Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

Abstract

Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

Keywords: Acinetobacter; Acinetobacter baumannii; Acinetobacter calcoaceticus.

FIG 1

Host fate during Acinetobacter infection is determined in two stages. (A) Early clearance of the microbe by the three primary innate effectors, complement (circled 1), neutrophils (circled 2), and macrophages (circled 3), results in prevention of a sustained LPS-TLR4 activation and subsequent cytokine storm. (B) If the organism can resist initial innate effector clearance and replicate, it triggers sustained LPS activation of TLR4, resulting in cytokine storm and sepsis syndrome. One mechanism by which the organism may be able to evade clearance is by expression of an altered capsule that resists complement and phagocytic uptake (denoted by thicker shell around the bacteria).