C-reactive protein and procalcitonin for antimicrobial stewardship in COVID-19

Abstract Purpose Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread around the world. Differentiation between pure viral COVID-19 pneumonia and secondary infection can be challenging. In patients with elevated C-reactive protein (CRP) on admission physicians often decide to prescribe antibiotic therapy. However, overuse of anti-infective therapy in the pandemic should be avoided to prevent increasing antimicrobial resistance. Procalcitonin (PCT) and CRP have proven useful in other lower respiratory tract infections and might help to differentiate between pure viral or secondary infection. Methods We performed a retrospective study of patients admitted with COVID-19 between 6th March and 30th October 2020. Patient background, clinical course, laboratory findings with focus on PCT and CRP levels and microbiology results were evaluated. Patients with and without secondary bacterial infection in relation to PCT and CRP were compared. Using receiver operating characteristic (ROC) analysis, the best discriminating cut-off value of PCT and CRP with the corresponding sensitivity and specificity was calculated. Results Out of 99 inpatients (52 ICU, 47 Non-ICU) with COVID-19, 32 (32%) presented with secondary bacterial infection during hospitalization. Patients with secondary bacterial infection had higher PCT (0.4 versus 0.1 ng/mL; p = 0.016) and CRP (131 versus 73 mg/L; p = 0.001) levels at admission and during the hospital stay (2.9 versus 0.1 ng/mL; p < 0.001 resp. 293 versus 94 mg/L; p < 0.001). The majority of patients on general ward had no secondary bacterial infection (93%). More than half of patients admitted to the ICU developed secondary bacterial infection (56%). ROC analysis of highest PCT resp. CRP and secondary infection yielded AUCs of 0.88 (p < 0.001) resp. 0.86 (p < 0.001) for the entire cohort. With a PCT cut-off value at 0.55 ng/mL, the sensitivity was 91% with a specificity of 81%; a CRP cut-off value at 172 mg/L yielded a sensitivity of 81% with a specificity of 76%. Conclusion PCT and CRP measurement on admission and during the course of the disease in patients with COVID-19 may be helpful in identifying secondary bacterial infections and guiding the use of antibiotic therapy.

Download Full-text

Procalcitonin Increase Is Associated with the Development of Critical Care-Acquired Infections in COVID-19 ARDS

Antibiotics ◽

10.3390/antibiotics10111425 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1425

Author(s):

Owen Richards ◽

Philip Pallmann ◽

Charles King ◽

Yusuf Cheema ◽

Charlotte Killick ◽

...

Keyword(s):

Bacterial Infection ◽

Secondary Infection ◽

Ventilator Associated Pneumonia ◽

C Reactive Protein ◽

Comparative Efficacy ◽

Blood Cell Count ◽

Single Centre ◽

Secondary Bacterial Infection ◽

Reactive Protein ◽

Insight Into

Secondary bacterial infection in COVID-19 patients is associated with increased mortality and disproportionately affects critically ill patients. This single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients. Adult patients admitted to an intensive care unit (ICU) with confirmed SARS-CoV-2 infection between 9 March 2020 and 5 June 2020 were recruited to the study. For daily biomarker and secondary infection, laboratory-confirmed bloodstream infection (LCBI) and ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) data were collected. We observed a PCT rise in 53 (81.5%) of the patients, a C-reactive protein (CRP) rise in 55 (84.6%) and a white blood cell count (WBC) rise in 61 (93.8%). Secondary infection was confirmed in 33 (50.8%) of the patients. A PCT rise was present in 97.0% of patients with at least one confirmed VAP/VAT and/or LCBI event. CRP and WBC rises occurred in 93.9% and 97.0% of patients with confirmed VAP/VAT and/or LCBI, respectively. Logistic regression analysis found that, when including all biomarkers in the same model, there was a significant association between PCT rise and the occurrence of LCBI and/or VAP/VAT (OR = 14.86 95%CI: 2.20, 342.53; p = 0.021). Conversely, no statistically significant relationship was found between either a CRP rise (p = 0.167) or a WBC rise (p = 0.855) and the occurrence of VAP/VAT and/or LCBI. These findings provide a promising insight into the usefulness of PCT measurement in predicting the emergence of secondary bacterial infection in ICU.

Download Full-text

C-reactive protein or procalcitonin combined with rhinorrhea for discrimination of viral from bacterial infections in hospitalized adults in non-intensive care units with lower respiratory tract infections

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01672-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shengchen Duan ◽

Xiaoying Gu ◽

Guohui Fan ◽

Fei Zhou ◽

Guangfa Zhu ◽

...

Keyword(s):

Intensive Care ◽

Respiratory Tract ◽

Bacterial Infection ◽

Lower Respiratory Tract ◽

Bacterial Infections ◽

Clinical Characteristics ◽

Clinical Symptoms ◽

C Reactive Protein ◽

Reactive Protein ◽

Tract Infections

Abstract Background Whether procalcitonin (PCT) or C-reactive protein (CRP) combined with certain clinical characteristics can better distinguish viral from bacterial infections remains unclear. The aim of the study was to assess the ability of PCT or CRP combined with clinical characteristics to distinguish between viral and bacterial infections in hospitalized non-intensive care unit (ICU) adults with lower respiratory tract infection (LRTI). Methods This was a post-hoc analysis of a randomized clinical trial previously conducted among LRTI patients. The ability of PCT, CRP and PCT or CRP combined with clinical symptoms to discriminate between viral and bacterial infection were assessed by portraying receiver operating characteristic (ROC) curves among patients with only a viral or a typical bacterial infection. Results In total, 209 infected patients (viral 69%, bacterial 31%) were included in the study. When using CRP or PCT to discriminate between viral and bacterial LRTI, the optimal cut-off points were 22 mg/L and 0.18 ng/mL, respectively. When the optimal cut-off for CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) combined with rhinorrhea was used to discriminate viral from bacterial LRTI, the AUCs were 0.81 (95% CI: 0.75–0.87) and 0.80 (95% CI: 0.74–0.86), which was statistically significantly better than when CRP or PCT used alone (p < 0.001). When CRP ≤ 22 mg/L, PCT ≤ 0.18 ng/mL and rhinorrhea were combined, the AUC was 0.86 (95% CI: 0.80–0.91), which was statistically significantly higher than when CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) was combined with rhinorrhea (p = 0.011 and p = 0.021). Conclusions Either CRP ≤ 22 mg/L or PCT ≤ 0.18 ng/mL combined with rhinorrhea could help distinguish viral from bacterial infections in hospitalized non-ICU adults with LRTI. When rhinorrhea was combined together, discrimination ability was further improved.

Download Full-text

#54: Sensitivity and Specificity of Procalcitonin vs C Reactive Protein in Identifying Pediatric Bacterial infections

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piab031.035 ◽

2021 ◽

Vol 10 (Supplement_2) ◽

pp. S16-S16

Author(s):

Sara Kim ◽

Avni Bhatt ◽

Silvana Carr ◽

Frances Saccoccio ◽

Judy Lew

Keyword(s):

Urinary Tract ◽

Sensitivity And Specificity ◽

Urinary Tract Infections ◽

Bacterial Infections ◽

C Reactive Protein ◽

Reactive Protein ◽

Culture Positivity ◽

Serious Bacterial Infections ◽

Tract Infections ◽

Culture Positive

Abstract Background Procalcitonin (PCT) and c-reactive protein (CRP) have been utilized in children to assess risk for serious bacterial infections. However, there have been different cut-offs reported for PCT and CRP, which yield different sensitivity and specificity. This study aims to compare the sensitivity and specificity of PCT and CRP in detecting serious bacterial infections (SBIs), specifically urinary tract infections, bacteremia and meningitis. Methods In this retrospective, single center cohort study from January 2018 to June 2019, we analyzed children with a fever greater than 38C with both PCT and CRP value within 24 hours of admission. Each patient had a blood, urine and/or cerebrospinal fluid culture collected within 48 hours of admission. No antibiotics were administered from the admitting hospital prior to collection of the PCT or CRP. Our gold standard was a positive culture obtained from blood, cerebrospinal fluid, or urine. The statistical analysis included categorical variables as percentages and compared them using the Fisher exact test. The optimal cutoff values for PCT or CRP were based on ROC curve analysis and Youden Index. Sensitivity and specificity analysis were based on literature review cut offs and ROC curves cut offs. Results Among 202 children, we had 45 culture positive patients (11 urinary tract infections, 4 meningitis, and 32 bacteremia). The patients with culture positivity had higher PCT levels (7.9 ng/mL vs 2.5 ng/mL, P=0.0111), CRP levels (110.9 mg/L vs 49.6 mg/L, P<0.0001) and temperature (39.2C vs 39C, P<0.0052). The area under the curve (AUC) comparing culture positivity vs negativity for all culture types was 0.72 (p<0.0001) for PCT and 0.66 (p=0.001) for CRP. In Figure 1, the AUC for culture positive bacteremia was 0.68 (p=0.0011) for PCT and 0.70 (p=0.0003). The AUC for culture positive urinary tract infections (UTI) only was 0.86 (p=0.0001) for PCT and 0.70 (p=0.3607). For the cut-off value for PCT at 0.5 ng/mL, the sensitivity and specificity was 64% (95% confidence interval [CI] 0.5–0.77) and 70% (95% CI 0.62–0.77) respectively in identifying children with bacterial infection. For the cut-off value for CRP at 20 mg/L, the sensitivity and specificity was 67% (95% CI 0.52–0.79) and 52% (95% CI 0.44–0.59) respectively in identifying children with bacterial infection. Conclusion In this study, PCT and CRP are nearly equivalent classifiers for detecting SBIs as a group and bacteremia, but PCT is statistically better for urinary tract infections; however, the clinical utility is unknown.

Download Full-text

A study on validity of C-reactive protein in deciding the duration of antibiotic therapy in suspected neonatal bacterial infection

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20173796 ◽

2017 ◽

Vol 4 (5) ◽

pp. 1838 ◽

Cited By ~ 1

Author(s):

Prashanth Siddaiah ◽

Pradeep Nanjappa Shetty ◽

Krishna N. W. ◽

Sowmya Jagadeeshwara

Keyword(s):

Antibiotic Therapy ◽

Bacterial Infection ◽

Negative Predictive Value ◽

Antibiotic Treatment ◽

Predictive Value ◽

Decision Criterion ◽

C Reactive Protein ◽

Neonatal Septicemia ◽

Reactive Protein ◽

Serum Crp

Background: Neonatal septicemia is defined as generalized bacterial infection of newborns documented by positive blood culture in first four weeks of life. Objective of present study was to determine whether C-Reactive protein can be used as a parameter to identify the time point when antibiotic treatment can safely be discontinued in a defined major subgroup of neonates treated for suspected bacterial infection.Methods: A total of 50 neonates with birth weight more than 1500gms with suspected septicemia were enrolled in the prospective study. Serum CRP were determined 24-48 hours after the first dose of antibiotics. If CRP was less than 6mg/l, infants were considered unlikely to be infected and the antibiotic treatment was stopped. If CRP was more than 6mg/l, antibiotics were continued and CRP measured on alternative days in one subgroup (2a) and on seventh day in another subgroup (2b). CRP was the single decision criterion to stop the antibiotic therapy. Negative predictive value with respect to further treatment was determined.Results: Duration of antibiotic therapy could be reduced to less than seven days in 54% cases and < 72 hours in 48% cases.Conclusions: Negative predictive value of serial CRP is 100% in deciding the duration of antibiotic therapy in suspected neonatal septicemia.

Download Full-text

C-Reactive Protein Is an Independent Predictor of 30-Day Bacterial Infection Post-Liver Transplantation

Biomolecules ◽

10.3390/biom11081195 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1195

Author(s):

Jiong Yu ◽

Xiaowei Shi ◽

Jing Ma ◽

Ronggao Chen ◽

Siyi Dong ◽

...

Keyword(s):

Liver Transplantation ◽

Bacterial Infection ◽

Systemic Inflammation ◽

Bacterial Infections ◽

Cox Regression ◽

Prognostic Models ◽

C Reactive Protein ◽

Reactive Protein ◽

Clinically Significant ◽

The Relationship

The relationship between aseptic systemic inflammation and postoperative bacterial infection is unclear. We investigated the correlation of systemic inflammation biomarkers with 30-day clinically significant bacterial infections (CSI) after liver transplantation (LT). This retrospective study enrolled 940 patients who received LT and were followed for 30 days. The primary end point was 30-day CSI events. The cohort was divided into exploratory (n = 508) and validation (n = 432) sets according to different centers. Area under the receiver operated characteristic (AUROC) and Cox regression models were fitted to study the association between baseline systemic inflammation levels and CSI after LT. A total of 255 bacterial infectious events in 209 recipients occurred. Among systemic inflammation parameters, baseline C-reactive protein (CRP) was independently associated with 30-day CSI in the exploratory group. The combination of CRP and organ failure number showed a good discrimination for 30-day CSI (AUROC = 0.80, 95% CI, 0.76–0.84) and the results were confirmed in an external verification group. Additionally, CRP levels were correlated with bacterial product lipopolysaccharide. In conclusion, our study suggests that pre-transplantation CRP is independent of other prognostic factors for 30-day CSI post-LT, and can be integrated into tools for assessing the risk of bacterial infection post-LT or as a component of prognostic models.

Download Full-text

Cytokines and Chemokines as Biomarkers of Community-Acquired Bacterial Infection

Mediators of Inflammation ◽

10.1155/2013/190145 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 27

Author(s):

Michal Holub ◽

David A. Lawrence ◽

Nancy Andersen ◽

Alžběta Davidová ◽

Ondřej Beran ◽

...

Keyword(s):

Bacterial Infection ◽

Bacterial Infections ◽

Viral Infections ◽

Elevated Serum ◽

Serum Concentrations ◽

C Reactive Protein ◽

Reactive Protein ◽

Cytokines And Chemokines ◽

Luminex Technology ◽

Limited Usefulness

Routinely used biomarkers of bacterial etiology of infection, such as C-reactive protein and procalcitonin, have limited usefulness for evaluation of infections since their expression is enhanced by a number of different conditions. Therefore, several inflammatory cytokines and chemokines were analyzed with sera from patients hospitalized for moderate bacterial and viral infectious diseases. In total, 57 subjects were enrolled: 21 patients with community-acquired bacterial infections, 26 patients with viral infections, and 10 healthy subjects (control cohorts). The laboratory analyses were performed using Luminex technology, and the following molecules were examined: IL-1Ra, IL-2, IL-4, IL-6, IL-8, TNF-α, INF-γ, MIP-1β, and MCP-1. Bacterial etiology of infection was associated with significantly (P<0.001) elevated serum concentrations of IL-1Ra, IL-2, IL-6, and TNF-αin comparison to levels observed in the sera of patients with viral infections. In the patients with bacterial infections, IL-1Ra and IL-8 demonstrated positive correlation with C-reactive protein, whereas, IL-1Ra, TNF-α, and MCP-1 correlated with procalcitonin. Furthermore, elevated levels of IL-1Ra, IL-6, and TNF-αdecreased within 3 days of antibiotic therapy to levels observed in control subjects. The results show IL-1Ra as a potential useful biomarker of community-acquired bacterial infection.

Download Full-text

Evolution of laboratory markers for systemic bacterial infections

Terapevticheskii arkhiv ◽

10.17116/terarkh20178911105-110 ◽

2017 ◽

Vol 89 (11) ◽

pp. 105-110

Author(s):

N L Ryabkova ◽

N N Vezikova

Keyword(s):

Bacterial Infection ◽

Proinflammatory Cytokines ◽

Bacterial Infections ◽

C Reactive Protein ◽

Reactive Protein ◽

Laboratory Markers ◽

Systemic Bacterial Infection

The paper reviews the data available in the literature on existing laboratory markers for systemic bacterial infection, among which C-reactive protein, proinflammatory cytokines, procalcitonin test, and presepsin receive primary emphasis.

Download Full-text

Thrombocytosis as a Predictor of Serious Bacterial Infection in Febrile Infants

Journal of Nepal Health Research Council ◽

10.33314/jnhrc.v16i41.1673 ◽

2019 ◽

Vol 16 (41) ◽

pp. 401-404

Author(s):

Deepak Mishra ◽

Amit Kumar Das ◽

Ram Hari Chapagain ◽

Nitu Kumari Jha ◽

Ganesh Kumar Rai

Keyword(s):

Bacterial Infection ◽

Bacterial Infections ◽

Diagnostic Marker ◽

Common Finding ◽

P Value ◽

C Reactive Protein ◽

Cross Sectional ◽

Reactive Protein ◽

Young Infants

Background: Most of the febrile infants <90 days old will have no more than a mild viral infection but there is a substantial minority that will be diagnosed as having serious bacterial infection at a reported prevalence of 10–14%. A simple, readily available, inexpensive diagnostic marker that yields results quickly and also accurately identifies bacterial infections in febrile infants would be of great value in management of these infants. This study aims to assess the role of thrombocytosis in predicting serious bacterial infection in young febrile infants beyond neonatal period.Methods: A hospital based cross-sectional observational study was conducted from May 2016 to April 2017 on 76 febrile infants of age group 29-90 days in Kanti Children’s Hospital.Results: The incidence of serious bacterial infection was found 43 (56.6%). Thrombocytosis, elevated C-reactive protein and pyuria were significantly higher in serious bacterial infection cases (p value <0.05). Thrombocytosis alone had the sensitivity of only 53.5%, but had specificity of 90.9%. Elevated C-reactive protein had the best sensitivity (81.4%). Combination of leukocytosis, elevated C-reactive protein, pyuria and thrombocytosis had better sensitivity (93.0%) than these parameters alone. The overall ability of platelet count to identify infants with SBI was only moderate (AUC: 0.722). Elevated C-reactive protein was found to have better ability to identify infants with serious bacterial infection (AUC: 0.846).Conclusions: Thrombocytosis is a common finding in young infants diagnosed with serious bacterial infection. It has however, moderate ability in identifying infants with serious bacterial infection. Combining thrombocytosis with elevated C-reactive protein, leukocytosis and pyuria has better sensitivity in diagnosing serious bacterial infection than these individual parameters alone. Hence, combining these parameters may help in early prediction of febrile young infants at risk of serious bacterial infection.Keywords: Febrile young infants; serious bacterial infection; thrombocytosis.

Download Full-text

Potential usefulness of C-reactive protein and procalcitonin determination in patients admitted for neurological disorders in rural Democratic Republic of Congo

Scientific Reports ◽

10.1038/s41598-019-51925-z ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Emmanuel Bottieau ◽

Deby Mukendi ◽

Jean-Roger Lilo Kalo ◽

Pascal Lutumba ◽

Barbara Barbé ◽

...

Keyword(s):

Bacterial Infection ◽

Neurological Disorders ◽

Bacterial Infections ◽

Democratic Republic ◽

Democratic Republic Of Congo ◽

Single Case ◽

C Reactive Protein ◽

Republic Of Congo ◽

Reactive Protein ◽

Invasive Bacterial Infection

Abstract In low-resource hospitals of central Africa, neurological disorders are frequent and etiologies very diverse. The difficulty to identify invasive bacterial infections in this setting results in major antibiotic overuse. Biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) may help discriminate these conditions. We retrospectively determined the concentrations of CRP and PCT in the sera of patients consecutively enrolled from 2012 to 2015 in an etiological study on neurological disorders at the rural hospital of Mosango, Democratic Republic of Congo. Invasive bacterial infection had been diagnosed by the demonstration of a bacterial pathogen in cerebrospinal fluid or blood cultures or the presence of radiological pneumonia. Sera of 313 (89.2%) and 317 (90.3%) of the 351 enrolled participants were available for determination of CRP and PCT concentrations respectively. Areas under the receiver operating characteristic curves for invasive bacterial infection, diagnosed in 19 tested cases, were 94.3% for CRP and 91.7% for PCT. No single case had a normal CRP concentration (<10 mg/L). Our data, although limited, suggest that CRP or PCT concentrations may help discriminate invasive bacterial infections in patients with neurological disorders in tropical settings and that normal CRP values could assist in withholding antibiotics.

Download Full-text

Detection of C-Reactive Protein by Liquid-Gated Carbon Nanotube Field Effect Transistors (LG-CNTFET): A Promising Tool against Antibiotic Resistance

Engineering Proceedings ◽

10.3390/i3s2021dresden-10114 ◽

2021 ◽

Vol 6 (1) ◽

pp. 15

Author(s):

Luis Antonio Panes-Ruiz ◽

Tom Stückemann ◽

Leif Riemenschneider ◽

Markus Löffler ◽

Viktor Bezugly ◽

...

Keyword(s):

Carbon Nanotube ◽

Field Effect ◽

Bacterial Infections ◽

Field Effect Transistors ◽

High Sensitivity ◽

C Reactive Protein ◽

Reactive Protein ◽

Promising Tool ◽

Potential Biomarker ◽

Tract Infections

Respiratory tract infections have the highest rates of antibiotic prescriptions where symptoms like fever, cough, and rigors are regularly misinterpreted and where bacterial infections cannot be distinguished from viral ones. Nevertheless, it has been recently suggested that C-reactive protein (CRP), a protein produced by the liver in response to infection, could serve as a potential biomarker for the precise differentiation of these two types of infections. Thus, its quick and accurate detection would potentially reduce the unnecessary antibiotic use. To this end, we present an easy and sensitive approach for the selective detection of C-reactive protein (CRP) by liquid-gated carbon nanotube field effect transistors (LG-CNTFET). Herein, CNT-networks were deposited between electrodes via controlled dielectrophoretic deposition and then functionalized with a novel specific antibody and a polyethylene glycol (PEG) layer in order to overcome the Debye screening. The successful fabrication and functionalization were confirmed by scanning electron microscopy. The results showed a selective and reproducible detection down to picomolar concentrations in PBS buffer without complicated microfluidics. The simplicity and high sensitivity of this sensor platform make it a promising tool for the quick and precise differential diagnosis of viral and bacterial infections.

Download Full-text