Infectious Disease and Microbiology – Dicrocoelium dendriticum

Overview

Dicrocoelium dendriticum is a trematode helminth, commonly referred to as the lancet liver fluke. Human infection is rare and is usually asymptomatic, although the parasite may occasionally involve the biliary tract and cause symptoms such as biliary colic.

Microbiologic Characteristics

D. dendriticum is a trematode (fluke) that primarily inhabits the biliary system of its usual mammalian hosts.

Human infection is unusual and generally occurs accidentally.

Epidemiology

Dicrocoelium dendriticum has a worldwide distribution, but true human infection is rare.

Its eggs may sometimes be identified in human stool specimens without indicating genuine infection.

Spurious Passage of Eggs

A particularly important point is that eggs of D. dendriticum may appear in stool after a person eats infected animal liver.

In this situation, the parasite has not established infection in the patient. The eggs are simply passing through the gastrointestinal tract.

Therefore, detection of D. dendriticum ova in stool does not always prove true human parasitism.

Clinical Infection

Most true infections are asymptomatic.

When symptoms occur, they are usually related to the biliary tract and may include:

• Right upper quadrant discomfort

• Intermittent biliary pain

• Biliary colic

Symptomatic disease is exceptional.

Diagnosis

Diagnosis is based on parasitologic examination of stool specimens for characteristic eggs.

Because false-positive or spurious egg passage can occur, stool findings should be interpreted together with the clinical picture and dietary history.

Repeated stool examinations may help distinguish true infection from transient passage after ingestion of infected animal liver.

Treatment

Treatment is generally unnecessary in asymptomatic patients.

For the rare patient with symptomatic infection in whom other causes of biliary symptoms have been excluded, the source recommends:

Praziquantel 25 mg/kg orally every 8 hours for 3 doses

High-Yield Clinical Pattern

Dicrocoelium eggs found in stool

• ●

No compatible symptoms

• ●

Recent ingestion of animal liver

→ Consider spurious passage rather than true infection

Exam Essentials

Organism: Dicrocoelium dendriticum

Type: Trematode helminth

Common name: Lancet liver fluke

Distribution: Worldwide

Human infection: Rare

Typical course: Usually asymptomatic

Possible manifestation: Biliary colic

Diagnosis: Stool parasitologic examination

Important pitfall: Eggs in stool may represent spurious passage after eating infected animal liver

Treatment for symptomatic true infection: Praziquantel

Key clinical pearl: Finding Dicrocoelium dendriticum eggs in stool does not automatically mean true infection; first consider spurious passage from recently consumed infected liver.

Infectious Disease and Microbiology – Cyclospora cayetanensis

Overview

Cyclospora cayetanensis is an intestinal protozoan parasite that causes cyclosporiasis, an enteric infection characterized primarily by prolonged, watery diarrhea. Infection is commonly associated with ingestion of contaminated food or water and may affect both immunocompetent and immunocompromised individuals.

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Microbiologic Characteristics

Cyclospora cayetanensis is a coccidian protozoan parasite.

Important microbiologic features include:

• Protozoan organism

• Oocysts demonstrate variable acid-fast staining

• Previously described as a coccidian-like body

• Oocysts can demonstrate characteristic autofluorescence under ultraviolet fluorescence microscopy

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Epidemiology

Cyclospora has a worldwide distribution, although the frequency of recognized infection varies considerably by geographic region.

Cases have historically been reported from areas including:

• Nepal

• Peru

• The Caribbean

• India

• Pakistan

• Sri Lanka

• Mexico

• Morocco

• Turkey

• Malaysia

• Australia

Cases also occur in travelers returning from endemic regions.

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Infection Without Travel

Although travel history can provide an important clue, absence of international travel does not exclude cyclosporiasis.

Locally acquired infections and outbreaks can occur, including among otherwise healthy individuals.

In patients with prolonged diarrhea, immunocompromising conditions may influence the severity and duration of illness, but Cyclospora infection is certainly not restricted to immunocompromised patients.

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Transmission

Humans acquire cyclosporiasis primarily by consuming food or water contaminated with sporulated oocysts.

Fresh produce has been an important vehicle in recognized outbreaks.

Unlike some other intestinal parasites, freshly excreted Cyclospora oocysts are not immediately infectious. They must mature in the environment before becoming capable of infecting another person.

Therefore, direct person-to-person transmission is relatively unlikely.

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Clinical Infection

The characteristic manifestation is prolonged watery diarrhea.

Symptoms may include:

• Frequent watery stools

• Abdominal cramping

• Bloating

• Nausea

• Loss of appetite

• Fatigue

• Weight loss

• Malaise

Symptoms may persist for an extended period and can follow a relapsing pattern if infection is untreated.

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Disease in Immunocompetent Patients

In immunocompetent individuals, cyclosporiasis may eventually be self-limited, although symptoms can persist for weeks.

The prolonged duration of watery diarrhea is an important diagnostic clue.

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Disease in Immunocompromised Patients

Immunocompromised patients may experience more persistent or severe gastrointestinal disease.

Historically, prolonged infection has been particularly recognized in patients with advanced HIV infection.

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Diagnosis

Diagnosis depends primarily on detecting Cyclospora oocysts in stool specimens.

Because oocysts may not be continuously shed, examination of multiple stool specimens may improve diagnostic sensitivity.

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Concentrated Stool Examination

Concentration techniques can increase the likelihood of detecting the parasite.

A modified acid-fast stain, such as a modified Kinyoun technique, can demonstrate the oocysts.

Importantly, staining may be variable, so some oocysts may stain strongly while others stain only weakly or not at all.

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Fluorescence Microscopy

Fresh stool specimens can also be examined using fluorescence microscopy.

Cyclospora oocysts demonstrate characteristic autofluorescence, which can help distinguish them from other intestinal organisms.

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Molecular Diagnosis

Where available, molecular gastrointestinal panels or specific PCR-based assays can also detect Cyclospora cayetanensis.

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Treatment

The preferred antimicrobial treatment is:

Trimethoprim-sulfamethoxazole (TMP-SMX)

The source describes a regimen of:

TMP-SMX 160/800 mg orally every 12 hours

Treatment duration may need to be longer in immunocompromised patients than in otherwise healthy individuals.

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Alternative Treatment

For patients unable to receive TMP-SMX, alternative therapy may be considered.

The source lists:

Ciprofloxacin 500 mg orally every 12 hours

However, alternative agents may be less effective than TMP-SMX, making TMP-SMX the preferred therapy when it can be safely administered.

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Recurrent Infection

Recurrence can occur, particularly in immunocompromised patients.

The source describes secondary prophylaxis with intermittent TMP-SMX following treatment in selected patients with recurrent disease.

The need for prolonged or suppressive therapy should be individualized according to immune status and recurrence risk.

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Prevention

Prevention focuses on reducing exposure to contaminated food and water.

Important measures include:

• Safe drinking water

• Appropriate sanitation

• Careful handling of fresh produce

• Washing fruits and vegetables

• Avoiding potentially contaminated food or water during travel

Because oocysts require environmental maturation before becoming infectious, direct transmission from freshly passed stool is less efficient than with several other intestinal pathogens.

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High-Yield Clinical Pattern

Traveler or foodborne exposure

Prolonged or relapsing watery diarrhea

Variably acid-fast oocysts with autofluorescence

→ Think Cyclospora cayetanensis

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Exam Essentials

Organism: Cyclospora cayetanensis

Type: Protozoan parasite

Disease: Cyclosporiasis

Distribution: Worldwide

Transmission: Contaminated food or water

Major manifestation: Prolonged watery diarrhea

Stool finding: Oocysts with variable acid-fast staining

Special diagnostic clue: Autofluorescence under fluorescence microscopy

Diagnosis: Concentrated stool examination, modified acid-fast staining, fluorescence microscopy, or molecular testing

Preferred treatment: TMP-SMX

Important complication: Persistent or recurrent disease, particularly with immunosuppression

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Key clinical pearl: The classic combination is prolonged watery diarrhea + variably acid-fast stool oocysts + autofluorescence = Cyclospora cayetanensis.

Infectious Disease and Microbiology – Curvularia Species

Overview

Curvularia species are dematiaceous (darkly pigmented), filamentous fungi that are uncommon causes of human infection. They most often produce keratitis or cutaneous and subcutaneous infections, although invasive disease involving the lungs, heart, bone, or other deep tissues can rarely occur.

Important species include C. boedijn, C. geniculata, C. lunata, C. pallescens, and C. senegalensis.

Microbiologic Characteristics

Curvularia species are dematiaceous filamentous fungi (molds).

In infected tissues, fungal elements may appear as:

• Yeast-like forms

• Pseudohyphae

• Septate, pigmented hyphae

The presence of melanin within the fungal cell wall produces the characteristic dark pigmentation associated with dematiaceous fungi.

Epidemiology

Human infection with Curvularia is rare.

These organisms are environmental molds, and human disease generally follows exposure or traumatic introduction of fungal material into tissues.

Keratitis

Fungal keratitis is an important manifestation of Curvularia infection.

Infection may follow corneal trauma, particularly when the eye has been exposed to environmental or plant material.

Clinical manifestations may include:

• Eye pain

• Redness

• Photophobia

• Excessive tearing

• Corneal ulceration

• Reduced visual acuity

Severe infection can threaten vision if not recognized and treated promptly.

Skin and Subcutaneous Tissue Infection

Curvularia may cause localized cutaneous or subcutaneous fungal infection, often following traumatic inoculation.

Patients may develop:

• Nodules

• Plaques

• Ulcerative lesions

• Cysts or abscess-like lesions

• Chronic localized inflammation

These infections fall within the broader spectrum of disease caused by dematiaceous fungi.

Deep-Tissue Infection

Deep invasive disease is uncommon but may occur, particularly in patients with impaired host defenses.

Reported manifestations include:

• Pneumonia

• Endocarditis

• Osteomyelitis

Other organs may occasionally become involved in disseminated disease.

Phaeohyphomycosis

Infections caused by dematiaceous fungi in which pigmented septate hyphae or yeast-like fungal elements are demonstrated in tissue are generally classified within the spectrum of phaeohyphomycosis.

Thus, Curvularia species are important potential causes of phaeohyphomycotic infection.

Diagnosis

Diagnosis is primarily established through:

• Tissue biopsy

• Fungal culture

Both methods are useful because histopathology demonstrates tissue invasion while culture helps identify the specific fungal organism.

Tissue Biopsy

Histopathologic examination may demonstrate pigmented, septate fungal hyphae, pseudohyphae, or yeast-like elements within infected tissue.

The pigmentation provides an important clue that the infection is caused by a dematiaceous fungus.

Culture

Fungal culture allows identification of Curvularia species and helps distinguish the organism from other pigmented molds.

Clinical specimens should be obtained directly from the involved tissue whenever possible.

Treatment

Historically, amphotericin B has been used for serious Curvularia infections.

Treatment depends on:

• Site of infection

• Severity

• Degree of tissue invasion

• Immune status

• Antifungal susceptibility

Additional Treatment

Azole antifungal agents have also been used for infections caused by dematiaceous fungi.

However, the source notes that clinical data regarding their effectiveness against Curvularia are limited.

Whenever possible, treatment of serious disease should be guided by fungal identification and antifungal susceptibility information.

Surgical Management

Localized infections may also benefit from surgical excision or debridement, particularly when there is extensive infected or necrotic tissue.

Keratitis requires prompt ophthalmologic management because progressive corneal disease can result in permanent visual impairment.

High-Yield Clinical Pattern

Environmental or plant-related trauma

• ●

Keratitis or chronic subcutaneous lesion

• ●

Pigmented, septate fungal hyphae in tissue

→ Think dematiaceous fungal infection such as Curvularia

Exam Essentials

Genus: Curvularia

Type: Dematiaceous filamentous fungus

Pigmentation: Darkly pigmented fungal elements

Tissue morphology: Yeasts, pseudohyphae, or septate pigmented hyphae

Frequency: Rare human pathogen

Common manifestations: Keratitis and skin/subcutaneous infection

Rare invasive infections: Pneumonia, endocarditis, osteomyelitis

Disease category: Phaeohyphomycosis

Diagnosis: Tissue biopsy + fungal culture

Traditional treatment: Amphotericin B

Other therapy: Azoles have been used, but supporting data are limited

Key clinical pearl: Curvularia is a dematiaceous mold that should be considered when pigmented septate hyphae are found in a patient with fungal keratitis or a chronic cutaneous/subcutaneous infection.

Infectious Disease and Microbiology – Cunninghamella bertholletiae

Overview

Cunninghamella bertholletiae is a rare filamentous fungal pathogen that can cause mucormycosis, particularly in severely immunocompromised patients. Infection can be rapidly progressive and invasive, with the potential for extensive tissue destruction and dissemination.

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Microbiologic Characteristics

C. bertholletiae is a filamentous fungus (mold) traditionally classified among the organisms causing mucormycosis.

The organism characteristically produces:

• Broad, hyaline hyphae

• Nonseptate or sparsely septate hyphae

• Filamentous growth

Like other causes of mucormycosis, the fungus can invade blood vessels, resulting in vascular thrombosis, tissue ischemia, and necrosis.

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Epidemiology

Cunninghamella bertholletiae is distributed worldwide, but human infection is rare.

Disease occurs predominantly in patients with impaired host defenses.

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Major Risk Groups

Infection occurs more frequently in:

• Immunosuppressed patients

• Patients receiving intensive immunosuppressive therapy

• Patients with severe underlying disease

• Patients undergoing hemodialysis

Profound immunosuppression substantially increases the risk of invasive fungal disease.

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Mucormycosis

The principal infection caused by C. bertholletiae is mucormycosis, historically referred to as zygomycosis.

Mucormycosis is an aggressive invasive fungal infection characterized by fungal invasion of tissues and blood vessels.

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Angioinvasion and Tissue Necrosis

A major pathogenic feature is angioinvasion.

Fungal hyphae invade blood vessels, which can lead to:

Vascular invasion → thrombosis → impaired blood supply → tissue infarction and necrosis

This process helps explain the rapid progression and potentially high severity of invasive mucormycosis.

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Clinical Manifestations

Depending on the site of infection and degree of immunosuppression, mucormycosis may involve:

• Lungs

• Sinuses and rhinocerebral structures

• Skin and soft tissues

• Gastrointestinal tract

• Multiple organs in disseminated infection

Pulmonary or disseminated disease is particularly concerning in severely immunocompromised patients.

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Diagnosis

Diagnosis requires rapid recognition because invasive mucormycosis can progress quickly.

The principal diagnostic methods are:

• Identification of fungal hyphae in tissue biopsy

• Fungal culture

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Tissue Biopsy

Histopathologic examination may demonstrate characteristic broad, hyaline, sparsely septate or nonseptate hyphae invading tissue.

Evidence of vascular invasion, thrombosis, infarction, and necrosis supports the diagnosis of invasive mucormycosis.

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Culture

Fungal culture can help identify Cunninghamella and distinguish it from other molds responsible for invasive fungal disease.

Whenever possible, both histopathology and culture should be obtained.

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Treatment

The traditional treatment for severe C. bertholletiae infection is:

Intravenous amphotericin B

Because mucormycosis is potentially life-threatening, antifungal treatment should be initiated promptly when invasive disease is strongly suspected.

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Additional Antifungal Therapy

Older literature contains limited information regarding the effectiveness of azole antifungals against Cunninghamella.

Itraconazole has historically been evaluated, but evidence for its effectiveness is limited.

Selection of antifungal therapy should take into account the organism, disease severity, infection site, susceptibility information, and patient characteristics.

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Surgical Management

When anatomically feasible, surgical removal of infected or necrotic tissue can be an important component of mucormycosis treatment.

Management may therefore require:

Systemic antifungal therapy + aggressive surgical debridement + correction of underlying risk factors

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High-Yield Clinical Pattern

Severely immunocompromised or hemodialysis patient

Rapidly progressive invasive fungal infection

Broad, nonseptate/sparsely septate hyaline hyphae in tissue

→ Consider mucormycosis, including Cunninghamella bertholletiae

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Exam Essentials

Organism: Cunninghamella bertholletiae

Type: Filamentous fungus (mold)

Hyphae: Broad, hyaline, nonseptate or sparsely septate

Distribution: Worldwide

Frequency: Rare

Major risk factor: Immunosuppression

Additional association: Hemodialysis

Major disease: Mucormycosis

Important pathogenic feature: Angioinvasion with thrombosis and tissue necrosis

Diagnosis: Tissue biopsy + fungal culture

Traditional treatment: IV amphotericin B

Older alternative studied: Itraconazole, with limited supporting data

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Key clinical pearl: Cunninghamella bertholletiae should be considered in a severely immunocompromised patient with rapidly invasive mucormycosis and broad, sparsely septate or nonseptate hyphae on tissue biopsy.

Infectious Disease and Microbiology – Crimean–Congo Hemorrhagic Fever Virus

Overview

Crimean–Congo hemorrhagic fever virus (CCHFV) is a tick-borne enveloped RNA virus that causes a potentially severe viral hemorrhagic fever. It is found across parts of Eastern Europe, Central Asia, the Balkans, the Middle East, and Africa.

Severe disease can involve hepatitis, jaundice, thrombocytopenia, disseminated intravascular coagulation, and major bleeding.

Microbiologic Characteristics

Crimean–Congo hemorrhagic fever virus belongs to the Nairovirus genus.

It is an:

• Enveloped virus

• Single-stranded RNA virus

• Segmented RNA virus

• Virus with helical symmetry

The genome contains three RNA segments.

Epidemiology

CCHFV is transmitted primarily through the bite of infected ticks.

The virus is endemic in several geographic regions, including:

• Eastern Europe

• Central Asia

• The Balkans

• The Middle East

• Africa

People with occupational or environmental exposure to ticks or infected animals are at increased risk.

Transmission

The major route of transmission is:

Tick bite → human infection

Person-to-person spread may also occur through direct exposure to infected blood or body fluids, which is particularly important in healthcare settings.

Clinical Manifestations

Crimean–Congo hemorrhagic fever can range from a nonspecific febrile illness to a severe hemorrhagic syndrome.

Early symptoms may include:

• Fever

• Headache

• Myalgia

• Malaise

• Nausea and vomiting

• Abdominal discomfort

Severe cases may progress rapidly.

Hemorrhagic Fever

The characteristic severe syndrome includes:

• Acute hepatitis

• Jaundice

• Thrombocytopenia

• Disseminated intravascular coagulation

• Petechiae or ecchymoses

• Mucosal bleeding

• Gastrointestinal or other internal bleeding

• Shock

The combination of thrombocytopenia and coagulation abnormalities contributes substantially to the bleeding tendency.

Hepatic Involvement

Acute hepatitis can be prominent.

Patients may develop:

• Markedly elevated liver enzymes

• Jaundice

• Hepatic dysfunction

• Coagulopathy

Severe hepatic injury is associated with a worse prognosis.

Mortality

Severe Crimean–Congo hemorrhagic fever has historically been associated with a high case-fatality rate, often cited around 30–40% in severe cases.

Outcome depends on disease severity, supportive care, and host factors.

Diagnosis

Laboratory diagnosis can include:

• PCR

• Viral antigen detection

• Serologic testing

• Viral culture in specialized laboratories

PCR is especially useful during the acute phase because it directly detects viral nucleic acid.

Infection Control

Patients with suspected or confirmed disease require strict infection-control precautions because transmission can occur through blood and body fluids.

Healthcare workers should use appropriate barrier protection, including gloves, gowns, eye protection, and respiratory protection when indicated by the procedure.

Treatment

Management is primarily supportive.

Treatment may include:

• Fluid and electrolyte management

• Hemodynamic support

• Blood-product replacement when indicated

• Management of coagulopathy

• Organ support in critically ill patients

Antiviral Therapy

There is no universally established specific antiviral treatment with consistently proven benefit.

Supportive care therefore remains the central component of management.

Prevention

Prevention focuses on reducing tick exposure and preventing contact with infected blood or tissues.

Important measures include:

• Tick-bite prevention

• Protective clothing

• Appropriate use of repellents

• Safe handling of animals and animal tissues

• Strict hospital infection-control precautions

• Isolation of affected patients when clinically indicated

Related Bunyavirus Syndromes

Other historically grouped bunyavirus-associated diseases include:

• California encephalitis

• Rift Valley fever

• Hemorrhagic fever with renal syndrome

• Hantavirus pulmonary syndrome

These diseases differ substantially in vectors, reservoirs, geography, and clinical presentation.

High-Yield Clinical Pattern

Tick exposure in an endemic region

• ●

Acute fever

• ●

Thrombocytopenia + hepatitis + bleeding/DIC

→ Think Crimean–Congo hemorrhagic fever

Exam Essentials

Virus: Crimean–Congo hemorrhagic fever virus

Genus: Nairovirus

Genome: Segmented single-stranded RNA

Segments: 3

Envelope: Present

Symmetry: Helical

Vector: Tick

Geography: Eastern Europe, Central Asia, Balkans, Middle East, Africa

Major syndrome: Viral hemorrhagic fever

Key findings: Hepatitis, jaundice, thrombocytopenia, DIC, bleeding

Diagnosis: PCR, antigen detection, serology

Treatment: Primarily supportive

Severe-case mortality: High

Prevention: Tick avoidance and strict infection-control precautions

Key clinical pearl: Tick exposure + hemorrhagic fever + thrombocytopenia + hepatitis + DIC is the classic pattern for Crimean–Congo hemorrhagic fever.

Infectious Disease and Microbiology – Coxsackievirus Group

Overview

Coxsackieviruses are members of the enterovirus group and are divided mainly into coxsackievirus A and coxsackievirus B, each of which contains multiple serotypes.

They are common worldwide pathogens and are responsible for a wide range of clinical syndromes, including mucocutaneous disease, respiratory illness, myocarditis, meningitis, and neonatal disseminated infection.

Microbiologic Characteristics

Coxsackieviruses are:

• Single-stranded, positive-sense RNA viruses

• Nonenveloped (naked)

• Viruses with icosahedral symmetry

Because they are nonenveloped, they are relatively resistant to environmental conditions compared with enveloped viruses.

Epidemiology

Coxsackievirus infections occur worldwide and are a common cause of human illness.

Transmission is mainly through the fecal–oral route, although respiratory spread can also occur, particularly in syndromes involving the upper respiratory tract.

Children are commonly affected, but infection can occur at any age.

Hand-Foot-and-Mouth Disease

Coxsackievirus A is classically associated with hand-foot-and-mouth disease.

This syndrome is characterized by:

• Oral vesicles or ulcers

• Vesicular or papular lesions on the hands

• Lesions on the feet

• Fever

• Malaise

The mucosal lesions represent an enanthem, while the skin lesions represent an exanthem.

Herpangina

Herpangina is another classic coxsackievirus-associated syndrome.

It usually presents with:

• Fever

• Sore throat

• Painful vesicles or ulcers in the posterior oropharynx

• Difficulty swallowing

Coxsackievirus A is an important cause.

Upper Respiratory Tract Infection

Coxsackieviruses may produce nonspecific upper respiratory tract infections characterized by symptoms such as:

• Sore throat

• Rhinorrhea

• Cough

• Fever

• Malaise

Pleurodynia

Coxsackievirus B is classically associated with epidemic pleurodynia, also called Bornholm disease.

Patients may develop sudden episodes of:

• Severe chest pain

• Upper abdominal pain

• Fever

• Pain worsened by respiration or movement

The pain is related to inflammation of the chest wall and intercostal muscles.

Myopericarditis

Coxsackievirus B is an important viral cause of myocarditis and pericarditis.

Clinical manifestations may include:

• Chest pain

• Dyspnea

• Palpitations

• Arrhythmias

• Signs of heart failure

• Pericarditic pain

Severe myocarditis can occasionally result in substantial cardiac dysfunction.

Acute Hemorrhagic Conjunctivitis

Certain enteroviruses, including some coxsackievirus strains, may cause acute hemorrhagic conjunctivitis.

Patients may develop:

• Red eyes

• Eye discomfort

• Photophobia

• Conjunctival hemorrhage

• Excessive tearing

Central Nervous System Infection

Coxsackieviruses are important causes of aseptic meningitis.

They may also cause:

• Encephalitis

• Meningoencephalitis

• Rare paralytic syndromes

Neurologic infection may occur in both children and adults.

Chronic Meningoencephalitis

A particularly important complication can occur in severely immunocompromised patients, especially those with agammaglobulinemia.

These patients may develop chronic enteroviral meningoencephalitis because they lack adequate antibody-mediated immunity to control the infection.

Neonatal Disseminated Infection

Newborns can develop severe disseminated coxsackievirus infection.

This may involve multiple organs and can produce:

• Sepsis-like illness

• Myocarditis

• Hepatitis

• Meningoencephalitis

• Coagulopathy

• Shock

Neonatal disease may be rapidly progressive and life-threatening.

Diagnosis

Diagnosis can be established using:

• PCR

• Virologic culture

• Serologic testing

PCR is particularly useful for detecting enteroviral RNA in appropriate clinical specimens, including cerebrospinal fluid in suspected meningitis.

Treatment

Treatment is primarily supportive and symptomatic.

Management depends on the clinical syndrome and may include:

• Hydration

• Antipyretics and analgesics

• Cardiac monitoring for myocarditis

• Respiratory support when necessary

• Intensive supportive care in severe neonatal infection

Specific Antiviral Therapy

There is no routinely available specific antiviral treatment for most coxsackievirus infections.

Most uncomplicated infections resolve spontaneously.

Prevention

Prevention is based primarily on reducing transmission.

Important measures include:

• Careful hand hygiene

• Proper disposal of fecal material

• Avoiding close contact with infected secretions

• Enteric precautions during the contagious period

• Respiratory precautions when appropriate, such as during herpangina

Older recommendations include enteric isolation for approximately 1 week.

High-Yield Clinical Associations

Coxsackievirus A

→ Hand-foot-and-mouth disease

→ Herpangina

Coxsackievirus B

→ Pleurodynia

→ Myocarditis

→ Pericarditis

Both groups

→ Aseptic meningitis and other enteroviral syndromes

Exam Essentials

Group: Enterovirus

Genome: Positive-sense single-stranded RNA

Envelope: None

Capsid: Icosahedral

Distribution: Worldwide

Major syndromes: Hand-foot-and-mouth disease, herpangina, pleurodynia, myopericarditis, meningitis

Severe neonatal disease: Disseminated infection

High-risk chronic CNS disease: Agammaglobulinemia

Diagnosis: PCR, culture, serology

Treatment: Supportive

Specific antiviral: None routinely available

Prevention: Enteric and respiratory hygiene precautions

Key clinical pearl: The classic exam distinction is coxsackie A → hand-foot-and-mouth disease and herpangina, whereas coxsackie B → pleurodynia and myopericarditis.

Infectious Disease and Microbiology – Corynebacterium Species

Overview

Non-diphtherial Corynebacterium species are aerobic Gram-positive bacilli that are usually low-virulence organisms but can occasionally cause serious invasive disease. Important species include C. bovis, C. pilosum, C. pseudodiphtheriticum, C. striatum, and C. xerosis, among others.

These organisms are uncommon causes of infection, but they become more clinically significant in patients with neutropenia, prosthetic devices, or underlying cardiac disease.

Microbiologic Characteristics

Corynebacterium species are:

• Aerobic

• Gram-positive

• Bacillary organisms

Many species can colonize the skin or mucosal surfaces, which means that positive cultures must sometimes be interpreted carefully to distinguish true infection from contamination or colonization.

Epidemiology

These species are rare causes of human infection.

Clinically significant disease is more likely in patients with:

• Neutropenia

• Prosthetic heart valves

• Other implanted prosthetic material

• Severe underlying illness

• Prolonged hospitalization

Endocarditis

Non-diphtherial Corynebacterium species can cause infective endocarditis involving either:

• Native heart valves

• Prosthetic heart valves

Prosthetic valve infection is especially important because organisms may adhere to foreign material and become difficult to eradicate with antibiotics alone.

Septicemia

Septicemia is uncommon but occurs more frequently in neutropenic patients.

Patients may present with:

• Fever

• Chills

• Hypotension

• Persistent bacteremia

• Clinical evidence of sepsis

Repeated recovery of the same Corynebacterium species from blood cultures increases the likelihood that the isolate represents true infection rather than contamination.

Respiratory Tract Infections

These organisms can occasionally cause:

• Pneumonia

• Tracheitis

• Other respiratory tract infections

Respiratory disease is more likely in debilitated, hospitalized, or immunocompromised patients.

Prosthetic Material Infection

Corynebacterium species may infect implanted or prosthetic material.

Examples include:

• Prosthetic heart valves

• Vascular devices

• Orthopedic hardware

• Other implanted foreign bodies

Because biofilm formation and persistent colonization may occur, antimicrobial therapy alone may not always be sufficient.

Diagnosis

Diagnosis is made by culture from the appropriate clinical specimen.

Depending on the infection, samples may include:

• Blood cultures

• Respiratory specimens

• Tissue samples

• Prosthetic-device cultures

• Other sterile-site specimens

Clinical interpretation is important because some Corynebacterium species may be dismissed incorrectly as contaminants.

Treatment of Endocarditis

For severe endocarditis, a regimen described in the source is:

Vancomycin plus an aminoglycoside

This combination may be used initially in serious infection while awaiting susceptibility results.

Prosthetic Material Removal

When infection involves prosthetic material, removal of the infected device or prosthesis is frequently necessary.

Persistent infection despite apparently appropriate antimicrobial treatment should increase suspicion that the foreign material is acting as a continuing source.

Additional Antimicrobial Options

Therapy may need to be modified according to:

• Clinical response

• Site of infection

• Species identification

• In vitro susceptibility testing

Potential alternative agents include:

• Penicillin G

• Tetracycline

• Macrolides

• Rifampicin

• First-generation cephalosporins

• Teicoplanin

Treatment should be individualized because susceptibility patterns may vary among species.

High-Yield Clinical Pattern

Prosthetic valve or implanted device

• ●

Persistent bacteremia with a Corynebacterium species

• ●

Failure to clear infection with antibiotics alone

→ Consider true invasive Corynebacterium infection with infected prosthetic material

Exam Essentials

Genus: Corynebacterium

Type: Aerobic Gram-positive bacillus

Overall frequency: Rare cause of infection

Important syndromes: Endocarditis, septicemia, pneumonia, tracheitis, prosthetic-device infection

High-risk group for septicemia: Neutropenic patients

Diagnosis: Culture

Serious endocarditis treatment: Vancomycin plus an aminoglycoside

Important source-control measure: Removal of infected prosthetic material

Alternative agents: Penicillin G, tetracyclines, macrolides, rifampicin, first-generation cephalosporins, or teicoplanin

Key clinical pearl: When a non-diphtherial Corynebacterium species is repeatedly isolated from blood in a patient with a prosthetic valve, implanted device, or neutropenia, it should not automatically be dismissed as a contaminant.

Infectious Disease and Microbiology – Corynebacterium pseudotuberculosis

Overview

Corynebacterium pseudotuberculosis is an aerobic Gram-positive bacillus that primarily causes disease in animals and is only a rare cause of human infection. Human disease is usually associated with occupational or environmental exposure to infected animals.

The characteristic human manifestation is suppurative granulomatous lymphadenitis.

Microbiologic Characteristics

C. pseudotuberculosis is an aerobic, Gram-positive bacillus belonging to the genus Corynebacterium.

It is primarily an animal pathogen, with humans serving as accidental hosts following zoonotic exposure.

Epidemiology

Human infection is rare.

Most cases occur in people with significant contact with animals, particularly individuals whose occupations involve livestock or animal handling.

Potential exposure groups include:

• Farmers

• Veterinarians

• Abattoir workers

• Animal handlers

• Other individuals with close livestock exposure

Transmission

Human infection generally follows exposure to infected animals or contaminated animal material.

The organism may enter through breaks in the skin and subsequently spread through lymphatic channels to regional lymph nodes.

Suppurative Granulomatous Lymphadenitis

The classic human infection is suppurative granulomatous lymphadenitis.

Affected lymph nodes may become:

• Enlarged

• Painful or tender

• Inflamed

• Suppurative

• Chronically infected

The disease can resemble other causes of chronic granulomatous lymphadenopathy.

Differential Diagnosis

Important alternative causes of chronic or suppurative lymphadenitis include:

• Tuberculosis

• Nontuberculous mycobacterial infection

• Cat-scratch disease

• Tularemia

• Fungal infection

• Other bacterial lymphadenitis

A history of animal exposure provides an important clue to C. pseudotuberculosis infection.

Diagnosis

Definitive diagnosis is established by culture of material obtained from the infected lymph node or another appropriate specimen.

The organism can be cultured on:

Blood agar incubated with approximately 10% CO₂

Microbiologic identification is important because the clinical appearance can mimic several other causes of granulomatous lymphadenitis.

Treatment

Macrolide antibiotics may be used for C. pseudotuberculosis infection.

Treatment is often combined with appropriate management of the infected lymph nodes.

Surgical Management

Excision of infected lymph nodes may be necessary, particularly when lymphadenitis is persistent, suppurative, or inadequately responsive to antimicrobial therapy.

Thus, effective management may require both:

Antimicrobial therapy + surgical excision

Additional Treatment

Alternative antimicrobial agents include:

• Tetracyclines

• Penicillin G

Whenever possible, treatment of significant infection should be guided by culture and antimicrobial susceptibility results.

High-Yield Clinical Pattern

Animal or livestock exposure

• ●

Chronic enlarged lymph nodes

• ●

Suppurative granulomatous lymphadenitis

→ Think Corynebacterium pseudotuberculosis

Exam Essentials

Organism: Corynebacterium pseudotuberculosis

Type: Aerobic Gram-positive bacillus

Transmission: Zoonotic exposure, usually involving animals

Human infection: Rare

Classic manifestation: Suppurative granulomatous lymphadenitis

Diagnosis: Culture

Culture condition: Blood agar with approximately 10% CO₂

Treatment: Macrolide antibiotic

Source control: Excision of infected lymph nodes when indicated

Alternatives: Tetracycline or penicillin G

Key clinical pearl: The combination of animal exposure and chronic suppurative granulomatous lymphadenitis should raise suspicion for Corynebacterium pseudotuberculosis.

Infectious Disease and Microbiology – Corynebacterium minutissimum

Overview

Corynebacterium minutissimum is an aerobic Gram-positive bacillus best known as a common cause of erythrasma, a superficial skin infection that typically affects intertriginous areas. Although usually limited to the skin, the organism can rarely cause invasive disease such as bacteremia, sepsis, or endocarditis, particularly in immunocompromised patients.

Microbiologic Characteristics

C. minutissimum is an aerobic, Gram-positive bacillus belonging to the genus Corynebacterium.

It is primarily associated with superficial cutaneous infection, but under certain conditions it can invade deeper tissues or enter the bloodstream.

Epidemiology

C. minutissimum is a relatively common cause of superficial skin infection.

Erythrasma is especially associated with warm, moist areas of the body and is often seen in skin folds.

Erythrasma

The most characteristic infection caused by C. minutissimum is erythrasma.

It typically presents as:

• Well-demarcated reddish-brown patches

• Mild scaling

• Minimal inflammation

• Involvement of intertriginous areas such as the groin, axillae, or toe webs

The lesions may be asymptomatic or mildly pruritic.

Wood’s Lamp Examination

A classic diagnostic finding in erythrasma is coral-red fluorescence under a Wood’s lamp.

This occurs because C. minutissimum produces porphyrin compounds that fluoresce under ultraviolet light.

This finding is highly useful in distinguishing erythrasma from other intertriginous dermatoses.

Systemic Infection

Although uncommon, C. minutissimum can cause more serious invasive infections.

Reported manifestations include:

• Sepsis

• Endocarditis

• Bacteremia

• Subcutaneous tissue infection

These complications are more likely in patients with significant immunosuppression, particularly those with neutropenia.

Subcutaneous Tissue Infection

The organism may occasionally invade deeper tissues and produce localized subcutaneous infection.

Such cases should be evaluated carefully because they may indicate impaired host defenses or deeper tissue involvement.

Diagnosis

Diagnosis is based on:

• Culture of the organism from an appropriate clinical specimen

• Wood’s lamp examination in suspected erythrasma

The combination of a typical intertriginous rash and coral-red fluorescence strongly supports the diagnosis of erythrasma.

Treatment of Erythrasma

A classic systemic treatment regimen is:

Erythromycin 250 mg orally every 6 hours for 14 days

Local treatment with:

2% aqueous clindamycin

may also be effective.

Additional Treatment

Another option is:

Tetracycline 250 mg orally every 6 hours

Treatment choice may depend on severity, extent of disease, tolerance, and antimicrobial susceptibility where relevant.

Treatment of Systemic Infection

For serious systemic infection caused by C. minutissimum, such as sepsis or endocarditis:

Vancomycin is an important treatment option.

Management should also include evaluation for the source of infection and any underlying immunosuppressive condition.

High-Yield Clinical Pattern

Brown-red rash in a skin fold

• ●

Coral-red fluorescence with Wood’s lamp

→ Think Corynebacterium minutissimum causing erythrasma

Exam Essentials

Organism: Corynebacterium minutissimum

Type: Aerobic Gram-positive bacillus

Classic disease: Erythrasma

Typical site: Intertriginous skin folds

Key diagnostic clue: Coral-red fluorescence under Wood’s lamp

Other infections: Subcutaneous infection, sepsis, endocarditis

High-risk group for invasive disease: Neutropenic patients

Diagnosis: Culture and Wood’s lamp examination

Treatment of erythrasma: Erythromycin or topical clindamycin

Treatment of systemic infection: Vancomycin

Key clinical pearl: The classic association is erythrasma + coral-red Wood’s lamp fluorescence = Corynebacterium minutissimum.

Infectious Disease and Microbiology – Corynebacterium jeikeium

Overview

Corynebacterium jeikeium is an uncommon aerobic Gram-positive bacillus that acts mainly as an opportunistic pathogen. Infection is seen most often in patients with significant immunosuppression, particularly those with neutropenia or advanced HIV infection.

Microbiologic Characteristics

C. jeikeium is an aerobic, Gram-positive bacillus belonging to the genus Corynebacterium.

It is generally considered a low-frequency pathogen but can cause serious invasive disease in susceptible hosts.

Epidemiology

C. jeikeium infection is rare and occurs worldwide.

The organism is encountered primarily in hospitalized or immunocompromised patients, especially those with impaired host defenses or indwelling vascular devices.

Risk Groups

Clinically significant infection is most strongly associated with immunosuppression.

Important risk groups include:

• Patients with neutropenia

• Patients with advanced HIV infection

• Patients with prolonged hospitalization

• Patients with central venous catheters or other intravascular devices

Clinical Infections

C. jeikeium can cause several serious infections in vulnerable patients.

Sepsis

Bloodstream infection may progress to sepsis, particularly in severely immunocompromised patients.

Patients may present with fever, hypotension, systemic inflammatory findings, and other signs of invasive infection.

Endocarditis

C. jeikeium may cause infective endocarditis, especially in patients with underlying risk factors such as prosthetic material, prolonged bacteremia, or intravascular devices.

Central Venous Catheter-Associated Infection

Central venous catheters are an important potential source of infection.

Catheter-associated disease may present with:

• Persistent fever

• Positive blood cultures

• Local catheter-site inflammation

• Bacteremia or sepsis

Removal of an infected catheter may be required in addition to antimicrobial therapy.

Pneumonia

C. jeikeium can occasionally cause pneumonia, particularly in immunosuppressed patients.

Clinical manifestations may include fever, cough, dyspnea, hypoxemia, and pulmonary infiltrates.

Meningitis

Although uncommon, C. jeikeium can cause meningitis, particularly in patients with severe immune compromise.

This represents a serious invasive manifestation requiring prompt antimicrobial treatment.

Diagnosis

Diagnosis is made by culture from the appropriate clinical specimen.

Potential specimens include:

• Blood

• Catheter-related samples

• Cerebrospinal fluid

• Respiratory specimens

• Other normally sterile-site samples

Because corynebacteria may sometimes be dismissed as contaminants, repeated isolation of C. jeikeium in a compatible clinical setting should be taken seriously.

Treatment

Vancomycin is the principal treatment for serious C. jeikeium infection.

This is particularly important because the organism may show resistance to multiple other antimicrobial classes.

Additional Treatment

An alternative regimen described in older sources is:

Penicillin G combined with an antipseudomonal aminoglycoside

However, treatment should ideally be guided by antimicrobial susceptibility testing, especially in severe invasive disease.

High-Yield Clinical Pattern

Immunocompromised or neutropenic patient

• ●

Central venous catheter or prolonged hospitalization

• ●

Gram-positive bacillus in blood cultures

→ Consider Corynebacterium jeikeium

Exam Essentials

Organism: Corynebacterium jeikeium

Type: Aerobic Gram-positive bacillus

Epidemiology: Rare, worldwide infection

Major risk groups: Neutropenic and immunosuppressed patients

Important infections: Sepsis, endocarditis, catheter-associated infection, pneumonia, meningitis

Diagnosis: Culture

First-line treatment: Vancomycin

Alternative: Penicillin G plus an antipseudomonal aminoglycoside

Key clinical pearl: Corynebacterium jeikeium should not automatically be dismissed as a contaminant when isolated from a seriously immunocompromised patient, particularly when bacteremia or a central venous catheter infection is suspected.