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Tick-Borne Diseases, Relapsing Fever: Treatment & Medication
Updated: Dec 9, 2008
- Overview
- Differential Diagnoses & Workup
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Treatment
Emergency Department Care
ED care of these patients focuses on the establishment of the diagnosis of relapsing fever and excluding other treatable infections with which it can be confused. As well, data from a randomized study published in 2006 shows that, for postexposure treatment, a 5-day course of doxycycline was effective at preventing tick-borne relapsing fever.2
Consultations
An infectious diseases consultation may be appropriate.
Medication
In the treatment of relapsing fever, antimicrobials are the drugs of choice. However, following the antimicrobial treatment, patients may develop a Jarisch-Herxheimer (JH) reaction, which can be severe, especially in louse-borne relapsing fever when patients' host defenses may be otherwise compromised. This reaction has been reported to occur in 50% of patients with tick-borne relapsing fever.
The JH reaction produces apprehension, diaphoresis, fever, tachycardia, and tachypnea with an initial pressor response followed rapidly by hypotension. The JH reaction can be fatal. Recent studies have shown that tumor necrosis factor-a (TNF-a) may be partly responsible for the reaction.3 Preadministration of glucocorticoids does little to limit the JH reaction, but antibodies to TNF-a do help.
Note that the regimens listed below are for tick-borne disease. Adults with louse-borne relapsing fever can be treated with a single 500 mg dose PO/IV of tetracycline, chloramphenicol, or erythromycin or 100 mg of doxycycline. Penicillin also can be used for louse-borne disease.
Antipyretics are indicated to reduce fever.
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Tetracycline (Sumycin)
Useful for louse- and tick-borne cases. DOC for the latter. Treats susceptible bacterial infections of both gram-positive and gram-negative organisms as well as infections caused by Mycoplasma, Chlamydia, and Rickettsia species. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s) of susceptible bacteria.
Adult
500 mg PO qid for 7-14 d
Pediatric
<8 years: Not recommended
> 8 years: 10-20 mg/lb/d (25-50 mg/kg) PO qid; 25-50 mg/kg/d divided q6h
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Documented hypersensitivity; severe hepatic dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
JH reaction may develop with use of antimicrobials; photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Doxycycline (Doryx, Bio-Tab)
Has advantage of covering other tick-borne diseases and ease of bid dosing.
Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria.
Adult
Acute infection: 200 mg PO/IV immediately and 100 mg hs followed by 100 mg bid for 3 d; alternatively, 300 mg immediately followed by 300 mg in 1 h or 100 mg PO/IV bid for 7 d
Pediatric
<8 years: Not recommended
>8 years: 2-5 mg/kg/d PO/IV in 1-2 divided doses; not to exceed 200 mg/d
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Documented hypersensitivity; severe hepatic dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Erythromycin (Erythrocin, Ery-Tab)
DOC for patients who are allergic to or cannot tolerate tetracyclines. Is also safe in pregnant patients, although estolate salt should be avoided.
In children, age, weight, and severity of infection determine proper dosage. When twice-a-day dosing is desired, half-total daily dose may be taken q12h. For more severe infections, dosage may be doubled.
Adult
250 mg erythromycin stearate/base (or 400 mg ethylsuccinate) PO q6h 1 h ac, or 500 mg q12h for 10 d; alternatively, 333 mg PO q8h; increase up to 4 g/d depending on severity of infection for 10 d
Pediatric
30-50 mg/kg/d (15-25 mg/lb/d) PO in divided doses; for severe infections, double the dose
Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin, increases risk of rhabdomyolysis
Documented hypersensitivity; hepatic impairment
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI side effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur
Chloramphenicol (Chloromycetin)
Is also useful for patients allergic to tetracycline. If a question of Rocky Mountain spotted fever exists, this is a useful drug.
Binds to 50S bacterial ribosomal subunits and interferes with or inhibits protein synthesis. Is effective against gram-negative and gram-positive bacteria.
Adult
50-100 mg/kg/d PO/IV divided q6h for 10 d; not to exceed 4 g/d
Pediatric
50-75 mg/kg/d PO/IV divided q6h
Concurrently with barbiturates, chloramphenicol serum levels may decrease while barbiturate levels may increase causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serum chloramphenicol levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; chloramphenicol levels may be increased or decreased
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use only for indicated infections, or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)
Antipyretics
In treating relapsing fever, bed rest and mild analgesic-antipyretic therapy are often helpful in relieving the associated lethargy, malaise, and fever associated with the disease.
Aspirin (Bayer Aspirin, Bufferin, Ascriptin)
Lowers elevated body temperature through vasodilation of peripheral vessels, thus enhancing dissipation of excess heat. Also acts on hypothalamus heat-regulating center to reduce fever.
Adult
325-650 mg PO q4-6h; not to exceed 4 g/d
Pediatric
10-15 mg/kg/dose PO q4-6h; not to exceed 60-80 mg/kg/d
Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Documented hypersensitivity; liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, asthma; because of association of aspirin with Reye syndrome, do not use in children (<16 y) with flu
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants
Ibuprofen (Motrin, Nuprin)
One of the few NSAIDs indicated for reduction of fever.
Adult
200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d
Pediatric
<6 months: Not established
6 months to 12 years: 20-40 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate upward; not to exceed 2.4 g/d
>12 years: Administer as in adults
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy
Acetaminophen (Tylenol, Anacin Free Aspirin, Feverall)
DOC for treatment of pain in patients with documented hypersensitivity to aspirin or NSAIDs, those with upper GI disease, or those taking oral anticoagulants.
Inhibits action of endogenous pyrogens on heat-regulating centers.
Adult
325-650 mg PO q4-6h or 1000 mg tid/qid; not to exceed 4 g/d
Pediatric
<12 years: 10-15 mg/kg/dose PO q4-6h prn; not to exceed 2.6 g/d
>12 years: 325-650 mg PO q4h; not to exceed 5 doses in 24 h
Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
Documented hypersensitivity; known G-6-PD deficiency
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; acetaminophen is contained in many OTC products and combined use with these products may result in cumulative acetaminophen doses exceeding recommended maximum dose
More on Tick-Borne Diseases, Relapsing Fever |
| Overview: Tick-Borne Diseases, Relapsing Fever |
| Differential Diagnoses & Workup: Tick-Borne Diseases, Relapsing Fever |
Treatment & Medication: Tick-Borne Diseases, Relapsing Fever |
| Follow-up: Tick-Borne Diseases, Relapsing Fever |
| Multimedia: Tick-Borne Diseases, Relapsing Fever |
| References |
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References
Southern PM, Sandford JP. Relapsing fever: a clinical and microbiological review. Med. 1969;48:129-43.
[Best Evidence] Hasin T, Davidovitch N, Cohen R, et al. Postexposure treatment with doxycycline for the prevention of tick-borne relapsing fever. N Engl J Med. Jul 13 2006;355(2):148-55. [Medline].
Fekade D, Knox K, Hussein K, et al. Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha. N Engl J Med. Aug 1 1996;335(5):311-5. [Medline].
Anda P, Sanchez-Yebra W, del Mar Vitutia M, et al. A new Borrelia species isolated from patients with relapsing fever in Spain. Lancet. Jul 20 1996;348(9021):162-5. [Medline].
Cadavid D, Barbour AG. Neuroborreliosis during relapsing fever: review of the clinical manifestations, pathology, and treatment of infections in humans and experimental animals. Clin Infect Dis. Jan 1998;26(1):151-64. [Medline].
Centers for Disease Control and Prevention (CDC). Acute respiratory distress syndrome in persons with tickborne relapsing fever--three states, 2004-2005. MMWR Morb Mortal Wkly Rep. Oct 19 2007;56(41):1073-6. [Medline].
Dworkin MS, Anderson DE Jr, Schwan TG, et al. Tick-borne relapsing fever in the northwestern United States and southwestern Canada. Clin Infect Dis. Jan 1998;26(1):122-31. [Medline].
Dworkin MS, Schwan TG, Anderson DE Jr, Borchardt SM. Tick-borne relapsing fever. Infect Dis Clin North Am. Sep 2008;22(3):449-68, viii. [Medline].
Horton JM, Blaser MJ. The spectrum of relapsing fever in the Rocky Mountains. Arch Intern Med. May 1985;145(5):871-5. [Medline].
Nordstrand A, Barbour AG, Bergstrom S. Borrelia pathogenesis research in the post-genomic and post-vaccine era. Curr Opin Microbiol. Feb 2000;3(1):86-92. [Medline].
Paul WS, Maupin G, Scott-Wright AO, et al. Outbreak of tick-borne relapsing fever at the north rim of the Grand Canyon: evidence for effectiveness of preventive measures. Am J Trop Med Hyg. Jan 2002;66(1):71-5. [Medline].
Raoult D, Roux V. The body louse as a vector of reemerging human diseases. Clin Infect Dis. Oct 1999;29(4):888-911. [Medline].
Further Reading
Keywords
tick-borne diseases, tick bite, relapsing fever, Borrelia, louse-borne relapsing fever, human body louse, Pediculus humanus, P humanus, Borrelia recurrentis, B recurrentis, lice, ticks, Ornithodoros, spirochetemia, Borrelia parkeri, B parkeri, Ornithodoros parkeri, O parkeri, Borrelia hermsii, B hermsii, Ornithodoros hermsii, O hermsii, soft tick
Treatment & Medication: Tick-Borne Diseases, Relapsing Fever