Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant<i>Staphylococcus aureus</i>Coinfection in Children With Influenza-related Critical Illness

Wardenburg, Juliane Bubeck; Moffitt, Kristin; Kong, Michele; Sanders, Ronald C.; Hefley, Glenda; Téllez, David; Typpo, Katri; Markovitz, Barry P.; Morzov, Rica Sharon P.; Graciano, Ana Lía; Cvijanovich, Natalie Z.; Flori, Heidi R.; Brumfield, Becky; Anas, Nick; Schwarz, Adam; Vargas-Shiraishi, Ofelia; McQuillen, Patrick S.; Sapru, Anil; Mourani, Peter M.; Czaja, Angela S.; Carroll, Christopher L.; Giuliano, John S.; Tala, Joana; Palmieri, Lisa; McLaughlin, Gwenn E.; Paden, Matthew L.; Tarquinio, Keiko M.; Stone, Cheryl; Coates, Bria M.; Pinto, Neethi; Sullivan, Janice E.; Montgomery, Vicki; Randolph, Adrienne G.; Xu, Ruifei; Agan, Anna A.; Novak, Tanya; Newhams, Margaret M; Bembea, Melania M.; Kudchadkar, Sapna R.; Kurachek, Stephen C.; Hartman, Mary E.; Doctor, Allan; Barrale, Tina; Truemper, Edward J.; Mahapatra, Sidharth; Dawson, Machelle; Kustka, Lucinda; Malone, Kristin; Schrack, Melanie; Katyal, Chhavi; Ackerman, Kate G.; Daugherty, L. Eugene; Shein, Steven L.; Lemon, Eloise; DeFrancesco, Kathryn; Hall, Mark W.; Steele, Lisa; Thomas, Neal J.; Spear, Debra; Weiss, Scott L.; Fitzgerald, Julie C; Bush, Jenny; Graham, Kathryn; Barr, Frederick E.; Higgerson, Renee A.; Christie, LeeAnn M.; Bowens, Cindy Darnell; Thompson, Marita; Loftis, Laura; Jaimon, Nancy; Wilson, Douglas F.; Gedeit, Rainer; Murkowski, Kathy; Siegel, Katherine; Dugas, Marc-André

doi:10.1093/cid/ciy495

Cited by 39 publications

(32 citation statements)

References 36 publications

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“…This limitation is mitigated in part by the multicentric design and use of Monte Carlo cross validation methods. Second, bacterial coinfection is a known risk factor for more severe and sustained PARDS ( 21 ). However, we did not include coinfection in the predictive models because it is a difficult diagnosis to make prospectively at day 2 ( 21 , 44 ).…”

Section: Discussionmentioning

confidence: 99%

“…Second, bacterial coinfection is a known risk factor for more severe and sustained PARDS ( 21 ). However, we did not include coinfection in the predictive models because it is a difficult diagnosis to make prospectively at day 2 ( 21 , 44 ). Third, the outcome was treated as a binary variable, without incorporating mortality.…”

Section: Discussionmentioning

confidence: 99%

“…Data were prospectively collected by the PALISI Pediatric Intensive Care Influenza Investigators across 34 international PICUs from November 2009 to April 2018. Detailed methods have been previously reported ( 20 , 21 ). Children (< 18 yr) were admitted to a PICU with severe acute respiratory infection symptoms and microbiologically confirmed influenza virus infection.…”

Section: Methodsmentioning

confidence: 99%

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Machine Learning Predicts Prolonged Acute Hypoxemic Respiratory Failure in Pediatric Severe Influenza

Sauthier¹,

Jouvet

Newhams

et al. 2020

Critical Care Explorations

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Machine Learning Predicts Prolonged Acute Hypoxemic Respiratory Failure in Pediatric Severe Influenza

Sauthier¹,

Jouvet

Newhams

et al. 2020

Critical Care Explorations

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show abstract

“…Current data still lacks proof that the clinical presentation with viral-bacterial co-infections directly leads to worse outcomes, but a growing body of evidence suggests that influenza-bacterial co-infections are associated with higher morbidity and higher mortality [65,[73][74][75][76]. In fact, a recent study showed that the presence of co-infection in adults with influenza-associated acute respiratory syndrome requiring extra-corporeal membrane oxygenation was significantly associated with a fourfold increase in mortality [77], and another study in children with Staphylococcus aureus co-infection with influenza-related critical illness also showed a ninefold significant increase in mortality [78].…”

Section: Role Of Viral-bacterial Co-infections and Their Effect On Oumentioning

confidence: 99%

Influenza virus-related critical illness: pathophysiology and epidemiology

2019

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Influenza virus affects the respiratory tract by direct viral infection or by damage from the immune system response. In humans, the respiratory epithelium is the only site where the hemagglutinin (HA) molecule is effectively cleaved, generating infectious virus particles. Virus transmission occurs through a susceptible individual’s contact with aerosols or respiratory fomites from an infected individual. The inability of the lung to perform its primary function of gas exchange can result from multiple mechanisms, including obstruction of the airways, loss of alveolar structure, loss of lung epithelial integrity from direct epithelial cell killing, and degradation of the critical extracellular matrix. Approximately 30–40% of hospitalized patients with laboratory-confirmed influenza are diagnosed with acute pneumonia. These patients who develop pneumonia are more likely to be < 5 years old, > 65 years old, Caucasian, and nursing home residents; have chronic lung or heart disease and history of smoking, and are immunocompromised. Influenza can primarily cause severe pneumonia, but it can also present in conjunction with or be followed by a secondary bacterial infection, most commonly by Staphylococcus aureus and Streptococcus pneumoniae . Influenza is associated with a high predisposition to bacterial sepsis and ARDS. Viral infections presenting concurrently with bacterial pneumonia are now known to occur with a frequency of 30–50% in both adult and pediatric populations. The H3N2 subtype has been associated with unprecedented high levels of intensive care unit (ICU) admission. Influenza A is the predominant viral etiology of acute respiratory distress syndrome (ARDS) in adults. Risk factors independently associated with ARDS are age between 36 and 55 years old, pregnancy, and obesity, while protective factors are female sex, influenza vaccination, and infections with Influenza A (H3N2) or Influenza B viruses. In the ICU, particularly during the winter season, influenza should be suspected not only in patients with typical symptoms and epidemiology, but also in patients with severe pneumonia, ARDS, sepsis with or without bacterial co-infection, as well as in patients with encephalitis, myocarditis, and rhabdomyolysis.

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“…Linezolid therapy has been reported to produce a survival advantage in patients with nosocomial MRSA pneumonia (3,4). A recent study also suggested that vancomycin is insufficient to treat MRSA pneumonia in children with influenza-related critical illness (30). In animal studies, it has been shown that treatment with linezolid but not vancomycin significantly delayed weight loss compared with placebo during postinfluenza MRSA pneumonia (31).…”

Section: Discussionmentioning

confidence: 99%

Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia

et al. 2019

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Postinfluenza methicillin-resistant Staphylococcus aureus (MRSA) infection can quickly develop into severe, necrotizing pneumonia, causing over 50% mortality despite antibiotic treatments. In this study, we investigated the efficacy of antibiotic therapies and the impact of S. aureus alpha-toxin in a model of lethal influenza virus and MRSA coinfection. We demonstrate that antibiotics primarily attenuate alpha-toxin-induced acute lethality, even though both alpha-toxin-dependent and -independent mechanisms significantly contribute to animal mortality after coinfection. Furthermore, we found that the protein synthesis-suppressing antibiotic linezolid has an advantageous therapeutic effect on alpha-toxin-induced lung damage, as measured by protein leak and lactate dehydrogenase (LDH) activity. Importantly, using a Panton-Valentine leucocidin (PVL)-negative MRSA isolate from patient sputum, we show that linezolid therapy significantly improves animal survival from postinfluenza MRSA pneumonia compared with vancomycin treatment. Rather than improved viral or bacterial control, this advantageous therapeutic effect is associated with a significantly attenuated proinflammatory cytokine response and acute lung damage in linezolid-treated mice. Together, our findings not only establish a critical role of alpha-toxin in the extreme mortality of secondary MRSA pneumonia after influenza but also provide support for the possibility that linezolid could be a more effective treatment than vancomycin to improve disease outcomes.

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Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistantStaphylococcus aureusCoinfection in Children With Influenza-related Critical Illness

Abstract: Influenza-MRSA coinfection is associated with high fatality in critically ill children. These data support early addition of a second anti-MRSA antibiotic to vancomycin in suspected severe cases.

Cited by 39 publications

References 36 publications

Machine Learning Predicts Prolonged Acute Hypoxemic Respiratory Failure in Pediatric Severe Influenza

Machine Learning Predicts Prolonged Acute Hypoxemic Respiratory Failure in Pediatric Severe Influenza

Influenza virus-related critical illness: pathophysiology and epidemiology

Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia

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