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The antibiotic course has had its day

BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j3418 (Published 26 July 2017) Cite this as: BMJ 2017;358:j3418

Rapid Response:

Duration of antibiotic therapy: Fixed duration versus personalization/Individualization of antibiotic therapy duration: which one to be preferred?

Sir,

We too feel that fixed duration antibiotic therapy may expose patients to under-treatment or overtreatment by an antibiotic. Underexposure is associated with therapeutic failure and consequent adverse outcomes. Longer exposure to antibiotic is associated with selective growth of resistant populations and emergence of a drug resistant colony. In our view, it is better to go for personalized duration of antibiotic therapy rather than a fixed duration antibiotic course. Personalized duration can balance both under and over treatment as the duration of treatment is decided on the basis of patient disease activity parameters. (1) Personalization balances disease progression and its complications and risk associated with antibiotic use i.e. resistance to antibiotics and adverse drug reactions. (2)

There are many personalization strategies like use of clinical markers and biomarkers for deciding duration of antibiotic therapy. The Infectious Disease Society of America (IDSA) recommends discontinuation of antibiotic therapy in patients suffering from community acquired pneumonia after 5 days if he fulfils clinical stability criteria. (2, 3). In addition to clinical stability criteria, biomarkers are being used increasingly to decide the requirement, monitoring and the duration of treatment. Several algorithms are in use based on procalcitonin (PCT), C reactive protein (CRP) and risk assessment tools based on level of pro-adrenomedullin (ProADM). PCT has been used as a decision maker tool in CAP, sepsis, urinary tract infections, postoperative infections, meningitis etc. (4, 5, 6) In severe infections, use of PCT kinetics as a decision maker tool resulted in shorter duration of antibiotic therapy with early cessation. These biomarker based treatment strategies did not result in increase in mortality, recurrence of infection or failure of treatment or increase in adverse effect. (6) Personalization also added economic advantage. In “SAPS”study, use of PCT based protocol resulted in mean reduction in antibiotic cost by €34 per patient. (7)
ProADM is used along with clinical scoring systems for risk stratification. (3, 4) Many other promising biomarkers are evaluated in different clinical scenarios e.g. sTREM-1 (pneumonia, meningitis and sepsis), suPAR/CD87 (sepsis), ProADM (pneumonia), Presepsin (sepsis), PTX3 (sepsis) etc. (9, 10)

Regarding future prospectives, we need to focus on more personalized strategies like use of precision peptides for killing bacteria and at the same time preserving microbiota. Use of system pharmacology approach and machine learning techniques can help us further individualizing the approach. CRISPR-Cas has been used to target specific antibiotic resistance genes to remove drug-resistant organisms selectively in pure cultures and in complex microbial consortia. (11) So, to conclude, we think that use of personalized antibiotic therapy is the future of antibiotic therapy. It is the need of the hour, to develop new biomarkers and gather evidence on the same from adequately powered clinical studies.

Reference:
1. Llewelyn MJ, Fitzpatrick JM, Darwin E, et al. The antibiotic course has had its day. BMJ 2017;358:j3418.
2. Lee JS, Giesler DL, Fine MJ. Duration of Antibiotic Therapy for Community-Acquired Pneumonia in the Era of Personalized Medicine. JAMA 2016;316(23):2544-2545.
3. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27-72.
4. Schuetz P, Litke A, Albrich WC, et al. Blood biomarkers for personalized treatment and patient management decisions in community-acquired pneumonia. Curr Opin Infect Dis. 2013;26 (2):159-67.
5. Póvoa P, Salluh JI. Biomarker-guided antibiotic therapy in adult critically ill patients: a critical review. Ann Intensive Care. 2012; 2 (1):32.
6. Sager R, Kutz A, Mueller B, Schuetz P. Procalcitonin-guided diagnosis and antibiotic stewardship revisited. BMC Med. 2017;15(1):15.
7. de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819-27.
8. Westwood M, Ramaekers B, Whiting P, et al. Procalcitonin testing to guide antibiotic therapy for the treatment of sepsis in intensive care settings and for suspected bacterial infection in emergency department settings: a systematic review and cost-effectiveness analysis. Health Technol Assess. 2015; 19: 1-236.
9. Vincent JL, Bassetti M, François B, et al. Advances in antibiotic therapy in the critically ill. Crit Care. 2016;20(1):133.
10. Nora D, Salluh J, Martin-Loeches I, Póvoa P. Biomarker-guided antibiotic therapy—strengths and limitations. Annals of Translational Medicine. 2017;5(10):208.
11. de la Fuente-Nunez C, Torres MD, Mojica FJ, et al. Next-generation precision antimicrobials: towards personalized treatment of infectious diseases. Curr Opin Microbiol. 2017;37:95-102.

Competing interests: No competing interests

04 August 2017
Dr. Phulen Sarma
Medical Pharmacologist
Harish Kumar, Ajay Prakash, Abhishek Mishra, Rahul Singh, Shweta Sinha, Hariom Soni, Subodh Kr. Yadav, Anusuya Bhattacharyya, Ashutosh Singh, Gaurav Muktesh, Narender Dhaka, Bikash Medhi
PGIMER Chandigarh
Room No 4004 Department of Pharmacology, PGIMER