Medical Care
For the initial office visit or emergency department treatment, see Diphtheria in the Medscape Reference Emergency Medicine section.
C diphtheriae
Since the early 1900s, diphtheria antitoxin (DAT), produced in horses, has been the mainstay of therapy. The antiserum works only to neutralize the toxin before it enters the cell. The antiserum is thought to be more effective in less severely ill patients and in those who are treated earlier in the disease course. Therefore, more severely ill patients and those with longer symptom duration are given higher doses than those with less severe disease of shorter duration. Whether this is an effective way of dosing the antiserum has never been tested.
Many people show signs of hypersensitivity reactions to the horse antiserum, and a test dose is usually given, with epinephrine available in case the patient has a severe reaction. However, because the mortality rate associated with antiserum has declined markedly, desensitization with increasing doses of antiserum is recommended.
Antibiotics treatment is the second arm of treatment. The goal is both to kill the organism and to terminate toxin production. Many antibiotics are effective, including penicillin, erythromycin, clindamycin, rifampin, and tetracycline; erythromycin or penicillin is the treatment of choice and is usually given for 14 days.
Supportive care is also important, including rest, airway management, observation for development of secondary lung infections, and management of cardiac and neurologic disease complications.
Diphtheroids
Antibiotics are the treatment of choice for nondiphtherial corynebacteria infections. Many species and groups are sensitive to various antibiotics, including penicillins, macrolide antibiotics, rifampin, and fluoroquinolones. However, antibiotic susceptibility can vary, and susceptibility testing is recommended. A review by Riegel et al on identification and antimicrobial sensitivity in 415 corynebacterial isolates from clinical specimens of patients hospitalized in Strasbourg, France, demonstrated that many species or groups were susceptible to ampicillin, cefotaxime, and rifampicin. [52] Many species or groups were resistant to erythromycin, and 2 groups (ie, JK, C urealyticum) were resistant to nearly every drug tested.
Another review, by Spanik et al, examined risk factors for disease with corynebacteria. [53] Of 123 episodes of breakthrough bacteremia during antibiotic prophylaxis in patients with cancer, 10% were from corynebacteria causing indwelling catheter infections. In this review, catheter removal and modification of antimicrobial therapy, depending on susceptibility testing, were independent risk factors for an improved outcome.
In another review of antimicrobial treatment options for corynebacterial mastitis, Corynebacterium kroppenstedtii was susceptible to most antibiotics except beta lactams, while Corynebacterium tuberculostearicum was resistant to most antibiotics. [7] Clarithryomycin has also been used for treatment of granulomatous mastitis, although typically therapy must be continued for months. [9]
Surgical Care
The mainstay of treatment for these infections is nonsurgical. However, a case report discussed necrotizing lymphadenitis that was unresponsive to repeated antibiotic therapy, requiring surgical drainage and adequate debridement of the infected area. [54]
Consultations
The World Health Organization expanded its network of laboratories after the outbreaks of diphtheria in the Russian republics; the Diphtheria Surveillance Network integrates epidemiologic and microbiologic aspects of potentially toxigenic corynebacteria. [48]
In 2014, the WHO published a flowchart for case classification of suspected or documented corynebacterial infections. [55] This includes infections of C diphtheriae as well as diphtheroid organisms.
The US Centers for Disease Control and Prevention (CDC) is the source for antitoxin (ie, DAT) in the United States. If treating suspected cases of diphtheria, contact the diphtheria duty officer at 800-CDC-INFO (800-232-4636).
Report all suspected cases of diphtheria to local and state health departments. Local infectious disease specialists who work with the CDC are available 24 hours a day through the local public health department for help with symptoms and disease management.
Cardiologists, pulmonary specialists, and neurologists may help in the care of patients who have specific disease complications.
Prevention
Vaccination
As mentioned above, childhood immunization is the prevention method of choice. Diphtheria/tetanus/pertussis (DTP) vaccine, given at ages 2, 4, and 6 months; at age 15 months to 18 months; and at least 5 years later (age 4-6 y) is the immunization regimen recommended by the American Academy of Pediatrics, the Advisory Committee on Immunization Practices, and the American Academy of Family Physicians.
Unvaccinated people older than 7 years or people whose immunization status is unknown should receive three doses of the adult formulation of the tetanus-diphtheria toxoid (Td). The first two doses are given 4 weeks to 8 weeks apart, and the third dose is given 6 months to 12 months later.
The first booster dose of Td should be given at least 5 years after the last immunization and every 10 years thereafter. A reduced antigen booster (combined with tetanus and pertussis) is available that is highly immunogenic with low reactogenicity. [56]
Adverse reactions include local induration, pain, redness, and, occasionally, low-grade fevers. Serum sickness hypersensitivity reactions are reported in some adults.
Vaccination coverage levels are monitored by the CDC National Immunization Survey, which estimates vaccination coverage for the 50 states. Compared with the baseline year of 1992, national coverage with 4 or more doses of DTP increased significantly, from 55% to 78%.
In comparison, some industrialized countries have much lower immunization levels. In a recent seroepidemiologic study from Spain, only 26% of the sample population of 3944 men and women aged 5 years to 59 years were fully protected and more than 85% of those aged 20 years to 39 years had little or no protection against diphtheria. [57] In other Western countries, serologic protection was found in 50% to 80% of subjects, with some countries showing a greater protection rate in older subjects (eg, Sweden) and some countries showing a greater protection rate in younger subjects (eg, Germany, France, Turkey, Slovakia).
Risks for travelers, therefore, are higher in parts of the world where immunization levels are low and the disease is prevalent. The Health Protection Agency Centre for Infections in the United Kingdom recommends boosters every 10 years for travelers planning to visit areas of endemic disease. [58] The CDC has an up-to-date Web site on diphtheria prevention for the public at www.cdc.gov/travel/diseases/dtp.htm.
In 2008, the Advisory Committee on Immunization Practices (ACIP) issued guidelines on the prevention of pertussis, tetanus, and diphtheria in pregnant and postpartum women and their infants. Details can be found at http://www.medscape.com/viewarticle/574587. In 2012, the American College of Obstetrics and Gynecology announced their findings that the toxoid in Tdap vaccine was not associated with adverse fetal outcomes and published their revised guidelines. [59]
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The corynebacterial tox gene is regulated by the corynebacterial iron-binding repressor, labeled DtxR. Binding of ferrous iron to the DtxR molecule forms a complex that binds to the tox gene operator and inhibits transcription. Depletion of iron from the system removes the repression and allows the toxin to be produced.
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The characteristic thick membrane of diphtheria infection in the posterior pharynx.
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Cervical edema and cervical lymphadenopathy from diphtheria infection produce a bullneck appearance in this child. Courtesy of Immunize.org, formerly Immunization Action Coalition (IAC) [https://www.immunize.org/].
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Final case classification of corynebacteria infections. Courtesy of the World Health Organization (WHO) [Surveillance standards for vaccine-preventable diseases, 2nd ed, 2018, https://apps.who.int/iris/handle/10665/275754].
