Version May 2024
INTRODUCTION — Acinetobacter is a gram-negative coccobacillus that has emerged from an organism of questionable pathogenicity to an infectious agent of importance to hospitals worldwide [1]. The organism has the ability to accumulate diverse mechanisms of resistance, leading to the emergence of strains that are resistant to all commercially-available antibiotics [2].
The microbiology, pathogenesis, epidemiology, and disease associations of Acinetobacter infection will be reviewed here. The treatment and prevention of Acinetobacter infection are discussed separately. (See "Acinetobacter infection: Treatment and prevention".)
EPIDEMIOLOGY — The epidemiology of Acinetobacter infections is broad and includes infection associated with tropical environments, wars and natural disasters, and hospital outbreaks in temperate climates [3-7]. It naturally inhabits water and soil, and other possible reservoirs include pets, arthropods, and food animals [5,8-10]. In humans, Acinetobacter can colonize skin, wounds, and the respiratory and gastrointestinal tracts [11]. It can also inhabit oral biofilms, predisposing to pneumonia in the event of aspiration into the lower respiratory tract [12,13].
Some Acinetobacter strains can survive environmental desiccation for weeks, a characteristic that promotes transmission through fomite contamination in hospitals [14-16].
Association with climate — Historically, Acinetobacter has been a pathogen of humid climates. Years before Acinetobacter became a concern in intensive care units (ICUs) in the United States, it was cited as the cause of 17 percent of cases of ventilator-associated pneumonias in a Guatemalan ICU, second only to Pseudomonas, which caused 19 percent of cases [17].
Since the 1970s, Acinetobacter infections have become an increasingly common nosocomial problem in temperate climates [18]. Their emergence is likely related in part to their survival ability and their rapid development of resistance to the major antibiotic classes [19].
Nevertheless, nosocomial Acinetobacter infections have been observed more frequently in the summer than in other seasons; in one review of 3447 Acinetobacter infections reported to the United States Centers for Disease Control and Prevention (CDC) between 1987 and 1996, infection rates were approximately 50 percent higher from July to October than at other times of the year [20]. Possible explanations include more humid ambient air (which favors growth of Acinetobacter in its natural habitats) and potentially preventable environmental contaminants, such as condensate from air-conditioning units, which have been implicated as a cause of epidemic Acinetobacter infections.
Disease associations — Acinetobacter is most notorious for its association with health care-associated infections, particularly among patients in the intensive care unit (ICU). However, it has also been associated with community-acquired infections in Asia and Australia as well as infections related to wars and natural disasters.
Health care-associated infections — Acinetobacter is an important cause of hospital-acquired infections globally. A 2016 report from the United States, the National Healthcare Safety Network (NHSN), reviewed the most frequent antimicrobial-resistant pathogens associated with health care-associated infections [21].
Acinetobacter species accounted for the following proportions among the most common gram-negative isolates:
●Ventilator-associated pneumonia isolates – 12.8 percent
●Central line-associated bloodstream infection isolates – 8.8 percent
●Catheter-associated urinary tract infection isolates – 1.3 percent
●Surgical site infection isolates – 1.3 percent
Infections with A. baumannii tend to occur in debilitated patients in ICUs (among both children and adults) [22] and among residents of long-term care facilities (particularly facilities caring for ventilator-dependent patients). Additional risk factors include recent surgery, central vascular catheterization, tracheostomy, mechanical ventilation, enteral feeding, and treatment with third generation cephalosporin, fluoroquinolone, or carbapenem antibiotics [1,23-26]. Risk factors among neonates include low birth weight, total parenteral nutrition, and central venous catheters [27,28]. Most information about health care-associated Acinetobacter infections is based on data from outbreak investigations [17].
Acinetobacter outbreaks have also been traced to common-source contamination (particularly contaminated respiratory and ventilator equipment), and to cross-infection by the hands of health care workers caring for colonized or infected patients [17,29,30]. Once Acinetobacter is introduced into a hospital, serial or overlapping outbreaks caused by various multidrug-resistant strains are frequently observed. Subsequently, endemicity of multiple strains is established, with a single endemic strain predominating at any one time [17]. Prolonged colonization may contribute to the endemicity of A. baumannii after an outbreak; in one study, colonization persisted for up to 42 months and affected 17 percent of patients [31].
Dramatic multihospital outbreaks have been described in the United States, Europe, South America, Africa, Asia, and the Middle East [2,24,32,33]. As an example, a monoclonal outbreak of a carbapenemase producing (OXA-40) Acinetobacter was described in the greater Chicago area in 2005; subsequently, at least five hospitals, three long-term care facilities, and more than 200 patients were affected by this outbreak [2].
The occurrence of monoclonal outbreaks in multiple hospitals suggests spread between institutions, presumably by movements of patients or personnel, or by exposure to common-source contamination of food or equipment. Such outbreaks highlight the importance of ongoing surveillance and measures to prevent the introduction of Acinetobacter into, and spread from, long term care facilities.
Data regarding the prognosis of patients with Acinetobacter infections are limited. While such patients usually have high mortality rates [34], it is unclear whether mortality can be attributed to Acinetobacter infection. In a matched cohort study of trauma patients, the effect of Acinetobacter infections on mortality was inconclusive [35]. Cases had a longer stay in the intensive care unit and a higher rate of organ failure than control patients with infections other than Acinetobacter. Risk factors for mortality in patients with Acinetobacter infections include imipenem resistance, intensive care unit stay, female sex, old age, pneumonia, diabetes mellitus, and septic shock [36,37].
Community-acquired infection — Community acquired Acinetobacter infection has been reported in Australia and Asia; in Australia, community-acquired pneumonia occurs more frequently during the wet (monsoon) season [3,4,6,38]. In tropical northern Australia, A. baumannii accounts for 10 percent of cases of severe community-acquired pneumonia [39].
Community-acquired infections have been characterized by pharyngeal carriage of the organism, aggressive pneumonia, and high case fatality rates. Risk factors include tobacco use, chronic obstructive pulmonary disease, diabetes, alcoholism, and cancer [3,4,38,39]. Community-acquired bloodstream infections have also been observed [4,38,40].
In the United States, community-acquired infections are rare [41]. The reason for the higher prevalence of Acinetobacter infections in certain geographic areas is not known, but it may be due in part to differences in temperature and humidity that influence colonizing bacteria.
Wars and natural disasters — Acinetobacter should be included in the differential diagnosis of infections sustained among deployed military personnel and following exposure to natural disasters in a tropical environment.
Wartime Acinetobacter infections have been reported during the Korean War, the Vietnam War, and the wars in Iraq and Afghanistan, and resistance rates are high [42-46]. In one study, A. baumannii accounted for 63 percent of all bacterial isolates recovered from war wounds in US troops situated in Iraq and Afghanistan between 2007 and 2008 [47].According to another report, Acinetobacter isolates from military personnel had a lower rate of susceptibility to imipenem than isolates from non-deployed personnel (63 versus 87 percent) [46].
The genetic variability and reappearance of Acinetobacter in personnel participating in several military operations over several decades suggests multiple sources, including local foods, battlefield wound contamination, and environmental spread and cross-infection in field and referral hospitals [43,48,49].
The prevalence of Acinetobacter infections has also been disproportionately high in the setting of natural disasters. Among 17 patients evacuated in critical condition due to soft tissue injuries and fractures after the Southeast Asia tsunami in 2004, multi-drug resistant Acinetobacter was isolated from 20 percent of wounds, as well as from blood and respiratory secretions [50]. Following the 1999 Marmara earthquake in Turkey, A. baumannii was the most prevalent nosocomial pathogen in a Turkish ICU, where it had only rarely been isolated previously [51].
MICROBIOLOGY — The genus Acinetobacter comprises gram-negative coccobacilli that are non-motile, strictly aerobic, catalase-positive, and oxidase-negative [52]. It had previously encompassed a heterogeneous collection of non-pigmented, oxidase-positive and oxidase-negative gram-negative rods [53,54].
Acinetobacter is easily isolated in standard cultures, although identification can be delayed since it is relatively nonreactive in many biochemical tests commonly used to differentiate among gram-negative bacilli. Acinetobacter species appear as short, broad gram-negative rods in the rapid growth phase but assume a more coccobacillary shape in the stationary phase. They are indole-negative and do not ferment glucose or reduce nitrate.
More than 30 different species belonging to the genus Acinetobacter have been identified [55,56]. Most of these species are environmental organisms and have not been associated with human disease [57]. A. baumannii, A. calcoaceticus, and A. lwoffi are the species most frequently reported in the clinical literature. The term A. calcoaceticus-A. baumannii complex (ACB) is sometimes used since it is difficult to differentiate among Acinetobacter species on the basis of phenotypic characteristics [58]. The ACB is comprised of genospecies 1 (A. calcoaceticus), genospecies 2 (A. baumannii), genospecies 3, and genospecies 13TU [59-61].
Acinetobacter baumannii (genospecies 2 of the ACB complex) is the most resistant of the genospecies and has the greatest clinical importance [62]. This pathogen is the most frequently isolated species (>90 percent of Acinetobacter spp isolates) and is typically associated with outbreaks in the hospital setting. It is characterized by its resistance to harsh environment factors, a property that enables such organisms to spread rapidly and develop resistance to all conventional antimicrobials [56,63]. Other species that have been associated with disease include A. johnsonii, A. lwoffi, and A. calcoaceticus subsp anitratus [64]. More recently, A. junii has been described as an opportunistic pathogen in the setting of prior antimicrobial therapy, invasive procedures, and malignancy [65].
PATHOGENESIS — Five main pathogenic mechanisms have thus far been described:
●Biofilm formation — Colonization of environmental surfaces is promoted by adhesion via pili and the subsequent formation of biofilms [64]. Biofilm-associated protein (Bap) is needed for biofilm maintenance and maturation [12]. Bap is also important for colonization as it facilitates adherence to cells [12]. High biofilm producing strains are less sensitive to desiccation than low biofilm producing strains; thus, biofilm production seems critical for Acinetobacter’s well-established ability to survive under dry conditions [66].
●Outer membrane protein A (OmpA) — Production of OmpA is essential for making an intact biofilm [12]. It is also essential for adherence to epithelial cells. It induces cell apoptosis by entering the cell and stimulating the release of cytochrome c and apoptosis-inducing factor. OmpA also helps bind Factor H, which is an inhibitor of the alternative complement pathway [12].
●K1 capsule — Approximately one-third of strains produce a polysaccharide capsule that works with the cell wall liposaccharide to prevent complement activation [67]. The capsule may also delay phagocytosis.
●Siderophore-mediated iron-acquisition system — Acinetobacter can survive iron-deficient conditions [68] for long periods of time. This is due to its "acinetobactin," a catechol siderophore that can sequester iron from the host [12].
●Fimbriae — As mentioned above, fimbriae help attach the organism to environmental surfaces. They also help colonize biotic surfaces, such as bronchial epithelial cells [63].
CLINICAL FEATURES — The most frequent clinical manifestations of Acinetobacter infection are ventilator-associated pneumonia and bloodstream infections [58]. Additionally, in humans, Acinetobacter can colonize skin, wounds, and the respiratory and gastrointestinal tracts [11]. It may be difficult to distinguish between colonization and true infection, particularly since many infections occur in the setting of colonization.
Hospital-acquired pneumonia — Acinetobacter pneumonia occurs predominantly in 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. (See "Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia".)
Most cases of nosocomial Acinetobacter pneumonia occur in previously colonized patients. True Acinetobacter pneumonia must be distinguished from airway colonization in mechanically ventilated patients. (See "Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia", section on 'Diagnostic evaluation'.)
A. baumannii was among the most common pathogens causing nosocomial pneumonia in a prospective observational study from 27 ICUs in nine different European countries; in Greece and Turkey, it was the most common isolate [69]. Nosocomial pneumonia secondary to Acinetobacter is associated with multidrug-resistant isolates and with mortality rates of 35 to 70 percent, although attributable mortality is difficult to determine since most patients have concurrent life-threatening conditions [3,25,70-73]. Coexisting conditions appear to be a major predictor of outcome [25,74-76]. One study noted higher mortality among patients with infection due to multidrug-resistant Acinetobacter than among patients with infection due to susceptible Acinetobacter strains or uninfected patients; however, when the severity of illness and underlying diseases were considered, the main difference was that patients with multidrug-resistant infection had longer hospital and ICU stays [74].
Overall, positive blood cultures and signs of sepsis usually portend a bad prognosis [76,77]. As an example, severe sepsis and septic shock were independent predictors or 30-day mortality in a study of patients with nosocomial A. baumannii/calcoaceticus complex pneumonia [77]. Additionally, patients with pneumonia due to Acinetobacter spend more ventilator days in the ICU before detection of positive cultures than do patients with pneumonia due to other gram-negative bacilli or uninfected patients [25].
Community-acquired pneumonia — Community-acquired Acinetobacter pneumonia is typically characterized by a fulminant illness with an abrupt onset and rapid progression to respiratory failure and hemodynamic instability [3,4,6]. Septic shock ensues in around one-third of patients. This infection seems to be more common in Southeast Asia and Australia compared with other regions and has been increasingly reported as a highly fatal disease [78].
Bloodstream infection — Acinetobacter accounts for 1.5 to 2.4 percent of nosocomial bloodstream infections [79-81]. The most frequent sources of Acinetobacter bacteremia are vascular catheters and the respiratory tract [80,82,83]. Less common primary sites include wounds and the urinary tract. In one study, approximately 36 percent of 111 cases of Acinetobacter bloodstream infections were polymicrobial and included skin flora, suggesting that some blood isolates represented contamination from the skin or environment [80].
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 [80-82,84-87].
Septic shock develops in up to one-third of patients with Acinetobacter bacteremia [83,84]; mortality ranges from 20 to 60 percent, although the mortality attributable to bacteremia itself is difficult to determine in the setting of multiple comorbidities [76,80,82-84,88,89]. Bacteremia associated with Acinetobacter pneumonia is associated with higher mortality than bacteremia associated with catheter infection (39 versus 4 percent, respectively) [82,84]. In addition, multidrug resistance and mechanical ventilation have been associated with 30-day mortality in patients with A. baumannii bacteremia [90].
Other clinical manifestations of Acinetobacter bloodstream infection are similar to those reported for gram-negative bacillary bacteremia in general. (See "Gram-negative bacillary bacteremia in adults", section on 'Clinical manifestations'.)
Endocarditis — Acinetobacter spp are a rare cause of infective endocarditis in native and prosthetic heart valves [91-94]. In a study of 171 patients with prosthetic heart valve endocarditis resulting from nosocomial bacteremia, two cases were attributable to Acinetobacter [95]. Acinetobacter endocarditis is typically characterized by 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 [91]. (See "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)
Meningitis — Acinetobacter is an infrequent cause of nosocomial meningitis [96-98]. Among 95 cases of meningitis following craniotomy, two were due to Acinetobacter spp [96]. Risk factors include neurosurgical procedures, cerebrospinal fluid (CSF) leak, prior antibiotic therapy, and intracranial hemorrhage [99-101]. Nosocomial outbreaks of Acinetobacter meningitis have been reported in association with the intrathecal administration of contaminated methotrexate [102] and with contaminated suctioning equipment in a neurosurgical unit [103]. Mortality ranges from 20 to 30 percent; neurologic deficits in surviving patients can be severe [97,101,104].
Community-acquired Acinetobacter meningitis is rare; it primarily occurs in previously healthy individuals in warm climates, and is usually not drug resistant [105].
Most patients with Acinetobacter meningitis 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 [99,100]. Other clinical manifestations of Acinetobacter central nervous system infections are similar to those reported for meningitis in general. (See "Clinical features and diagnosis of acute bacterial meningitis in adults".)
Skin contamination with Acinetobacter can be mistaken for true infection [100,106]. In a retrospective analysis of 54 patients with CSF cultures growing Acinetobacter, the organism was considered clinically insignificant in 34 (63 percent) [100]. The isolation of Acinetobacter from multiple CSF specimens and the typical clinical and laboratory findings of bacterial meningitis were highly suggestive of true infection.
Skin, soft tissue, and bone infection — Acinetobacter may contaminate surgical and traumatic wounds, leading to severe soft tissue infection that can also progress to osteomyelitis [107]. Surgical wound infections with Acinetobacter are frequently related to the presence of prosthetic material and usually require extensive debridement. 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 [108-113]. Traumatic wound infections due to multidrug-resistant Acinetobacter complex have been increasingly recognized after war injuries; environmental contamination of field hospitals appears to play an important role in these infections. (See 'Wars and natural disasters' above.)
Most Acinetobacter skin infections start with a skin break. Cellulitis starts as a well demarcated edematous patch with erythema, often having a peau d'orange appearance (picture 1) [114]. It then transforms into a sandpaper-like lesion characterized by numerous vesicles that might later evolve into hemorrhagic bullae.
Urinary tract infection — The urinary tract can become colonized readily with Acinetobacter, particularly in the setting of indwelling urinary catheters; the incidence of infection is low [79,115]. In a review of 5000 urinary tract infections in medical intensive care units in the United States, 1.6 percent was due to Acinetobacter; 95 percent of these infections were associated with urinary catheters [79]. Community-acquired urinary tract infection can occur but is rare [116,117].
In the absence of other signs or symptoms of infection, isolation of Acinetobacter may be attributed to colonization.
Other infections — Acinetobacter can cause colonization or infection of the eye. Colonization has been observed in contact lens wearers [118]. Ocular infection can include corneal ulcers, endophthalmitis, periorbital cellulitis, and infection after penetrating trauma [119-124]. In one series including 750 cases of corneal ulcers, Acinetobacter was the third most common cause, accounting for 7 percent of cases [121]. Most infections occurred postoperatively, usually following cataract surgery or other ocular surgeries. (See "Bacterial endophthalmitis" and "Orbital cellulitis".)
Acinetobacter can cause nosocomial sinusitis in patients admitted to the intensive care unit; mechanical ventilation is the most important predisposing factor [125,126]. Acinetobacter sinusitis has been associated with the development of pneumonia, as the infected sinuses serve as reservoirs for dissemination to the lower respiratory tract [125]. (See "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis", section on 'Clinical features'.)
Acinetobacter peritonitis has been described in patients undergoing peritoneal dialysis [127-129]. The most common manifestations are abdominal pain and a cloudy dialysate. (See "Clinical manifestations and diagnosis of peritonitis in peritoneal dialysis", section on 'Clinical presentation'.)
DIAGNOSIS — The diagnosis of Acinetobacter infection is made by the growth of Acinetobacter from a patient specimen (eg, sputum, blood, cerebrospinal fluid) in the setting of other clinical findings that suggest an infection at that site. Since Acinetobacter colonization is common and treatment difficult and potentially associated with substantial toxicity, distinction between colonization and infection, with treatment reserved for true infections, is important. As an example, Acinetobacter isolated from sputum of a ventilated patient is more likely to represent colonization than infection in the absence of fever, leukocytosis, increased respiratory secretions, need for additional respiratory support, or a new abnormality on chest imaging. For cases of pneumonia, quantitative or semiquantitative cultures on sputum specimens may also be helpful in distinguishing between infection and colonization. (See "Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia", section on 'Diagnostic evaluation'.)
The diagnoses of infections that have been associated with Acinetobacter spp are discussed in detail elsewhere:
●(See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults".)
●(See "Detection of bacteremia: Blood cultures and other diagnostic tests".)
●(See "Complications of abdominal surgical incisions", section on 'Clinical manifestations and diagnosis' and "Overview of the evaluation and management of surgical site infection", section on 'Clinical features'.)
SUMMARY
●The epidemiology of Acinetobacter infections is broad and includes hospital-acquired infection, community-acquired infections in tropical environments, and infections that occur in the setting of wars and natural disasters. Some strains can survive environmental desiccation for months, a characteristic that promotes transmission through fomite contamination in hospitals. (See 'Epidemiology' above.)
●Health care-associated infections tend to occur in debilitated patients in intensive care units (among both children and adults) and among residents of long-term care facilities (particularly facilities caring for ventilator-dependent patients). Additional risk factors include recent surgery, central vascular catheterization, tracheostomy, mechanical ventilation, enteral feedings, and treatment with third generation cephalosporin, fluoroquinolone, or carbapenem antibiotics. (See 'Health care-associated infections' above.)
●More uncommonly, Acinetobacter is a cause of community-acquired infections. In particular, Acinetobacter has been described as a cause of severe community-acquired pneumonia in Australia and Asia, particularly during the wet season. Additionally, wartime Acinetobacter infections have been reported in the Korean War, the Vietnam War, and the wars in Iraq and Afghanistan. Acinetobacter infections have also been associated with natural disasters including tsunamis and earthquakes. (See 'Community-acquired infection' above and 'Wars and natural disasters' above.)
●Acinetobacter is easily isolated in standard cultures, although identification can be delayed since it is relatively nonreactive in many biochemical tests commonly used to differentiate among gram-negative bacilli. On Gram stain, Acinetobacter species appear as short, broad gram-negative rods in the rapid growth phase but assume a more coccobacillary shape in the stationary phase. (See 'Microbiology' above.)
●Acinetobacter baumannii (genospecies 2 of the ACB complex) is the most resistant of the genospecies and has the greatest clinical importance. This pathogen is the most frequently isolated species (>90 percent of Acinetobacter spp isolates) and is typically associated with outbreaks in the hospital setting. (See 'Microbiology' above.)
●Hospital-acquired pneumonia and bloodstream infections are the most common infections associated with Acinetobacter. These Acinetobacter infections are associated with high mortality rates, partly because of prevalent comorbid conditions. Other less common infections include meningitis, wound or surgical site infections, and urinary tract infections. (See 'Clinical features' above.)
●The diagnosis of Acinetobacter infection is made by the growth of Acinetobacter from a patient specimen (eg, sputum, blood, cerebrospinal fluid) in the setting of other clinical findings that suggest an infection at that site. Acinetobacter can colonize skin, wounds, and the respiratory and gastrointestinal tracts. It is important but may be difficult to distinguish between colonization and true infection, particularly since many infections occur in the setting of colonization. (See 'Diagnosis' above.)
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