Patients who are admitted to the hospital after sustaining a large burn injury are at high risk for developing hospital-associated infections. If patients survive the initial 72 hours after a burn injury, infections are the most common cause of death. Ventilator-associated pneumonia is the most important infection in this patient population. The risk of infections caused by multidrug-resistant bacterial pathogens increases with hospital length of stay in burn patients. In the first days of the postburn hospitalization, more susceptible, Gram-positive organisms predominate, whereas later more resistant Gram-negative organisms are found. These findings impact the choice of empiric antibiotics in critically ill burn patients. A proactive infection control approach is essential in burn units. Furthermore, a multidisciplinary approach to burn patients with a team that includes an infectious disease specialist and a pharmacist in addition to the burn surgeon is highly recommended.
Chronic coinfections of Staphylococcus aureus and Pseudomonas aeruginosa frequently fail to respond to antibiotic treatment, leading to significant patient morbidity and mortality. Currently, the impact of interspecies interaction on S. aureus antibiotic susceptibility remains poorly understood. In this study, we utilize a panel of P. aeruginosa burn wound and cystic fibrosis (CF) lung isolates to demonstrate that P. aeruginosa alters S. aureus susceptibility to bactericidal antibiotics in a variable, strain-dependent manner and further identify 3 independent interactions responsible for antagonizing or potentiating antibiotic activity against S. aureus. We find that P. aeruginosa LasA endopeptidase potentiates lysis of S. aureus by vancomycin, rhamnolipids facilitate proton-motive force-independent tobramycin uptake, and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) induces multidrug tolerance in S. aureus through respiratory inhibition and reduction of cellular ATP. We find that the production of each of these factors varies between clinical isolates and corresponds to the capacity of each isolate to alter S. aureus antibiotic susceptibility. Furthermore, we demonstrate that vancomycin treatment of a S. aureus mouse burn infection is potentiated by the presence of a LasA-producing P. aeruginosa population. These findings demonstrate that antibiotic susceptibility is complex and dependent not only upon the genotype of the pathogen being targeted, but also on interactions with other microorganisms in the infection environment. Consideration of these interactions will improve the treatment of polymicrobial infections.
Background
Infections are an important cause of morbidity and mortality after burn injuries. Here, we describe the timeline of infections and pathogens after burns.
Methods
A retrospective study was performed in a large tertiary care burn center from 2004 through 2013. Analyses were performed on healthcare-associated infections (HAI) meeting Centers for Disease Control and Prevention criteria and on all positive cultures. Incidence rates (IR) per 1,000 days were calculated for specific HAI categories and pathogens, and across hospitalization time (week 1, 2–3 and 4+).
Results
Among 5,524 patients the median burn size was 4% of total body surface area (interquartile range, 2–10%). 7% of patients developed an HAI, of whom 33% had more than one HAI episode. Gram-positive bacteria were isolated earlier and Gram-negative later during hospitalization. Of 1,788 bacterial isolates, 44% met criteria for multi-drug resistance and 23% for extensive drug resistance. Bacteria tended to become increasingly resistant to antibiotics as time from admission increased.
Conclusions
We observed differences in infection type, pathogen and antibiotic resistant bacterium risk across time of hospitalization. These results may guide infection prevention in various stages of the post-burn admission.
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