rod-shaped bacterial infection (e.g. bacillus Calmette-Guerin)



OVERVIEW

Definition

Bacteria of the genus Corynebacterium (Corynebacterium) are named for the rod-like shape of their expanded bodies at one or both ends.

Corynebacterium infection is an infection of the body with Corynebacterium, and different Corynebacterium infections can cause different diseases.

There are 103 species and subspecies of bacteria in the genus Corynebacterium, and Corynebacterium diphtheriae is commonly associated with humans, in addition to Corynebacterium pseudodiphtheriae, Corynebacterium ulcerans, Corynebacterium conjunctivum desiccatum, Corynebacterium jacobacterium, etc., which are collectively referred to as Corynebacterium diphtheriae-like bacteria [1].

Corynebacterium diphtheriae infection is the most common in humans, and the infection can cause diphtheria, which is mainly characterized by sore throat, fever, nausea, vomiting and other manifestations.

The population of Corynebacterium diphtheriae is generally susceptible; Corynebacterium-like diphtheriae is generally non-pathogenic, mostly conditionally pathogenic, and causes infection only when the body’s immunity is reduced [2].

Morbidity

Corynebacterium infections are most common with Corynebacterium diphtheriae infections, which are distributed worldwide [3].

It is often endemic in crowded areas with poor sanitation.

It can occur in all seasons, but is more prevalent in spring and winter.

The population is generally susceptible, but children and people with low immunity are more likely to be infected.

Since the launch of vaccination in China, the incidence rate has declined, and most of the cases are disseminated, with a case fatality rate of less than 5%.

Causes

Causes

Corynebacterium infections are caused by infection with Corynebacterium, and the basic conditions leading to epidemics are the following three aspects.

Source of infection

Corynebacterium diphtheriae: The infectious sources are mainly patients with diphtheria and carriers of Corynebacterium diphtheriae.

Corynebacterium diphtheriae-like bacillus: It exists in the body itself and can be widely parasitized on human skin, throat, external ear canal, nasal cavity, vulva, urinary tract, etc.

Transmission pathway

Droplet transmission: Inhalation of droplets with Corynebacterium diphtheriae through the respiratory tract can cause infection.

Contact transmission: Infection is caused by direct contact with carriers and patients with Corynebacterium diphtheriae, or by contact with objects contaminated with Corynebacterium diphtheriae [4].

Corynebacterium diphtheriae-like organisms are present in the body itself and can cause infection when the body’s immunity is lowered.

Susceptible population

Corynebacterium diphtheriae is generally susceptible in the population, but is more common in pediatric patients.

Corynebacterium diphtheriae-like organisms are more susceptible to infection when the body is immunocompromised.

Pathogenesis

Diphtheria toxin is the main pathogenic substance of Corynebacterium diphtheriae. After invading the human body, Corynebacterium diphtheriae grows and reproduces locally in the nasal cavity, pharynx and other parts of the human body and produces and secretes diphtheria toxin, which leads to inflammatory oozing, tissue necrosis, and coagulation and the formation of a pseudomembrane [5].

Pseudomembrane and submucosal tissues are tightly adhered, if the pseudomembrane and mucous membrane are edematous and detached, it can cause respiratory obstruction symptoms, and in severe cases, it can cause asphyxiation and even death.

After the diphtheria toxin is released into the blood, it can combine with cardiomyocytes, peripheral nerves, adrenal tissue cells, etc., causing hoarseness, myocarditis, soft palate paralysis, dysphagia and other systemic toxic symptoms.

Symptoms

Main symptoms

The incubation period of Corynebacterium infection is 1 to 7 days, usually 2 to 4 days.

According to the site of lesions and the severity of toxic symptoms can be divided into 4 types. According to the incidence, pharyngeal diphtheria is the most common and can occur at all ages, laryngeal diphtheria is the second most common, nasal diphtheria is less common, and is more common in infants and young children, while other parts of the body are even less common.

The clinical manifestations of infection with different rod-shaped bacilli vary somewhat, among which the following symptoms are common.

Corynebacterium diphtheriae infection

It is most common clinically and accounts for about 80% of cases in epidemics. It can be divided into 4 types according to the extent of its pseudomembrane and the severity of local and systemic symptoms.

Ordinary type: slow onset, clinical symptoms include sore throat, redness and swelling, moderate fever, malaise, loss of appetite, enlarged submandibular lymph nodes and tenderness, infants and children may show salivation, inactivity or crying, and grayish-white flaky pseudomembrane in the pharynx which is not easy to be peeled off with unclear boundary.

Mild type: clinical symptoms such as low fever, sore throat, only in the tonsils can be seen in a point or a small piece of pseudomembrane.

Severe type: clinical symptoms such as high fever, nausea, vomiting, pallor, often accompanied by cervical lymph node enlargement, tenderness, expanded pseudomembrane, and the pseudomembrane is thick, with clear boundaries, and is grayish yellow or black.

Extremely severe: Clinical manifestations may include high fever, pallor, dyspnea, rapid pulse, drop in blood pressure, purple lips, etc. In severe cases, cardiac arrhythmia, cardiac enlargement, toxic shock, and even death may occur [6].

It is common in children aged 1 to 5 years, with progressive obstruction as the main manifestation, often showing “barking” cough, hoarseness or loss of voice, cicadas sound when breathing, dyspnea.

In severe cases of obstruction, there is a triple concave sign in inspiration, and in severe cases, there will be panic, profuse sweating, cyanosis, and even coma.

Commonly found in infants and children, clinical symptoms may include nasal congestion, thick, plasma bloody nasal discharge, redness around the nostrils, vesiculation and crusting.

Corynebacterium diphtheriae-like infection

Corynebacterium diphtheriae-like organism can attack several parts of the body, and infection of different parts can cause related symptoms.

Infection of the pharynx: symptoms such as soreness, redness and swelling of the throat.

Infection of the conjunctiva: redness, swelling, discomfort and itchiness of the eyes.

Infection of the vagina: redness and swelling of the vulva, increased leukorrhea and other symptoms.

Infection of the urethra: there may be symptoms such as increased urethral discharge, urinary urgency, frequent urination and painful urination.

Complications

Toxic myocarditis

It is the most common complication, mostly seen in the 1st to 2nd week of the disease.

It can occur regardless of the severity of the disease, but is most common in those with extensive primary lesions or delayed antitoxin therapy.

Patients have heart rate, heart sound, heart rhythm changes, heart shadow enlargement, electrocardiogram abnormality and cardiac enzyme spectrum abnormality, heart failure and peripheral circulatory failure are the main causes of diphtheria death in severe cases, and sudden onset of death can also occur in the recovery period.

Peripheral nerve paralysis

Peripheral nerve paralysis is a common complication of severe diphtheria, which occurs in the third to fourth week of the disease.

It manifests as flaccid paralysis, with soft palate paralysis being the most common, and the patient’s speech is slurred, with nasal sound, choking on drinking water, and loss of palpebral reflex. The second is paralysis of the eye muscles, with strabismus, drooping eyelids and dilated pupils. In facial nerve paralysis, the corners of the mouth are skewed and the nasolabial folds become shallow.

The paralysis usually disappears within 2 to 3 months without sequelae.

Toxic nephropathy

Rare, mainly manifested as decreased urine output, leukocytes and tubular pattern in urine, usually without hematuria.

Secondary infection

May be secondary to other bacterial infections causing pneumonia, purulent cervical lymphadenitis, perilymphadenitis, otitis media, sinusitis, sepsis, etc.

Consultation

Department of Medicine

Department of Infectious Diseases

If symptoms such as sore throat, fever, headache, nausea, vomiting, fatigue, dyspnea, enlarged lymph nodes, etc. occur, even if the symptoms are not serious, you should seek medical treatment promptly and it is recommended to consult the Department of Infectious Diseases first.

Emergency Department

When symptoms such as high fever (>39℃), dyspnea, cyanosis, irritability, nasal flutter, etc. occur, it is important to seek prompt medical attention, either by calling 120 emergency or consulting the Emergency Department.

Preparation for medical treatment

Preparation for consultation: registration, preparation of information, common problems

Tips for seeking medical treatment

A full body checkup may be required, so wear loose-fitting clothing.

If you have a fever before the visit, you can first apply physical cooling, such as warm towels on the forehead or underarms.

Preparation checklist for seeking medical treatment

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Is there any soreness, redness, swelling or discomfort in the throat?

Is there fever, headache, nausea, vomiting, etc.?

Is there any fatigue, loss of appetite, etc.?

When did the above symptoms appear?

Have you been in contact with similar patients with symptoms recently?

Have you received DPT3 vaccination?

Test results in the past 6 months, which can be brought to the doctor.

Laboratory tests: blood test, urine test, etc.

Medication in the past 3 months, if available, bring along the box or package for medical consultation

Antipyretics: ibuprofen, acetaminophen, etc.

Antibiotics: e.g. amoxicillin, azithromycin, etc.

Diagnosis

Diagnosis is based on

medical history

Patients with this disease may have the following epidemiologic history.

Currently in the fall or winter months or in an area where Corynebacterium infections are endemic.

History of travel to areas where Corynebacterium infections are endemic.

Clinical manifestations

Infected with different Corynebacterium species, patients may present with different clinical symptoms, most of which are characterized by sore throat, fever, headache, nausea, vomiting, malaise, dyspnea, and enlarged lymph nodes [7].

In severe cases, high fever and dyspnea may be present.

Infection of other parts of the body, such as the pharynx can have sore throat, redness and swelling; infection of the conjunctiva can have redness, swelling, discomfort and itchy sensation of the eyes; infection of the vagina can have redness and swelling of the vulva, leukorrhea; infection of the urethra: there can be increased secretion at the urethral orifice, urgency, frequency and pain of urination, and other symptoms.

Throat and tonsils can be seen covered by a thick gray membrane.

In severe cases, patients can be seen to be cyanotic and pale.

Laboratory examination

Leukocytes are mildly elevated, with neutrophilia and thrombocytopenia in severe cases, but this test is not specific and only suggests that the patient may have a bacterial infection.

Leukocytes and erythrocytes can be detected in the urine, but this test result is not specific and only suggests that the patient may have infectious inflammation.

Pathogenesis

The detection of Corynebacterium is the “gold standard” for the diagnosis of Corynebacterium infection [8].

Methods include bacterial smear, bacterial culture, and diphtheria toxin test.

Specimen collection with a sterile swab directly from the patient’s nasal cavity, pharynx and other lesions of the pseudomembrane and its edges, made into a smear specimen, staining can be seen after the black or dark gray rods, can prove the existence of Corynebacterium infection.

Bacterial culture and diphtheria toxin test can further define the type of organisms. Positive culture result of Corynebacterium diphtheriae or detection of virulence can confirm the diagnosis of Corynebacterium diphtheriae infection.

Serologic tests

Polymerase Chain Reaction (PCR) can detect the gene fragments of Corynebacterium diphtheriae. Negative results can rule out Corynebacterium diphtheriae infection, while positive results require bacterial culture for further clarification.

Differential diagnosis

Symptoms of Corynebacterium infection need to be differentiated from inflammation of the mucous membranes of the throat caused by herpes simplex virus, Candida and other infections, which can be differentiated by bacterial smear, bacterial culture, diphtheria toxin test, PCR, and other methods.

Treatment

Aim of treatment: relieve symptoms and prevent complications.

Treatment principle: early treatment with diphtheria antitoxin and antibiotics, and active symptomatic treatment.

General treatment

Those who are diagnosed with infection should be quarantined and treated, and bed rest should be given for 2 weeks for light cases and 4 weeks for heavy cases, and those who are complicated with myocarditis should be absolutely bed rested, and premature activity is very likely to cause sudden death.

Give timely infusion of fluids, high-calorie diet, antipyretic, oxygen, strengthen oral care and other symptomatic supportive treatment, closely monitor the patient’s vital signs.

Pathogen treatment

Antitoxin treatment

Application of refined diphtheria antitoxin is a specific therapeutic measure for the treatment of this disease, but it can only neutralize the free exotoxin in the local lesions and blood, but not the toxin that has been combined with cells.

It should be used as early as possible, and the best effect is applied within 3 days at the beginning of the disease. The dosage should be determined according to the severity of the poisoning symptoms, the size of the pseudomembrane range and the treatment sooner or later, and it is not calculated according to the body weight.

Diphtheria antitoxin is injected once in full. Half of the amount is injected intramuscularly, half of the amount is diluted 20 times with glucose solution and slowly dripped intravenously, the whole amount is given once, and the same amount can be given again if the condition does not improve after 12 hours.

Before diphtheria antitoxin injection, skin allergy test must be done, and only the negative one can be applied, and the positive one can be injected according to the desensitization method, but it can not be injected intravenously.

Anti-infection treatment

Corynebacterium diphtheriae infection: early and timely injection of diphtheria antitoxin and administration of penicillin G, macrolides or cephalosporin antibiotics [9].

Corynebacterium diphtheriae-like infection: commonly treated with vancomycin.

Surgical treatment

Tracheotomy can be carried out prophylactically in patients with pharyngeal obstruction that severely affects respiration.

Prognosis

Cure

Corynebacterium diphtheriae infections are most often curable with aggressive treatment, and most symptoms disappear once the infection is cleared.

Corynebacterium diphtheriae can acquire immunity for a longer period of time after becoming ill and is virtually immune to re-infection.

Harmfulness

After Corynebacterium diphtheriae infection, untimely treatment can lead to the development of pseudomembrane to the nasopharynx, larynx, trachea, bronchus, lungs, etc., resulting in respiratory obstruction, and in severe cases, it can lead to asphyxiation and death.

Secondly a large number of exotoxins released into the blood can cause cardiac and neurofibrillary lesions and severe toxemia, which adversely affects the growth and development of children.

Daily

Daily management

Isolate the patient and tell him/her to pay attention to rest, and keep the indoor air fresh and circulating.

Adjust the diet structure, pay attention to light, easy to digest and high nutrition, avoid greasy and stimulating food, and carry out nutritional support intervention if necessary.

Keep the patient’s mouth clean to prevent secondary infection.

Use high-temperature boiling method, 5% phenol solution, 3% Lysol solution to soak and disinfect the used articles, and incinerate the used handkerchiefs.

Prevention

One can help to minimize Corynebacterium infections in the following ways.

Managing the source of infection

Isolate patients and treat them until 2 consecutive negative bacterial cultures are obtained the day after symptoms disappear, and release them from isolation no earlier than 7 days after treatment.

Carriers are isolated for 7 days and treated with penicillin or erythromycin and isolated until 3 negative nasopharyngeal swab cultures are obtained.

Close contacts are under medical observation for 7 days, and those who have not received full immunization against diphtheria toxoid can be prophylaxed by intramuscular injection of diphtheria antitoxin serum, noting that allergy testing is required before injection [10].

Cut off the infectious pathway

Patients should cover their mouths and noses with tissues when sneezing, and wear masks and protective clothing when contacting patients.

Strictly disinfect the items used by patients by boiling at high temperature for 15 minutes, disinfecting by immersion in 3% Lysol solution, and spraying the indoor air with the above disinfectant.

When Corynebacterium difficile is prevalent, reduce mass gatherings and temporarily suspend classes in early childhood and elementary school if necessary.

Protecting susceptible people

Reduce activities in crowded areas, wear masks when entering public environments, take good personal protection, and wash hands and ventilate frequently.

Recommended vaccination for infants and young children, currently commonly used “DPT” triple vaccine, in addition to diphtheria, tetanus toxoid vaccine can also be used.

For people traveling to endemic areas, diphtheria exotoxin antibody testing, no protection should be given to diphtheria antitoxin serum vaccination.