C-reactive protein: A tool in the follow-up of nosocomial pneumonia

doi:10.1016/j.jinf.2010.06.005

Journal of Infection

Volume 61, Issue 3, September 2010, Pages 205-211

https://doi.org/10.1016/j.jinf.2010.06.005 Get rights and content

Summary

Objectives

The aim of this study was to examine the clinical usefulness of serial C-reactive protein (CRP) dosages in patients with nosocomial pneumonia (NP).

Methods

Prospective and observational study performed in a 24-beds Intensive Care Unit. Sixty four patients with NP, including non-ventilated patients and those with ventilator-associated pneumonia were included. Daily measurements of CRP were performed and CRP ratios were calculated from the day of antibiotic prescription (D0) until day 10. Patients were than classified according to the CRP ratios in 2 groups: ‘good’ response (CRP ratios lower than 0.67 at day 10) and ‘poor’ response (non-response or bi-phasic response).

Results

The poor response group (n = 34) had a mortality rate of 53% in comparison to 20% in the good response group (n = 30) (RR = 2.65; 95% CI, 1.21–5.79, p = 0.01). Significant differences between the two groups were found on CRP ratios at Day 4 (p = 0.01). The adequacy of antibiotic therapy was much lower in the group poor response in comparison to the group good response, 14% vs. 67% (p = 0.008), respectively.

Conclusions

Daily CRP measurements in patients with nosocomial pneumonia may be useful in the identification of patients with poor outcome, as early as day 4, and detect patients with inappropriate antimicrobial therapy.

Introduction

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are common complications in intensive care unit (ICU) patients and are important causes of increased morbidity and mortality; they are also related to increased lengths of hospital and ICU stay and increased costs.1, 2, 3 The EPIC (European Prevalence of Infection in Intensive Care) study showed that ICU-acquired pneumonia accounted for as many as 47% of all infections.⁴ The more recent EPIC II (Extended Prevalence of Infections of Infection in Intensive Care) study done in 75 countries shows 71% of all patients in the ICU receiving antibiotics as prophylaxis or treatment and an even greater prevalence of infections with the lungs accounting for 64% of the infections.⁵ More than 50% of all antibiotics prescribed in the ICU are prescribed for HAP and mortality rates in patients with HAP range from 20% to 70%.6, 7

C-reactive protein (CRP) is an acute phase protein synthesized by the liver. Serum levels of CRP increase approximately 4–6 h after the start of the inflammatory process.8, 9 CRP serum concentrations have been used to help diagnose infection,10, 11, 12, 13, 14, 15, 16 identify patients with higher risk of organ failure and death⁹ and in the follow-up of treatment.17, 18, 19, 20, 21, 22 High serum CRP concentrations have been reported to be predictive of ICU readmission and in-hospital mortality after ICU discharge in heterogeneous populations of critically ill patients.23, 24

Serum CRP concentrations often decrease prior to the clinical resolution of sepsis.²¹ Persistently increased serum CRP concentrations after antimicrobial therapy were indicative of poor outcome and inadequate prescription of antibiotics in critically ill patients with community-acquired pneumonia (CAP).20, 22 In patients with microbiologically confirmed VAP, high CRP levels were associated with a poor outcome.¹⁷ As none of the currently available tests to diagnosis and follow patients with nosocomial pneumonia can, when performed alone, provide an accurate prognosis, complementary diagnostic procedures should be used to guide therapeutic decisions.²⁵ Further investigation in this area is, therefore, critical. The aim of this study was to examine the clinical usefulness of serial CRP measurements in patients with nosocomial pneumonia (NP).

Section snippets

Material and methods

This prospective, observational study was conducted from December 2006 to December 2007 in a mixed ICU of a tertiary university hospital (24-bed ICU; Hospital de Base de São José do Rio Preto). The study was approved by the Local Research and Ethics Committee, and the need for informed consent was waived in view of the observational nature.

The study population included patients with nosocomial pneumonia, defined as the presence of a new or progressive infiltrate on chest X-ray more than 48 h

Statistics

Standard descriptive statistics were used to describe the study population. Continuous variables are presented as mean ± standard deviation (SD) or median [25–75% interquartile range] (IQ) and categorical variables as number and percentage, unless otherwise indicated. Continuous variables were compared with Student’s t test or analysis of variance (ANOVA) for repeated measurements. Bonferroni adjustment was used for multiple comparisons.

Receiver-operating characteristic (ROC) curves were

Results

A total of 155 patients with nosocomial pneumonia were screened; of these, 68 patients were included in the study. A total of 87 patients were excluded (1 because of age <16 years; 1 with pulmonary cancer; 2 with severe liver failure; 12 with contraindications to BAL and/or TA sampling; 9 with aspiration pneumonia; 14 with an estimated survival <4 days; 44 with uncontrolled infection in another site; and 4 because of logistic problems in performing fiber bronchoscopy). Of the 68 patients

Discussion

In this study, we explored the evolution of serum CRP levels in the ten days following prescription of antibiotics to patients with nosocomial pneumonia (VAP and HAP). Patients with a “poor” response, including those with no-response and with a bi-phasic response, had a significant higher mortality rate than patients with a “good” response. There was also a trend toward higher mortality rate when only patients with documented NP were considered. There were significant differences in the CRP

Conflicts of interest

The authors declare that they have no conflicts of interest.

Acknowledgments

Marcelo S. Moreno made substantial contributions in design of the study, acquisition of the data, analysis and interpretation of the data, and in the process of writing of the manuscript.

Henrique Nietmann made substantial contibuitions in acquisition of data.

Celso Murilo Matias made substantial contibuitions in acquisition of data.

Suzana M. Lobo made substantial contributions in design of the study, analysis and interpretation of the data, and in the process of writing of the manuscript.

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Cited by (24)

C-reactive protein and albumin kinetics after antibiotic therapy in community-acquired bloodstream infection
2020, International Journal of Infectious Diseases
We assessed C-reactive protein (CRP) and plasma albumin (PA) kinetics to evaluate community-acquired bloodstream infection (CA-BSI) patients’ 1-year outcomes.
Population-based study, with CRP and PA measurements on day 1 (D1) and D4. Relative CRP variations in relation to D1 CRP value were evaluated (CRP-ratio). Patients were classified as fast response, slow response, non-response, and biphasic response.
A total of 935 patients were included. At D4, the CRP-ratio was lower in survivors on D365 in comparison with D4–D30 non-survivors and D30–D365 non-survivors (p < 0.001). In comparison with fast response patients, non-response and biphasic response patients had 2.74 and 5.29 increased risk, respectively, of death in D4–D30 and 2.77 and 3.16 increased risk, respectively, of death in D31–D365. PA levels remained roughly unchanged from D1–D4, but lower D1 PA predicted higher short and long-term mortality (p < 0.001). The discriminative performance of the CRP-ratio and D1 PA to identify patients with poor short and long-term mortality after adjustments was acceptable (AUROC = 0.79).
Serial CRP measurements at D1 and D4 after CA-BSI is clinically useful to identify patients with poor outcome. Individual patterns of CRP-ratio response with PA at D1 further refine our ability of predicting short or long-term mortality.
Patterns of C-reactive protein ratio predicts outcomes in healthcare-associated pneumonia in critically ill patients with cancer
2017, Journal of Critical Care
Citation Excerpt :
From D0 to D6/D7, the CRP-ratio showed a significant and steady decrease in survivors, whereas in nonsurvivors it remained roughly unchanged. Several studies have confirmed that serial CRP measurements are useful in the monitoring of clinical course as well as in the assessment of patient outcome in several infections such as community-acquired pneumonia [34] [35], nosocomial pneumonia [36], ventilator-associated pneumonia [37] [38] [39] and severe bloodstream infection [16]. However, the present study is an original description of this association in cancer patients, a population where response to antibiotic therapy is less predictable due to cancer-related conditions and, namely in HCAP, where MR pathogen infections are more often diagnosed.
Describe the patterns of C-reactive protein relative changes in response to antibiotic therapy in critically ill cancer patients with healthcare-associated pneumonia (HCAP) and its ability to predict outcome.
Secondary analysis of a prospective cohort of critically ill cancer patients with HCAP. CRP was sampled every other day from D0 to D6 of antibiotic therapy. Patients were classified according to an individual pattern of CRP-ratio response: fast – CRP at D4 of therapy was < 0.4 of D0 CRP; slow – a continuous but slow decrease of CRP; non – CRP remained ≥ 0.8 of D0 CRP; biphasic – initial CRP decrease to levels < 0.8 of the D0 CRP followed by a secondary rise ≥ 0.8.
129 patients were included and septic shock was present in 74% and invasive mechanical ventilation was used in 73%. Intensive care unit (ICU) and hospital mortality rates were 47% and 64%, respectively. By D4, both CRP and CRP-ratio of survivors were significantly lower than in nonsurvivors (p < 0.001 and p = 0.004, respectively). Both time-dependent analysis of CRP-ratio of the four previously defined patterns (p < 0.001) as ICU mortality were consistently different [fast 12.9%, slow 43.2%, biphasic 66.7% and non 71.8% (p < 0.001)].
CRP-ratio was useful in the early prediction of poor outcomes in cancer patients with HCAP.
Biomarkers kinetics in the assessment of ventilator-associated pneumonia response to antibiotics - results from the BioVAP study
2017, Journal of Critical Care
Citation Excerpt :
We could identify 4 individual patterns of CRP-ratio kinetics to antibiotic therapy [11]. Similar to previous findings [11,13], in the present study VAP patients with a fast and slow response pattern had a much better prognosis than those presenting the other patterns. Besides, we divided VAP patients according to their patterns of PCT-ratio response using the same criteria.
Our aim was to evaluate the role of biomarker kinetics in the assessment of ventilator-associated pneumonia (VAP) response to antibiotics.
We performed a prospective, multicenter, observational study to evaluate in 37 microbiologically documented VAP, the kinetics of C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM). The kinetics of each variable, from day 1 to 6 of therapy, was assessed with a time dependent analysis comparing survivors and non-survivors.
During the study period kinetics of CRP as well as its relative changes, CRP-ratio, was significantly different between survivors and non-survivors (p = 0.026 and p = 0.005, respectively). On day 4 of antibiotic therapy, CRP of survivors was 47% of the initial value while it was 96% in non-survivors. The kinetics of other studied variables did not distinguish between survivors and non-survivors. In survivors the bacterial load also decreased markedly. Adequate initial antibiotic therapy was associated with lower mortality (p = 0.025) and faster CRP decrease (p = 0.029).
C-reactive protein kinetics can be used to identify VAP patients with poor outcome as soon as four days after the initiation of treatment. (Trial registration - NCT02078999; registered 3 August 2012).
C-reactive protein (CRP) measurement in geriatric patients hospitalized for acute infection
2017, European Journal of Internal Medicine
Citation Excerpt :
Persistently elevated serum CRP levels are also associated with organ dysfunction, mortality, and duration of ICU stay [54]. The optimal timing for a second CRP measurement after ICU admission has been proposed as 3 days in community-acquired sepsis [55] and 4 days in ICU-acquired pneumonia [56]. Namely, a decrease in serum CRP after 3 days of ICU stay, at an average rate of at least 10% per day, is protective against hospital mortality.
The physiology of inflammatory response is modified by the aging process and is substantially affected by multimorbidity and disability. Infection is the most frequent cause of acute inflammation in both adult and older subjects. C-reactive protein (CRP) is the most used biomarker of inflammation, and a substantial amount of literature has demonstrated its importance and clinical usefulness in adult subjects. However, the clinical significance of serum CRP determination has not been completely clarified in older subjects with acute infection, especially in the light of the age-related rearrangements in immunity and cytokine production. Thus, in the present review, we focus on the existing knowledge about serum CRP level interpretation in geriatric patients hospitalized with acute infection. Our aims were to determine the significance of CRP measurement at hospital admission for establishing a diagnosis of infection and/or a prognosis and to evaluate whether it is indicated to repeat hs-CRP measurements during hospital stay for monitoring disease course and, possibly, guiding the discharge timing. We concluded that CRP dosage at hospital admission is helpful to detect acute infection, and particularly sepsis, in geriatric patients, and that CRP elevation may provide valuable short-term prognostic information. At the current state of art, serial CRP measurements are instead not indicated to monitor disease course and plan hospital discharge in this setting.
New markers in pneumonia
2013, Clinica Chimica Acta
Citation Excerpt :
The serial measurements of CRP in a patient may represent the progression of the clinical course and also help assess the response to antibiotic therapy. In a cohort study of 64 HAP patients, the CRP ratios of Day 10 to the admission day could separate the “good” and “poor” responses at 53% and 20% mortality rates, respectively [35]. In a multicenter prospective observational study of community-acquired sepsis, Póvoa et al. indicated that, as early as Day 3 onward, the CRP concentrations of survivors decrease to a level that was significantly lower than that of non-survivors [36].
Pneumonia is one of the most common causes of death from infectious diseases worldwide, and the most common fatal infection acquired in hospitals. Despite advances in prevention strategies, such as antibiotic therapies and intensive care, significant improvement in the mortality rate is still lacking. This high mortality is largely due to the limitations in current clinical practices and laboratory tests, which delay the timing of adequate antibiotic therapy. In recent years, many indicators (biomarkers) are present in scenarios where infectious pathogens invade into the body. These biomarkers, as reflected in specific biological responses to infections, have been reported to demonstrate the ability to facilitate the diagnosis, risk stratification, and management of pneumonia. This review provides a schematic overview of these new potential biomarkers based on the categories of (1) microorganisms and their derivatives, (2) inflammation mediators, (3) inflammation response proteins, and (4) stress-sensing proteins. In addition, approaches to identifying new biomarkers are also briefly introduced. Although no current biomarker can solely achieve a definitive diagnosis, many of them can be complemented, rather than replaced outright, in routine clinical practices to improve decision-making processes regarding pneumonia.
Failure to reduce C-reactive protein levels more than 25% in the last 24 hours before intensive care unit discharge predicts higher in-hospital mortality: A cohort study
2012, Journal of Critical Care
Citation Excerpt :
Dynamic analysis of biologic variables seems more relevant than isolated values to predict outcomes in critical care illness [12-14]. Evaluation of CRP trend pattern in the first days of ICU admission has been reported as useful in discriminating outcomes in community-acquired pneumonia [15] and septic patients [16] and useful to help in the clinical decision-making process regarding ICU-acquired infections [17-19]. Therefore, we hypothesized that a reduction in the CRP values in the last 24 hours before ICU discharge would be useful to predict in-hospital outcomes.
To discharge a patient from the intensive care unit (ICU) is a complex decision-making process because in-hospital mortality after critical illness may be as high as up to 27%. Static C-reactive protein (CRP) values have been previously evaluated as a predictor of post-ICU mortality with conflicting results. Therefore, we evaluated the CRP ratio in the last 24 hours before ICU discharge as a predictor of in-hospital outcomes.
A retrospective cohort study was performed in 409 patients from a 6-bed ICU of a university hospital. Data were prospectively collected during a 4-year period. Only patients discharged alive from the ICU with at least 72 hours of ICU length of stay were evaluated.
In-hospital mortality was 18.3% (75/409). Patients with reduction less than 25% in CRP concentrations at 24 hours as compared with 48 hours before ICU discharge had a worse prognosis, with increased mortality (23% vs 11%, P = .002) and post-ICU length of stay (26 [7-43] vs 11 [5-27] days, P = .036). Moreover, among hospital survivors (n = 334), patients with CRP reduction less than 25% were discharged later (hazard ratio, 0.750; 95% confidence interval, 0.602-0.935; P = .011).
In this large cohort of critically ill patients, failure to reduce CRP values more than 25% in the last 24 hours of ICU stay is a strong predictor of worse in-hospital outcomes.

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C-reactive protein: A tool in the follow-up of nosocomial pneumonia

Summary

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Material and methods

Statistics

Results

Discussion

Conflicts of interest

Acknowledgments

Adv Immunol

Chest

Clin Microbiol Infect

J Infect

Chest

Chest

Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia

Am J Respir Crit Care Med

Diretrizes brasileiras para tratamento das pneumonias adquiridas no hospital e das associadas à ventilação mecânica – 2007

J Bras Pneumol

Incidence, risk factors and mortality of nosocomial pneumonia in intensive care units: a prospective study

Ann Clin Microbiol Antimicrob

The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee

JAMA

EPIC II Group of Investigators. International study of the prevalence and outcomes of infection in intensive care units

JAMA

Epidemiology of ventilator-associated pneumonia

Chest

What is ventilator-associated pneumonia and why is it important?

Respir Care

Markers and mediators of inflammatory response in infection and sepsis

RBTI

C-reactive protein: a valuable marker of sepsis

Intensive Care Med

Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: a prospective observational study

Crit Care