Measuring levels of the biomarker procalcitonin in people in intensive care gives an accurate indication of the severity of bacterial infection they are experiencing. This in turn gives a clear indication as to the nature and length of any antibiotics course they require. New research says that by using procalcitonin levels to prescribe antibiotics rather than the current arbitrary guidelines, people's exposure to antibiotics could be decreased and it is hoped that the increasing rate of antibiotic resistance, which is becoming serious, could be slowed. The findings are reported in an Article Online First (www.thelancet.com) and in an upcoming edition of The Lancet—written by Professor Michel Wolff, Hôpital Bichat–Claude-Bernard, Paris, France, and colleagues.
Procalcitonin, a calcitonin precursor hormone, is judged to be a fairly specific marker for severe bacterial infection in patients with suspected sepsis. Guidance about blood procalcitonin concentration has substantially reduced antibiotic use in patients presenting at the emergency department or admitted to hospital for lower-respiratory-tract infections. Despite these encouraging results, the potential usefulness of procalcitonin as an instrument to guide antibiotic use in all intensive care units has not yet been shown. In this study, the authors looked at the effectiveness of using procalcitonin to reduce antibiotic exposure in intensive care.
In this randomised controlled trial, patients were assigned in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60, and number of days without antibiotics by day 28.
Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in the final analyses. Mortality of patients in the procalcitonin group seemed to be no worse than the control group at day 28 (21% vs 20%) and day 60 (30% vs 26%). Patients in the procalcitonin group had almost three more days without antibiotics by day 28 (14∙3 days vs 11∙6 days).
The authors point out that, despite lower antibiotic exposure in the procalcitonin group than in the control group, they were unable to show a between-group difference for the rates of emerging multidrug-resistant bacteria. However, they add: "Nonetheless, we stress that infection is the tip of the iceberg compared with digestive colonisation. Rectal, nasal, and axillary swab screening was not routinely done and might more accurately show antibiotic selective pressure. Moreover, a 3-day reduction of antibiotic use for only a small subset of admitted patients might not be sufficient to record a decreased resistance-emergence rate, especially for some intensive care units with high cross-transmission rates."
The authors say that the costs of each procalcitonin analysis in France is around 10-15 Euros. Procalcitonin levels need to be monitored daily throughout the course of antibiotics in intensive care—but the authors say this cost should be compared with the costs of unnecessary antibiotics—especially when broad spectrum or newly-licensed (and therefore usually more expensive) agents are used. They cite one study which placed the cost of antibiotic use in the intensive care setting at 114 Euros per patient per day.
They conclude: "The diverse clinical characteristics and reasons for admissions to the intensive care unit for patients enrolled in this study suggest that our conclusions could be applicable to most non-surgical patients in the intensive care unit, including those who are immunocompromised. A procalcitonin-guided strategy could reduce antibiotic selective pressure with potential benefits in the era of multiresistance."
In an accompanying Comment, Dr Marin H Kollef, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, MO, USA, says: "Experience so far suggests that unnecessary antibiotic use can be curtailed in the hospital setting, particularly within intensive care units. Whether the ideal strategy involves the use of a serum marker such as procalcitonin or a locally applied practice protocol remains to be established."
Professor Michel Wolff, Hôpital Bichat–Claude-Bernard, Paris, France. T) + 33 6 87 33 28 45 E) michel.wolff@bch.aphp.fr
Dr Marin H Kollef, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, MO, USA. T) +1 314-454-8764 E) mkollef@dom.wustl.edu
For full Article and Comment, see: http://press.thelancet.com/prorata.pdf
Journal
The Lancet