Acinetobacter Infections¶

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

Key Clinical Points¶

A. baumannii survives environmental desiccation for weeks, facilitating hospital outbreaks.
Colonization vs infection differentiation is critical; airway/skin colonization does not always indicate active disease.
IDSA 2024 recommends sulbactam-durlobactam + carbapenem for carbapenem-resistant A. baumannii.
Mortality: 65% for nosocomial pneumonia, 70% for carbapenem-resistant bloodstream infections.
A. baumannii has intrinsic AmpC beta-lactamases (upregulated by ISAba1) and can acquire OXA-family carbapenemases.
Biofilm formation via exopolysaccharide/pilus production enables persistence on surfaces and medical devices.
High-dose ampicillin-sulbactam enhances sulbactam binding to PBPs, optimizing cell wall inhibition.
A. baumannii may mimic N. meningitidis on CSF Gram stain (gram-negative paired cocci).
Outbreaks linked to poor hand hygiene, equipment contamination, and airborne spread in unbarriered areas.
Sulbactam-durlobactam shows lower nephrotoxicity and improved mortality compared to colistin.

DEFINITION & CLASSIFICATION¶

• Classification: Gram-negative, oxidase-negative, nonmotile, nonfermenting coccobacilli. • Identification: Phenotypic differentiation is difficult; molecular methods (MALDI-TOF-MS, PCR) are required for A. baumannii identification. • Persistence: Ability to survive desiccation for weeks is critical for hospital persistence.

1.1 Historical Classification¶

• Originally named Micrococcus calcoaceticus (1911). • Renamed multiple times since 1950. • Current classification: Acinetobacter.

1.2 Morphology & Identification¶

• Gram-negative coccobacilli. • Oxidase-negative, nonmotile, nonfermenting. • Easily cultured on standard media. • Phenotypic differentiation difficult; molecular methods (MALDI-TOF-MS, PCR) required for A. baumannii identification.

EPIDEMIOLOGY¶

• Global Impact: Rising incidence as a global nosocomial pathogen; CDC estimates 12,000 annual infections in the US (7,300 multidrug-resistant). • Transmission Drivers: Outbreaks linked to ICU stays, carbapenem use, and healthcare worker hand hygiene lapses. • Community Cases: Rare in temperate climates; occurs during warm/humid months (risk factors: alcohol abuse, diabetes, smoking, chronic lung disease). • Disaster/War Zones: Linked to trauma victims (tsunamis, earthquakes); common infections include soft tissue injuries and bloodstream infections.

2.1 Health Care–Associated Infections¶

• Predominant in ICUs. • Risk factors: Prolonged ICU stay, mechanical ventilation, central venous catheters, carbapenem exposure. • Outbreaks reported in Ohio, Michigan, Illinois, Indiana.

2.2 Community-Acquired Infections¶

• Rare in temperate climates; occurs during warm/humid months. • Risk factors: Alcohol abuse, diabetes, smoking, chronic lung disease.

2.3 Disaster & War Zone Infections¶

• Linked to trauma victims (tsunamis, earthquakes). • Common infections: Soft tissue injuries, bloodstream infections, pneumonia. • Military outbreaks linked to field hospital surfaces, not pre-injury colonization.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Genetics: Pangenome includes a small core genome and large accessory genome enabling rapid adaptation. • Virulence Factors: ◦ Biofilm formation (exopolysaccharide/pilus). ◦ Quorum sensing (abaI autoinducer synthase). ◦ Lipid A modification (enables desiccation survival & antibiotic resistance). ◦ Extracellular capsule (complement evasion). ◦ Phospholipases C/D (cytotoxicity, invasion). ◦ Secretion systems (Type II/VI/V; produce lipase and toxins). • Resistance Mechanisms: ◦ Porin reduction. ◦ Efflux pumps (quinolones, tetracyclines, tigecycline). ◦ AmpC beta-lactamases (class C, upregulated by ISAba1). ◦ OXA-family carbapenemases (OXA-23/51/24/40/58/143/235).

3.1 Virulence Factors¶

• Biofilm formation (exopolysaccharide/pilus). • Quorum sensing (abaI autoinducer synthase). • Lipid A modification (antibiotic resistance, desiccation survival). • Extracellular capsule (complement evasion). • Phospholipases C/D (cytotoxicity, invasion). • Type II/VI/V secretion systems (lipase, antibacterial toxins, biofilm adherence).

3.2 Resistance Mechanisms¶

• Porin reduction. • Efflux pumps (quinolones, tetracyclines, tigecycline). • AmpC beta-lactamases (class C, upregulated by ISAba1). • OXA-family carbapenemases (OXA-23/51/24/40/58/143/235).

CLINICAL FEATURES¶

• Pneumonia: Nosocomial; late-onset in ventilated patients; fever, increased sputum production; 65% mortality for carbapenem-resistant strains. • Bloodstream Infections (BSI): ICU-associated; fever (>95%), septic shock (25-30%), DIC; 40% mortality (70% for carbapenem-resistant); polymicrobial growth in 20-36% of cases. • Skin and Soft Tissue Infections (SSTI): Common in combat trauma (gunshot wounds) and burn units; progression: edematous → sandpaper → necrotizing bullae (peau d'orange). • Meningitis: Associated with outbreaks, trauma, or neurosurgery; 30% present with petechial rash; CSF Gram stain mimics N. meningitidis.

4.1 Pneumonia¶

• Nosocomial: Ventilated patients, late-onset. • Symptoms: Fever, increased sputum production. • Radiology: Lobar consolidation, pleural effusion. • Mortality: 65% (carbapenem-resistant strains).

4.2 Bloodstream Infections¶

• ICU-associated (central lines/pneumonia). • Symptoms: Fever (>95%), septic shock (25-30%), DIC. • Mortality: 40% (70% for carbapenem-resistant). • Polymicrobial growth: 20-36%.

4.3 Skin and Soft Tissue Infections¶

• Combat trauma: Gunshot wounds, orthopedic devices. • Burn units: Delayed healing, graft loss. • Clinical progression: Edematous → sandpaper → necrotizing bullae.

4.4 Meningitis & Other¶

• Outbreaks, trauma, neurosurgery. • Petechial rash (30%). • CSF Gram stain mimic: N. meningitidis (gram-negative paired cocci). • Keratitis: Contact lens use. • Endocarditis: Native/prosthetic valves.

DIFFERENTIAL DIAGNOSIS¶

• Gram Stain Mimics: N. meningitidis (appears as gram-negative paired cocci in CSF). • Colonization vs. Infection: Airway, skin, or wound colonization may not indicate active disease; differentiation is critical for management. • Other Gram-Negatives: Kluyvera, Raoultella (carbapenemase producers), Edwardsiella (H2S producing).

5.1 Gram Stain Mimics¶

• Neisseria meningitidis. • Appearance: Gram-negative paired cocci in CSF. • Differentiation critical for meningitis management.

5.2 Colonization vs Infection¶

• Airway colonization eq pneumonia. • Skin/wound colonization vs infection challenging to distinguish.

DIAGNOSTIC APPROACH¶

Microbiological Identification:
Culture: Easily recovered on standard media.
Molecular methods: MALDI-TOF-MS, PCR for A. baumannii identification due to phenotypic similarity.
Differentiation: H2S production (Edwardsiella) vs no H2S (Acinetobacter).
Environmental Sampling:
Natural reservoirs: Water, soil, fruits/vegetables.
Human colonization: Skin, respiratory/gastrointestinal tracts.
Hospital spread: Contaminated equipment (ventilators), air in unbarriered ICUs.

6.1 Microbiological Identification¶

• Standard culture media: Easily recovered. • Molecular methods: MALDI-TOF-MS, PCR. • Biochemical differentiation: H2S production (Edwardsiella) vs no H2S (Acinetobacter).

6.2 Environmental Sampling¶

• Natural reservoirs: Water, soil, fruits/vegetables. • Human colonization: Skin, respiratory/gastrointestinal tracts. • Hospital spread: Contaminated equipment, poor hand hygiene.

MANAGEMENT & TREATMENT¶

Empirical Therapy:
Recommendation (IDSA 2024): Sulbactam-durlobactam + carbapenem.
Consideration: Local resistance patterns and patient colonization status.
Definitive Therapy:
Preferred: Ampicillin-sulbactam (enhances sulbactam binding to PBPs, optimizing cell wall inhibition).
Alternatives: Cefepime, meropenem, or imipenem based on susceptibility testing.
Carbapenem-Resistant Strains:
Sulbactam-durlobactam (preferred over colistin due to lower nephrotoxicity).
Colistin (reserved for specific cases; preferred for urinary tract infections).
Meningitis Management:
High-dose ampicillin-sulbactam for CNS penetration.
Specific Drug Regimens (Table 167-1):
Sulbactam: 6–9 g/d (not available as single drug in many countries; different dosing if with ampicillin).
Sulbactam-durlobactam: 1 g/1 g q6h or 2 g q8h (infuse over 3 h).
Imipenem-cilastatin: 500 mg q6h or 2g q8h (carbapenem-susceptible only; infuse over 3 h).
Colistin: Dosing per international consensus guidelines.
Tigecycline: 200-mg loading dose followed by 100 mg q12h; 200 mg q12h (use in combination therapy).

7.1 Empirical Therapy¶

• IDSA 2024 recommendation: Sulbactam-durlobactam + carbapenem. • Consider local resistance patterns and patient colonization status.

7.2 Definitive Therapy¶

• Ampicillin-sulbactam (preferred). • Alternatives: Cefepime, meropenem, or imipenem based on susceptibility testing.

7.3 Specific Drug Classes¶

• Sulbactam-durlobactam: Lower nephrotoxicity vs colistin. • Ampicillin-sulbactam: Enhances sulbactam binding to PBPs.

7.4 Infection Control (Figure 167-1)¶

Hand Hygiene & Contact Precautions: Primary defense against transmission via healthcare worker hands.
Equipment Management:
Daily and terminal disinfection.
Limits on shared equipment.
Disinfection of equipment between patients.
Environmental/Patient Separation:
Physical separation from A. baumannii-positive patients.
Cohorting nursing personnel.
Chlorhexidine baths.
Antibiotic stewardship.

PROGNOSIS & COMPLICATIONS¶

• Mortality Factors: - High mortality linked to carbapenem/colistin resistance, delayed antimicrobial initiation, and ICU severity of illness. - Nosocomial pneumonia: 65% mortality. - Carbapenem-resistant BSI: 70% mortality. • Clinical Complications: - Septic shock (25-30%). - DIC. - Polymicrobial bacteremia (20-36%). - Burn wound complications: Healing delays, graft loss.

8.1 Mortality Factors¶

• Resistance to carbapenems/colistin. • Delayed antimicrobial initiation. • ICU severity of illness.

8.2 Complications¶

• Septic shock (25-30%). • DIC. • Polymicrobial bacteremia. • Burn wound complications: Healing delays, graft loss.

SPECIAL CONSIDERATIONS¶

• Healthcare Settings: Focus on infection control (hand hygiene, environmental decontamination). • Disaster Zones: Trauma-associated soft tissue infections. • Specific Sites: - Burn units: High risk for graft loss and bloodstream infection. - Meningitis: Requires CNS-penetrating antibiotics (ampicillin-sulbactam).

9.1 Health Care Settings¶

• Infection control: Hand hygiene, surface decontamination. • Outbreak management: Contact precautions, cohorting.

9.2 Community & Disaster¶

• Disaster zones: Soft tissue infections from trauma. • Military outbreaks: Field hospital acquisition, not pre-injury colonization.

9.3 Specific Sites¶

• Burn units: High risk for graft loss and bloodstream infection. • Meningitis: Requires CNS-penetrating antibiotics (ampicillin-sulbactam).

KEY PEARLS & CLINICAL TRAPS¶

• Gram Stain Trap: A. baumannii mimics N. meningitidis (gram-negative paired cocci) in CSF. • Colonization Rule: Airway/skin colonization eq infection; do not treat unless clinical evidence of disease exists. • Persistence: Biofilm formation via exopolysaccharide/pilus allows survival on surfaces. • Treatment Choice: Sulbactam-durlobactam is preferred over colistin due to lower nephrotoxicity. • Mortality Alert: Mortality exceeds 65% for nosocomial pneumonia and 70% for carbapenem-resistant BSI.

Reference Tables¶

TABLE 167-1 Therapeutic Options for the Management of Multidrug- Resistant Acinetobacter baumannii Infections…¶

Harrison's 22e, p.1297

ANTIBIOTIC	DOSINGa	COMMENTS
Sulbactam	6–9 g/d	Unavailable as single drug in many countries (including the United States). Different dosing strategies proposed if administered with ampicillin.
	3 g q4h 9 g q8h 27 g q24h
Sulbactam- durlobactam	1 g/1 g q6h	Infuse over 3 h
	2 g q8h
Imipenem- cilastatin	500 mg q6h	Carbapenem-susceptible isolates only; infuse over 3 h
	2g q8h
Colistin	Dosing per the international consensus guidelines on polymixins (Tsuji BT et al, Pharmacotherapy 39:10, 2019)	Colistin is preferred for urinary tract infections.
	Dosing per the international consensus guidelines on polymixins (Tsuji BT et al, Pharmacotherapy 39:10, 2019)
Tigecycline	200-mg loading dose followed by 100 mg q12h	Use in combination therapy
	200 mg q12h
Shared e	quipment
-Daily and terminal disinfection
-Limits on shared equipment -Disinfection of equipment between patients