal pathogen was the key to the successful outcome of the patients., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

Staphylococcus aureus produces a family of exotoxins which are structural homologues of superantigens and thus are called staphylococcal superantigen-like proteins (SSLs). Amongst the 14 SSL genes, ssl1 (SAOUHSC_00383) has been cloned in the pQE30 expression vector, overexpressed in Escherichia coli M15 (pREP4) cells and the protein purified to homogeneity. The protein was crystallized using 6% Tacsimate pH 6.0, 0.1 M MES pH 6.0, 25%(w/v) polyethylene glycol 3350, 100 mM NDSB 256 at 298 K by the sitting-drop vapour-diffusion method. The crystals belonged to space group P21, with unit-cell parameters a = 77.9, b = 70.5, c = 126.5 Å, β = 106.2°. X-ray diffraction data were collected and processed to a maximum resolution of 2.5 Å. The crystal contains six molecules in the asymmetric unit.

A twelve-year-old girl was admitted to the paediatric department with progressive joint problems following a mild trauma. Diagnostic follow-up showed a Staphylococcus aureus infection. Generally, S. aureus infection mainly involves the skin and the nasal mucosa. In some cases it can cause a fulminant invasive infection in previously healthy young patients. If this is the case, it is important to consider PVL (Panton-Valentine-leukocidin)-positive S. aureus and underlying immune deficiencies when performing a differential diagnosis. In addition, it is important to remember that previous trauma can cause increased susceptibility to septic arthritis or osteomyelitis in children, as is seen in this case. Aggressive treatment of an invasive S. aureus infection is important even in apparently healthy young patients, to prevent morbidity or mortality.

We report the observation of a septic arthritis of the knee complicated within first 36 hours by multiorgan failure including acute respiratory distress syndrome (ARDS), heart failure, acute renal failure and disseminated intravascular coagulation (DIC). A diagnosis of staphylococcal arthritis was suspected confirmed by direct examination, and culture showed a Staphylococcus aureus sensitive to methicillin. The sample sent to the National Reference Centre for Staphylococci (Lyon, France) for genetic analysis confirmed the isolate positive for the PVL gene expression. The fulminating evolution of a septic S. aureus arthritis in an otherwise healthy man should probably evoke the possibility of LPV strain. Anti-PLV antibiotics with anti-staphylococcal activity, such as clindamycin and linezolid should be started without waiting for typing of the S. aureus strain., (Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Inhibitors of peptide deformylase (PDF) represent a new class of antibacterial agents with a novel mechanism of action. Mutations that inactivate formyl methionyl transferase (FMT), the enzyme that formylates initiator methionyl-tRNA, lead to an alternative initiation of protein synthesis that does not require deformylation and are the predominant cause of resistance to PDF inhibitors in Staphylococcus aureus. Here, we report that loss-of-function mutations in FMT impart pleiotropic effects that include a reduced growth rate, a nonhemolytic phenotype, and a drastic reduction in production of multiple extracellular proteins, including key virulence factors, such as α-hemolysin and Panton-Valentine leukocidin (PVL), that have been associated with S. aureus pathogenicity. Consequently, S. aureus FMT mutants are greatly attenuated in neutropenic and nonneutropenic murine pyelonephritis infection models and show very high survival rates compared with wild-type S. aureus. These newly discovered effects on extracellular virulence factor production demonstrate that FMT-null mutants have a more severe fitness cost than previously anticipated, leading to a substantial loss of pathogenicity and a restricted ability to produce an invasive infection.

Staphylococcus aureus is a leading cause of intramammary infections (IMI) and bovine mastitis is an important disease for the dairy industry. As this bacterium probably expresses specific genes for establishment of IMI, we studied the transcriptional profile of four S. aureus strains recovered from experimentally infected cows. Microbial RNA was extracted from bacteria isolated from milk, reverse-transcribed and labeled for hybridization to sub-genomic microarrays to detect candidate genes for further investigations. Several S. aureus genes were expressed during IMI; some were detected in samples from more than one strain, more than one cow and at more than one time point during infection. A selection of four genes showing strong expression and with putative functions in pathogenesis was further studied by qPCR. By comparing the expression in different media in vitro, we found that gene SACOL2171 was induced by iron restriction whereas the expression of the transcriptional regulator SACOL2325 and the ABC transporter SACOL0718-720 (vraFG) were induced by milk. In addition, the putative exotoxin SACOL0442 seemed to require the intramammary environment for expression. Gene-disrupted mutants for SACOL0720 and SACOL0442 showed no growth defect in vitro but were attenuated during bovine IMI, causing infections with significant reductions in bacterial and somatic cell counts. The milk from the mammary quarters infected with these mutants also showed better appearance and composition than milk from quarters infected with the wild type. In conclusion, we have identified genes that are most likely important for S. aureus IMI. These represent novel candidates to include in a vaccine., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Fatal exudative dermatitis (FED) is a recently described condition affecting red squirrels (Sciurus vulgaris) on the Isle of Wight and Jersey (Simpson et al., 2010a). Staphylococcus aureus strains isolated from skin lesions in cases of FED were characterised by molecular and phenotypic approaches. The strains were found to belong to a single MLST clonal complex (CC49) representing either ST49 or a novel single locus variant thereof (ST1957), were closely related by other molecular typing approaches, and all possessed the leukotoxin M encoding gene (lukM). In contrast S. aureus was either not isolated from none-FED cases or belonged to distinct and diverse molecular types that, with one exception, did not encode lukM. All isolates from FED cases were susceptible to all antimicrobials tested, including penicillin, and all proved negative for mecA and mecC as well as 14 other staphylococcal toxin genes. As all squirrels affected by FED were infected with S. aureus of the same lineage and encoded the lukM gene, it is possible that strains of this lineage may be involved in the pathogenesis of the dermatitis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Panton-Valentine leukocidin (PVL) toxin producing strains of Staphylococcus aureus are known to cause skin and soft tissue infection. They can also cause necrotising pneumonia in otherwise healthy individuals. Here we report a case of severe, necrotising, haemorrhagic pneumonia in a 12-year-old boy who presented with a four-day history of a sore throat and fever. During his admission he deteriorated and needed full ventilatory support but despite all efforts he died. Postmortem examination lung swabs confirmed the presence of PVL-associated S aureus. There is a need to improve awareness of this disease among medical practitioners as early diagnosis and appropriate management can save lives.

Background: An eight (8) months prospective study was carried out to control an outbreak of nosocomial pneumonia due to a Panton-Valentine Leukocidin (PVL) producing Staphylococcus aureus, in the paediatrics' unit at the Zou/Collines Departmental Hospital (CHDZ/C), (Benin)., Methods: Between 1(st) September 2004 and 30(th) May 2005 an investigation was conducted that involved the screening of all patients suspected to have nosocomial pneumonia, hospital environment sampling and the follow-up of cases until the end of hospital admission period. Isolates were identified, tested for antimicrobial susceptibility and analysed for PVL production. The study period was divided into Period I, corresponding to the outbreak period and Period II, after the complete renovation of the Unit along with hand washing promotion., Results: A total of 453 patients were admitted during the period of the study; (235 during Period I and 218 during Period II) in the malnourished children sector. Twenty eight (28) cases of pneumonia due to S. aureus were discovered and PVL-producing S. aureus constituted 61% (17/28) of identified cases. The mortality rate among the PVL- producing strains was 15/17 (88%) while it was 1/11 (9%) among non PVL-producing strains. Enhanced hygiene measures helped to terminate the outbreak., Conclusions: This study showed that PVL was strongly linked to nosocomial pneumonia. PVL-producing S aureus can be controlled in the hospital by a combination of the promotion of preventive measures, decontamination of the environment and the early use of the correct antibiotic at the appropriate dose and for an adequate duration.

Objective: The authors had for aim to describe the epidemiological and clinical characteristics, and the treatment of patients presenting with skin and soft tissue infections due to Panton-Valentine leukocidin (PVL) producing Staphylococcus aureus in the Nord-Pas-de-Calais (NPDC) region, North of France., Methods: We included patients presenting with PVL producing S. aureus infection from seven hospitals in the NPDC region, between February 2004 and April 2008. We retrospectively collected patient data using a standardized questionnaire. The features of patients presenting with skin and soft tissue were then analyzed., Results: PVL producing S. aureus was isolated from 64 patients. Fifty-four patients presented with skin and soft tissue infections. The mean age of patients was 23.8 years (63% male patients). The mean number of persons living with the infected patient was 4.5 (vs. 2.5 in NPDC). The lesions were abscesses with inflammatory signs in 64.8% of the cases (20% were necrotic). Among the patients, 70.3% carried a methicillin resistant strain. Antibiotics per os were used for 83.3% of patients; the first-line antibiotics were considered inadequate in 53.3% of the cases. Among the patients, 83.3% underwent surgery. Fourteen out of 38 patients with available data had been exposed to antibiotic therapy during the three months before hospital management., Conclusion: Recent exposure to antibiotics and living with a high number of persons are reasons to suspect a PVL producing S. aureus infection in patients with skin abscess., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Community-acquired methicillin-resistant Staphylococcus aureus (caMRSA) is an emerging pathogen which causes potentially severe infections in young and healthy individuals due to the ability of most strains to produce Panton-Valentine leukocidin (PVL). The aim of this study was to evaluate the prevalence of PVL-positive (PVL(+))-MRSA strains in Western Austria in the period from December 2005 to May 2010 and to characterize the identified PVL(+)-MRSA strains., Methods: Six hundred and fifty MRSA strains from Innsbruck Medical University hospital, district hospitals, and general practitioners were investigated for the presence of lukS-lukF gene (encoding for PVL). Antimicrobial resistance testing, SCCmec-, agr-, MLST- and spa-typing, as well as arcA determination were performed on PVL(+)-MRSA., Results: Among 650 MRSA strains collected from various body sites from hospitalized patients and outpatients, 31 strains (4.8 %) were positive for lukS-lukF and thus identified as PVL(+)-MRSA. Agr-1 was the most common agr-type (n = 18, 58.1 %) and SCCmec-IV or variants IVa and IVc were the most common SCCmec types (n = 27, 87.1 %). All tested strains showed in-vitro susceptibility to vancomycin and rifampicin, but resistance against cotrimoxazol (6.4 %), clindamycin (9.7 %), gentamicin (9.7 %), fusidic acid (12.9 %), levofloxacin (12.9 %), and erythromycin (61.3 %) was found. Most lukS-lukF-positive MRSA detected in our survey shared ST8 and t008 and were positive for arcA., Conclusions: The major lukS-lukF-positive MRSA lineage found in our population was ST8, t008 and positive for arcA which is mainly found in the USA. In contrast, ST80 strains were not found as frequently in our region as in many other European countries.

Staphylococcus aureus harboured by Panton-Valentine leukocidin (PVL) is emerging as a serious problem worldwide. There has been an increase in the incidence of necrotizing lung infections in otherwise healthy young people with very high mortality rate associated with these strains. This report documents a confirmed case of necrotizing pneumonia due to methicillin-susceptible S. aureus (MSSA) harbouring Panton-Valentine leukocidin genes. An apparently healthy 49-year old man was admitted to our hospital for dyspnea and he quickly developed acute respiratory distress syndrome. MSSA harbouring Panton-Valentine leukocidin genes were cultured from the abscess fluid and from multiple blood specimens. Aggressive antibiotic therapy was started and intensive supportive care led finally to a complete recovery. Rapid identification of Panton-Valentine leukocidin in MSSA samples should be supposed when a young, immunocompetent patient, develops a necrotizing pneumonia. Bactericidal antistaphylococcal antibiotics are recommended for the treatment as soon as possible to avoid the potentially devastating consequences of this kind of S. aureus.

Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus results in leukocyte destruction and tissue necrosis (Pediatric Dermatology 2007;24:401). It can be associated with a spectrum of clinical manifestations that range from localized staphylococcal skin infections to sometimes severe necrotizing pneumonia (Clin Infect Dis 1999;29:1128). We report a case of four siblings, three brothers whose atopic dermatitis was complicated by cutaneous lesions and furunculosis, while their 21-month-old sister had a fatal PVL positive staphylococcal pneumonia., (© 2011 Wiley Periodicals, Inc.)

Pneumonia caused by Panton-Valentine leukocidin-producing Staphylococcus aureus is associated with a high fatality rate. There have been few reported cases in HIV-1-co-infected patients. Here we report a fatal case of severe community-acquired pneumonia caused by Panton-Valentine leukocidin-producing S. aureus in a 45-year-old woman with HIV-2 infection.

Objectives: To investigate the effect of subinhibitory concentrations of cell wall active antibiotics on virulence gene expression and biofilm formation in Staphylococcus aureus Newman and in laboratory strains., Methods: Promoter regions of spa, lukE and agr RNAIII were cloned upstream of a modified luxABCDE reporter. Using disc diffusion assays, the effects of antibiotics were observed on gene expression and quantitative real-time PCR was employed to confirm the results. Assays were performed to measure biofilm formation in wild-type S. aureus and respective spa-deficient and small colony variant mutants in the presence of subinhibitory concentrations of antibiotics., Results: Expression of spa and lukE was stimulated by subinhibitory concentrations of penicillin and cefalotin, while agr RNAIII expression was not affected. Denser biofilms were formed by S. aureus Newman and its small colony variant in the presence of subinhibitory concentrations of cefalotin., Conclusions: Subinhibitory concentrations of certain antibiotics have been shown to stimulate virulence gene expression in S. aureus; this may alter the progression of infection and thus render antimicrobial therapy unreliable. The use of appropriate combinations of antibiotics might be an approach to avoiding this situation. Promoter-lux reporters are sensitive tools for studying the modulation of transcription by antibiotic inhibitors, and could be used to predict novel therapeutic combinations for the treatment of infection.

Background: The pathogenicity of staphylococcus aureus is dependent largely upon its ability to secrete a number of virulence factors, therefore, anti-virulence strategy to combat S. aureus-mediated infections is now gaining great interest. It is widely recognized that some plant essential oils could affect the production of staphylococcal exotoxins when used at subinhibitory concentrations. Perilla [Perilla frutescens (L.) Britton], a natural medicine found in eastern Asia, is primarily used as both a medicinal and culinary herb. Its essential oil (perilla oil) has been previously demonstrated to be active against S. aureus. However, there are no data on the influence of perilla oil on the production of S. aureus exotoxins., Methodology/principal Findings: A broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of perilla oil against S. aureus strains. Hemolysis, tumour necrosis factor (TNF) release, Western blot, and real-time RT-PCR assays were performed to evaluate the effects of subinhibitory concentrations of perilla oil on exotoxins production in S. aureus. The data presented here show that perilla oil dose-dependently decreased the production of α-toxin, enterotoxins A and B (the major staphylococcal enterotoxins), and toxic shock syndrome toxin 1 (TSST-1) in both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA)., Conclusions/significance: The production of α-toxin, SEA, SEB, and TSST-1 in S. aureus was decreased by perilla oil. These data suggest that perilla oil may be useful for the treatment of S. aureus infections when used in combination with β-lactam antibiotics, which can increase exotoxins production by S. aureus at subinhibitory concentrations. Furthermore, perilla oil could be rationally applied in food systems as a novel food preservative both to inhibit the growth of S. aureus and to repress the production of exotoxins, particularly staphylococcal enterotoxins.

Panton-Valentine Leucocidin (PVL), one of the β-barrel pore-forming staphylococcal leucotoxins, is known to be associated to furuncles and some severe community pneumonia. However, it is still uncertain how many other virulence factors are also associated to furuncles and what the risk factors of furuncles are in immuno-compromised status of patients, especially the HIV (+) patients. In this paper, we use antigen immunoprecipitation and multiplex PCR approach to determine the presence of 19 toxins, 8 adhesion factors and the PFGE profiles associated to furuncles in three independent patient study groups of S. aureus (SA) isolates collected from the Cayenne General Hospital (French Guiana). The patient groups were made of: 16 isolates from HIV (-) patients, 9 from HIV (+) patients suffering from furuncles, and 30 control isolates from patients with diverse secondary infected dermatitis. Our data reveals that the majority (96%) of SA strains isolated from HIV patient-derived furuncles significantly produced PVL (p<10(-7)), whereas only 10% of SA strains produced this toxin in secondary infected dermatosis. A high prevalence of LukE-LukD-producing isolates (56 to 78%) was recorded in patient groups. Genes encoding clumping factor B, collagen- and laminin-binding proteins (clfB, cna, lbp, respectively) were markedly frequent (30 to 55%), without being associated to a specific group. Pulse field gel electrophoresis evidenced 24 overall pulsotypes, whereas the 25 PVL-producing isolates were distributed into 15 non clonal fingerprints. These pulsotypes were not specific PVL-producing isolates. PVL appears to be the major virulence factor associated to furuncles in Europe and in South America regardless of the immune status of the HIV patients.

Aim: To determine the antimicrobial activity of costus (Saussurea lappa) oil against Staphylococcus aureus, and to evaluate the influence of subinhibitory concentrations of costus oil on virulence-related exoprotein production in staph. aureus., Methods and Results: Minimal inhibitory concentrations (MICs) were determined using a broth microdilution method, and the MICs of costus oil against 32 Staph. aureus strains ranged from 0.15 to 0.6 μl ml(-1) . The MIC(50) and MIC(90) were 0.3 and 0.6 μl ml(-1) , respectively. Western blot, haemolytic, tumour necrosis factor (TNF) release and real-time RT-PCR assays were performed to evaluate the effects of subinhibitory concentrations of costus oil on virulence-associated exoprotein production in Staph. aureus. The data presented here show that costus oil dose dependently decreased the production of α-toxin, toxic shock syndrome toxin 1 (TSST-1) and enterotoxins A and B in both methicillin-sensitive Staph. aureus (MSSA) and methicillin-resistant Staph. aureus (MRSA)., Conclusion: Costus oil has potent antimicrobial activity against Staph. aureus, and the production of α-toxin, TSST-1 and enterotoxins A and B in Staph. aureus was decreased by costus oil., Significance and Impact of the Study: The data suggest that costus oil may deserve further investigation for its potential therapeutic value in treating Staph. aureus infections. Furthermore, costus oil could be rationally applied in food products as a novel food preservative both to inhibit the growth of Staph. aureus and to repress the production of exotoxins, particularly staphylococcal enterotoxins., (© 2010 The Authors. Journal of Applied Microbiology © 2010 The Society for Applied Microbiology.)

Panton-Valentine leukocidin (PVL) is a cytotoxin which causes leukocyte destruction and tissue necrosis. Although it is produced by fewer than 5% of Staphylococcus aureus strains, PVL-producing S. aureus is emerging as a serious problem worldwide. There has been a marked increase in the incidence of necrotizing lung infections with a very high mortality associated with these strains. This report describes a fatal case of hospital-acquired necrotizing pneumonia caused by PVL-positive methicillin-susceptible S. aureus in a patient with a brain tumor.

Objective: Panton-Valentine leukocidin expressing Staphylococcus aureus pneumonia, an infection that affects predominantly young people, has a mortality rate of > 70% despite aggressive conventional management. Little information is available on the management of patients with Panton-Valentine leukocidin expressing S. aureus pneumonia with extracorporeal membrane oxygenation support. As a large extracorporeal membrane oxygenation center, we reviewed our experience and outcomes with Panton-Valentine Leukocidin expressing S. aureus pneumonia., Data Sources: Locally held register of all extracorporeal membrane oxygenation patients at Glenfield Hospital., Study Selection: Retrospective study including all patients with sputum-positive Panton-Valentine leukocidin expressing S. aureus pneumonia managed with extracorporeal membrane oxygenation support at a single extracorporeal membrane oxygenation center., Data Synthesis: On review of our database held from September 1989 until date, there were four patients with sputum-confirmed Panton-Valentine leukocidin expressing S. aureus pneumonia managed with extracorporeal membrane oxygenation. Refractory hypoxemia and/or uncompensated hypercapnia despite optimal conventional management were the indications for extracorporeal membrane oxygenation. After varying periods on extracorporeal membrane oxygenation with appropriate antibiotic and ancillary care, all four patients were discharged home., Conclusions: Panton-Valentine leukocidin expressing S. aureus pneumonia can cause severe, necrotizing pneumonia associated with acute respiratory distress syndrome, which can be particularly challenging to manage. Extracorporeal membrane oxygenation support permits low pressure lung ventilation, avoiding barotrauma to lungs made friable by Panton-Valentine leukocidin expressing S. aureus infection. Although this is a small number of patients, the results are encouraging.

Panton-Valentine leukocidin (PVL) has been linked to invasive community-acquired methicillin-resistant Staphylococcus aureus infections. However, the association between disease and PVL-positive methicillin-susceptible Staphylococcus aureus (MSSA) has not been widely reported. We aimed to examine the epidemiology of PVL in clinical MSSA isolates from patients presenting to Auckland City Hospital. Four hundred eleven MSSA clinical isolates and 93 nasal carriage isolates were collected and tested for the presence of the lukSF-PV genes using PCR. The results were examined in light of host and disease factors. Multilocus sequence typing (MLST) was performed on a random subset of isolates to ensure that there was no single PVL-positive MSSA clone responsible for disease in Auckland. The prevalence of the lukSF-PV genes in MSSA isolates associated with disease (124/335; 37%) was not significantly different from the prevalence of the lukSF-PV genes in MSSA nasal carriage isolates (29/93; 31% [P = 0.33]). PVL-positive MSSA isolates in Auckland are genetically diverse and come from a number of different clonal complexes. PVL-positive infections peaked at between 10 and 20 years of age, with a subsequent decline. Pacific ethnicity, age, diagnosis of skin and soft tissue infection (SSTI), community-onset infection, and the need for surgical intervention were found by multivariate analysis to be independently associated with PVL-positive MSSA infection. More than one-third of MSSA infections in our patient population are caused by PVL-positive strains. Those patients with PVL-positive MSSA infection were more likely to be of Pacific ethnicity, be younger in age, have community-onset infection, have SSTI, and need surgical intervention.

The presence of Panton-Valentine leukocidin expressing Staphylococcus aureus colonization was investigated with a qualitative nucleic acid hybridization assay among 122 children and 19 staff in a child care center. Genotyping of 5 Panton-Valentine leukocidin-positive isolates by pulsed-field gel electrophoresis revealed that one child and a teacher from the same class were colonized with the clonally related strains. This finding allowed us to suggest that close contact with colonized people is a risk factor for being colonized.

We describe a rare case of multifocal necrotizing fasciitis (NF) complicating a single vaccine injection. Injection of hepatitis B vaccine of a 16-year-old immunocompetent woman developed into rapidly spreading multifocal NF of the right arm and the thighs, with septic shock. Treatment with antimicrobial therapy and surgical debridements allowed amputation to be avoided with a favourable outcome. The etiological agent was a methicillin-sensitive Staphylococcus aureus (MSSA) isolate harboring the Panton-Valentine leukocidin (PVL) and five enterotoxins. PVL has recently been reported in large series of methicillin-resistant SA cases and has been associated with necrotizing infections. Some strains of MSSA could harbor PVL and enterotoxins. PCR investigation is not frequent but could improve the understanding of the mechanisms of lesions. This case is in keeping with the increasing incidence of MSSA harboring PVL and enterotoxins with multifocal dissemination NF and emphasizes the necessary precautions for skin decontamination before vaccine injection.

Staphylococcus aureus is a major cause of skin and soft tissue infections, such as furuncles, carbuncles, and abscesses, but it also frequently colonizes the human skin and mucosa without causing clinical symptoms. Panton-Valentine leukocidin (PVL) is a pore-forming toxin that has been associated with soft tissue infections and necrotizing pneumonia. We have compared the genotypes, virulence gene repertoires, and phage patterns of 74 furunculosis isolates with those of 108 control strains from healthy nasal carriers. The large majority of furunculosis strains were methicillin sensitive. Clonal cluster (CC) 121 (CC121) and CC22 accounted for 70% of the furunculosis strains but for only 8% of the nasal isolates. The PVL-encoding genes luk-PV were detected in 85% of furunculosis strains, while their prevalence among colonizing S. aureus strains was below 1%. luk-PV genes were distributed over several lineages (CCs 5, 8, 22, 30, and 121 and sequence type 59). Even within the same lineages, luk-PV-positive phages characterized furunculosis strains, while their luk-PV-negative variants were frequent among nasal strains. The very tight epidemiological linkage between luk-PV and furunculosis, which could be separated from the genetic background of the S. aureus strain as well as from the gene makeup of the luk-PV-transducing phage, lends support to the notion of an important role for PVL in human furunculosis. These results make a case for the determination of luk-PV in recurrent soft tissue infections with methicillin-sensitive as well as methicillin-resistant S. aureus.

We describe a case of fatal pneumonia in a previously healthy 14-year-old boy. The patient was severely affected at the time of admission with high fever, tachypnea, tachycardia and peripheral cyanosis. The condition worsened despite treatment with antibiotics as well as respiratory and pressure support. Acidosis and critical leucopenia supervened and the patient died just short of 24 hours after admission. Subsequent bacterial cultivation showed Panton-Valentine Leucocidin-producing Staphylococcus aureus.

Panton-Valentine leukocidin toxin producing Staphylococcus aureus (PVLSA) is known to be responsible for recurrent soft tissue infections and more serious invasive infections including necrotising pneumonia, pyomyositis, and osteomyelitis. Most reported cases involving musculoskeletal infection in adults are associated with methicillin-resistant S. aureus (MRSA) PVL-producing strains. We present the case of an adult male with PVL toxin-producing methicillin-sensitive S. aureus (MSSA) osteomyelitis of the tibia which has not previously been described in adults and highlight issues of recognition, treatment, and surgical management of PVLSA osteomyelitis.

Background: Postinfluenza Staphylococcus aureus pneumonias are increasingly recognized as a major form of life-threatening infections., Methods: A mouse model of postinfluenza S. aureus pneumonia was developed. Mice were intranasally infected with bacteria alone or bacteria plus virus. Infection was assessed by mouse survival, lung histopathology, bacterial density in the lungs, and cellular response to infection., Results: Mice infected with both influenza virus and S. aureus showed higher mortality, greater lung parenchymal damage, and greater bacterial density at metastatic tissue sites than mice infected with only S. aureus. At 4 h, more polymorphonuclear leukocytes and fewer CD11c(+) cells were found in lung samples from mice infected with virus and bacteria than in those from mice infected with bacteria. alpha-Hemolysin and protein A were maximally expressed 4 h after infection, and Panton-Valentine leukocidin was maximally expressed 72 h after infection, with higher levels of alpha-hemolysin expression in mice infected with bacteria alone. Interferon gamma expression was higher in tissue collected from mice infected with virus plus bacteria than in those from bacteria-infected mice., Conclusions: The results from this model demonstrate diverse effects caused by antecedent influenza virus infection, which have a profound influence on the morbidity and mortality associated with S. aureus pneumonia.