Diseases Caused by Gram-Negative Enteric Bacilli¶
Chapter 166 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Gram-negative enteric bacilli (GNB) are major pathogens in healthcare-associated infections, with rising resistance to antimicrobials.
- Enterobacterales (e.g., E. coli, Klebsiella, Proteus) cause extraintestinal infections, including pneumonia, UTIs, and sepsis.
- Antimicrobial stewardship is critical due to the prevalence of carbapenem-resistant Enterobacterales (CRE) and extended-spectrum beta-lactamases (ESBLs).
- Diagnosis relies on molecular testing (e.g., MALDI-TOF, NAATs) and resistance gene detection for targeted therapy.
- Treatment options are limited by resistance, requiring carbapenems, polymyxins, or newer agents like ceftazidime-avibactam and ceftolozane-tazobactam.
1. DEFINITION & OVERVIEW¶
Gram-negative enteric bacilli (GNB) are part of the Enterobacterales order, including Escherichia coli, Klebsiella, Proteus, Enterobacter, and others. They cause a wide range of infections, from mild gastroenteritis to severe sepsis. The postantibiotic era has intensified due to rising antimicrobial resistance, particularly with carbapenem-resistant Enterobacterales (CRE) and ESBL-producing strains.
Table 166-1: Interactions of Extraintestinal Pathogenic Escherichia coli with the Human Host¶
| BACTERIAL GOAL | HOST OBSTACLE | BACTERIAL SOLUTION |
|---|---|---|
| Extraintestinal attachment | Flow of urine, mucociliary escalator | Multiple adhesins (e.g., type 1, S, and F1C fimbriae; P pili) |
| Nutrient sequestration | Iron via lactoferrin and transferrin | Cellular lysis and extracellular scavenging |
| Initial avoidance of host bactericidal activity | Complement, phagocytic cells, antimicrobial peptides | Capsular polysaccharide, lipopolysaccharide |
| Late avoidance of host bactericidal activity | Acquired immunity (specific antibodies), antibiotic treatment | Cell entry, acquisition of antimicrobial resistance |
1.1 Structure and Function¶
GNB possess an outer membrane with lipopolysaccharide (LPS), porins, and efflux pumps. These features contribute to antimicrobial resistance and pathogenicity. Virulence factors include adhesins, toxins, and iron acquisition systems.
1.2 Pathogenesis¶
GNB use adhesins (e.g., fimbriae) to colonize host tissues. Virulence factors like Shiga toxin (STEC), iron acquisition systems, and efflux pumps enable survival in hostile environments. Resistance to complement and phagocytosis is critical for extracellular survival.
2. EPIDEMIOLOGY¶
GNB infections are increasingly common due to aging populations, antimicrobial resistance, and healthcare-associated transmission. Klebsiella pneumoniae and E. coli are leading causes of sepsis and UTIs. CRE prevalence is highest in Asia, Eastern Europe, and Latin America. Risk factors include LTCF residence, immunocompromise, and prior antibiotic use.
2.1 Incidence and Prevalence¶
E. coli causes 80–90% of cystitis in women. Klebsiella and Proteus are common in hospital-acquired infections. ESBL-producing GNB account for 25% of K. pneumoniae isolates in the US (2015–2017).
2.2 Demographics¶
LTCFs and hospitals are reservoirs for resistant GNB. Neonates, immunocompromised patients, and elderly are at higher risk for severe infections.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
GNB pathogenesis involves adhesins, toxins, and resistance mechanisms. ESBLs and carbapenemases (e.g., KPC, NDM) mediate resistance. Virulence factors like Shiga toxin (STEC) and iron acquisition systems enable survival in host environments.
Table 166-2: Common Antimicrobial Resistance Mechanisms in Enterobacterales¶
| ANTIMICROBIALS | MOST SIGNIFICANTLY COMMON MEDIATORS OF RESISTANCE |
|---|---|
| Efflux | Tetracyclines, fluoroquinolones (FQ) |
| Target site alteration | FQ, trimethoprim-sulfamethoxazole (TMP-SMX), polymyxins |
| Enzymatic modification | Aminoglycosides (AAC, ANT, APH) |
| Carbapenemases | Serine-based (KPC, OXA), metallo-b-lactamases (NDM, VIM) |
3.1 Resistance Mechanisms¶
Efflux pumps, enzymatic hydrolysis (ESBLs, carbapenemases), and target modification (e.g., DNA gyrase mutations) confer resistance. AmpC β -lactamases and porin mutations contribute to non-CP-CRE.
3.2 Virulence Factors¶
Adhesins (fimbriae, pili), toxins (Shiga, hemolysin), and iron acquisition systems (siderophores) drive pathogenicity. Type VI secretion systems enhance survival in host niches.
4. CLINICAL FEATURES¶
Symptoms vary by infection site: UTIs (dysuria, fever), pneumonia (cough, hypoxia), sepsis (fever, hypotension). STEC infections cause bloody diarrhea and hemolytic uremic syndrome (HUS). Klebsiella pneumoniae leads to lung abscesses and empyema.
4.1 Extraintestinal Infections¶
Pneumonia, UTIs, sepsis, and abscesses (e.g., liver, spleen) are common. STEC/EHEC cause hemorrhagic colitis and HUS. Klebsiella pneumoniae is associated with pyogenic liver abscesses.
4.2 Intestinal Pathogens¶
ETEC causes traveler’s diarrhea; EPEC leads to watery diarrhea in children. STEC/EHEC produce bloody diarrhea and HUS. EAEC causes persistent diarrhea in immunocompromised hosts.
5. DIFFERENTIAL DIAGNOSIS¶
Distinguish GNB infections from other pathogens like C. difficile, Shigella, and Salmonella. Consider non-infectious causes (e.g., IBD, IBS) for chronic diarrhea. For sepsis, differentiate from viral infections and other bacterial causes.
6. INVESTIGATIONS & DIAGNOSIS¶
Culture of sterile site specimens (blood, CSF) confirms infection. Molecular testing (NAATs, MALDI-TOF) identifies pathogens. Shiga toxin detection via ELISA or PCR is critical for STEC/EHEC. Resistance gene detection guides therapy.
6.1 Diagnostic Criteria¶
Positive blood cultures, imaging for abscesses, and molecular testing for ESBLs/CRE. Shiga toxin detection in stool for STEC/EHEC.
6.2 Imaging¶
CT for abscesses, ultrasound for pyelonephritis, and X-ray for pneumonia. MRI for CNS infections.
7. MANAGEMENT & TREATMENT¶
Empirical therapy with carbapenems (imipenem, meropenem) or ceftazidime-avibactam for severe infections. Avoid broad-spectrum agents in colonized but not infected patients. De-escalate to narrower-spectrum agents once resistance data is available.
7.1 Antimicrobial Therapy¶
Carbapenems (best for CRE), polymyxins, and β -lactam/ β -lactamase inhibitors (e.g., piperacillin-tazobactam). Fosfomycin, nitrofurantoin, and tigecycline are alternatives for non-ESBL strains.
7.2 Source Control¶
Drain abscesses, remove infected devices, and address underlying conditions (e.g., urinary catheters). Surgical debridement for necrotizing fasciitis.
8. PROGNOSIS & COMPLICATIONS¶
Mortality is high in sepsis (20–60%) and septic shock. Complications include renal failure (HUS), abscess formation, and Clostridioides difficile infection. Non-CP-CRE may have poor outcomes due to limited treatment options.
9. SPECIAL CONSIDERATIONS¶
Pregnant women are at risk for pyelonephritis. Neonates may develop meningitis or necrotizing enterocolitis. Elderly patients face higher mortality from sepsis. In LTCFs, GNB spread is common due to antimicrobial use and poor hygiene.
10. KEY POINTS & CLINICAL PEARLS¶
- GNB infections are increasingly resistant to antimicrobials, requiring carbapenems or newer agents.
- Molecular testing and resistance gene detection are critical for targeted therapy.
- Source control (e.g., drainage, device removal) is essential for cure.
- Avoid broad-spectrum antibiotics in colonized but not infected patients.
- Monitor for HUS in STEC/EHEC infections and use plasmapheresis if needed.