5. Extraintestinal enterobacterales

Enterobacterales Causing Extrainestinal Infections

Objectives

  • Describe the general characteristics and habitat of important Enterobacterales species causing human infections.

  • Explain the role of enterobacterial virulence factors in the pathogenesis of infections.

  • Compare epidemiology of community-acquired and healthcare-associated infections caused by Enterobacterales.

  • Provide examples of important antibiotic resistance mechanisms in Enterobacterales.

General Characteristics of Enterobacterales

  • Can be cultured on McConkey agar: Lactose positive/negative.

  • Gram staining: Gram-negative and may vary in motility.

  • Mucoid colonies may occur, indicating the production of a capsule.

  • Facultative anaerobic bacteria, can thrive in both aerobic and anaerobic environments.

Key Pathogens in Enterobacterales

Primary Pathogens

  • Shigella

  • Salmonella

  • Yersinia

Opportunistic Pathogens

  • Escherichia coli

  • Klebsiella pneumoniae

  • Citrobacter

  • Enterobacter

  • Morganella

  • Providencia

  • Serratia

  • Proteus

Habitat of Enterobacterales

  • Colonize the large intestine of healthy individuals, particularly E. coli.

  • Generally non-pathogenic in the colon but can cause infection when they access other body sites.

  • Ecological distribution shown through 16S rRNA studies.

  • Present in various environments: human, agricultural and aquatic animals, plants, insects.

Environmental Contamination

  • Healthcare settings show possible contamination by Enterobacterales, particularly Klebsiella pneumoniae as a significant vector for drug resistance genes.

Clinical Case Examples

Case 1

  • Patient: 27-year-old Korean man

  • Symptoms: Fever, abdominal pain, liver abscess confirmed via CT.

  • Diagnosis and Treatment: Klebsiella pneumoniae cultured; treated with ceftriaxone and metronidazole; fully recovered after 7 days.

Case 2

  • Patient: 68-year-old man on mechanical ventilation.

  • Symptoms: Fever and worsening respiratory secretions.

  • Diagnosis and Treatment: Cultured ESBL-producing Klebsiella pneumoniae; treated with meropenem and amikacin.

Case 3

  • Patient: 11-day-old male with fever and irritability.

  • Symptoms: Bulging fontanelle indicating potential meningitis.

  • Diagnosis: Blood culture and CSF analysis needed for confirmation.

Klebsiella pneumoniae In Human Diseases

Classical Diseases

  • Urinary tract infections, pneumonia, bloodstream infections.

  • Common in patients with underlying conditions (COPD, diabetes).

Hypervirulent Strains

  • Cause serious infections such as pyogenic liver abscess, meningitis, and pneumonia in otherwise healthy individuals. Associated with visible string test.

Virulence Factors of Klebsiella pneumoniae

  • Capsule: Most significant virulence factor contributing to immune evasion.

In classical:

  • siderophores: enterobactin and yersinibactin are produced to scavenge iron from the host, facilitating bacterial growth and survival in iron-limited environments.

In hypervirilant:

  • aerobactin and salmochelin (siderophores), which enhance iron acquisition and promote pathogenicity.

Virulence Factors in Related Species

Proteus, Morganella, Providencia spp.

  • Commonly isolated from community-acquired urinary tract infections.

  • Key virulence traits: Motility, fimbriae, urease production leading to kidney stone formation.

    • urease production incr. the urine pH with consequent kidney stone formation

  • may occur in previous healthy individuals

  • proteus is typically seen in older males with some urinary problems / catherer / prostate problem

Enterobacter spp.

  • Enterobacter cloacae frequently isolated from healthcare infections.

  • primarily cause hospital aq. infections in patients who are long-term hospitalised

    • UTI, ventilator associated pneumonia, and bloodstream infections

  • Virulence factors include motility and chromosomal ampC cephalosporinase leading to resistance.

Serratia spp.

  • Opportunistic pathogens linked to infections in immunocompromised individuals.

    • causes skin, pulmonary and CNS infections in immunocompromised patients

  • Characterized by environmental abundance → damp conditions

  • may produce red pigment → prodigiosin

  • intrinsically resistant to ampicillin, macrolides, first gen. cephalosporins and colistin

Infection Epidemiology

Community-acquired Infections

  • Predominantly caused by E. coli, Klebsiella pneumoniae, Proteus spp.

Healthcare-associated Infections

  • Klebsiella sp.

  • E. coli

  • Enterobacter cloacae

  • Klebsiella Enterobacter aerogenes

  • Citrobacter freundii

  • Citrobacter koseri

  • Serratia marcescens

Major Infections Caused by Enterobacterales

  • Community-acquired:

    • Urinary tract infections

    • pneumonia

    • bloodstream infections

    • neonatal meningitis

    • (liver abscess)

  • Healthcare-associated:

    • Urinary tract infections

    • bloodstream infections

    • meningitis

    • pneumonia

    • intra-abdominal inf.

Case 3

  • Patient: 11-day-old full-term male.

  • Presentation: Fever to 38.3 °C, poor feeding, and irritability.

  • History: No maternal infections during pregnancy; routine newborn care.

  • Family: Living with mother, father, and 2 healthy school-aged siblings.

  • Feeding: Powdered infant formula reconstituted with nonsterile water.

  • Physical Examination: Notable for febrile and irritable state with a bulging anterior fontanelle.

  • Laboratory Tests:

    • Peripheral blood white blood cell count: 5.9 × 10^3/mL (19% neutrophils, 20% bands).

    • Platelet count: 466 × 10^3/mL.

    • Nasopharyngeal swab: Negative for common respiratory viral pathogens.

    • Blood culture and CSF analysis were obtained.

    • CSF analysis: Elevated leukocyte and protein levels, low glucose level.

    • Gram stain of CSF: No organisms observed.

→ Cronobacter sakazakii

  • survives harsh environmental conditions, like high temp. and desiccation

  • causes (in neonates and infants):

    • bacteraemia

    • necr. enterocolitis

    • meningitis

    • sepsis

  • causes (in adult pop)

    • wound or urinary tract inf.

  • powdered infant formula are the source of most neonatal meningitis

Diagnostic Tests

  • Involve gram staining and isolation from body samples.

  • Culture from sterile sites is straightforward; others may require careful interpretation.

  • Identification: Transition from biochemical testing to modern MALDI-TOF MS techniques.

  • Antibiotic susceptibility testing is critical.

Antibiotic Resistance Challenges

  • Increased mortality and healthcare costs linked to infections from resistant strains.

  • Key mechanisms of resistance:

    • ESBL production and its implications in cephalosporin resistance.

    • ampC cephalosporinase production

      • acq. in E.coli, Klebsiella spp., proteus spp.

    • Carbapenem resistance often due to carbapenemase production.

      • or: porin loss or downreg. ± efflux upreg. AND prod. of an ESBL or ampC cephalosporinase

      • very problematic!!

Global High-Risk Clones

  • E. coli ST131: Resistant to fluoroquinolones, ESBL producer.

  • K. pneumoniae CG258: Notable for KPC carbapenemase production.

Treatment and Prevention

  • Tailored antibiotic treatment based on susceptibility.

  • Infection control measures critical for multi-drug resistant organisms.

    • contact iso, protective wear for HC workers

  • no specific prevention → bacteria are part of normal human microbiome

Klebsiella Granulomatis

  • Causative agent of granuloma inguinale (donovanosis) → STD mostly seen tropical countries

  • Symptoms: Painless ulcers of genitalia without lymphadenopathy, diagnosed via microscopy.

    • differential: syphilis

  • Treatment: Azithromycin regimen for effective therapy

    • 1 g orally once per week x 3, or until all lesions have completely healed

  • Diagnostic: can be cultured in cell culture only, IC organism