Mayo Clinic Antimicrobial Therapy quick guide - part 8 pps

predominantly a disease of children aged 1-5 years caused primarily by MAC, lymphadenitis in adults and for many cases in children living in regions where tuberculosis TB is endemic Diss

isoniazid, rifampin, pyrazinamide, and ethambutol daily for 6 months (preferred) a)

Using all 4 drugs for duration of therapy is justified because of possible drug resistance

If source patient (index case) is known to have a drug-susceptible isolate, then pyrazinamide and ethambutol may possibly be stopped after 2 months

isoniazid, rifampin, pyrazinamide, and ethambutol for first 2 months, followed by isoniazid and rifampin for 2 more months (4 months total)

a Can discontinue ethambutol if susceptibility data are available and isolate is sensitive to isoniazid, rifampin, and pyrazinamide If pyrazinamide is not used, continue ethambutol for first 2 months for susceptible

d Use of pyrazinamide not recommended, and streptomycin should

be avoided during pregnancy Streptomycin can be harmful to fetus; effects of pyrazinamide on fetus not well studied.

e Pregnant women taking isoniazid should also receive vitamin B f Exceptions to this rule include ritonavir and efavirenz. *TB/HIV Drug Interactions Available from: http://www.cdc.gov/

b Adjunctive dexamethasone is recommended for all patients with central nervous system (CNS) tuberculosis (TB), particularly tho

c Usual dexamethasone dose for CNS TB is 12 mg daily (adults) for 3 weeks, which is then gradually tapered over the following 3

Nontuberculosis Mycobacterial Infections Mycobacteria Classification, Identification, and Diagnosis Runyon Classification of Nontuberculosis Mycobacteria (NTM) •

Auramine-rhodamine stain (fluorescence microscopy):

Specialized Diagnostic Criteria for NTM Pulmonary Disease •

be isolated as environmental contaminant or airway commensal or as minimal disease 1)

Major Syndromes of Select NTM Mycobacteria Pulmonary Disease •

predominantly a disease of children aged 1-5 years caused primarily by MAC,

lymphadenitis in adults and for many cases in children living in regions where tuberculosis (TB) is endemic

Disseminated Disease (Typically in Immunosuppressed Patients) •

Corticosteroid use, transplant recipients, hematologic malignancies 1)

Select Nontuberculosis Mycobacteria M avium-intracellulare Complex (MAC) General Information: Pulmonary Disease •

Risk factors or associations with pulmonary MAC disease 1)

of disease progression; patients with minimal pulmonary disease may not require treatment

of active symptoms, radiologic findings on chest radiograph (or CT scan), and positive MAC cultures

TB with predominance of upper lobe cavitary disease; about 50% of cases •

Typically men; heavy smoking, alcoholism; aged <60 years

bronchiectasis with nodular disease; 40% of cases •

Typically women; nonsmoking, no alcoholism; mean age, 70 years

Hypersensitivity-like pulmonary disease a)

azithromycin) plus ethambutol and plus rifampin (or rifabutin) a)

Daily therapy (for cavitary or severe disease) or thrice-weekly therapy

disease or bronchiectasis: Flutter valve, postural drainage,

Treatment of Hypersensitivity MAC Lung Disease •

Remove source of exposure (eg, avoid contaminated hot tub)

Moderate to severe cases: Consider corticosteroid taper (4-8 weeks) or combination drug therapy for shorter periods (3-6 months) or both

Treatment of Children With NTM Cervical Lymphadenitis (MAC,

Combination drug therapy if surgical excision is incomplete

Treatment of Disseminated MAC Disease (Advanced HIV or AIDS Patients) •

Combination therapy with daily clarithromycin (or azithromycin) plus ethambutol with or without rifabutin (or rifampin)

Duration of therapy in HIV-positive patients: Lifelong or consider discontinuing after at least 12 months in asymptomatic patients with sustained increase in CD4 counts >100 cells/mcL for more than 6 months after highly active antiretroviral therapy

Avoid adverse drug interactions (eg, rifabutin and select antiretroviral drugs) in HIV patients (for more information, see the Centers for Disease Control and Prevention Web site*)

Hepatitis, STD, and TB Prevention, Division of Tuberculosis Elimination Atlanta (GA): Centers for Disease Control and Prevention [updated 2004 Jan 20; cited 2007 Jul 14] Available from: http://www.cdc.gov/tb/TB_HIV_Drugs/default.htm.

M kansasii General Information •

on chest radiographs, although noncavitary and nodular bronchiectasis disease can occur

ethambutol for at least 12 months of negative sputum cultures in pulmonary disease; rifampin is the cornerstone of treatment and the only drug associated

M marinum General Information •

Known as “swimming pool granuloma” or “fish tank granuloma”; associated with exposure to salt water, freshwater, fish tanks, and swimming pools

Infection acquired by skin inoculation; preferential growth in cooler areas of body 27-32°C (ie, extremities)

Clinical Disease •

nodules commonly in line of lymphatic drainage (“ascending” appearance similar to that of cutaneous sporotrichosis) 1)

Typically appears on extremities (eg, elbows, knees, dorsum of feet and hands)

Treatment: Variable Approaches (Typically Less Virulent Mycobacteria) •

months (typically 1-2 months after symptoms resolve); single-drug therapy may be an alternate approach for

azithromycin) plus ethambutol; rifampin can be added for bone and other more serious forms of disease

trimethoprim-sulfamethoxazole (tmp/smx); minocycline or doxycycline; moxifloxacin or ciprofloxacin

M leprae: Leprosy, Hansen Disease General Information •

diagnosis is made clinically with supporting tissue histology and microbial stains

Clinical Syndromes •

distributed), thickened dermis; cooler areas of body mostly affected; nasal collapse (ie, saddle-nose deformity), ear lobes; skin biopsy shows many bacilli

selective loss of pain and temperature most common; peripheral nerves may become large and palpable; prominent neurological involvement; skin biopsy shows only few bacilli

Other clinical findings of leprosy 1)

Peripheral neuritis: Ulnar nerve tropism leading to clawing of 4th and 5th fingers with decreased motor skill (“claw hand”) and decreased sensory and fine touch; may be associated with skin lesions

with borderline lepromatous disease who undergo a shift toward more tuberculoid (paucibacillary) forms; may develop after induction of therapy

and may contain erythema and edema of existing skin lesions with painful neuropathy and

ulceration; treat severe reactions with a corticosteroid taper

including erythema nodosum leprosum a)

Immune complex–mediated vasculitis; often ulceration with damage to nerves

The Rapidly Growing Mycobacteria: M fortuitum, M chelonae, M abscessus General Information •

Infectious Syndromes lung disease; bronchiectasis 2)M abscessus

Chest radiograph typically shows multilobar, patchy reticulonodular infiltrate with upper lobe predominance; cavitation less common (15% of cases)

Skin and soft-tissue infections 1)

Usually related to trauma or surgery; develops into wound infection; abscesses common

Cutaneous infections and hypersensitivity reactions can occur (eg, due to contaminated hot tubs or pedicure equipment)

Bone and joint infections 1)

susceptible to tobramycin, which is more active than amikacin against

difficult to treat successfully (especially pulmonary disease)

Commonly drug resistant; treatment considerations include clarithromycin and amikacin

M scrofulaceum Clinical Disease •

Surgical excision for localized lymphadenitis and cutaneous disease

M haemophilum General Information •

Wide geographical distribution (Europe, Israel, Australia, Canada, United Kingdom, Africa, Fiji, and US)

Isolated lymphadenitis in children and immunocompetent patients may be treated with surgical excision alone

M terrae Complex: M terrae, M triviale, M nonchromogenicum, M hiberniae Clinical Disease •

extremities, including hand, wrist, fingers; often in association with trauma

M xenopi General Information •

Obligate thermophile; enhanced growth at 42°C (commonly isolated from hot water taps and showerheads)

Consider clarithromycin, moxifloxacin, rifampin, and ethambutol; role of isoniazid is unclear and may not be beneficial

M ulcerans General Information •

Tropical rain forests of Africa, Australia, southwestern Asia, and South and Central America; Papua New Guinea; Malaysia

Grows at cooler temperatures; predilection for extremities; prolonged incubation period (>3 months); slow growth; optimal growth at temperatures of 28-33°C

Clinical Disease •African Buruli ulcer or Australian Bairnsdale ulcer; cutaneous necrotic painless ulcer; progressive,

granulomatous; may involve large skin areas; can become disfiguring

M bovis General Information •

considered contaminants; infections usually occur in immunosuppressed patients (eg, HIV-positive patients or transplant recipients); AFB stain may show some banding (similar to that for

M malmoense General Information •Northern Europe (2nd most common NTM isolate from sputum and cervical lymph nodes from children), Finland, Zaire, Japan; rare in US but sometimes found in Florida, Texas, Georgia

Involvement of blood, marrow, liver, spleen, enteric tissue

cefoxitin, fluoroquinolone, minocycline, doxycycline, tmp/smx, and imipenem

Additional Information Griffith et al Am J Respir Crit Care Med 2007;175:367-416 Erratum

Bacillus anthracis Brucella

Coxiella burnetii Echinococcus

Erysipelothrix insidiosa Francisella tularensis Leptospira interrogans Rhodococcus equi Toxoplasma gondii Yersinia pestis

Anthrax Brucellosis Q fever Hydatid cyst; alveolar cyst Erysipeloid; soft-tissue infection Tularemia Leptospirosis Respiratory tract infection Toxoplasmosis Plague

Italy, Greece); Latin America, Middle East (eg, Saudi Arabia, Syria, Iraq, Kuwait)

Human infection routes 1)

Clinical disease 1)

headache, back pain, splenomegaly (20-30%), adenopathy (10-20%), hepatomegaly (20-30%)

Treatment (duration varies by syndrome from weeks to months):

plus rifampin, doxycycline plus gentamicin or streptomycin; trimethoprim-sulfamethoxazole (tmp/ smx) plus rifampin

Q Fever (Coxiella burnetii) •

birth products, and milk from infected farm animals (eg, cattle, sheep, goats) and other animals (eg, dogs, cats, rabbits, pigeons, rats)

Human infection routes 1)

flulike illness, pneumonia, or hepatitis a)

may show classic doughnut-shaped granulomas (lipid vacuole surrounded by fibrinoid ring); hepatic fibrosis, cirrhosis

antibody titers >1:200 for antiphase II IgG and >1:50 for antiphase II IgM indicates acute infection; single antiphase I IgG titer >1:800 and IgA titer >1:100 indicate evidence of chronic infection

those with chronic disease 1)

alternate treatments include tmp/smx, rifampin, fluoroquinolone

symptomatic and those with chronic disease; doxycycline plus hydroxychloroquine; alternate treatments include doxycycline plus rifampin or fluoroquinolone or tmp/smx; prolonged duration of combination therapy; valve replacement (common)

Tularemia (Francisella tularensis) (See information on tularemia in section on Tick-Borne Infections)

Anthrax (Bacillus anthracis) •

goats); zoonotic transmission is more likely in Iran, Iraq, Turkey, Pakistan, and sub-Saharan Africa; spores can survive for long periods in soil

Clinical disease 1)

direct contact with infected animals, hides or wool from infected animals, or infected soil; painless papules develop into vesicles, which lead to ulcers, which then lead to black eschars surrounded by gelatinous haloes and nonpitting edema; painful regional adenopathy

(ie, woolsorter’s disease); typically biphasic clinical pattern with hemorrhagic mediastinitis, hemoptysis, and respiratory distress; high mortality

prevalence in rural areas; animal sources of infection (eg, rodents, cattle, swine, dogs, horses, sheep, goats)

water or soil contaminated by urine from infected animals, such as during recreational (eg, triathlons, swimming) and occupational (eg, dairy farmers, sewer workers) activities 1)

mucous membranes (eg, conjunctiva, nasopharyngeal and genital epithelium) and progress to hematologic dissemination

life-threatening; infections produce small-vessel vasculitis with multisystem disease; distinct biphasic course 1) Acute “septicemic” phase a)

Sudden headache, retro-ocular pain, myalgias, fever, nausea and vomiting, conjunctival suffusion, transient and mucosal rashes

Patients may improve for a few days, then have recurring fever with immunologic sequelae

More severe disease: Intravenous (IV) penicillin, ampicillin, doxycycline, ceftriaxone or cefotaxime

Plague (Yersinia pestis) •

animal tissues; from animal bites or scratches or from bites of fleas; human-to-human transmission by pneumonic plague; aerosol inhalation (bioterrorism hazard)

Clinical disease 1)

Bubonic plague (febrile lymphadenitis) a)

Rapidly tender, enlarged, infected lymph node (bubo) with fever

shows classic bipolar “safety-pin” morphology; culture and serology; PCR (investigational)

days; alternate drugs include doxycycline, chloramphenicol, tmp/smx

Rhodococcus equi •

herbivores and contaminated soil of horse farms; organism is gram positive and also partially acid-fast staining

patients (eg, human immunodeficiency virus [HIV] infection or AIDS; patients with low cell-mediated immunity) 1)

swine (major reservoir) but also found in sheep, horses, cattle, chickens, crabs, fish, dogs, and cats; occupational exposure in abattoir workers, butchers, fishermen, farmers, and veterinarians

Clinical disease 1)

Infectious Syndromes cellulitis; fingers most commonly involved, violaceous skin infection; highly painful; local lymphangitis and adenitis in about 30% of cases 2)Diffuse cutaneous disease:

often complicated by endocarditis with extensive valve destruction; more common with alcoholism and chronic liver disease

treatment but treatment quickens healing; penicillin, carbapenem, cephalosporin, clindamycin, doxycycline, or macrolide; and resistant to vancomycin, sulfonamides, and aminoglycosides

Echinococcus sp (E granulosus and E multilocularis) •

Africa, southern Europe, Latin America, Mediterranean, North and East Africa, Australia, New Zealand, western China

oncospheres penetrate the gut wall and travel by blood and lymphatics to liver (80%), lungs (18%), or (less commonly) kidneys, bones, brain, eyes

Clinical disease 1)

association with livestock and working dogs fed slaughtered animals a)

liver affected in about two-thirds of patients, lungs in 25%; less common in brain, muscles, kidneys, bones, heart, pancreas

septate (representing daughter cysts) and prominent wall

postoperative medical therapy (albendazole or mebendazole; possible combination of either with praziquantel)

reaspiration (PAIR) with pre- and postprocedure medical therapy

Toxoplasmosis (Toxoplasma gondii) •

reservoir; also found in lambs and pigs, and in bears and other carnivores

Human infection routes 1)

Ingestion of raw or undercooked meat containing tissue cysts; ingestion of food, water, or soil contaminated with cat feces containing infective oocysts

Clinical disease in immunosuppressed patients 1)

at corticomedullary junction and basal ganglia; especially common in patients with advanced HIV infection or AIDS; reactivated (nonprimary) disease

assays (often more helpful when applied with head imaging for suspicion of toxoplasma encephalitis, such as in AIDS patients)

Infections Through Animal Bites Rabies •

reduced by preemptive measures 1)

Good wound care (immediate soap and water) can reduce rabies risk by 90%