Gram-Negative Bacilli: Definition and Clinical Significance
Gram-negative bacilli are rod-shaped bacteria that do not retain crystal violet stain in the Gram staining procedure, appearing pink/red under microscopy, and represent a diverse group of clinically important pathogens responsible for significant morbidity and mortality, particularly in healthcare settings.
Major Gram-Negative Bacilli Organisms
Enterobacterales (Enteric Gram-Negatives)
- Escherichia coli - Most common cause of urinary tract infections and a frequent cause of bacteremia 1
- Klebsiella pneumoniae - Major cause of hospital-acquired pneumonia and bloodstream infections, increasingly multidrug-resistant 1
- Klebsiella oxytoca - Less common but clinically significant 2
- Enterobacter species (E. cloacae, E. aerogenes) - Associated with treatment failure when cephalosporins are used due to inducible resistance 1, 3
- Serratia marcescens - Common in bacteremic pneumonias 4
- Proteus species (P. mirabilis, P. vulgaris) - Urinary tract pathogens 3, 2
- Providencia species (P. rettgeri, P. stuartii) - Opportunistic pathogens 3, 2
- Citrobacter species (C. freundii, C. diversus) - Hospital-acquired infections 3
- Morganella morganii - Opportunistic pathogen 2
Non-Fermenting Gram-Negative Bacilli
- Pseudomonas aeruginosa - Highly problematic due to intrinsic multidrug resistance and ability to acquire adaptive resistance during therapy, particularly lethal in bacteremic pneumonia with ~70% mortality 1, 5
- Acinetobacter baumannii - Critical priority pathogen with propensity for biofilm production and carbapenem resistance 1
- Stenotrophomonas maltophilia - Intrinsically resistant to carbapenems 1
- Burkholderia cepacia - Most strains resistant to ciprofloxacin 3
Other Clinically Important Gram-Negative Bacilli
- Haemophilus influenzae - Respiratory pathogen, including ampicillin-resistant strains 3, 2
- Haemophilus parainfluenzae - Respiratory infections 3
- Moraxella catarrhalis - Respiratory pathogen 3
- Legionella pneumophila - Atypical pneumonia 1, 2
- Neisseria gonorrhoeae - Sexually transmitted pathogen 3, 2
- Campylobacter jejuni - Gastrointestinal pathogen 3
- Salmonella species (S. typhi, S. enteritidis) - Enteric fever and gastroenteritis 3, 2
- Shigella species (S. boydii, S. dysenteriae, S. flexneri, S. sonnei) - Dysentery 3
- Yersinia enterocolitica - Gastrointestinal infections 2
- Pasteurella multocida - Animal bite infections 2
- Aeromonas hydrophila - Water-associated infections 3, 2
- Vibrio species (V. cholerae, V. parahaemolyticus, V. vulnificus) - Gastrointestinal and wound infections 2
Clinical Context and Epidemiology
Changing Epidemiology
Gram-negative bacteria account for approximately 60% of neonatal sepsis in low- and lower-middle-income countries and represent 60-70% of microbiologically documented infections in certain populations 1. However, in catheter-related bloodstream infections among adults over the past two decades, rates have decreased and been supplanted by gram-positive organisms 1.
High-Risk Populations
Patients at greatest risk for gram-negative bacillary infections include those who are 1:
- Critically ill or septic
- Neutropenic
- Elderly or debilitated with chronic underlying disease 6
- Have femoral catheters in place
- Have received prior antibiotic therapy
- Have structural lung disease or are on corticosteroids 1
Antimicrobial Resistance Patterns
The incidence of multidrug-resistant gram-negative pathogens has increased dramatically, with resistance to third- and fourth-generation cephalosporins ranging from 59-84% and aminoglycoside resistance from 42-69% in certain regions 1. Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae and E. coli are associated with poor outcomes when treated with cephalosporins or piperacillin-tazobactam versus carbapenems 1.
Mortality Impact
Gram-negative bacillary pneumonia carries approximately 50% mortality overall, with Pseudomonas aeruginosa, E. coli, and Klebsiella pneumoniae approaching 70% mortality 6. Patients with catheter-related bloodstream infections due to multidrug-resistant gram-negative pathogens are at greater risk for inappropriate initial therapy, resulting in increased morbidity and mortality 1.
Microbiologic Characteristics
Mechanism of Pathogenicity
Gram-negative bacilli function primarily as opportunistic pathogens, with colonization of the oropharyngeal flora occurring with increasing age, chronic disease, and debility 7, 6. The urinary tract is the most frequent source of bacteremia, though in 30% of patients the source cannot be identified 7.
Resistance Mechanisms
Resistance occurs through 2:
- Hydrolysis by β-lactamases (including ESBLs and carbapenemases)
- Alteration of penicillin-binding proteins
- Decreased permeability
- Biofilm production (particularly Acinetobacter, Pseudomonas, Stenotrophomonas) 1