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Acinetobacter Infections

Chapter 167 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial

Detailed clinical reference synthesised from Harrison's Principles of Internal Medicine, 22nd Edition

🔑 Key Clinical Points

  1. Acinetobacter baumannii is the most clinically relevant species, capable of surviving environmental desiccation for weeks, facilitating hospital outbreaks.
  2. Differentiation between colonization and infection is challenging; airway colonization does not always indicate pneumonia.
  3. IDSA 2024 Guidance recommends sulbactam-durlobactam in combination with a carbapenem as the preferred regimen for carbapenem-resistant A. baumannii.
  4. Mortality rates for nosocomial pneumonia due to A. baumannii are reported as high as 65%, and up to 70% for carbapenem-resistant bloodstream infections.
  5. A. baumannii possesses intrinsic AmpC beta-lactamases and can acquire extended-spectrum beta-lactamases and carbapenemases (OXA family).
  6. Biofilm formation via exopolysaccharide production and pilus formation is a key virulence mechanism facilitating persistence on surfaces and devices.
  7. High-dose ampicillin-sulbactam increases binding of sulbactam to penicillin-binding proteins (PBP2 and PBP3), optimizing inhibition of cell wall synthesis.
  8. A. baumannii may appear as gram-negative paired cocci on cerebrospinal fluid Gram stain, mimicking Neisseria meningitidis.
  9. Outbreaks are facilitated by inappropriate hand hygiene, contamination of equipment, and air spread in areas without physical barriers.
  10. Sulbactam-durlobactam combination therapy showed lower nephrotoxicity and improved mortality compared to colistin in randomized trials.

📑 Table of Contents

📋 Figures in This Chapter

# Type Description
1 🖼 Figure Strategies for the prevention of dissemination of Acinetobacter

1. DEFINITION & OVERVIEW

  • Acinetobacter species were first described in 1911 and named Micrococcus calcoaceticus.
  • Since 1950, the genus has been renamed multiple times and is now known as Acinetobacter.
  • Acinetobacter species are gram-negative, oxidase-negative, nonmotile, nonfermenting coccobacilli.
  • They are easily recovered on standard culture media.
  • Differentiation among Acinetobacter species on the basis of phenotypic characteristics alone is very difficult.
  • Molecular-based methods such as matrix-assisted laser desorption–ionization–time-of-flight mass spectrometry (MALDI-TOF-MS) and quantitative real-time polymerase chain reaction (PCR) are usually necessary to identify Acinetobacter baumannii, the most clinically relevant species of the genus.
  • Acinetobacter species are naturally encountered in water and soil and have also been recovered from fruits and vegetables.
  • In humans, Acinetobacter can be found on the skin and in the respiratory and gastrointestinal tracts.
  • A. baumannii is capable of surviving environmental desiccation for weeks, which is important from an infection-control perspective as it allows this organism to persist in the hospital environment and on equipment.

1.1 Historical Classification

  • Originally named Micrococcus calcoaceticus.
  • Renamed multiple times since 1950.
  • Currently classified as Acinetobacter.

1.2 Morphology & Identification

  • Gram-negative coccobacilli.
  • Oxidase-negative.
  • Nonmotile.
  • Nonfermenting.
  • Easily recovered on standard culture media.
  • Phenotypic differentiation is very difficult.
  • Molecular methods (MALDI-TOF-MS, PCR) are usually necessary for A. baumannii identification.

2. EPIDEMIOLOGY

  • Acinetobacter was historically considered a pathogen of hot and humid climates.
  • In recent years, hospital outbreaks caused by A. baumannii have been reported worldwide, even in temperate climates.
  • In the United States, the Centers for Disease Control and Prevention (CDC) estimates that 12,000 Acinetobacter infections occur every year.
  • Of these, 7,300 are caused by multidrug-resistant strains.
  • 500 deaths are attributable to these infections.
  • The increase in the number of infections with A. baumannii is suspected to be due to the rapid spread of certain genetically distinct lineages.
  • Of the three international clonal lineages (ICLs), ICL I and ICL II are multidrug resistant.
  • The predominance of these lineages remains unexplained, although it has been proposed that this population structure is the result of two waves of expansion.
  • The first wave followed a bottleneck (possibly linked to a restricted ecologic niche) that occurred in the distant past.
  • The second wave is ongoing and is being driven by the rapid expansion of a limited number of multidrug-resistant clones.
  • The COVID-19 pandemic resulted in a setback to the efforts to control the spread of multidrug-resistant organisms, with significant increases in the rates of infections with carbapenem-resistant Acinetobacter reported worldwide.
  • Spread of A. baumannii across different regions is facilitated by the movement of patients between health care systems and throughout the continuum of health care.
  • Within the hospital, environmental spread of A. baumannii occurs as a result of inappropriate hand hygiene among workers providing health care for infected or colonized patients and the contamination of hospital equipment, such as respiratory therapy and ventilation equipment.
  • The air surrounding the patient may also play a role in environmental colonization with A. baumannii, especially in inpatient areas without physical barriers between patients and with an inadequate number of air exchanges.
  • Community-acquired infections caused by Acinetobacter have been described in Australia and Asia.
  • Few cases have been reported in regions with a temperate climate, and even those few cases have taken place during warm and humid months.
  • Risk factors for community-acquired pneumonia due to this organism include a history of alcohol abuse, diabetes mellitus, smoking, and chronic lung disease.
  • Infections caused by A. baumannii occur frequently among patients admitted to intensive care units (ICUs).
  • Risk factors for colonization and infection with this pathogen include nursing home residence, prolonged ICU stay, central venous catheterization, tracheostomy, mechanical ventilation, enteral feedings, and treatment with third-generation cephalosporins, fluoroquinolones, and carbapenems.
  • Acquisition of carbapenem-resistant A. baumannii is most common among patients exposed to carbapenems.
  • Disaster Medicine: A. baumannii is linked to infections among victims of trauma during tsunamis, earthquakes, and terrorist attacks.
  • The types of infections most frequently observed in these settings are soft tissue injuries, but bloodstream infections and pneumonia have also been reported.
  • Outbreaks of A. baumannii infection in ICUs caring for disaster victims have been described.
  • A. baumannii infections resulting from trauma to soft tissues in the setting of natural disasters, such as tsunamis and earthquakes, have been reported.
  • The implication is that A. baumannii should be considered in the differential diagnosis of soft tissue infections following exposure to tropical and subtropical environments.
  • War Zone–Associated Infections: Infections caused by Acinetobacter in war zones include skin and soft tissue infections associated with traumatic injuries and bloodstream infections.
  • Outbreak investigations of A. baumannii infections among military personnel returning from Iraq and Afghanistan suggested the acquisition of A. baumannii in field hospitals rather than colonization of the skin before an injury.
  • This view is supported by the recovery of A. baumannii isolates with similar genetic characteristics from inanimate surfaces in field hospitals and from patients.
  • A. baumannii is an infrequent cause of urinary tract infections.
  • The majority of cases reported are catheter-associated infections, reflecting the ability of A. baumannii to form biofilms on these devices.
  • A few reports have described community-acquired infections occurring in the setting of nephrolithiasis and after renal transplantation.

2.1 Health Care–Associated Infections

  • Frequent among patients admitted to ICUs.
  • Risk factors: Nursing home residence, prolonged ICU stay, central venous catheterization, tracheostomy, mechanical ventilation, enteral feedings.
  • Treatment with third-generation cephalosporins, fluoroquinolones, and carbapenems increases risk.
  • Acquisition of carbapenem-resistant A. baumannii is most common among patients exposed to carbapenems.
  • Outbreaks described in Ohio, Michigan, Illinois, and Indiana.

2.2 Community-Acquired Infections

  • Described in Australia and Asia.
  • Few cases in temperate climates.
  • Cases in temperate climates occur during warm and humid months.
  • Risk factors: Alcohol abuse, diabetes mellitus, smoking, chronic lung disease.

2.3 Disaster & War Zone Infections

  • Linked to trauma victims during tsunamis, earthquakes, terrorist attacks.
  • Frequent infections: Soft tissue injuries, bloodstream infections, pneumonia.
  • Outbreaks in ICUs caring for disaster victims.
  • War zones: Skin and soft tissue infections, bloodstream infections.
  • Acquisition in field hospitals rather than skin colonization before injury.

3. ETIOLOGY & PATHOPHYSIOLOGY

  • Analysis of the A. baumannii pangenome (the sum of the core and dispensable genomes) has shown that its organization is characterized by a small core genome and a large accessory or dispensable genome.
  • This organization reflects A. baumannii's high plasticity, which enables it to acquire exogenous genetic material.
  • With few exceptions, gene functions associated with virulence are found in the core genome.
  • This observation suggests a limited role for the acquisition of new virulence traits in the recent nosocomial expansion of A. baumannii clones.
  • Genes associated with resistance to antimicrobial agents are found in both the species core genome and the accessory genome.
  • In the accessory genome, these genes have been found in alien islands, often flanked by integrases, transposases, or insertion sequences.
  • This pattern suggests possible acquisition by horizontal gene transfer from other Acinetobacter strains or even from different bacterial species present in the immediate environment.
  • Acquisition of these antimicrobial resistance genes is hypothesized to have led to the recent rapid expansion of highly homogeneous clonal lineages.
  • Main difference from nonclonal A. baumannii appears to be their antimicrobial resistance.
  • A. baumannii seems to have greater virulence potential than other Acinetobacter species.
  • Evidence: Ability to grow at 37°C and to resist uptake by macrophages.
  • Initial A. baumannii colonization of the host and the environment is facilitated by the organism's ability to adhere to surfaces and human cells and to create biofilms.
  • The ability to form a biofilm is phenotypically associated with exopolysaccharide production and pilus formation.
  • A quorum-sensing molecule encoded by the abaI autoinducer synthase gene has been implicated in A. baumannii biofilm formation on abiotic surfaces.
  • Outer-membrane porins appear to mediate cell apoptosis.
  • A. baumannii can survive in harsh environments within the host and on inanimate surfaces by modifying the structure of its lipid A.
  • Consequence: Decrease in susceptibility to antibiotics and antimicrobial peptides and an increase in survival upon desiccation.
  • Acinetobacter species produce an extracellular capsule that protects the bacteria from external threats, including complement-mediated killing.
  • Studies of mouse models showed that Acinetobacter species can increase capsule production in the presence of subinhibitory levels of antibiotic—an ability that leads to increased resistance to complement-mediated killing and a hypervirulent phenotype.
  • Phospholipase C and phospholipase D have been identified as virulence factors in A. baumannii.
  • These enzymes exert cytotoxic effects on epithelial cells and facilitate their invasion.
  • Iron-acquisition systems are also important virulence mechanisms in A. baumannii.
  • Through secretion of siderophores (low-molecular-mass ferric-binding compounds), A. baumannii is able to grow despite iron deficiencies in the surrounding environment (e.g., in the human host).
  • Several protein-secretion systems have been identified in A. baumannii.
  • The most recently described is a type II secretion system.
  • The substrate for this system, the LipA lipase, is required for growth on medium containing lipids as a sole carbon source.
  • Mutants lacking the genes for the type II secretion system or its substrate exhibit defective in vivo growth in a neutropenic murine model of bacteremia.
  • A. baumannii also has a type VI secretion system whose primary function seems to be to secrete antibacterial toxins that kill competing bacteria, including other strains in the same species.
  • The type V autotransporter system has been characterized in A. baumannii.
  • In a murine systemic model of Acinetobacter infection, the Acinetobacter trimeric autotransporter mediates biofilm formation and maintenance.
  • Adherence to extracellular matrix components such as collagen I, II, and IV; and virulence.
  • Outer-membrane vesicles (OMVs) play a special role in protein secretion.
  • Many A. baumannii strains secrete OMVs containing various virulence factors, including outer-membrane protein A (OmpA), proteases, and phospholipases.
  • The membrane proteins in OMVs are responsible for eliciting a potent innate immune response.
  • Several studies have shown that A. baumannii OMVs could be used as an acellular vaccine to effectively control A. baumannii infections.
  • Nosocomial strains of Acinetobacter can deploy multiple mechanisms of resistance.
  • Mechanisms: Alterations in porins and efflux pumps and expression of beta-lactamases.
  • More specifically, Acinetobacter species can reduce the expression of porins, thus hindering the passage of beta-lactam antibiotics into the periplasmic space.
  • These species can overexpress bacterial efflux pumps and decrease the concentration of beta-lactam antibiotics in the periplasmic space.
  • Efflux pumps can also actively remove quinolones, tetracyclines, chloramphenicol, disinfectants, and tigecycline.
  • Acinetobacter species possess chromosomally encoded cephalosporinases and are capable of acquiring beta-lactamases, including serine and metallo-beta-lactamases.
  • AmpC beta-lactamases are class C beta-lactamases intrinsic to all A. baumannii strains.
  • Although these enzymes are expressed at low levels and are not inducible, the addition of the insertion sequence ISAba1 next to the AmpC gene increases beta-lactamase production, with resulting resistance to most cephalosporins.
  • Carbapenem resistance in Acinetobacter species is mostly tied to the emergence of Ambler class D oxacillinases of group 2d.
  • Some are intrinsic and chromosomal (e.g., OXA-51-like) while others are acquired and are found in plasmids or are chromosomally encoded (e.g., OXA-23-like, 24 [33-like, 40-like], 58-like, 143-like, and 235-like).

3.1 Virulence Factors

  • Greater virulence potential than other Acinetobacter species.
  • Growth at 37°C.
  • Resistance to macrophage uptake.
  • Biofilm formation (exopolysaccharide, pilus).
  • Quorum sensing (abaI autoinducer synthase).
  • Outer-membrane porins (cell apoptosis).
  • Lipid A modification (survival, antibiotic resistance).
  • Extracellular capsule (complement protection).
  • Phospholipase C and D (cytotoxicity, invasion).
  • Iron acquisition (siderophores).
  • Type II secretion system (LipA lipase).
  • Type VI secretion system (antibacterial toxins).
  • Type V autotransporter system (biofilm, adherence).
  • Outer-membrane vesicles (OMVs) (protein secretion, immune response).

3.2 Resistance Mechanisms

  • Alterations in porins.
  • Efflux pumps (quinolones, tetracyclines, chloramphenicol, disinfectants, tigecycline).
  • Chromosomally encoded cephalosporinases.
  • Acquired beta-lactamases (serine, metallo).
  • Intrinsic AmpC beta-lactamases (class C).
  • ISAba1 insertion sequence (increases beta-lactamase production).
  • Ambler class D oxacillinases (OXA-51-like, OXA-23-like, etc.).

4. CLINICAL FEATURES

  • A. baumannii is a notorious cause of nosocomial pneumonia, most frequently among patients requiring prolonged mechanical ventilation.
  • The onset of disease tends to be later than that caused by other gram-negative bacilli.
  • Clinical symptoms of hospital-acquired or ventilator-associated pneumonia due to A. baumannii are similar to those of nosocomial or ventilator-associated pneumonia due to other nosocomial pathogens.
  • Most common indicators of infection include fever and increased sputum production.
  • The positivity of respiratory cultures in most cases may present a challenge for the clinician since airway colonization with A. baumannii may not always indicate a diagnosis of pneumonia.
  • Airway colonization with A. baumannii is a known risk factor for infection itself.
  • Radiologic findings are nonspecific and can include lobar consolidations and pleural effusions, with cavitations being rarely seen.
  • The crude mortality rates associated with nosocomial pneumonia due to A. baumannii are reported as high as 65%.
  • Since these infections occur in debilitated patients, their attributable mortality has been difficult to establish.
  • Community-acquired pneumonia due to A. baumannii is relatively rare.
  • Clinical presentation is characterized by fever, severe respiratory symptoms, and multiple-organ dysfunction.
  • Patients frequently have a cough productive of purulent sputum, shortness of breath, and chest pain.
  • Imaging studies usually show lobar consolidation.
  • Mortality rates associated with this process are >50%.
  • Bloodstream infections due to A. baumannii are most frequent among ICU patients.
  • Usually occur in the presence of a central venous catheter or as a secondary complication of hospital-acquired or ventilator-associated pneumonia.
  • Fever is the most common sign of infection (developing in >95% of cases).
  • Presentation with septic shock and disseminated intravascular coagulopathy has been described in as many as 25 to 30% of patients, respectively.
  • A. baumannii bloodstream infections often result in higher hospitalization costs and longer ICU stays.
  • Crude mortality rates from this infection are as high as 40%.
  • Rates can be as high as 70% from infections caused by carbapenem-resistant isolates.
  • In patients with infections caused by extremely drug-resistant strains, poor outcomes are thought to be driven by delays in the initiation of adequate antimicrobial therapy.
  • Polymicrobial growth has been reported in 20–36% of bacteremia episodes.
  • Skin and soft tissue infections: A. baumannii species have been described as part of the skin flora, yet the majority of the organisms from this genus that colonize the skin are not those associated with nosocomial infections.
  • Discerning infection from wound colonization is challenging.
  • Gunshot wounds and the presence of orthopedic external-fixation devices are common among patients with combat trauma–associated A. baumannii skin and soft tissue infections.
  • A case series of eight U.S. military patients described the clinical presentation of their infections as evolving from an edematous peau d'orange appearance to a sandpaper appearance with overlying vesicles and then to a necrotizing process with hemorrhagic bullae.
  • Other case series have also included necrotizing fasciitis.
  • A. baumannii is an important pathogen in burn units worldwide.
  • Large burns provide ideal conditions for A. baumannii and facilitate patient-to-patient transmission.
  • The presence of A. baumannii in wounds contributes to healing delays and graft loss.
  • In addition, wound colonization is a risk factor for bloodstream infections among patients with extensive burn injuries.
  • Meningitis: Central nervous system infections with A. baumannii have been reported in the context of outbreaks, traumatic injuries, neurosurgical procedures, and external ventricular drains.
  • One case series described a petechial rash in up to 30% of patients.
  • Acinetobacter species may look similar to Neisseria meningitidis on a Gram stain of cerebrospinal fluid; both appear as gram-negative paired cocci.
  • Eradication of A. baumannii from the cerebrospinal fluid can be challenging and requires careful selection of antibiotics that adequately penetrate the site of infection.
  • Other Miscellaneous Infections: A few cases of A. baumannii keratitis associated with the use of contact lenses have been reported.
  • Cases of native- and prosthetic-valve endocarditis have also been described.

4.1 Pneumonia

  • Nosocomial: Prolonged mechanical ventilation.
  • Later onset than other gram-negative bacilli.
  • Symptoms: Fever, increased sputum production.
  • Culture positivity challenge: Colonization vs infection.
  • Radiology: Lobar consolidations, pleural effusions, rarely cavitations.
  • Mortality: Up to 65%.
  • Community-acquired: Rare, fever, severe respiratory symptoms, multiple-organ dysfunction.
  • Imaging: Lobar consolidation.
  • Mortality: >50%.

4.2 Bloodstream Infections

  • Most frequent among ICU patients.
  • Central venous catheter or secondary to pneumonia.
  • Signs: Fever (>95% of cases).
  • Complications: Septic shock, DIC (25-30%).
  • Mortality: 40% (carbapenem-resistant 70%).
  • Polymicrobial growth: 20-36%.

4.3 Skin and Soft Tissue Infections

  • Part of skin flora, but colonization vs infection challenging.
  • Combat trauma: Gunshot wounds, orthopedic devices.
  • Presentation: Edematous peau d'orange -> sandpaper -> vesicles -> necrotizing process with hemorrhagic bullae.
  • Necrotizing fasciitis reported.
  • Burn units: Important pathogen, healing delays, graft loss.
  • Risk factor for bloodstream infections in burn injuries.

4.4 Meningitis & Other

  • Meningitis: Outbreaks, trauma, neurosurgery, external ventricular drains.
  • Petechial rash: Up to 30%.
  • Gram stain mimic: Neisseria meningitidis (gram-negative paired cocci).
  • Treatment challenge: Penetration of antibiotics.
  • Keratitis: Contact lens use.
  • Endocarditis: Native and prosthetic valves.

5. DIFFERENTIAL DIAGNOSIS

  • Acinetobacter species may look similar to Neisseria meningitidis on a Gram stain of cerebrospinal fluid.
  • Both appear as gram-negative paired cocci.
  • Differentiation is important for meningitis cases.
  • Airway colonization with A. baumannii may not always indicate a diagnosis of pneumonia.
  • Other gram-negative organisms such as Hafnia, Kluyvera, Cedecea, Pantoea, Ewingella, Leclercia, Raoultella, and Photorhabdus spp. are occasionally isolated from diverse clinical specimens, including blood, sputum, urine, cerebrospinal fluid, joint fluid, bile, and wounds.
  • Such organisms cause infection predominantly in compromised hosts or in association with an invasive procedure or foreign body.
  • Cephalosporinases from Kluyvera have been implicated as the progenitors of CTX-M ESBLs.
  • Kluyvera and Raoultella may produce carbapenemases.

5.1 Gram Stain Mimics

  • Neisseria meningitidis.
  • Appearance: Gram-negative paired cocci.
  • Context: Cerebrospinal fluid.
  • Differentiation: Important for meningitis.

5.2 Colonization vs Infection

  • Airway colonization does not always indicate pneumonia.
  • Skin colonization vs infection challenging.
  • Wound colonization vs infection challenging.

6. INVESTIGATIONS & DIAGNOSIS

  • Although E. tarda can readily be isolated and identified, most laboratories do not routinely screen for or identify it in stool samples.
  • Production of hydrogen sulfide is a characteristic biochemical property (Edwardsiella).
  • For Acinetobacter: Easily recovered on standard culture media.
  • Differentiation among Acinetobacter species on the basis of phenotypic characteristics alone is very difficult.
  • Molecular-based methods such as matrix-assisted laser desorption–ionization–time-of-flight mass spectrometry (MALDI-TOF-MS) and quantitative real-time polymerase chain reaction (PCR) are usually necessary to identify Acinetobacter baumannii.
  • Acinetobacter species are naturally encountered in water and soil and have also been recovered from fruits and vegetables.
  • In humans, Acinetobacter can be found on the skin and in the respiratory and gastrointestinal tracts.
  • A. baumannii is capable of surviving environmental desiccation for weeks.
  • This characteristic is important from an infection-control perspective as it allows this organism to persist in the hospital environment and on equipment.
  • Acquisition of carbapenem-resistant A. baumannii is most common among patients exposed to carbapenems.
  • Spread of A. baumannii across different regions is facilitated by the movement of patients between health care systems and throughout the continuum of health care.
  • Within the hospital, environmental spread of A. baumannii occurs as a result of inappropriate hand hygiene among workers providing health care for infected or colonized patients and the contamination of hospital equipment, such as respiratory therapy and ventilation equipment.
  • The air surrounding the patient may also play a role in environmental colonization with A. baumannii, especially in inpatient areas without physical barriers between patients and with an inadequate number of air exchanges.
  • Prevalence of colonization with A. baumannii at the time of admission or during a stay in a long-term acute-care hospital (LTACH) or nursing home is variable and depends on regional flora.
  • Outbreaks of A. baumannii in acute-care hospitals and LTACHs that share patients have been described in Ohio, Michigan, Illinois, and Indiana.

6.1 Microbiological Identification

  • Standard culture media: Easily recovered.
  • Phenotypic differentiation: Very difficult.
  • Molecular methods: MALDI-TOF-MS, PCR.
  • Biochemical properties: Hydrogen sulfide production (Edwardsiella, not Acinetobacter).

6.2 Environmental Sampling

  • Water and soil.
  • Fruits and vegetables.
  • Skin, respiratory, gastrointestinal tracts.
  • Hospital equipment: Respiratory therapy, ventilation equipment.
  • Air: Inpatient areas without physical barriers.

7. MANAGEMENT & TREATMENT

  • Treatment of Acinetobacter infections is challenging due to difficulties in differentiating colonization versus infection and because Acinetobacter can develop resistance to most available antibiotics.
  • Therefore, the choice of empirical therapy should be based on local epidemiology and, if available, the patient's colonization status with a carbapenem-resistant isolate.
  • Definitive therapy should be determined by antimicrobial susceptibility testing.
  • Antimicrobial options for the management of infections caused by A. baumannii are displayed in Table 167-1.
  • Acinetobacter species possess intrinsic beta-lactamases that inactivate first- and second-generation cephalosporins.
  • Through acquisition of extended-spectrum beta-lactamases, these organisms can also become resistant to third- and fourth-generation cephalosporins, along with carbapenems.
  • Nevertheless, when the isolate is susceptible, beta-lactam agents should be used.
  • Ampicillin-sulbactam (due to its sulbactam component) is the treatment of choice, with cefepime, meropenem, and imipenem as alternative options based on in vitro susceptibility testing.
  • Currently, there is no antibiotic regimen that has been proven superior for the treatment of carbapenem-resistant A. baumannii.
  • The 2024 Infectious Diseases Society of America (IDSA) 'Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections' recommends sulbactam-durlobactam in combination with a carbapenem as their preferred regimen.
  • High-dose ampicillin-sulbactam in combination with either polymyxin B, minocycline, tigecycline, or cefiderocol is an alternative.
  • Pairing of sulbactam with durlobactam makes a novel diazabicyclooctane non-beta-lactam beta-lactamase inhibitor with activity against the Acinetobacter-derived cephalosporinase and class D beta-lactamases including carbapenemases of the OXA family.
  • High-dose ampicillin-sulbactam increases binding of sulbactam to its penicillin-binding proteins (PBP) targets (PBP2 and PBP3) in order to optimize inhibition of cell wall synthesis.
  • This recommendation is based on two meta-analyses of small clinical trials and observational data.
  • In a randomized clinical trial including 125 patients with carbapenem-resistant A. baumannii, patients treated with sulbactam-durlobactam had a 28-day all-cause mortality of 19% compared to 32% in patients treated with colistin, and with lower rates of nephrotoxicity in the sulbactam-durlobactam arm.
  • Cefiderocol is a siderophore cephalosporine with in vitro stability against the Acinetobacter-derived cephalosporinase and other extended-spectrum beta-lactamases.
  • However, A. baumannii isolates with reduced cefiderocol susceptibility have been described.
  • In a randomized clinical trial that included 54 critically ill patients with carbapenem-resistant A. baumannii, the end-of-study mortality was 50% in the cefiderocol arm, compared to 18% in the best available therapy arm (mostly consisting of colistin).
  • Different dosing strategies proposed if administered with ampicillin.
  • Polymyxins are cationic detergents that have become less popular as a result of nephrotoxicity and neurotoxicity.
  • Additionally, polymyxins are difficult to dose, have a narrow therapeutic window, and do not reach optimal tissue concentration in the lungs, which is a common site of infection for A. baumannii.
  • Despite its disadvantages, polymyxin B and polymyxin E (colistin) have been reintroduced in clinical practice as they retain in vitro activity against carbapenem-resistant A. baumannii.
  • In a randomized study of patients with pneumonia due to carbapenem-resistant Acinetobacter, patients receiving colistin in combination with high-dose ampicillin-sulbactam had a higher rate of clinical improvement by day 5 compared to those receiving colistin monotherapy.
  • The combination of colistin plus meropenem was long favored due to this strategy had comparable outcomes to colistin monotherapy.
  • Colistin is preferred for urinary tract infections.
  • Several tetracycline derivatives have in vitro activity against A. baumannii.
  • Of them, tigecycline and minocycline could be considered as part of a combination regimen, used at high doses when minimum inhibitory concentrations are low.
  • Although doxycycline is a widely available agent with established breakpoints against A. baumannii, it is usually less active than minocycline.
  • Eravacycline is a newer tetracycline with promising activity against A. baumannii; however its use has been limited; it is currently being marketed to treat more resistant strains.
  • Bacteriophage therapy against multidrug-resistant A. baumannii has been reported with varied success rates.
  • Furthermore, dosing and duration of therapy vary by syndrome and resistance can also arise during treatment.

7.1 Empirical Therapy

  • Based on local epidemiology.
  • Patient colonization status with carbapenem-resistant isolate.
  • Beta-lactam agents if susceptible.

7.2 Definitive Therapy

  • Determined by antimicrobial susceptibility testing.
  • IDSA 2024 Guidance: Sulbactam-durlobactam + carbapenem preferred.
  • Alternative: High-dose ampicillin-sulbactam + polymyxin B/minocycline/tigecycline/cefiderocol.

7.3 Specific Drug Classes

  • Sulbactam: Unavailable as single drug in many countries (including the United States). Different dosing strategies proposed if administered with ampicillin.
  • Sulbactam-durlobactam: Novel diazabicyclooctane non-beta-lactam beta-lactamase inhibitor.
  • Meropenem: Carbapenem-susceptible isolates only.
  • Imipenem-cilastatin: Carbapenem-susceptible isolates only.
  • Cefiderocol: Siderophore cephalosporine, in vitro synergy.
  • Colistin: Preferred for urinary tract infections.
  • Polymyxin B: Preferred over colistin for bloodstream infections.
  • Tigecycline: Use in combination therapy.
  • Minocycline: Use in combination therapy.
  • Eravacycline: Limited use, marketed for resistant strains.

8. PROGNOSIS & COMPLICATIONS

  • Infections caused by A. baumannii can be associated with high mortality rates.
  • Factors contributing to higher mortality are thought to include severity of the patient's underlying illness and drug resistance in the infecting strain.
  • Crude mortality rates associated with nosocomial pneumonia due to A. baumannii are reported as high as 65%.
  • Crude mortality rates from bloodstream infection are as high as 40%.
  • Rates can be as high as 70% from infections caused by carbapenem-resistant isolates.
  • In patients with infections caused by extremely drug-resistant strains, poor outcomes are thought to be driven by delays in the initiation of adequate antimicrobial therapy.
  • Polymicrobial growth has been reported in 20–36% of bacteremia episodes.
  • A. baumannii bloodstream infections often result in higher hospitalization costs and longer ICU stays.

8.1 Mortality Factors

  • Severity of underlying illness.
  • Drug resistance in infecting strain.
  • Delays in initiation of adequate antimicrobial therapy.

8.2 Complications

  • Septic shock.
  • Disseminated intravascular coagulopathy.
  • Hepatic and intra- and extraperitoneal abscesses.
  • Endocarditis.
  • Mycotic aneurysm.
  • Septic arthritis.
  • Osteomyelitis.
  • Necrotizing fasciitis.
  • Empyema.

9. SPECIAL CONSIDERATIONS

  • Health Care–Associated Infections: Occur frequently among patients admitted to intensive care units (ICUs).
  • Risk factors: Nursing home residence, prolonged ICU stay, central venous catheterization, tracheostomy, mechanical ventilation, enteral feedings, treatment with third-generation cephalosporins, fluoroquinolones, and carbapenems.
  • Community-Acquired Infections: Described in Australia and Asia.
  • War Zone–Associated Infections: Skin and soft tissue infections associated with traumatic injuries and bloodstream infections.
  • Disaster Medicine: A. baumannii is linked to infections among victims of trauma during tsunamis, earthquakes, and terrorist attacks.
  • Urinary Tract Infections: A. baumannii is an infrequent cause of urinary tract infections.
  • The majority of cases reported are catheter-associated infections, reflecting the ability of A. baumannii to form biofilms on these devices.
  • A few reports have described community-acquired infections occurring in the setting of nephrolithiasis and after renal transplantation.
  • Meningitis: Central nervous system infections with A. baumannii have been reported in the context of outbreaks, traumatic injuries, neurosurgical procedures, and external ventricular drains.
  • Other Miscellaneous Infections: A few cases of A. baumannii keratitis associated with the use of contact lenses have been reported.
  • Cases of native- and prosthetic-valve endocarditis have also been described.

9.1 Health Care Settings

  • ICU patients.
  • Nursing home residence.
  • Central venous catheterization.
  • Tracheostomy.
  • Mechanical ventilation.
  • Enteral feedings.

9.2 Community & Disaster

  • Australia and Asia.
  • Tsunamis, earthquakes, terrorist attacks.
  • Trauma victims.
  • Field hospitals.

9.3 Specific Sites

  • Urinary tract: Catheter-associated.
  • Meningitis: Outbreaks, trauma, neurosurgery.
  • Keratitis: Contact lenses.
  • Endocarditis: Native and prosthetic valves.

10. KEY PEARLS & CLINICAL TRAPS

  • A. baumannii is capable of surviving environmental desiccation for weeks.
  • This characteristic is important from an infection-control perspective as it allows this organism to persist in the hospital environment and on equipment.
  • Differentiation between colonization and infection is challenging.
  • Airway colonization with A. baumannii may not always indicate a diagnosis of pneumonia.
  • A. baumannii may look similar to Neisseria meningitidis on a Gram stain of cerebrospinal fluid; both appear as gram-negative paired cocci.
  • IDSA 2024 Guidance recommends sulbactam-durlobactam in combination with a carbapenem as their preferred regimen.
  • High-dose ampicillin-sulbactam increases binding of sulbactam to its penicillin-binding proteins (PBP) targets (PBP2 and PBP3) in order to optimize inhibition of cell wall synthesis.
  • Mortality rates for nosocomial pneumonia due to A. baumannii are reported as high as 65%.
  • Mortality rates for carbapenem-resistant bloodstream infections can be as high as 70%.
  • Biofilm formation via exopolysaccharide production and pilus formation is a key virulence mechanism facilitating persistence on surfaces and devices.

Figures & Illustrations

Reproduced from Harrison's 22nd Edition.

Figure 1

Strategies for the prevention of dissemination of Acinetobacter *— Figure...

Caption: FIGURE 167-1 Strategies for the prevention of dissemination of Acinetobacter — Figure 167-1 Strategies for the prevention of dissemination of Acinetobacter baumannii in health care facilities. The figure illustrates infection control measures including hand hygiene, contact precautions, physical separation of positive and negative patients, rectal surveillance, cohorting of nursing personnel, daily and terminal disinfection, limits on shared equipment, disinfection of equipment between patients, chlorhexidine baths, and antibiotic stewardship.

Generated from Harrison's Principles of Internal Medicine, 22nd Edition.