Procalcitonin to guide obtaining bloodcultures in the ICU.

In health care costs have increased in total over the past decades. To cite
from the 2009 report on health care related costs in the Netherlands as
published by the Central Bureau of Statistics (CBS): *In de periode 1972-2008
zijn de uitgaven aan zorg jaarlijks met gemiddeld 7,3 procent gegroeid: van 6,5
miljard euro in 1972 tot 79,1 miljard euro in 2008. Dat is meer dan een
verelfvoudiging. Gecorrigeerd voor prijsveranderingen zijn de uitgaven aan zorg
in deze periode jaarlijks met gemiddeld 2,9 procent toegenomen. Ook als
percentage van het bruto binnenlands product (bbp) zijn de uitgaven aan zorg
gestegen, van 8,7 procent in 1972 naar13,3 procent in 2008. Deze toename is
echter voor het grootste deel toe te rekenen aan het verschil in
prijsontwikkeling tussen het bbp en de zorguitgaven. De prijsontwikkeling van
de uitgaven aan zorg lag meestal hoger dan die van het bbp*.

The Netherlands has been a country well known for a prudent use of resources.
For many years the Netherlands is being ranked as one of the lowest antibiotics
consuming countries or even the lowest use of antibiotics in Europe . In their
2008 publication of Nethmap , the Stichting Werkgroep Antibiotica Beleid
(SWAB), a Dutch Foundation of the Working Party on Antibiotic Policy, in
collaboration with the RIVM, the National Institute for Public Health and the
Environment of the Netherlands, published a comprehensive and extensive insight
into emerging trends in antibiotic resistance and ecological pressure. In
short, pressures and resistance is on the rise in the Netherlands, despite its
prudent selection of anti-microbial agents. Though this report did not report
on economical aspects of antimicrobial usage, its European counterpart, the
EMEA has published these effects since then. Their report claims that costs
associated with antibiotic resistance should be estimated in the range of 1,5
billion euro per annum .
With no new antibiotics on the way and ever increasing costs for adequate
health care, a quest has commenced to find new ways to deal with bacterial
infection with still maintaining or (preferably) decreasing the current
spending budget. One of these research pathways has lead to the study of
biomarker usage to evaluate bacterial infections and antibiotic stewardship.
The most studied biomarker in this respect is a novel acute phase reactant
labeled procalcitonin. A biomarker specific for bacterial infections,
procalcitonin has been tested to tailor antibiotic usage to individual patient
need in targeted populations, like intensive care medicine, pulmonary medicine,
the emergency room, pediatrics and general practice.

The precursor hormone of calcitonin is procalcitonin. This chain of 116 amino
acids has now been studied in a high-sensitive format in no less than 13
randomized controlled trials. Though all these trials all studied different
populations under different circumstances, there is common ground to be found
amongst the results. One common result of these trials is that mortality never
differed between the procalcitonin or the control groups, proving the
procalcitonin algorithm intervention to be safe.

Another common result found across these published trials was a very large
reduction in antibiotic usage. Even in low antibiotic usage countries in
Western-Europe, like Switzerland and Denmark, savings of more than 23% (ICU) up
to 77.9% (general practice) were published. Currently, two large validation
trials in the Netherlands are underway , .

As these Dutch trials are underway, a new application for this novel biomarker
is being described in two recent publications , . Being highly specific for
bacterial infection, procalcitonin is being suggested to be used as a pretest
evaluation for the far more expensive blood culture. Both these trials report
that a cut-off of 0.25 ng/ml or less could save blood cultures in large
volumes. In the Dutch trial of urosepsis patients about 40% of all blood
cultures could have been saved, while the Swiss trial on community acquired
pneumonia patients reporting potential savings of up to 37% of all blood
cultures. Both trials reported an accurate prediction of bacteriemia in their
studied populations of about 96-97%. Other studies reported a negative
predictive value of about 88-94%.

The Dutch study group in the Leids Universitair Medisch Centrum reported that
using this regimen could save as much as US$36 per patient with urosepis when
the procalcitonin assay was already paid for. The remarkable finding was
further emphasized by the Swiss results who reported a similar amount in its
cost-effectiveness analysis.

It is likely that such a regimen is usable and feasible on the ICU. We propose
that this new application for procalcitonin be applied in a new trial to
demonstrate its safety and economical effectiveness to reduce the number of
blood cultures needed while still maintaining a high level of care without
increased morbidity and mortality.

The trial aims to investigate whether procalcitonin measurements can reduce the
amount of blood cultures in the ICU safely and cost-effectively.

Multicenter cross-over clinical trial

All patients on the intensive care in whom the treating physician establishes a
medical need for a blood culture are possible eligible for this trial.
The participating ICU*s (2 per medical center Erasmusmc and Maasstad
ziekenhuis) will be stratified and randomized by treatment regimen into a
control (standard of care) treatment and the PCT-guided treatment.
Randomization is thus performed per cluster allocation, being an assigned ICU.
All patients included into this trial and admitted on a participating unit will
follow the regimen specified for that specific time period for that unit.
Participating units will switch the allocated regimen after 3 months between
the control (standard of care) treatment and the PCT-guided treatment. The
washout period is 1 month, in which >95% of patients in the previous period has
left the unit.

NVT