Abstract

Despite the introduction of new inflammatory markers, C-reactive protein (CRP) remains commonly used in patients hospitalised with severe infections. However, evidence on the usefulness of consecutive CRP measurements is still unclear. The clinical relevance of consecutive CRP measurements was studied in follow-up of antibiotic treatment in patients with severe community-acquired pneumonia (CAP).

In a prospective multicentre trial, CRP levels were measured on admission, and on days 3 and 7. Patients were followed clinically for 28 days.

Aetiology could be determined in 137 (47.4%) out of the 289 patients included. In 122 (38.8%) patients, initial antibiotic therapy was appropriate. A decline of <60% in CRP levels in 3 days and a decline of <90% in CRP levels in 7 days were both associated with an increased risk of having recieved inapproriate empiric antibiotic treatment (day 0�3, odds ratio (OR) 6.98, 95% confidence interval (CI) 1.56�31.33 and day 0�7, OR 3.74, 95% CI 1.12�13.77).

In conclusion, consecutive C-reactive protein measurements are useful in the first week in follow-up of antibiotic treatment for severe community-acquired pneumonia when taking the causative microorganism and use of steroids into account. A delayed normalisation of C-reactive protein levels is associated with a higher risk of having received inappropriate antibiotic treatment.

• Antibiotic treatment
• community-acquired pneumonia
• C-reactive protein
• follow-up

Community-acquired pneumonia (CAP) is the major cause of death due to infectious diseases in the western world and accounts for an increasing figure of ≥20 admissions per 1,000 inhabitants annually�1. Current guidelines advise combination therapy with β-lactam and macrolide antibiotics for initial treatment of severe CAP�Consequently, management of severe CAP accounts for high utilisation of healthcare resources and antibiotic consumption, leading to a risk of emerging resistance. In the USA, annual estimated costs for treating CAP exceed US$12 billon and in several countries an increase in macrolide-resistant strains has been observed�4,�5.

Once aetiology of CAP has been established, pathogen-directed antibiotic therapy can be initiated and a test indicative of aetiology early in the course of disease would be a worthwhile target for the reduction of antibiotic consumption. Unfortunately, thus far no biomarker has been found to have sufficient sensitivity and specificity to guide initial therapy, and protocols for guidance of empirical antibiotic treatment must be relied on�2,�3. However, an alert for an unfavourable response to treatment early in follow-up, as an increased inflammatory response, suboptimal drug levels, or inappropriate empirical treatment, could help in optimising treatment for CAP patients. Before aetiology has been established, or when aetiology cannot be established, an indicator of the appropriateness of empirical antibiotic therapy may contribute to a more tailored approach in antibiotic treatment early in the course of the disease. Furthermore, such an indicator might help in continuing tailored antibiotic therapy, determining the length of antimicrobial treatment, and guiding a switch from intravenous to oral antibiotic therapy�6. Hypothetically, these strategies may contribute to a reduction in antibiotic consumption.

The determination of the serum concentration of C-reactive protein (CRP) is a rapid, simple and inexpensive procedure and consecutive CRP measurements have become routine clinical practice in the follow-up of patients hospitalised with severe infections�7. However, despite its frequent use, evidence on the usefulness of consecutive CRP measurements for follow-up of antibiotic treatment for severe CAP is lacking. Few studies have addressed CRP kinetics in the follow-up of CAP previously, and these are on a relatively small scale and have not taken aetiology into account�8,�9. A recent study has pointed out that high serum levels of CRP, interleukin (IL)-6 or, procalcitonin (PCT) are associated with a higher risk of any treatment failure�10. However, the introduction of newer inflammatory markers, such as PCT, IL-6 and neopterin emphasises the need to clarify the position of the older and less costly markers, such as CRP�11. To determine the clinical relevance of consecutive CRP measurements in follow-up of antibiotic treatment in patients with severe CAP, the present study examined the predictive value of delayed normalisation of CRP levels for the risk of having received inappropriate empirical antibiotic therapy or developing an unfavourable outcome.