Corynebacterium Diphtheria : Clinical Features, Complications, Laboratory Diagnosis and Medical Management

Corynebacterium Diphtheria : Clinical Features, Complications, Laboratory Diagnosis and Medical Management

Clinical Features

The incubation period of diphtheria is 2–5 days (range, 1–10 days).

Disease can involve almost any mucous membrane. For clinical purposes, it is convenient to classify diphtheria into a number of manifestations, depending on the anatomic site of disease.

Anterior Nasal Diphtheria

The onset of anterior nasal diphtheria is indistinguishable from that of the common cold and is usually character­ized by a mucopurulent nasal discharge (containing both mucus and pus) which may become blood-tinged. A white membrane usually forms on the nasal septum. The disease is usually fairly mild because of apparent poor systemic absorption of toxin in this location, and it can be terminated rapidly by diphtheria antitoxin and antibiotic therapy.

Pharyngeal and Tonsillar Diphtheria

The most common sites of diphtheria infection are the pharynx and the tonsils. Infection at these sites is usually associated with substantial systemic absorption of toxin. The onset of pharyngitis is insidious. Early symptoms include malaise, sore throat, anorexia, and low-grade fever (<101°F). Within 2–3 days, a bluish-white membrane forms and extends, varying in size from covering a small patch on the tonsils to covering most of the soft palate. Often by the time a physician is contacted, the membrane is greyish-green, or black if bleeding has occurred. There is a minimal amount of mucosal erythema surrounding the membrane. The pseudomembrane is firmly adherent to the tissue, and forcible attempts to remove it cause bleeding. Extensive pseudomembrane formation may result in respiratory obstruction.

While some patients may recover at this point without treatment, others may develop severe disease. Fever is usually not high, even though the patient may appear quite toxic. Patients with severe disease may develop marked edema of the submandibular areas and the anterior neck along with lymphadenopathy, giving a characteristic “bullneck” appearance. If enough toxin is absorbed, the patient may develop severe prostration, striking pallor, rapid pulse, stupor, and coma, and may even die within 6 to 10 days.

Laryngeal Diphtheria

Laryngeal diphtheria can be either an extension of the pharyngeal form or can involve only this site. Symptoms include fever, hoarseness, and a barking cough. The membrane can lead to airway obstruction, coma, and death

Cutaneous (Skin) Diphtheria

In the United States, cutaneous diphtheria has been most often associated with homeless persons. Skin infections are quite common in the tropics and are probably responsible for the high levels of natural immunity found in these populations. Skin infections may be manifested by a scaling rash or by ulcers with clearly demarcated edges and membrane, but any chronic skin lesion may harbor C. diphtheriae along with other organisms. Generally, the organisms isolated from cases in the United States were nontoxigenic. The severity of the skin disease with toxigenic strains appears to be less than from other sites. Cutaneous diphtheria is no longer reported to the National Notifiable Diseases Surveillance System in the United States.

Rarely, other sites of involvement include the mucous membranes of the conjunctiva and vulvovaginal area, as well as the external auditory canal.

Complications

Most complications of diphtheria, including death, are attributable to effects of the toxin. The severity of the disease and complications are generally related to the extent of local disease. The toxin, when absorbed, affects organs and tissues distant from the site of invasion. The most frequent complications of diphtheria are myocarditis and neuritis.

Myocarditis may present as abnormal cardiac rhythms and can occur early in the course of the illness or weeks later, and can lead to heart failure. If myocarditis occurs early, it is often fatal.
Neuritis most often affects motor nerves and usually resolves completely. Paralysis of the soft palate is most frequent during the third week of illness. Paralysis of eye muscles, limbs, and diaphragm can occur after the fifth week. Secondary pneumonia and respiratory failure may result from diaphragmatic paralysis.

Other complications include otitis media and respiratory insufficiency due to airway obstruction, especially in infants.

Death

The overall case-fatality rate for diphtheria is 5%–10%, with higher death rates (up to 20%) among persons younger than 5 and older than 40 years of age. The case-fatality rate for diphtheria has changed very little during the last 50 years.

Laboratory Diagnosis

Diagnosis of diphtheria is usually made on the basis of clinical presentation since it is imperative to begin presumptive therapy quickly.

Culture of the lesion is done to confirm the diagnosis. It is critical to take a swab of the pharyngeal area, especially any discolored areas, ulcerations, and tonsillar crypts. Culture medium containing tellurite is preferred because it provides a selective advantage for the growth of this organism. If diphtheria bacilli are isolated, they must be tested for toxin production.

A blood agar plate is also inoculated for detection of hemolytic streptococcus. Gram stain and Kenyon stain of material from the membrane itself can be helpful when trying to confirm the clinical diagnosis. The Gram stain may show multiple club-shaped forms that look like Chinese characters. Other Corynebacterium species (diphtheroids) that can normally inhabit the throat may confuse the interpreta­tion of direct stain. However, treatment should be started if clinical diphtheria is suggested, even in the absence of a Gram stain.

In the event that prior antibiotic therapy may have impeded a positive culture in a suspect diphtheria case, three sources of evidence can aid in presumptive diagnosis: 1) a positive polymerase chain reaction test for diphtheria tox genes, or 2) isolation of C. diphtheriae from cultures of specimens from close contacts, or 3) a low nonprotective diphtheria antibody titer (less than 0.1 IU) in serum obtained prior to antitoxin administration. This is done by commercial labo­ratories and requires several days. To isolate C. diphtheriae from carriers, it is best to inoculate a Löffler or Pai slant with the throat swab. After an incubation period of 18–24 hours, growth from the slant is used to inoculate a medium containing tellurite.

Medical Management

Diphtheria Antitoxin

Diphtheria antitoxin, produced in horses, was used for treatment of diphtheria in the United States since the 1890s. It is not indicated for prophylaxis of contacts of diphtheria patients. Since 1997, diphtheria antitoxin has been available only from CDC, through an Investigational New Drug (IND) protocol. Diphtheria antitoxin does not neutralize toxin that is already fixed to tissues, but it will neutralize circulating (unbound) toxin and prevent progression of disease. The patient must be tested for sensitivity before antitoxin is given.

Consultation on the use of diphtheria antitoxin is available through the duty officer at the CDC through CDC’s Emergency Operations Center at 770-488-7100.

After a provisional clinical diagnosis is made, appropriate specimens should be obtained for culture and the patient placed in isolation. Persons with suspected diphtheria should be given diphtheria antitoxin and antibiotics in adequate dosage. Respiratory support and airway maintenance should also be administered as needed.

Antibiotics

Treatment with erythromycin orally or by injection (40 mg/kg/day; maximum, 2 gm/day) for 14 days, or procaine penicillin G daily, intramuscularly (300,000 U/ day for those weighing 10 kg or less, and 600,000 U/ day for those weighing more than 10 kg) for 14 days. The disease is usually not contagious 48 hours after antibiotics are instituted. Elimination of the organism should be documented by two consecutive negative cultures after therapy is completed.

Preventive Measures

For close contacts, especially household contacts, a diphtheria booster, appropriate for age, should be given. Contacts should also receive antibiotics—benzathine penicillin G (600,000 units for persons younger than 6 years old and 1,200,000 units for those 6 years old and older) or a 7- to 10-day course of oral erythromycin (40 mg/kg/ day for children and 1 g/day for adults). For compliance reasons, if surveillance of contacts cannot be maintained, they should receive benzathine penicillin G. Identified carriers in the community should also receive antibiotics. Maintain close surveillance and begin antitoxin at the first signs of illness.

Contacts of cutaneous diphtheria should be treated as described above; however, if the strain is shown to be nontoxigenic, investigation of contacts should be discon­tinued.

Corynebacterium Diphtheria : Clinical Features, Complications, Laboratory Diagnosis and Medical Management 2019-01-07T06:29:00-08:00 Rating: 4.5 Diposkan Oleh: David Maharoni