Antibiotic duration for common bacterial infections-a systematic review

Abstract

Background: Reducing antibiotic duration is a key stewardship intervention to mitigate antimicrobial resistance (AMR). We examined current evidence informing antibiotic duration for common bacterial infections to identify any gaps in terms of settings, patient populations and infectious conditions. Trial methodologies were assessed to identify areas for improvement.

Methods: MEDLINE and Embase were searched up to July 2024 for randomized trials comparing antibiotic durations in hospital and community settings (PROSPERO 2021, CRD42021276209). A narrative synthesis of the results was performed with a review on the major guidelines published by IDSA, NICE, WHO and other international societies to assess the impact of these trials on practice guidance.

Results: Out of 315 studies, 85% concluded equivalence or non-inferiority of shorter courses. Adult bacterial sinusitis, community-acquired pneumonia, female cystitis/pyelonephritis, uncomplicated cellulitis and intra-abdominal infection with adequate source control and perioperative prophylaxis had robust evidence supporting shorter durations. Few trials studied severe infections, such as bloodstream infections and ventilator-associated pneumonia. Twenty-three (7%) of the trials were conducted in intensive care settings and only 43 trials (14%) enrolled patients from low-to-middle- or low-income countries. Only 15% of studies were at low risk for bias.

Conclusions: Reducing antibiotic duration likely remains an important strategy for antibiotic stewardship, and an area of active research. While shorter antibiotic courses may be suitable for many bacterial infections, more evidence is needed for severe infections and in low- and middle-income settings.

Figure 1.

PRISMA flow diagram.

Figure 2.

Types of bacterial infections studied by antibiotic duration randomized trials over time. The top panel shows the total number of published randomized trials per year from 1969 to 31 July 2024. The bottom panel shows the number of trials for each type of infection over time. The shading intensity of the boxes represents the number of trials per year.

Figure 3.

Characteristics of antibiotic duration trials over time. Each panel is labelled with a trial characteristic: (a) age group of the trial participants; (b) the healthcare setting that the participants were enrolled from; (c) the minimum income level of the country/countries where the participants were enrolled from; (d) the type of intervention studied in the trials; (e) the trial hypothesis design; and (f) the participant populations that the conclusions of the trials were based on. The proportion of the trials published each year with a certain characteristic (y-axis) is plotted against the year of publication (x-axis) to illustrate the changes in these trial characteristics over time. ASP, antibiotic stewardship programme.

Figure 4.

Antibiotic duration trials classified by bacterial infection syndromes. Each plot presents trial results for a type of bacterial infection. The number of trials included in each plot is shown in brackets. The vertical lines joining the points in each plot represent the durations compared in each trial. Line colours indicate whether trials concluded that long duration was superior to short duration (orange), not different or non-inferior (black) or inferior (teal) in terms of clinical outcomes. Solid vertical lines show the durations allocated to the study participants (plotted only when a trial defined arbitrary durations as the intervention). Dotted vertical lines show the actual mean duration observed during the trial (plotted only when reported). Studies represented by single points were trials that used procalcitonin but failed to reduce antibiotic durations. Complicated UTI encompassed simple cystitis in males, catheter-associated UTI and pyelonephritis. The single trial shown in the Gram-positive BSI panel studied staphylococcal bloodstream infection (BSI). Only trials that reported antibiotic durations were included in this figure. Four trials were excluded from this figure as the antibiotic durations in these trials were vastly different from the other trials within the same infection syndrome. CAP, community-acquired pneumonia; VAP, ventilator-associated pneumonia; UTI, urinary tract infection; OM, osteomyelitis.