Corynebacterium Infections Workup

Updated: Feb 18, 2022
  • Author: Lynda A Frassetto, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Laboratory Studies

C diphtheriae

Obtain clinical specimens and information regarding the patient's contacts.

Obtain a CBC count and urinalysis because patients often have a moderate elevation in leukocytes and may have mild proteinuria (1+ to 2+ by dipstick).

In the past, C diphtheriae grew on a nutritionally inadequate medium devised by Friedrich Loeffler; the diphtheria organisms initially outgrew the other throat flora. With the Loeffler stain, the bacteria show metachromatic granules and a palisading morphology said to resemble Chinese characters.

Today, diagnoses of C diphtheriae infection can be confirmed definitively by culture on blood agar or selective tellurite media, which inhibits the growth of normal oral flora; C diphtheriae develops a black colony with a characteristic gray-brown halo. Potentially toxigenic species (eg, C diphtheriae, C ulcerans, C pseudotuberculosis) have cystinase but not pyrazinamidase activity.

Traditionally, toxin production was demonstrated by injecting toxin material into guinea pigs and watching to see if they died. The Elek plate test for biologic activity of the toxin, an immunoprecipitation test, was developed in 1949 and replaced the in vivo guinea pig test. Even though the test was recently modified and standardized, interpretation can be difficult.

Other recent tests for toxigenicity include PCR detection of the A and B subunits of the tox gene, PCR detection of the A fragment of the toxin, and rapid enzyme immunoassay using a monoclonal antibody to the A fragment. However, some studies identify bacterial isolates that contain the A fragment of the toxin, which is not biologically active. Reports from Russia and Ukraine suggest that the number of these false-positive results is increasing.

The modified Elek tests take 24 hours to 48 hours for results; PCR detection and the enzyme immunoassay test reportedly yield results within a few hours.

Epidemiologic studies have also used typing of ribosomal bacterial RNA to detect and type strains of pathogenic corynebacteria. [48]


In the past, diphtheroid species were identified by culture. A wide variety of colony types may be observed. Many require special media to grow (eg, sheep's blood agar, Loeffler or tellurite plates) and some grow quite slowly. The colony types also have a range of biochemical characteristics, making identification difficult. For this reason, clinical suspicion of diphtheroid infection requires communication with the microbiology laboratory so that the appropriate cultures can be processed. More recently, 16S ribosomal ribonucleic acid (rRNA) probes have been designed for the identification of both genus and species of corynebacteria.  A minireview by Bernard (2012)  [22]  also discusses more recent laboratory techniques for speciation, such as matrix-assisted laser desoprtoin ionization - time of flight (AMLDI-TOF), where bacterial proteins are liberated from the cell, ionized, detected by mass spectrometry, and the resulting pattern compared to a bacterial protein database. 

As mentioned above, toxigenic strains of C ulcerans and C pseudotuberculosis are reported. Therefore, consider testing for toxin production.

Cerebrospinal fluid (CSF) abnormalities include pleocytosis and elevated protein levels; the degree of inflammation in the CSF does not appear to correlate with the degree of neurologic dysfunction.

Several systems for isolating and detecting specific bacterial proteins may be useful for identifying corynebacterium species. [49] A multiplex PCR system for C diphtheriae, C ulcerans, and C pseudotuberculosis has been reported; it can simultaneously identify and determine the toxigenicity of these corynebacterial species with zoonotic potential. [50, 51]


Other Tests


ECG changes include conduction abnormalities and repolarization changes. As many as 30% of patients with respiratory tract diphtheria demonstrate abnormal ECG results within a week to 10 days of developing respiratory symptoms.

Patients who develop clinical or ECG changes associated with cardiac disease have a mortality rate that is three times to four times higher than patients with normal ECG results.


At autopsy, the heart is pale brown, soft, and enlarged, with a characteristic streaky appearance.

Neutral fat accumulations are observed in approximately 50% of patients, with extensive hyaline degeneration and necrosis with inflammatory changes.

Electron microscopy demonstrates swollen disorganized mitochondria that contain dense osmophilic granules.

The coronary vessels, valves, endocardial surfaces, and epicardial surfaces are unaffected.

Microscopic examination of the affected nerves shows myelin sheath and axon degeneration. In particular, the large myelinated fibers are affected, demonstrating characteristic segmental demyelination.

In fatal cases, the kidneys demonstrate interstitial edema and necrosis at autopsy.