|Year : 2020 | Volume
| Issue : 1 | Page : 20-24
Patterns of C-reactive protein ratio response in ventilation-associated pneumonia
Waleed S Abdelhady Mohamed
Department of Critical Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
|Date of Submission||03-Dec-2018|
|Date of Acceptance||12-Dec-2018|
|Date of Web Publication||16-Apr-2020|
MD Waleed S Abdelhady Mohamed
Department of Critical Medicine, Faculty of Medicine, University of Alexandria, Alexandria
Source of Support: None, Conflict of Interest: None
Introduction Physicians frequently use serum biomarkers to assist in clinical response to antibiotic therapy in patients having ventilator-associated pneumonia (VAP). C-reactive protein (CRP) is one of these biomarkers and probably the most widely used.
Aim of the work This study was aimed to evaluate the course of CRP and identify the patterns of CRP ratio response to antibiotic therapy during the first week in patients with VAP who are admitted to Critical Care Medicine Department in Alexandria University Hospital.
Patients and methods This study will be conducted on 60 adult patients of both sexes who admitted to Critical Care Department, Alexandria Main University Hospital of patients complicated with VAP. All cases were subjected to: history taking from the patient or next of kin including: age, gender, associated medical diseases, Acute Physiology and Chronic Health Evaluation II, and sequential organ failure assessment score. CRP was assessed on admission (D0), day1 (D1), and day 5 (D5).
Results The study patients were classified into two groups: group I ‘good response’ to treatment of pneumonia and group II ‘poor response’ to treatment of pneumonia. The patients who showed good response were 36 (60.0%), whereas 24 (40.0%) patients showed poor response.
Discussion In our study, survivors showed a continuous and significant decrease of CRP ratio during the first week of antibiotic therapy. Conversely, in nonsurvivors, CRP ratio remained elevated, and at D5, a CRP ratio of higher than 0.5 was associated with a fivefold increase in the risk of death in the ICU. Interestingly, in our study, patients with nonresponse CRP ratio pattern presented a significantly higher ICU mortality than patients with fast or slow response patterns.
Conclusion The use of serial CRP determinations is useful in monitoring therapeutic response of serious infection, allowing early identification of complications or antibiotic failures.
Keywords: C-reactive protein, response to antibiotics, ventilator-associated pneumonia
|How to cite this article:|
Abdelhady Mohamed WS. Patterns of C-reactive protein ratio response in ventilation-associated pneumonia. Res Opin Anesth Intensive Care 2020;7:20-4
|How to cite this URL:|
Abdelhady Mohamed WS. Patterns of C-reactive protein ratio response in ventilation-associated pneumonia. Res Opin Anesth Intensive Care [serial online] 2020 [cited 2020 Jun 2];7:20-4. Available from: http://www.roaic.eg.net/text.asp?2020/7/1/20/282600
| Introduction|| |
Ventilator-associated pneumonia (VAP), which may be defined according to the CDC/NHSN Protocol Corrections, Clarification, and Additions April 2013 , as a pneumonia where the patient is on mechanical ventilation for more than two calendar days when all elements of the pneumonia infection criterion were first present together, with day of ventilator placement being day 1, and the ventilator was in place on the date of event or the day before. VAP affects as many as 10–20% of patients receiving mechanical ventilation for more than 48 h . Patients with VAP represent a significant subset of ICU patients with hospital-acquired pneumonia (HAP). Up to 90% of ICU episodes of HAP occur while patients are mechanically ventilated. Endotracheal intubation is thought to increase the risk of developing pneumonia by facilitating colonization of the respiratory tract with potential bacterial pathogens: additional factors predisposing the critically ill toward the development of VAP include severity of illness, organ failure, increasing age, prior use of antibiotics, prior surgery, and red cell transfusions .
HAP in the critically ill carries appreciable morbidity and mortality  associated mortality rates of up to 50% have been observed with VAP and lengths of ICU and hospital stay are significantly prolonged, with estimated additional costs .
Pneumonia is the second most common nosocomial infection in the ICU, and a very high proportion (71%) of intensive care patients receive antibiotic therapy . The duration of antibiotic therapy is clearly an important consideration in the optimal antimicrobial management of critically ill patients with VAP; too short a course of therapy risks treatment failure, whereas too long a course of therapy carries unnecessary costs and poses potential risks for the individual patient and to other patients through the emergence of resistant organisms.
The optimal duration of antibiotic therapy for VAP is uncertain, whether administered according to a fixed course, or discontinued after resolution of clinical features or biomarker. Furthermore, VAP is not a homogenous disease and higher risk of treatment failure associated with short-course therapy might be expected .
Understanding the pathogenesis of VAP is important for establishing the principles for therapy and strategies for prevention ,. The aerodigestive tract above the vocal cords is heavily colonized with bacteria . A complex array of host defense mechanisms protect the trachea and lungs from bacterial infection. Mechanical host defenses filter and humidify air, whereas the cough response, mucus, and cilia trap and clear bacteria entering the lower airway. In addition, a variety of humoral and cellular immune mechanisms are highly effective in preventing infection . In critically ill patients, host defenses may be impaired owing to malnutrition, chronic diseases, or immunosuppressant. Moreover, bacterial adherence is favored by reduced immunoglobulin A, augmented protease production, denuded mucus membrane, and elevated airway pH .
After prescription of antibiotics, the evaluation of the individual clinical response and the assessment of resolution of pneumonia usually rely on the monitoring of the same criteria used for clinical diagnosis. Commonly used variables, such as temperature and white blood cell count, have a limited value in the assessment of clinical response to antibiotics ,, as both present significant improvements late in the course and can be influenced by drugs frequently used in ICU, such as steroids, antipyretics, or beta blockers.
To overcome these limitations, physicians frequently use serum biomarkers to assist in the clinical decision making process, namely in the assessment of clinical response to antibiotic therapy.
C-reactive protein (CRP) is one of these biomarkers and probably the most widely used .
| Aim of the work|| |
This study was aimed to evaluate the course of CRP and identify the patterns of CRP ratio response to antibiotic therapy during the first week in patients with VAP who are admitted to Critical Care Medicine Department in Alexandria University Hospital.
| Patients and methods|| |
This study will be conducted on 60 adult patients of both sexes complicated with VAP who were admitted to Critical Care Department, Alexandria Main University Hospital. The acceptance of ethical committee of the faculty was obtained at the beginning of this study. They were defined according to the CDC/NHSN Protocol Corrections, Clarification and Additions, April 2013 .
All cases were subjected to the following:
- History taking from the patient or next of kin including: age, sex, and associated medical diseases.
- Investigations, including the following:
APACHE II and SOFA.
Vital signs, mental status according GSC, chest examination, assessment of clinical pulmonary infection score (CPIS), and hypoxic index.
Laboratory evaluation, including CRP on admission, day 1, and then day 5; radiological investigation; microbiological study; and VAP prevention strategies.
End points of the study were as follows:
- Days of mechanical ventilation.
- Length of ICU stay.
- 28-day mortality.
- Incidence of different complications.
| Results|| |
The study patients were classified into two groups: group I with ‘good response’ to treatment of pneumonia and group II with ‘poor response’ to treatment of pneumonia. The patients who showed good response included 36 (60.0%) patients, whereas 24 (40.0%) patients showed poor response ([Table 1],[Table 2],[Table 3], [Figure 1] and [Figure 2]).
|Table 1 Basic characteristic feature of the patients regarding the response to treatment|
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| Discussion|| |
In the present study, we described the patterns of serial measurements of CRP ratio and its relation with clinical resolution of severe VAP in a large cohort of patients requiring intensive care admission. With the resolution of infection, the concentration of CRP decreases at a rate that is dependent on its half-life, as this marker exhibits a first-order elimination kinetics, so the assessment of relative variations is more informative about the course of infection than absolute variations ,.
In our study, survivors showed a continuous and significant decrease of CRP ratio during the first week of antibiotic therapy. Conversely, in nonsurvivors, CRP ratio remained elevated, and at D5, a CRP ratio of higher than 0.5 was associated with a fivefold increase in the risk of death in the ICU. Interestingly, in our study, patients with the nonresponse CRP ratio pattern presented a significantly higher ICU mortality than patients with fast or slow response patterns. Additionally, the identification of CRP ratio pattern of response to antibiotics, during the first week of therapy, was useful in the recognition of the individual clinical evolution of patients with severe VAP .
These data suggest that persistently elevated CRP values are indicative of poor response to antibiotic therapy. This could be a result of inadequate initial antibiotic therapy, the presence of other infectious complications , or a newly developed infection in another location. Several studies have confirmed that serial measurements of CRP are useful in the monitoring of clinical course as well as assessment of patient outcome in different severe infections. In all of these studies, survivors by D1–D5 presented values of CRP ratio of between 0.5 and 0.8 of the initial value ,.
This means that, after 72–96 h of antibiotic therapy, the CRP of survivors decreases by 30–50% of the initial concentration. Besides, serial measurements of CRP allow the identification of various patterns of response to antibiotic therapy, as previously described by our group. This concept of patterns of CRP ratio response to antibiotics has been tested in different clinical settings and reproduced by different research groups. In a recent study, Moreno and colleagues studied the value of daily measurements of CRP in a cohort of 64 patients with nosocomial pneumonia ,.
In their study, patients were classified according to the CRP ratio in two groups: ‘good’ response (CRP ratios of lower than 0.67 at D10) and ‘poor’ response (nonresponse or biphasic response). The poor-response group (n=34) had a mortality rate of 53% in comparison with 20% in the good-response group (n=30) (relative risk=2.65, 95% confidence interval=1.21–5.79; P=0.01). Significant differences between the two groups were found on CRP ratios at D4 (P=0.01). Moreover, in a cohort of 891 patients who had community-acquired sepsis and who were admitted to the ICU, Povoa et al.  found that patterns of CRP ratio response to antibiotics presented a marked correlation with hospital mortality.Patients with a nonresponse pattern had a 2.5 times higher probability of dying in comparison with patients with fast response (adjusted odds ratio (AOR)=2.5, 95% confidence interval=1.6–4.0; P<0.001). Slow responders showed a nonsignificant increase on the odds of mortality in comparison with the fast responders (AOR=1.5, 95% confidence interval=0.9–2.5; P=0.124). The results of the present study were in agreement with this concept in the population of patients with severe VAP. In all of these studies, the patterns of CRP ratio response allowed the early identification (between D3 and D4) of patients with poor response to antibiotics and consequently with poor prognosis. In our study, by D5, a CRP concentration of above 0.5 of the initial level was a marker of poor outcome ,.
| Conclusion|| |
CRP is not the perfect marker of infection, as a variety of noninfectious conditions can increase their concentrations. However, the interpretation of noninfectious causes of CRP elevations are usually straightforward.
On the contrary, infection, especially in critically ill patients, can present a diagnostic challenge. As a result, CRP elevations without an obvious cause should prompt the search for an infection.
The use of serial CRP determinations is useful in monitoring therapeutic response of serious infection, allowing early identification of complications or antibiotic failures.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]