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Invited Commentary
Global Health
February 12, 2020

Defining Optimal Empirical Antibiotic Regimens in a Rapidly Changing Landscape of Resistance

Author Affiliations
  • 1Division of Experimental Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • 2Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
JAMA Netw Open. 2020;3(2):e1921150. doi:10.1001/jamanetworkopen.2019.21150

When faced with a patient with a suspected bacterial infection, clinicians are forced to make quick decisions about which is the best antibiotic to use. They need to incorporate patient-level factors, including the syndrome in question, which comorbidities are present, and how ill the patient is. They need to incorporate population-level factors, such as the common organisms in their community and the resistance patterns to commonly used antibiotics. The traditional aids for these decisions have typically been antibiogram reports, which, on the basis of historical data obtained from regional microbiology laboratories, describe the percentage susceptibilities of individual organisms to individual antibiotics. For a clinician managing patients with syndromes such as sepsis, these typical antibiograms may not be the ideal tool, because the inciting organism is likely unknown, multiple organisms may be involved, and/or multiple drugs in combination may be needed. Bielicki et al1 systematically searched the literature for microbiological data in neonatal sepsis across a number of Asian countries and determined, through a Bayesian decision-tree model informing a weighted-incidence syndromic combination algorithm (WISCA), that currently recommended empirical antibiotic regimens for neonatal sepsis in the region are likely inadequate.

With the growing antimicrobial resistance crisis, ensuring that the right antibiotic is given to the right patient at the right time should be a major focus for health systems globally. A number of reports over recent years have described WISCAs, which were initially proposed in 2012.2 These algorithms describe the likelihood for adequacy of a typical antibiotic regimen for a clinical syndrome such as sepsis, by taking into account as much local data as are available and weighing those data on the basis of the likelihood of pathogens causing that syndrome. As a decision aid, WISCAs have been shown in small analyses3 to be more useful than typical antibiograms.

The WISCAs created under a Bayesian decision-tree approach reflect how clinical decisions are made in real life.4 However, these approaches are often avoided because of their supposed difficulty, particularly in comparison with traditional antibiograms, which report simple percentages. Bayesian statistics allow for inference with intuitive explanation, although this is often lost because of mathematical formulas that may superficially appear complex. Simply, this is in line with the basic idea of constantly updated knowledge streams, during which our understanding is updated each time new data become available, taking existing knowledge (the prior) with the new information (the likelihood). The 95% credible intervals illustrate the 95% chance that the unknown parameter, such as the coverage of an antibiotic regimen, is within the estimated interval, whereas interpreting the traditional 95% confidence interval involves a hypothetical thought process of repeating the same experiments an infinite number of times.

In the context of antibiotic resistance, as shown by Bielicki et al,1 the use of prior information can maximize the available data to better estimate the coverage of empirical antibiotic regimens. Bielicki et al1 used a Bayesian WISCA decision-tree model to estimate the coverage offered by 3 recommended empirical antibiotic regimens for neonates with sepsis across a number of Asian countries. They identified data on the incidence of bacteria and their antimicrobial susceptibilities through a systematic review of previously published work in the region to estimate the coverage of aminopenicillin-gentamicin, a third-generation cephalosporin, or meropenem, informed by priors based on expected sensitivities of major pathogens to these agents.

Their findings should raise concern: currently, globally recommended first-line and second-line empirical antibiotic regimens for neonatal sepsis will cover well below an adequate proportion of suspected pathogens. In most of the regions studied, this proportion fell well below one-half.1 This reflects point prevalence work on which antibiotics are currently being used, where only a small proportion of clinicians use the globally recommended empirical agents in their setting, and meropenem is the most commonly used agent in neonates.5 Clearly, better-defined strategies to determine which patient should receive which antibiotics are urgently needed.

Using published literature to estimate microbiological data locally comes with problems, such as biasing the results toward academic institutions and ensuring timeliness and accuracy of collected data. However, given the patchiness of available microbiological testing in the region,6 the published literature may reflect the best available data to inform these decisions, in the absence of scaled-up solutions for more available antimicrobial resistance data dissemination. Given the diversity that exists within a single country, or even within a single health system, relying on national-level estimates to inform local practice may not be accurate.7 In the absence of local data, however, national estimates remain the most reliable, but serve as an important argument to augment the testing capabilities across regions with a high burden of antimicrobial resistance. From a larger perspective, global bodies that provide recommendations for empirical therapy for syndromes may need to reflect on the rapidly changing epidemiological landscape and explicitly incorporate language regarding local resistance patterns and likely causative pathogens.8

The antimicrobial resistance crisis continues to unfold, with an ongoing arms race between clinicians wanting to ensure the best therapy for their patient and increasing resistance among bacteria. Incorporating better modeling techniques as practical decision aids to clinicians can help cool down that battle, but only if the microbiological data used to inform those models are up-to-date, local, and reliable.

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Article Information

Published: February 12, 2020. doi:10.1001/jamanetworkopen.2019.21150

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Park JJH et al. JAMA Network Open.

Corresponding Author: Srinivas Murthy, MD, CM, MHSc, Department of Pediatrics, Faculty of Medicine, University of British Columbia, 4500 Oak St, Vancouver, BC V6H 3V4, Canada (srinivas.murthy@cw.bc.ca).

Conflict of Interest Disclosures: None reported.

References
1.
Bielicki  JA, Sharland  M, Heath  PT,  et al.  Evaluation of the coverage of 3 antibiotic regimens for neonatal sepsis in the hospital setting across Asian countries.  JAMA Netw Open. 2020;3(2):e1921124. doi:10.1001/jamanetworkopen.2019.21124Google Scholar
2.
Hebert  C, Ridgway  J, Vekhter  B, Brown  EC, Weber  SG, Robicsek  A.  Demonstration of the weighted-incidence syndromic combination antibiogram: an empiric prescribing decision aid.  Infect Control Hosp Epidemiol. 2012;33(4):381-388. doi:10.1086/664768PubMedGoogle ScholarCrossref
3.
Randhawa  V, Sarwar  S, Walker  S, Elligsen  M, Palmay  L, Daneman  N.  Weighted-incidence syndromic combination antibiograms to guide empiric treatment of critical care infections: a retrospective cohort study.  Crit Care. 2014;18(3):R112. doi:10.1186/cc13901PubMedGoogle ScholarCrossref
4.
Gill  CJ, Sabin  L, Schmid  CH.  Why clinicians are natural bayesians.  BMJ. 2005;330(7499):1080-1083. doi:10.1136/bmj.330.7499.1080PubMedGoogle ScholarCrossref
5.
Jackson  C, Hsia  Y, Basmaci  R,  et al.  Global divergence from World Health Organization treatment guidelines for neonatal and pediatric sepsis.  Pediatr Infect Dis J. 2019;38(11):1104-1106. doi:10.1097/INF.0000000000002433PubMedGoogle ScholarCrossref
6.
Zellweger  RM, Carrique-Mas  J, Limmathurotsakul  D, Day  NPJ, Thwaites  GE, Baker  S; Southeast Asia Antimicrobial Resistance Network.  A current perspective on antimicrobial resistance in Southeast Asia.  J Antimicrob Chemother. 2017;72(11):2963-2972. doi:10.1093/jac/dkx260PubMedGoogle ScholarCrossref
7.
Takemura  H, Mochizuki  T.  Comparison between local and national epidemiology of antimicrobial resistance using the JANIS data.  J Infect Chemother. 2018;24(11):868-872. doi:10.1016/j.jiac.2018.08.016PubMedGoogle ScholarCrossref
8.
Elias  C, Moja  L, Mertz  D, Loeb  M, Forte  G, Magrini  N.  Guideline recommendations and antimicrobial resistance: the need for a change.  BMJ Open. 2017;7(7):e016264. doi:10.1136/bmjopen-2017-016264PubMedGoogle Scholar
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    1 Comment for this article
    EXPAND ALL
    Good tool in resistant microbial world
    Muna Malik, M.PHIL Microbiology | Post Graduate Medical Institute, Ameer Ud din Medical college, Lahore General Hospital, Lahore Pakistan.
    A very interesting topic, and a good tool is discussed here. Antimicrobial resistance is increasing day by day in the world and we are at the verge where we will find nothing to fight against these super multidrug resistance bacteria. In developing countries like Pakistan, we are making our antibiograms in hospitals and they are helping the clinicians for treat patients. But these are just the data of drug resistance among hospital bugs. WISCA is still not used in Pakistan for collecting data for empirical antimicrobial therapies, which is commonly used in developed countries among hospital acquired infections [1]. I think we should use this tool for empirical antimicrobial therapies to over come the resistance trend in developing countries and improve the quality of human life in such countries.

    1. Tandogdu Z, Koves B, Cai T, Cek M, Tenke P, Naber K, Wagenlehner F, Johansen TE. Condition-specific surveillance in health care-associated urinary tract infections as a strategy to improve empirical antibiotic treatment: an epidemiological modelling study. World journal of urology. 2020 Jan 1;38(1):27-34.
    CONFLICT OF INTEREST: None Reported
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