infecção por Helicobacter pylori
Um regime para erradicação do H pylori é geralmente definido como aquele que oferece taxas de cura confiáveis de pelo menos 90%.[128]Graham DY, Lee YC, Wu MS. Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol. 2014 Feb;12(2):177-86;e3;discussion e12-3.
http://www.cghjournal.org/article/S1542-3565%2813%2900773-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23751282?tool=bestpractice.com
Tratamento de primeira linha
Dois regimes de erradicação quádrupla de primeira linha, recomendados por orientação, mostraram ter taxas de cura de pelo menos 90%:[91]Malfertheiner P, Megraud F, O'Morain CA, et al; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection - the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30.
https://gut.bmj.com/content/66/1/6.long
http://www.ncbi.nlm.nih.gov/pubmed/27707777?tool=bestpractice.com
[129]Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.
https://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdf
http://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
[130]McNicholl AG, Bordin DS, Lucendo A, et al. Combination of bismuth and standard triple therapy eradicates Helicobacter pylori infection in more than 90% of patients. Clin Gastroenterol Hepatol. 2020 Jan;18(1):89-98.
http://www.ncbi.nlm.nih.gov/pubmed/30978536?tool=bestpractice.com
[131]Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology. 2016 Jul;151(1):51-69;e14.
http://www.ncbi.nlm.nih.gov/pubmed/27102658?tool=bestpractice.com
[132]Wang Z, Wu S. Doxycycline-based quadruple regimen versus routine quadruple regimen for rescue eradication of Helicobacter pylori: an open-label control study in Chinese patients. Singapore Med J. 2012 Apr;53(4):273-6.
http://smj.sma.org.sg/5304/5304a7.pdf
http://www.ncbi.nlm.nih.gov/pubmed/22511052?tool=bestpractice.com
[133]Akyildiz M, Akay S, Musoglu A, et al. The efficacy of ranitidine bismuth citrate, amoxicillin and doxycycline or tetracycline regimens as a first line treatment for Helicobacter pylori eradication. Eur J Intern Med. 2009 Jan;20(1):53-7.
http://www.ncbi.nlm.nih.gov/pubmed/19237093?tool=bestpractice.com
[134]Niv Y. Doxycycline in eradication therapy of Helicobacter pylori - a systematic review and meta-analysis. Digestion. 2016;93(2):167-73.
https://www.karger.com/Article/FullText/443683
http://www.ncbi.nlm.nih.gov/pubmed/26849820?tool=bestpractice.com
Inibidor da bomba de prótons (IBP) (por exemplo, omeprazol - outros IBPs também são adequados) associado a amoxicilina, claritromicina e metronidazol
IBP associado a bismuto, metronidazol e tetraciclina (ou doxiciclina, se a tetraciclina não estiver disponível).
Embora algumas diretrizes recomendem 10 a 14 dias de terapia, 14 dias de terapia geralmente são recomendados, pois o aumento da duração do tratamento melhora a taxa de erradicação sem aumentar significativamente os eventos adversos.[91]Malfertheiner P, Megraud F, O'Morain CA, et al; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection - the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30.
https://gut.bmj.com/content/66/1/6.long
http://www.ncbi.nlm.nih.gov/pubmed/27707777?tool=bestpractice.com
[129]Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.
https://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdf
http://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
[131]Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology. 2016 Jul;151(1):51-69;e14.
http://www.ncbi.nlm.nih.gov/pubmed/27102658?tool=bestpractice.com
[135]Gisbert JP, McNicholl AG. Optimization strategies aimed to increase the efficacy of H. pylori eradication therapies. Helicobacter. 2017 Aug;22(4).
http://www.ncbi.nlm.nih.gov/pubmed/28464347?tool=bestpractice.com
[136]Alsamman MA, Vecchio EC, Shawwa K, et al. Retrospective analysis confirms tetracycline quadruple as best Helicobacter pylori regimen in the USA. Dig Dis Sci. 2019 Oct;64(10):2893-8.
http://www.ncbi.nlm.nih.gov/pubmed/31187323?tool=bestpractice.com
[137]Sun Q, Liang X, Zheng Q, et al. High efficacy of 14-day triple therapy-based, bismuth-containing quadruple therapy for initial Helicobacter pylori eradication. Helicobacter. 2010 Jun;15(3):233-8.
http://www.ncbi.nlm.nih.gov/pubmed/20557366?tool=bestpractice.com
[138]Calvet X, García N, López T, et al. A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther. 2000 May;14(5):603-9.
https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2036.2000.00744.x?sid=nlm%3Apubmed
http://www.ncbi.nlm.nih.gov/pubmed/10792124?tool=bestpractice.com
[139]Ford A, Moayyedi P. How can the current strategies for Helicobacter pylori eradication therapy be improved? Can J Gastroenterol. 2003 Jun;17 suppl B:36B-40B.
http://www.ncbi.nlm.nih.gov/pubmed/12845349?tool=bestpractice.com
[140]Fuccio L, Minardi ME, Zagari RM, et al. Meta-analysis: duration of first-line proton-pump inhibitor based triple therapy for Helicobacter pylori eradication. Ann Intern Med. 2007 Oct 16;147(8):553-62.
http://www.ncbi.nlm.nih.gov/pubmed/17938394?tool=bestpractice.com
[141]Flores HB, Salvana A, Ang ELR, et al. Duration of proton-pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis. Gastroenterology. 2010;138(S-340).[142]Yuan Y, Ford AC, Khan KJ, et al. Optimum duration of regimens for Helicobacter pylori eradication. Cochrane Database Syst Rev. 2013 Dec 11;(12):CD008337.
http://www.ncbi.nlm.nih.gov/pubmed/24338763?tool=bestpractice.com
[143]Liou JM, Chen CC, Lee YC, et al. Systematic review with meta-analysis: 10- or 14-day sequential therapy vs. 14-day triple therapy in the first line treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 2016 Feb;43(4):470-81.
https://onlinelibrary.wiley.com/doi/full/10.1111/apt.13495
http://www.ncbi.nlm.nih.gov/pubmed/26669729?tool=bestpractice.com
Tratamento de segunda linha
Os pacientes que falham na terapia de primeira linha devem ser tratados novamente com esquemas que não incluem antibióticos usados anteriormente, exceto para amoxicilina e tetraciclina, pois a resistência aos antibióticos posteriores é rara.[21]Bhutto A, Morley JE. The clinical significance of gastrointestinal changes with aging. Curr Opin Clin Nutr Metab Care. 2008 Sep;11(5):651-60.
http://www.ncbi.nlm.nih.gov/pubmed/18685464?tool=bestpractice.com
[91]Malfertheiner P, Megraud F, O'Morain CA, et al; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection - the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30.
https://gut.bmj.com/content/66/1/6.long
http://www.ncbi.nlm.nih.gov/pubmed/27707777?tool=bestpractice.com
[129]Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.
https://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdf
http://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
Aqueles com alergia à penicilina devem ser considerados para testes de alergia.
Os regimes de segunda linha após a falha do regime de primeira linha incluem:[21]Bhutto A, Morley JE. The clinical significance of gastrointestinal changes with aging. Curr Opin Clin Nutr Metab Care. 2008 Sep;11(5):651-60.
http://www.ncbi.nlm.nih.gov/pubmed/18685464?tool=bestpractice.com
[91]Malfertheiner P, Megraud F, O'Morain CA, et al; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection - the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30.
https://gut.bmj.com/content/66/1/6.long
http://www.ncbi.nlm.nih.gov/pubmed/27707777?tool=bestpractice.com
[129]Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.
https://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdf
http://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
IBP associado a amoxicilina e levofloxacino
IBP em alta dose associado a amoxicilina em alta dose
IBP associado a rifabutina e amoxicilina.
Quatorze dias de terapia são recomendados para esses regimes, embora o regime à base de rifabutina possa ser administrado por 10 a 14 dias.[129]Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.
https://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdf
http://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
[144]Fiorini G, Zullo A, Vakil N, et al. Rifabutin triple therapy is effective in patients with multidrug-resistant strains of Helicobacter pylori. J Clin Gastroenterol. 2018 Feb;52(2):137-40.
http://www.ncbi.nlm.nih.gov/pubmed/27136964?tool=bestpractice.com
[145]Graham DY, Canaan Y, Maher J, et al. Rifabutin-based triple therapy (RHB-105) for Helicobacter pylori eradication: a double-blind, randomized, controlled trial. Ann Intern Med. 2020 Jun 16;172(12):795-802.
http://www.ncbi.nlm.nih.gov/pubmed/32365359?tool=bestpractice.com
Devido à complexidade e à baixa adesão, a terapia quádrupla sequencial sem bismuto e híbrida sem bismuto não é mais recomendada.[129]Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.
https://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdf
http://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
[146]Fallone CA, Moss SF, Malfertheiner P. Reconciliation of recent Helicobacter pylori treatment guidelines in a time of increasing resistance to antibiotics. Gastroenterology. 2019 Jul;157(1):44-53.
http://www.ncbi.nlm.nih.gov/pubmed/30998990?tool=bestpractice.com
A terapia dupla de alta dose, definida como a administração de uma alta dose de um IBP associado a uma alta dose de amoxicilina, é eficaz após a falha da terapia de primeira linha (70% a 89%) e contorna a questão da resistência à claritromicina, ao metronidazol e à levofloxacina.[147]Howden CW. Emerging regimens for H. pylori infection should enhance efficacy and circumvent resistance. Dig Dis Sci. 2019 Oct;64(10):2691-2.
https://link.springer.com/article/10.1007%2Fs10620-019-05747-8
http://www.ncbi.nlm.nih.gov/pubmed/31346952?tool=bestpractice.com
[148]Yang X, Wang JX, Han SX, et al. High dose dual therapy versus bismuth quadruple therapy for Helicobacter pylori eradication treatment: a systematic review and meta-analysis. Medicine (Baltimore). 2019 Feb;98(7):e14396.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408008
http://www.ncbi.nlm.nih.gov/pubmed/30762742?tool=bestpractice.com
Os regimes à base de rifabutina são terapias de resgate eficazes, uma vez que a resistência à erradicação do H pylori a esse medicamento antituberculose comumente usado é incomum.[91]Malfertheiner P, Megraud F, O'Morain CA, et al; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection - the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30.
https://gut.bmj.com/content/66/1/6.long
http://www.ncbi.nlm.nih.gov/pubmed/27707777?tool=bestpractice.com
[98]Stenstrom B, Mendis A, Marshall B. Helicobacter pylori - the latest in diagnosis and treatment. Aus Fam Physician. 2008 Aug;37(8):608-12.
http://www.ncbi.nlm.nih.gov/pubmed/18704207?tool=bestpractice.com
[73]Malfertheiner P. Helicobacter pylori infection - management from a European perspective. Dig Dis. 2014;32(3):275-80.
http://www.ncbi.nlm.nih.gov/pubmed/24732193?tool=bestpractice.com
[128]Graham DY, Lee YC, Wu MS. Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol. 2014 Feb;12(2):177-86;e3;discussion e12-3.
http://www.cghjournal.org/article/S1542-3565%2813%2900773-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23751282?tool=bestpractice.com
[129]Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.
https://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdf
http://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
[131]Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology. 2016 Jul;151(1):51-69;e14.
http://www.ncbi.nlm.nih.gov/pubmed/27102658?tool=bestpractice.com
[149]Liang X, Xu X, Zheng Q, et al. Efficacy of bismuth-containing quadruple therapies for clarithromycin-, metronidazole-, and fluoroquinolone-resistant Helicobacter pylori infections in a prospective study. Clin Gastroenterol Hepatol. 2013 Jul;11(7):802-7;e1.
http://www.cghjournal.org/article/S1542-3565%2813%2900116-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23376004?tool=bestpractice.com
[150]Vakil N. H. pylori treatment: new wine in old bottles? Am J Gastroenterol. 2009 Jan;104(1):26-30.
http://www.ncbi.nlm.nih.gov/pubmed/19098845?tool=bestpractice.com
[151]Vakil N, Megraud F. Eradication therapy for Helicobacter pylori. Gastroenterology. 2007 Sep;133(3):985-1001.
http://www.ncbi.nlm.nih.gov/pubmed/17854602?tool=bestpractice.com
[152]Graham DY, Rimbara E. Understanding and appreciating sequential therapy for Helicobacter pylori eradication. J Clin Gastroenterol. 2011 Apr;45(4):309-13.
http://www.ncbi.nlm.nih.gov/pubmed/21389810?tool=bestpractice.com
[153]Hsu PI, Wu DC, Wu JY, et al. Modified sequential Helicobacter pylori therapy: proton pump inhibitor and amoxicillin for 14 days with clarithromycin and metronidazole added as a quadruple (hybrid) therapy for the final 7 days. Helicobacter. 2011 Apr;16(2):139-45.
http://www.ncbi.nlm.nih.gov/pubmed/21435092?tool=bestpractice.com
[154]Hu Y, Zhu Y, Lu N-H. Novel and effective therapeutic regimens for Helicobacter pylori in an era of increasing antibiotic resistance front cell. Infect Microbiol. 2017 May 5;7:168.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418237
http://www.ncbi.nlm.nih.gov/pubmed/28529929?tool=bestpractice.com
Embora a mielotoxicidade tenha sido observada em 2% dos pacientes tratados, todos eles se recuperaram sem aumento da suscetibilidade à infecção.[155]Gisbert JP, Calvet X. Review article: rifabutin in the treatment of refractory Helicobacter pylori infection. Aliment Pharmacol Ther. 2012 Jan;35(2):209-21.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2036.2011.04937.x
http://www.ncbi.nlm.nih.gov/pubmed/22129228?tool=bestpractice.com
Resistência a antibióticos
O tratamento empírico inicial de primeira linha padrão para infecção por H pylori é a terapia tripla que consiste em um IBP, amoxicilina e claritromicina por 14 dias.[91]Malfertheiner P, Megraud F, O'Morain CA, et al; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection - the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30.
https://gut.bmj.com/content/66/1/6.long
http://www.ncbi.nlm.nih.gov/pubmed/27707777?tool=bestpractice.com
[129]Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.
https://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdf
http://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
No entanto, o sucesso do tratamento com este regime é atualmente <80%, tanto nos EUA quanto na Europa, principalmente relacionado a um aumento na prevalência de resistência à claritromicina e baixa adesão ao tratamento; evidências sugerem que este regime não deve mais ser recomendado.[130]McNicholl AG, Bordin DS, Lucendo A, et al. Combination of bismuth and standard triple therapy eradicates Helicobacter pylori infection in more than 90% of patients. Clin Gastroenterol Hepatol. 2020 Jan;18(1):89-98.
http://www.ncbi.nlm.nih.gov/pubmed/30978536?tool=bestpractice.com
[156]Savoldi A, Carrara E, Graham DY, et al. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization regions. Gastroenterology. 2018 Nov;155(5):1372-82;e17.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905086
http://www.ncbi.nlm.nih.gov/pubmed/29990487?tool=bestpractice.com
A resistência a outros antibióticos, tradicionalmente usados em regimes de erradicação do H pylori, também aumentou. Nos EUA, a resistência ao metronidazol é de 20% e ao levofloxacino de 31%. Felizmente, a resistência aos antibióticos à tetraciclina e à amoxicilina é baixa a rara.[156]Savoldi A, Carrara E, Graham DY, et al. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization regions. Gastroenterology. 2018 Nov;155(5):1372-82;e17.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905086
http://www.ncbi.nlm.nih.gov/pubmed/29990487?tool=bestpractice.com
[157]Shiota S, Reddy R, Alsarraj A, et al. Antibiotic resistance of Helicobacter pylori among male United States veterans. Clin Gastroenterol Hepatol. 2015 Sep;13(9):1616-24.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905083
http://www.ncbi.nlm.nih.gov/pubmed/25681693?tool=bestpractice.com
A baixa adesão ao tratamento está relacionada a esquemas de tratamento complexos e efeitos adversos de antibióticos.
Confirmação da eficácia do tratamento
O sucesso (ou falha) do tratamento deve ser confirmado por meio do teste respiratório da ureia, teste do antígeno fecal ou biópsia com imuno-histoquímica ou teste rápido da urease.[128]Graham DY, Lee YC, Wu MS. Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol. 2014 Feb;12(2):177-86;e3;discussion e12-3.
http://www.cghjournal.org/article/S1542-3565%2813%2900773-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23751282?tool=bestpractice.com
Os testes devem ser realizados pelo menos quatro semanas após a conclusão do regime de erradicação. Os IBPs, que são bacteriostáticos contra o H pylori, devem ser suspensos de uma a duas semanas antes do teste.[129]Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol. 2017 Feb;112(2):212-39.
https://gi.org/wp-content/uploads/2017/02/ACGManagementofHpyloriGuideline2017.pdf
http://www.ncbi.nlm.nih.gov/pubmed/28071659?tool=bestpractice.com
[158]Wang YK, Kuo FC, Liu CJ, et al. Diagnosis of Helicobacter pylori infection: current options and developments. World J Gastroenterol. 2015 Oct 28;21(40):11221-35.
https://www.wjgnet.com/1007-9327/full/v21/i40/11221.htm
http://www.ncbi.nlm.nih.gov/pubmed/26523098?tool=bestpractice.com
[159]El-Serag HB, Kao JY, Kanwal F, et al. Houston Consensus Conference on testing for Helicobacter pylori infection in the United States. Clin Gastroenterol Hepatol. 2018 Jul;16(7):992-1002;e6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913173
http://www.ncbi.nlm.nih.gov/pubmed/29559361?tool=bestpractice.com
[160]Laine L, Estrada R, Trujillo M, et al. Effect of proton-pump inhibitor therapy on diagnostic testing for Helicobacter pylori. Ann Intern Med. 1998 Oct 1;129(7):547-50.
http://www.ncbi.nlm.nih.gov/pubmed/9758575?tool=bestpractice.com
Existem algumas evidências de que certos testes do antígeno fecal que usam anticorpos monoclonais podem ser confiáveis, mesmo na presença de IBP.[161]Kodama M, Murakami K, Okimoto T, et al. Influence of proton pump inhibitor treatment on Helicobacter pylori stool antigen test. World J Gastroenterol. 2012 Jan 7;18(1):44-8.
https://www.wjgnet.com/1007-9327/full/v18/i1/44.htm
http://www.ncbi.nlm.nih.gov/pubmed/22228969?tool=bestpractice.com
Tratamento individualizado
O manejo do paciente deve ser individualizado e adaptado. Os colaboradores consideram que uma abordagem única para a erradicação do H pylori não é necessariamente do melhor interesse dos pacientes. A decisão de realizar ou não a terapia de erradicação do H pylori deve ser baseada na indicação clínica, idade, história familiar e comorbidades subjacentes do paciente, bem como benefícios potenciais contra danos de esquemas de antibioticoterapia de primeira e segunda linha. Uma boa administração de antibióticos melhora os desfechos de saúde do paciente e reduz a resistência aos antibióticos.