Diphtheria

Antitoxin:

·         Equine hyper-immune antiserum reduces mortality by neutralizing toxin prior to cellular entry. Critical to administer ASAP w/ presumptive diagnosis.

·         There is an approximately 10 percent risk of hypersensitivity and/or serum sickness. Before intravenous administration of antitoxin, tests for sensitivity to horse serum should be performed according to instructions provided with the material.

·         Hypersensitivity to horse proteins determined by 1:100 dilution antitoxin scratched or pricked into the skin. If negative, proceed w/ 0.02 nl of 1:1000 dilution. Have adrenaline available if anaphylaxis reaction develops. Also if positive reaction – requires desensitization protocol.

·         Protocol for scratch test available at : https://www.cdc.gov/diphtheria/downloads/skintest-guide.pdf . However, if based on Guidance on the use of Diphtheria Anti-toxin (Public Health England, March 2021), if negative history of animal allergy and no prior exposure to equine immunoglobulin, then may proceed with slow IV infusion of the full recommended dose. Monitor patient carefully for anaphylaxis and / or serum sickness.

·         Antitoxin dose (based on National Antimicrobial Guideline 2019):

o    Pharyngeal / Laryngeal disease of 2 days duration – 20,000 to 40,000 units STAT

o    Nasopharyngeal disease – 40,000 to 60,000 units STAT

o    Systemic disease of ≥ 3 days or any patient with diffuse neck swelling (“bull neck”) – 80,000 to 120,000 units STAT

 

Administration of Antitoxin:

FUKKM [Online]	Therapeutic: 10,000 - 30,000 units by IM or IV. Increase to 40,000 - 100,000 units in severe cases. Doses up to 30,000 units may be given IM
Handbook of Drug Reconstitution and Dilution (Tawau Hospital, 2018)	Diphtheria Antitoxin Cold chain item, DO NOT freeze) Availability: 10,000 units / 10 mL Injection Pusat Simpanan: HWKKS, HDOK, Hospital Tawau   Reconstitution: Not required For mild to moderately severe case: Give IM, undiluted For severe case: Give as IV. Dilute with 250-500 mL normal saline, administered over 2-4 hours.

 

Antibiotics:

Antibiotic therapy has three major benefits: it kills the organism and thus prevents further toxin from being formed, it slows the spread of local infection, and it reduces transmission.

 

The antibiotics of choice are erythromycin (500 mg four times daily for 14 days) or procaine penicillin G (300,000 units every 12 hours for patients ≤10 kg and 600,000 units every 12 hours for patients >10 kg intramuscularly) until the patient can take oral medicine, followed by oral penicillin V (250 mg four times daily) for a total treatment course of 14 days. Erythromycin has been favored given reports of greater efficacy compared with penicillin, although one report of 71 patients noted that 21 percent of cases had positive cultures for C. diphtheriae two weeks after completion of treatment. For this reason, repeat cultures should be obtained at least two weeks after completing therapy to ensure eradication of the organism.

 

Antibiotic choices (based on National Antimicrobial Guideline 2019):

1. Erythromycin Lactobionate 500mg IV q6h

    - followed by Erythromycin Ethylsuccinate 800 mg PO q12h for total of 14 days #

 

OR

 

2. Benzylpenicillin 50,000 units/kg to a maximum of 1.2 MU IV q12h

    - followed by Phenoxymethylpenicillin (Pen V) 250mg PO q6h for total of 14 days

 

# If based on Micromedex: Erythromycin Ethylsuccinate – Diphtheria due to Corynebacterium diphtheriae, To antitoxin, Adjunct: PO 400 mg QID; MAX 4 g/day, depending on type and severity of infection

 

Follow-up 

§  Follow-up cultures should be performed at 24 to 48 hours and two weeks following infection to document clearance.

§  Isolation should be continued until two successive cultures, taken at least 24 hours apart following cessation of antibiotic therapy, are negative

§  Patients should receive diphtheria toxoid immunization during their convalescence since natural infection does not induce immunity.

 

Contact Prophylaxis 

ü  Close contacts include household members and other persons with a history of direct contact with a case-patient (eg, caretakers, relatives, or friends who regularly visit the home) as well as medical staff exposed to oral or respiratory secretions of a case-patient.

ü  Close contacts need to be identified, cultured, and considered for antimicrobial prophylaxis.

ü  If immunizations are not current, age-appropriate diphtheria toxoid immunization should be administered.

ü  After cultures have been obtained, contacts should be treated with:

*         A single dose of penicillin G benzathine (600,000 units intramuscularly [IM] for individuals <6 years of age and 1.2 million units IM for individuals ≥6 years of age), or

*         Oral erythromycin: 40-50 mg/kg/day for children or 250-500 mg four times daily for 7 to 10 days*

 

Based on Uptodate: Drug Information: Erythromycin (systemic): Oral Erythromycin 500 mg (in base) is equivalent to Erythromycin Ethylsuccinate 800 mg

 

ü  Close contacts should have cultures taken immediately and are given the prophylactic antibiotic regimen. They should be closely monitored for signs or symptoms of disease. If culture-positive, they should have their cultures repeated after finishing the course of treatment and be re-treated for a further 10 days.

 

Asymptomatic Carrier

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

ü  Carriers should receive an age-appropriate vaccine containing diphtheria toxoid as a booster, if they have not received one within the last 5 years.

 

Disease typically no longer contagious after 48h of therapy.

 

 

References:

1.     https://www.cdc.gov/diphtheria/downloads/skintest-guide.pdf

2.     https://litfl.com/diphtheria-antitoxin/#:~:text=Diphtheria%20antitoxin%20is%20based%20on,infusion%20(follow%20local%20guidelines).

3.     UptoDate: Clinical manifestations, diagnosis, and treatment of diphtheria

4.     Uptodate: Drug Information; Erythromycin (Systemic)

5.     National Antimicrobial Guideline, 2019 (Malaysia)

6.     Handbook of Drug Reconstitution and Dilution (Tawau Hospital, 2018)

7.     Formulari Ubat Kementerian Kesihatan Malaysia (FUKKM), online.

8.     Sanford: Corynebacterium diphtheriae

9.       Micromedex: Erythromycin Ethylsuccinate

10.  Guidance on the use of Diphtheria Anti-toxin (Public Health England, March 2021), via: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/970567/18026_IMW025.04_immunoglobulin_handbook_diphtheria_Butana_March2021.pdf

11.  BMJ Best Practice: Diphtheria

 

All information as per updated on 17 May 2021

All references accessed on 17 May 2021

( J. Ho )