Klebsiella pneumoniae
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Quick Answer: Klebsiella pneumoniae is a Gram-negative, encapsulated, non-motile facultative anaerobe in the Enterobacteriaceae family. It is a major opportunistic pathogen causing pneumonia, urinary tract infections, bacteremia, and liver abscesses - particularly in immunocompromised hosts. It has become a significant concern due to the emergence of multidrug-resistant strains, including carbapenem-resistant Klebsiella pneumoniae (CRKP).
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"Klebsiella pneumoniae"[MeSH Terms]
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Klebsiella pneumoniae gram stain morphology culture
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Klebsiella pneumoniae lung pneumonia histology
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Klebsiella pneumoniae
Classification & Microbiology
Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultatively anaerobic rod belonging to the family Enterobacteriaceae. Key microbiological features:
- Capsule (K antigen): Large polysaccharide capsule - the organism's primary virulence factor. Blocks complement deposition and opsonophagocytosis. Gives colonies a glistening, mucoid appearance on agar. On Gram stain, a visible negative space (halo) may be seen around the rods.
- Indole negative (unlike K. oxytoca, which is indole positive)
- Non-motile (unlike most Enterobacteriaceae)
- Ferments lactose (produces acid and gas)
- Urease and ONPG positive
(Quick Compendium of Clinical Pathology 5th ed., p. 180; Sherris & Ryan's Medical Microbiology, 8th ed.)
Pathotypes
There are two clinically important pathotypes:
| Feature | Classical Kp (cKp) | Hypervirulent Kp (hvKp) |
|---|---|---|
| Host | Immunocompromised, debilitated | Previously healthy individuals |
| Setting | Hospital/healthcare-associated | Community-acquired |
| Geography | Global | Asia, South Africa (emerging globally) |
| Key infection | HAP, VAP, UTI, BSI | Primary liver abscess, endophthalmitis, meningitis |
| Metastatic spread | Rare | Yes - from liver abscess to eye, CNS, lungs |
| Resistance | High (ESBL, KPC) | Usually susceptible (but MDR strains emerging) |
| String test | Variable | Often positive (hypermucoviscous) |
| Biomarkers | - | iucA, iroB, peg-344, rmpA, rmpA2 (all 5 = definitive) |
(Harrison's Principles of Internal Medicine, 22nd ed., 2025)
Virulence Factors
- Polysaccharide capsule - antiphagocytic, anti-complement
- Lipopolysaccharide (LPS/O antigen) - endotoxin activity, serum resistance
- Fimbriae (type 1 and type 3) - adhesion to uroepithelium and respiratory mucosa
- Siderophores (in hvKp: aerobactin iucA, salmochelin iroB) - iron acquisition, greatly enhance virulence
- Rmp proteins (rmpA, rmpA2) - upregulate capsule production, confer hypermucoviscosity
- Outer membrane proteins - contribute to antibiotic resistance
Clinical Syndromes
1. Pneumonia
K. pneumoniae is the most frequent cause of Gram-negative bacterial pneumonia.
- Classic population: Chronic alcoholics, malnourished patients, diabetics, COPD patients, debilitated elderly
- Classic features: Lobar consolidation (often upper lobe, right side), "currant jelly sputum" (thick, blood-tinged mucoid sputum due to abundant capsular polysaccharide), "bulging fissure sign" on CXR
- Modern presentations are often less dramatic - patchy infiltrate rather than massive lobar consolidation
- Complications: lung abscess, empyema, pulmonary necrosis, pleural effusion
- Hospital-acquired: ventilator-associated pneumonia (VAP) is a major concern
(Robbins, Cotran & Kumar Pathologic Basis of Disease; Robbins & Kumar Basic Pathology)
2. Urinary Tract Infection
- cKp causes only 1-2% of UTIs in healthy adults but 5-17% of complicated UTIs (structural/functional abnormalities, catheter use)
- hvKp more commonly presents as renal or prostatic abscess via bacteremic spread rather than ascending infection
3. Primary Liver Abscess (hvKp hallmark)
- Characteristic of the hypervirulent pathotype, especially in Southeast Asia
- Occurs in previously healthy, often younger individuals
- CT shows solitary right lobe abscess
- Metastatic spread to eye (endophthalmitis - can cause blindness), CNS, lungs, joints
- Often requires percutaneous drainage + prolonged antibiotics
4. Bacteremia / Sepsis
- Klebsiella bacteremia can arise from any infected site: urinary tract (15-30%), respiratory tract (15-30%), abdominal (hepatic abscess) (15-30%), intravascular device (5%)
- Associated with high mortality in MDR strains
5. Other Infections
- Neonatal sepsis and meningitis in LMICs
- Wound and soft tissue infections
- Rhinoscleroma (K. rhinoscleromatis) - chronic granulomatous nasal infection; Mikulicz cells
- Granuloma inguinale/Donovanosis (K. granulomatis)
- Pneumonia in severely malnourished children in low- and middle-income countries
Clinical Image - Hypervirulent K. pneumoniae
The image below (from Harrison's Principles, 22nd ed.) shows:
- Top: Abdominal CT of a healthy 24-year-old - primary liver abscess (red arrow) with metastatic spread to the spleen (black arrow)
- Middle: Endophthalmitis in a healthy 33-year-old
- Bottom: Positive string test - mucoid colony stretching >5 mm with inoculating loop, indicating hypermucoviscous phenotype
Laboratory Diagnosis
- Gram stain: Gram-negative rods, sometimes with visible capsular halo
- Grows readily on standard media (blood agar, MacConkey agar - pink/lactose-fermenting)
- Mucoid, glistening colonies; string test can be performed
- Indole negative (K. pneumoniae sensu stricto); Urease positive
- Definitive hvKp identification: PCR/genomic detection of all 5 biomarkers: iucA, iroB, peg-344, rmpA, rmpA2
(Harrison's Principles of Internal Medicine, 22nd ed.)
Antibiotic Resistance - Major Concern
K. pneumoniae is a WHO priority pathogen for antimicrobial resistance research.
Resistance Mechanisms
| Mechanism | Details |
|---|---|
| Intrinsic ampicillin resistance | Chromosomal penicillinase |
| ESBL (Extended-Spectrum Beta-Lactamase) | Most commonly CTX-M type; hydrolysis of 3rd-gen cephalosporins and penicillins; ~25% of US hospital isolates (higher in Asia, South America, Africa) |
| AmpC beta-lactamase | Resistance to beta-lactam/beta-lactamase inhibitor combinations |
| KPC (K. pneumoniae Carbapenemase) | Serine carbapenemase; most common carbapenemase in the US; confers resistance to virtually all beta-lactams; now found in many Enterobacteriaceae (hence renamed CRE) |
| MBL (Metallo-beta-lactamase) | NDM-type; high prevalence in Eastern Europe, Asia; not inhibited by avibactam |
| OXA-48 | Oxacillinase-type carbapenemase |
| Porin loss + efflux pumps | Contribute to high-level carbapenem resistance |
(Quick Compendium of Clinical Pathology 5th ed.; Harrison's 22nd ed.)
Treatment by Resistance Profile
| Organism | Preferred Treatment |
|---|---|
| Susceptible Kp | 3rd-gen cephalosporins, fluoroquinolones, TMP-SMX |
| ESBL-producing Kp | Carbapenems (meropenem, ertapenem); oral options limited |
| KPC-producing CRE | Ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam |
| NDM-producing CRE | Cefiderocol, aztreonam-avibactam, polymyxins (combination) |
| Extensively resistant | Consult Infectious Diseases; combination therapy |
(Harriet Lane Handbook, 23rd ed.; Harrison's 22nd ed.; Washington Manual of Medical Therapeutics)
Risk Factors for Acquisition
- Hospitalization / LTCF residence
- Mechanical ventilation (VAP)
- Indwelling urinary catheter (complicated UTI)
- Diabetes mellitus
- Chronic alcoholism
- COPD / structural lung disease
- Immunosuppression (neutropenia, transplant, steroids)
- Broad-spectrum antibiotic use (selects for MDR strains)
- Asian origin / travel (for hvKp and NDR strains)
Epidemiology (2025 Update)
A 2025 systematic review and meta-analysis (PMID 41208438) analyzed the global prevalence of hypervirulent K. pneumoniae, highlighting that hvKp is no longer confined to Asia and is an emerging global threat - particularly as MDR and hvKp lineages increasingly converge. A 2024 systematic review (PMID 38147789) documented secondary Klebsiella infections in COVID-19 patients as a major contributor to mortality in the pandemic era.
Summary Table
| Feature | Detail |
|---|---|
| Gram stain | Gram-negative rod |
| Motility | Non-motile |
| Capsule | Large polysaccharide (K antigen) - mucoid colonies |
| Indole | Negative (K. pneumoniae); Positive (K. oxytoca) |
| Key infections | Pneumonia, UTI, liver abscess, bacteremia |
| Classic sputum | "Currant jelly" (thick, blood-tinged) |
| Classic patient | Alcoholic/diabetic/malnourished OR healthy young (hvKp) |
| String test | Positive in hvKp (hypermucoviscous) |
| Key resistance genes | ESBL (CTX-M), KPC, NDM, OXA-48 |
| Carbapenemase prevalence (US) | ~8.6% of K. pneumoniae isolates (USNHSN 2015-2017) |
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