Citrobacter freundii: Introduction, Morphology, Pathogenicity, Lab Diagnosis, Treatment, Prevention, and Keynotes

Introduction

Citrobacter freundii is a Gram-negative bacterium belonging to the Enterobacteriaceae family. It is commonly found in the environment, including soil, water, and the intestinal tracts of humans and animals. Citrobacter freundii is an opportunistic pathogen, meaning it can cause infections in individuals with weakened immune systems or underlying health conditions.

Infections caused by C. freundii typically occur in healthcare settings, such as hospitals, and are commonly associated with urinary tract infections (UTIs), respiratory tract infections, bloodstream infections (septicemia), and wound infections. It can also cause meningitis, particularly in neonates and individuals with compromised immune systems.

The symptoms of Citrobacter freundii infections vary depending on the site of infection. UTIs may present with symptoms such as frequent urination, pain or burning during urination, and cloudy or bloody urine. Respiratory tract infections can cause symptoms such as cough, chest pain, and difficulty breathing. Bloodstream infections can lead to fever, chills, and overall malaise.

It is known to be resistant to multiple antibiotics, which can complicate treatment. The appropriate antibiotic therapy depends on the specific strain and its susceptibility to various drugs. Infections are typically treated with broad-spectrum antibiotics, such as third-generation cephalosporins or fluoroquinolones, based on the antimicrobial susceptibility testing.

Morphology

Citrobacter freundii is a Gram-negative bacterium with a distinct morphology. Here are some characteristics of the morphology of C. freundii:

Citrobacter freundii growth on CLED agar of Urine Culture
Fig. Citrobacter freundii growth on CLED agar of Urine Culture
  1. Shape: Citrobacter freundii appears as rod-shaped or bacillus-shaped bacteria. These cells are elongated and cylindrical in form.
  2. Size: The average size of its cells is around 1-2 micrometers in width and 2-6 micrometers in length.
  3. Gram Staining: It is Gram-negative, which means it does not retain the crystal violet stain in the Gram staining process. Instead, it takes up the counterstain (safranin) and appears pink or red under a microscope.
  4. Capsule: Some strains of C. freundii may produce a polysaccharide capsule surrounding the cell wall. This capsule can contribute to the bacterium’s pathogenicity and resistance to host immune responses.
  5. Flagella: Itis often motile due to the presence of peritrichous flagella. These flagella are distributed around the bacterial cell and provide the bacterium with the ability to move in liquid environments.
  6. Colony Morphology: On solid culture media, C. freundii colonies typically appear as smooth, round, and slightly raised colonies. The color can vary depending on the specific strain, ranging from white to yellow or pink.
Citrobacter freundii in Wet mount of Culture Microscopy
Fig. Citrobacter freundii in Wet mount of Culture Microscopy

It’s important to note that the morphology of C. freundii can vary slightly among different strains and growth conditions. Microbiological laboratories use various techniques to identify and differentiate C. freundii from other bacterial species, including biochemical tests, serotyping, and molecular methods.

Pathogenicity

Citrobacter freundii can be considered an opportunistic pathogen, meaning it primarily causes infections in individuals with compromised immune systems or underlying health conditions. While it is a part of the normal intestinal flora in humans and animals, it can become pathogenic under certain circumstances.

Here are some key points regarding the pathogenicity of C. freundii:

  1. Infections: Citrobacter freundii can cause a range of infections, including urinary tract infections (UTIs), respiratory tract infections, bloodstream infections (septicemia), wound infections, and meningitis. It is particularly associated with urinary tract infections in healthcare settings.
  2. Virulence Factors: It possesses various virulence factors that contribute to its pathogenicity. These factors include adhesins, which allow the bacterium to attach to host tissues, and toxins that can damage host cells and contribute to tissue invasion.
  3. Antibiotic Resistance: It has shown the ability to develop antibiotic resistance, which can complicate treatment. Resistance mechanisms can involve the production of enzymes that inactivate antibiotics or alterations in the bacterial cell wall that prevent drug entry.
  4. Biofilm Formation: It is capable of forming biofilms, which are communities of bacteria encased in a protective matrix. Biofilms can adhere to surfaces, such as urinary catheters or medical devices, making them more resistant to antibiotics and immune responses.
  5. Immune System Evasion: C. freundii has mechanisms to evade the host immune system. It can modify its surface structures to avoid recognition by the immune system or impair immune cell function.

It is worth noting that the severity of its infections can vary widely depending on the individual’s immune status and underlying health conditions. In healthy individuals, it may not cause significant disease. However, in immunocompromised individuals or those with prolonged hospital stays, it can lead to more severe infections.

Lab Diagnosis

The laboratory diagnosis of C. freundii involves a series of tests and techniques to identify and confirm the presence of the bacterium. Here are the common methods used for the lab diagnosis of Citrobacter freundii:

Gram Negative Rods of Citrobacter freundii
Fig. Gram Negative Rods of Citrobacter freundii
  1. Gram Staining: A Gram stain is typically the first step in identifying bacteria. It is Gram-negative and will appear as pink or red rods under a microscope.
  2. Culture and Colony Morphology: It can be cultured on appropriate agar plates, such as MacConkey agar or blood agar. It typically forms smooth, round, and slightly raised colonies. The colonies may have varying colors, ranging from white to yellow or pink.
  3. Biochemical Tests: Several biochemical tests can help differentiate C. freundii from other bacteria. These tests include:
    • Indole test: C. freundii is typically indole-positive, meaning it produces indole from the amino acid tryptophan.
    • Citrate utilization test: It is positive for citrate utilization, which means it can use citrate as a sole carbon source.
    • Lactose fermentation: It ferments lactose, so it will produce acid and gas when cultured on lactose-containing media.
    • Voges-Proskauer test: C. freundii is typically Voges-Proskauer negative, meaning it does not produce the specific metabolites detected by this test.
  4. Antimicrobial Susceptibility Testing: C. freundii is known to exhibit multidrug resistance. Therefore, antimicrobial susceptibility testing is crucial to determine the appropriate antibiotic treatment. The Kirby-Bauer disk diffusion method or automated systems can be employed to assess the susceptibility of the bacterium to various antibiotics.
  5. Molecular Identification: Molecular methods, such as polymerase chain reaction (PCR) and DNA sequencing, can provide a more precise identification of Citrobacter freundii. These methods target specific genetic markers or sequences unique to the bacterium, allowing for accurate species identification.

It’s important to perform these tests in a clinical laboratory setting by trained professionals. The results of the laboratory diagnosis should be interpreted in conjunction with the patient’s clinical presentation and other relevant information.

Treatment


The treatment of C. freundii infections typically involves antibiotic therapy. However, it is important to note that C. freundii is known to exhibit multidrug resistance, which means it may be resistant to several commonly used antibiotics. Therefore, the choice of antibiotics should be based on the results of antimicrobial susceptibility testing specific to the strain causing the infection. Here are some general considerations for the treatment of Citrobacter freundii infections:

  1. Antibiotic Selection: The choice of antibiotics should be guided by local antibiotic susceptibility patterns and the individual strain’s resistance profile. In many cases, third-generation cephalosporins, such as ceftriaxone or ceftazidime, are effective against C. freundii. Fluoroquinolones, such as ciprofloxacin or levofloxacin, may also be considered. However, it is important to note that resistance to these antibiotics is increasing, and susceptibility testing is crucial to determine the most appropriate treatment.
  2. Combination Therapy: In severe infections or when dealing with multidrug-resistant strains, combination therapy with multiple antibiotics may be necessary. This approach aims to broaden the spectrum of activity and enhance the efficacy of treatment. The specific combination of antibiotics should be determined by susceptibility testing and consultation with an infectious disease specialist.
  3. Duration of Treatment: The duration of treatment varies depending on the type and severity of the infection. In uncomplicated urinary tract infections, a shorter course of antibiotics (e.g., 7-10 days) may be sufficient. However, for more severe infections, such as bloodstream infections or pneumonia, a longer course (e.g., 10-14 days or more) is often required. The duration of treatment should be individualized based on the patient’s response to therapy and clinical improvement.
  4. Antimicrobial Stewardship: Given the propensity of Citrobacter freundii to develop antibiotic resistance, it is crucial to practice antimicrobial stewardship. This involves using antibiotics judiciously, avoiding unnecessary or inappropriate antibiotic use, and ensuring optimal dosing and duration of treatment.

It is important to note that the above recommendations are general guidelines, and the specific treatment plan should be determined by a healthcare professional based on the individual patient, the site of infection, and the antimicrobial susceptibility profile of the strain causing the infection.

AST of Citrobacter freundii
Fig. AST of Citrobacter freundii

Prevention

Preventing Citrobacter freundii infections involves implementing measures to minimize the risk of exposure and transmission of the bacterium. Here are some general prevention strategies:

  1. Hand Hygiene: Proper hand hygiene is essential in preventing the spread of C. freundii and other infectious agents. Wash your hands thoroughly with soap and water for at least 20 seconds, especially after using the restroom, before preparing or consuming food, and after coming into contact with potentially contaminated surfaces.
  2. Infection Control Practices: In healthcare settings, strict adherence to infection control practices is crucial to prevent the transmission of C. freundii. This includes appropriate disinfection of equipment and surfaces, adherence to hand hygiene protocols, and implementation of isolation precautions when necessary.
  3. Catheter Care: For individuals with urinary catheters, proper care and maintenance are essential to reduce the risk of urinary tract infections. Follow guidelines for catheter insertion, maintenance, and timely removal when no longer necessary.
  4. Antibiotic Stewardship: Misuse and overuse of antibiotics contribute to the development of antibiotic-resistant strains of Citrobacter freundii. Follow healthcare professionals’ instructions regarding antibiotic usage, complete the full prescribed course, and avoid using antibiotics without proper medical guidance.
  5. Food Safety: Practice proper food handling and preparation techniques to prevent contamination. This includes thorough cooking of meats, proper storage of perishable foods, and avoiding cross-contamination between raw and cooked foods.
  6. Environmental Hygiene: Maintain cleanliness and hygiene in the environment, particularly in healthcare facilities. Regular cleaning and disinfection of surfaces and equipment can help prevent the spread of C. freundii.
  7. Immunization: Stay up to date with recommended vaccinations, such as those for respiratory infections, to reduce the risk of complications from respiratory tract infections caused by Citrobacter freundii and other pathogens.

Keynotes

Here are some key points to note about Citrobacter freundii:

  1. Classification: It is a Gram-negative bacterium belonging to the Enterobacteriaceae family. It is a rod-shaped bacterium with flagella, allowing it to be motile.
  2. Natural Habitat: It can be found in various environmental sources, including soil, water, and the intestinal tracts of humans and animals.
  3. Opportunistic Pathogen: While generally part of the normal intestinal flora, Citrobacter freundii can become an opportunistic pathogen, causing infections primarily in individuals with weakened immune systems or underlying health conditions.
  4. Infection Types: It can cause a range of infections, including urinary tract infections (UTIs), respiratory tract infections, bloodstream infections (septicemia), wound infections, and meningitis.
  5. Antibiotic Resistance: Citrobacter freundii is known to exhibit multidrug resistance, which means it can be resistant to multiple antibiotics. Proper antimicrobial susceptibility testing is crucial to guide appropriate antibiotic therapy.
  6. Virulence Factors: C. freundii possesses virulence factors such as adhesins and toxins, which contribute to its ability to attach to host tissues, invade cells, and cause damage.
  7. Diagnosis: Laboratory diagnosis of Citrobacter freundii involves techniques such as Gram staining, culture, biochemical tests, and molecular identification to confirm its presence and differentiate it from other bacteria.
  8. Prevention: Preventing Citrobacter freundii infections involves practicing good hand hygiene, implementing infection control measures in healthcare settings, ensuring proper catheter care, promoting antibiotic stewardship, and following food safety practices.
  9. Individual Variations: The severity of Citrobacter freundii infections can vary depending on the individual’s immune status and underlying health conditions. Treatment should be tailored to the specific strain and patient’s circumstances.

It’s important to consult healthcare professionals for accurate diagnosis, treatment, and management of C. freundii infections or any health concerns.

Further Reading

  1. “Citrobacter freundii: An Emerging Nosocomial Pathogen” – This review article published in The Journal of Hospital Infection provides an overview of Citrobacter freundii as an emerging nosocomial (hospital-acquired) pathogen, its clinical significance, antibiotic resistance, and infection control measures.
  2. “Citrobacter Infections in Humans: A Systematic Review” – This systematic review, published in Journal of Microbiology, Immunology, and Infection, summarizes the clinical characteristics, epidemiology, risk factors, and treatment options for Citrobacter infections in humans, including Citrobacter freundii.
  3. “Virulence Factors of Citrobacter freundii and Their Roles in Pathogenesis” – This research article, published in Frontiers in Microbiology, discusses the various virulence factors of Citrobacter freundii and their contributions to the pathogenesis of infections caused by this bacterium.
  4. “Antimicrobial Resistance in Citrobacter Species: Mechanisms and Clinical Implications” – This comprehensive review article, published in The Lancet Infectious Diseases, focuses on the mechanisms of antimicrobial resistance in Citrobacter species, including Citrobacter freundii, and the clinical implications of resistance in the treatment of infections.
  5. “Clinical and Microbiological Characteristics of Citrobacter spp. Bloodstream Infections” – This study, published in Antimicrobial Agents and Chemotherapy, investigates the clinical and microbiological characteristics of bloodstream infections caused by Citrobacter species, including Citrobacter freundii, providing insights into its pathogenesis and antibiotic resistance patterns.

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