The social role of C-reactive protein point-of-care testing to guide antibiotic prescription in Northern Thailand

New and affordable point-of-care testing (POCT) solutions are hoped to guide antibiotic prescription and to help limit antimicrobial resistance (AMR)—especially in low- and middle-income countries where resource constraints often prevent extensive diagnostic testing. Anthropological and sociological research has illuminated the role and impact of rapid point-of-care malaria testing. This paper expands our knowledge about the social implications of non-malarial POCT, using the case study of a C-reactive-protein point-of-care testing (CRP POCT) clinical trial with febrile patients at primary-care-level health centres in Chiang Rai province, northern Thailand. We investigate the social role of CRP POCT through its interactions with (a) the healthcare workers who use it, (b) the patients whose routine care is affected by the test, and (c) the existing patient-health system linkages that might resonate or interfere with CRP POCT. We conduct a thematic analysis of data from 58 purposively sampled pre- and post-intervention patients and healthcare workers in August 2016 and May 2017. We find widespread positive attitudes towards the test among patients and healthcare workers. Patients’ views are influenced by an understanding of CRP POCT as a comprehensive blood test that provides specific diagnosis and that corresponds to notions of good care. Healthcare workers use the test to support their negotiations with patients but also to legitimise ethical decisions in an increasingly restrictive antibiotic policy environment. We hypothesise that CRP POCT could entail greater patient adherence to recommended antibiotic treatment, but it could also encourage riskier health behaviour and entail potentially adverse equity implications for patients across generations and socioeconomic strata. Our empirical findings inform the clinical literature on increasingly propagated point-of-care biomarker tests to guide antibiotic prescriptions, and we contribute to the anthropological and sociological literature through a novel conceptualisation of the patient-health system interface as an activity space into which biomarker testing is introduced

A retrospective review of the management of acute infections and the indications for antibiotic prescription in primary care in Northern Thailand

Introduction Antibiotic use in low-income and middle-income countries continues to rise despite the knowledge that antibiotic overuse can lead to antimicrobial resistance. There is a paucity of detailed data on the use of antibiotics in primary care in low-resource settings. Objective To describe the presentation of acute infections and the indications for antibiotic prescription. Design A 2-year retrospective review of routinely collected data. Setting All 32 primary care units in one district in northern Thailand. Participants Patients attending primary care with a history of fever, documented temperature, International Statistical Classification of Diseases 10 code for infection or prescribed a systemic antibiotic. Patients attending after the initiation of a study on C-reactive protein testing in four centres were excluded. Outcome measures The proportion of patients prescribed an antibiotic and the frequency of clinical presentations. Results 762 868 patients attended the health centres, of whom 103 196 met the inclusion criteria, 5966 were excluded resulting in 97 230 attendances consisting of 83 661 illness episodes. 46.9% (39 242) of the patients were prescribed an antibiotic during their illness. Indications for antibiotic prescription in the multivariable logistic regression analysis included male sex (adjusted OR (aOR) 1.21 (95% CI 1.16 to 1.28), p37.5°C (aOR 1.24 (95% CI 1.03 to 1.48), p=0.020). 77.9% of the presentations were for respiratory-related problems, of which 98.6% were upper respiratory tract infections. The leading infection diagnoses were common cold (50%), acute pharyngitis (18.9%) and acute tonsillitis (5%) which were prescribed antibiotics in 10.5%, 88.7% and 87.1% of cases, respectively. Amoxicillin was the most commonly prescribed antibiotic. Conclusions Nearly half of the patients received an antibiotic, the majority of whom had a respiratory infection. The results can be used to plan interventions to improve the rational use of antibiotics. Further studies in private facilities, pharmacies and dental clinics are required

A retrospective review of the management of acute infections and the indications for antibiotic prescription in primary care in Northern Thailand

Introduction Antibiotic use in low-income and middle-income countries continues to rise despite the knowledge that antibiotic overuse can lead to antimicrobial resistance. There is a paucity of detailed data on the use of antibiotics in primary care in low-resource settings. Objective To describe the presentation of acute infections and the indications for antibiotic prescription. Design A 2-year retrospective review of routinely collected data. Setting All 32 primary care units in one district in northern Thailand. Participants Patients attending primary care with a history of fever, documented temperature, International Statistical Classification of Diseases 10 code for infection or prescribed a systemic antibiotic. Patients attending after the initiation of a study on C-reactive protein testing in four centres were excluded. Outcome measures The proportion of patients prescribed an antibiotic and the frequency of clinical presentations. Results 762 868 patients attended the health centres, of whom 103 196 met the inclusion criteria, 5966 were excluded resulting in 97 230 attendances consisting of 83 661 illness episodes. 46.9% (39 242) of the patients were prescribed an antibiotic during their illness. Indications for antibiotic prescription in the multivariable logistic regression analysis included male sex (adjusted OR (aOR) 1.21 (95% CI 1.16 to 1.28), p<0.001), adults (aOR 1.77 (95% CI 1.57 to 2), p<0.001) and a temperature >37.5°C (aOR 1.24 (95% CI 1.03 to 1.48), p=0.020). 77.9% of the presentations were for respiratory-related problems, of which 98.6% were upper respiratory tract infections. The leading infection diagnoses were common cold (50%), acute pharyngitis (18.9%) and acute tonsillitis (5%) which were prescribed antibiotics in 10.5%, 88.7% and 87.1% of cases, respectively. Amoxicillin was the most commonly prescribed antibiotic. Conclusions Nearly half of the patients received an antibiotic, the majority of whom had a respiratory infection. The results can be used to plan interventions to improve the rational use of antibiotics. Further studies in private facilities, pharmacies and dental clinics are required

Prevalence and susceptibility profiles of group a streptococcus in primary care patients with a sore throat and fever in Thailand and the utility of C-Reactive protein and clinical scores for its identification

Pharyngitis is usually caused by a viral infection for which antibiotics are often unnecessarily prescribed, adding to the burden of antimicrobial resistance. Identifying who needs antibiotics is challenging; microbiological confirmation and clinical scores are used but have limitations. In a cross-sectional study nested within a randomized controlled trial, we estimated the prevalence and antibiotic susceptibility profiles of group A Streptococcus (GAS) in patients presenting to primary care with a sore throat and fever in northern Thailand. We then evaluated the use of C-reactive protein (CRP) and clinical scores (Centor and FeverPAIN) to identify the presence of GAS. One hundred sixty-nine patients were enrolled, of whom 35 (20.7%) had β-hemolytic Streptococci (BHS) isolated from throat swab culture, and 11 (6.5%) had GAS. All GAS isolates were sensitive to penicillin G. The median CRP of those without BHS isolation was 10 mg/L (interquartile range [IQR] £ 8–18), compared with 18 mg/L (IQR 9–71, P = 0.0302) for those with GAS and 14 mg/L (IQR £ 8–38, P = 0.0516) for those with any BHS isolated. However, there were no significant relationships between CRP > 8 mg/L (P = 0.112), Centor ³ 3 (P = 0.212), and FeverPAIN ³ 4 (P = 1.000), and the diagnosis of GAS compared with no BHS isolation. Identifying who requires antibiotics for pharyngitis remains challenging and necessitates further larger studies. C-reactive protein testing alone, although imperfect, can reduce prescribing compared with routine care. Targeted CRP testing through clinical scoring may be the most cost-effective approach to ruling out GAS infection

Prevalence and susceptibility profiles of group a streptococcus in primary care patients with a sore throat and fever in Thailand and the utility of C-Reactive protein and clinical scores for its identification

Pharyngitis is usually caused by a viral infection for which antibiotics are often unnecessarily prescribed, adding to the burden of antimicrobial resistance. Identifying who needs antibiotics is challenging; microbiological confirmation and clinical scores are used but have limitations. In a cross-sectional study nested within a randomized controlled trial, we estimated the prevalence and antibiotic susceptibility profiles of group A Streptococcus (GAS) in patients presenting to primary care with a sore throat and fever in northern Thailand. We then evaluated the use of C-reactive protein (CRP) and clinical scores (Centor and FeverPAIN) to identify the presence of GAS. One hundred sixty-nine patients were enrolled, of whom 35 (20.7%) had β-hemolytic Streptococci (BHS) isolated from throat swab culture, and 11 (6.5%) had GAS. All GAS isolates were sensitive to penicillin G. The median CRP of those without BHS isolation was 10 mg/L (interquartile range [IQR] £ 8–18), compared with 18 mg/L (IQR 9–71, P = 0.0302) for those with GAS and 14 mg/L (IQR £ 8–38, P = 0.0516) for those with any BHS isolated. However, there were no significant relationships between CRP > 8 mg/L (P = 0.112), Centor ³ 3 (P = 0.212), and FeverPAIN ³ 4 (P = 1.000), and the diagnosis of GAS compared with no BHS isolation. Identifying who requires antibiotics for pharyngitis remains challenging and necessitates further larger studies. C-reactive protein testing alone, although imperfect, can reduce prescribing compared with routine care. Targeted CRP testing through clinical scoring may be the most cost-effective approach to ruling out GAS infection

Effect of point-of-care C-reactive protein testing on antibiotic prescription in febrile patients attending primary care in Thailand and Myanmar: an open-label, randomised, controlled trial

Background In southeast Asia, antibiotic prescription in febrile patients attending primary care is common, and a probable contributor to the high burden of antimicrobial resistance. The objective of this trial was to explore whether C-reactive protein (CRP) testing at point of care could rationalise antibiotic prescription in primary care, comparing two proposed thresholds to classify CRP concentrations as low or high to guide antibiotic treatment. Methods We did a multicentre, open-label, randomised, controlled trial in participants aged at least 1 year with a documented fever or a chief complaint of fever (regardless of previous antibiotic intake and comorbidities other than malignancies) recruited from six public primary care units in Thailand and three primary care clinics and one outpatient department in Myanmar. Individuals were randomly assigned using a computer-based randomisation system at a ratio of 1:1:1 to either the control group or one of two CRP testing groups, which used thresholds of 20 mg/L (group A) or 40 mg/L CRP (group B) to guide antibiotic prescription. Health-care providers were masked to allocation between the two intervention groups but not to the control group. The primary outcome was the prescription of any antibiotic from day 0 to day 5 and the proportion of patients who were prescribed an antibiotic when CRP concentrations were above and below the 20 mg/L or 40 mg/L thresholds. The primary outcome was analysed in the intention-to-treat and per-protocol populations. The trial is registered with ClinicalTrials.gov, number NCT02758821, and is now completed. Findings Between June 8, 2016, and Aug 25, 2017, we recruited 2410 patients, of whom 803 patients were randomly assigned to CRP group A, 800 to CRP group B, and 807 to the control group. 598 patients in CRP group A, 593 in CRP group B, and 767 in the control group had follow-up data for both day 5 and day 14 and had been prescribed antibiotics (or not) in accordance with test results (per-protocol population). During the trial, 318 (39%) of 807 patients in the control group were prescribed an antibiotic by day 5, compared with 290 (36%) of 803 patients in CRP group A and 275 (34%) of 800 in CRP group B. The adjusted odds ratio (aOR) of 0·80 (95% CI 0·65–0·98) and risk difference of −5·0 percentage points (95% CI −9·7 to −0·3) between group B and the control group were significant, although lower than anticipated, whereas the reduction in prescribing in group A compared with the control group was not significant (aOR 0·86 [0·70–1·06]; risk difference −3·3 percentage points [–8·0 to 1·4]). Patients with high CRP concentrations in both intervention groups were more likely to be prescribed an antibiotic than in the control group (CRP ≥20 mg/L: group A vs control group, p<0·0001; CRP ≥40 mg/L: group B vs control group, p<0·0001), and those with low CRP concentrations were more likely to have an antibiotic withheld (CRP <20 mg/L: group A vs control group, p<0·0001; CRP <40 mg/L: group B vs control group, p<0·0001). 24 serious adverse events were recorded, consisting of 23 hospital admissions and one death, which occurred in CRP group A. Only one serious adverse event was thought to be possibly related to the study (a hospital admission in CRP group A). Interpretation In febrile patients attending primary care, testing for CRP at point of care with a threshold of 40 mg/L resulted in a modest but significant reduction in antibiotic prescribing, with patients with high CRP being more likely to be prescribed an antibiotic, and no evidence of a difference in clinical outcomes. This study extends the evidence base from lower-income settings supporting the use of CRP tests to rationalise antibiotic use in primary care patients with an acute febrile illness. A key limitation of this study is the individual rather than cluster randomised study design which might have resulted in contamination between the study groups, reducing the effect size of the intervention

Effect of point-of-care C-reactive protein testing on antibiotic prescription in febrile patients attending primary care in Thailand and Myanmar: an open-label, randomised, controlled trial

Background In southeast Asia, antibiotic prescription in febrile patients attending primary care is common, and a probable contributor to the high burden of antimicrobial resistance. The objective of this trial was to explore whether C-reactive protein (CRP) testing at point of care could rationalise antibiotic prescription in primary care, comparing two proposed thresholds to classify CRP concentrations as low or high to guide antibiotic treatment. Methods We did a multicentre, open-label, randomised, controlled trial in participants aged at least 1 year with a documented fever or a chief complaint of fever (regardless of previous antibiotic intake and comorbidities other than malignancies) recruited from six public primary care units in Thailand and three primary care clinics and one outpatient department in Myanmar. Individuals were randomly assigned using a computer-based randomisation system at a ratio of 1:1:1 to either the control group or one of two CRP testing groups, which used thresholds of 20 mg/L (group A) or 40 mg/L CRP (group B) to guide antibiotic prescription. Health-care providers were masked to allocation between the two intervention groups but not to the control group. The primary outcome was the prescription of any antibiotic from day 0 to day 5 and the proportion of patients who were prescribed an antibiotic when CRP concentrations were above and below the 20 mg/L or 40 mg/L thresholds. The primary outcome was analysed in the intention-to-treat and per-protocol populations. The trial is registered with ClinicalTrials.gov, number NCT02758821, and is now completed. Findings Between June 8, 2016, and Aug 25, 2017, we recruited 2410 patients, of whom 803 patients were randomly assigned to CRP group A, 800 to CRP group B, and 807 to the control group. 598 patients in CRP group A, 593 in CRP group B, and 767 in the control group had follow-up data for both day 5 and day 14 and had been prescribed antibiotics (or not) in accordance with test results (per-protocol population). During the trial, 318 (39%) of 807 patients in the control group were prescribed an antibiotic by day 5, compared with 290 (36%) of 803 patients in CRP group A and 275 (34%) of 800 in CRP group B. The adjusted odds ratio (aOR) of 0·80 (95% CI 0·65–0·98) and risk difference of −5·0 percentage points (95% CI −9·7 to −0·3) between group B and the control group were significant, although lower than anticipated, whereas the reduction in prescribing in group A compared with the control group was not significant (aOR 0·86 [0·70–1·06]; risk difference −3·3 percentage points [–8·0 to 1·4]). Patients with high CRP concentrations in both intervention groups were more likely to be prescribed an antibiotic than in the control group (CRP ≥20 mg/L: group A vs control group, p<0·0001; CRP ≥40 mg/L: group B vs control group, p<0·0001), and those with low CRP concentrations were more likely to have an antibiotic withheld (CRP <20 mg/L: group A vs control group, p<0·0001; CRP <40 mg/L: group B vs control group, p<0·0001). 24 serious adverse events were recorded, consisting of 23 hospital admissions and one death, which occurred in CRP group A. Only one serious adverse event was thought to be possibly related to the study (a hospital admission in CRP group A). Interpretation In febrile patients attending primary care, testing for CRP at point of care with a threshold of 40 mg/L resulted in a modest but significant reduction in antibiotic prescribing, with patients with high CRP being more likely to be prescribed an antibiotic, and no evidence of a difference in clinical outcomes. This study extends the evidence base from lower-income settings supporting the use of CRP tests to rationalise antibiotic use in primary care patients with an acute febrile illness. A key limitation of this study is the individual rather than cluster randomised study design which might have resulted in contamination between the study groups, reducing the effect size of the intervention