Yves Gillet

Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients

BACKGROUND Between 1986 and 1998, eight cases of community-acquired pneumonia due to Staphylococcus aureus strains carrying the gene for the Panton-Valentine leukocidin (PVL) were recorded in France, six of which were fatal. We aimed to assess the clinical features of these eight cases, and those of other cases identified prospectively, and to compare them with the characteristics of patients with pneumonia caused by PVL-negative strains. METHODS We compared eight retrospective and eight prospective cases of PVL-positive S aureus pneumonia with 36 cases of PVL-negative S aureus pneumonia. For all patients, we recorded age, length of hospital stay, risk factors for infection, signs and symptoms, laboratory findings, antibiotic treatment, and serial radiological findings. FINDINGS Median age was 14.8 years (IQR 5.4-24.0) for the PVL-positive patients and 70.1 years (59.2-81.4) for the others (p=0.001). Influenza-like illness had occurred during the 2 days before admission in 12 of the 16 PVL-positive patients, but in only three of 33 PVL-negative patients (p<0.001). PVL-positive infections were more often marked by: temperature greater than 39 degrees C (p=0.01), heart rate above 140 beats per min (p=0.02), haemoptysis (p=0.005), onset of pleural effusion during hospital stay (p=0.004), and leucopenia (p=0.001). The survival rate 48 h after admission was 63% for the PVL-positive patients and 94% for PVL-negative individuals (p=0.007). Histopathological examination of lungs at necropsy from three cases of necrotising pneumonia associated with PVL-positive S aureus showed extensive necrotic ulcerations of the tracheal and bronchial mucosa and massive haemorrhagic necrosis of interalveolar septa. INTERPRETATION PVL-producing S aureus strains cause rapidly progressive, haemorrhagic, necrotising pneumonia, mainly in otherwise healthy children and young adults. The pneumonia is often preceded by influenza-like symptoms and has a high lethality rate.

COMMUNITY-ACQUIRED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS INFECTIONS IN FRANCE: EMERGENCE OF A SINGLE CLONE THAT PRODUCES PANTON-VALENTINE LEUKOCIDIN

To characterize the clinical and bacteriologic characteristics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, we reviewed 14 cases that were diagnosed in previously healthy patients during an 18-month period in France. Eleven patients had skin or soft-tissue infections. Two patients died of CA-MRSA necrotizing pneumonia. A case of pleurisy occurred in a child who acquired CA-MRSA from his mother, who had a breast abscess. The Panton-Valentine leukocidin genes and the lukE-lukD leukocidin genes were detected in all 14 isolates. The clonal origin of all of the isolates was demonstrated on the basis of their pulsotypes and antibiotic resistance profiles. All isolates had an agr3 allele. The combination of the Panton-Valentine leukocidin determinant (which encodes a virulence factor for primary skin infection and pneumonia) with the mecA gene (which confers antibiotic resistance and epidemicity) appears to have created a superadapted S. aureus strain that is spreading in the community.

Factors Predicting Mortality in Necrotizing Community-Acquired Pneumonia Caused by Staphylococcus aureus Containing Panton-Valentine Leukocidin

BACKGROUND Necrotizing pneumonia due to Panton-Valentine leukocidin-producing strains of Staphylococcus aureus is associated with a high mortality rate. We sought factors associated with vital outcome in 50 cases occurring from 1986 through 2005. METHODS We compared the clinical and biological characteristics of 50 patients according to their vital outcome and examined the characteristics of the corresponding S. aureus isolates. RESULTS The overall mortality rate was 56%, and the median survival time was 10 days. All of the deaths were attributed to S. aureus infection and were secondary to refractory shock and/or respiratory failure. Fatal outcome was associated with classical severity factors, such as the need for mechanical ventilation or inotrope support, and with onset of the acute respiratory distress syndrome. Airway bleeding was strongly associated with fatal outcome (P=.002). Patients who had focal staphylococcal infection before the onset of pneumonia had a significantly lower mortality rate (P=.002). The main biological feature associated with death was leukopenia (P<.001). In multivariate analysis, leukopenia and erythroderma occurring within the first 24 h after admission to the hospital were independently associated with fatal outcome. Erythroderma was not associated with toxic shock syndrome toxin. CONCLUSIONS Airway bleeding, erythroderma, and leukopenia are associated with fatal outcome from Panton-Valentine leukocidin-positive S. aureus necrotizing pneumonia. More work is needed to develop more efficacious therapy against this highly lethal disease.

Pediatric bone and joint infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus.

Background: Panton-Valentine leukocidin (PVL) is a necrotizing toxin secreted by Staphylococcus aureus. PVL-positive S. aureus osteomyelitis and arthritis have been described. Methods: We analyzed demographic, clinical, laboratory, microbiologic, and imaging data in a study group of 14 pediatric cases with PVL-positive S. aureus osteomyelitis and arthritis diagnosed between 2001 and 2005 and compared results with a control group of 17 pediatric cases of PVL-negative S. aureus osteomyelitis and arthritis treated in our institution during the same period. Treatments and outcome were studied. Results: The severity of PVL-positive S. aureus bone and joint infections was indicated by the presence of severe sepsis in all cases and of septic shock in 6 of the 14 patients. By comparison, severe sepsis was not noted in the control group (P = 0.004). On admission, the median C-reactive protein value was significantly higher in the study group (202.6 mg/L versus 83 mg/L in the control group; P = 0.001). Eleven patients with PVL-positive infection had local extension of the infection by magnetic resonance imaging and 7 patients had severe deep-seated infectious complications by computed tomography. By contrast only 1 patient in the control group presented with bone abscess without extension and none had deep-seated infection (P < 0.001). The median length of hospitalization was 45.5 days in the study group versus 13 days in the control group (P < 0.001). The median duration of intravenous antibacterial chemotherapy was 48 days versus 11.3 days in the control group (P < 0.001). Ten patients (71%) of the study group required surgical procedures with a mean of 3 procedures (range, 1–5) whereas 3 patients (17%) of the control group required 1 surgical drainage each (P = 0.002). All the patients survived, but only 2 patients of the study group were free of long-term complications, whereas there were no long-term complications noted in the control group. Conclusion: PVL-positive S. aureus bone and joint infection is severe and requires prolonged treatment. Local complications are more frequent and often need repeated surgical drainage.

Toxin involvement in staphylococcal scalded skin syndrome.

The production of staphylococcal exfoliative toxin A (ETA) and toxin B (ETB), toxic shock syndrome toxin (TSST-1), and enterotoxins A-E was analyzed in 60 Staphylococcus aureus strains isolated from children with scalded skin syndrome (15 with generalized exfoliative syndrome, 28 with bullous impetigo, and 17 with staphylococcal scarlet fever). All strains isolated from patients with generalized exfoliative syndrome or bullous impetigo produced ETA and/or ETB and caused a Nikolskys sign when injected subcutaneously into newborn mice. In contrast, exfoliative toxin was detected in an S. aureus strain from only one of 17 case of staphylococcal scarlet fever; the 16 other S. aureus strains produced TSST-1 and/or an enterotoxin. In conclusion, enterotoxins or TSST-1 are more frequently associated with staphylococcal scarlet fever than are exfoliative toxins. Hence staphylococcal scarlet fever may well represent an abortive form of toxic shock syndrome rather than a milder form of staphylococcal scalded skin syndrome.

Early Impact of 13-Valent Pneumococcal Conjugate Vaccine on Community-Acquired Pneumonia in Children

BACKGROUND Pneumococcal serotypes 1, 3, 5, 7F, and 19A were the most implicated in community-acquired pneumonia (CAP) after implementation of 7-valent pneumococcal conjugate vaccine (PCV7). In France, the switch from PCV7 to 13-valent pneumococcal conjugate vaccine (PCV13) occurred in June 2010. An active surveillance network was set up to analyze the impact of PCV13 on CAP. METHODS An observational prospective study performed in 8 pediatric emergency departments from June 2009 to May 2012 included all children between 1 month and 15 years of age with chest radiography-confirmed pneumonia. Three 1-year periods were defined: pre-PCV13, transitional, and post-PCV13. RESULTS During the 3-year study period, among the 953 274 pediatric emergency visits, 5645 children with CAP were included. CAP with pleural effusion and documented pneumococcal CAP were diagnosed in 365 and 136 patients, respectively. Despite an increase (4.5%) in number of pediatric emergency visits, cases of CAP decreased by 16% (2060 to 1725) between pre- and post-PCV13 periods. The decrease reached 32% in infants in the same periods (757 to 516; P < .001). Between pre- and post-PCV13 periods, the proportion of CAP patients with a C-reactive protein level >120 mg/dL decreased from 41.3% to 29.7% (P < .001), the number of pleural effusion cases decreased by 53% (167 to 79; P < .001) and the number of pneumococcal CAP cases decreased by 63% (64 to 24; P = .002). The number of additional PCV13 serotypes identified decreased by 74% (27 to 7). CONCLUSIONS Our data suggest a strong impact of PCV13 on CAP, pleural effusion, and documented pneumococcal pneumonia, particularly cases due to PCV13 serotypes.

Influenza burden in children newborn to eleven months of age in a pediatric emergency department during the peak of an influenza epidemic.

Background. The aim of this study was to determine the burden of influenza-related diseases in children 0 to 11 months of age during the peak of the 2001 to 2002 influenza epidemic. Methods. This was a prospective study at the Pediatric Emergency Department of Edouard Herriot tertiary teaching hospital in Lyon, France. The study included 304 infants 0 to 11 months of age. Consecutive patients were systematically enrolled during the 4 weeks of the influenza epidemic peak (Weeks 3 to 6, 2002). Influenza viruses were detected by antigen detection and virus culture from nasal swabs. Structured telephone interviews were conducted on Days 8 and 15 after virus detection. There was also a 6-month survey into the medicoadministrative database to detect late complications that required delayed hospitalization of influenza-positive children. Results. Influenza virus was detected in 99 (33%) of 304 patients (A/H3N2 in 30% and B in 3%). Nonrespiratory symptoms were the dominant clinical manifestations in 30% of influenza-positive children. One child with influenza presented with febrile seizures. Twenty (20%) children with influenza were hospitalized. Parents reported recovery from the illness in 63 and 94% of children on Days 8 and 15, respectively. The median length of an influenza episode was 8 days. Conclusions. Our results confirm the high prevalence of influenza-related morbidity in infants during the epidemic peak. One child in three consulting to the pediatric emergency room had a virologically confirmed influenza infection regardless of the body temperature. Every fifth child with influenza was admitted to hospital, which corresponds to an admission rate of 237 per 100 000 children 0 to 11 months of age.

Prompt and Successful Toxin-Targeting Treatment of Three Patients with Necrotizing Pneumonia Due to Staphylococcus aureus Strains Carrying the Panton-Valentine Leukocidin Genes

ABSTRACT Three patients with extensive necrotizing pneumonia due to Panton-Valentine leukocidin-positive Staphylococcus aureus strains and with aggravating factors (leukopenia count of less than 3 × 109/liter in all three cases and hemoptysis in two cases) were successfully treated with toxin-suppressing agents introduced rapidly after hospital admission.

Human parechovirus infections, Lyon, France, 2008-10: evidence for severe cases.

BACKGROUND Although data documenting the frequency and severity of human parechovirus type 3 (HPeV-3) infection in infants have been published in Canada, the USA, the UK and the Netherlands, no data from France are available. OBJECTIVES To determine the detection frequency of HPeV in cerebrospinal fluid (CSF) samples collected from children aged <5 years hospitalized between 2008 and 2010 in the University Hospital of Lyon and to describe the clinical, virological and biological characteristics associated with HPeV infection. STUDY DESIGN A total of 1128 CSF samples were retrospectively tested using the Parechovirus-Rgene™ real-time RT-PCR assay. Positive samples were typed by sequencing using the CDC method. Retrospective analysis of the medical charts was performed. RESULTS Over a 3-year period, 33/1128 (2.9%) CSF samples were found to be HPeV-positive. In 2010, 9.3% of the children aged <3 months (32% in June) were detected HPeV-positive. The median age at diagnosis was 26 days (8-131 days). Most patients (86%) presented with fever or a sepsis-like syndrome. Three patients (2 with septic shock syndrome, 1 with severe respiratory distress) required hospitalization in an intensive care unit. An HPeV-3 acute infection was identified in an 11-day-old girl who died from sudden infant death syndrome. Of 29 patients genotyped, 28 were infected with HPeV-3 and one with HPeV-4. CONCLUSIONS HPeV is a significant cause of sepsis and severe sepsis in children <3 months. Routine screening for HPeV in CSF and blood should thus be performed more extensively and could improve clinical management.

Panton–Valentine leukocidin is expressed at toxic levels in human skin abscesses

Pus samples were prospectively collected from patients with Staphylococcus aureus skin infections and tested for Panton-Valentine leukocidin (PVL). PVL was detected at concentrations that were toxic for rabbit skin in all specimens from patients infected with strains harbouring PVL genes.