Corynebacterium diphtheriae: Difference between revisions
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Corynebacterium diphtheriae
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m (Text replacement - " species]]" to "]]") |
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+ | ==Background== |
||
− | = Corynebacterium diphtheriae = |
||
+ | ===History=== |
||
+ | *The name diphtheria is derived from the Greek word for leather, based on the appearance of the pseudomembrane that the organism produces |
||
− | == History == |
||
+ | ===Microbiology=== |
||
− | * Derived from the Greek word for leather |
||
+ | *Non-spore-forming, [[Shape::pleomorphic]], unencapsulated, nonmotile [[Stain::Gram-positive]] [[Shape::bacillus]] with clubbed ends |
||
− | == Microbiology == |
||
+ | *Needs to be cultured on special media, so notify the lab |
||
+ | **On Loeffler medium, outgrows other throat flora by 12 to 18 hours |
||
+ | *Classic "Chinese character" appearance on Gram stain (pallisading) of all [[Corynebacterium species|corynebacteria]] |
||
+ | *Metachromatic granules on methylene blue |
||
+ | *Four biovars: ''gravis'', ''intermedius'', ''mitis'', and ''belfanti'' |
||
+ | **Based on morphology, fermentation, and hemolysis, but now more often based on PCR ribotyping |
||
+ | **Not clinically significant |
||
+ | *Exotoxin production is provided by the ''tox'' gene |
||
+ | **The gene is carried by bacteriophages, which convert non-toxigenic strains into toxigenic ones |
||
+ | **Toxin production is not necessary for the life cycle |
||
+ | ===Pathophysiology=== |
||
− | * Non-spore-forming, pleomorphic, unencapsulated, nonmotile Gram-positive bacillus with clubbed ends |
||
− | * Needs to be cultured on special media, so notify the lab |
||
− | ** On Loeffler medium, outgrows other throat flora by 12 to 18 hours |
||
− | * Classic "Chinese character" appearance on Gram stain of all Corynebacteria |
||
− | * Metachromatic granules on methylene blue |
||
− | * Four biovars: gravis, intermedius, mitis, and belfanti |
||
− | ** Based on morphology, fermentation, and hemolysis, but now more often based on PCR ribotyping |
||
− | ** Not clinically significant |
||
+ | *Toxigenic strains produce a polypeptide exotoxin that is cleaved into two segments, which comprise three domains |
||
− | == Pathophysiology == |
||
+ | **Segment B contains the receptor-binding and transmembrane domains, and facilitates binding to heparin-binding epidermal growth factor receptor |
||
+ | **Segment A is the active segment, which enters the cytosol after B binds and inactivates mammalian tRNA translocase (elongation factor 2), thus stopping protein synthesis and killing the cell |
||
+ | ***A single molecule is enough to kill a cell |
||
+ | *The exotoxin affects all cells, but heart, nerves, and kidneys are particularly sensitive |
||
+ | *In the respiratory tract, exotoxin causes the formation of a necrotic coagulum of fibrin, WBCs, RBCs, and epithelial cells |
||
+ | **Appears clinically as a pseudomembrane |
||
+ | *The lethal dose may be as low as 100 ng/kg body weight |
||
+ | ===Epidemiology=== |
||
− | * Contains a polypeptide exotoxin that is cleaved into segment A, the active segment, and B, which binds receptors on susceptible cells (heparin-binding epidermal growth factor receptor) |
||
− | * Segment A enters the cytosol after B binds, and inactivates mammalian tRNA translocase (elongation factor 2), which stops protein synthesis |
||
− | ** Affects all cells, but heart, nerves, and kidneys are particularly sensitive |
||
− | * In the respiratory tract, causes the formation of a necrotic coagulum of fibrin, WBCs, RBCs, and epithelial cells |
||
− | ** Appears clinically as a pseudomemrane |
||
+ | *Spread by droplets and direct contact, and via fomites |
||
− | == Epidemiology == |
||
+ | *Mostly occurs in colder months |
||
+ | *Asymptomatic carriage is an important reservoir for the organism, with 3-5% carriage rates in endemic areas |
||
+ | **May also be carried by horses, cattle, and domestic cats |
||
+ | *Disease is rare in immunized populations |
||
+ | *Risk factors include travel or residence within an epidemic or endemic setting, and a history of inadequate vaccination |
||
+ | **Currently, the highest rates are seen in India, and particularly in Kerala state in people older than 10 years |
||
+ | *Maternal antibodies provide immunity until about 6 months |
||
+ | ==Clinical Manifestations== |
||
− | * Spread by droplets and direct contact, and via fomites |
||
− | * Mostly occurs in colder months |
||
− | * Asymptomatic carriage is an important reservoir for the organism, with 3-5% carriage rates in endemic areas |
||
− | == |
+ | ===Diphtheria=== |
− | * |
+ | *Clinical syndrome of pharyngeal infection with systemic toxicity caused by ''C. diphtheriae'' and ''[[Corynebacterium ulcerans|C. ulcerans]]'' |
+ | *Incubation period of [[Usual incubation period::2 to 4 days]] |
||
+ | *Low-grade fever, hoarseness, pain, and laryngeal pseudomembrane that can cause stridor and obstruction |
||
+ | **Pseudomembrane starts white but later dirty gray with patches of green or black |
||
+ | **Bleeding if membrane is removed |
||
+ | **Can have a bullneck appearance |
||
+ | *Can also have serosanguineous nasal discharge and cervical lymphadenopathy |
||
+ | *Palatal paralysis and cranial nerve defects may cause dysphagia |
||
+ | *Systemic symptoms related to extent of local disease |
||
− | === |
+ | =====Myocarditis===== |
+ | *Occurs in 10-25% of cases |
||
− | * Incubation period of 2-4 days |
||
+ | *Can range from acute heart failure and cardiogenic shock to more subacute heart failure and dilatation |
||
− | * Low-grade fever, hoarseness, pain, and laryngeal pseudomembrane that can cause stridor and obstruction |
||
+ | **Can be monitored with AST (?and troponin?) |
||
− | ** Pseudomembrane starts white but later dirty gray with patches of green or black |
||
+ | *ECG may show ST-T wave changes and [[first-degree heart block]], which can progress to [[complete heart block]] |
||
− | ** Bleeding if membrane is removed |
||
+ | **Mortality is higher with ECG changes, and highest with AV blocks and LBBB |
||
− | ** Can have a bullneck appearance |
||
+ | **Can be permanent |
||
− | * Can also have serosanguineous nasal discharge and cervical lymphadenopathy |
||
+ | **Monitor for arrhythmias |
||
− | * Palatal paralysis and cranial nerve defects may cause dysphagia |
||
− | * Systemic symptoms related to extent of local disease |
||
− | ==== |
+ | =====Neurotoxicity===== |
+ | *Acutely, can manifest as paralysis of the soft palate and posterior pharynx, causing dysphagia |
||
− | * 10-25% of cases |
||
+ | **Followed by cranial nerve defects |
||
− | * Can range from acute heart failure and cardiogenic shock to more subacute heart failure and dilatation |
||
+ | *After 10 days to 3 months, can develop a peripheral motor neuropathy from demyelination |
||
− | ** Can be monitored with AST (?and troponin?) |
||
+ | **Typically descending paralysis by can still be confused with [[Guillain-Barré syndrome]] |
||
− | * ECG may show ST-T wave changes and first-degree heart block, which can progress to complete heart block |
||
+ | **Generally fully resolves with time |
||
− | ** Mortality is higher with ECG changes, and highest with AV blocks and LBBB |
||
− | ** Can be permanent |
||
− | ** Monitor for arrhythmias |
||
− | ==== |
+ | =====Acute Tubular Necrosis===== |
+ | *Caused by both the toxin itself and the septic shock |
||
− | * Acutely, can manifest as paralysis of the soft palate and posterior pharynx, causing dysphagia |
||
− | ** Followed by cranial nerve defects |
||
− | * After 10 days to 3 months, can develop a peripheral motor neuropathy from demyelination |
||
− | ** Generally fully resolves with time |
||
− | ==== |
+ | ====Complications and Prognosis==== |
+ | *Suffocation from aspiration of the pseudomembrane |
||
− | * Caused by both the toxin itself and the septic shock |
||
+ | *Rarely, bacteremia, endocarditis, and arthritis from hematogenous spread |
||
+ | *Can have post-infectious, autoimmune-mediated complications including neuropathy and carditis |
||
+ | *Mortality 3-12% even now, usually from asphyxiation or [[myocarditis]], but is rare in immunized patients |
||
+ | ===Cutaneous Diphtheria=== |
||
− | === Differential Diagnosis === |
||
+ | *Usually caused by non-toxigenic strains |
||
− | * Mononucleosis |
||
+ | *Can also cause chronic non-healing ulcers with dirty-gray membrane (or not), often with concomitant [[Staphylococcus aureus]] or [[Streptococcus pyogenes]] |
||
− | * Streptococcal or viral pharyngitis |
||
+ | *Generally not invasive and can cause immunity, but also contributes to the organism's reservoir |
||
− | * Vincent angina |
||
− | * Acute epiglottitis |
||
− | === |
+ | ===Asymptomatic Carrier State=== |
+ | *''C. diphtheriae'' not particularly invascive and can colonize the respiratory tract and skin |
||
− | * Clinical diagnosis based on: |
||
+ | *Common in areas that do not vaccinate, as well as inner cities and rural areas |
||
− | ** Mildly painful tonsilitis or pharyngitis with a membrane, especially if the memrane extends to the uvula and soft palate |
||
− | ** Adenopathy and cervical swelling, especially if assocaited with memranous pharyngitis and signs of systemic toxicity |
||
− | ** Hoarseness and stridor |
||
− | ** Palatal paralysis |
||
− | ** Serosanguineous nasal discharge with associated mucosal membrane |
||
− | ** Temperature not over 102.5ºF (39ºC) |
||
− | ** History of travel to endemic country |
||
− | * Can confirm with culture and Gram stain ("Chinese characters") |
||
− | * PCR for the toxin gene exists |
||
− | === |
+ | ===Non-Toxigenic Strains=== |
+ | *As well as cutaneous diphtheria, these strains can also cause [[bacteremia]] and [[endocarditis]], particularly in those with chronic alcohol use, dental disease, and intravenous drug use |
||
− | * Treat presumptively while awaiting confirmation of the diagnosis |
||
− | * Start with with diphtheria antitoxin (DAT) |
||
− | ** Antiserum made in horses |
||
− | ** Prevents toxin from entering the cell |
||
− | ** First must rule out horse protein hypersensitivity |
||
− | *** History of allergy |
||
− | *** Scratch test: drop of 1:1000 dilution applied to superficial scratch; if no wheal in 15 minutes, inject 0.02 mL of 1:1000 dilution intracutaneously |
||
− | **** Epipen at the ready! |
||
− | ** Dose depends on duration of symptoms |
||
− | *** ≤48 hours: 20,000-40,000 units |
||
− | *** ≥3 days: 80,000-120,000 units, including anyone with neck swelling |
||
− | *** Nasopharyngeal: 40,000-80,000 units |
||
− | ** Diluted in 250-500 mL NS and infused over 60-120 minutes |
||
− | ** 10% risk of serum sickness |
||
− | * Adults |
||
− | ** Penicillin G 600,000 units IM q12h |
||
− | ** Pencillin V 250 mg |
||
− | ** Erythromycin 500 mg qid |
||
− | ** Duration 14 days |
||
− | * Culture 2 weeks after treatment for test-of-cure |
||
+ | ==Differential Diagnosis== |
||
− | === Infection Control === |
||
+ | *[[Infectious mononucleosis]] |
||
− | * Must be in isolation throughout therapy and until two negative cultures at 24 hour intervals |
||
+ | *Streptococcal or viral [[pharyngitis]] |
||
+ | *[[Vincent angina]] |
||
+ | *[[Acute epiglottitis]] |
||
+ | *Retropharyngeal space infection |
||
+ | *Oropharyngeal candidiasis |
||
+ | *Acute HIV syndrome |
||
+ | ==Diagnosis== |
||
− | === Complications and Prognosis === |
||
+ | *Clinical diagnosis based on: |
||
− | * Suffocation from aspiration of the pseudomembrane |
||
+ | **Mildly painful tonsilitis or pharyngitis with a membrane, especially if the memrane extends to the uvula and soft palate |
||
− | * Rarely, bacteremia, endocarditis, and arthritis from hematogenous spread |
||
+ | **Adenopathy and cervical swelling, especially if assocaited with memranous pharyngitis and signs of systemic toxicity |
||
− | * Mortality 3-12% even now, usually from asphyxiation or myocarditis, but is rare in immunized patients |
||
+ | **Hoarseness and stridor |
||
+ | **Palatal paralysis |
||
+ | **Serosanguineous nasal discharge with associated mucosal membrane |
||
+ | **Temperature not over 102.5ºF (39ºC) |
||
+ | **History of travel to endemic country |
||
+ | *Collected specimens from nose or throat, and any mucosal or cutaneous lesions |
||
+ | **Ideally collected from below the pseudomembrane |
||
+ | **Can also collect a piece of pseudomembrane |
||
+ | **Notify lab, who will use modified Tinsdale agar or cystine-tellurite blood agar |
||
+ | **Gram stain should show classic coryneform "Chinese letter" appearance, which may be dismissed as normal respiratory flora unless specific testing for diphtheria is requested |
||
+ | *Culture requires Tinsdale medium (contains teluride and cysteine), inhibits non-pathogenic [[Corynebacterium]] |
||
+ | *PCR for the toxin gene exists, and is followed by serology to demonstrate toxin production |
||
+ | *Serology is done for ''tox'' gene positive strains using the Elek test |
||
+ | ==Management== |
||
− | == Cutaneous Diphteria == |
||
+ | ===Pharyngeal Diphtheria=== |
||
− | * Can also cause chronic non-healing ulcers with dirty-gray membrane, often with concommitant ''Staph. aureus'' or group A streptococci |
||
− | * Generally not invasive and can cause immunity, but also contribute to the organism's reservoir |
||
+ | *Supportive management, with a focus on airway protection |
||
− | == Carrier State == |
||
+ | **Preemptive intubation is recommended in most situations |
||
+ | **May require tracheotomy if severe |
||
+ | **May be useful to add [[carnithine]] to improve myocardial function |
||
+ | *If concern for pharyngeal diphtheria, then need to treat presumptively with antitoxin and penicillin while awaiting confirmation of the diagnosis |
||
+ | *Start with with equine-derived diphtheria antitoxin (DAT) |
||
+ | **Prevents toxin from entering the cell |
||
+ | **First must rule out horse protein hypersensitivity |
||
+ | ***History of allergy |
||
+ | ***Scratch test: drop of 1:1000 dilution applied to superficial scratch; if no wheal in 15 minutes, inject 0.02 mL of 1:1000 dilution intracutaneously |
||
+ | ****Epipen at the ready! |
||
+ | **Dose depends on duration of symptoms |
||
+ | ***≤48 hours: 20,000-40,000 units |
||
+ | ***≥3 days: 80,000-120,000 units, including anyone with neck swelling |
||
+ | ***Nasopharyngeal: 40,000-80,000 units |
||
+ | **Diluted in 250-500 mL NS and infused over 60-120 minutes |
||
+ | **10% risk of serum sickness |
||
+ | *Also treat with a 14-day course of an appropriate antibiotic |
||
+ | **[[Is treated by::Procaine penicillin G]] 600,000 units IM q12h (300,000 units if weight ≤10 kg) |
||
+ | ***Can switch or oral [[penicillin]] once able to take oral medication |
||
+ | **[[Is treated by::Erythromycin]] 40 mg/kg/day (max 2 g) PO/IV divided qid |
||
+ | *Test of cure should be done at least 24 hours after completing treatment, with two cultures from both nose and throat at least 24 hours apart |
||
+ | **If still positive, extend treatment for another 10 days |
||
+ | *After acute illness, still need to vaccinate since infection does not generate long-term immunity |
||
+ | ===Cutaneous Diphtheria=== |
||
− | * ''C. diphtheriae'' not particularly invascive and can colonize the respiratory tract and skin |
||
− | * Common in areas that do not vaccinate, as well as inner cities and rural areas |
||
− | * Should be treated to prevent infection with benzathine penicillin G 600,000 to 1,200,000 units IM once |
||
+ | *Treated with a 14-day course of antibiotics, as above |
||
− | == Prophylaxis == |
||
+ | *Test of cure should be done at least 24 hours after completing treatment, with two cultures from cutaneous lesions at least 24 hours apart |
||
+ | ===Asymptomatic Carrier State=== |
||
− | * Healthcare workers, close contacts, etc. regardless of immunization status |
||
− | * Collect culture specimens before treatment (for public health tracing) |
||
− | * Treated to prevent infection with benzathine penicillin G 600,000 to 1,200,000 units IM once |
||
− | * Immunize if not immunized |
||
+ | *Should be treated to prevent transmission to others |
||
− | == Vaccination == |
||
+ | *[[Benzathine penicillin G]] 600,000 units (<6 years) to 1,200,000 units (≥6 years) IM once, or [[erythromycin]] 40 mg/kg/day (max 1 g) for 7 to 10 days |
||
+ | *If cultures still positive after treatment, do another 10-day course of [[erythromycin]] (more effective than [[penicillin]]) |
||
+ | |||
+ | ==Prevention== |
||
+ | |||
+ | ===Infection Control=== |
||
+ | |||
+ | *Contact precautions for cutaneous diphtheria, contact and droplet precautions for pharyngeal diphtheria |
||
+ | *Must be in isolation until treatment is completed ''and'' until two negative cultures collected at least 24 hours apart |
||
+ | |||
+ | ===Prophylaxis=== |
||
+ | |||
+ | *Indicated for healthcare workers exposed to nasopharyngeal secretions, household contacts, other habitual close contacts, people sharing utensils or kitchen facilities, and childcare workers |
||
+ | **Indicated ''regardless of'' immunization status |
||
+ | **Even if the contact is transient, but excludes those who were wearing appropriate PPE at the time |
||
+ | *Procedure |
||
+ | **Monitor for symptoms for 7 days |
||
+ | **Collect culture specimens before treatment |
||
+ | **Antimicrobial prophylaxis with either [[benzathine penicillin G]] 600,000 units (<30 kg) to 1,200,000 units (≥30 kg) IM once, or [[erythromycin]] 40 mg/kg/day (max 1 g) for 7 to 10 days |
||
+ | **Repeat culture after treatment, and repeat a 10-day course of [[erythromycin]] if still positive (more effective than [[penicillin]]) |
||
+ | *If previously vaccinated, give a Td/Tdap booster if it's been more than 5 years from last dose |
||
+ | *If not fully vaccinated, complete the vaccine series |
||
+ | |||
+ | ===Vaccination=== |
||
+ | |||
+ | *The available vaccine is against diphtheria toxin, so protects against the harmful effects of infection but does not directly prevent infection |
||
+ | **Asymptomatic carriage still occurs, though at a lower population level |
||
+ | *Diphtheria toxoid vaccine is given as a ≥3-dose series in childhood |
||
+ | **Typically in combination with others (e.g. DTaP-IPV-HiB at 2, 4, 6, and 18 months) |
||
+ | **Adult catch-up schedule would be Tdap followed 4 weeks later by Td followed 6 to 12 months later by another Td |
||
+ | *Adults should get a Tdap booster in adulthood at least once, and Td booster every 10 years |
||
+ | |||
+ | {{DISPLAYTITLE:''Corynebacterium diphtheriae''}} |
||
+ | [[Category:Gram-positive bacilli]] |
Latest revision as of 15:35, 18 February 2022
Background
History
- The name diphtheria is derived from the Greek word for leather, based on the appearance of the pseudomembrane that the organism produces
Microbiology
- Non-spore-forming, pleomorphic, unencapsulated, nonmotile Gram-positive bacillus with clubbed ends
- Needs to be cultured on special media, so notify the lab
- On Loeffler medium, outgrows other throat flora by 12 to 18 hours
- Classic "Chinese character" appearance on Gram stain (pallisading) of all corynebacteria
- Metachromatic granules on methylene blue
- Four biovars: gravis, intermedius, mitis, and belfanti
- Based on morphology, fermentation, and hemolysis, but now more often based on PCR ribotyping
- Not clinically significant
- Exotoxin production is provided by the tox gene
- The gene is carried by bacteriophages, which convert non-toxigenic strains into toxigenic ones
- Toxin production is not necessary for the life cycle
Pathophysiology
- Toxigenic strains produce a polypeptide exotoxin that is cleaved into two segments, which comprise three domains
- Segment B contains the receptor-binding and transmembrane domains, and facilitates binding to heparin-binding epidermal growth factor receptor
- Segment A is the active segment, which enters the cytosol after B binds and inactivates mammalian tRNA translocase (elongation factor 2), thus stopping protein synthesis and killing the cell
- A single molecule is enough to kill a cell
- The exotoxin affects all cells, but heart, nerves, and kidneys are particularly sensitive
- In the respiratory tract, exotoxin causes the formation of a necrotic coagulum of fibrin, WBCs, RBCs, and epithelial cells
- Appears clinically as a pseudomembrane
- The lethal dose may be as low as 100 ng/kg body weight
Epidemiology
- Spread by droplets and direct contact, and via fomites
- Mostly occurs in colder months
- Asymptomatic carriage is an important reservoir for the organism, with 3-5% carriage rates in endemic areas
- May also be carried by horses, cattle, and domestic cats
- Disease is rare in immunized populations
- Risk factors include travel or residence within an epidemic or endemic setting, and a history of inadequate vaccination
- Currently, the highest rates are seen in India, and particularly in Kerala state in people older than 10 years
- Maternal antibodies provide immunity until about 6 months
Clinical Manifestations
Diphtheria
- Clinical syndrome of pharyngeal infection with systemic toxicity caused by C. diphtheriae and C. ulcerans
- Incubation period of 2 to 4 days
- Low-grade fever, hoarseness, pain, and laryngeal pseudomembrane that can cause stridor and obstruction
- Pseudomembrane starts white but later dirty gray with patches of green or black
- Bleeding if membrane is removed
- Can have a bullneck appearance
- Can also have serosanguineous nasal discharge and cervical lymphadenopathy
- Palatal paralysis and cranial nerve defects may cause dysphagia
- Systemic symptoms related to extent of local disease
Myocarditis
- Occurs in 10-25% of cases
- Can range from acute heart failure and cardiogenic shock to more subacute heart failure and dilatation
- Can be monitored with AST (?and troponin?)
- ECG may show ST-T wave changes and first-degree heart block, which can progress to complete heart block
- Mortality is higher with ECG changes, and highest with AV blocks and LBBB
- Can be permanent
- Monitor for arrhythmias
Neurotoxicity
- Acutely, can manifest as paralysis of the soft palate and posterior pharynx, causing dysphagia
- Followed by cranial nerve defects
- After 10 days to 3 months, can develop a peripheral motor neuropathy from demyelination
- Typically descending paralysis by can still be confused with Guillain-Barré syndrome
- Generally fully resolves with time
Acute Tubular Necrosis
- Caused by both the toxin itself and the septic shock
Complications and Prognosis
- Suffocation from aspiration of the pseudomembrane
- Rarely, bacteremia, endocarditis, and arthritis from hematogenous spread
- Can have post-infectious, autoimmune-mediated complications including neuropathy and carditis
- Mortality 3-12% even now, usually from asphyxiation or myocarditis, but is rare in immunized patients
Cutaneous Diphtheria
- Usually caused by non-toxigenic strains
- Can also cause chronic non-healing ulcers with dirty-gray membrane (or not), often with concomitant Staphylococcus aureus or Streptococcus pyogenes
- Generally not invasive and can cause immunity, but also contributes to the organism's reservoir
Asymptomatic Carrier State
- C. diphtheriae not particularly invascive and can colonize the respiratory tract and skin
- Common in areas that do not vaccinate, as well as inner cities and rural areas
Non-Toxigenic Strains
- As well as cutaneous diphtheria, these strains can also cause bacteremia and endocarditis, particularly in those with chronic alcohol use, dental disease, and intravenous drug use
Differential Diagnosis
- Infectious mononucleosis
- Streptococcal or viral pharyngitis
- Vincent angina
- Acute epiglottitis
- Retropharyngeal space infection
- Oropharyngeal candidiasis
- Acute HIV syndrome
Diagnosis
- Clinical diagnosis based on:
- Mildly painful tonsilitis or pharyngitis with a membrane, especially if the memrane extends to the uvula and soft palate
- Adenopathy and cervical swelling, especially if assocaited with memranous pharyngitis and signs of systemic toxicity
- Hoarseness and stridor
- Palatal paralysis
- Serosanguineous nasal discharge with associated mucosal membrane
- Temperature not over 102.5ºF (39ºC)
- History of travel to endemic country
- Collected specimens from nose or throat, and any mucosal or cutaneous lesions
- Ideally collected from below the pseudomembrane
- Can also collect a piece of pseudomembrane
- Notify lab, who will use modified Tinsdale agar or cystine-tellurite blood agar
- Gram stain should show classic coryneform "Chinese letter" appearance, which may be dismissed as normal respiratory flora unless specific testing for diphtheria is requested
- Culture requires Tinsdale medium (contains teluride and cysteine), inhibits non-pathogenic Corynebacterium
- PCR for the toxin gene exists, and is followed by serology to demonstrate toxin production
- Serology is done for tox gene positive strains using the Elek test
Management
Pharyngeal Diphtheria
- Supportive management, with a focus on airway protection
- Preemptive intubation is recommended in most situations
- May require tracheotomy if severe
- May be useful to add carnithine to improve myocardial function
- If concern for pharyngeal diphtheria, then need to treat presumptively with antitoxin and penicillin while awaiting confirmation of the diagnosis
- Start with with equine-derived diphtheria antitoxin (DAT)
- Prevents toxin from entering the cell
- First must rule out horse protein hypersensitivity
- History of allergy
- Scratch test: drop of 1:1000 dilution applied to superficial scratch; if no wheal in 15 minutes, inject 0.02 mL of 1:1000 dilution intracutaneously
- Epipen at the ready!
- Dose depends on duration of symptoms
- ≤48 hours: 20,000-40,000 units
- ≥3 days: 80,000-120,000 units, including anyone with neck swelling
- Nasopharyngeal: 40,000-80,000 units
- Diluted in 250-500 mL NS and infused over 60-120 minutes
- 10% risk of serum sickness
- Also treat with a 14-day course of an appropriate antibiotic
- Procaine penicillin G 600,000 units IM q12h (300,000 units if weight ≤10 kg)
- Can switch or oral penicillin once able to take oral medication
- Erythromycin 40 mg/kg/day (max 2 g) PO/IV divided qid
- Procaine penicillin G 600,000 units IM q12h (300,000 units if weight ≤10 kg)
- Test of cure should be done at least 24 hours after completing treatment, with two cultures from both nose and throat at least 24 hours apart
- If still positive, extend treatment for another 10 days
- After acute illness, still need to vaccinate since infection does not generate long-term immunity
Cutaneous Diphtheria
- Treated with a 14-day course of antibiotics, as above
- Test of cure should be done at least 24 hours after completing treatment, with two cultures from cutaneous lesions at least 24 hours apart
Asymptomatic Carrier State
- Should be treated to prevent transmission to others
- Benzathine penicillin G 600,000 units (<6 years) to 1,200,000 units (≥6 years) IM once, or erythromycin 40 mg/kg/day (max 1 g) for 7 to 10 days
- If cultures still positive after treatment, do another 10-day course of erythromycin (more effective than penicillin)
Prevention
Infection Control
- Contact precautions for cutaneous diphtheria, contact and droplet precautions for pharyngeal diphtheria
- Must be in isolation until treatment is completed and until two negative cultures collected at least 24 hours apart
Prophylaxis
- Indicated for healthcare workers exposed to nasopharyngeal secretions, household contacts, other habitual close contacts, people sharing utensils or kitchen facilities, and childcare workers
- Indicated regardless of immunization status
- Even if the contact is transient, but excludes those who were wearing appropriate PPE at the time
- Procedure
- Monitor for symptoms for 7 days
- Collect culture specimens before treatment
- Antimicrobial prophylaxis with either benzathine penicillin G 600,000 units (<30 kg) to 1,200,000 units (≥30 kg) IM once, or erythromycin 40 mg/kg/day (max 1 g) for 7 to 10 days
- Repeat culture after treatment, and repeat a 10-day course of erythromycin if still positive (more effective than penicillin)
- If previously vaccinated, give a Td/Tdap booster if it's been more than 5 years from last dose
- If not fully vaccinated, complete the vaccine series
Vaccination
- The available vaccine is against diphtheria toxin, so protects against the harmful effects of infection but does not directly prevent infection
- Asymptomatic carriage still occurs, though at a lower population level
- Diphtheria toxoid vaccine is given as a ≥3-dose series in childhood
- Typically in combination with others (e.g. DTaP-IPV-HiB at 2, 4, 6, and 18 months)
- Adult catch-up schedule would be Tdap followed 4 weeks later by Td followed 6 to 12 months later by another Td
- Adults should get a Tdap booster in adulthood at least once, and Td booster every 10 years