Figure 133.1 Diagnostic and treatment approach to diphtheria.
Specific diagnosis of diphtheria depends completely on demonstration of the organism in stained smears and its recovery by culture. In experienced hands, methylene blue-stained preparations are positive in 75% to 85% of cases. The bacilli can be recovered by culture in Loeffler’s or Tindale’s medium within 8 to 12 hours if patients have not been receiving antimicrobial agents. Corynebacterium diphtheriae can be seen as gram-positive bacilli in a “Chinese letter” distribution pattern on Gram or methylene blue stain (Figure 133.2); one can find metachromatic granules on Loeffler’s stain and black colonies with halos with growth on Tindale’s medium. The presence of β-hemolytic streptococci does not rule out diphtheria because such streptococci are recovered in up to 20% to 30% of patients with diphtheria.
Figure 133.2 Gram-positive bacilli in a “Chinese letter” distribution pattern on Gram stain.
Toxin detection should be performed to differentiate toxigenic from nontoxigenic strains, but is not the reason not to administer antitoxin. Toxin production can be demonstrated by the ELEK test and or rapid enzyme immunoassay (ELISA).
The differential diagnosis of tonsillar-pharyngeal diphtheria should include streptococcal pharyngitis, adenoviral exudative pharyngitis, infectious mononucleosis, and Vincent’s angina, among others (Table 133.1).
| Affected area | Other conditions |
|---|---|
| Nose | Sinusitis, foreign body, snuffles of congenital syphilis, rhinitis |
| Fauces and pharynx | Streptococcal or adenoviral exudative pharyngitis, ulcerative pharyngitis (herpetic, Coxsackie-viral), infectious mononucleosis, oral thrush, peritonsillar abscess, retropharyngeal abscess, Vincent’s angina, lesions associated with agranulocytosis or leukemia |
| Larynx | Laryngotracheobronchitis, epiglottitis |
| Skin | Impetigo, pyogenic ulcers, herpes simplex infection |
Therapy
The best and most effective treatment of diphtheria is prevention by immunization with diphtheria toxoid. The most important aspect of treatment is to administer the antitoxin and antibiotics as soon as diphtheria is clinically suspected, without awaiting laboratory confirmation. The patient should be hospitalized, isolated, and kept in bed for 10 to 14 days (see Figures 133.1 and 131.3).
Use of antitoxin
The antitoxin is equine, and the minimal effective dose remains undefined; therefore, dosage is based on empiric judgment. It is usually accepted that for patients with mild or moderate cases, including those with tonsillar and pharyngeal membrane, 20 000 to 40 000 units for pharyngeal disease of <48 hours duration, 40 000 to 60 000 units for nasopharyngeal disease, and 80 000 to 100 000 units for >3 days of illness or “bull neck” is appropriate. Doses should be given intravenously over 60 minutes as recommended by the American Academy of Pediatrics.
Before administration of the antitoxin, any history of allergy or reactions to horse serum or horse dander must be determined. All patients must be tested for antitoxin sensitivity with dilute horse antitoxin in saline 1:10 and an eye test. This is followed by a scratch test with a 1:100 dilution; if negative in half an hour, the scratch test is followed by an intradermal test, 1:100 dilution. If all tests are negative, antitoxin can be given. The intravenous route is recommended. A slow intravenous infusion of 0.5 mL antitoxin in 10 mL saline is followed in half an hour by the balance of the dose in a dilution of 1:20 with saline, infused at a rate not to exceed 1 mL/min. Others give the antitoxin dose intramuscularly in mild to moderate cases only.
If the patient is sensitive to horse serum, desensitization should be carried out with care, preferably in an intensive care unit. Epinephrine, intubation equipment, and respiratory assistance should be available. The following doses of horse serum antitoxin should be injected at 15-minute intervals if no reaction occurs:
During all tests and on injection of antitoxin, a syringe containing epinephrine 1:1000 dilution in saline should be at hand to be used immediately in a dose of 0.01 mL/kg subcutaneously or intramuscularly at any sign of anaphylaxis. A good precaution is to have open venous access with normal saline prior to the test. If needed, a similar amount of epinephrine diluted to a final concentration of 1:10 000 in saline may be given slowly intravenously and repeated in 5 to 15 minutes. Other information and instructions in the package insert accompanying the antitoxin should be observed.
Antibiotics
Corynebacterium diphtheriae is susceptible to several antimicrobial agents. After cultures have been performed, antibiotics should be administered to prevent multiplication of the microorganism at the site of infection and to eliminate the carrier state. The antibiotics of choice are erythromycin (500 mg four times a day for 14 days) or penicillin G 25 000 to 50 000 units to a maximum of 1.2 million units IV every 12 hours until the patient can take oral penicillin V (250 mg QID) for a total of 14 days. Erythromycin has been favored since reports show greater efficacy than penicillin.
Supportive measures
Complications such as dehydration, malnutrition, and congestive heart failure should be diagnosed promptly and properly treated. In cases of severe laryngeal involvement, marked toxicity, or shock, corticosteroids (prednisone 3 to 5 mg/kg/day) have been advocated, but there are no hard data on their effectiveness. For laryngeal obstruction with respiratory stridor, a tracheotomy must be performed promptly.
Before the patient is discharged, specimens from throat and nose or suspected lesions should be cultured. At least two and preferably three consecutive negative cultures should be obtained.
After recovery, toxoid administration against tetanus and diphtheria (Td) should be administered to complete a primary immunization series if the patient has not been immunized.
Carriers
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