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GROUP 8 ENTEROBACTER SPECIES: A COMPREHENSIVE OVERVIEW INTRODUCTION Enterobacter are ubiquitous in nature, their presence in the intestinal tracts of animals results in their wide distribution in soil, water, and sewage. They are also found in plants. In humans, m...

GROUP 8 ENTEROBACTER SPECIES: A COMPREHENSIVE OVERVIEW INTRODUCTION Enterobacter are ubiquitous in nature, their presence in the intestinal tracts of animals results in their wide distribution in soil, water, and sewage. They are also found in plants. In humans, multiple Enterobacter species are known to act as opportunistic pathogens (disease-causing organisms), including E. cloacae, E. aerogenes, E. gergoviae, and E. agglomerans. Pathogenic Enterobacter can cause any of a variety of conditions, including eye and skin infections, meningitis, bacteremia , pneumonia, and UTI. In many instances, illness caused by E. cloacae or by E. aerogenes is associated with exposure to the organisms in nosocomial settings, such as hospitals or nursing homes Enterobacter has become increasingly resistant to many previously effective antibiotics. In 2017, the World Health Organization issued a list of antibiotic-resistant bacteria in which carbapenem-resistant Enterobacteriaceae (CRE) was in the critical priority group for an urgent need to develop new antibiotics. GENERAL CHARACTERISTICS Morphology and Structure: Enterobacter species appear as rod- shaped (bacilli) organisms, typically measuring 0.5 to 3.0 micrometres in length, characterized by their flagella, contributing to motility and virulence. Biochemical Properties: These bacteria are catalase positive and oxidase negative. They ferment lactose, producing acid and gas, a key trait for identification in a clinical laboratory setting. Growth Conditions: Enterobacter can thrive in an environmental conditions, with optimal growth occurring at 37°C, enabling them to colonize human hosts effectively. They flourish in both aerobic and anaerobic conditions. Classification: Enterobacter species are classified within the family Enterobacteriaceae, with species like Enterobacter cloaca and Enterobacter aerogenes being particularly notable in clinical contexts. EPIDEMIOLOGY Enterobacter infections occur worldwide, with incidence rates showing variability based on geographic location and environmental factors that influence infection prevalence. Transmission primarily occurs via the healthcare environment, where contaminated surfaces and medical equipment facilitate the spread of Enterobacter among patients. According to the National Nosocomial Infections Surveillance System, Enterobacter spp. was responsible for approximately five to seven percent of hospital-acquired bacteraemias in the United States. Among isolates in the ICU, it was found that Enterobacter was the third most common pathogen in the respiratory tract, the fourth most common pathogen in surgical wounds, and the fifth most common pathogen in the urinary tract and the bloodstream. PATHOGENIC AND VIRULENCE FACTORS Virulence of this bacterium depends on a variety of factors. Like other gram-negative enteric bacilli, the bacteria use adhesins to bind to host cells. The presence of a lipopolysaccharide (LPS) capsule can aid the bacteria in avoiding opsonophagocytosis. The LPS capsule can initiate a cascade of inflammation in the host cell and may further lead to sepsis. Enterobacter cloaca species are resistant to aminoglycosides, resistance has been associated with a bacterial genetic element known as an integron. Integrons contain genes that confer antibiotic resistance. Efflux Pumps: These mechanisms can pump out antibiotics from the bacterial cell, contributing to multidrug resistance. Biofilm Formation:Enterobacter species can form biofilms on surfaces, including catheters and other medical devices. Biofilms protect the bacteria from the host immune response and increase resistance to antibiotics. The presence of beta-lactamases in Enterobacter spp. is the primary mechanism of antimicrobial resistance. Beta lactamases can hydrolyze the beta-lactam ring seen in penicillin and cephalosporins. The presence of this enzyme has contributed to an increase in the number of resistant Enterobacter pathogens. CLINICAL MANIFAESTATION(DISEASES) Enterobacter infections are associated with an extensive range of clinical manifestations. The most common clinical syndromes are bacteremia, lower respiratory tract infections, UTIs, surgical site infections, and intravascular device-associated infections. Less commonly occurring infections are nosocomial meningitis, sinusitis, and osteomyelitis. Enterobacter infections can have very similar clinical presentations as other facultative anaerobic gram-negative rod bacterial infections, to the point that they can often be indistinguishable. Enterobacter bacteremia has been widely studied. Fever is the most common presentation in this syndrome, as well as systemic inflammatory response (SIRS), hypotension, shock, and leukocytosis, as seen in many other bloodstream presentations. Enterobacter pneumonia commonly presents with cough, shortness of breath, and consolidations found on a chest x-ray. Enterobacter UTI can present with dysuria, frequency, urgency, and positive leukocyte esterase or nitrites on urinalysis. RISK FACTORS Risk factors that predispose to infection include the following: Prolonged recent use of antimicrobial treatment Immunocompromised states, particularly malignancy and diabetes Presence of invasive medical devices Admission to the ICU Recent hospitalization or invasive procedure CLINICAL FINDINGS The clinical findings associated with infections caused by Enterobacter species can vary widely depending on the site of infection, the patient’s underlying health status, and the specific species involved. Enterobacter species, particularly Enterobacter cloacae and Enterobacter aerogenes, are opportunistic pathogens that can lead to a range of infections, especially in immunocompromised patients or those in healthcare settings. Here are some common clinical findings associated with Enterobacter infections: Urinary tract infections Respiratory tract infections Meningitis Endocarditis GI infectoins LABORATORY DIAGNOSIS The gold standard for diagnosing Enterobacter infections is the utilization of cultures. It is recommended that at least two sets of blood cultures be obtained, one aerobic and one anaerobic bottle. MacConkey agar can be used to determine if the specimen is lactose fermenting. Furthermore, indole testing can be performed to differentiate indole negative Klebsiella and Enterobacter and indole positive E. Coli. Enterobacter spp are motile, in contrast to Klebsiella, which is not motile. Other important laboratory studies include: Gram stain (may be helpful in the rapid determination of gram-negative rods before cultures are available) Complete blood count Complete metabolic panel Urinalysis with culture TREATMENT REGIMEN The use of third-generation cephalosporins is not recommended in severe Enterobacter infections due to increased likelihood of resistance, particularly in Enterobacter cloacae and Enterobacter aerogenes, two of the most clinically relevant Enterobacter species. Fourth-generation cephalosporins are relatively stable among AmpC beta-lactamases, so they are considered an acceptable treatment option if Extended-Spectrum beta-lactamase (ESBL) is not present. ESBL enzymes are able to hydrolyze the oxyimino cephalosporins, which may render third and fourth generation cephalosporins ineffective. Carbapenems have been shown to be the most potent treatments for multidrug-resistant Enterobacter infections. Meropenem and Imipenem have been shown to be effective against E. cloacae and E. aerogenes. Carbapenems were not generally affected by ESBL in the past. However, resistance has been increasing in recent years. PUBLIC HEALTH CONCERNS Outbreak Management: Rapid identification and intervention strategies are crucial to managing Enterobacter outbreaks, minimizing transmission in healthcare settings and protecting patient safety. Surveillance: Ongoing surveillance of Enterobacter infections in healthcare settings aids in tracking incidence and resistance trends, proving essential for public health strategies. Infection Control Measures: Implementation of stringent infection control protocols, such as hand hygiene and proper sterilization of equipment, is vital in preventing Enterobacter infections. Antibiotic Stewardship: Promoting responsible prescribing practices is essential in combating antimicrobial resistance attributed to Enterobacter species and ensuring effective treatment options remain available. REFERENCES Sanders WE, Sanders CC. Enterobacter spp.: pathogens poised to flourish at the turn of the century. Clin Microbiol Rev. 1997 Apr;10(2):220-41. [PMC free article] [PubMed] Davin-Regli A, Pagès JM. Enterobacter aerogenes and Enterobacter cloacae; versatile bacterial pathogens confronting antibiotic treatment. Front Microbiol. 2015;6:392. [PMC free article] [PubMed] Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004 Aug 01;39(3):309-17. [PubMed] Chow JW, Fine MJ, Shlaes DM, Quinn JP, Hooper DC, Johnson MP, Ramphal R, Wagener MM, Miyashiro DK, Yu VL. Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy. Ann Intern Med. 1991 Oct 15;115(8):585-90. [PubMed] Rawat D, Nair D. Extended-spectrum β-lactamases in Gram Negative Bacteria. J Glob Infect Dis. 2010 Sep;2(3):263-74. [PMC free article] [PubMed] Suay-García B, Pérez-Gracia MT. Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections. Antibiotics (Basel). 2019 Aug 19;8(3) [PMC free article] [PubMed] White BP, Patel S, Tsui J, Chastain DB. Adding double carbapenem therapy to the armamentarium against carbapenem-resistant Enterobacteriaceae bloodstream

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