Antibioticoterapia
As recomendações de tratamento são baseadas em dados empíricos.[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
[121]Thomas RJ, Dumler JS, Carlyon JA. Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis. Expert Rev Anti Infect Ther. 22009 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 e Anaplasma phagocytophilum são resistentes aos antibióticos normalmente utilizados, como as penicilinas, as cefalosporinas, os macrolídeos, os aminoglicosídeos e as quinolonas.[122]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
[123]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
[124]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
[125]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
[126]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
[127]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
[128]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
[129]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
No entanto, a resposta às tetraciclinas (sobretudo, a doxiciclina) é excelente na maioria dos casos, e nunca foi relatada nenhuma recidiva após uma terapia bem-sucedida.[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
[121]Thomas RJ, Dumler JS, Carlyon JA. Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis. Expert Rev Anti Infect Ther. 22009 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
A rifampicina é um bom agente de segunda linha em pacientes que não conseguem tolerar as tetraciclinas ou nos quais as tetraciclinas são contraindicadas.[122]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
[127]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
[128]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]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
O uso do cloranfenicol não é mais recomendado com base em testes de suscetibilidade in vitro.
Na ampla maioria dos casos, ocorre defervescência 24 a 72 horas após o início do tratamento. O paciente deve ser reavaliado caso não seja observada nenhuma melhora 72 horas após o tratamento.[121]Thomas RJ, Dumler JS, Carlyon JA. Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis. Expert Rev Anti Infect Ther. 22009 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
No entanto, em pacientes nos quais o tratamento seja protelado por vários dias, a melhora pode levar mais tempo.
Adultos
A doxiciclina é recomendada como tratamento de primeira linha para adultos.[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
Embora geralmente não seja usada durante a gestação, ela pode ser usada nos casos graves ou com risco à vida. A tetraciclina é menos tolerada que a doxiciclina e requer administração mais frequente. Ela não é recomendada para gestantes devido aos efeitos adversos no desenvolvimento ósseo e dentário do feto.[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
[131]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
A rifampicina pode ser usada como tratamento de segunda linha em pacientes alérgicos às tetraciclinas ou que apresentem outras contraindicações. O ciclo de tratamento é de, pelo menos, 3 dias após a remissão da febre, geralmente de 5 a 10 dias.[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
Crianças
A doxiciclina é recomendada como tratamento de primeira linha para todas as crianças, independentemente da idade, pois o risco de efeitos adversos dentários e ósseos é considerado insignificante com o ciclo curto de tratamento usado com essa indicação.[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
[132]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
A rifampicina pode ser usada como tratamento de segunda linha para crianças alérgicas à doxiciclina. O ciclo de tratamento é de, pelo menos, 3 dias após a remissão da febre, geralmente de 5 a 10 dias.[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