Corynebacterium infections
Approximately 20 years ago, taxonomic changes were made to diverse genera previously included within the coryneform groups. The reclassification is based on the degree of homology of RNA oligonucleotides between groups. Based on this reclassification, for example, Corynebacterium haemolyticum became Arcanobacterium haemolyticum and JK group became Corynebacterium jeikeium (Coyle, 1990).
Prior to the 1990s, the incidence of diphtheria had been declining. However, cases of epidemic diphtheria in the former Soviet Union have been recently reported. The more common scenario today is bacteremia with nondiphtherial corynebacteria associated with device infections (venous access catheters, heart valves, neurosurgical shunts, peritoneal catheters), as well as meningitis, septic arthritis, and urinary tract infections.
Types:
C diphtheriae
C diphtheriae infection is classically characterized by a local inflammation, usually in the upper respiratory tract, associated with toxin-mediated cardiac and neural disease. Three strains of C diphtheriae are recognized, in decreasing order of virulence: gravis, intermedius, and mitis. These strains all produce an identical toxin, but the gravis strain is potentially more virulent because it grows faster and depletes the local iron supply, allowing for earlier and greater toxin production. Toxin production is encoded on the tox gene, which, in turn, is carried on a lysogenic beta phage. When DNA of the phage integrates into the host bacteria's genetic material, the bacteria develop the capacity to produce this polypeptide toxin.
The toxin is a single polypeptide with an active (A) domain, a binding (B) domain, and a hydrophobic segment known as the T domain, which helps release the active part of the polypeptide into the cytoplasm. In the cytosol, the A domain catalyzes the transfer of an adenosine diphosphate-ribose molecule to one of the elongation factors (eg elongation factor 2 [EF2]) responsible for protein synthesis. This transfer inactivates the factor, thereby inhibiting cellular protein synthesis. Inhibiting all the protein synthesis in the cell causes the cell death.
In this manner, the toxin is responsible for many of the clinical manifestations of the disease. As little as 0.1 µg can cause death in guinea pigs. In 1890, von Behring and Kitasato demonstrated that sublethal doses of the toxin induced neutralizing antibodies against the toxin in horses. In turn, this antiserum passively protected the animals against death following challenge infection
corynebacteria ( diphtheroids)
Nondiphtherial corynebacteria are ubiquitous in nature and commonly colonize human skin and mucous membranes. Only recently has the role of these organisms in human infections been appreciated. In fact, many of these organisms cannot be speciated or typed easily, even in research laboratories, although recent advances in polymerase chain reaction (PCR) technology are improving our ability to identify these bacteria. Seven or 8 major species or groups are labeled. The review by Coyle and Lipsky is an in-depth evaluation of the role of coryneform bacteria in causing infections.
Specific pathogenic groups or species include the following:
- Corynebacterium ulcerans
- Corynebacterium pseudotuberculosis (also known as Corynebacterium ovis)
- Corynebacterium pyogenes
- A haemolyticum
- Corynebacterium aquaticum
- Corynebacterium pseudodiphtheriticum (also known as Corynebacterium hofmannii)
- Group D2 (also known as Corynebacterium urealyticum)
- Group E
- Corynebacterium jeikeium (ie, group JK)
Treatment:
Antitoxins: Administered to neutralize toxin responsible for diphtheria
Antibiotics: Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Erythromycin: Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. In children, age, weight, and severity of infection determine proper dosage. When bid dosing desired, half of total daily dose may be taken q12h. For more severe infections, double dose. Parenteral erythromycin is available as gluceptate or lactobionate. All PO dosage forms produce relatively similar effective base serum concentrations. Equivalent dosage of various formulations may be used for base.
May increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; lovastatin and simvastatin increase risk of rhabdomyolysis.
Caution in liver disease; estolate formulation may cause cholestatic jaundice; adverse GI effects common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur
Vancomycin (Vancocin): Antibiotic useful against gram-positive organisms, particularly C jeikeium. Useful to treat septicemia, skin structure infections, and IV line infections/bacteremias.
Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; if taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants.
Caution in renal failure; neutropenia; red man syndrome caused by IV infusion that is too rapid (dose given over few min) but rarely happens when dose given over 2 h or by PO route; red man syndrome not allergic reaction.
Rifampin (Rifadin): Nondiphtherial corynebacteria often are susceptible.
Obtain CBC and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; high-dose intermittent therapy and interruption of therapy associated with thrombocytopenia, which is reversible with discontinuation of therapy as soon as purpura occurs; if treatment continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur; can cause reddish discoloration of urine, sweat, sputum, and tears; soft contact lenses may be permanently stained.
Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur)