Acinetobacter spp.

Acinetobacter spp. are aerobic, Gram-negative coccobacilli commonly found in soil, water, and human skin and throat flora. These bacteria, which include over 34 identified species, are non-motile but exhibit twitching motility, thriving optimally at 33-37°C. 

Clinically, Acinetobacter baumannii is the most significant due to its high virulence and multidrug resistance, leading to severe infections and high mortality rates in immunocompromised patients and those with multi-organ disease. 

Acinetobacter spp. primarily spread in healthcare settings, particularly in ICUs, causing infections such as ventilator-associated pneumonia, bloodstream infections, and wound infections. 

Management involves removing infected devices, debridement of necrotic tissue, and using effective antibiotics like meropenem, colistin, and sulbactam. 

The increasing antibiotic resistance of Acinetobacter spp. poses significant challenges, necessitating stringent infection control measures and continuous epidemiological surveillance.

What is Acinetobacter spp.?

Acinetobacter spp. are aerobic Gram-negative coccobacilli commonly found in soil, water, and as part of the human skin and throat flora. [2.] 

The genus has undergone extensive taxonomic revisions, and modern molecular techniques have identified over 34 species. [2.] 

Acinetobacter spp. are non-motile, although some exhibit twitching motility, and are strictly aerobic, thriving optimally at 33-37°C. [2., 3.] 

Although generally low in virulence, it can cause serious infections in immunocompromised patients and those with multi-organ disease. [3.] 

Clinically, Acinetobacter baumannii, A. nosocomialis, and A. pittii are the most significant, with A. baumannii being particularly notorious for its high virulence and multidrug resistance, often leading to severe infections and high mortality rates. [3., 4.] 

These bacteria primarily spread in healthcare settings; Acinetobacter spp. thrive in hospital settings, especially in ICUs, where they can cause ventilator-associated pneumonia, bloodstream infections, urinary tract infections and wound infections among critically ill patients. [3.] 

Management of Acinetobacter infections involves the removal of infected devices, thorough debridement of necrotic tissue, and the use of effective antibiotics such as meropenem, colistin, and sulbactam. [3.] 

Their resistance to common antibiotics poses significant challenges in healthcare, necessitating stringent infection control measures and continuous epidemiological surveillance.

Antimicrobial Resistance Markers [5.] 

One of the most notable characteristics of Acinetobacter spp. is their ability to develop resistance to multiple classes of antibiotics. This resistance is best studied in relationship to the antibiotic resistance seen with Acinetobacter baumannii, considered the most virulent and antibiotic-resistant strain. 

A. baumannii has developed a well-known antibiotic resistance to carbapenem.  Carbapenem belongs to the beta-lactam family of antibiotics, which includes penicillins and cephalosporins.

The rising trend of carbapenem resistance in Acinetobacter baumannii is concerning due to limited therapeutic options. This resistance is attributed to several mechanisms:

Metallo-β-lactamases (MBLs)

These enzymes hydrolyze carbapenems efficiently, rendering them ineffective against A. baumannii by breaking down the antibiotic molecules.

Carbapenem-Hydrolyzing Class D β-Lactamases (CHDLs)

These enzymes hydrolyze carbapenems, with varying efficiencies, contributing significantly to resistance by deactivating the antibiotic.

Intrinsic Oxacillinase

The OXA-51/69 variants, when overexpressed, can hydrolyze carbapenems and reduce the susceptibility of A. baumannii to these antibiotics.

Porin Modifications

Loss or alteration of the CarO protein and other porins reduces carbapenem uptake into the bacterial cell, thereby decreasing the antibiotic's effectiveness.

Penicillin-Binding Protein (PBP) Modifications

Alterations in PBPs reduce the binding affinity of carbapenems, thereby diminishing their antibacterial activity.

Acinetobacter spp. Virulence Factors [6.] 

Virulence factors are molecules produced by pathogens that contribute to their ability to cause infection and disease in their host.

Many of the virulence factors associated with Acinetobacter spp. have been identified and studied while researching A. baumannii, the most pathogenic strain of Acinetobacter spp.  

Virulence factors associated with A. baumannii include:

Outer Membrane Proteins (Omps)

• OmpA: involved in adhesion, invasion, autophagy induction, cellular injury, and biofilm formation. It triggers multiple signaling pathways, leading to cellular damage and immune evasion.

• CarO: plays a role in bacterial adhesion and colonization, affecting neutrophil infiltration and inflammation.

• Omp33: contributes to water transport, adherence, invasion, and cytotoxicity by triggering apoptosis.

• OprD/OccAB1: facilitates the transport of molecules, including antibiotics, and contributes to virulence but not directly to antibiotic resistance.

• OmpW: involved in environmental stress resistance and cytotoxicity, contributing to iron uptake and bacterial survival.

Lipopolysaccharides (LPS)

LPS is a lipid A component that induces inflammatory cytokines and contributes to serum resistance, aiding in immune evasion and promoting inflammatory responses.

Capsular Polysaccharides (CPS)

Synthesized by the K-locus gene cluster, CPS aids in immune evasion, resistance to phagocytosis, desiccation, and antibiotic penetration, enhancing virulence and mucoid phenotype formation.

Phospholipases

Phospholipase C and D disrupt epithelial cell membranes, contribute to cytotoxicity, and aid in iron acquisition by lysing human erythrocytes.

Pili and Motility

• Type IV Pili: promote twitching motility, DNA uptake, and biofilm formation.

• Chaperone–Usher Pilus System: csu pilus aids in biofilm formation and adherence to host cells, regulated by BfmRS and GacSA systems.

Iron Acquisition

Utilizes siderophores, outer membrane vesicles, and heme molecules to acquire iron, crucial for survival and virulence. Acinetobactin, a major siderophore, facilitates iron uptake under acidic conditions, enhancing colonization and infection.

Secretion Systems

• T1SS: exports biofilm-associated proteins, aiding in adherence and biofilm maintenance.

• T2SS: Secretes virulence factors like lipases and phospholipases, contributing to lipid assimilation, serum resistance, and immune modulation.

• T4SS: Transfers genetic elements, aiding in the spread of drug-resistant genes.

• T5SS: Includes proteins like AbFhaB and Ata, which mediate adhesion, invasion, and immune response modulation.

• T6SS: Delivers toxic proteins to neighboring bacteria, promoting competitive advantage and virulence.

GigA, GigB, and GigC

These regulators respond to environmental stress signals, aiding in bacterial survival and virulence under challenging conditions.

Thioredoxin A (TrxA)

Crucial for oxidative stress resistance, immune evasion, and regulation of cell surface hydrophobicity and type IV pilus system.

Polyphosphate Kinase (PPK)

PPK1 is essential for polyphosphate synthesis, affecting motility, biofilm formation, and resistance to external pressures. 

Laboratory Testing for Acinetobacter spp.

Test Type, Sample Collection and Preparation

The presence of Acinetobacter spp. is typically assessed by culturing samples taken from the nasopharynx, wounds, or body fluid samples.

Because Acinetobacter spp. is typically a hospital-acquired infection, sample collection and testing most commonly occur in a hospital and/or clinical setting.  

Interpretation of Acinetobacter spp. Testing

Optimal Levels of Acinetobacter spp. 

Acinetobacter spp. is a potentially pathogenic species that is tested in clinical or hospital settings when there is concern for nosocomial infection with this organism.  Optimal levels of this bacterium are undetectable.  

Clinical Significance of Elevated Levels of Acinetobacter spp. 

The presence of elevated levels of Acinetobacter spp. in cultured tissue or fluid indicates the presence of colonization or an infection with this organism.  

Treatment of Acinetobacter spp. Infection

Due to increasing antibiotic resistance of Acinetobacter spp., selecting the appropriate treatment for an individual is essential.

Treatment decisions will be guided by the individual's potential medication allergies, as well as susceptibility of the organism present to various antibiotic therapies.  

Common Antibiotic Therapies Used for Acinetobacter spp. Infection [1.] 

Acinetobacter baumannii, the most common strain of Acinetobacter spp. infection, is inherently multidrug-resistant with limited antibiotics effective against it. 

Avoid treating colonization; however, infections require treatment.

Bacterial colonization is defined as the presence and growth of bacteria on or in a host without causing disease or eliciting an immune response. Colonization generally does not trigger an inflammatory response or symptoms.

Colonization often occurs on external surfaces like skin or mucous membranes, and it can be beneficial or neutral to the host (e.g., normal gut flora).

In contrast, an infection is the invasion and multiplication of bacteria in host tissues, causing cellular injury and eliciting an immune response that is ultimately harmful to the host.

Medications to which Acinetobacter is usually sensitive include: [1.]

• Amikacin

• Colistin

• Meropenem

• Minocycline

• Polymyxin B

• Rifampin

• Sulbactam/durlobactam

• Tigecycline

First-, second-, and third-generation cephalosporins, macrolides, and penicillins generally have little or no activity against Acinetobacter and may predispose to colonization. 

Some strains are sensitive to cefepime, ceftazidime, and some combination antibiotics.

Both monotherapy and combination therapy (e.g., amikacin, minocycline, or colistin ± rifampin) have been used successfully. 

While combination therapy is often suggested, conclusive data on its superiority in preventing failure or resistance development are lacking. It can be considered for empiric therapy in areas with high antimicrobial resistance rates or for isolates resistant to multiple antibiotic classes.

FAQ: Understanding Acinetobacter spp. 

Acinetobacter spp. refers to a group of bacteria that are increasingly recognized for their role in causing healthcare-associated infections. These bacteria are known for their resistance to multiple antibiotics, posing significant challenges in clinical settings. 

What is Acinetobacter spp.?

Acinetobacter spp. is a group of gram-negative bacteria commonly found in the environment, particularly in soil and water. They have become significant pathogens in healthcare settings, capable of causing a range of infections, especially in immunocompromised patients.

What Types of Infections Can Acinetobacter spp. Cause?

Acinetobacter spp. can cause various infections, including:

• Pneumonia: Often associated with ventilator use in hospitals.

• Bloodstream infections: Particularly in patients with central lines or other invasive devices.

• Wound infections: Common in burn patients or those with open wounds.

• Urinary tract infections: Often related to catheter use.

• Skin and soft tissue infections: Including cellulitis and abscesses.

Why is Acinetobacter spp. Significant in Healthcare Settings?

Acinetobacter spp. is significant because it is highly resistant to multiple antibiotics, making infections difficult to treat. It can survive on surfaces for extended periods, facilitating its spread within healthcare facilities and leading to outbreaks of infections.

How is Acinetobacter spp. Infection Diagnosed?

Diagnosis typically involves collecting samples from the site of infection (e.g., sputum, blood, wound swab) and performing laboratory tests, such as cultures and molecular methods, to identify the presence of Acinetobacter spp.

What are the Symptoms of an Acinetobacter spp. Infection?

Symptoms depend on the site of infection but can include:

• Pneumonia: Cough, fever, shortness of breath, chest pain

• Bloodstream infections: Fever, chills, rapid heart rate, confusion

• Wound infections: Redness, swelling, pain, pus drainage

• Urinary tract infections: Frequent urination, pain during urination, blood in urine

How is Acinetobacter spp. Infection Treated?

Treatment is challenging due to antibiotic resistance. Options may include:

• Combination antibiotic therapy tailored to the sensitivity profile of the bacteria

• Use of last-resort antibiotics 

• Supportive care and management of symptoms

• Removal of infected or colonized medical devices when possible

How Can the Spread of Acinetobacter spp. Be Prevented?

Preventive measures include:

• Adhering to strict hand hygiene protocols

• Implementing robust infection control practices in healthcare settings

• Regular cleaning and disinfection of medical equipment and surfaces

• Judicious use of antibiotics to reduce selective pressure

What is the Importance of Monitoring Acinetobacter spp. In a Hospital Setting?

Testing for Acinetobacter spp. provides the opportunity for swift treatment and eradication of this potentially pathogenic organism.  It requires an understanding of the prevalence and resistance patterns of these bacteria. 

What are the Risk Factors for Acinetobacter spp. Infections?

Risk factors include:

• Hospitalization, especially in intensive care units

• Use of invasive devices such as ventilators and catheters

• Recent surgery

• Prolonged antibiotic use

• Weakened immune system or chronic medical conditions

When Should I Seek medical Attention for Acinetobacter spp. Symptoms?

Seek medical attention if you experience symptoms of an infection, particularly if you have been hospitalized or have risk factors such as a compromised immune system. 

Early diagnosis and appropriate treatment are key to managing Acinetobacter spp. infections effectively.