Severe burns inflict extensive tissue damage, prompting the release of proinflammatory cytokines, damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs), collectively contributing to the dysregulated host immune response observed in burn patients.² This immunocompromised state, compounded by factors such as impaired neutrophil function, complement depletion, and disruption of mucocutaneous defenses, predisposes burn patients to opportunistic infections, including bacteremia.⁵

The pathogenesis of bacteremia in severe burn patients is multifaceted, encompassing a spectrum of microbial etiologies ranging from common skin commensals to nosocomial pathogens in healthcare environments. Burn wound colonization is a primary reservoir for these pathogens, facilitating their hematogenous dissemination and seeding distant sites, thereby perpetuating a cycle of systemic infection and organ dysfunction.⁶

Streptococcus mitis, a part of the Viridans Group Streptococci (VGS), is commonly found as part of the oral microbiota in humans. On sheep blood agar, Streptococcus mitis is alpha-hemolytic. While it is typically considered a commensal bacterium and rare-causing disease, it can act as an opportunistic pathogen under certain conditions, particularly in individuals with compromised immune systems or in specific host environments such as burn wounds.⁷ In this patient, Streptococcus mitis could enter the blood system due to burn injuries and mucosal lesions from the oral cavity.

Streptococcus mitis may contribute to pathogenicity in burn infections through various virulence factors, including adhesion and biofilm formation, extracellular enzymes, toxin production, and immunomodulatory factors.⁷ Streptococcus mitis possesses surface adhesins that enable it to adhere to host tissues and form biofilms. Biofilm formation on burn wounds can promote bacterial colonization, enhance resistance to host immune defenses, and facilitate persistent infection. The virulence factors like IgA1 protease and zinc metalloprotease C, neuraminidases A and B, autolysin, pneumolysin, several choline-binding proteins, and PavA were present in some strains of Streptococcus mitis.⁸ These enzymes may degrade host proteins, disrupt tissue integrity, and promote the spread of infection within the burn wound and to surrounding tissues.

Some strains of Streptococcus mitis can produce toxins such as hemolysins, which can lyse host cells and contribute to tissue necrosis. These toxins may exacerbate tissue damage, impair wound healing, and promote the systemic spread of infection, leading to septic complications in burn patients. Streptococcus mitis cell surface consists of a lipid bilayer, cell wall peptidoglycan (PG), cell wall-associated teichoic acids (WTA), membrane-associated lipoteichoic acids (LTA), and a variety of proteins that can modulate host immune responses.⁹ Based on the bioinformatic study, most Streptococcus mitis strains should contain the same type IV LTA as Streptococcus pneumoniae.¹⁰ In addition, some strains of Streptococcus mitis can express serotype-1 capsule, similar to serotype-1 from Streptococcus pneumoniae.¹¹ These can influence inflammatory signaling pathways and contribute to the dysregulated immune response observed in burn patients. These immunomodulatory factors may exacerbate tissue inflammation, impair wound healing, and promote systemic complications associated with burn infections.¹²

Klebsiella pneumoniae is a Gram-negative bacterium commonly associated with hospital-acquired infections, including those occurring in severe burn patients. Klebsiella pneumoniae is one of the most predominant bacteria in burn infections after Pseudomonas aeruginosa and Acinetobacter baumannii.¹³ In the context of burn injuries, Klebsiella pneumoniae can exhibit several virulence factors that contribute to its pathogenicity and exacerbate the clinical course in affected individuals. Klebsiella pneumoniae is known for its ability to produce a thick polysaccharide capsule, which serves as a major virulence determinant. In severe burn patients, the presence of a robust capsule can enhance the ability of Klebsiella pneumoniae to colonize burn wounds and disseminate systemically, leading to invasive infections and septic complications.¹⁴

Klebsiella pneumoniae can adhere to host tissues and medical devices, facilitating colonization of burn wounds and other anatomical sites.¹⁵ Moreover, Klebsiella pneumoniae can form biofilms on abiotic surfaces, such as catheters, endotracheal tubes, and wound dressings, as well as on biotic surfaces within the burn wound environment. Biofilms are highly structured microbial communities that display increased resistance to antimicrobial factors and host defenses.¹⁶ Biofilm formation poses a significant challenge in managing burn patients.

Klebsiella pneumoniae can secrete various virulence factors, including capsules, exopolysaccharides associated with mucoviscosity, lipopolysaccharides (LPSs), adhesins, and iron uptake systems.¹⁷ Klebsiella pneumoniae can secrete siderophores and scavenge iron from host proteins, allowing Klebsiella pneumoniae to thrive in iron-limited environments such as the burn wound. The ability to obtain iron is critical to the growth and replication of bacteria.¹⁸ There are four iron carriers in Klebsiella pneumoniae; enterobactin, yersiniabactin, salmochelin, and aerobactin. Enteromycin has the highest affinity for iron and is considered the primary iron absorption system.¹⁹ Hemolysins lyse host cells and contribute to tissue damage. At the same time, proteases degrade host proteins and extracellular matrix components, promoting bacterial dissemination and tissue destruction in severe burn patients.

Due to its enhanced resistance and recently focused hypervirulence, Klebsiella pneumoniae has been of more significant concern worldwide in the past decades.²⁰ Klebsiella pneumoniae is notorious for its ability to acquire antimicrobial resistance through various mechanisms, including the production of ג-lactamases, efflux pumps, and alterations in outer membrane proteins. This resistance can limit the efficacy of commonly used antibiotics in treating Klebsiella pneumoniae infections, complicating the management of burn patients and necessitating alternative antimicrobial agents or combination therapies.¹⁴ Klebsiella pneumoniae can modulate host immune responses by producing immunomodulatory molecules such as lipopolysaccharide (LPS) and capsular polysaccharides. These molecules can trigger excessive inflammation, leading to tissue damage and organ dysfunction in severe burn patients.²

Cefuroxime is a second-generation cephalosporin antibiotic with a broad spectrum and can be active against gram-negative and gram-positive bacteria, including Streptococcus Spp and Klebsiella pneumoniae.²¹ Cefuroxime is generally recommended for burn patients because it has relatively good effectiveness, is cheaper, and does not promote drug resistance. Cefuroxime is an antibiotic usually used in Dr. Soetomo General Academic Hospital for burn patients.²²

Streptococcus mitis and Klebsiella pneumoniae have different virulence factors and mechanisms of pathogenesis, but their interactions within the host environment can influence disease outcomes. Understanding the virulence factors employed by Streptococcus mitis and Klebsiella pneumoniae in burn infections is crucial for devising effective therapeutic strategies to mitigate bacterial pathogenicity, prevent complications, and improve clinical outcomes in affected individuals. Further research into the molecular mechanisms underlying Streptococcus mitis and Klebsiella pneumoniae virulence in burn patients is warranted to inform the development of targeted interventions for managing infections caused by these opportunistic pathogens.