Colistin, also known as polymyxin E, is a last-resort antibiotic used primarily against multidrug-resistant Gram-negative bacteria. Its unique mechanism of action involves disruption of the bacterial outer membrane, leading to cell death. Despite its potent activity against several problematic pathogens, certain organisms are intrinsically resistant to colistin. Understanding which bacteria possess this intrinsic resistance is critical for effective antimicrobial therapy, infection control, and prevention of treatment failures.
Mechanism of Colistin Action
Colistin acts by interacting with lipopolysaccharides (LPS) and phospholipids in the outer membrane of Gram-negative bacteria. This interaction disrupts membrane integrity, causing leakage of cellular contents and bacterial cell death. However, bacteria that lack specific LPS structures or possess outer membrane modifications may not be susceptible to colistin, leading to intrinsic resistance.
Definition of Intrinsic Resistance
Intrinsic resistance refers to the natural ability of a bacterial species to withstand the effects of an antibiotic, independent of previous exposure or acquired resistance mechanisms. Unlike acquired resistance, intrinsic resistance is genetically encoded and universally present in all strains of the species. For colistin, intrinsic resistance is typically associated with structural or functional properties of the bacterial outer membrane that prevent colistin from binding effectively.
Gram-Negative Bacteria with Intrinsic Colistin Resistance
While colistin is highly effective against many Gram-negative pathogens, some organisms exhibit inherent resistance. These organisms generally share specific structural features in their outer membrane that reduce susceptibility to polymyxins.
Proteus Species
Proteus species, includingProteus mirabilis, are intrinsically resistant to colistin. The resistance is linked to modifications of the lipid A component of LPS, which prevent colistin from binding efficiently. Clinically, Proteus infections are commonly associated with urinary tract infections, wound infections, and bacteremia, and colistin should not be used as monotherapy against these bacteria.
Serratia Species
Serratia species, particularlySerratia marcescens, also demonstrate intrinsic colistin resistance. Alterations in outer membrane permeability and LPS structure confer this resistance. Serratia can cause nosocomial infections, including urinary tract infections, respiratory tract infections, and sepsis, making awareness of colistin resistance essential in hospital settings.
Burkholderia Species
Burkholderia species, such asBurkholderia cepaciacomplex, are notorious for intrinsic resistance to multiple antibiotics, including colistin. The resistance mechanism involves LPS modifications and efflux pumps that reduce intracellular accumulation of colistin. Burkholderia infections are particularly concerning in immunocompromised patients and individuals with cystic fibrosis, requiring alternative antimicrobial strategies.
Providencia Species
Providencia species, includingProvidencia stuartii, exhibit intrinsic resistance to colistin. These organisms are often implicated in catheter-associated urinary tract infections and nosocomial outbreaks. Their natural resistance to polymyxins necessitates careful selection of antibiotics for treatment.
Edwardsiella Species
Edwardsiella, a genus of Gram-negative bacteria primarily associated with aquatic environments and fish pathogens, is also intrinsically resistant to colistin. Though human infections are rare, they can occur in immunocompromised patients. Clinicians should be aware of intrinsic resistance patterns when treating suspected infections.
Mechanisms Underlying Intrinsic Resistance
Intrinsic resistance to colistin is typically mediated by several key mechanisms
- Lipid A ModificationMany resistant bacteria modify lipid A with molecules such as 4-amino-4-deoxy-L-arabinose or phosphoethanolamine, reducing colistin binding affinity.
- Outer Membrane CompositionVariations in outer membrane proteins and LPS density decrease colistin permeability.
- Efflux PumpsSome bacteria possess efflux systems that actively expel colistin before it can exert its bactericidal effect.
- Biofilm FormationBiofilm-producing bacteria can reduce colistin penetration, although this is more commonly associated with acquired resistance.
Clinical Implications
Intrinsic resistance to colistin has significant clinical implications. Using colistin against naturally resistant organisms may lead to treatment failure, prolonged hospital stays, and increased morbidity. Therefore, identification of the causative pathogen and understanding its resistance profile is essential before initiating therapy.
Importance in Multidrug-Resistant Infections
Colistin is often reserved for multidrug-resistant infections, particularly those caused byEscherichia coli,Klebsiella pneumoniae, andPseudomonas aeruginosa. However, infections caused by intrinsically resistant bacteria such as Proteus, Serratia, and Burkholderia require alternative agents. Empiric use of colistin without awareness of intrinsic resistance can compromise patient outcomes.
Laboratory Identification
Laboratory testing is crucial for detecting colistin resistance. Standard susceptibility testing methods include broth microdilution, which is preferred due to the unreliability of automated systems in detecting polymyxin resistance. Accurate identification of intrinsic resistance prevents inappropriate use and supports effective antimicrobial stewardship.
Alternative Treatment Options
For infections caused by organisms intrinsically resistant to colistin, alternative antimicrobial therapies must be considered. Options include
- Carbapenems, if the organism is susceptible.
- Third- or fourth-generation cephalosporins, based on sensitivity testing.
- Trimethoprim-sulfamethoxazole for specific strains like Burkholderia or Providencia.
- Combination therapy for multidrug-resistant infections, guided by susceptibility results.
Preventive Measures and Stewardship
Preventing infections caused by intrinsically resistant bacteria involves strict adherence to infection control practices, especially in healthcare settings. Hand hygiene, environmental cleaning, and catheter care are essential. Additionally, antimicrobial stewardship programs play a crucial role in ensuring colistin is used appropriately, reserved for susceptible organisms, and not employed against inherently resistant bacteria.
Understanding which organisms are intrinsically resistant to colistin is vital for effective antimicrobial therapy. Bacteria such as Proteus, Serratia, Burkholderia, Providencia, and Edwardsiella exhibit natural resistance due to structural and functional characteristics of their outer membrane. Clinicians must consider these resistance patterns when selecting antibiotics to avoid treatment failures and improve patient outcomes. Accurate laboratory testing, adherence to infection control practices, and prudent antimicrobial stewardship are key strategies in managing infections caused by colistin-resistant pathogens, ensuring that colistin remains a valuable tool in the fight against multidrug-resistant infections.