Introduction
The genus Enterobacter, which is a member of the Enterobacteriaceae family, is mostly linked to infections that are relevant to healthcare. Currently, there are 22 different types of Enterobacter. However, not all animals are known to transmit sickness to humans. Enterobacter species are responsible for a large number of nosocomial infections as well as less common community-acquired illnesses, such as osteomyelitis, endocarditis, lung infections, soft tissue infections, and urinary tract infections (UTI). Other Enterobacter species can be a part of the microflora of the mammalian gastrointestinal system, in addition to being found on the surfaces of human skin, in water, some foods, soil, and sewage.
It was recognized that the Enterobacter species could lead to nosocomial infections beginning in the 1970s. Enterobacter is a typical bacterium identified in respiratory sputum, surgical wounds, and blood reported in isolates from intensive care units (ICU), according to the National Nosocomial Infections Surveillance System.
Many formerly efficient antibiotics are no longer useful against Enterobacter. In a list of antibiotic-resistant bacteria that the World Health Organization published in 2017, carbapenem-resistant Enterobacteriaceae (CRE) was included as a critical priority group for the urgent need to discover new antibiotics.
What Is the Etiology of Enterobacter Infections?
Enterobacter is a gram-negative, rod-shaped, facultatively anaerobic bacteria in the Enterobacteriaceae family. Additionally, it must digest lactose, have flagella, be urease-positive, and not generate spores. Numerous factors affect the pathogenicity of this bacterium. Like other gram-negative enteric bacilli, these bacteria use adhesins to bind to host cells.
A lipopolysaccharide (LPS) capsule may help the bacteria evade opsonophagocytosis. The LPS capsule can start a chain reaction of inflammation in the host cell, which could ultimately result in sepsis.
The main mechanism of antibiotic resistance is the existence of beta-lactamases in Enterobacter spp. Penicillin and Cephalosporins include the beta-lactam ring, which can be hydrolyzed by beta-lactamases. A rise in resistant Enterobacter pathogens has been attributed to the presence of this enzyme.
What Are the Clinical Manifestations of Enterobacter Infections?
A wide variety of clinical symptoms are linked to Enterobacter infections. Bacteremia, lower respiratory tract infections, urinary tract infections (UTIs), surgical site infections, and infections linked to intravascular devices are the most prevalent clinical syndromes. Nosocomial meningitis (inflammation of protective brain coverings occurring 48 hours after admission), sinusitis, and osteomyelitis (serious bone infection) are less frequent infections. Clinically speaking, Enterobacter infections and other facultative anaerobic gram-negative rod bacterial infections can frequently be confused with one another.
Research on Enterobacter bacteremia is extensive. The most typical bloodstream symptom in this syndrome is fever, which also frequently manifests as the systemic inflammatory response (SIRS - a serious condition causing inflammation of the whole body), hypotension (decreased blood pressure), shock, and leukocytosis (elevated white blood cells in the blood).
Enterobacter pneumonia symptoms:
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Chest X-ray consolidations.
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Coughing.
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Shortness of breath.
Enterobacter UTI symptoms:
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Dysuria.
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Frequent urination.
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Urgency.
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A positive urinalysis for leukocyte esterase or nitrites.
What Are the Risk Factors for Enterobacter Infections?
The likelihood of infection is increased by the following risk factors:
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Long-term recent antimicrobial therapy.
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Immune-compromised conditions, especially cancer and diabetes.
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Intrusive medical equipment is present.
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Admission to the intensive care unit.
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Recently undergone invasive treatment or hospitalization.
How Is Enterobacter Infection Evaluated?
Utilizing cultures is the gold standard for identifying infections with Enterobacter. It is advised to obtain at least two bottles of blood cultures, one for aerobic and one for anaerobic conditions. In order to find out if the sample is lactose fermenting, use MacConkey agar. Additionally, indole testing can be used to distinguish between E. coli and Klebsiella, which are indole positive and negative, respectively. Unlike Klebsiella, which is immobile, Enterobacter spp. can move.
Additional significant lab investigations include:
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Gram stain (may be useful in the quick identification of gram-negative rods before the availability of cultures).
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Total blood count.
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Complete metabolic panel.
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Cultured urine analysis.
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In order to direct management, appropriate imaging that is in accordance with the specific organ system implicated can be useful.
How Is Enterobacter Infection Treated?
Antibiotic resistance is becoming more and more of a problem while treating infections produced by Enterobacter. Beta-lactams, beta-lactamase inhibitors, Fluoroquinolones, Aminoglycosides, and Sulfamethoxazole or Trimethoprim are a few possible therapies.
1. Medical Care:
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Cephalosporins: In general, first and second-generation Cephalosporins are ineffective against infections caused by Enterobacter. Even though third-generation Cephalosporin therapy may be successful in treating some Enterobacter strains, it can also result in multiresistant illnesses. Third-generation Cephalosporins are likely to select or induce derepressed Enterobacter AmpC beta-lactamase genetic variations, causing the enzyme to overproduce and the emergence of resistance. Due to the increased risk of resistance, especially in Enterobacter cloacae and Enterobacter aerogenes, two of the most clinically significant Enterobacter species, the use of third-generation Cephalosporins is not advised in severe Enterobacter infections. Other resistance methods include the insertion of the plasmid-derived transferable AmpC gene and a mutation in the AmpR repressor.
Fourth-generation Cephalosporins are seen as a suitable therapeutic choice if Extended-Spectrum beta-lactamase (ESBL - enzymes that break down and destroy the antibiotics) is absent since they are relatively stable among AmpC beta-lactamases. The Oxyimino Cephalosporins can be hydrolyzed by ESBL enzymes, which may render third and fourth-generation Cephalosporins useless.
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Carbapenems: The most effective therapies for multidrug-resistant Enterobacter infections are Carbapenems. It has been demonstrated that Meropenem and Imipenem work well against E. cloacae and E. aerogenes. In the past, ESBL did not typically affect Carbapenems. However, in recent years, resistance has grown more pronounced. Multiple plasmid-mediated enzymes are involved in the methods through which Enterobacter develops resistance to Carbapenems, allowing for easy horizontal transfer and the emergence of widespread resistance.
Polymyxins, Tigecycline, Fosfomycin, and Carbapenems (used in a double Carbapenem regimen) are possible treatments for Carbapenem-resistant Enterobacter (CRE). The idea behind a double Carbapenem regimen, which may appear counterintuitive, is that one Carbapenem acts as the "sacrificial" drug because of its higher affinity to the carbapenemase, allowing the concurrent Carbapenem with a lesser affinity to retain a higher concentration. In CRE cases with more severe clinical signs, like septic shock and quickly advancing disease, a combination of antimicrobial drugs has been demonstrated to be more effective than monotherapy.
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Polymyxin: Colistin has been discovered to be the foundation of efficient combination therapy for CRE bloodstream infections. Colistin may be used with other medications, including Carbapenems, Tigecycline, and Fosfomycin. Colistin resistance, however, has grown during the past few years. It is advised to use a combination regimen to treat Colistin-resistant CRE, which includes two different Carbapenems or Tigecycline as the main ingredient. Colistin, Fosfomycin, and Aminoglycosides are a few examples of other drugs that can be taken with Tigecycline. People who already have kidney illnesses need to exercise caution because drugs like Colistin and Aminoglycosides can exacerbate the condition.
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Monotherapy and Combination Therapy: Aminoglycosides and Fosfomycin are the preferred treatments as monotherapy if susceptible to CRE UTIs (urinary tract infections) where patients are not in critical condition. Fosfomycin has limited oral bioavailability, hence it is not advised for pyelonephritis (kidney inflammation due to infection). Due to their low urine excretion, Tigecycline and Colistin are not advised for CRE UTI. Combination therapy using Carbapenem in addition to Colistin or aminoglycoside is a viable treatment option for patients with a CRE UTI who are in critical condition.
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Once the patient has made progress while being treated as an inpatient, intravenous antibiotics may be changed to oral antibiotics, and Fluoroquinolones, Sulfamethoxazole, or Trimethoprim may be used to finish the treatment as an outpatient regimen due to its natural resistance to macrolides and its limited permeability of the outer cell envelope, Enterobacter.
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A variety of drug combinations are needed for the highly complex and variable CRE treatment. Research on experimental medications is still ongoing because of the persistence of resistance.
2. Surgical Care:
Surgery is advised for abscesses, infected collections, and osteomyelitis foci (infection of the bone), as well as other sites of infection. In some cases, this alternative to percutaneous drainage under CT (computed tomography) guidance must be taken into account by the doctor. The severity of the illness and the volume of collection that needs to be drained are important considerations for deciding the best course of action for the patient. Valvular replacement is also recommended for endocarditis (heart valve inflammation), especially in individuals with emboli or untreatable heart failure.
Conclusion
The infection site (bloodstream, meninges, lungs, etc.), time to diagnosis and treatment, antibiotic resistance, and underlying host vulnerabilities all affect the prognosis of Enterobacter cloacae complex infections. Generally speaking, the death rate is high, which is comparable to diseases brought on by other invasive gram-negative bacilli.
