Dogs, dirty mouths, cancer, and booze: What you need to know about Capnocytophaga

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There are multiple associations in medicine where the mere mention of a location, occupation, or risk factor elicits a response with regards to the disease. In infectious disease, there are multiple such as “spelunking” being associated with histoplasmosis, IV drug abuser associated with MRSA endocarditis, or cows placentas being associated with Q fever. When it comes to animal-related infections, Bartonella and Pasteurella tend to be grouped as those infections that are associated with domestic animals, namely dogs and cats. Another interesting one is capnocytophaga, which has been traditionally identified as a cause of severe septic shock after interaction with dogs. This will be a short and sweet post, as there is little robust therapy when it comes to infection with these organisms.

Characteristics

Capnocytophaga is a gram-negative bacteria and as a genus, consist of 8 different species (1). Of importance, C. canimorsus and C. cynodegmi are associated with animal bites, while C. ochracea and C. granulosa are found in subgingival plaque. As such, several strains of Capnocytophaga tend to be commensal organisms and part of the oral microbiome and may have a role in diseases such as gingivitis, periodontal disease, and oropharyngeal mucositis (2,3). These guys tend to be considered fastidious organisms because they grow slowly in blood-enriched media and require increased carbon dioxide (1). The time frame for growth in blood cultures tends to vary, with one report of C. canimorsus finding that time to positivity ranged from 2-7 days (4), with 2 case reports identifying the organism after 6 and 8 days of incubation. (5, 6), however it can take as long as 25 days prior to identification (7). In some instances, the organism can be misidentified as other gram negative rods such as V. vulnificus (8), with another cohort finding that 55% of strains were reported as an unidentified gram negative rod (14). The organism has been isolated from blood, CSF, heart valves, wounds, a cornea and an adrenal gland (9). While not terribly important, some biochemical test differ between human and animal strains, with human strains being catalase and oxidase negative and animal strains being positive on both:

Gram stains reveal the organism is slender, medium to long, and have tapered ends which may tip you off :

These are “fusiforms’ ‘ meaning they have a spidle-like shape. Another similar one is fusibacterium.

Disease and Risk Factors

Given their usual environment, these organisms tend to not be terribly pathogenic. Indeed, the usual patient is someone who is older (usually greater than 40), and is in some way, immunocompromised (usually alcoholism and leukemia). Patients who have an underlying malignancy tend to be infected with human-oral strains while others tend to have animal-associated strains. One retrospective cohort study evaluated 39 cases of C. canimorsus septicemia (10). Mean age of cases was 59.1, and male to female ratio was 2.9:1. Within this cohort, 4 had prior splenectomy, 7 had alcoholism, 8 had CAD, and 3 had hypertension. 22 had reported prior contact with a dog, with 17 suffering from  a dog bite prior to presentation. Incubation ranged from 1 to 8 days, with the most common symptoms reported being fevers and chills:

14 had meningitis and 6 of those who died were found to have DIC. A 32-year cohort of 56 patients found that the majority of cases occurred in older patients (70% were over the age of 50) and were mostly in males (57%; 14). Only 3 were found to have functional asplenia and 27 had a dog bite:

Another case series of 10 patients with capnocytophaga spp found that 8 of them developed septic shock in the setting of mucositis or candida (11). 2 had empyema due to Capnocytophaga with concomitant oral streptococci being isolated in the setting of an esophageal lesion and mucositis. Median time to isolate here was 7 days. Notably, all of these had either cirrhosis or a malignancy. Similarly, in another cohort of 24 patients (12) who had severe chemotherapy-induced neutropenia, Capnocytophaga was isolated as their cause of bacteremia. 22 of the 25 were found to have severe oral mucositis. Similarly, another cohort of 28 patients who were found to have Capnocytophaga bacteremia (mostly human strains) all had hematological malignancies (13). 

The largest cohort evaluated 82 patients from 3 centers, with 96% requiring hospitalization and 29% being admitted to the ICU (15). Of these, 46 had bacteremia, with most of the human-oral associated capnocytophaga bacteremia being associated with HSCT, neutropenia, active immunosuppression compared to the C. canimorsus group:

In those who did not have bacteremia, 47% actually had head and neck infections. Besides cellulitis and bacteremia, infective endocarditis, empyema, osteomyelitis, and meningitis have also been reported (1). In certain cases, bacteremia cases have been complicated by DIC and TTP, especially in those with anatomical and functional asplenia (5, 6). Interestingly, in these cases, the presenting symptom was either headaches or severe abdominal pain, with one instance leading to an exploratory laparotomy. 

Treatment

There is no standardized therapy in terms of type of antibiotic, route, or duration, as there is little robust data on this and most of it comes from case series. Despite this, some reviews have looked at susceptibility patterns, though it should be noted there are no CLSI or EUCAST standards out there (16). The active antibiotics tend to be clindamycin, tetracyclines, linezolid, beta-lactam/beta-lactamase inhibitor combinations and imipenem (17). For instance, in one cohort of 10 patients, resistance to MTZ, aminoglycosides, and glycopeptides was seen (11):

In another cohort, amikacin and ciprofloxacin accounted for most resistances, with one isolate being resistant to penicillins, though not to amox-clav (13). 

Older studies have reported fairly consistent susceptibility to beta-lactams (18), however capnocytophaga strains that produce beta-lactamases have been reported. In one cohort, 8 strains were found to produce beta-lactamases that conferred resistance to broad-spectrum beta-lactams (12):

As seen above, however, the presence of a BLI restores the susceptibility for beta-lactams. In a larger cohort (19), similar findings were reported, with piperacillin-tazobactam  and amox-clav having adequate susceptibility:

Further, imipenem was also fairly susceptible, though the three cephalosporins had high MICs. While there is no standard of treatment, bacteremias tend to get pip-tazo or other BL/BLI combination upfront. Mendel and UpToDate suggest this or a carbapenem, with PO amox-clav being a reasonable option for less severe disease. While there is no duration of therapy stated in any source, I think a relatively short course (7 days, though I think one could argue given how little data there is, it would be unreasonable to treat it as any other gram negative) even for bacteremia would be fine as long as there is no metastatic focus or other disease. 

References:

  1. [edited by] John E. Bennett, Raphael Dolin, Martin J. Blaser. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. Philadelphia, PA :Elsevier/Saunders, 2015.
  2. Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, Lakshmanan A, Wade WG. The human oral microbiome. J Bacteriol. 2010 Oct;192(19):5002-17. doi: 10.1128/JB.00542-10. Epub 2010 Jul 23. PMID: 20656903; PMCID: PMC2944498.
  3. Curtis MA, Zenobia C, Darveau RP. The relationship of the oral microbiotia to periodontal health and disease. Cell Host Microbe. 2011;10(4):302-306. doi:10.1016/j.chom.2011.09.008
  4. Le Moal G, Landron C, Grollier G, Robert R, Burucoa C. Meningitis due to Capnocytophaga canimorsus after receipt of a dog bite: case report and review of the literature. Clin Infect Dis. 2003 Feb 1;36(3):e42-6. doi: 10.1086/345477. Epub 2003 Jan 13. PMID: 12539089.
  5. Christiansen CB, Berg RM, Plovsing RR, Møller K. Two cases of infectious purpura fulminans and septic shock caused by Capnocytophaga canimorsus transmitted from dogs. Scand J Infect Dis. 2012 Aug;44(8):635-9. doi: 10.3109/00365548.2012.672765. Epub 2012 Apr 12. PMID: 22497463.
  6. Brichacek M, Blake P, Kao R. Capnocytophaga canimorsus infection presenting with complete splenic infarction and thrombotic thrombocytopenic purpura: a case report. BMC Res Notes. 2012 Dec 26;5:695. doi: 10.1186/1756-0500-5-695. PMID: 23267527; PMCID: PMC3583747.
  7. Coutance G, Labombarda F, Pellissier A, et al. Capnocytophaga canimorsus endocarditis with root abscess in a patient with a bicuspid aortic valve. Heart Int. 2009;4(1):e5. doi:10.4081/hi.2009.e5
  8. Hazırolan G. Capnocytophaga sputigena: A rarely encountered gram-negative bacterium in microbiology laboratories. J Infect Public Health. 2021 May;14(5):683-684. doi: 10.1016/j.jiph.2020.09.021. Epub 2020 Nov 26. PMID: 33250368.
  9. Brenner DJ, Hollis DG, Fanning GR, Weaver RE. Capnocytophaga canimorsus sp. nov. (formerly CDC group DF-2), a cause of septicemia following dog bite, and C. cynodegmi sp. nov., a cause of localized wound infection following dog bite. J Clin Microbiol. 1989 Feb;27(2):231-5. doi: 10.1128/jcm.27.2.231-235.1989. PMID: 2915017; PMCID: PMC267282.
  10. Pers C, Gahrn-Hansen B, Frederiksen W. Capnocytophaga canimorsus septicemia in Denmark, 1982-1995: review of 39 cases. Clin Infect Dis. 1996 Jul;23(1):71-5. doi: 10.1093/clinids/23.1.71. PMID: 8816132.
  11. Bonatti H, Rossboth DW, Nachbaur D, Fille M, Aspöck C, Hend I, Hourmont K, White L, Malnick H, Allerberger FJ. A series of infections due to Capnocytophaga spp in immunosuppressed and immunocompetent patients. Clin Microbiol Infect. 2003 May;9(5):380-7. doi: 10.1046/j.1469-0691.2003.00538.x. PMID: 12848750.
  12. Maury S, Leblanc T, Rousselot P, Legrand P, Arlet G, Cordonnier C. Bacteremia due to Capnocytophaga species in patients with neutropenia: high frequency of beta-lactamase-producing strains. Clin Infect Dis. 1999 May;28(5):1172-4. doi: 10.1086/517772. PMID: 10452663.
  13. Martino R, Rámila E, Capdevila JA, Planes A, Rovira M, Ortega Md, Plumé G, Gómez L, Sierra J. Bacteremia caused by Capnocytophaga species in patients with neutropenia and cancer: results of a multicenter study. Clin Infect Dis. 2001 Aug 15;33(4):E20-2. doi: 10.1086/322649. Epub 2001 Jul 20. PMID: 11462207.
  14. Janda JM, Graves MH, Lindquist D, Probert WS. Diagnosing Capnocytophaga canimorsus infections. Emerg Infect Dis. 2006 Feb;12(2):340-2. doi: 10.3201/eid1202.050783. PMID: 16494769; PMCID: PMC3373098.
  15. Chesdachai S, Tai DBG, Yetmar ZA, Misra A, Ough N, Abu Saleh O. The Characteristics of Capnocytophaga Infection: 10 Years of Experience. Open Forum Infect Dis. 2021 Apr 15;8(7):ofab175. doi: 10.1093/ofid/ofab175. PMID: 34327254; PMCID: PMC8314946.
  16. Mendes FR, Bruniera FR, Schmidt J, et al. Capnocytophaga sputigena bloodstream infection in hematopoietic stem cell transplantations: two cases report and review of the literature. Rev Inst Med Trop Sao Paulo. 2020;62:e48. doi:10.1590/s1678-9946202062048
  17. Jolivet-Gougeon A, Sixou JL, Tamanai-Shacoori Z, Bonnaure-Mallet M. Antimicrobial treatment of Capnocytophaga infections. Int J Antimicrob Agents. 2007 Apr;29(4):367-73. doi: 10.1016/j.ijantimicag.2006.10.005. Epub 2007 Jan 23. PMID: 17250994.
  18. Arlet G, Sanson-Le Pors MJ, Casin IM, Ortenberg M, Perol Y. In vitro susceptibility of 96 Capnocytophaga strains, including a beta-lactamase producer, to new beta-lactam antibiotics and six quinolones. Antimicrob Agents Chemother. 1987 Aug;31(8):1283-4. doi: 10.1128/AAC.31.8.1283. PMID: 3498438; PMCID: PMC174921.
  19. Arlet G, Sanson-Le Pors MJ, Casin IM, Ortenberg M, Perol Y. In vitro susceptibility of 96 Capnocytophaga strains, including a beta-lactamase producer, to new beta-lactam antibiotics and six quinolones. Antimicrob Agents Chemother. 1987 Aug;31(8):1283-4. doi: 10.1128/AAC.31.8.1283. PMID: 3498438; PMCID: PMC174921.

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