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Review
. 2022 May 6;11(5):627.
doi: 10.3390/antibiotics11050627.

Variation in Antibiotic Treatment Failure Outcome Definitions in Randomised Trials and Observational Studies of Antibiotic Prescribing Strategies: A Systematic Review and Narrative Synthesis

Rebecca Neill  1 , David Gillespie  2 , Haroon Ahmed  1
Affiliations
Review

Variation in Antibiotic Treatment Failure Outcome Definitions in Randomised Trials and Observational Studies of Antibiotic Prescribing Strategies: A Systematic Review and Narrative Synthesis

Rebecca Neill et al. Antibiotics (Basel). .

Abstract

Antibiotic treatment failure is used as an outcome in randomised trials and observational studies of antibiotic treatment strategies and may comprise different events that indicate failure to achieve a desired clinical response. However, the lack of a universally recognised definition has led to considerable variation in the types of events included. We undertook a systematic review of published studies investigating antibiotic treatment strategies for common uncomplicated infections, aiming to describe variation in terminology and components of the antibiotic treatment failure outcomes. We searched Medline, Embase, and the Cochrane Central Register of Clinical trials for English language studies published between January 2010 and January 2021. The population of interest was ambulatory patients seen in primary care or outpatient settings with respiratory tract (RTI), urinary tract (UTI), or skin and soft tissue infection (SSTI), where different antibiotic prescribing strategies were compared, and the outcome was antibiotic treatment failure. We narratively summarised key features from eligible studies and used frequencies and proportions to describe terminology, components, and time periods used to ascertain antibiotic treatment failure outcomes. Database searches identified 2967 unique records, from which 36 studies met our inclusion criteria. This included 10 randomised controlled trials and 26 observational studies, with 20 studies of RTI, 12 of UTI, 4 of SSTI, and 2 of both RTI and SSTI. We identified three key components of treatment failure definitions: prescription changes, escalation of care, and change in clinical condition. Prescription changes were most popular in studies of UTI, while changes in clinical condition were most common in RTI and SSTI studies. We found substantial variation in the definition of antibiotic treatment failure in included studies, even amongst studies of the same infection subtype and study design. Considerable further work is needed to develop a standardised definition of antibiotic treatment failure in partnership with patients, clinicians, and relevant stakeholders.

Keywords: observational study; randomised trial; treatment failure.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA diagram of included and excluded studies.
Figure 2
Figure 2
Time in days for ascertaining death in RTI studies.
Figure 3
Figure 3
Time in days for ascertaining WHO danger signs in RTI studies.
Figure 4
Figure 4
Time in days for ascertaining prescription change attributable to treatment failure in UTI studies.
See this image and copyright information in PMC

References

    1. Reynolds F.W. Treatment-failures following the use of penicillin in late syphilis. Am. J. Syph. Gonorrhea Vener. Dis. 1948;32:233–242. - PubMed
    1. Grossman L.A., Hunt J.S. Typhoid fever; a treatment failure with streptomycin. Am. Pract. Dig. Treat. 1946;1:45. - PubMed
    1. Jehan F., Nisar I., Kerai S., Balouch B., Brown N., Rahman N., Rizvi A., Shafiq Y., Zaidi A.K. Randomized Trial of Amoxicillin for Pneumonia in Pakistan. N. Engl. J. Med. 2020;383:24–34. doi: 10.1056/NEJMoa1911998. - DOI - PMC - PubMed
    1. Hazir T., Nisar Y.B., Abbasi S., Ashraf Y.P., Khurshid J., Tariq P., Asghar R., Murtaza A., Masood T., Maqbool S. Comparison of oral amoxicillin with placebo for the treatment of world health organization-defined nonsevere pneumonia in children aged 2–59 months: A multicenter, double-blind, randomized, placebo-controlled trial in pakistan. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2011;52:293–300. doi: 10.1093/cid/ciq142. - DOI - PubMed
    1. Ambroggio L., Test M., Metlay J.P., Graf T.R., Blosky M.A., Macaluso M., Shah S.S. Comparative Effectiveness of Beta-lactam Versus Macrolide Monotherapy in Children with Pneumonia Diagnosed in the Outpatient Setting. Pediatr. Infect. Dis. J. 2015;34:839–842. doi: 10.1097/INF.0000000000000740. - DOI - PMC - PubMed

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