Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

asymptomatic close contacts of respiratory and cutaneous cases

1st line – prophylactic antibiotics

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INITIAL
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asymptomatic close contacts of respiratory and cutaneous cases
1st line – 

prophylactic antibiotics

Close contacts should have swabs taken for culture from their nose, throat, and any skin lesions. They should receive prophylactic antibiotics, and be closely monitored for signs or symptoms of disease.[43]​ If pre-treatment cultures are positive, these should be repeated after finishing the course of treatment, and persistently positive cultures should be re-treated for a further 10 days.[41]

US guidelines, based on clinical trial evidence, recommend oral erythromycin or penicillin for diphtheria chemoprophylaxis.​​​[43]​

UK guidelines support use of oral azithromycin or clarithromycin, which are more tolerable to patients, simpler to administer, and have not been associated with any reported treatment failures.[41] If there is history of intolerance to the oral antibiotics or concerns about adherence, a single dose of intramuscular benzathine benzylpenicillin may be used.[43]​ The World Health Organization (WHO) guidelines do not currently offer any recommendations for the prevention of infection in close contacts, but do recommend macrolides in preference to penicillins for the treatment of diphtheria.[45]

Health and social care staff who have had unprotected (e.g., not wearing a facemask), close, face-to-face contact with an infected patient or their secretions should be managed as close contacts, with nasal and pharyngeal cultures taken and prophylactic antibiotics prescribed. Examples of close contact include: performing a physical examination on, feeding, or bathing a patient; bronchoscopy; intubation; or administration of bronchodilators. Exposure to cutaneous diphtheria lesions may include unprotected contact with the lesions or their drainage, such as when changing lesion dressings or handling potentially infectious secretions without wearing recommended personal protective equipment (PPE) (i.e., gown and gloves).​[57][58]

Treatment course: typically 7-10 days for oral antibiotics; however, treatment duration recommendations may vary and you should consult your local guidance.

Primary options

erythromycin base: children: 10-15 mg/kg orally four times daily, maximum 2000 mg/day; adults: 500 mg orally four times daily

OR

azithromycin: children: 10-12 mg/kg orally once daily, maximum 500 mg/day; adults: 500 mg orally once daily

OR

clarithromycin: children: 7.5 mg/kg orally twice daily, maximum 1000 mg/day; adults: 500 mg orally twice daily

Secondary options

phenoxymethylpenicillin: children: 10-15 mg/kg orally four times daily, maximum 2000 mg/day; adults: 500 mg orally four times daily

OR

benzathine benzylpenicillin: children <30 kg body weight: 0.6 million units as a single dose; children ≥30 kg body weight and adults: 1.2 million units intramuscularly as a single dose

Plus – diphtheria toxoid immunisation

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INITIAL
|
asymptomatic close contacts of respiratory and cutaneous cases
Plus – 

diphtheria toxoid immunisation

Treatment recommended for ALL patients in selected patient group

If the diphtheria immunisations of a close contact are not up to date, the person should receive an age-appropriate vaccine containing diphtheria toxoid as a booster or to bring them back on schedule for their immunisation programme.​​​[32][43]

Consider – exclusion from work (high-risk occupations)

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INITIAL
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asymptomatic close contacts of respiratory and cutaneous cases
Consider – 

exclusion from work (high-risk occupations)

Additional treatment recommended for SOME patients in selected patient group

Health and social care workers and other staff in high risk occupations (e.g., those who work with unimmunised children and those involved in milk production) should be excluded from work until culture results are known; if cultures are negative for toxin-producing C diphtheriae, they may return to work whilst completing post-exposure antibiotic therapy.[41]​​

ACUTE

respiratory diphtheria

1st line – hospitalisation + monitoring + infection control measures + diphtheria antitoxin

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ACUTE
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respiratory diphtheria
1st line – 

hospitalisation + monitoring + infection control measures + diphtheria antitoxin

Patients with suspected nasopharyngeal diphtheria should be promptly hospitalised and monitored for signs of respiratory compromise.

Pharyngeal oedema, pseudomembrane formation, and paralysis of the palatal muscles can contribute to respiratory compromise and are usually signalled by the development of dysphagia or dysphonia.

Intubation may be necessary to prevent airway obstruction and aspiration. Cardiac monitoring is also essential as myocarditis, heart failure, and various arrhythmias can develop later in the disease course.

Strict droplet and contact isolation are of paramount importance.

A single dose of diphtheria antitoxin should be given as soon as possible after the diagnosis of respiratory diphtheria is clinically suspected. The WHO strongly recommends against routine sensitivity testing prior to administration of antitoxin.[45]

Consider pre-medication with antihistamines and corticosteroids, and monitor closely for adverse events including anaphylaxis.

In the US, antitoxin is only available from the Centers for Disease Control and Prevention, while in the UK it is available from designated centres after discussion with the UK Health Security Agency.[41][51]​​​ ​Doses of diphtheria antitoxin may differ between guidelines and you should consult your local guidance for more information.

Primary options

diphtheria antitoxin (equine): consult specialist for guidance on dose

Plus – antibiotic therapy

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ACUTE
|
respiratory diphtheria
Plus – 

antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Appropriate antibiotics should be administered to all patients. Cultures should be taken prior to antibiotic treatment if possible, but this should not be allowed to delay treatment. Oral therapy is preferred where possible, but parenteral therapy may be required in severely ill patients or those who are unable to swallow.

If available, local antimicrobial susceptibility testing should be carried out to guide antibiotic treatment.​[41][45]

The WHO recommends an oral macrolide antibiotic (e.g., azithromycin, erythromycin) as first-line treatment in preference to penicillin antibiotics in patients with suspected or confirmed diphtheria infection. Penicillins can still be used where macrolides are unavailable and penicillin susceptibility has been microbiologically confirmed.[45]

Antibiotic recommendations may differ between guidelines. In the US, the CDC currently only recommends erythromycin or penicillin.[43]​ In the UK, the UK Health Security Agency (UKHSA) recommends all macrolides (including clarithromycin) for mild disease, and combination therapy (with a macrolide plus intravenous penicillin and the possibility of adding a third option) for severe disease.[41]

Cultures should be repeated after the initial course of treatment, to ensure eradication. Two negative cultures taken 24 hours apart following treatment constitute eradication of the organisms.[43]​ In outbreak settings where repeat microbiological culture is not possible, patients are often regarded as non-infectious after 48 hours of antibiotic therapy.​[56]

Treatment course: a 14-day course of oral antibiotics is generally deemed acceptable for treatment of respiratory or cutaneous diphtheria.[41][55]​ However, clinicians should consult their local guidelines for further information as treatment duration recommendations may vary. For example, the UK guidelines suggest that a 7 to 10-day course may be sufficient if azithromycin is used, but recommend 14 days for all other antibiotics.[41]

Primary options

erythromycin base: children: 10-15 mg/kg orally four times daily, maximum 2000 mg/day; adults: 500 mg orally four times daily

OR

azithromycin: children: 10-12 mg/kg orally once daily, maximum 500 mg/day; adults: 500 mg orally once daily

Secondary options

phenoxymethylpenicillin: children: 10-15 mg/kg orally four times daily, maximum 2000 mg/day; adults: 500 mg orally four times daily

OR

benzylpenicillin sodium: children: 25 mg/kg intravenously every 6 hours, increased to 50 mg/kg every 4-6 hours if necessary, maximum 2.4 g/dose; adults: 1.2 to 2.4 g intravenously every 6 hours

Plus – airway protection ± ventilation

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ACUTE
|
respiratory diphtheria
Plus – 

airway protection ± ventilation

Treatment recommended for ALL patients in selected patient group

Securing the airway is an absolute priority in patients whose airway is at risk. Signs and symptoms that may indicate a need for airway intervention include drooling of saliva, difficulty in breathing due to pharyngeal oedema or pseudomembrane formation, and dysphonia or dysphagia (which are suggestive of paralysis of the soft palate due to neurological involvement).

Intubation and mechanical ventilation may be necessary to maintain airway patency and prevent cardiorespiratory arrest.[27]​​

Plus – diphtheria toxoid immunisation

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ACUTE
|
respiratory diphtheria
Plus – 

diphtheria toxoid immunisation

Treatment recommended for ALL patients in selected patient group

Diphtheria disease does not always confer immunity, therefore the patient should also receive an age-appropriate diphtheria toxoid-containing vaccine during convalescence.​​​[32]​​[43]​

cutaneous diphtheria

1st line – monitoring + isolation measures

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ACUTE
|
cutaneous diphtheria
1st line – 

monitoring + isolation measures

Although severe disease is occasionally reported, patients with cutaneous diphtheria usually have mild disease and can be treated on an outpatient basis. Home isolation and contact precautions should be followed until treatment is complete and cultures from lesion swabs are negative.

Plus – antibiotic therapy

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ACUTE
|
cutaneous diphtheria
Plus – 

antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Antibiotic options are the same for respiratory and cutaneous diphtheria.

Cultures should be taken prior to antibiotic treatment if possible, but this should not be allowed to delay treatment. Oral therapy is preferred where possible, but parenteral therapy may be required in severely ill patients or those who are unable to swallow.

If available, local antimicrobial susceptibility testing should be carried out to guide antibiotic treatment.​[41][45]

The WHO recommends an oral macrolide antibiotic (e.g., azithromycin, erythromycin) as first-line treatment in preference to penicillin antibiotics in patients with suspected or confirmed diphtheria infection. Penicillins can still be used where macrolides are unavailable and penicillin susceptibility has been microbiologically confirmed.[45]

Antibiotic recommendations may differ between guidelines. In the US, the CDC currently only recommends erythromycin or penicillin.[43]​ In the UK, the UKHSA recommends all macrolides (including clarithromycin) for mild disease, and combination therapy (with a macrolide plus intravenous penicillin and the possibility of adding a third option) for severe disease.[41]

Cultures should be repeated after the initial course of treatment, to ensure eradication. Two negative cultures taken 24 hours apart following treatment constitute eradication of the organisms.[43]​ In outbreak settings where repeat microbiological culture is not possible, patients are often regarded as non-infectious after 48 hours of antibiotic therapy.​[56]

Treatment course: a 14-day course of oral antibiotics is generally deemed acceptable for treatment of respiratory or cutaneous diphtheria.[41][55]​ However, clinicians should consult their local guidelines for further information as treatment duration recommendations may vary. For example, UK guidelines suggest that a 7 to 10-day course may be sufficient if azithromycin is used, but recommend 14 days for all other antibiotics.[41]

Primary options

erythromycin base: children: 10-15 mg/kg orally four times daily, maximum 2000 mg/day; adults: 500 mg orally four times daily

OR

azithromycin: children: 10-12 mg/kg orally once daily, maximum 500 mg/day; adults: 500 mg orally once daily

OR

clarithromycin: children: 7.5 mg/kg orally twice daily, maximum 1000 mg/day; adults: 500 mg orally twice daily

Secondary options

phenoxymethylpenicillin: children: 10-15 mg/kg orally four times daily, maximum 2000 mg/day; adults: 500 mg orally four times daily

OR

benzylpenicillin sodium: children: 25 mg/kg intravenously every 6 hours, increased to 50 mg/kg every 4-6 hours if necessary, maximum 2.4 g/dose; adults: 1.2 to 2.4 g intravenously every 6 hours

Consider – diphtheria antitoxin

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ACUTE
|
cutaneous diphtheria
Consider – 

diphtheria antitoxin

Additional treatment recommended for SOME patients in selected patient group

Antitoxin is probably of no value for local manifestations of cutaneous diphtheria, but it may still be considered because toxic systemic sequelae of cutaneous diphtheria can occur, albeit rarely.​[5] No clinical trials have been done to evaluate the use of antitoxin in cutaneous diphtheria.

The World Health Organization (WHO) strongly recommends against routine sensitivity testing prior to administration of antitoxin.[45]

Consider pre-medication with antihistamines and corticosteroids, and monitor closely for adverse events including anaphylaxis.

In the US, antitoxin is only available from the CDC, while in the UK it is available from designated centres after discussion with the UKHSA.[41][51]​ Doses of diphtheria antitoxin may differ between guidelines and you should consult your local guidance for more information.

Primary options

diphtheria antitoxin (equine): consult specialist for guidance on dose

Plus – diphtheria toxoid immunisation

Back
ACUTE
|
cutaneous diphtheria
Plus – 

diphtheria toxoid immunisation

Treatment recommended for ALL patients in selected patient group

Diphtheria disease does not always confer immunity, therefore the patient should also receive an age-appropriate diphtheria toxoid-containing vaccine during convalescence.​​​[32]​​[43]​

asymptomatic carriers

1st line – isolation measures + antibiotic therapy

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ACUTE
|
asymptomatic carriers
1st line – 

isolation measures + antibiotic therapy

Close contacts with positive culture results from screening swabs, but who do not display signs or symptoms of disease, are identified as asymptomatic carriers.

Respiratory isolation (masks and standard measures such as hand-washing) is necessary for those with respiratory colonisation. For asymptomatic carriers with cutaneous diphtheria, contact isolation (gloves and gowns) is sufficient.

Antibiotic treatment should be administered, and swabs should be repeated on completion of therapy.

Isolation should be continued until two successive cultures, taken at least 24 hours apart following cessation of antibiotic therapy, are negative.[43]​​​​ In outbreak settings where microbiological facilities are insufficient to permit repeated sample processing for culture, patients are often deemed to be sufficiently non-infectious to lift isolation and infection control measures after 48 hours of antibiotic therapy.​[56]

Antibiotic treatment options for asymptomatic carriers are the same as those used for acute disease.​​[41] If available, local antimicrobial susceptibility testing should be carried out to guide antibiotic treatment.​​[41][45]

Positive post-treatment culture results warrant a repeat course of antibiotic treatment.​​[41]

The WHO recommends an oral macrolide antibiotic (e.g., azithromycin, erythromycin) as first-line treatment in preference to penicillin antibiotics in patients with suspected or confirmed diphtheria infection. Penicillins can still be used where macrolides are unavailable and penicillin susceptibility has been microbiologically confirmed.[45]

Antibiotic recommendations may differ between guidelines. In the US, the CDC currently only recommends erythromycin or penicillin.[43]​ In the UK, the UKHSA recommends all macrolides (including clarithromycin) for mild disease, and combination therapy (with a macrolide plus intravenous penicillin and the possibility of adding a third option) for severe disease.[41]

Primary options

erythromycin base: children: 10-15 mg/kg orally four times daily, maximum 2000 mg/day; adults: 500 mg orally four times daily

OR

azithromycin: children: 10-12 mg/kg orally once daily, maximum 500 mg/day; adults: 500 mg orally once daily

OR

clarithromycin: children: 7.5 mg/kg orally twice daily, maximum 1000 mg/day; adults: 500 mg orally twice daily

Secondary options

phenoxymethylpenicillin: children: 10-15 mg/kg orally four times daily, maximum 2000 mg/day; adults: 500 mg orally four times daily

OR

benzylpenicillin sodium: children: 25 mg/kg intravenously every 6 hours, increased to 50 mg/kg every 4-6 hours if necessary, maximum 2.4 g/dose; adults: 1.2 to 2.4 g intravenously every 6 hours

Plus – diphtheria toxoid immunisation

Back
ACUTE
|
asymptomatic carriers
Plus – 

diphtheria toxoid immunisation

Treatment recommended for ALL patients in selected patient group

Carriers should receive an age-appropriate vaccine containing diphtheria toxoid as a booster.[43]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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