Antibiotic therapy
Treatment recommendations are based on empiric data.[62]Bakken JS, Krueth J, Wilson-Nordskog C, et al. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA. 1989 Nov;160(5):803-9.
http://www.ncbi.nlm.nih.gov/pubmed/8604172?tool=bestpractice.com
[69]Dumler JS, Madigan JE, Pusterla N, et al. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis. 2007 Jul 15;45 Suppl 1:S45-51.
http://www.ncbi.nlm.nih.gov/pubmed/17582569?tool=bestpractice.com
[77]Olano JP, Walker DH. Human ehrlichioses. Med Clin North Am. 2002 Mar;86(2):375-92.
http://www.ncbi.nlm.nih.gov/pubmed/11982308?tool=bestpractice.com
[122]Thomas RJ, Dumler JS, Carlyon JA. Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis. Expert Rev Anti Infect Ther. 2009 Aug;7(6):709-22.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739015/?tool=pubmed
http://www.ncbi.nlm.nih.gov/pubmed/19681699?tool=bestpractice.com
Ehrlichia chaffeensis and Anaplasma phagocytophilum are resistant to commonly used antibiotics such as penicillins, cephalosporins, macrolides, aminoglycosides, and quinolones.[123]Branger S, Rolain JM, Raoult D. Evaluation of antibiotic susceptibilities of Ehrlichia canis, Ehrlichia chaffeensis, and Anaplasma phagocytophilum by real-time PCR. Antimicrob Agents Chemother. 2004 Dec;48(12):4822-8.
https://journals.asm.org/doi/10.1128/AAC.48.12.4822-4828.2004
http://www.ncbi.nlm.nih.gov/pubmed/15561862?tool=bestpractice.com
[124]Maurin M, Abergel C, Raoult D. DNA gyrase-mediated natural resistance to fluoroquinolones in Ehrlichia spp. Antimicrob Agents Chemother. 2001 Jul;45(7):2098-105.
https://journals.asm.org/doi/10.1128/AAC.45.7.2098-2105.2001
http://www.ncbi.nlm.nih.gov/pubmed/11408229?tool=bestpractice.com
[125]Maurin M, Bakken JS, Dumler JS. Antibiotic susceptibilities of Anaplasma (Ehrlichia) phagocytophilum strains from various geographic areas in the United States. Antimicrob Agents Chemother. 2003 Jan;47(1):413-5.
https://journals.asm.org/doi/10.1128/AAC.47.1.413-415.2003
http://www.ncbi.nlm.nih.gov/pubmed/12499227?tool=bestpractice.com
[126]Rolain JM, Maurin M, Bryskier A, et al. In vitro activities of telithromycin (HMR 3647) against Rickettsia rickettsii, Rickettsia conorii, Rickettsia africae, Rickettsia typhi, Rickettsia prowazekii, Coxiella burnetii, Bartonella henselae, Bartonella quintana, Bartonella bacilliformis, and Ehrlichia chaffeensis. Antimicrob Agents Chemother. 2000 May;44(5):1391-3.
https://journals.asm.org/doi/10.1128/AAC.44.5.1391-1393.2000
http://www.ncbi.nlm.nih.gov/pubmed/10770788?tool=bestpractice.com
[127]Brouqui P, Raoult D. In vitro antibiotic susceptibility of the newly recognized agent of ehrlichiosis in humans, Ehrlichia chaffeensis. Antimicrob Agents Chemother. 1992 Dec;36(12):2799-803.
https://journals.asm.org/doi/10.1128/AAC.36.12.2799
http://www.ncbi.nlm.nih.gov/pubmed/1482148?tool=bestpractice.com
[128]Klein MB, Nelson CM, Goodman JL. Antibiotic susceptibility of the newly cultivated agent of human granulocytic ehrlichiosis: promising activity of quinolones and rifamycins. Antimicrob Agents Chemother. 1997 Jan;41(1):76-9.
https://journals.asm.org/doi/10.1128/AAC.41.1.76
http://www.ncbi.nlm.nih.gov/pubmed/8980758?tool=bestpractice.com
[129]Horowitz HW, Hsieh TC, Aguero-Rosenfeld ME, et al. Antimicrobial susceptibility of Ehrlichia phagocytophila. Antimicrob Agents Chemother. 2001 Mar;45(3):786-8.
https://journals.asm.org/doi/10.1128/AAC.45.3.786-788.2001
http://www.ncbi.nlm.nih.gov/pubmed/11181361?tool=bestpractice.com
[130]Hunfeld KP, Bittner T, Rodel R, et al. New real-time PCR-based method for in vitro susceptibility testing of Anaplasma phagocytophilum against antimicrobial agents. Int J Antimicrob Agents. 2004 Jun;23(6):563-71.
http://www.ncbi.nlm.nih.gov/pubmed/15194126?tool=bestpractice.com
However, response to tetracyclines (mainly doxycycline) is excellent in most cases, and relapse after successful therapy has never been reported.[69]Dumler JS, Madigan JE, Pusterla N, et al. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis. 2007 Jul 15;45 Suppl 1:S45-51.
http://www.ncbi.nlm.nih.gov/pubmed/17582569?tool=bestpractice.com
[77]Olano JP, Walker DH. Human ehrlichioses. Med Clin North Am. 2002 Mar;86(2):375-92.
http://www.ncbi.nlm.nih.gov/pubmed/11982308?tool=bestpractice.com
[122]Thomas RJ, Dumler JS, Carlyon JA. Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis. Expert Rev Anti Infect Ther. 2009 Aug;7(6):709-22.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739015/?tool=pubmed
http://www.ncbi.nlm.nih.gov/pubmed/19681699?tool=bestpractice.com
Rifampin is a good second-line agent in patients who cannot tolerate tetracyclines or in whom tetracyclines are contraindicated.[123]Branger S, Rolain JM, Raoult D. Evaluation of antibiotic susceptibilities of Ehrlichia canis, Ehrlichia chaffeensis, and Anaplasma phagocytophilum by real-time PCR. Antimicrob Agents Chemother. 2004 Dec;48(12):4822-8.
https://journals.asm.org/doi/10.1128/AAC.48.12.4822-4828.2004
http://www.ncbi.nlm.nih.gov/pubmed/15561862?tool=bestpractice.com
[128]Klein MB, Nelson CM, Goodman JL. Antibiotic susceptibility of the newly cultivated agent of human granulocytic ehrlichiosis: promising activity of quinolones and rifamycins. Antimicrob Agents Chemother. 1997 Jan;41(1):76-9.
https://journals.asm.org/doi/10.1128/AAC.41.1.76
http://www.ncbi.nlm.nih.gov/pubmed/8980758?tool=bestpractice.com
[129]Horowitz HW, Hsieh TC, Aguero-Rosenfeld ME, et al. Antimicrobial susceptibility of Ehrlichia phagocytophila. Antimicrob Agents Chemother. 2001 Mar;45(3):786-8.
https://journals.asm.org/doi/10.1128/AAC.45.3.786-788.2001
http://www.ncbi.nlm.nih.gov/pubmed/11181361?tool=bestpractice.com
[131]Dhand A, Nadelman RB, Aguero-Rosenfeld M, et al. Human granulocytic anaplasmosis during pregnancy: case series and literature review. Clin Infect Dis. 2007 Sep 1;45(5):589-93.
http://www.ncbi.nlm.nih.gov/pubmed/17682993?tool=bestpractice.com
The use of chloramphenicol is no longer recommended based on in vitro susceptibility testing.
In the vast majority of cases, defervescence occurs 24 to 72 hours after treatment is started. The patient should be reevaluated if no improvement is seen after 72 hours of treatment.[122]Thomas RJ, Dumler JS, Carlyon JA. Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis. Expert Rev Anti Infect Ther. 2009 Aug;7(6):709-22.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739015/?tool=pubmed
http://www.ncbi.nlm.nih.gov/pubmed/19681699?tool=bestpractice.com
However, in patients in whom the treatment is delayed for several days, improvement may take longer.
Adults
Doxycycline is recommended first line in adults.[21]Centers for Disease Control and Prevention. Tickborne diseases of the United States: a reference manual for health care providers. 6th ed. Atlanta (GA): U.S Department of Health and Human Services, Centers for Disease Control and Prevention; 2022.[68]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016 May 13;65(2):1-44.
http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htm?s_cid=rr6502a1_w
http://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com
Although it is not usually used in pregnancy, it can be used in serious or life-threatening cases. Tetracycline is less well tolerated than doxycycline and requires more frequent dosing. It is not recommended in pregnant women due to adverse effects on fetal osseous and dental development.[69]Dumler JS, Madigan JE, Pusterla N, et al. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis. 2007 Jul 15;45 Suppl 1:S45-51.
http://www.ncbi.nlm.nih.gov/pubmed/17582569?tool=bestpractice.com
[132]Purvis JJ, Edwards MS. Doxycycline use for rickettsial disease in pediatric patients. Pediatr Infect Dis J. 2000 Sep;19(9):871-4.
http://www.ncbi.nlm.nih.gov/pubmed/11001111?tool=bestpractice.com
Rifampin may be used second line in patients who are allergic, or have other contraindications, to tetracyclines. Treatment course is at least 3 days after fever ends, usually 5 to 10 days.[68]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016 May 13;65(2):1-44.
http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htm?s_cid=rr6502a1_w
http://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com
Children
Doxycycline is recommended first line in all children, regardless of age, as the risk of dental and osseous adverse effects is considered negligible with the short course of treatment used for this indication.[21]Centers for Disease Control and Prevention. Tickborne diseases of the United States: a reference manual for health care providers. 6th ed. Atlanta (GA): U.S Department of Health and Human Services, Centers for Disease Control and Prevention; 2022.[69]Dumler JS, Madigan JE, Pusterla N, et al. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis. 2007 Jul 15;45 Suppl 1:S45-51.
http://www.ncbi.nlm.nih.gov/pubmed/17582569?tool=bestpractice.com
[133]Lantos P, Krause PJ. Ehrlichiosis in children. Semin Pediatr Infect Dis. 2002 Oct;13(4):249-56.
http://www.ncbi.nlm.nih.gov/pubmed/12491230?tool=bestpractice.com
Rifampin may be used second line in children allergic to doxycycline. Treatment course is at least 3 days after fever ends, usually 5 to 10 days.[68]Biggs HM, Behravesh CB, Bradley KK, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States. MMWR Recomm Rep. 2016 May 13;65(2):1-44.
http://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htm?s_cid=rr6502a1_w
http://www.ncbi.nlm.nih.gov/pubmed/27172113?tool=bestpractice.com