The Natural History of Antibiotic-Treated Lower Limb Cellulitis: Analysis of Data Extracted From a Multicenter Clinical Trial

Abstract

Background: Although cellulitis is a relatively common skin infection, there remains uncertainty about management, particularly the length and route of antimicrobials required. Further information on the symptomatology and biomarker changes associated with cellulitis over time would guide clinicians and patients as to the expected natural history.

Methods: We extracted data from a randomized clinical trial (NCT01876628) of clindamycin as adjunctive therapy in cellulitis to illustrate the evolution of local parameters (pain, swelling, local erythema, and warmth) and the resolution of biomarkers over time.

Results: Data from 247 individuals with mild to moderate unilateral lower limb cellulitis, who attended at least 1 face-to-face interview following recruitment, were used to examine response dynamics. Although there was a local improvement in swelling, warmth, erythema, and pain by day 5 compared with baseline, some individuals still had evidence of local inflammation at 10 days. Most biomarkers demonstrated a return to normal by day 3, although the initial fall in albumin only returned to baseline by day 10.

Conclusions: Although there was initial resolution, a significant number of individuals still had local symptoms persisting to day 10 and beyond. Clinicians can use these data to reassure themselves and their patients that ongoing local symptoms and signs after completion of antibiotic treatment do not indicate treatment failure or warrant extension of the initial antibiotic treatment or a change in antibiotic class or mode of administration.

Keywords: cellulitis; leg; lower limb; natural history.

Figure 1.

Box plots showing median, IQR, and maximum/minimum values. A and B, The circumference of the affected and unaffected lower limbs at baseline and at the day 5 and day 10 assessments, respectively. D and E, The local temperature of the affected and unaffected lower limbs at baseline and at the day 5 and day 10 assessments, respectively. ****P < .0001; ***P < .001; **P < .01; *P < .05. C and F Trend lines of the median and IQR of the circumference (C) and the local temperature (F) of the affected and unaffected limbs from baseline to day 10. The numbers above and below the lines represent the number of observations included at each time point. Data from day 1 have been omitted due to small numbers (n < 20). Abbreviation: IQR, interquartile range; ns, non-signficant.

Figure 2.

Box plots showing median, IQR, and maximum/minimum values. A, The percentage of affected skin area at baseline and at the day 5 and day 10 assessments, respectively. C, Pain scores at baseline and at the day 5 and day 10 assessments, respectively. ****P < .0001; ***P < .001; **P < .01; *P < .05. B and D, Trend lines of the median and IQR of the percentage of affected skin area (B) and the local temperature (D) of the affected limb from baseline to day 10. The numbers above the lines represent the number of observations included at each time point. Data from day 1 have been omitted due to small numbers (n < 20). Abbreviation: IQR, interquartile range.

Figure 3.

Box plots showing median, IQR, and maximum/minimum values. A, B, D, and F, The neutrophil count, lymphocyte count, NLR, and platelet count at baseline and at the day 5 and day 10 assessments, respectively. ****P < .0001; ***P < .001; **P < .01; *P < .05. C, The daily trend of the median and IQR of the neutrophil and lymphocyte counts. E and G, Trends for NLR and platelet count, respectively, to day 10. The numbers above and below the lines represent the number of observations included at each time point. Data from day 1 and day 2 have been omitted due to small numbers (n < 20). Abbreviations: IQR, interquartile range; NLR, neutrophil/lymphocyte ratio; ns, non-significant.

Figure 4.

Box plots showing median, IQR, and maximum/minimum values. A and C, Albumin and C-reactive protein measurements at baseline and at the day 5 and day 10 assessments, respectively. ****P < .0001; ***P < .001; **P < .01; *P < .05. B and D, The trends of the median and IQR of albumin and C-reactive protein, respectively, from baseline to day 10. The numbers above the lines represent the number of observations included at each time point. Data from day 1 and 2 have been omitted due to small numbers (n < 20). Abbreviation: IQR, interquartile range; ns, non-significant.