eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease
Diphtheria: Treatment & Medication
Updated: Jul 29, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Critical care needs and complications must be addressed. Mechanical ventilation may be inevitable because the combination of airway obstruction by the diphtheritic membrane and peripharyngeal edema pose a fatality risk in patients with diphtheria.
Specific antitoxin is the mainstay of therapy and should be administered on the basis of clinical diagnosis because it neutralizes free toxin only. Efficacy diminishes with elapsing time after the onset of mucocutaneous symptoms. Only an equine preparation is available in the United States from Connaught Laboratories (Swiftwater, Pennsylvania) or from the CDC.
Antitoxin is administered once at an empiric dose based on the degree of toxicity, site and size of the membrane, and duration of illness. Most authorities prefer the intravenous route, with infusion over 30-60 minutes. Antitoxin is probably of no value for local manifestations of cutaneous diphtheria, but its use is prudent because toxic sequelae can occur. Commercially available immunoglobulin preparations for intravenous use contain antibodies to diphtheria toxin; their use for therapy of diphtheria is not proved or approved. Antitoxin is not recommended for asymptomatic carriers.
When an asymptomatic carrier is identified, the following steps are taken:
- Antimicrobial prophylaxis is administered for 7-10 days.
- An age-appropriate preparation of diphtheria toxoid is immediately administered if the patient has not received a booster injection within 1 year.
- Individuals are placed in strict isolation (respiratory tract colonization) or contact isolation (cutaneous colonization only) until at least 2 subsequent cultures taken 24 hours apart after cessation of therapy demonstrate negative results.
- Repeat cultures are performed at a minimum of 2 weeks after completion of therapy in patients and carriers; if results are positive, an additional 10-day course of oral erythromycin should be administered and follow-up cultures performed.
- Antimicrobial agents fail to eradicate carrier status in 100% of individuals.
Surgical Care
Otolaryngeal assessment is needed in patients with severe respiratory or neurologic complications or as part of critical care.
Consultations
- Cardiologist: Elevation of serum aspartate aminotransferase concentrations closely parallels the severity of myonecrosis. In electrocardiographic tracings, a prolonged PR interval, changes in the ST-T wave, and single or progressive cardiac dysrhythmias can occur, such as first-degree, second-degree, and third-degree heart block, atrioventricular dissociation, and ventricular tachycardia. Toxic cardiomyopathy and myocarditis are also complications that need to be evaluated and monitored by a pediatric cardiologist.
- Neurologist: Neurologic complications parallel the extent of primary infection and are multiphasic in onset.
- Hypesthesia and local paralysis of the soft palate occur commonly. Weakness of the posterior pharyngeal, laryngeal, and facial nerves may follow, causing a nasal tone in the voice, difficulty in swallowing, and risk of death from aspiration.
- Cranial neuropathies characteristically occur in the fifth week and lead to oculomotor and ciliary paralysis, which manifest as strabismus, blurred vision, or difficulty with accommodation.
- Symmetric polyneuropathy begins within 10 days to 3 months after oropharyngeal infection and principally causes motor function deficit with diminished deep tendon reflexes.
- Proximal muscle weakness of the extremities progressing distally and, more commonly, distal weakness progressing proximally are described. Clinical and cerebrospinal fluid (CSF) findings in distal weakness are indistinguishable from findings of polyneuropathy of Landry-Guillain-Barré syndrome. Paralysis of the diaphragm can ensue.
Medication
Antibiotic agents
Antimicrobial therapy is indicated to halt toxin production, treat localized infection, and prevent transmission of the organism to patient contacts. C diphtheriae is usually susceptible to various agents in vitro, including penicillin, erythromycin, clindamycin, rifampin, and tetracycline. Resistance to erythromycin is common in closed populations if the drug has been used broadly.
Penicillin and erythromycin are only recommended for treatment. Erythromycin is marginally superior to penicillin for eradication of nasopharyngeal infection. Antibiotic therapy is not a substitute for antitoxin therapy. Elimination of the organism should be documented by at least 2 successive cultures from the nose and throat (or skin) obtained 24 h apart after completion of therapy. Treatment with erythromycin is repeated if culture results remain positive.
Penicillin G, aqueous crystalline (Pfizerpen)
Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.
Adult
Eliminate carrier state: 2-3 million U/d IV/IM divided q4-6h for 10-12 d
Pediatric
Treatment: 100,000-150,000 U/kg/d IV/IM divided qid for 14 d
Cutaneous diphtheria: 7-10 d has been administered
Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in impaired renal function
Penicillin G procaine
Long-acting parenteral penicillin (IM only) to treat moderately severe infections caused by penicillin G–sensitive microorganisms.
Adult
600,000 U/d IM divided bid for 10 d
Pediatric
Treatment: 25,000-50,000 U/kg/d IM divided bid for 14 d
Cutaneous diphtheria: 7-10 d has been administered
Increases risk of bleeding when administered concurrently with warfarin; ethacrynic acid, aspirin, indomethacin, and furosemide may compete with penicillin G for renal tubular secretion, increasing penicillin serum concentrations
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Never use IV route to administer penicillin G procaine
Penicillin G benzathine (Bicillin L-A, Permapen)
Administered only IM. A tissue depot is created at the site of IM injection and slowly releases active drug into the systemic circulation. Penicillin serum concentrations are lower but more prolonged with the benzathine form than with the procaine form; serum levels of penicillin G are detected for as many as 30 d following administration.
Adult
Prophylaxis: 1.2 million U IM single dose
Pediatric
Prophylaxis:
<27 kg: 600,000 U IM single dose
>27 kg: Administer as in adults
Probenecid can increase penicillin effectiveness by decreasing clearance; coadministration with tetracyclines can decrease effectiveness of penicillin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in impaired renal function
Erythromycin (E.E.S., Ery-Tab)
Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest.
Adult
250-500 mg PO qid
Pediatric
40-50 mg/kg/d PO/IV divided tid/qid; not to exceed 2 g/d; treatment is repeated if culture results are positive
Antimicrobial prophylaxis: 40-50 mg/kg/d PO for 7 d; not to exceed 2 g/d
Potent inhibitor of CYP450 3A4; coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Documented hypersensitivity; hepatic impairment
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in liver disease; estolate formulation may cause cholestatic jaundice; adverse GI tract effects are common (administer doses pc); discontinue if nausea, vomiting, malaise, abdominal colic, or fever occur
Antipyretic agents
These agents inhibit central synthesis and release of prostaglandins that mediate the effect of endogenous pyrogens in the hypothalamus; thus, they promote the return of the set-point temperature to normal.
Ibuprofen (Advil, Motrin)
One of the few NSAIDs indicated for reduction of fever.
Adult
200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d
Pediatric
10 mg/kg/dose PO q8h for pain and/or fever; not to exceed 2.4 g/d for older children
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effects of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease; recent GI tract bleeding or perforation; renal insufficiency; high risk of bleeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Category D in third trimester of pregnancy; caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy
Acetaminophen (Tylenol, FeverAll, Tempra)
Reduces fever by acting directly on hypothalamic heat-regulating centers, which increases dissipation of body heat via vasodilation and sweating.
Adult
325-650 mg PO q4-6h or 1000 mg tid/qid; not to exceed 4 g/d
Pediatric
15 mg/kg/dose PO q4-6h prn; not to exceed 2.6 g/d for older children
Rifampin can reduce analgesic effect of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
Documented hypersensitivity; G-6-P deficiency
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hepatotoxicity possible in chronic alcoholism and overdose or chronic use of acetaminophen; severe or recurrent pain and high or continued fever may indicate serious illness; contained in many OTC products and combined use with OTC products may result in cumulative doses exceeding recommended maximum dose
Antitoxin
Antibodies are directed to a particular pathogen, usually in the form of antisera (from animal origin) or immunoglobulins. These agents are used for passive immunization resulting in immediate protection of short duration.
Antitoxin is the mainstay of therapy. It likely has no value in local manifestations of cutaneous diphtheria, but its use is prudent because toxic sequelae can occur, causing rapid deterioration of the patient. Follow with administration of appropriate diphtheria toxoid for active immunization during convalescence.
Diphtheria antitoxin
For passive transient protection against or treatment of diphtheria infections. Neutralizes only free toxin.
Only an equine preparation is available in the United States from Connaught Laboratories (Swiftwater, Pa) or from the CDC. Appropriate antibiotic therapy should be administered simultaneously with the antitoxin. Not recommended for asymptomatic carriers.
Adult
Pharyngeal or laryngeal (<48 h): 20,000-40,000 U IV infused over 30-60 min
Nasopharyngeal: 40,000-60,000 U IV infused over 30-60 min
Extensive illness (>3 d) or brawny neck swelling: 80,000-120,000 U IV infused over 30-60 min
Pediatric
Administer as in adults
None reported
Documented hypersensitivity; equine hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Due to presence of horse serum, agents for emergency treatment of anaphylaxis should be available; may cause erythema or urticaria at site of injection
Vaccines
Active immunization increases resistance to infection. Vaccines consist of microorganisms or cellular components that act as antigens. Administration of the vaccine stimulates the production of antibodies with specific protective properties.
Universal immunization is the only effective control measure. Diphtheria toxoid is typically combined with tetanus and acellular pertussis for children younger than 7 years. In children and adults, the immunization may be administered into deltoid or midlateral thigh muscles. In infants, the preferred site of administration is the midlateral thigh muscles. A specific formulation, Tdap, is recommended for adolescents and adults.4,5
DTaP (Tripedia, Daptacel, Infanrix)
May be administered into deltoid or midlateral thigh muscles in children and adults. In infants, preferred site of administration is the midlateral thigh muscles.
Adult
0.5 mL IM diphtheria and tetanus toxoids (Td) and dose according to previous vaccine history
Pediatric
Primary immunization series: 0.5 mL IM at ages 2, 4, 6, between 15-18 mo, and between 4-6 y
Catch up schedule for primary immunization for ages 7-18 years: 0.5 mL IM (administer Td) for 3 doses; allow 4 wk between doses 1 and 2, and 6 mo between doses 2 and 3; follow with booster dose 6 mo after third dose (may substitute Tdap for booster dose if age appropriate)
Adolescent booster dose (10-18 years): Tdap 0.5 mL IM once as a single dose
Patients receiving immunosuppressants, including corticosteroids or radiation therapy, may remain susceptible despite immunization because of poor immune response; cimetidine may enhance or augment delayed-hypersensitivity responses to skin test antigens; avoid concurrent use with systemic chloramphenicol because it may impair amnestic response to tetanus toxoid; concurrent use of tetanus immunoglobulin may delay development of active immunity by several days (interaction is nevertheless clinically insignificant and does not preclude concurrent use); immunosuppressive drugs (eg, corticosteroids, antineoplastic agents) may decrease immune response (defer primary diphtheria immunization until immunosuppressive therapy is discontinued)
Documented hypersensitivity; history of neurologic symptoms or signs following DTaP administration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Routine immunization of symptomatic and asymptomatic persons infected with HIV is recommended; may cause transient redness, swelling, or pain at site of injection; infrequently causes fever
Tdap (Adacel, Boostrix)
Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine. Promotes active immunity to diphtheria, tetanus, and pertussis by inducing production of specific neutralizing antibodies and antitoxins. Indicated for active booster immunization for tetanus, diphtheria, and pertussis prevention for persons aged 10-64 y (Adacel approved for ages 11-64 y, Boostrix approved for ages 10-18 y). Preferred vaccine for adolescents scheduled for booster.
Adult
One-time alternative to Td in adults when pertussis component is also indicated: 0.5 mL IM once as a single dose into deltoid muscle; at least 5 y should elapse since last dose vaccine containing tetanus, diphtheria, and/or pertussis; booster with Td recommended q10y
>65 years: Not indicated
Pediatric
<10 years: Not indicated
10-18 years: Administer as in adults; preferred vaccine for adolescents scheduled for booster
Patients receiving immunosuppressants, including corticosteroids or radiation therapy, may remain susceptible despite immunization because of a poor immune response
Documented hypersensitivity; encephalopathy within 7 d following pertussis-containing vaccine; progressive neurologic disorder; uncontrolled epilepsy; progressive encephalopathy
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Routine immunization of symptomatic and asymptomatic persons infected with HIV is recommended; may cause transient redness, swelling, or pain at injection site; infrequently causes fever; administer only if benefit outweighs risk to individuals with bleeding disorders (eg, hemophilia, thrombocytopenia) or in patients receiving anticoagulant therapy; caution upon fever, shock, persistent crying, Guillain-Barré syndrome, or seizures following previous DTP or DTaP vaccine (consider administering Td instead)
More on Diphtheria |
| Overview: Diphtheria |
| Differential Diagnoses & Workup: Diphtheria |
 Treatment & Medication: Diphtheria |
| Follow-up: Diphtheria |
| References |
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References
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Further Reading
Keywords
diphtheria, Corynebacterium diphtheriae, strangling angel of children, toxin-mediated disease, mitis diphtheria, gravis diphtheria, intermedius diphtheria, diphtheroids, coryneform bacteria, respiratory tract infection, thrombocytopenia, cardiomyopathy, tonsillar diphtheria, pharyngeal diphtheria, respiratory failure, circulatory collapse, laryngotracheobronchitis, respiratory tract obstruction, septicemia, rhinitis, impetigo
