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CITROBACTER SPP.

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Citrobacter spp.

SYNONYM OR CROSS REFERENCE: Citrobacter amalonaticus, Citrobacter braakii, Citrobacter farmeri, Citrobacter freundii, Citrobacter koseri, Citrobacter sedlakii, Citrobacter werkmanii, Citrobacter Youngae, Ballerup group, Bethesda group, Bethesda-Ballerup group Footnote 1, Footnote 2.

CHARACTERISTICS: Citrobacter spp., of the Enterobacteriaceae family, are gram-negative, facultative anaerobic bacteria that appear as rods or coccobacilli at 0.3-1 µm in diameter and 0.6-6 µm long Footnote 3. Citrobacter spp. are motile using their peritrichous flagella Footnote 1, Footnote 2. They ferment mannitol with production of gaseous H2S, and they can also use citrate as sole carbon source Footnote 2, Footnote 4. The genus can be divided in 43 O-serogroups, based on the O antigen of the lipopolysaccharide (LPS) and in 20 chemogroup, based on the sugar composition of the LPS.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Citrobacter are rare opportunistic nosocomial pathogens Footnote 5. Citrobacter normally cause urinary tract infections, blood stream infections, intra abdominal sepsis, brain abscesses, and pneumonia and other neonatal infection Footnote 6, such as meningitis, neonatal sepsis, joint infection or general bacteremia Footnote 7. CNS infections are more common for infants under 2 months old than for older children or immunocompromised adult patients, but rare cases have been reported. C. koseri and C. ferundii cause neonatal meningitis that can lead to brain abscesses Footnote 1, Footnote 5. Citrobacter infections can be fatal, with 33-48 % overall death rates, and 30% for neonates Footnote 6, Footnote 7. Infant survivors may experience significant damage to CNS, including profound retardation, hemiparesis, seizures, etc.

EPIDEMIOLOGY: Citrobacter is of worldwide prevalence as it is a component of normal intestinal flora Footnote 1, Footnote 5. Neonates (particularly those who are premature) and immunocompromised, elderly or debilitated patients are at increased risk of infection Footnote 4, Footnote 7.

INFECTIOUS DOSE: Approximately 10 7 CFU/mL Footnote 8.

HOST RANGE: Hosts include human and animals and aquatic organisms (catfish) Footnote 2, Footnote 9, Footnote 10.

MODE OF TRANSMISSION: Citrobacter may be spread by direct contact with hospital staff members, mother to child transmission or through ingestion of environmental sources (fecal-oral route) but person-to-person transmission is more prevalent Footnote 7, Footnote 11. Parsley contaminated with Citrobacter contained in swine manure has caused an outbreak of Citrobacter in Canada Footnote 11. The outbreak caused 8 urinary tract infection, and 1 death.

INCUBATION PERIOD: In neonates disease can develop within a few hours of birth to 42 days after delivery Footnote 7.

COMMUNICABILITY: Human-to-human transmission is possible; however, the infectious period is unknown.

SECTION III - DISSEMINATION

RESERVOIR: Human and animal intestines, soil, water, sewage and food Footnote 7.

ZOONOSIS: None.

VECTORS: None.

SECTION IV - STABILITY AND VIABILITY

DRUG SUCEPTIBILITY: Citrobacter spp. are susceptible to aminoglycosides, chloramphenicol, imipenim/cilastatin, trimetoprim, and trimetoprim/sulfamethazole Footnote 7.

DRUG RESISTANCE: Resistance has been shown against cephalosporins, ceftazidime , piperacillintazobactam, antipseudomona penicillins Footnote 13, ampicillin Footnote 7, cephalothin Footnote 3, and carbenicillin.

SUCEPTIBILITY TO DISINFECTANTS: Phenolic disinfectants, 1% sodium hypochlorite, 70% ethanol, formaldehyde, glutaraldehyde, iodophore and paracetic acid are effective against Citrobacter Footnote 14. Ethanol (0.41M) Footnote 15, chlorhexidine detergent scrub Footnote 16, hexachlorophene or iodophor preparations Footnote 17 and bleach Footnote 16 may also be effective.

PHYSICAL INACTIVATION: 90% of the Citrobacter organisms may be killed after 15 minutes at 230 MPa Footnote 18. Citrobacter are also inactivated by UV, microwave, gamma radiation, moist heat (121°C for at least 20 min) and dry heat (165-170°C for 2 h) Footnote 19-Footnote 22.

SURVIVAL OUTSIDE HOST: Soil and water Footnote 7.

SECTION V – FIRST AID / MEDICAL

SURVELLENCE: Monitor for symptoms. Citrobacter can be detected by serological methods, molecular methods, or polymerase chain reaction (PCR) generated DNA finger prints from mother to child Footnote 1. Infection can also be confirmed by other bacteriological and serological means Footnote 3.

FIRST AID TREATMENT: Administer appropriate drug therapy.

IMMUNIZATION: None available.

PROPHYLAXIS: Prophylaxis consists of antibiotics such as amoxicillin and a beta-lactamase inhibitor Footnote 23, Footnote 24.

SECTION VI - LABORATORY HAZARDS

LABORATORY ACQUIRED INFECTIONS: None reported to date.

SOURCES / SPECIMENS: Human feces Footnote 1, brain abscesses Footnote 7, cerebral fluids Footnote 25, laboratory mice Footnote 26, eye, urine, intestines, umbilicus, skins pustules, hands Footnote 7, environmental sources (soil, water) Footnote 24.

PRIMARY HAZARD: Workers must pay attention to ingestion and accidental parenteral inoculation Footnote 11.

SPECIAL HAZARD: None.

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 2 Footnote 27.

CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures.

PROTECTIVE CLOTHING: Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to splashes Footnote 17.

OTHER PRECAUTIONS: All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC). The use of needles, syringes, and other sharp objects should be strictly limited. Additional precautions should be considered with work involving animals or large scale activities Footnote 17.

SECTION VIII – HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up.

DISPOSAL: Decontaminate all wastes that contain or have come in contact with the infectious organism before disposing by autoclave, chemical disinfection, gamma irradiation, or incineration.

STORAGE: The infectious agent should be stored in leak-proof containers that are appropriately labelled.

SECTION IX - REGULATORY AND OTHER INFORMATION

REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

UPDATED: December 2011

PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada

Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright ©
Public Health Agency of Canada, 2011
Canada

REFERENCES:

Footnote 1
Holmes, B., & Aucken, H. M. (1998). Citrobacter, Enterobacter, Klebsiella, Serratia and other members of the Enterobacteriaceae. In L. Collier, A. Balows & M. Sussman (Eds.), Microbiology and Microbial infections: Systematic Bacteriology (9th ed., pp. 999-1033). London: Arnold.

Footnote 2
Knirel, Y. A., Kocharova, N. A., Bystrova, O. V., Katzenellenbogen, E., & Gamian, A. (2002). Structures and serology of the O-specific polysaccharides of bacteria of the genus Citrobacter. Archivum Immunologiae Et Therapiae Experimentalis, 50, 379-391.

Footnote 3
Abbott, S. L. (2007). Klebsiella, Enterobacter, Citrobacter, Serratia, Plesiomonas, and Other Enterobacteriaceae. In P. R. Murray, E. J. Baron, J. H. Jorgensen, M. A. Pfaller & M. L. Landry (Eds.), Manual of Clinical Microbiology (9 th ed., pp. 698-715). Washington, DC: ASM press.

Footnote 4
Chen, Y. S., Wong, W. W., Fung, C. P., Yu, K. W., & Liu, C. Y. (2002). Clinical features and antimicrobial susceptibility trends in Citrobacter freundii bacteremia. Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi, 35(2), 109-114.

Footnote 5
Ryan, K. J. (2004). Enterobacteriaceae. In K. J. Ryan, & C. G. Ray (Eds.), Sherris Medical Microbiology: An Introduction to Infectious diseases (4th ed., pp. 343-371). USA: McGraw-Hill,.

Footnote 6
Pepperell, C., Kus, J. V., Gardam, M. A., Humar, A., & Burrows, L. L. (2002). Low-Virulence Citrobacter Species Encode Resistance to Multiple Antimicrobials. Antimicrob. Agents Chemother., Nov.,46(11), 3555-3560.

Footnote 7
Doran, T. I. (1999). The role of Citrobacter in clinical disease of children: Review. Clinical Infectious Diseases, 28(2), 384-394.

Footnote 8
Tennant, S. M., Hartland, E. L., Phumoonna, T., Lyras, D., Rood, J. I., Robins-Browne, R. M., & Van Driel, I. R. (2008). Influence of Gastric Acid on Susceptibility to Infection with Ingested Bacterial Pathogens. Infect. Immun., Feb, 76(2), 639-645.

Footnote 9
MacDonald, T. T., Frankel, G., Dougan, G., Goncalves, N. S., & Simmons, C. (2003). Host defences to Citrobacter rodentium. International Journal of Medical Microbiology, 293(1), 87-93.

Footnote 10
Nawaz, M. (2008). Isolation and characterization of tetracycline-resistant Citrobacter spp. from catfish. Food Microbiol., 25(1), 85-91.

Footnote 11
Tschape, H., Prager, R., Streckel, W., Fruth, A., Tietze, E., & Bohme, G. (1995). Verotoxinogenic Citrobacter freundii associated with severe gastroenteritis and cases of haemolytic uraemic syndrome in a nursery school: green butter as the infection source. Epidemiology and Infection, 114(3), 441-450.

Footnote 12
Badger, J. L., Stins, M. F., & Kim, K. S. (1999). Citrobacter freundii invades and replicates in human brain microvascular endothelial cells. Infection and Immunity, 67(8), 4208-4215.

Footnote 13
Lavigne, J. P., Defez, C., Bouziges, N., Mahamat, S., & Sotto, A. (2007). Clinical and molecular epidemiology of multidrug-resistant Citrobacter spp. infections in a French university hospital. Eur J Clin Microbiol Infect Dis, 26, 439-441.

Footnote 14
Collins, C. H., & Kennedy, D. A. (1999). Decontamination. Laboratory-Acquired Infections: History, Incidence, Causes and Prevention. (4th ed., pp. 160-186). London, UK: Buttersworth.

Footnote 15
Ojajärvi, J. (1980). Effectiveness of hand washing and disinfection methods in removing transient bacteria after patient nursing. J Hyg (Lond)., 85(2), 193-203.

Footnote 16
Rutala, W., & Weber, D. (1997). Uses of inorganic hypochlorite (bleach) in health-care facilities. Clinical Microbiology Reviews, 10(4), 597-610.

Footnote 17
Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.

Footnote 18
Erkmen, O., & Doǧan, C. (2004). Kinetic analysis of Escherichia coli inactivation by high hydrostatic pressure in broth and foods. Food Microbiology, 21(2), 181-185.

Footnote 19
Katara, G., Hemvani, N., Chitnis, S., Chitnis, V., & Chitnis, D. S. (2008). Surface disinfection by exposure to germicidal UV light. Indian Journal of Medical Microbiology, 26(3), 241-242.

Footnote 20
Wu, Y., & Yao, M.Inactivation of bacteria and fungus aerosols using microwave irradiation. Journal of Aerosol Science, In Press, Corrected Proof doi:DOI: 10.1016/j.jaerosci.2010.04.004

Footnote 21
Farkas, J. (1998). Irradiation as a method for decontaminating food. A review. International Journal of Food Microbiology, 44(3), 189-204.

Footnote 22
Csucos, M., & Csucos, C. (1999). Microbiological obseration of water and wastewater. United States: CRC Press.

Footnote 23
M. G. MORGAN, C. STUART, A. T. LEANORD, M. ENRIGHT, & G. F. COLE. (1992). Citrobacter diversus brain abscess: case reports and molecular epidemiology. J. Med. Microbiol., 36, 273-278.

Footnote 24
Ferrer, F. A., Herndon, C. D., & McKenna, P. H. (1999). Citrobacter diversus urosepsis and cerebral abscess in a child with antenatal hydronephrosis. Urology, 54(6), 1097.

Footnote 25
Murray, P. R., Homes, B., & Aucken, H. M. (2005). Citrobacter, Enterobacter, Kelbsiella, Plesiomonas, Serratia, and other members of the Enterobacteriaceae. In S. P. Borriello, P. R. Murray & G. Funke (Eds.), Topley & Wilson's Microbiology & Microbial Infections (10th ed., pp. 1474-1506). Washington, DC, USA: Edward Arnold (Publishers) Ltd.

Footnote 26
Higgins, L. M., Frankel, G., Douce, G., Dougan, G., & MacDonald, T. T. (1999). Citrobacter rodentium infection in mice elicits a mucosal Th1 cytokine response and lesions similar to those in murine inflammatory bowel disease. Infection and Immunity, 67(6), 3031-3039.

Footnote 27
Human Pathogens and Toxins Act. S.C. 2009, c. 24. Government of Canada, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009, (2009).