• Lower Respiratory Infections
• Bacterial Infections
• Pneumonia Clinical Trials

To date, evidence regarding the effectiveness of procalcitonin (PCT)-guided antibiotic therapy has been obtained in randomized, controlled trials (RTCs), which may not be representative of routine clinical settings. Werner Albrich, MD, University of Basel, Kantonsspital Aarau, Aarau, Switzerland, presented data from a quality control survey [ISRCTN40854211] that monitored PCT-guided antibiotic therapy and algorithm adherence in simulated “real-life” conditions. The PCT algorithm effectively reduced antibiotic exposure without increasing complications. Regional and cultural differences did not affect outcomes. The integration of the PCT algorithm into daily practice requires ongoing reinforcement and involves a learning process by prescribing physicians [Schuetz P et al. Eur J Clin Microbiol Infect Dis 2010].

This was an observational, prospective, multicenter, international survey of consecutive patients with community-acquired lower respiratory tract infections (LRTIs) in emergency departments or physicians' offices in Switzerland (n=10), France (n=3), and the United States (n=1) from September 2009 to February 2011. PCT was measured using a rapid, sensitive immunoassay with a functional assay sensitivity of 0.06–0.09 ug/L (KRYPTOR®, Brahms or (Mini-)Vidas®, BioMérieux). Diagnostic workup, antibiotic choice(s), and management were at the physician's discretion.

The algorithm was based on the level of circulating PCT, which correlates with the likelihood for a bacterial infection, and was as follows:

• <0.1 μg/L - antibiotic therapy strongly discouraged

• 0.1 to 0.25 μg/L - antibiotic therapy discouraged

• 0.26 to 0.5 μg/L- antibiotic therapy recommended

• >0.5 μg/L - antibiotic therapy strongly recommended

The primary endpoint was duration of antibiotic treatment within 30 days (effectiveness). Compliance with the PCT algorithm, adverse medical outcomes (safety), and influence of PCT on antibiotic decision were secondary endpoints. A total of 1810 patients were enrolled (1520 with LRTI and 1425 with 30-day follow-up information). The majority presented with community-acquired pneumonia, followed by acute exacerbations of chronic obstructive pulmonary disease (COPD) and bronchitis.

There was good overall algorithm compliance (68.2%), which was affected by treatment site, country, experience, and diagnosis. Good compliance led to significantly shorter antibiotic duration (−43% or 3.8 fewer antibiotic days; HR, 1.27; 95% CI, 1.13 to 1.43; p<0.0001) but did not increase the risk of complications (adj. OR, 1.40; 95% CI, 0.78 to 2.52; p=0.26; Table 1).

Antibiotic duration in the ProReal study was shorter than that seen for standard care but longer than that seen in the PCT intervention group of the ProHosp RCT (Table 2) [Schuetz P et al. JAMA 2010].

PCT affected the decision to withhold or initiate antibiotics. Its greatest effect in patients with COPD exacerbation or bronchitis was to reduce initial prescription of antibiotic therapy, whereas for patients with pneumonia, it was most effective in shortening antibiotic duration. No significant increases in adverse medical outcome were detected.

Published evidence on PCT-guided antibiotic therapy to date has been obtained in trials in which physicians knew that they were being monitored, possibly resulting in higher adherence to the PCT algorithm. This study mirrors the use of PCT-guided antibiotic therapy in clinical practice, outside of trial conditions. If algorithm adherence is reinforced, antibiotic exposure can be markedly reduced with subsequent reduction of antibiotic-associated side effects and antibiotic resistance.

• © 2011 MD Conference Express