Identification of Factors Determining Patterns of Serum C-Reactive Protein Level Reduction in Response to Treatment Initiation in Patients with Drug-Susceptible Pulmonary Tuberculosis

Abstract

Background: Serum C-reactive protein (CRP) levels vary depending on radiological and bacteriological findings at the time of tuberculosis (TB) diagnosis. However, the utility of this biomarker in monitoring response to anti-TB treatment and identifying patients at risk of treatment failure is not well established. Objectives: This study evaluated the impact of patients' baseline characteristics and anti-TB drug plasma exposure on the early reduction in serum CRP levels and its relationship with treatment response. Methods: We enrolled 42 patients with drug-susceptible pulmonary TB, who received a standard six-month regimen. The plasma concentrations of four anti-TB drugs were analysed using LC-MS/MS. Clinically relevant data, including serum CRP levels before and 10-12 days after treatment initiation (CRP_10-12d), were obtained from electronic medical records and patient questionnaires. Results: In 10-12 days, the median serum CRP level decreased from 21.9 to 6.4 mg/L. Lower body mass index, positive sputum-smear microscopy results, and lung cavitations at diagnosis were related to higher biomarker levels at both time points; smoking had a more pronounced effect on serum CRP_10-12d levels. Variability in anti-TB drug plasma exposure did not significantly affect the reduction in serum CRP levels. The serum CRP_10-12d levels, or fold change from the baseline, did not predict the time to sputum culture conversion. Conclusions: Disease severity and patient characteristics may influence the pattern of early CRP reduction, while anti-TB drug plasma exposure had no significant effect at this stage. These early changes in serum CRP levels were not a predictor of response to anti-TB therapy.

Keywords: C-reactive protein; anti-tuberculosis drugs; pharmacokinetics; treatment response; tuberculosis.

Figure 1

Changes in serum CRP levels measured before anti-tuberculosis treatment initiation (CRP_b) and 10–12 days afterwards (CRP_10–12d) (A) and comparison across different subcategories ((B)—biological sex; (C)—age; (D)—smoking status; (E)—baseline sputum-smear microscopy results; (F)—localisation of lung lesions; (G)—presence of cavitary lesions; (H)—BMI category) using the Wilcoxon signed-rank test. BMI categories were assigned according to WHO classification [44]: underweight—BMI < 18.5 kg/m²; normal weight—18.5 kg/m² ≤ BMI < 25.0 kg/m²; overweight—BMI ≥ 25.0 kg/m². The upper and lower margins of the boxes indicate the first and third quartiles, respectively, with the horizontal line within the box indicating the median. The whiskers show the highest and lowest values within 1.5 times the interquartile range from the first and third quartile. The grey lines connect the paired data points for each patient. A p value of <0.05 was considered statistically significant. Abbreviations: CRP—C-reactive protein.