Procalcitonin-guided antibiotic treatment in heart failure

Abstract

Authors' reply Sir—We are grateful to Anja Sandek and colleagues for highlighting important points discussed in our paper. Circulating procalcitonin concentrations are similarly heightened in gram-positive and gram-negative infections1Müller B Becker KL Schächinger H et al.Precursors are reliable markers of sepsis on a medical intensive care unit.Crit Care Med. 2000; 28: 977-983Crossref PubMed Scopus (511) Google Scholar. Thus, endotoxin (lipopolysaccharide) is only one of several inducers of procalcitonin secretion. Accordingly, proinflammatory cytokines—eg, interleukin 1b, tumour necrosis factor α, and interleukin 6-induce and augment lipopolysaccharide-induced procalcitonin expression and secretion2Linscheid P Seboek D Nylen ES et al.In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue.Endocrinology. 2003; 144: 5578-5584Crossref PubMed Scopus (236) Google Scholar. Conversely, interferon gamma, released during viral infections, attenuates interleukin 1b-induced procalcitonin production in human cells. These findings might explain why procalcitonin is superior to other clinical and laboratory markers for diagnosing clinically relevant bacterial respiratory tract infections, as shown in our study. As Sandek and co-workers correctly state, raised procalcitonin concentrations can be identified in several non-infectious diseases3Müller B Becker KL Procalcitonin: how a hormone became a marker and mediator of sepsis.Swiss Med Wkly. 2001; 131: 595-602PubMed Google Scholar. In this respect, high procalcitonin concentrations during cardiogenic shock indicate bacterial challenge of the host after bacterial translocation during intestinal hypoperfusion. This bacterial challenge can lower the specificity, but not the sensitivity, of procalcitonin for the diagnosis of bacterial lower respiratory tract infections. In our study, 18 (7·4%) patients with lower respiratory tract infection as their main diagnosis had congestive heart failure. The presence of congestive heart failure did not result in heightened procalcitonin concentrations, assessed by a sensitive assay (Kryptor PCT, functional assay sensitivity 0·06 μg/L). Unfortunately, in the studies cited by Sandek and co-workers, an insensitive procalcitonin-assay was used (LUMITest PCT, 0·5 μg/L), which does not reliably measure the concentrations reported. In addition, negative culture results do not exclude a concomitant infection. To resolve this important question, we started a prospective study to correlate circulating brain natriuretic peptide and procalcitonin concentrations in patients with respiratory tract infections. The diagnostic accuracy of procalcitonin and its optimum cut-offs are completely dependent on use of a sensitive assay in an appropriate clinical setting. In a medical intensive care unit, for example, a cut-off of 1 μg/L was shown to be reliable for the diagnosis of sepsis1Müller B Becker KL Schächinger H et al.Precursors are reliable markers of sepsis on a medical intensive care unit.Crit Care Med. 2000; 28: 977-983Crossref PubMed Scopus (511) Google Scholar. Most sepsis is caused by pulmonary infections. In this context, bacterial lower respiratory tract infections can be viewed as sepsis precursors. Accordingly, the cut-off of procalcitonin to detect bacterial respiratory tract infections must be lowered. We have chosen cut-offs based on studies by our group1Müller B Becker KL Schächinger H et al.Precursors are reliable markers of sepsis on a medical intensive care unit.Crit Care Med. 2000; 28: 977-983Crossref PubMed Scopus (511) Google Scholar and others4Nylen ES Snider RH Thompson KA Rohatgi P Becker KL Pneumonitis-associated hyperprocalcitonemia.Am J Med Sci. 1996; 312: 12-18PubMed Scopus (0) Google Scholar, 5Becker KL Nylen ES White SC Müller B Snider RH Calcitonin gene family of peptides in inflammation infection and sepsis: a journey from calcitonin back to its precursors.J Clin Endocrinol Metab. 2004; 89: 1512-1525Crossref PubMed Scopus (390) Google Scholar. The reliability of our cut-off range of 0·1–0·5 μg/L is shown by the similar outcome of the two groups, despite the striking reduction of antibiotic use in the procalcitonin-guided group. Procalcitonin is not a substitute for a careful history and physical examination. However, as a surrogate marker it provides important additional information, and questions currently used gold standards for the clinical diagnosis of bacterial lower respiratory tract infections. Specifically, procalcitonin is also a sensitive tool in the presence of co-morbidities—eg, congestive heart failure. Procalcitonin-guided antibiotic treatment in heart failureMirjam Christ-Crain and colleagues1 support the use of procalcitonin assessments to decide on the administration of antibiotics in lower respiratory tract infections (Feb 21, p 600)1. The authors suggest that procalcitonin concentrations are normal when less than 0.1 μg/L, and that concentrations of more than 0·25 μg/L and 0·5 μg/L are cut-offs for consideration of and starting antibiotic treatment, respectively1. However, the specific cut-off, on which this decision is based, needs validation particularly in other illnesses. Full-Text PDF