Diphtheroids are bacteria that visually resemble the organism responsible for diphtheria, but they are generally harmless, non-toxin-producing residents of the human body. These organisms, primarily non-diphtheriae species of the genus Corynebacterium, are common commensals on the skin and mucous membranes. Despite their status as normal flora, they have emerged as significant opportunistic pathogens, especially in clinical settings. Accurate identification and recognition of their potential for causing disease is a growing concern for healthcare.
Defining Diphtheroids
Diphtheroids are Gram-positive bacteria taxonomically part of the genus Corynebacterium. The term is a historical label used to describe species similar in appearance to Corynebacterium diphtheriae, the agent of diphtheria. Unlike their notorious relative, diphtheroids lack the gene required to produce the powerful diphtheria toxin, which causes severe diphtheria symptoms.
These bacteria are described as aerobic, non-spore-forming, and pleomorphic, exhibiting various shapes. Under a microscope, they are Gram-positive rods, often appearing club-shaped or slightly curved, and are frequently found in V-shaped arrangements or stacked like “Chinese letters.” They are natural inhabitants of the human microbiota, commonly found on the skin, in the upper respiratory tract, and on mucosal surfaces.
The distinction between a harmless diphtheroid and the pathogenic C. diphtheriae is based on toxin production, not morphology. Diphtheroid species are generally innocuous in a healthy host. However, their widespread presence means they are often isolated in clinical cultures and must be carefully evaluated to determine if they are a contaminant or the actual cause of an infection.
Laboratory Identification Procedures
The initial step in the laboratory identification of diphtheroids involves the Gram stain, which reveals their characteristic Gram-positive, pleomorphic, rod shape and palisade arrangement. Following this, the bacteria are cultured on standard laboratory media, where they grow well as aerobic or facultatively anaerobic organisms. Traditional microbiology relied on specialized media like tellurite agar and biochemical tests to differentiate between species.
A major challenge in the clinical lab is confirming that an isolate is a non-toxigenic diphtheroid, and not the more dangerous C. diphtheriae. Differentiation often involves a battery of biochemical tests that analyze fermentation patterns and enzymatic activities. For example, potentially toxigenic species like C. diphtheriae and C. ulcerans possess cystinase activity, which helps distinguish them from many diphtheroids.
Modern identification has been streamlined by advanced molecular and proteomic techniques. Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) mass spectrometry is now widely used to identify Corynebacterium species by comparing their unique protein signatures to extensive databases. Furthermore, polymerase chain reaction (PCR) tests specifically search for the absence of the tox gene, definitively confirming the non-toxigenic status of the isolate and determining if it is a contaminant or a true pathogen.
Role as Opportunistic Pathogens
Diphtheroids are increasingly recognized as opportunistic pathogens, primarily causing infections in individuals with compromised immune systems or those with foreign medical devices. These bacteria, which typically live harmlessly on the skin, can gain entry to normally sterile sites when the body’s defenses are weakened or breached. Hospitalized patients, especially those with cancer, HIV, or long-term indwelling catheters, face a higher risk of serious infection.
One of the most concerning infections caused by diphtheroids is endocarditis, particularly in patients with prosthetic heart valves. Species like Corynebacterium jeikeium and Corynebacterium striatum are frequently implicated in these device-related infections. They are also a common cause of bloodstream infections, or sepsis, linked to central venous catheters used for long-term treatment.
Beyond the bloodstream, diphtheroids can cause infections in other sites. For example, Corynebacterium urealyticum causes urinary tract infections, and infections related to orthopedic implants and various wound infections are also common. The ability of many diphtheroid species to form a protective biofilm on medical devices significantly contributes to their persistence.
Management of Diphtheroid Infections
The management of clinically significant diphtheroid infections is complicated by the organisms’ common pattern of intrinsic and acquired antibiotic resistance. Many diphtheroid species are naturally resistant to a range of commonly used antibiotics, including penicillins and cephalosporins. This resistance often stems from the production of enzymes like beta-lactamases, which inactivate these drugs.
Due to the high prevalence of multi-drug resistance, the initial, or empirical, treatment for a suspected serious diphtheroid infection often involves an agent like vancomycin or linezolid. These drugs are typically effective against the most common resistant strains, such as C. striatum and C. amycolatum. However, empirical therapy is quickly followed by antibiotic susceptibility testing, known as an antibiogram, to determine the drug sensitivity of the specific isolate.
The definitive therapy must then be tailored based on the antibiogram results. In cases where the infection is linked to a medical device, such as a catheter or prosthetic valve, antibiotics alone may not be sufficient to clear the infection. The physical removal of the infected foreign material is often necessary to eliminate the source of the bacteria and achieve a successful clinical outcome.