You are in: eMedicine Specialties > Infectious Diseases > MEDICAL TOPICS Mediterranean Spotted FeverArticle Last Updated: May 5, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Jason F Okulicz, MD, Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Fellow, Department of Infectious Disease, Wilford Hall United States Air Force Medical Center Jason F Okulicz is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, Sigma Xi, and Southern Medical Association Coauthor(s): Mark S Rasnake, MD, Assistant Professor of Medicine, Uniformed Services University of Health Sciences; Associate Program Dire, Department of Infectious Diseases, Wilford Hall Medical Center, Lackland Air Force Base, Texas; Pierre A Dorsainvil, MD, Medical Director, HIV Specialist, Palm Beach County Main Detention Center; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Lake Ida Medical Center; Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital Editors: Joseph Richard Masci, MD, Chief of Infectious Diseases, Associate Director, Associate Professor, Department of Internal Medicine, Division of Infectious Diseases, Elmhurst Hospital Center, Mount Sinai School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Thomas M Kerkering, MD, Professor of Medicine and Microbiology, Department of Internal Medicine, Division of Infectious Disease, Brody School of Medicine at East Carolina University; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Michael E Zevitz, MD, Assistant Professor of Medicine, Finch University of the Health Sciences, The Chicago Medical School; Consulting Staff, Private Practice Author and Editor Disclosure Synonyms and related keywords: boutonneuse fever, Rhipicephalus sanguineus, tache noire, Rickettsia conorii, Marseilles fever, Kenya tick typhus, African tick bite fever, Indian tick typhus, Israeli tick typhus, rickettsiosis, Guillain-Barré syndrome, polyneuropathy, altered mental status, hepatomegaly, acute renal failure, thrombocytopenia, hypoxemia INTRODUCTIONSection 2 of 10
  BackgroundMediterranean spotted fever, also known as boutonneuse fever, is transmitted by the dog tick Rhipicephalus sanguineus and has a characteristic rash and a distinct mark, ie, a tache noire (black spot) at the site of the tick bite. The etiologic agent for this infection is Rickettsia conorii, which also is the agent for Marseilles fever, Kenya tick typhus, South African tick bite fever, Indian tick typhus, and Israeli tick typhus. The tache noire at the site of the tick bite seldom, if ever, is observed in Israeli spotted fever. Rickettsiae are obligate, intracellular gram-negative coccobacilli that measure 1 X 0.3 micrometers and are found within the cytoplasm and occasionally the nucleus of eukaryotic cells. Mediterranean spotted fever and African tick bite fever are different illnesses in the same geographic area. African tick bite fever differs from Mediterranean spotted fever in having local adenopathy and multiple eschars. The frequency of travel-associated cases has risen worldwide secondary to increased travel to endemic areas, including ecotourism. Life-threatening complications or permanent disabilities may result from delayed diagnosis and the common practice of prescribing beta-lactam antibiotics as empiric therapy. PathophysiologyThe pathophysiologic hallmark of infection is the invasion of vascular endothelial cells by the organism, causing endothelial injury and tissue necrosis, which is illustrated by the tache noire or eschar at the tick bite site. Thrombosis is not an important pathogenic mechanism with this infection, but deep venous thrombosis can occur late in the course of illness. FrequencyUnited StatesMediterranean spotted fever is uncommon in the United States. A similar disease, Rocky Mountain spotted fever, is found in the United States. Rocky Mountain spotted fever is caused by Rickettsia rickettsii, for which the ixodid tick is the vector. InternationalMediterranean spotted fever, caused by R conorii, is prevalent in southern Europe, Africa, and Central Asia, including India. Mortality/MorbidityUntil recently, Mediterranean spotted fever was characterized as a benign rickettsiosis; however, Guillain-Barré syndrome, polyneuropathy, altered mental status, hepatomegaly, acute renal failure, thrombocytopenia, hypoxemia, and death have been reported. Factors associated with more severe disease include older age, alcoholism, and G-6-PD deficiency. The overall mortality rate is approximately 2%. CLINICALSection 3 of 10
History
Physical
Causes
DIFFERENTIALSSection 4 of 10
Fever of Unknown Origin Kawasaki Disease Malaria Q Fever Rocky Mountain Spotted Fever Typhus West Nile Encephalitis
|
| Drug Name | Doxycycline (Vibramycin) |
|---|---|
| Description | Tetracycline with broad spectrum of activity. Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. |
| Adult Dose | 100 mg PO/IV bid |
| Pediatric Dose | <8 years: Not recommended >8 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; severe hepatic dysfunction |
| Interactions | Bioavailability minimally decreased with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Photosensitivity may rarely 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 half of pregnancy through age 8 y) can cause permanent discoloration of teeth |
| Drug Name | Ciprofloxacin (Cipro) |
|---|---|
| Description | Fluoroquinolone with activity against most gram-negative organisms but no activity against Bacteroides fragilis. Inhibits bacterial DNA synthesis and consequently growth. |
| Adult Dose | 750 mg PO q12h or 400 mg IV q12h |
| Pediatric Dose | 20-30 mg/kg/d PO divided q12h |
| Contraindications | Documented hypersensitivity |
| Interactions | Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT) |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; avoid in seizure disorders, those with CNS disorders, and pregnant and breastfeeding women |
| Drug Name | Levofloxacin (Levaquin) |
|---|---|
| Description | Second-generation quinolone. Acts by interfering with DNA gyrase in bacterial cells. Bactericidal. Highly active against gram-negative and gram-positive organisms, including Pseudomonas aeruginosa. |
| Adult Dose | 500 mg PO/IV qd |
| Pediatric Dose | <18 years: Not recommended >18 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; levofloxacin reduces therapeutic effects of phenytoin; probenecid may increase levofloxacin serum concentrations |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; caution in seizure disorder and pregnant and breastfeeding women |
| Drug Name | Chloramphenicol (Chloromycetin) |
|---|---|
| Description | Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria. |
| Adult Dose | 50-60 mg/kg/d PO/IV divided q6h |
| Pediatric Dose | Neonates: 25-50 mg/kg/d IV qd or divided bid Infants and children: 50-75 mg/kg/d PO/IV divided q6h |
| Contraindications | Documented hypersensitivity; G-6-PD deficiency |
| Interactions | 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 |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| 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 3 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, (dose-related adverse effects) caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome) |
| Drug Name | Azithromycin (Zithromax) |
|---|---|
| Description | Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. |
| Adult Dose | 500 mg PO/IV qd |
| Pediatric Dose | <6 months: Not established >6 months: 10 mg/kg/d PO/IV |
| Contraindications | Documented hypersensitivity; hepatic impairment; do not administer with pimozide |
| Interactions | May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine |
| Pregnancy | |
| Precautions | Site reactions can occur with IV route; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients |
| Drug Name | Clarithromycin (Biaxin) |
|---|---|
| Description | Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition. |
| Adult Dose | 500 mg PO bid |
| Pediatric Dose | <6 months: Not established >6 months: 15 mg/kg/d PO divided q12h |
| Contraindications | Documented hypersensitivity; coadministration of pimozide |
| Interactions | Toxicity increases with coadministration of fluconazole and pimozide; effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, carbamazepine, ergot alkaloids, triazolam, HMG-CoA reductase inhibitors Plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increases in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents; decreases metabolism of repaglinide, thus increasing serum levels and effects |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies |
Mediterranean Spotted Fever excerpt
Article Last Updated: May 5, 2006
