Carbapenem-Resistant Acinetobacter baumannii: Healthcare Threat

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major healthcare concern due to its ability to cause severe infections while resisting multiple antibiotics. It is particularly dangerous for hospitalized patients, especially those in intensive care units, where outbreaks are difficult to control. Its resistance to carbapenems—a class of last-resort antibiotics—limits treatment options and increases the risk of poor outcomes.

Addressing CRAB requires understanding its transmission, identification methods, and treatment strategies.

Characteristics Of The Organism

Acinetobacter baumannii is a Gram-negative, non-fermenting coccobacillus that thrives in healthcare environments, persisting on surfaces for extended periods. Its ability to survive desiccation and resist disinfectants makes it a formidable nosocomial pathogen. It colonizes dry hospital surfaces, medical equipment, and even the skin of healthcare workers, contributing to its persistence and transmission.

A defining feature of A. baumannii is its genetic adaptability, which allows it to rapidly acquire resistance through horizontal gene transfer. Mobile genetic elements such as plasmids, transposons, and integrons enable the bacterium to integrate resistance genes from other pathogens. Clinical strains often harbor multiple resistance islands—clusters of genes that confer resistance to β-lactams, aminoglycosides, and fluoroquinolones. This adaptability has driven the emergence of carbapenem-resistant strains, complicating treatment.

Additionally, A. baumannii forms biofilms, providing protection against desiccation, disinfectants, and host immune responses. Biofilm-associated infections, such as ventilator-associated pneumonia and catheter-related bloodstream infections, are particularly difficult to treat. The bacterium’s ability to adhere to surfaces like endotracheal tubes and catheters increases the risk of device-associated infections in hospitalized patients.

Mechanisms Leading To Carbapenem Resistance

Carbapenem resistance in Acinetobacter baumannii results from enzymatic degradation, reduced membrane permeability, active efflux, and target site modifications. These mechanisms often coexist, compounding resistance and limiting treatment options.

A primary contributor is the production of carbapenem-hydrolyzing β-lactamases, particularly OXA-type carbapenemases (OXA-23, OXA-24/40, and OXA-58) and metallo-β-lactamases (MBLs) such as NDM-1 and VIM-type enzymes. OXA-type carbapenemases efficiently degrade carbapenems while resisting traditional β-lactamase inhibitors. MBLs hydrolyze a broad spectrum of β-lactams, further complicating treatment. These resistance genes are often carried on plasmids or transposons, enabling rapid dissemination.

Beyond enzymatic degradation, alterations in outer membrane proteins (OMPs) reduce antibiotic influx. Porins like CarO and OmpA, which facilitate β-lactam uptake, are frequently downregulated or inactivated in resistant strains. The loss of CarO, for example, decreases susceptibility to imipenem and meropenem.

Efflux pumps contribute further by actively expelling antibiotics. Resistance-nodulation-division (RND) efflux systems such as AdeABC, AdeIJK, and AdeFGH reduce intracellular carbapenem concentrations. Overexpression of these pumps, often due to mutations in transcriptional repressors, leads to constitutive antibiotic extrusion. Studies show that inhibiting these pumps can partially restore carbapenem susceptibility.

Common Routes Of Spread In Healthcare

Acinetobacter baumannii persists on hospital surfaces and medical equipment, facilitating transmission through direct and indirect contact. It can survive on dry surfaces such as bed rails, ventilators, and infusion pumps for weeks, making thorough disinfection critical. Healthcare workers contribute to its spread when hand hygiene is inadequate or contaminated gloves and gowns are improperly reused.

Invasive procedures, such as central venous catheterization and mechanical ventilation, increase transmission risks. The bacterium frequently colonizes medical devices, leading to deep-seated infections. Cross-contamination occurs when aseptic techniques are not strictly followed or when improperly sterilized equipment is reused.

Patient-to-patient transmission is particularly concerning in intensive care units, where individuals with compromised health are in close proximity. Cohorting infected patients or failing to implement isolation measures accelerates the spread of multidrug-resistant strains. Asymptomatic carriers further complicate containment, shedding bacteria onto shared surfaces without showing symptoms.

Laboratory Identification

Detecting CRAB in clinical samples requires culture-based methods, susceptibility testing, and molecular diagnostics. Traditional microbiological approaches begin with isolation on selective media such as MacConkey agar, where A. baumannii appears as non-lactose fermenting colonies. Chromogenic agars designed for multidrug-resistant Gram-negative bacteria improve initial detection. Automated systems like VITEK 2, BD Phoenix, and MicroScan provide preliminary species identification and antimicrobial susceptibility profiles.

Carbapenem resistance is evaluated using phenotypic susceptibility testing, with broth microdilution considered the gold standard for determining minimum inhibitory concentrations (MICs). The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) define MIC breakpoints for carbapenems to classify isolates as resistant. When results are ambiguous, tests such as the modified Hodge test, Carba NP test, or inhibitor-based assays (boronic acid and EDTA) help differentiate between resistance mechanisms.

Potential Clinical Outcomes

CRAB infections are associated with high morbidity and mortality, particularly in critically ill patients. The pathogen causes ventilator-associated pneumonia, bloodstream infections, urinary tract infections, and wound infections, leading to prolonged hospital stays, increased healthcare costs, and high treatment failure rates. Mortality for CRAB-related ventilator-associated pneumonia can exceed 50%.

Beyond acute infections, CRAB can cause long-term complications. Bloodstream infections often lead to recurrent bacteremia, requiring repeated hospitalizations. Surgical site infections can result in delayed wound healing and secondary complications such as osteomyelitis. Limited treatment options force reliance on combination therapies, which may have significant toxicity or suboptimal efficacy. The burden on patients and healthcare systems underscores the need for improved infection control and novel treatment strategies.

Pharmacological Interventions

Treating CRAB infections is challenging due to resistance to most conventional antibiotics. The limited efficacy of β-lactams and fluoroquinolones has led to increased use of alternative agents, often in combination regimens. Polymyxins, including colistin and polymyxin B, disrupt the bacterial outer membrane, though their nephrotoxicity and neurotoxicity are concerns. Tigecycline, a glycylcycline antibiotic, is another option, though its low serum concentrations make it less effective for bloodstream infections. Sulbactam, traditionally a β-lactamase inhibitor, has intrinsic activity against A. baumannii and is often combined with other agents.

Combination therapy is preferred to improve outcomes. Regimens incorporating colistin with carbapenems, rifampin, or fosfomycin have shown synergistic effects. New β-lactam/β-lactamase inhibitor combinations, such as ceftazidime-avibactam, offer promise, though efficacy varies. Cefiderocol, a siderophore cephalosporin, has been approved for carbapenem-resistant Gram-negative bacteria, including A. baumannii, providing another treatment option. Ongoing clinical trials evaluating novel antimicrobial agents and optimized dosing strategies remain essential in combating CRAB infections.