Cre Infection: Symptoms, Types, Causes and Treatment

Carbapenem-resistant Enterobacteriaceae (CRE) infections are an urgent global health concern. These bacteria are part of a larger family that commonly cause infections such as pneumonia, urinary tract infections, and bloodstream infections. What makes CRE especially alarming is their resistance to carbapenems—antibiotics often reserved as a last line of defense against multidrug-resistant infections. As these organisms become more prevalent, understanding their symptoms, types, causes, and treatment options is essential for both healthcare professionals and the public. This article provides a detailed, evidence-based overview of CRE infections, guided by the latest scientific research.

Symptoms of Cre Infection

Recognizing CRE infections early can be challenging, as symptoms often overlap with those of other bacterial infections. However, timely identification is critical because these infections tend to progress quickly and can have severe outcomes, especially in vulnerable populations such as the elderly or immunocompromised.

Symptom	Description	Common Sites Affected	Source(s)
Fever	Elevated body temperature	All infection types	2 4 5
Cough	Productive or dry, sometimes severe	Respiratory tract	2 5
Shortness of breath	Difficulty breathing	Lungs (pneumonia)	2 5
Dysuria	Painful urination	Urinary tract	2 6
Abdominal pain	Localized or diffuse	Intra-abdominal	2 6
Sepsis	Systemic inflammatory response	Bloodstream	4 6
Confusion	Altered mental status	Severe/systemic disease	4

Table 1: Key Symptoms

Overview of CRE Infection Symptoms

CRE infections manifest differently depending on the site of infection, but several hallmark symptoms are shared across most cases.

Common Presentations

• Fever: Most patients with CRE infection exhibit fever, which is a classic sign of infection and inflammation. The presence of fever is a key trigger for further diagnostic evaluation, especially in hospitalized or high-risk patients 2 4.
• Local Symptoms by Site:
  • Respiratory Tract: Infections like pneumonia often present with cough (productive or dry), shortness of breath, and sometimes chest pain 2 5. In ventilated patients, such as those in the ICU, ventilator-associated pneumonia may be suspected if respiratory status worsens 5.
  • Urinary Tract: Urinary symptoms, such as dysuria (painful urination), increased frequency, and urgency, are common when the urinary tract is involved 2 6.
  • Intra-abdominal: CRE can cause abdominal pain, distension, and tenderness, especially in complicated intra-abdominal infections 2 6.
  • Bloodstream: Sepsis, a life-threatening response to infection, can result from CRE entering the bloodstream. Signs include fever, rapid heart rate, low blood pressure, and confusion or altered mental status 4 6.
• Systemic Signs: In severe cases, especially with bloodstream infection or sepsis, patients may experience delirium or confusion, rapid breathing, and other organ dysfunctions 4.

Atypical and Severe Presentations

• Immunocompromised and Elderly Patients: These populations may exhibit less typical symptoms, such as confusion without fever, or rapid progression to severe illness 4.
• Complications: Without prompt treatment, CRE infections can lead to septic shock, multi-organ failure, and death, especially in critical care settings 4 5.

Types of Cre Infection

CRE infections are not limited to a single syndrome or body site. Instead, they encompass a variety of clinical presentations, depending on where the bacteria take hold. The most common types are summarized below.

Infection Type	Description	Frequency/Notes	Source(s)
Pneumonia	Lung infection	Most common (esp. ICU)	2 5 6
Urinary Tract Infection	Infection of urinary system	Frequent in hospitals	2 6
Intra-abdominal	Infection in the abdominal area	Post-surgery/critical care	2 6
Bacteremia/Sepsis	Bloodstream infection	High mortality risk	2 4 6

Table 2: CRE Infection Types

Major Clinical Types

CRE infections most often present as:

Pneumonia

• Definition: Infection of the lower respiratory tract.
• Vulnerable Populations: Common in ventilated ICU patients, where it is termed ventilator-associated pneumonia (VAP) 2 5.
• Features: Presents with cough, shortness of breath, fever, and sometimes hypoxia.
• Prognosis: Associated with high mortality and prolonged hospital stays 5.

Urinary Tract Infection (UTI)

• Definition: Infection involving the urinary bladder, urethra, or kidneys.
• Risk Groups: Hospitalized patients, especially those using catheters 2 6.
• Symptoms: Dysuria, urgency, and sometimes fever or flank pain.
• Frequency: UTI is one of the most common clinical forms of CRE infection, particularly in patients with medical devices 6.

Intra-abdominal Infections

• Definition: Infections within the abdominal cavity, often post-surgical or in patients with chronic illness.
• Manifestation: Abdominal pain, tenderness, fever, and sometimes signs of sepsis 2 6.
• Complexity: These can be complicated and require both antibiotic and surgical management.

Bacteremia/Sepsis

• Definition: Infection of the bloodstream, which can lead to systemic inflammatory response and septic shock.
• Severity: Bacteremia due to CRE is a medical emergency with a very high risk of mortality 2 4 6.
• Symptoms: Fever, chills, confusion, and hypotension.

Less Common Types

Other forms such as skin/soft tissue infections and device-related infections (e.g., central line-associated bloodstream infections) have also been observed, particularly in patients with underlying health issues or extensive hospital stays 3 6.

Causes of Cre Infection

The rise of CRE infections is closely linked to modern healthcare practices and the widespread use of antibiotics. Understanding the causes is crucial for prevention and targeted interventions.

Cause/Risk Factor	Mechanism/Role	Populations at Risk	Source(s)
Antibiotic Exposure	Selects for resistant bacteria	Hospitalized, prior therapy	1 3 5 6
Medical Devices	Bypass natural defenses, harbor bacteria	ICU, catheterized, ventilated	3 5 6
Colonization	CRE presence in gut or skin precedes infection	Hospitalized, ICU	4 6
Healthcare Exposure	Cross-transmission, prior hospitalization	All, esp. overseas/ICU	1 4 6

Table 3: Causes and Risk Factors

Antibiotic Use and Selection Pressure

• Carbapenems and Broad-Spectrum Antibiotics: Repeated or prolonged exposure to powerful antibiotics, especially carbapenems, is a leading risk factor for the emergence and spread of CRE. Overuse of antibiotics can select for bacteria that harbor resistance genes 1 3 5 6.
• Other Antibiotics: Prior use of penicillins, glycopeptides, and beta-lactamase inhibitors also increases risk 1 5.

Medical and Hospital Interventions

• Invasive Devices: Use of devices such as urinary catheters, central lines, and ventilators provides a route for bacteria to bypass normal body defenses. Patients in the ICU, or those requiring long hospital stays, are at especially high risk 3 5 6.
• Colonization: CRE can first colonize the gastrointestinal tract or other mucosal surfaces without causing symptoms. Colonized patients are at much higher risk of subsequent infection, particularly if they become critically ill 4 6.

Healthcare-Associated Transmission

• Hospitalization: Admission to hospitals, especially with prior stays in high-prevalence regions or intensive care units, increases the chance of acquiring CRE 1 4 6.
• International Spread: Travel or healthcare exposure in areas with high CRE prevalence (e.g., certain countries or regions) is a major risk factor 1.
• Patient-to-Patient Spread: CRE can spread via contaminated hands of healthcare workers, medical equipment, or environmental surfaces 3 10.

Underlying Health Conditions

• Chronic Illnesses: Conditions like chronic kidney disease, diabetes, or immunosuppression further increase vulnerability 6.
• Previous CRE Colonization/Infection: Patients known to be colonized or previously infected with CRE are at much higher risk for new or recurrent infection 6.

Treatment of Cre Infection

Treating CRE infections is one of the most challenging tasks in modern medicine due to the bacteria’s resistance to many antibiotics. However, novel therapies and combination approaches offer hope for better outcomes.

Therapy/Strategy	Description	Efficacy/Notes	Source(s)
Polymyxins (colistin)	Last-resort antibiotic for CRE	High nephrotoxicity risk	2 5 9 10
Tigecycline	Tetracycline derivative	Better for E. coli than K. pneumoniae	2 5 9
Aminoglycosides	E.g., amikacin, plazomicin	Used in combination	5 9
Ceftazidime-Avibactam	Novel β-lactam/β-lactamase inhibitor	Active against KPC/OXA-48	9 10
Meropenem-Vaborbactam	Combination targeting KPC-producers	Improved outcomes over old regimens	7 9
Combination Therapy	Multiple drugs used together	Preferred for severe infection	9 11
Supportive Care	ICU, organ support for severe cases	Essential in septic shock	4 5

Table 4: CRE Treatment Options

Current and Emerging Therapeutic Options

Standard and Older Options

• Polymyxins (e.g., colistin, polymyxin B): Often used as a last resort due to high rates of kidney toxicity. Still, they remain one of the few options for multidrug-resistant CRE 2 5 9 10.
• Tigecycline: A tetracycline derivative with activity against many CRE strains. Its effectiveness varies: it is more potent against E. coli than K. pneumoniae 2 5 9.
• Aminoglycosides (amikacin, plazomicin): Sometimes effective, especially in combination therapies 5 9.

Newer and Promising Therapies

• Ceftazidime-Avibactam: A β-lactam/β-lactamase inhibitor combination with significant activity against KPC and OXA-48 CRE strains. It is generally well-tolerated and increasingly used as a preferred option 9 10.
• Meropenem-Vaborbactam: Clinical trials show this combination is more effective and less toxic than older regimens, especially for KPC-producing CRE 7 9. It offers increased clinical cure rates, reduced mortality, and lower nephrotoxicity compared to best available therapies 7.
• Plazomicin: A next-generation aminoglycoside with activity against some CRE strains 9.
• Eravacycline and Imipenem/Relebactam: Newer agents still under investigation or recently introduced, expanding the arsenal for CRE infections 9.

Combination Therapy

• Combination regimens (e.g., colistin with carbapenem, aminoglycoside, or tigecycline) are often more effective than single-drug therapy, particularly for severe or high-burden infections 9 11.
• High-dose or prolonged-infusion strategies may be used for certain drugs to overcome resistance mechanisms 9 11.

Individualized and Supportive Care

• Tailored Therapy: Treatment should be guided by the specific resistance genes present, susceptibility profiles, infection site, and patient factors 9.
• Supportive Measures: In severe cases, supportive care in intensive care units, including organ support, is often necessary 4 5.
• Infection Control: Strict hospital infection control and antibiotic stewardship are essential to prevent the spread of CRE and preserve the effectiveness of available drugs 3 10 11.

Conclusion

CRE infections represent one of the most formidable challenges in infectious disease today. Their rapid spread, high mortality rates, and dwindling treatment options make prevention, early detection, and targeted therapy critical. Here’s what you need to remember:

• Symptoms of CRE infection vary by site but often include fever, localizing signs, and, in severe cases, sepsis and confusion 2 4 5.
• Types of CRE infection include pneumonia, urinary tract infection, intra-abdominal infection, and bloodstream infection, with pneumonia and UTI being most common 2 5 6.
• Causes are closely linked to healthcare exposures, antibiotic use, medical devices, and underlying illnesses. Prior colonization and international healthcare contact further increase risk 1 3 4 5 6.
• Treatment is complex, involving older antibiotics (polymyxins, tigecycline), newer agents (ceftazidime-avibactam, meropenem-vaborbactam), and combination therapies. Individualized care and infection control are essential 7 9 10 11.

Key Takeaways:

• Early recognition and intervention are vital.
• Infection prevention, antibiotic stewardship, and strict hospital protocols are necessary to curb CRE spread.
• New therapies are emerging, but prudent use is critical to avoid further resistance.
• Multidisciplinary care—including infectious disease specialists and intensive monitoring—improves outcomes for patients with CRE infections.

CRE remains a serious public health threat, but continued research and vigilance offer hope for better management and, ultimately, control of these dangerous infections.