- Acinetobacters are strictly aerobic, oxidase-negative, plump gram-negative coccobacilli which are ubiquitous saprophytes, recovered in nature and in the hospitals.
- They are opportunistic pathogens that cause infections in the respiratory tract, urinary tract, and wounds; they also cause septicemia.
- Acinetobacter is subdivided into two groups: glucose oxidizing species ( A. baumannii is the most common) and glucose non-oxidizing species (A. lwoffii and A. haemolyticus are the most common).
- Most human infections are caused by A. baumannii.
Figure: Acinetobacter baumannii surface-exposed glycoconjugates.
Pathogenicity of A. baumannii
- 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 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.
- The 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.
- The intrusion of a microorganism requires cell-to-cell adhesion to establish infection.
- However, the capability of A. baumannii to anchor with cells/mucosal cells is low as compared to other microorganisms.
- The reduced adhesion and invasion of A. baumannii attribute to its low virulence; however, it possesses a hydrophobic ability that provides attachment to foreign materials such as plastics used in intravascular devices.
- Outer membrane protein A (OmpA) is associated with improving adhesion, specifically to the epithelial cells of the respiratory tract. It localizes in the mitochondria and nuclei and induces expression of proapoptotic molecule cytochrome c, resulting in cell death.
- A. baumannii evades alternative complement pathway-mediated killing by neutralizing factor H, a key regulator of the alternative complement pathway, with the help of OmpA. This phenomenon is known as serum resistance of A. baumannii.
- OmpA induces differentiation of CD4+, activation, and maturation of dendritic cells, and causes their premature apoptosis.
- Secretion of outer membrane vesicles that contain different virulence-related proteins (proteases, phospholipases, superoxide dismutase, and catalase) at the infection site accelerates the local innate immune response and ultimately leads to tissue damage.
- The outer membrane vesicles also augment biofilm formation on abiotic surfaces.
- The polysaccharide capsule plays a central role in guarding bacteria against phagocytosis by the host innate immune system. Lipopolysaccharides (LPSs) of A. baumannii consist of an O-antigen, the carbohydrate core, and a lipid A moiety. LPS is a chemotactic agent that recruits inflammatory cells and compels them to release their cytotoxic material.
- The ability of A. baumannii to form biofilms on biotic and abiotic surfaces is a well-studied mechanism of resistance. To survive in unfavorable conditions, it becomes metabolically inert in the deeper layers of biofilms. Poor penetration and the inability of antibiotics to act on metabolically inert bacteria augment its virulence.
Figure: Cell surface components and secretion systems identified in Acinetobacter spp.
Source: DOI: 10.1128/JB.00906-15
- The most frequent clinical manifestations of Acinetobacter infection are ventilator-associated pneumonia and bloodstream infections.
- Additionally, in humans, Acinetobacter can colonize skin, wounds, and the respiratory and gastrointestinal tracts.
- Acinetobacter pneumonia occurs predominantly in the intensive care unit (ICU) patients who require mechanical ventilation and tends to be characterized by a late-onset.
- Other clinical manifestations of Acinetobacter pneumonia are similar to those reported for hospital-acquired pneumonia in general such as dyspnea, productive cough, fever, chest pain, asymmetrical expansion of the chest, diminished resonance, egophony, etc.
- Community-acquired Acinetobacter pneumonia is typically characterized by a fulminant illness with an abrupt onset and rapid progression to respiratory failure and hemodynamic instability.
- Septic shock ensues in around one-third of patients.
- Acinetobacter accounts for 1.5 to 2.4 percent of nosocomial bloodstream infections.
- Risk factors for Acinetobacter bloodstream infection include intensive care, mechanical ventilation, prior surgery, prior use of broad-spectrum antibiotics, immunosuppression, trauma, burns, malignancy, central venous catheters, invasive procedures, and prolonged hospital stay
- Fever may be the only manifestation of the bacteremia. Septic shock develops in up to one-third of patients with Acinetobacter bacteremia.
- Acinetobacter spp are a rare cause of infective endocarditis in the native and prosthetic heart.
- Acinetobacterendocarditis is typically characterized by an acute onset with an aggressive course.
- Mortality tends to be higher in the setting of native valve endocarditis than prosthetic valve endocarditis, likely because of the low index of suspicion leading to delayed treatment in such cases.
- Acinetobacter is an infrequent cause of nosocomial meningitis.
- Risk factors include neurosurgical procedures, cerebrospinal fluid (CSF) leak, prior antibiotic therapy, and intracranial hemorrhage
- Mortality ranges from 20 to 30 percent; neurologic deficits in surviving patients can be severe.
- Most patients with Acinetobactermeningitis present with fever, meningeal signs, and/or seizures.
- Cerebral spinal fluid (CSF) typically demonstrates pleocytosis with neutrophilic predominance, elevated protein concentration, and a low CSF-to-serum glucose ratio. Other clinical manifestations of Acinetobactercentral nervous system infections are similar to those reported for meningitis in general.
Skin, soft tissue, and bone infection
- Acinetobactermay contaminate surgical and traumatic wounds, leading to severe soft tissue infection that can also progress to osteomyelitis
- Acinetobacter has rarely been associated with community-acquired or hospital-acquired skin infections such as cellulitis and folliculitis as well as skin abscesses and necrotizing fasciitis.
- Traumatic wound infections due to multidrug-resistant Acinetobactercomplex have been increasingly recognized after war injuries; environmental contamination of field hospitals appears to play an important role in these infections.
- Most Acinetobacterskin infections start with a skin break. Cellulitis starts as a well-demarcated edematous patch with erythema, often having a peau d’orange appearance. It then transforms into a sandpaper-like lesion characterized by numerous vesicles that might later evolve into hemorrhagic bullae.
- The urinary tract can become colonized readily with Acinetobacter, particularly in the setting of indwelling urinary catheters.
- Acinetobacter can cause colonization or infection of the eye. Colonization has been observed in contact lens wearers. Ocular infection can include corneal ulcers, endophthalmitis, periorbital cellulitis, and infection after penetrating trauma.
- Acinetobacter can cause nosocomial sinusitis in patients admitted to the intensive care unit; mechanical ventilation is the most important predisposing factor Acinetobacter sinusitis has been associated with the development of pneumonia, as the infected sinuses serve as reservoirs for dissemination to the lower respiratory tract.
- Acinetobacterperitonitis has been described in patients undergoing peritoneal dialysis. The most common manifestations are abdominal pain and a cloudy dialysate.
- Lee, C. R., Lee, J. H., Park, M., Park, K. S., Bae, I. K., Kim, Y. B., Lee, S. H. (2017). Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options. Frontiers in cellular and infection microbiology, 7, 55. doi:10.3389/fcimb.2017.00055
- Asif, M., Alvi, I. A., & Rehman, S. U. (2018). Insight into Acinetobacter baumannii: pathogenesis, global resistance, mechanisms of resistance, treatment options, and alternative modalities. Infection and drug resistance, 11, 1249–1260. doi:10.2147/IDR.S166750