Carbapenem-resistant Enterobacteriaceae Infections: Causes, Symptoms, Treatment, Risk Factors, Prevention

Carbapenem-resistant Enterobacteriaceae Infections or CRE infection are caused by a family of bacteria that is highly resistant to antibiotics, making it very difficult to treat. Often termed as ‘Killer Bacteria’, ‘Nightmare Bacteria’ and ‘Super Bug,’ Carbapenem-resistant Enterobacteriaceae Infections has limited treatment options and has a high mortality rate. Found on mobile genetic elements (a type of DNA), these enzymes can spread extensively. Due to this prevention and transmission of Carbapenem-resistant Enterobacteriaceae Infections has become a major public health objective in many countries across the world.

Carbapenem-resistant Enterobacteriaceae or CRE are gram-negative bacteria that are resistant to the antibiotic Carbapenem, which is considered to be the “drug of last resort”. This makes it extremely difficult to treat and control the infection. The bacteria when enters the body causes infection of various sorts viz., infection in the intestine, urinary tract, wound and bloodstream and also pneumonia. The Carbapenem-resistant Enterobacteriaceae can also colonize in the body without causing an infection of symptom. In the last decade, this infection has been spreading worldwide making it difficult for healthcare professionals to treat it. The best way to prevent spreading of the infection is by following infection control protocols in the proper way. Patients who have been admitted to hospitals in another city or country must report to their doctor if any symptoms related to infection are visible including an open wound not healing properly even after using antibiotics.

Colonization simply means that the bacteria are present in the body but is not resulting in any symptoms and disease. The colonizing Carbapenem-resistant Enterobacteriaceae strain can result in infection when they come in contact with body sites that are normally sterile like bloodstream, lungs and bladder. CRE infections are usually related to symptoms and can be different based on the body part where it occurs. In case of Carbapenem-resistant Enterobacteriaceae Infections in the lungs a patient can suffer from cough; whereas if it is in the bladder then urinary tract infection symptoms are visible. General symptoms like fever or chills, pus from the wound and high white blood cell count can be seen based on the area of infection.

Enterobacteriaceae became resistant to Carbapenem due to number of factors. Prior to the emergence of carbapenamases like Klebsiella pneumoniae carbapenemase or KPC, it is likely that most Carbapenem-resistant Enterobacteriaceae were resistant to carbapenems due to a combination of factors. The genes which code for KPC are on a highly mobile genetic element which can be passed on from one bacterium to another and in doing so spreading resistance. Other than KPC there are a number of carbapenemases that can result in resistance to the antibiotic carbapenem. Examples include – Verona Integron-Encoded Metallo-beta-lactamase (VIM) and New Delhi Metallo-beta-lactamase (NDM) and Imipenemase Metallo-beta-lactamase (IMP

The major reason for the cause of Carbapenem-resistant Enterobacteriaceae Infections is overuse of the antibiotic Carbapenem. Due to the excess use, the bacteria develop resistance to the antibiotic, but it is not the only cause of infection. If the CRE bacteria enter a person’s bloodstream, mortality rate can go up to over 40%. Carbapenem-resistant Enterobacteriaceae Infections can easily be transmitted through direct contact from person to person via contaminated feces and skin. Some of the other causes of Carbapenem resistant Enterobacteriaceae infections include –

• Long term hospital stay
• Overuse of antibiotics
• Organ/stem cell transplant
• Substandard hygiene procedure
• Use of mechanical ventilations
• Inadequate disinfection procedure on hospital equipments

Hospitals, long term care homes and nursing homes are the major sites for spreading of Carbapenem-resistant Enterobacteriaceae Infections. Most of the hospital infections for Carbapenem-resistant Enterobacteriaceae are said to be from long term care facilities. Using substandard safety practices including insufficient cleaning, not disinfecting medical cabinets and other medical equipments in the hospital are major risk factors for Carbapenem-resistant Enterobacteriaceae Infections or CRE infections. Other risk factors for this infection can include use of beta-lactam antibiotics and mechanical ventilations.

Diabetics are at a higher risk for getting Carbapenem-resistant Enterobacteriaceae Infections or CRE infection as compared to others. Studies have indicated that some patients exposed to long-term acute care (LTAC) can get the infection. Other risk factors include patients receiving nutrition via bloodstream and those breathing through ventilator. In some cases infections were also related to organ/stem cell transplant.

Based on the area or organ in the body that is infected, the symptoms can vary from patient to patient. Some of the symptoms that can be noted for any bacterial infection might be similar to Carbapenem-resistant Enterobacteriaceae Infections symptoms. These include heart rate exceeding 90 beats/minute, fever, hypotension and shock, septic shock, Ecthyma gangrenosum, and Cyanosis and mottling. Since most infections occur in hospitals, caregivers should watch out for symptoms like lethargy, fever and monitor any swelling, redness or sores including open wounds in the body of patients who were admitted in the hospitals or healthcare institutions for some time.

Different types of infections are associated with Enterobacteriaceae Infections. It includes –

• Bacteremia
• Endocarditis
• Osteomyelitis
• CNS infections
• Septic Arthritis
• Ophthalmic infections
• Intra-abdominal infections
• Skin and soft-tissue infections
• Urinary tract infections (UTIs)
• Lower Respiratory Tract Infections

Other than the general infection symptoms, one must look for specific symptoms. The specific symptoms vary according to the part of the body affected. If the infection is in the bladder, patients can experience urinary tract infection symptoms including fever and pain. Infection in the lung can lead to severe coughing and fever. Other symptoms to look for include sores or wounds that do not heal when treated with antibiotics.

In the last decade Carbapenem-resistant Enterobacteriaceae infections has been commonly reported across the United States. Initially it was indicated that carbapenem resistance in Enterobacteriaceae was due to overproduction of AmpC-mediated β-lactamases or extended-spectrum β-lactamases (ESBLs) in organisms with porin mutations. However, carbapenemases now have other means for carbapenem antibiotic resistance among CRE. In the United States, KPC-producing Enterobacteriaceae was first reported in North Carolina in a patient’s clinical specimen in 2001.

Afterwards outbreaks and transmission of the Carbapenem-resistant Enterobacteriaceae Infections or CRE infection was reported in more than 40 health care facilities in the country. A surveillance study conducted in New York City in 2002-2003 found that 9 out of 602 K. pneumoniae isolates contained blaKPC gene. Later an additional 20 KPC-producing isolates were identified from 2 hospital outbreaks and after that it has become nationally widespread.

Some global cases of Carbapenem-resistant Enterobacteriaceae Infections are linked to receiving medical care in the United States. Studies have indicated that hospital hand washing solutions are environmental reservoir for CRE. ICU sinks are also a major source of this bacterial infection and is easily transferred from one sink to another.

One of the best ways of preventing Carbapenem-resistant Enterobacteriaceae infections is by following the prescribed cleanliness and infection control protocols. Most infections occur to patients who are admitted for long term care in hospitals, healthcare facilities and nursing homes. Some of the methods that can be followed by hospitals to prevent infection include –

• Prescribe antibiotics strictly on necessity
• Use dedicated equipment and staff to care for CRE patients
• Regularly clean and disinfect rooms and hospital medical equipments
• Wash hands with soap and water or alcohol based sanitizer before and after caring for a patient
• Wear sterile gloves and gown before entering room of infected patient
• Remove glove and gown and wash hands with soap after exiting room of CRE infected patient
• Keep CRE infected patient in single room or with other patient who has same infection

Patients suffering from Carbapenem-resistant Enterobacteriaceae infections require long term hospitalization, laboratory tests, multiple and different types of imaging studies along with surgical and non-surgical procedures. Once the diagnosis is made the patient is treated with medications. The mortality rate associated with CRE infection or Carbapenem-resistant Enterobacteriaceae infections is high as there are very few antibiotics that can kill these bacteria. The only antibiotics that can treat Carbapenem-resistant Enterobacteriaceae Infections are –

• Polymyxins
• Fosfomycin
• Temocillin
• Tigecycline
• Aminoglycosides

Some experimental drugs are also being used to fight CRE infection and a few of them are currently under review by the FDA.

CRE infection can be deadly if not treated on time or a neglected. Patients must be informed about chances of developing the infection post hospitalization. Care givers must be informed about the symptoms to look for in the patients during or post hospitalizations for early diagnosis. Everyone must follow the preventive measures to stop the killer bacteria from spreading further.