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Tick-Borne Disease

26 June 2005 - Tick-borne diseases in the United States include Rocky Mountain spotted fever, Lyme disease, ehrlichiosis, tularemia, babesiosis, Colorado tick fever, and relapsing fever. It is important for family physicians to consider these illnesses when patients present with influenza-like symptoms. A petechial rash initially affecting the palms and soles of the feet is associated with Rocky Mountain spotted fever, whereas erythema migrans (annular macule with central clearing) is associated with Lyme disease.

Various other rashes or skin lesions accompanied by fever and influenza-like illness also may signal the presence of a tick-borne disease. Early, accurate diagnosis allows treatment that may help prevent significant morbidity and possible mortality. Because 24 to 48 hours of attachment to the host are required for infection to occur, early removal can help prevent disease. Treatment with doxycycline or tetracycline is indicated for Rocky Mountain spotted fever, Lyme disease, ehrlichiosis, and relapsing fever. In patients with clinical findings suggestive of tick-borne disease, treatment should not be delayed for laboratory confirmation.

If no symptoms follow exposure to tick bites, empiric treatment is not indicated. The same tick may harbor different infectious pathogens and transmit several with one bite. Advising patients about prevention of tick bites, especially in the summer months, may help prevent exposure to dangerous vector-borne diseases. (Am Fam Physician 2005;71:2323-30, 2331-2. Copyright 2005 American Academy of Family Physicians.)

Because people continue to interact with nature, patients will continue to present to physician offices with tick-borne diseases. It is important for family physicians to recognize these illnesses because early, accurate diagnosis may lessen the morbidity and mortality of these treatable diseases. This article provides an update on the more common tick-borne diseases. Agents and characteristics of tick-borne disease are summarized in Tables 1 and 2.1

Rocky Mountain Spotted Fever

EPIDEMIOLOGY

Rocky Mountain spotted fever is caused by Rickettsia rickettsii and is the most common rickettsial disease in the United States.2 The disease is limited to the Western hemisphere and occurs in all states except Maine, Hawaii, and Alaska. The disease is more common in the coastal Atlantic states from April to September, although infections may occur year-round further south.3 The wood tick (Dermacentor andersoni) is the principal vector in the western United States, whereas the dog tick (Dermacentor variabilis) is the most common vector in the eastern and southern United States. Transmission from person to person is not thought to occur. The incidence of Rocky Mountain spotted fever is highest in children five to nine years of age.4

SIGNS AND SYMPTOMS

Typically in tick-borne diseases, a tick bite is recalled by 50 to 70 percent of patients.3,4 The onset of symptoms of Rocky Mountain spotted fever usually begins five to seven days after inoculation. Common symptoms include generalized malaise, myalgias (especially in the back and leg muscles), fever, frontal headaches, nausea, and vomiting. Other symptoms may include nonproductive cough, sore throat, pleuritic chest pain, and abdominal pain. The classic presenting symptoms include sudden onset of headache, fever, and chills accompanied by an exanthem appearing within the first few days of symptoms. Initially, lesions appear on the palms, soles, wrists, ankles, and forearms.

The lesions are pink and macular and fade with applied pressure. The rash then extends to the axilla, buttocks, trunk, neck, and face, becoming maculopapular and then petechial (Figure 1(5)). The lesions may then coalesce to form large areas of ecchymosis and ulceration. Respiratory and circulatory failure, as well as neurologic compromise, may occur.6 Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at especially high risk for complications and poor outcomes.7

Strength of Recommendations

DIAGNOSIS

The diagnosis of Rocky Mountain spotted fever is based primarily on clinical signs and symptoms. If a rash is present, the use of skin biopsy and immunofluorescent staining for Rickettsia is highly specific, although with only slightly more than 60 percent sensitivity. Laboratory testing is of limited usefulness but may include thrombocytopenia and hyponatremia.8 Elevation of specific enzyme-linked immunosorbent assay (ELISA) and latex agglutination titers usually is delayed until the convalescence period.

TABLE 1

Causative Agents, Vectors, and Geographic Distribution of Tick- Borne Diseases

TABLE 2

Clinical Characteristics of Tick-Borne Diseases

Figure 1. Image of a patient with Rocky Mountain spotted fever; note late rash on trunk.

TREATMENT

Fever and headache during peak months of tick exposure in endemic areas should suggest Rocky Mountain spotted fever. Rash, thrombocytopenia, and hyponatremia make immediate treatment imperative. Antimicrobial agents for the treatment of Rocky Mountain spotted fever include tetracycline, doxycycline (Vibramycin), and chloramphenicol (Chloromycetin) for a minimum of seven days.9 Fluoroquinolones also may be effective, but are not recommended for routine use in patients with Rocky Mountain spotted fever because of a lack of evidence.10 For optimal effect, it is critical to treat patients early in the course of their illness. According to the Centers for Disease Control and Prevention, appropriate antibiotic treatment should be initiated immediately when there is a suspicion of Rocky Mountain spotted fever on the basis of clinical and epidemiologic findings. Treatment should not be delayed until laboratory confirmation is obtained.7

Lyme Disease

EPIDEMIOLOGY

Lyme disease is the most common vector-borne infectious disease in the United States.9 The disease is caused by the spirochete Borrelia burgdorferi. In the United States, the main vector is Ixodes scapularis (Figure 2(11)), commonly referred to as the black- legged or deer tick because the female tick often attaches itself to the white-tailed deer during the winter. Natural reservoirs for B. burgdorferi include the white-footed mouse and other small mammals. The larvae or nymphs of the tick feed on the white-footed mouse and become infected. Adult ticks or, more commonly, nymphs may then infect humans. Studies using animals have shown that infected nymphalstage ticks must remain attached for 36 to 48 hours or longer, and infected adult ticks must remain attached for 48 to 72 hours or longer, before the risk of transmission of B. burgdorferi becomes substantial.12-15 There is no evidence that Lyme disease can be transmitted by mosquitoes, flies, or fleas. Blood products have never been associated with transmission of Lyme disease.16

SIGNS AND SYMPTOMS

Lyme disease typically develops in three stages. Stage 1 (early localized) Lyme disease occurs seven to 10 days after tick bite. Findings include typical rash (erythema migrans) in 75 percent of patients at the site of the tick bite. The rash typically develops as an annular macule or papule with central clearing that may expand to a diameter of up to 50 cm. Other indications include influenza- like symptoms of low-grade fevers, fatigue, arthralgias, headaches, cough, and regional lymphadenopathy. Stage 2 (early disseminated) Lyme disease occurs a few weeks after the initial infection. Symptoms include multiple secondary cutaneous annular lesions, fever, adenopathy, and central nervous system symptoms. Cough and pharyngitis may occur. Stage 3 (late chronic disease) symptoms include chronic arthritis, central nervous system impairment, dermatitis, and keratitis. Other symptoms may include neurologic abnormalities such as meningoencephalitis, Bell's-like palsy, and radiculopathies, and myocardial abnormalities such as atrioventricular block, pericarditis, and cardiomegaly.8

DIAGNOSIS

Early diagnosis of Lyme disease in a patient with typical erythema migrans in an endemic area does not require laboratory confirmation. However, ELISA testing is 89 percent sensitive and 72 percent specific. Positive results on ELISA testing should be confirmed with Western blotting. Polymerase chain reaction testing, although not widely available, may be useful for the diagnosis, especially with fluid from the joints of the affected patient.3 Isolation of B. burgdorferi from most tissues and body fluids by culture is difficult to achieve and requires weeks to grow before it can be analyzed.

TREATMENT

The risk of infection with B. burgdorferi after a recognized tick bite is minimal, and is almost nonexistent if the tick was attached less than 36 hours. Routine antibiotic prophylaxis is not indicated.8,16 A cost-effectiveness analysis showed that prophylaxis with one 200-mg dose of doxycycline was cost-effective only if the likelihood of infection exceeded 3.5 percent, much higher than in the typical practice setting.17 If symptoms develop, antibiotic treatment is curative in most cases. Recommended antibiotic treatment includes doxycycline (100 mg orally twice per day if patient is older than 12 years) or amoxicillin (500 mg orally three times per day or 50 mg per kg per day orally for patients 12 years and younger). Cefuroxime (Ceft\in; 500 mg orally, twice per day) or erythromycin (250 mg orally, four times per day) can be prescribed for persons who are allergic to penicillin or cannot take tetracyclines. Treatment usually lasts 14 to 21 days for uncomplicated cases. Late or severe disease, particularly with neurologic or cardiovascular manifestations, requires treatment with intravenous antibiotics, with a switch to oral therapy once the patient is no longer in high-degree atrioventricular block. Treatment in these advanced cases should be administered for at least 30 days. Late disease may be associated with treatment failures, and re-treatment may be necessary.18

Ehrlichiosis

EPIDEMIOLOGY

Human ehrlichiosis has been reported in the United States with two identifiable subtypes. Human monocytic ehrlichiosis (HME) is caused by Ehrlichia chaffeensis, and human granulocytic ehrlichiosis (HGE) is caused by Anaplasma phagocytophilum (formerly called Ehrlichia equi or Ehrlichia phagocytophila). The two subtypes are clinically indistinguishable but epidemiologically distinct.19

HME occurs most frequently in the south-central and southeastern United States. It occurs year-round with the highest incidence in June and July. In contrast to the tendency of Lyme disease and Rocky Mountain spotted fever to occur in children, HME typically affects adults. E. chaffeensis is found in Amblyomma amencanum (Lone Star tick) and D. variabilis (dog tick). The white-tailed deer is the principal animal reservoir.

The majority of cases of HGE occur in the upper midwestern and northeastern United States. Adults who live in rural areas or have exposure to tick-infested areas are most likely to be affected. The I. scapularis species are the principal vectors, and the white- footed mouse and white-tailed deer are the principal hosts.

SIGNS AND SYMPTOMS

The signs and symptoms of ehrlichiosis include an influenza-like syndrome consisting of fever, chills, cough, malaise, headache, and myalgia. Symptoms begin approximately seven days after tick bite and include a maculopapular, macular, or petechial rash that affects the trunk and upper extremities and, in rare cases (less than 5 percent), the palms and soles. HME and HGE present with similar signs and symptoms, but HGE rarely presents with the rash. Clinical differentiation from Rocky Mountain spotted fever is difficult.

DIAGNOSIS

Laboratory findings in patients with HME and HGE include leukopenia, thrombocytopenia, and elevated serum transaminase levels. Patients presenting with a nonspecific influenza-like syndrome of fever, chills, malaise, headache, and myalgia coupled with leukopenia and thrombocytopenia should be treated empirically. The principal method of diagnosing human ehrlichiosis is detection of seroconversion during convalescence. A fourfold rise or fall in antibody titer with a minimum peak of 1:64 and a single serum antibody titer greater than or equal to 1:128 is necessary for the diagnosis.

TREATMENT

As with other tick-borne diseases, treatment of ehrlichiosis should be started before laboratory tests confirm the diagnosis. Doxycycline at a dosage of 100 mg twice per day for adults or 4.4 mg per kg per day in two divided doses for children who weigh less than 45.4 kg (99 lb, 14 oz) is the treatment of choice.20 Tetracycline 500 mg orally four times per day is an alternative. Chloramphenicol is considered an alternative to prevent tooth staining, but there is a small risk of aplastic anemia with its use. Treatment should be continued for at least three days after fever subsides and until evidence of clinical improvement, for a minimum of five to seven days.20 Severe cases may require longer treatment courses.

Tularemia

EPIDEMIOLOGY

Francisella tularensis is the bacterium that causes tularemia (also known as rabbit fever). The tick vectors include A. americanum and D. variabilis in the southeastern and south-central United States and D. andersoni in the west. Transmission of the bacteria occurs by ingestion, inoculation, inhalation, or contamination. In the winter, the most common route is through microlesions in the skin of hunters who have skinned infected rabbits. In the summer, transmission occurs via ticks, deer flies, and horse flies. Although less common, consumption of undercooked infected meat and contaminated water also can lead to infection.

SIGNS AND SYMPTOMS

Clinical manifestations of tularemia can be divided into various syndromes, including ulceroglandular (the most common), oculoglandular, oropharyngeal/gastrointestinal tract, pulmonary, and typhoidal tularemia.8 Illness usually begins three to five days after inoculation, with rapid onset of fever, chills, headache, malaise, fatigue, and myalgias. Cough is present in about one third of patients. Other findings may include skin ulcers, sore throat, pleural effusions, pneumonia, acute respiratory distress syndrome, and pericarditis.21 Nausea and vomiting also may occur. Within 24 to 48 hours, an inflamed papule appears at the infected site (e.g., finger, arm, eye, roof of the mouth) except in glandular or typhoidal tularemia. The papule becomes pustular and ulcerates, producing an ulcer crater with colorless exudate. Regional lymphadenopathy occurs and may suppurate and drain. In children, the cervical or posterior auricular nodes commonly are affected. In adults, the inguinal and femoral nodes are more likely to be affected.

DIAGNOSIS

Tularemia should be suspected if the patient has been exposed to rabbits, wild rodents, or ticks; has characteristic symptoms; and has a primary pustular lesion on an extremity. Isolation of the organism from skin lesions, lymph nodes, or sputum is diagnostic but dangerous because the organism can be highly infectious. The disease is considered a potential biologic weapon. Extreme caution should be maintained when handling infected tissues or culture media. Acute and convalescent titers also can confirm the diagnosis. Leukocytosis is common, but the white blood cell count may be normal. Abnormal chest radiographic findings (i.e., triad of oval opacities, hilar adenopathy, and pleural effusions) are more likely with tularemia than in other tick-borne diseases.22,23

TREATMENT

Treatment should begin before confirmatory laboratory tests are obtained. If available, the treatment of choice for tularemia is streptomycin (0.5 g intramuscularly every 12 hours until the patient's body temperature is normal; thereafter, 0.5 g per day for five days). Gentamicin (3 to 5 mg per kg per day, intramuscularly or intravenously in three divided doses for seven to 14 days) also is effective.24 If renal disease is present, the dose of gentamicin needs to be reduced. Chloramphenicol or tetracyclines also have been used, but relapses occasionally occur with these medications, and they may not prevent node suppuration.3

Babesiosis

EPIDEMIOLOGY

Babesiosis is the only tick-borne disease in the United States that is caused by a protozoan (Babesia divergens or Babesia microti). Transmission occurs by the vector tick (various species of Ixodes). Most cases occur in the northeastern United States.

SIGNS AND SYMPTOMS

Symptoms are similar to those of other tick-borne diseases and include influenza-like symptoms one week after inoculation. Fever, sweating, myalgias, and headache also occur. Babesiosis may resemble falciparum malaria, with high fever, hemolytic anemia, hemoglobinuria, jaundice, and renal failure, especially in asplenic patients. Asymptomatic infection may persist for years in younger adults.

DIAGNOSIS AND TREATMENT

Babesiosis usually is suspected in a patient with fever, hemolytic anemia, and an appropriate exposure history. The diagnosis is made by detection of protozoa in blood smears. A characteristic tetrad, the "Maltese cross," appears. Serologic testing and polymerase chain reaction testing also are available.

Mild disease requires only symptomatic treatment. For severe cases (e.g., persistent high fever, progressive anemia, rising parasitemia), patients should be treated with quinine (Quinamm; 650 mg of salt orally, three times per day for seven days) plus clindamycin (Cleocin; 600 mg orally, three times per day or 1.2 g administered intravenously twice per day for seven to 10 days), or with atovaquone (Mepron; 750 mg orally twice per day for seven to 10 days) plus azithromycin (Zithromax; 600 mg orally per day for seven to 10 days).25 Reduced dosing is required in children. Exchange transfusion has been used in severely ill patients with high parasitemia.

Colorado Tick Fever

EPIDEMIOLOGY AND TRANSMISSION

Colorado tick fever is caused by an RNA orbivirus transmitted by the D. andersoni wood tick. Between 200 and 300 cases are diagnosed each year, predominantly in the Rocky Mountain region. Because of its benign presentation, the infection often may go undetected, and the annual incidence probably is much higher.26 Patients who are immunocompromised or who have undergone a splenectomy are at increased risk for severe complications.

SIGNS AND SYMPTOMS

Influenza-like symptoms usually begin within one week after inoculation. Although approximately one third of patients have a sore throat, more extensive involvement of the respiratory system rarely occurs.2 The most significant feature is a biphasic or "saddleback" fever associated with meningitis, rash, and conjunctivitis.8 The disease usually lasts seven to 10 days.

DIAGNOSIS

Diagnosis usually is made with blood smears, which are stained for the virus with immunofluorescence. Other laboratory abnormalities may include leukopenia and thrombocytopenia.

TREATMENT

Treatment is supportive. No specific medication is indicated. At the onset of symptoms, most patients will be treated empirically with tetracycline, doxycycline, or chloramphenicol to cover for other tick-borne diseases.

Relapsing Fever

EPIDEMIOLOGY AND TRANSMISSION

Relapsing fever is caused by the spirochete within the genus Borrelia. Ticks of the Ornithodoros genus are th\e chief vectors. Hosts include rodents (e.g., rats, mice, chipmunks, squirrels), rabbits, and hares. In the United States, most cases occur west of the Mississippi River, especially in mountainous areas. The disease typically occurs sporadically or in small, often familial, clusters.8

SIGNS AND SYMPTOMS

The average inoculation period is one week. Influenzalike symptoms, arthralgias (possibly severe), dizziness, nausea, and vomiting are common. Fever usually is high (greater than 40C [104F]) and irregular in pattern, and sometimes is associated with delirium. Most patients have splenomegaly. Meningeal signs may be present. Other complications can include epistaxis, hemoptysis, iridocyclitis, coma, cranial nerve palsy, pneumonitis, myocarditis, and rupture of the spleen.

DIAGNOSIS

Diagnosis is made most easily by detection of spirochetes in blood, bone marrow, or cerebrospinal fluid during a febrile episode. Other laboratory findings may include normal or moderate elevations in the leukocyte count and thrombocytopenia.

TREATMENT

The treatment of choice is doxycycline (100 mg orally, twice per day for five to 10 days). Alternative therapy includes erythromycin (500 mg orally four times per day for five to 10 days).27 Therapy may lead to a JarischHerxheimer reaction (i.e., generalized malaise, headache, fever, sweating, rigors, seizures, or stroke), especially if given during the late febrile stage. Administering acetaminophen two hours before and after antibiotic administration may lessen the severity of the reaction. Steroids and nonsteroidal anti- inflammatory drugs do not prevent or modify the cardiopulmonary disturbances of the reaction.8

Combined Infections

The same tick may harbor different infectious pathogens and transmit several with one bite.28 For example, I. scapularis may transmit ehrlichiosis, Lyme disease, and babesiosis. Babesiosis occurs in 23 percent of patients with Lyme disease29; ehrlichiosis occurs in 10 to 30 percent of patients with Lyme disease; and 10 to 30 percent of patients with ehrlichiosis acquire Lyme disease or babesiosis concurrently. Combined infections are thought to cause more severe symptoms.19,28

Prevention of Tick Exposure

Measures to help prevent tick exposure include avoiding tick- infested areas (especially during the summer months), wearing long pants and tucking pant legs into socks, using tick repellents containing N,N-diethyl-mtoluamide(DEET) for the skin and permethrin for clothing, and using bed nets when sleeping on the ground or camping.

Early removal of ticks can help prevent disease because at least 24 to 48 hours of attachment to the host are required before infection occurs.19 The body of the tick should be grasped gently and vertical traction applied until it dislodges. Blunt, medium- tipped, angled forceps offer the best results. Commercially available devices are recommended over tweezers for tick removal. Tick removal methods that are not recommended include applying a hot match to the tick body; covering the tick with petroleum jelly, nail polish, alcohol, or gasoline; using injected or topical lidocaine; and passing a needle through the tick. When an improper technique is applied, parts of the proboscis may remain in the skin, which can lead to infection or granuloma formation.30

The authors indicate that they do not have any conflicts of interest. Sources of funding: none reported.

Rocky Mountain spotted fever is more common in the coastal Atlantic states from April to September.

Figure 2. Deer tick (Ixodes scapularis), also known as black- legged tick.

Symptoms of ehrlichiosis begin approximately seven days after tick bite and include a maculopapular, macular, or petechial rash.

REFERENCES

1. Gayle A, Ringdahl E. Tick-borne diseases. Am Fam Physician 2001; 64:461-6.

2. Byrd RP Jr, Vasquez J, Roy TM. Respiratory manifestations of tick-borne diseases in the Southeastern United States. South Med J 1997;90:1-4.

3. Beers MH, Berkow R. The Merck manual of diagnosis and therapy. 17th ed. Whitehouse Station, N.J.: Merck Research Laboratories, 1999.

4. Walker DH. Tick-transmitted infectious diseases in the United States. Annu Rev Public Health 1998;19:237-69.

5. Drage LA. Life-threatening rashes: dermatologic signs of four infectious diseases. Mayo Clin Proc 1999;74:68-72.

6. Kwitkowski VE, Demko SG. Infectious disease emergencies in primary care. Lippincotts Prim Care Pract 1999;3:108-25.

7. Centers for Disease Control and Prevention. Rocky Mountain spotted fever. Accessed online April 11, 2005, at: http:// www.cdc.gov/ncidod/ dvrd/rmsf/index.htm.

8. Steeve AC. Lyme borreliosis. In: Kasper DL Harrison TR. Harrison's Manual of medicine. 16th ed. New York: McGraw-Hill, 2005:995-9.

9. Shapiro ED. Tick-borne diseases. Adv Pediatr Infect Dis 1997;13:187-218.

10. Thorner AR, Walker DH, Petri WA Jr. Rocky Mountain spotted fever. Clin Infect Dis 1998;27:1353-9.

11. Black-legged tick. Accessed online April 11, 2005, at: http:/ /www. enature.com/fieldguide/snowSpecies_Ll.asp?imageID=18509.

12. Piesman J, Mather TN, Sinsky RJ, Spielman A. Duration of tick attachment and Borrelia burgdorferi transmission. J Clin Microbiol 1987;25:557-8.

13. Piesman J, Maupin GO, Campos EG, Happ CM. Duration of adult female Ixodes dammini attachment and transmission of Borrelia burgdorferi, with description of a needle aspiration isolation method. J Infect Dis 1991;163:895-7.

14. Piesman J. Dynamics of Borrelia burgdorferi transmission by nymphal Ixodes dammini ticks. J Infect Dis 1993;167:1082-5.

15. Falco RC, Fish D, Piesman J. Duration of tick bites in a Lyme disease-endemic area. Am J Epidemiol 1996;143:187-92.

16. Centers for Disease Control and Prevention. Lyme disease. Accessed online April 11, 2005, at: http://www.cdc.gov/ncidod/dvbid/ lyme/ index.htm.

17. Magid D, Schwartz B, Craft J, Schwartz JS. Prevention of Lyme disease after tick bites. A cost-effectiveness analysis. N Engl J Med 1992;327:534-41.

18. Treatment of Lyme disease. Med Lett Drugs Ther 2000;42:37-9.

19. Belman AL. Tick-borne diseases. Semin Pediatr Neurol 1999;6:249-66.

20. Centers for Disease Control and Prevention. Human ehrlichiosis in the United States. Accessed online April 11, 2005, at: http://www.cdc. gov/ncidod/dvrd/ehrlichia/index.htm.

21. Evans ME, Gregory DW, Schaffner W, McGee ZA. Tularemia: a 30- year experience with 88 cases. Medicine (Baltimore) 1985;64:251-69.

22. Miller RP, Bates JH. Pleuropulmonary tularemia. A review of 29 patients. Am Rev Respir Dis 1969;99:31-41.

23. Rubin SA. Radiographic spectrum of pleuropulmonary tularemia. AJR Am J Roentgenol 1978;131:277-81.

24. Dennis DT, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, et al. Tularemia as a biological weapon: medical and public health management. JAMA 2001;285:2763-73.

25. Drugs for parasitic infections. Med Lett Drugs Ther 2004. Accessed online April 11, 2005, at: http://www.medletter.com/ freedocs/parasitic.pdf.

26. Emmons RW. An overview of Colorado tick fever. Prog Clin Biol Res 1985;178:47-52.

27. Gilbert DN, Moellering RC, Eliopoulos GM, Sande MA. The Sanford guide to antimicrobial therapy. 34th ed. Hyde Park, Vt.: Antimicrobial Therapy, 2004:39.

28. Walker DH, Barbour AG, Oliver JH, Lane RS, Dumler JS, Dennis DT, et al. Emerging bacterial zoonotic and vector-borne diseases. Ecological and epidemiological factors. JAMA 1996;275:463-9.

29. Meldrum SC, Birkhead GS, White DJ, Benach JL, Morse DL. Human babesiosis in New York state: an epidemiological description of 136 cases. Clin Infect Dis 1992;15:1019-23.

30. Gammons M, Salam G. Tick removal. Am Fam Physician 2002;66:643-5.

ROBERT L. BRATTON, M.D., Mayo Clinic, Scottsdale, Arizona

G. RALPH COREY, M.D., Duke University Medical Center, Durham, North Carolina

The Authors

ROBERT L. BRATTON, M.D., is a consultant in the Department of Family Medicine at the Mayo Clinic, Scottsdale, Ariz., and associate professor of family medicine at the Mayo Medical School, Rochester, Minn. He received his medical degree from the University of Kentucky, Lexington, and completed a residency in family medicine at the Mayo Clinic, Rochester, Minn.

G. RALPH COREY, M.D., is professor of medicine and infectious diseases at Duke University Medical Center, Durham, N.C. He received his medical degree at Baylor University, Waco, Tex., and completed his internship, residency, and chief residency in internal medicine, and an infectious disease fellowship at Duke University Medical Center.

Address correspondence to Robert L. Bratton, M. D., Mayo Clinic Family Medicine - Thunderbird, 13737 N. 92nd St., Scottsdale, AZ 85260. Reprints are not available from the authors.

Copyright American Academy of Family Physicians Jun 15, 2005

Source: American Family Physician


South Dakota Law - Word File
Use of chloramphenicol restricted. The use of chloramphenicol is restricted to animals not raised for food production. The chemical may not be used in meat-, egg-, or milk-producing animals.


Chloramphenicol (Systemic)

Contents of this page:
Description
Before Using This Medicine
Proper Use of This Medicine
Precautions While Using This Medicine
Side Effects of This Medicine
Brand Names
Category

Description
Chloramphenicol (klor-am-FEN-i-kole) is used in the treatment of infections caused by bacteria. It works by killing bacteria or preventing their growth.

Chloramphenicol is used to treat serious infections in different parts of the body. It is sometimes given with other antibiotics. However, chloramphenicol should not be used for colds, flu, other virus infections, sore throats or other minor infections, or to prevent infections.

Chloramphenicol should only be used for serious infections in which other medicines do not work. This medicine may cause some serious side effects, including blood problems and eye problems. Symptoms of the blood problems include pale skin, sore throat and fever, unusual bleeding or bruising, and unusual tiredness or weakness. You and your doctor should talk about the good this medicine will do as well as the risks of taking it .

Chloramphenicol is available only with your doctor's prescription, in the following dosage forms:

Oral
Capsules (U.S. and Canada)
Oral suspension (U.S.)
Parenteral
Injection (U.S. and Canada)

Before Using This Medicine
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For chloramphenicol, the following should be considered:

Allergies—Tell your doctor if you have ever had any unusual or allergic reaction to chloramphenicol. Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes.

Pregnancy—Chloramphenicol has not been shown to cause birth defects in humans. However, use is not recommended within a week or two of your delivery date. Chloramphenicol may cause gray skin color, low body temperature, bloated stomach, uneven breathing, drowsiness, pale skin, sore throat and fever, unusual bleeding or bruising, unusual tiredness or weakness, or other problems in the infant.

Breast-feeding—Chloramphenicol passes into the breast milk and has been shown to cause unwanted effects, such as pale skin, sore throat and fever, unusual bleeding or bruising, unusual tiredness or weakness, or other problems in nursing babies. It may be necessary for you to take another medicine or to stop breast-feeding during treatment. Be sure you have discussed the risks and benefits of the medicine with your doctor.

Children—Newborn infants are especially sensitive to the side effects of chloramphenicol because they cannot remove the medicine from their body as well as older children and adults.

Older adults—Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of chloramphenicol in the elderly with use in other age groups.

Other medicines—Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking chloramphenicol, it is especially important that your health care professional know if you are taking any of the following:

Alfentanil or
Antidiabetics, oral (diabetes medicine you take by mouth) or
Phenobarbital or
Warfarin (e.g., Coumadin)—Use of chloramphenicol with these medicines may increase the chance of side effects of these medicines
Amphotericin B by injection (e.g., Fungizone) or
Antineoplastics (cancer medicine) or
Antithyroid agents (medicine for overactive thyroid) or
Azathioprine (e.g., Imuran) or
Colchicine or
Cyclophosphamide (e.g., Cytoxan) or
Ethotoin (e.g., Peganone) or
Flucytosine (e.g., Ancobon) or
Ganciclovir (e.g., Cytovene) or
Interferon (e.g., Intron A, Roferon-A) or
Mephenytoin (e.g., Mesantoin) or
Mercaptopurine (e.g., Purinethol) or
Methotrexate (e.g., Mexate) or
Phenytoin (e.g., Dilantin) or
Plicamycin (e.g., Mithracin) or
Zidovudine (e.g., AZT, Retrovir) or
X-ray treatment—Use of chloramphenicol with any of these medicines or with x-ray treatment may increase the risk of blood problems
Clindamycin (e.g., Cleocin) or
Erythromycins (medicine for infection) or
Lincomycin (e.g., Lincocin)—Use of chloramphenicol with any of these medicines may decrease the effectiveness of these medicines
Phenytoin (e.g., Dilantin)—Use of chloramphenicol with phenytoin may increase the chance of blood problems or increase the side effects of phenytoin

Other medical problems—The presence of other medical problems may affect the use of chloramphenicol. Make sure you tell your doctor if you have any other medical problems, especially:

Anemia, bleeding, or other blood problems—Chloramphenicol may cause blood problems

Liver disease—Patients with liver disease may have an increased risk of side effects

Proper Use of This Medicine
Chloramphenicol is best taken with a full glass (8 ounces) of water on an empty stomach (either 1 hour before or 2 hours after meals), unless otherwise directed by your doctor.

For patients taking the oral liquid form of this medicine:

Use a specially marked measuring spoon or other device to measure each dose accurately. The average household teaspoon may not hold the right amount of liquid.
To help clear up your infection completely, keep taking this medicine for the full time of treatment, even if you begin to feel better after a few days. Do not miss any doses.

Dosing—

The dose of chloramphenicol will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of chloramphenicol. If your dose is different, do not change it unless your doctor tells you to do so.

The number of capsules or teaspoonfuls of suspension that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are taking chloramphenicol.

For infections caused by bacteria:
For oral dosage forms (capsules and suspension):
Adults and teenagers—Dose is based on body weight. The usual dose is 12.5 milligrams (mg) per kilogram (kg) (5.7 mg per pound) of body weight every six hours.
Children—
Infants up to 2 weeks of age: Dose is based on body weight. The usual dose is 6.25 mg per kg (2.8 mg per pound) of body weight every six hours.
Infants 2 weeks of age and older: Dose is based on body weight. The usual dose is 12.5 mg per kg (5.7 mg per pound) of body weight every six hours; or 25 mg per kg (11.4 mg per pound) of body weight every twelve hours.
For injection dosage form:
Adults and teenagers—Dose is based on body weight. The usual dose is 12.5 mg per kg (5.7 mg per pound) of body weight every six hours.
Children—
Infants up to 2 weeks of age: Dose is based on body weight. The usual dose is 6.25 mg per kg (2.8 mg per pound) of body weight every six hours.
Infants 2 weeks of age and older: Dose is based on body weight. The usual dose is 12.5 mg per kg (5.7 mg per pound) of body weight every six hours; or 25 mg per kg (11.4 mg per pound) of body weight every twelve hours.
Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

To store this medicine:

Keep out of the reach of children.
Store away from heat and direct light.
Do not store the capsule form of this medicine in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.
Keep the oral liquid form of this medicine from freezing.
Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

Precautions While Using This Medicine
If your symptoms do not improve within a few days, or if they become worse, check with your doctor.

It is very important that your doctor check you at regular visits for any blood problems that may be caused by this medicine.

Chloramphenicol may cause blood problems. These problems may result in a greater chance of infection, slow healing, and bleeding of the gums. Therefore, you should be careful when using regular toothbrushes, dental floss, and toothpicks. Dental work, whenever possible, should be done before you begin taking this medicine or delayed until your blood counts have returned to normal. Check with your medical doctor or dentist if you have any questions about proper oral hygiene (mouth care) during treatment.

For diabetic patients:

This medicine may cause false test results with urine sugar tests. Check with your doctor before changing your diet or the dosage of your diabetes medicine.


Side Effects of This Medicine
Along with its needed effects, a medicine may cause some serious unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Stop taking this medicine and get emergency help immediately if any of the following side effects occur:

Rare--in babies only
Bloated stomach; drowsiness; gray skin color; low body temperature; uneven breathing; unresponsiveness

Also, check with your doctor immediately if any of the following side effects occur:

Less common
Pale skin; sore throat and fever; unusual bleeding or bruising; unusual tiredness or weakness (the above side effects may also occur up to weeks or months after you stop taking this medicine)

Rare
Confusion, delirium, or headache; eye pain, blurred vision, or loss of vision; numbness, tingling, burning pain, or weakness in the hands or feet; skin rash, fever, or difficulty in breathing

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome:

Less common
Diarrhea; nausea or vomiting

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.


Brand Names
In the U.S.—

Chloromycetin

In Canada—

Chloromycetin

Novochlorocap

Category
Antibacterial, systemic

Revised: 06/20/1995
http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202127.html


CHLORAMPHENICOL

Chloramphenicol is primarily bacteriostatic. It binds to the 50S subunit of the ribosome and inhibits bacterial protein synthesis. It has a wide spectrum of activity against gram-positive and gram-negative cocci and bacilli (including anaerobes), Rickettsia, Mycoplasma, and Chlamydia. Chloramphenicol therapy should be restricted to serious infections when other drugs are not as effective or are more toxic, because it rarely causes the potentially lethal complication of aplastic anemia.

Pharmacology: Chloramphenicol is well absorbed orally but not IM. Parenteral therapy should be IV. The drug is distributed widely in body fluids, and therapeutic concentrations are achieved in CSF. Chloramphenicol is metabolized in the liver to the inactive glucuronide. Both chloramphenicol and the glucuronide metabolite are excreted in the urine. Because of hepatic metabolism, active chloramphenicol does not accumulate in the plasma of patients with renal insufficiency.

Indications: Chloramphenicol is one of the drugs of choice for (1) typhoid fever and other serious Salmonella infections; (2) meningitis caused by susceptible Haemophilus influenzae, meningococci, or pneumococci when a -lactam antibiotic cannot be used; (3) serious infection caused by B. fragilis; and (4) rickettsial infection not responding to tetracycline or in which tetracycline cannot be used. Chloramphenicol is effective in H. influenzae, meningococcal, and pneumococcal meningitis caused by susceptible organisms, but is relatively ineffective in meningitis caused by Escherichia coli and other Enterobacteriaceae.

Adverse reactions: Two types of bone marrow depression may be caused by chloramphenicol: a reversible dose-related interference with iron metabolism and an irreversible idiosyncratic form of aplastic anemia. The reversible form is likely to occur with high doses, a prolonged course of treatment, and in patients with liver disease: Serum iron and saturation of serum iron-binding capacity increase, reticulocytes decrease, and vacuolization of RBC precursors, anemia, leukopenia, and thrombocytopenia develop. Irreversible idiosyncratic aplastic anemia occurs in < 1:25,000 patients given chloramphenicol. The onset may be delayed until after therapy has been discontinued.

Hypersensitivity reactions are uncommon. Optic and peripheral neuritis may occur with prolonged use of chloramphenicol. Nausea, vomiting, and diarrhea may occur.

The gray baby syndrome (see also Antibacterial Therapy under Neonatal Infections in Ch. 260), which is often fatal, occurs in newborns. It is related to high blood levels resulting from an inability of the immature liver to metabolize chloramphenicol and occurs with standard doses.

Administration and dosage: The dosage of chloramphenicol in adults and children is 50 mg/kg/day po or IV in divided doses q 6 h. In meningitis and occasionally in other serious infections, 75 to 100 mg/kg/day in divided doses is used. To avoid the gray baby syndrome, newborns <= 1 mo should not be given > 25 mg/kg/day initially. Doses should be adjusted to result in serum levels of 10 to 30 µg/mL (31 to 93 µmol/L) to avoid toxicity, especially in newborns, premature infants, and patients with hepatic disease. Chloramphenicol should not be given to women in labor. It should not be used topically because small amounts may be absorbed and can, rarely, cause aplastic anemia.

From www.merck.com/mrkshared/mmanual/section13/chapter153/153f.jsp


 

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