Table 1

Characteristics of included studies

Author, year, location	Sample size	Age (in years, unless stated), mean (SD)	Number of patients		Study setting	Study design	CRP cut-off	CRP test and method	Type of Infection	Comparator
Author, year, location	Sample size	Age (in years, unless stated), mean (SD)	CRP	Control	Study setting	Study design	CRP cut-off	CRP test and method	Type of Infection	Comparator
Antibiotic treatment duration studies (cut-offs to stop antibiotic treatment)
Numbenjapon et al,40 2015, Thailand	22	Neonates* CRP: 18.6 (NR) Control: 17.7 (NR)	11	11	NICU	RCT	<10 mg/L	NS	Neonatal sepsis: NS	Routine care (> 5 days of treatment)
Coggins et al,43 2013, USA	569	Premature* CRP: 29 (27–30) Control: 27 (25–29)	409	160	NICU	Retrospective cohort study	<10 mg/L	NS	Neonatal sepsis: EOS	Routine care
Oliveira et al, 41 2013, Brazil	94	Adults CRP: 59.6 (18.5) Control: 59.6 (13.3)	45	49	ICU	RCT	<25 mg/L	Laboratory	Sepsis	Procalcitonin (<0.1 ng/mL)
Gao et al, 45 2010, China	46	Adults CRP: 57.7 (10.4) Control: 58.7 (11.7)	18	28	Hospital (general setting)	Retrospective cohort study	NS	NS	Pyogenic liver abscess	Routine care/normal body temperature (> 14 days)
Couto et al, 44 2007, Brazil	223	Neonates* CRP: 30 (23–28) Control: 32 (24–40)	138†	85†	NICU	Prospective cohort study	<12 mg/L	Laboratory	Neonatal sepsis: LOS	Routine care (> 14 days)
Jaswal et al, 46 2003, India	28	Neonates NR	14	14	NICU	Prospective cohort study	<6 mg% (<60 mg/L)	NS	Neonatal sepsis: NS	Routine care (CRP test on 7th day)
Ehl et al, 21 1997, Germany	82	Premature* Total: 38 weeks	43	39	Low and intermediate care nursery	RCT	<10 mg/L	NS	Neonatal sepsis: NS	Routine care (> 5 days of treatment)
Antibiotic treatment initiation studies (cut-offs to withhold or initiate antibiotic treatment)
Do et al, 39 2016, Vietnam	1008	Adults‡ CRP: 16 (8–39) Control: 15 (8–41)	507	501	Primary care	RCT	≤20 mg/L—withhold >100 mg/L—initiate	Point of care	Acute RTI	Routine care
Do et al, 39 2016, Vietnam	1059	Children‡ CRP: 16 (8–39) Control: 15 (8–41)	526	533	Primary care	RCT	Patients <6 years old ≤10 mg/L—withhold >50 mg/L—initiate Patients 6–65 years old ≤20 mg/L—withhold >100 mg/L—initiate	Point of care	Acute RTI	Routine care
Rebnord et al, 26 2016, Norway	397	Children CRP: 2.13 (1.7) Control. 2.44 (1.9)	138	259	Primary care (out-of-hours service)	RCT	CRP vs no test (cut-off NS)	NS	Fever and/or respiratory symptoms	Routine care
Cals et al, 37 2013, Netherlands	379	Adults CRP: 49.4 (14.5) Control: 50.4 (15.6)	203	176	General practice	RCT	<20 mg/L—withhold 20–99 mg/L—discretion >100 mg/L—initiate	Point of care	RTI	Routine care
Little et al, 27 2013, Multi-national	4264	Adults CRP: 51 (17.5) Control: 50.9 (17.3)	2224	2040	General practice	RCT	<20 mg/L— withhold 21–50 mg/L—majority withhold 51–99 mg/L—minority withhold >100 mg/L—initiate	Point of care	RTI	Routine care
Llor et al, 42 2012, Spain	5385	Adults NR	545	4840	Primary care	Quasi-RCT	<20 mg/L—withhold >100 mg/L—initiate	Point of care	LRTI	Routine care
Cals et al, 38 2010, Netherlands	258	Adults CRP: 43 (13.4) Control: 45.5 (14)	129	129	General practice	RCT	<20 mg/L—withhold 20–99 mg/L—discretion >100 mg/L—initiate	NS	RTI	Routine care
Franz et al, 25 2004, Multi-national	1291	Neonates† CRP: 38 (24–42) Control: 38 (24–43)	656	635	NR	RCT	>10 mg/L—initiate	Laboratory	Neonatal sepsis: EOS	Routine care
Diederichsen et al, 24 2000, Denmark	812	Adults CRP: 37 (0–84) Control: 37 (0–90)	414	398	General practice	RCT	No strict guideline: <10 mg/L normal >50 mg/L abnormal	Point-of-care	Respiratory	Routine care

*Ages are mean gestational age in weeks.
†n is for total number of events per arm, not patients.
‡Adult (>15 years of age) and children (≤15 years of age) data from the study of Do et al were analysed separately.
§Median age (IQR) for entire population.
CRP, C-reactive protein; EOS, early-onset sepsis; ICU, intensive care unit; LOS, length of stay; LRTI, lower RTI; NICU, neonatal ICU; NR, Not reported; NS, not specified; RCT, randomised controlled trial; RTI, respiratory tract infection.