eMedicine Specialties > Infectious Diseases > Bacterial Infections

Trench Fever: Treatment & Medication

Author: Alfred Scott Lea, MD, Associate Professor of Internal Medicine and Infectious Diseases, University of Texas Medical Branch School of Medicine
Contributor Information and Disclosures

Updated: Feb 20, 2009

Treatment

Medical Care

No well-designed, double-blinded, controlled trials have documented the best antibiotic regimen for B quintana infection and its associated syndromes (including trench fever) in immunocompetent patients. Most therapeutic recommendations are based on anecdotal clinical experience.

In the laboratory, B quintana seems to be sensitive to advanced-generation beta-lactams, chloramphenicol, macrolides, tetracyclines, fluoroquinolones (not ciprofloxacin), aminoglycosides, rifampin, and cotrimoxazole.13,18,44 Microbiologic susceptibility studies may not accurately predict clinical efficacy since B quintana seems to respond clinically to bacteriostatic agents such as doxycycline, erythromycin, and azithromycin.35 Only gentamicin is bactericidal in vitro.45 Since gentamicin does not achieve bactericidal levels within human erythrocytes, it is not believed to be optimal for monotherapy but is regularly used in combination with doxycycline.

It is critical to use two antibiotics with good in vitro activity against B quintana for serious or complicated infections.18 Successful treatment in immunocompromised patients is anecdotal, and most recommendations suggest longer treatment regimens combined with close clinical and microbiological follow-up.

The following are current recommendations for each of the identified clinical syndromes associated with B quintana in immunocompetent patients:

  • Trench fever/urban trench fever: Uncomplicated disease responds to doxycycline (100 mg PO twice daily for 28 d) and gentamicin (3 mg/kg IV daily for 14 d).18 . Macrolides and ceftriaxone have also been shown to be effective.6,35,12
  • Chronic B quintana bacteremia: A small randomized study found that a combination of doxycycline (100 mg PO twice daily for 28 d) with gentamicin (3 mg/kg/d IV for 14 d) effectively eradicated bacteremia.46,18 In some cases, therapy of much longer duration (up to 4 y) has been required.13 Serial cultures demonstrating eradication of the bacteremia are pivotal in determining duration of therapy.
  • Chronic lymphadenopathy: Erythromycin (500 mg PO 4 times a day for 3 mo) is the first-line therapy. Doxycycline (100 mg PO twice daily for 3 mo) is the alternative.18,6 Gentamicin (3 mg/kg IV daily for 14 d) can be added in difficult cases.
  • Bacillary angiomatosis: Erythromycin (500 mg PO 4 times a day for 3 mo) is the agent of choice.18 Doxycycline (100 mg PO twice daily for 3 mo) is an effective alternative. Gentamicin (3 mg/kg/d IV for 14 d) can be added in refractory cases.6 Fluoroquinolones and ceftriaxone have shown success in individual cases.
  • B quintana endocarditis: Doxycycline (100 mg PO twice daily for 6 wk) given in combination with gentamicin (3 mg/d IV daily for 14 d) is the regimen of choice.18 Rocephin should be added to the regimen if culture results are negative. Most patients require valvular heart surgery.33,34

Surgical Care

Surgical biopsy may be used to establish a definitive diagnosis of B quintana endocarditis, lymphadenopathy, or bacillary angiomatosis, when necessary.

In addition to numerous descriptions of small numbers of patients with B quintana endocarditis, two large studies (both performed by the same group of investigators) have described the treatment and outcomes of the disease.33,34 Their findings have suggested that most cases require valvular cardiac surgery.

Consultations

  • Consult with an infectious disease specialist for help with diagnosis and treatment.
  • Consult with a microbiology laboratory for help with blood and tissue specimen handling for optimal culture, serologic, and PCR-genomic testing.

Diet

  • No dietary restrictions are necessary in patients with Bartonella infection, including trench fever and urban trench fever.

Activity

  • No activity restrictions are necessary unless the patient has cardiac failure due to Bartonella endocarditis or its complications.
  • The patient should improve hygiene and living conditions.
  • Individuals should not donate blood or tissue if they are at risk for Bartonella infection.

Medication

The goal of antibiotic therapy is to eradicate all forms of the infection, minimizing morbidity and mortality.

Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Doxycycline (Vibramycin)

Broad-spectrum, synthetically derived antibiotic in the tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations. Bacteriostatic, and its mechanism of antimicrobial action is inhibition of protein synthesis by binding to the 50S subunit of the ribosome. Tetracyclines as a class cause a dramatic response with disappearance of the associated symptoms and defervescence, usually in 1-2 days.

Adult

100 mg PO/IV bid

Pediatric

<8 years: Not recommended

>8 years, <100 lb: 2 mg/lb/d PO/IV divided bid
> 8 years, >100 lb: Administer as in adults
Alternatively, 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 to same or similar drug; severe hepatic insufficiency

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 half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconi-like syndrome may occur with outdated tetracyclines


Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Bactericidal and works by arrests bacterial growth by binding to one or more of the penicillin-binding proteins.

Adult

2.0 g IV qd

Pediatric

50-75 mg/kg/d IV qd or divided q12h; not to exceed 4 g/d

Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

More than 10% of the treated subjects, children in particular, develop hematological changes (eosinophilia, thrombocytosis, less frequently leucopenia); an increase of transaminases is not uncommon (5-7%); ceftriaxone causes reversible biliary pseudolithiasis mainly in young women and children (ie, "sludge" in the gallbladder), occasionally with colic; dose adjustment necessary in renal failure; other rare adverse effects include headaches, dizziness, nausea, vomiting, abdominal pains, reduction of the renal functions, vaginitis, etc; pain can occur at the site of injection; since ceftriaxone may suppress bilirubin from the protein binding, it could favor a bilirubin encephalopathy in neonates; avoid in predelivery/neonates


Gentamicin (Garamycin, Jenamicin)

Aminoglycoside antibiotic for gram-negative coverage bacteria, including Pseudomonas species. Synergistic with beta-lactamase against enterococci. Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits.
Dosing regimens are numerous and are adjusted based on CrCl and changes in volume of distribution, as well as body space into which agent needs to distribute. Dose of gentamicin may be given IV/IM. Each regimen must be followed by at least trough level drawn on third or fourth dose, 0.5 h before dosing; may draw peak level 0.5 h after 30-min infusion.
Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.

Adult

Serious infections and normal renal function: 3 mg/kg/dose IV q8h
Loading dose: 1-2.5 mg/kg IV
Maintenance dose: 1-1.5 mg/kg IV q8h
Extended dosing regimen for life-threatening infections: 5 mg/kg/d IV divided q6-8h
Follow each regimen by at least a trough level drawn 0.5 h prior to the fourth dose; may draw a peak level 0.5 h after 30-min infusion

Pediatric

<5 years: 2.5 mg/kg/dose IV q8h
>5 years: 1.5-2.5 mg/kg/dose IV q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults

Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because aminoglycosides enhance effects of neuromuscular blocking agents, prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)

Documented hypersensitivity; non-dialysis–dependent renal insufficiency

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

Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

More on Trench Fever

Overview: Trench Fever
Differential Diagnoses & Workup: Trench Fever
Treatment & Medication: Trench Fever
Follow-up: Trench Fever
Multimedia: Trench Fever
References
Further Reading
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References

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Further Reading

  • Maurin M, Raoult D. Bartonella (Rochalimaea) quintana infections. Clin Microbiol Rev. Jul 1996;9(3):273-92. [Medline].
  • Rolain JM, Brouqui P, Koehler JE, Maguina C, Dolan MJ, Raoult D. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother. Jun 2004;48(6):1921-33. [Medline].

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Keywords

trench fever, 5-day fever, five-day fever, quintan fever, shinbone fever, shin bone fever, shank fever, tibialgic fever, His-Werner disease, Russian intermittent fever, Meuse fever, Polish fever, Wolhynia fever, urban trench fever, Bartonella quintana bacteremia, perivascular lymphocytic infiltrates, valve replacement, Bartonella quintana endocarditis, bartonellosis, Bartonella quintana, B quintana, bacillary angiomatosis, peliosis

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Contributor Information and Disclosures

Author

Alfred Scott Lea, MD, Associate Professor of Internal Medicine and Infectious Diseases, University of Texas Medical Branch School of Medicine
Alfred Scott Lea, MD is a member of the following medical societies: American Academy of Wound Management, American College of Physicians, American Medical Association, Harris County Medical Society, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey M Zaks, MD, Clinical Associate Professor of Medicine, Wayne State University School of Medicine; Vice President, Medical Affairs, Chief Medical Officer, Department of Internal Medicine, Providence Hospital
Jeffrey M Zaks, MD is a member of the following medical societies: American College of Cardiology, American College of Healthcare Executives, American College of Physician Executives, and American Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech, Carilion School of Medicine, Roanoke, Virginia
Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

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
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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