Antimicrobial resistance and severe respiratory infection
ESKAPE: Emerging Multi-Drug Resistant Pneumonia Pathogens!
ESKAPE pathogens are a group of bacteria with a remarkable ability to survive antimicrobial treatment and spread in healthcare environments. Several can cause severe hospital-acquired or ventilator-associated pneumonia, particularly in critically ill, immunocompromised or heavily treated patients.
- Antimicrobial resistance
- Hospital-acquired pneumonia
- Ventilator-associated pneumonia
- Carbapenem resistance
- MRSA
- Resistant Gram-negative bacteria
ESKAPE refers to bacteria
The acronym does not include viruses or fungi. It describes six bacterial groups that are especially adept at evading antimicrobial treatment.
A positive culture is not always infection
Some patients carry resistant organisms without active disease. Symptoms, imaging, inflammation and the quality of the respiratory sample must be interpreted together.
What does ESKAPE mean?
These organisms do not all cause pneumonia with the same frequency. Some, particularly Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus, are major respiratory pathogens in hospital and intensive-care settings.
Enterococcus faecium is a major ESKAPE pathogen but is much more commonly associated with bloodstream, urinary, abdominal and device-related infections than primary pneumonia.
Important correction about Stenotrophomonas
Stenotrophomonas maltophilia is not one of the six ESKAPE organisms. It is nevertheless an important resistant hospital pathogen and can cause severe respiratory infection, particularly in immunocompromised or ventilated patients.
Why are these pathogens important in pneumonia?
Resistant pneumonia can be difficult to distinguish initially from infection caused by a susceptible organism. The consequences of selecting an ineffective antibiotic can be serious in a critically ill patient.
Delayed effective treatment
Standard empirical antibiotics may not cover the organism, delaying active therapy while culture results are awaited.
Limited treatment options
Resistance to beta-lactams, carbapenems, fluoroquinolones, aminoglycosides or other agents may narrow the available choices.
Greater toxicity
Some remaining antibiotics require close kidney, liver, neurological or blood monitoring.
Healthcare transmission
Resistant organisms can spread through contaminated hands, surfaces, equipment and devices.
Biofilm formation
Several pathogens can form protective communities on airway devices and damaged respiratory surfaces.
Severe host vulnerability
Infection often occurs in people already affected by critical illness, immune suppression or advanced lung disease.
Resistant ESKAPE pneumonia is most relevant to complex or recurrent chest infection , hospital-acquired pneumonia and ventilator-associated pneumonia.
The six ESKAPE pathogens
Acinetobacter baumannii
Epidemiology
A persistent healthcare-associated Gram-negative organism, especially important in intensive care, prolonged admission and ventilator-associated pneumonia.
Resistance
Carbapenem-resistant strains may carry several resistance mechanisms and can remain difficult to eradicate from the care environment.
Clinical significance
Severe pneumonia can occur in critically ill patients and may be accompanied by bloodstream infection and sepsis.
Pseudomonas aeruginosa
Epidemiology
Found in water and moist environments and associated with hospitals, intensive care, bronchiectasis, cystic fibrosis and structural lung disease.
Resistance
It combines low outer-membrane permeability, efflux pumps, enzyme production and an ability to acquire additional resistance genes.
Clinical significance
It can cause severe hospital-acquired pneumonia and chronic airway infection and may form biofilms that complicate eradication.
Staphylococcus aureus
Epidemiology
Often carried on the skin or in the nose. It can cause community or healthcare-associated infection when normal barriers are disrupted.
Resistance
Methicillin-resistant S. aureus, or MRSA, is resistant to standard anti-staphylococcal beta-lactam antibiotics.
Clinical significance
Pneumonia may follow influenza, occur in hospital or be associated with necrosis, abscess formation and sepsis.
Klebsiella pneumoniae
Epidemiology
An Enterobacterales organism that can inhabit the gastrointestinal tract and cause pneumonia, urinary, abdominal and bloodstream infection.
Resistance
Strains may produce extended-spectrum beta-lactamases or carbapenemases such as KPC, NDM, OXA-48-like or related enzymes.
Clinical significance
Resistant disease occurs particularly in healthcare settings and may cause rapidly progressive pneumonia, sepsis or metastatic infection.
Enterobacter species
Epidemiology
Enterobacter species are healthcare-associated Enterobacterales that can cause respiratory, bloodstream, urinary and device-related infection.
Resistance
Some possess inducible AmpC beta-lactamases and may develop resistance during treatment with particular antibiotics.
Clinical significance
Pneumonia is most relevant in hospitalised, ventilated or immunocompromised patients.
Enterococcus faecium
Epidemiology
A gastrointestinal organism that becomes important in heavily treated, critically ill and immunocompromised patients.
Resistance
Vancomycin-resistant enterococci, or VRE, can be resistant to several major antimicrobial classes.
Pneumonia relevance
True enterococcal pneumonia is uncommon. Isolation from a respiratory sample requires careful clinical interpretation.
Stenotrophomonas maltophilia: important, but not ESKAPE
Vulnerable patients
Infection is most important in people with haematological malignancy, transplantation, immune suppression, intensive-care admission or prolonged ventilation.
Intrinsic resistance
The organism is naturally resistant to many antibiotics, including carbapenems, and requires susceptibility-guided treatment.
Colonisation versus infection
It may colonise damaged airways or ventilator circuits. A positive sample does not by itself establish pneumonia.
Why it is frequently discussed alongside ESKAPE organisms
It shares several clinically important features: healthcare association, intrinsic or acquired antimicrobial resistance, biofilm formation and infection in vulnerable patients.
How do multidrug-resistant bacteria evade antibiotics?
Drug-destroying enzymes
Beta-lactamases can break down penicillins, cephalosporins or carbapenems before the medicine reaches its target.
Altered drug targets
Changes in bacterial proteins can prevent an antibiotic from binding effectively.
Efflux pumps
Bacteria can actively pump antimicrobial molecules out of the cell.
Reduced permeability
Changes in membrane channels can stop antibiotics entering the bacterium.
Biofilms
Structured bacterial communities can limit antimicrobial penetration and protect slower-growing cells.
Gene transfer
Resistance genes can move between bacteria on plasmids and other mobile genetic elements.
Resistance is selected, not created by the patient’s body
The person does not become resistant to antibiotics. Bacteria with resistance mechanisms survive antimicrobial exposure and may then multiply or spread.
Who is at greater risk?
Intensive-care admission
Critical illness, invasive monitoring and prolonged care increase exposure and vulnerability.
Mechanical ventilation
An endotracheal tube bypasses normal upper-airway defences and can support biofilm formation.
Recent broad-spectrum antibiotics
Antibiotic exposure can suppress susceptible organisms and select resistant populations.
Prolonged hospital stay
Longer admission increases contact with healthcare-associated flora and equipment.
Immune suppression
Chemotherapy, transplantation, corticosteroids and some biological medicines may reduce infection defence.
Structural lung disease
Bronchiectasis, cystic fibrosis and advanced COPD can permit persistent Gram-negative airway colonisation.
Previous resistant cultures
Earlier carriage or infection increases the probability that a new illness involves the same or a related resistant organism.
Healthcare devices
Tracheostomies, central lines and other devices can act as surfaces for bacterial adherence and transmission.
Overseas healthcare exposure
Recent admission in a region with different resistance patterns can influence the organisms and mechanisms considered.
Patients with chronic structural airway disease may benefit from a dedicated bronchiectasis assessment .
Colonisation is not the same as pneumonia
| Feature | Colonisation | Active pneumonia |
|---|---|---|
| Organism | Present on a body surface or in airway secretions | Organism is contributing to lower-respiratory infection |
| Symptoms | No new infection syndrome | New or worsening cough, sputum, fever, breathlessness or deterioration |
| Imaging | No new pneumonia-compatible change | New infiltrate, consolidation or other compatible abnormality |
| Inflammation | No clear systemic inflammatory response | May have raised inflammatory markers, fever or sepsis |
| Treatment | Usually does not require antibiotics | Requires clinical assessment and targeted antimicrobial treatment |
Treating colonisation can cause harm
Unnecessary antibiotics may produce adverse effects, disrupt the normal microbiome and select even more resistant organisms.
How is resistant pneumonia diagnosed?
- Identify a compatible illness Clinicians assess fever, respiratory symptoms, oxygen requirement, sputum, sepsis and the timing of deterioration.
- Review the healthcare setting Recent hospital admission, intensive care, ventilation, devices and previous antibiotics alter the resistance risk.
- Arrange chest imaging Chest X-ray or CT may demonstrate consolidation, infiltrates, cavities or complications.
- Collect respiratory samples Sputum, tracheal aspirate or bronchoalveolar lavage may be sent for microscopy, culture and susceptibility testing.
- Obtain blood cultures when appropriate These may identify associated bloodstream infection.
- Use rapid molecular tests selectively Some tests can detect organisms or resistance genes before conventional cultures are complete.
- Compare with earlier microbiology Previous resistant isolates can guide initial treatment while new results are pending.
- Reassess when results return Empirical therapy should be narrowed, changed or stopped according to microbiology and clinical progress.
The quality of the sample matters
Saliva contaminated by upper-airway organisms may be misleading. A good-quality lower-respiratory sample is more useful when deciding whether a cultured organism is clinically significant.
Treatment principles
Start promptly when illness is severe
Critically ill patients may need empirical treatment that covers likely resistant pathogens before definitive culture results are available.
Use previous microbiology
Earlier sputum, blood or screening cultures can provide valuable clues about colonisation and resistance.
Obtain cultures before antibiotics
Samples should be taken promptly where this does not delay urgently required treatment.
De-escalate when possible
Once results are available, treatment should be narrowed to the least broad effective regimen.
Optimise the dose
Severe pneumonia may require adjusted doses, prolonged infusions, drug-level monitoring or renal-dose modification.
Control the source
Infected devices, empyema, abscesses or obstructed airways may need procedural management as well as antibiotics.
Antibiotic selection cannot be safely generalised
MRSA, carbapenem-resistant Acinetobacter, multidrug-resistant Pseudomonas, carbapenemase-producing Enterobacterales and Stenotrophomonas require different medicines. Treatment should be guided by infection specialists, microbiologists and susceptibility results.
How did antimicrobial resistance become such a problem?
Resistance develops naturally through mutation and gene exchange, but the speed and scale of selection are strongly influenced by how antimicrobials are used across human health, animal health and the environment.
Unnecessary prescribing
Antibiotics given for viral illness or non-infective symptoms create exposure without clinical benefit.
Inadequate treatment
The wrong drug, dose, route or duration may fail to control infection and select resistant bacteria.
Excessively broad treatment
Broad-spectrum antibiotics affect many bacterial species and may select resistance beyond the intended target.
Poor infection control
Resistant strains can spread between patients even when antibiotic prescribing is appropriate.
Global movement
People, animals, food and healthcare systems allow resistant organisms and genes to move between regions.
Environmental contamination
Antimicrobial residues and resistant bacteria can enter water, soil and wastewater systems.
Do not stop antibiotics early without medical advice
Modern antibiotic courses are deliberately tailored to the infection. Take the medicine exactly as prescribed and speak to the treating clinician before changing or stopping it.
Preventing resistant respiratory infection
Hand hygiene
Effective hand cleaning remains one of the most important ways to reduce healthcare transmission.
Device care
Ventilator bundles, early device removal and meticulous line and tracheostomy care reduce infection risk.
Antimicrobial stewardship
Antibiotics should be prescribed only when indicated and reviewed when microbiology becomes available.
Vaccination
Influenza, COVID-19 and pneumococcal vaccination can reduce respiratory infections that lead to hospitalisation or secondary bacterial pneumonia.
Isolation precautions
Contact precautions or dedicated equipment may be used for particular resistant organisms.
Good chronic lung care
Airway clearance, smoking cessation and appropriate treatment of bronchiectasis, COPD and asthma support respiratory defence.
When should urgent help be sought?
Seek urgent medical assessment for:
- severe or rapidly worsening breathlessness;
- blue or grey lips or skin;
- new confusion, severe drowsiness or collapse;
- very low or rapidly falling oxygen levels;
- high fever with marked weakness or low blood pressure;
- significant coughing of blood;
- rapid deterioration during chemotherapy, transplantation or substantial immune suppression.
Call 999 for immediately life-threatening symptoms.
Frequently asked questions
What exactly are ESKAPE pathogens?
They are six bacterial groups associated with difficult healthcare infections and a strong ability to develop or acquire antimicrobial resistance.
Is Stenotrophomonas part of ESKAPE?
No. It is a separate resistant Gram-negative pathogen, but it is often discussed alongside ESKAPE organisms because it can cause difficult healthcare-associated respiratory infection.
Are all ESKAPE organisms common causes of pneumonia?
No. Acinetobacter, Pseudomonas, Klebsiella and Staphylococcus aureus are especially important in pneumonia. Enterococcus faecium rarely causes primary pneumonia.
What does multidrug resistant mean?
It means the organism is resistant to several relevant antimicrobial classes, reducing the number of treatments likely to work.
Does a resistant bacterium always cause more severe disease?
Not necessarily. Resistance mainly makes treatment more difficult. Severity also depends on the infection site, organism virulence and the patient’s health.
Can a person carry MRSA or resistant Gram-negative bacteria without being ill?
Yes. This is called colonisation. Antibiotics are not usually needed unless there is evidence of active infection or a specific decolonisation indication.
How is the correct antibiotic chosen?
Clinicians use the infection site, severity, earlier culture results, local resistance patterns and laboratory susceptibility testing.
Are carbapenems effective against every resistant infection?
No. Carbapenem-resistant Acinetobacter, Pseudomonas and Enterobacterales may be resistant to these drugs and require other treatment.
Can resistant pneumonia be treated?
Often yes, but treatment may be more complex and require specialist antibiotics, dose optimisation, combination treatment or source control.
How can families reduce their risk?
Use antibiotics only as prescribed, maintain good hand hygiene, follow infection-control advice and keep relevant vaccinations up to date.
Should every positive sputum culture be treated?
No. The result may represent colonisation. Treatment depends on symptoms, imaging, inflammation, sample quality and the wider clinical picture.
Can resistance spread between bacteria?
Yes. Mobile genetic elements such as plasmids can carry resistance genes between bacteria.
Conclusion
ESKAPE pathogens are a major focus of antimicrobial-resistance research because they cause serious healthcare-associated infections and can evade several major antibiotic classes.
The six organisms are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species.
Several are particularly important causes of hospital-acquired and ventilator-associated pneumonia. However, the presence of a resistant organism in a respiratory sample does not automatically mean that active pneumonia is present.
Effective management depends on accurate sampling, susceptibility testing, timely treatment of severe infection, careful de-escalation and strong infection-prevention measures.
Patients with persistent or recurrent respiratory infection can read about the London Chest Specialist chest infection assessment service .
References and further information
- World Health Organization. WHO bacterial priority pathogens list 2024. View the WHO report
- Miller WR, Arias CA. ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics. Nature Reviews Microbiology. 2024. View the review
- National Institute for Health and Care Excellence. Pneumonia: diagnosis and management. NICE guideline NG250. View the NICE pneumonia guideline
- London Chest Specialist. Chest infection diagnosis and treatment. Read about complex chest infection assessment
- London Chest Specialist. Bronchiectasis diagnosis and treatment. Read about specialist bronchiectasis care
- London Chest Specialist. Chronic cough specialist assessment. Read about chronic cough investigation
- London Chest Specialist. Breathlessness diagnosis and treatment. Read about specialist breathlessness assessment
Recurrent or Resistant Chest Infection?
Specialist respiratory review can help interpret sputum cultures, resistance results, previous antibiotic exposure, chest imaging and underlying conditions such as bronchiectasis or immune dysfunction.
