1. Review of Otorrhea Microbiology:
Is there a Pathogenic Role of
Corynebacter?
Matthew G. Crowson, M.D.
OHNS Resident, Duke University Medical Center, Durham, NC
Katherine Callahan
Hamilton College, Clinton, NY
James E. Saunders, M.D.
Section of Otolaryngology, Dartmouth-Hitchcock Medical Center,
Lebanon, NH
3. Introduction
• Corynebacteria spp. commonly found on the skin,
and are biofilm producers on skin and medical
devices5
– Often reported as “Normal Cutaneous Flora”
– Shown to produce toxins such as diphtheria-like toxin,
dermonecrotic toxin, and soluble hemolysin.1
– Have been associated with pharyngitis, cutaneous
infections.2
– Cultured from suppurative otitis media, otitis externa,
myringitis, otitis media with perforation, cholesteatoma,
post-tube otorrhea, and mastoiditis. (Saunders et al. 2010)
• Do non-diptherioid Corynebacteria species play a role
in the pathophysiology of chronic purulent ear
disease?
http://eyemicrobiology.upmc.com/Images/Sub/PhotoGallery/Bacteria/P
hotoDiphGram.jpg
4. Methods
• 140 microbiology cultures from purulent otorrhea in 77 patients
• Microbiology laboratory was asked to speciate Corynebacteria, provide
antibiotic sensitivities
Group ‘A’
Corynebacteria spp. and
all other pathogens
OR
Corynebacteria spp. only
Group ‘B’
All other pathogens
• Pre-culture
• Clinical diagnosis
• Otorrhea, Otalgia
• Hearing loss, hearing aid use
• History of otologic surgery
• Post-culture
• Clinical diagnosis
• Antibiotic requirement, first-line
& second-line antibiotic
• Otologic surgery
5. Results – Species Census
n (%) n (%)
NCF 68 (30.9) Serratia marcescens 4 (1.8)
Staph Aureus spp. (all) 54 (24.5) Stenotrophomonas maltophilia 4 (1.8)
Staph Aureus (MSSA) 26 Alcaligenes 3 (1.4)
Staph Aureus (MRSA) 21 Proteus Penneri 3 (1.4)
Staph Aureus (Coag Negative) 6 Citrobacter koseri 2 (0.9)
Staph (other) 1 Bacteroides Fragilis 1 (0.5)
Corynebacterium spp. 38 (17.3) Brevibacterium 1 (0.5)
Pseudomonas 11(5.0) Burkholderia cepacia 1 (0.5)
Streptococcus (all) 8 (3.6) Enterobacter cloacae 1 (0.5)
Group B Streptoccocus 4 Klebsiella oxytoca 1 (0.5)
Group G Streptoccocus 1 Klebsiella pneumoniae 1 (0.5)
Group A Streptoccocus 1 Klebsiella ornithinolytica 1 (0.5)
Group F Streptococcus 2 Morganella morgagni 1 (0.5)
Achromobacter xylosoxidans 6 (2.7) Providencia rettgeri 1 (0.5)
Turicella 5 (2.3) S. Pneumoniae 1 (0.5)
Acinetobacter lwoffi 4 (1.8) Total number of strains isolated 220
6. Corynebacterium Positive Cultures
• 6 unique patients (8.33%)
produced cultures with
Corynebacterium spp. without
other potential pathogens
present
• Corynebacterium spp. with
cohabitating bacteria identified
in 32 (24.1%) of all cultures in 24
(33.3%) unique patients
n (%)
Staph Aureus Spp. (all) 7 (22)
Staph Aureus (MSSA) 6
Staph Aureus (MRSA) 1
Staph Aureus (Coag Negative) 0
Isolated Corynebacterium Spp. 6 (19)
Acinetobacter lwoffi 2 (6.3)
Streptococcus (all) 2 (6.3)
Group B Streptoccocus 1
Group G Streptoccocus 1
Alcaligenes 1 (3.1)
Citrobacter koseri 1 (3.1)
Klebsiella oxytoca 1 (3.1)
Serratia marcescens 1(3.1)
Stenotrophomonas maltophilia 1 (3.1)
Turicella 1 (3.1)
Pseudomonas 0 (0)
Other (NCF) 16 (50)
7. Diagnoses and Clinical History
n (% of patients)
Diagnoses Corynebacteria-Positive Other Pathogens p-value
Chronic otitis media 8 (33.3) 17 (35.4) 1.00
Chronic granular myringitis 7 (29.2) 4 (9.1) 0.035
Chronic mastoiditis 6 (25.0) 8 (16.7) 0.53
Cholesteatoma 2 (8.3) 3 (6.3) 1.00
Chronic otitis externa 1 (4.2) 11 (22.9) 0.051
Acute mastoiditis 0 (0) 1 (2.1) 1.00
Acute otitis media 0 (0) 3 (6.3) 0.55
Chronic TM perforation 0 (0) 1 (2.1) 1.00
n (% of patients)
Clinical History Corynebacteria-Positive Other Pathogens p-value
Hearing Loss 21 (87.5) 33 (68.8) 0.15
Previous Otologic Surgery 20 (83.3) 32 (66.7) 0.17
Otorrhea 19 (79.2) 41 (85.4) 0.52
Hearing Aid Use 11 (45.8) 9 (18.8) 0.025
Otalgia 1 (4.2) 13 (27.1) 0.026
8. Antibiotic therapy for patients with otologic infections and
Corynebacteria-positive cultures versus other pathogens
100%
46%
8%
46%
94%
44%
9%
47%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Antbiotic Required Topical Monotherapy Oral Monotherapy Combination Therapy
Corynebacteria-positive
Other pathogens
9. Antibiotic susceptibilities of Corynebacteria isolates
58.0% of Corynebacteria isolates were resistant to topical ciprofloxacin compared to
32.0% of non-Corynebacteria species isolates (p = 0.01).
35%
8%
68%
89%
100%
58%
71%
24%
11%
100%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Ciprofloxacin Clindamycin Penicillin Tobramycin Vancomycin Clarithromycin
Susceptible
Resistant
10. Discussion Points
• Corynebacteria spp. were the second most
common pathogenic species identified behind
Staphylococci spp.
• Corynebacteria-positive infections were
associated with:
– Pre-culture diagnosis of chronic granular myringitis
– Hearing aid use prior to presentation
– Less otalgia.
• Majority of patients with Corynebacteria-positive
infections harbored at least one resistant strain
and Corynebacteria isolates were highly resistant
to first-line fluoroquinolone therapy
11. Conclusions
• Cornyebacteria spp. are:
– Common in these otologic infections
– May be the only pathogen
– Often highly resistant to ciprofloxacin ototopical
therapy
• Due to the resistance profile demonstrated in this study
– Culture recalcitrant infections
– Microbiology laboratories should report
Cornyebacteria sensitivities for otologic infections
12. Acknowledgements
• American Otologic Society
• Joan Buchinski, RN – Dartmouth Hitchcock Medical Center
• Canadian Medical Association Librarians
13. References
1. Lipsky B a, Goldberger a C, Tompkins LS, Plorde JJ. Infections caused by nondiphtheria corynebacteria.
Reviews of infectious diseases. 2013;4(6):1220–35.
2. Funke G, Graevenitz A Von. Clinical microbiology of coryneform bacteria. Clinical Microbiology ….
1997;10(1).
3. Otsuka Y, Kawamura Y. Corynebacterium resistens sp. nov., a new multidrug-resistant coryneform
bacterium isolated from human infections. Journal of clinical …. 2005;43(8):3713–3717.
4. Kaźmierczak AK, Szarapińska-Kwaszewska JK, Szewczyk EM. Opportunistic coryneform organisms--
residents of human skin. Polish journal of microbiology / Polskie Towarzystwo Mikrobiologów = The
Polish Society of Microbiologists. 2005;54(1):27–35.
5. Kwaszewska AK, Brewczyńska A, Szewczyk EM. Hydrophobicity and biofilm formation of lipophilic skin
corynebacteria. Polish journal of microbiology / Polskie Towarzystwo Mikrobiologów = The Polish
Society of Microbiologists. 2006;55(3):189–93.
6. Henneveld K, Rosychuk R a W, Olea-Popelka FJ, Hyatt DR, Zabel S. Corynebacterium spp. in dogs and
cats with otitis externa and/or media: a retrospective study. Journal of the American Animal
Hospital Association. 2012;48(5):320–6.
7. Saunders JE, Raju RP, Boone JL, Hales NW, Berryhill WE. Antibiotic resistance and otomycosis in the
draining ear: culture results by diagnosis. American journal of otolaryngology. 2010;32(6):470–6.
8. Saunders J, Raju R. Current bacteriology of suppurative otitis: resistant patterns and outcomes
analysis. Otology & Neurotology, 2009.
9. Simonet M, De Briel D, Boucot I, Minck R, Veron M. Coryneform bacteria isolated from middle ear
fluid. Journal of clinical microbiology. 1993;31(6):1667–8.
Editor's Notes
Non-diphtheroid Corynebacteria spp. have historically been categorized as clinically insignificant normal cutaneous flora. These species live in abundance on human skin and mucosal surfaces, and have been thought to be to only become pathogenic as an opportunist in patients with marked immunosuppression.1 As a result, of this ‘NCF’ categorization Corynebacteria spp. are not routinely speciated or checked for antibiotic sensitivity. However, there is mounting evidence suggesting that the pathogenic potential of non-diphtheroid Corynebacteria spp. may be underestimated.2–4
Clinical Observation
“Normal Cutaneous Flora” as a common result in cultures sourced from the ear
Clinical Question
Do non-diptherioid Corynebacteria species play a role in the pathophysiology of common infectious/inflammatory ear disease?
To help answer the question we speciated NCF to make our series unique.
We intentionally speciated and sensitivities for Coryne
Patients and Cultures– This retrospective study was performed with the approval of the institutional review board at Dartmouth-Hitchcock Medical Center (DHMC). The study population consisted of 140 microbiology bacterial cultures taken from the ears of 77 unique adult and pediatric patients collected at DHMC between November 2010 and October 2012. These cultures were acquired from patients presenting with otorrhea and clinical suspicion of acute and/or chronic otologic infection. Seven (7) cultures and 5 patients were excluded from subsequent analysis due to cultures taken from post-operative wound infections. The DHMC microbiology laboratory was requisitioned to determine speciation of Corynebacterium species, in addition to all routine bacterial and fungal pathogens. Standard antibiotic resistance assays were requested of all pathogens and Corynebacterium species as appropriate. We performed a retrospective review of the demographics, symptomology, and therapeutic management of the infections. Information extracted from the medical records of the patients included age, gender, indication and location of ear culture (left or right), pre-culture clinical diagnosis, presence of otorrhea (yes/no), otalgia (yes/no), pre-culture hearing loss (yes or no), pre-culture hearing aid use (yes or no), previous otologic surgery (yes or no), previous otologic surgery procedure type, post-culture clinical diagnosis, post-culture antibiotic requirement (yes or no), post-culture first-line antibiotic type, post-culture second-line antibiotic type (if necessary), post-culture otologic surgery procedure (yes or no), and post-culture otologic surgery type. The symptom, diagnoses, and surgical or medical management frequencies were tabulated for all unique patients. In the event that patients had multiple cultures over a period of time, a unifying diagnosis was determined through review of consecutive records.
Microbiological Cultures – Cultures from the external auditory canal, tympanic membrane, middle ear space, and/or mastoid cavities were obtained in the appropriate fashion for suspected infections using a Calgi® micorswab or aspirate technique. Care was taken not to touch the surrounding ear canal to avoid skin contaminants. Information extracted from the microbiology laboratory reports included gram stain morphology and result, bacteria speciation, fungal speciation, and antibiotic susceptibility interpretation and minimal inhibitory concentration (MIC) values. In absence of formal susceptibility interpretation for tobramycin, we cross-referenced the laboratory MIC (mcg/mL) values with published resistance thresholds of ≤4, 8, ≥16 classified as susceptible (S), intermediate (I), and resistant (R) respectively.
Statistical Analysis – For the purposes of statistical analyses, two comparison groups were formed according to bacterial species identified in the culture samples. The first group contained all unique patients who had either a Corynebacterium positive culture at time of culture, or any history of Corynebacterium positive culture if multiple cultures were obtained in a unique patient during the study period. The second group contained all unique patients with cultures positive for pathogens other than Corynebacterium. Both culture groups contained co-habitating pathogenic and non-pathogenic flora (i.e. normal cutaneous flora). Bivariate analyses were completed using the GraphPad Software (La Jolla, CA) Quick Calculations Toolset. Two-by-two contingency tables were created, and two-tailed Fisher’s Exact Tests were performed on all symptom, medical management, and surgical management frequency sets between the Corynebacterium positive cohort versus the other pathogen cohort. P-values were reported, with statistical significance fixed at p <0.05.
We had asked our laboatory to specifically speciate Corynebacterium, so we still have NCF. Corynebacterium were the second most common species behind Staph and ahead of Pseudomonas.
A total of 119 (89.5%) of cultures had at least one identifiable bacteria species, and 15 (11.3%) cultures had an identifiable fungal species. A total of 220 bacterial strains were identified across all cultures (Table 1). Corynebacterium spp. with co-habitating pathogens and flora were identified in 32 (24.1%) of all cultures in 24 (33.3%) unique patients with otologic infections
Corynebacterium positive cultures and speciated pathogens
Figure 1. Antibiotic therapy strategy employed for patients presenting with otologic infections and cultures with either Corynebacteria-positive cultures or other pathogens.
The agents used for oral therapy appropriately varied depending on reported antibiotic susceptibility of the pathogen. There was no significant difference when comparing the frequency of post-culture antibiotic use versus no antibiotic use in patients with Corynebacteria-positive cultures or patients with other pathogens (p = 0.5461). There was no significant difference between patients with Corynebacteria-positive cultures or patients with other pathogens when comparing the frequency of use of monotherapy topical agents, monotherapy oral agent, or combination oral with topical antibiotic therapy (p values = 1.000).
Figure 2. Antibiotic susceptibilities of 28 Corynebacteria isolates found in 20 unique patients.
28 specific Corynebacteria isolate species in 20 unique patients were subjected to standard antibiotic susceptibility assays
34.0% were resistant to at least one topical antibiotic (Ciprofloxacin/Dexamethasone, and/or Tobramycin)
48.0% had resistance to at least one oral antibiotic (clindamycin, penicillin, vancomycin, and/or clarithromycin)
Directly comparing specific antibacterial agent susceptibilities Corynebacteria isolates to the other bacterial species:
58.0% of Corynebacteria isolates were resistant to topical ciprofloxacin compared to 32.0% of non-Corynebacteria species isolates (p = 0.01).
No significant difference between Corynebacteria and non-Corynebacteria species with respect to topical tobramycin resistance or sensitivity status (p > 0.05).
Cipro – among the most, if not *the* most commonly used first-line agent for these infections
Saunders Conclusions:
1) We don’t routinely speciate, report or do sensitivities
2) Corny is a common bacteria in these infections
3) Coryne may be the only pathogen
4) Coryne is often resistant to cipro gtts
So the take home would be
1) Culture recalcitrant infections
2) ask your lab to coryne sensitivities NOT just another innocent bystander amongst the NCF
I’d like to thank my co-author Katherine Callahan for their work on this study, in particular, Dr. Saunders for his mentorship.
