C. freundii

Emery Haley, PhD, Scientific Writer

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Clinical Summary

C. freundii is recognized as a classical gram-negative, urease-variable, biofilm-forming uropathogen. 
C. freundii is associated with complicated UTI in older adult and pediatric populations. 
In symptomatic UTI patients, C. freundii: 
- Is not a contaminant (is found in catheter-collected urine specimens). 
- Is viable (can grow out on culture). 
- Is pathogenic (associated with elevated urine biomarkers of infection). 
Reported severe complications of C. freundii UTI include polymicrobial bacteremia and urosepsis. 
Multidrug-resistant C. freundii (especially among hospital-acquired UTIs) is a significant global health threat.

Bacterial Characteristics

Gram-stain

Gram-negative

Morphology

Bacillus

Growth Requirements

Non-fastidious (grows well in standard urine culture conditions)
Facultative anaerobe

Nitrate Reduction

Yes

Urease

Variable

Biofilm Formation

Yes

Pathogenicity

Colonizer or Pathobiont

Clinical Relevance in UTI

C. freundii is a urease-variable microorganism [1] capable of forming biofilms.[2]  C. freundii is typically considered to be among the common classical uropathogens in older adults,[3]  but is also being increasingly recognized as common in pediatric UTIs.[4] 

In a study of older adult males and females with clinically suspected complicated UTI, C. freundii was detected in both midstream voided and in-and-out-catheter collected specimens indicating that it was truly present in the bladder, not simply a contaminant picked up during voiding.[5]  Furthermore, elevated markers of immune system activation in the urinary tract have been measured from the same clinical urine specimens in which C. freundii was detected, indicating that the presence of C. freundii was associated with an immune response to urinary tract infection.[6–8]   

Hospital-acquired C. freundii UTIs pose a particularly serious threat, as these infections increasingly display multidrug- or pandrug-resistant.[9–11]  Although not considered one of the six highest priority “ESKAPE” pathogens, The World Health Organization (WHO) has included this organism in the 2024 Bacterial Priority Pathogens List (BPPL).[111] Severe complications of C. freundii UTI, including polymicrobial bacteremia and urosepsis, have been reported.[12–14] 

Together, these findings indicate that C. freundii should be seriously considered as a uropathogen and demonstrate the value of detecting this organism, particularly in individuals with recurrent UTI and/or risk factors for persistent or complicated UTI.

Treatment

Evidence of Efficacy (Checkmarks): Cefepime, Ciprofloxacin, Doxycycline, Gentamicin, Levofloxacin, Meropenem, Nitrofurantoin, Piperacillin/Tazobactam, Sulfamethoxazole/Trimethoprim, and Trimethoprim.

References

1. BacDive | The Bacterial Diversity Metadatabase Available online: https://bacdive.dsmz.de/ (accessed on 11 February 2025).
2. Shinu, P. Antimicrobial Resistance, Phenotypic Characteristics, and Biofilm Production in Citrobacter Freundii Isolates Obtained from Urinary Tract Infections. J. Pharmacol. Pharmacother. 2022, 13, 375–381, doi:10.1177/0976500×221147747.
3. Gajdács, M.; Ábrók, M.; Lázár, A.; Burián, K. Urinary Tract Infections in Elderly Patients: A 10-Year Study on Their Epidemiology and Antibiotic Resistance Based on the WHO Access, Watch, Reserve (AWaRe) Classification. Antibiotics 2021, 10, 1098, doi:10.3390/antibiotics10091098.
4. Acevedo, H. Pediatric Citrobacter Urinary Tract Infections: A Case Report Highlighting Emerging Trends. Am. J. Méd. Clin. Res. Rev. 2024, 03, 01–06, doi:10.58372/2835-6276.1166.
5. Wang, D.; Haley, E.; Luke, N.; Mathur, M.; Festa, R.; Zhao, X.; Anderson, L.A.; Allison, J.L.; Stebbins, K.L.; Diaz, M.J.; et al. Emerging and Fastidious Uropathogens Were Detected by M-PCR with Similar Prevalence and Cell Density in Catheter and Midstream Voided Urine Indicating the Importance of These Microbes in Causing UTIs. Infect. Drug Resist. 2023, Volume 16, 7775–7795, doi:10.2147/idr.s429990.
6. Haley, E.; Luke, N.; Mathur, M.; Festa, R.A.; Wang, J.; Jiang, Y.; Anderson, L.A.; Baunoch, D. The Prevalence and Association of Different Uropathogens Detected by M-PCR with Infection-Associated Urine Biomarkers in Urinary Tract Infections. Res. Rep. Urol. 2024, 16, 19–29, doi:10.2147/rru.s443361.
7. Akhlaghpour, M.; Haley, E.; Parnell, L.; Luke, N.; Mathur, M.; Festa, R.A.; Percaccio, M.; Magallon, J.; Remedios-Chan, M.; Rosas, A.; et al. Urine Biomarkers Individually and as a Consensus Model Show High Sensitivity and      Specificity for Detecting UTIs. BMC Infect Dis 2024, 24, 153, doi:10.1186/s12879-024-09044-2.
8. Parnell, L.K.D.; Luke, N.; Mathur, M.; Festa, R.A.; Haley, E.; Wang, J.; Jiang, Y.; Anderson, L.; Baunoch, D. Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/ML Indicate a Lower Threshold for Diagnosing UTIs. MDPI 2023, 13, 1–15, doi:10.3390/diagnostics13162688.
9. Fonton, P.; Hassoun-Kheir, N.; Harbarth, S. Epidemiology of Citrobacter Spp. Infections among Hospitalized Patients: A Systematic Review and Meta-Analysis. BMC Infect. Dis. 2024, 24, 662, doi:10.1186/s12879-024-09575-8.
10. Zhang, M.; Yin, Z.; Chen, B.; Yu, Z.; Liang, J.; Tian, X.; Li, D.; Deng, X.; Peng, L. Investigation of Citrobacter Freundii Clinical Isolates in a Chinese Hospital during 2020–2022 Revealed Genomic Characterization of an Extremely Drug-Resistant C. Freundii ST257 Clinical Strain GMU8049 Co-Carrying BlaNDM-1 and a Novel BlaCMY Variant. Microbiol. Spectr. 2024, 12, e04254-23, doi:10.1128/spectrum.04254-23.
11. Sung, K.; Nawaz, M.; Revollo, J.; Miranda, J.A.; Feye, K.; Park, M.; Khan, S.A. Complete Genome Sequence of Cephalosporin and Tetracycline-Resistant Citrobacter Freundii CF51 Isolate from a Patient with Urinary Tract Infection. Microbiol. Resour. Announc. 2024, 13, e00325-24, doi:10.1128/mra.00325-24.
12. Lee, R.; Choi, S.-M.; Jo, S.J.; Lee, J.; Cho, S.-Y.; Kim, S.-H.; Lee, D.-G.; Jeong, H.-S. Clinical Characteristics and Antimicrobial Susceptibility Trends in Citrobacter Bacteremia: An 11-Year Single-Center Experience. Infect. Chemother. 2019, 51, 1–9, doi:10.3947/ic.2019.51.1.1.
13. Jabeen, I.; Islam, S.; Hassan, A.K.M.I.; Tasnim, Z.; Shuvo, S.R. A Brief Insight into Citrobacter Species – a Growing Threat to Public Health. Front. Antibiot. 2023, 2, 1276982, doi:10.3389/frabi.2023.1276982.
14. Gupta, N.; Yadav, A.; Choudhary, U.; Aropa, D.R. Citrobacter Bacteremia in a Tertiary Care Hospital. Scand. J. Infect. Dis. 2003, 35, 765–768, doi:10.1080/00365540310016376.

About the Author

Dr. Emery Haley is a scientific writing specialist with over ten years of experience in translational cell and molecular biology. As both a former laboratory scientist and an experienced science communicator, Dr. Haley is passionate about making complex research clear, approachable, and relevant. Their work has been published in over 10 papers and focuses on bridging the gap between the lab and real-world patient care to help drive better health outcomes.

Urologists

Primary Care Physicians

Gastroenterologists

Gynecologists

Medical Directors

Post-Acute Care

Healthcare at Home

Urology Clinic

Immediate Care/Urgent Care

Telemedicine

C. freundii

CHECK BACK SOON FOR OUR FULL BLOG ON THE IMPORTANCE OF CITROBACTER FREUNDII

Clinical Summary

Bacterial Characteristics

Gram-stain

Morphology

Growth Requirements

Nitrate Reduction

Urease

Biofilm Formation

Pathogenicity

Clinical Relevance in UTI

Treatment

References

About the Author

Urologists

Primary Care Physicians

Gastroenterologists

Gynecologists

Medical Directors

Post-Acute Care

Healthcare at Home

Urology Clinic

Immediate Care/Urgent Care

Telemedicine

CHECK BACK SOON FOR OUR FULL BLOG ON THE IMPORTANCE OF CITROBACTER FREUNDII

Clinical Summary

Bacterial Characteristics

Gram-stain

Morphology

Growth Requirements

Nitrate Reduction

Urease

Biofilm Formation

Pathogenicity

Clinical Relevance in UTI

Treatment

References

About the Author

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