An ideal marker for bacterial infections should allow an early diagnosis, inform about the course and prognosis of the disease and facilitate therapeutic decisions. Procalcitonin (ProCT) covers these features better as compared to other, more commonly used biomarkers, and thus, the current hype on ProCT has a solid scientific basis. A superior diagnostic accuracy of ProCT has been shown for a variety of infections, eg respiratory tract infections, meningitis, acute infectious endocarditis and pancreatitis. Importantly, a ProCT-based therapeutic strategy can safely and markedly reduce antibiotic usage in lower respiratory tract infections, the major cause of sepsis. Being a hormokine mediator, immunoneutralisation of ProCT might offer new hope for more effective treatment options in sepsis. It is now evidence-based that ProCT provides more information and, thereby, questions the currently used "gold standards" for the diagnosis of clinically relevant bacterial infections. Yet, ProCT is less than a perfect marker. ProCT can be increased in non-infectious conditions, and may remain low in infections. The diagnosis of bacterial infections will continue to require a critical clinical awareness, careful patient history, dedicated physical examination, and appropriate cultures. This review aims to help the clinician to understand the physiopathological basis, to appreciate strengths and weaknesses of this biomarker, and thereby to promote a rational implementation of ProCT in a routine setting.

Procalcitonin in bacterial infections--hype, hope, more or less?

Septic syndromes represent a major although largely underrecognized healthcare problem worldwide, accounting for thousands of deaths every year. It is now agreed that sepsis deeply perturbs immune homeostasis by inducing an initial tremendous systemic inflammatory response which is accompanied by an anti-inflammatory process, acting as negative feedback. This compensatory inhibitory response secondly becomes deleterious as nearly all immune functions are compromised. These alterations might be directly responsible for worsening outcome, as they may play a major role in the decreased resistance to nosocomial infections in patients who survived initial resuscitation. Consequently, immunostimulatory therapies may now be assessed for the treatment of sepsis. This review focuses on immune dysfunctions described in septic patients and on their potential use as markers on a routine standardized basis for prediction of adverse outcome or of occurrence of secondary nosocomial infections. This constitutes a prerequisite to a staging system for individualized treatment for these hitherto deadly syndromes.

Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony.

The evaluation of tests for neonatal sepsis is important because the infection may present a very serious threat to the baby. There is an urgent need to know whether the baby has sepsis to institute treatment as quickly as possible. Confirmation of the diagnosis may take time, and diagnostic tests are used to obtain a rapid indication of the infection status. These tests are not perfect. Some real cases of infection will produce negative test results, whereas some babies without infection will test positive. The potential usefulness of the test will depend, above all, on the clinical condition of the baby. If the baby is really very sick, the test will not give very much additional information. Similarly, if the baby is evidently well, a clinical examination will be sufficient and a positive test result would not dramatically increase the probability that the baby is infected. It is in situations in which the clinical picture leaves the physician in doubt about the infection status that a diagnostic test is likely to be most useful. Thus, the result of a diagnostic test must be evaluated in the light of the clinical condition of the baby.

Extensive literature exists on single laboratory tests or combinations of tests, as well as tests used together with risk factors and/or clinical signs, to diagnose neonatal sepsis. In many instances, the results of the evaluations have been conflicting. There are several possible explanations for the divergent results, and the purpose of this review is to update readers on the topic and raise issues that should be addressed in the future.

Throughout pregnancy and until the membranes rupture, the fetus is relatively protected from the microbial flora of the mother by the chorioamniotic membranes, the placenta, and poorly understood antibacterial factors in amniotic fluid (1). However, there …

/pdf/diagnosis-of-neonatal-sepsis-a-clinical-and-laboratory-5boo7y41e2.pdf

Diagnosis of Neonatal Sepsis: A Clinical and Laboratory Challenge

Background: Single-center trials have shown that monocytic HLA-DR is a good marker for monitoring the severity of temporary immunodepression after trauma, major surgery, or sepsis. A new test for measuring monocytic HLA-DR is now available.

Methods: We evaluated a new test reagent set for monocytic HLA-DR expression (BD Quantibrite™ HLA-DR/Monocyte reagent; Becton Dickinson) in single-laboratory and interlaboratory experiments, assessing preanalytical handling, lyse-no-wash (LNW) vs lyse-wash (LW) values, reference values, and the effect of use of different flow cytometers and different instrument settings on test variance.

Results: For preanalytical handling, EDTA anticoagulation, storage on ice as soon as possible, and staining within 4 h after blood collection gave results comparable to values obtained for samples analyzed immediately after collection (mean increase of ∼4% in monocytic HLA-DR). Comparison of LNW and LW revealed slightly higher results for LNW (∼18% higher for LNW compared with LW; r = 0.982). Comparison of different flow cytometers and instrument settings gave CVs <4%, demonstrating the independence of the test from these variables and suggesting that this method qualifies as a standardized test. CV values from the interlaboratory comparison ranged from 15% (blood sample unprocessed before transport) to 25% (stained and fixed before transport).

Conclusions: For the BD Quantibrite HLA-DR/Monocyte test, preanalytical handling is standardized. Single-laboratory results demonstrated the independence of this test from flow cytometer and instrument settings. Interlaboratory results showed greater variance than single-laboratory values. This interlaboratory variance was partly attributable to the influence of transport and can be reduced by optimization of transport conditions.

/pdf/monitoring-temporary-immunodepression-by-flow-cytometric-khpvn9mw5b.pdf

Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study.

Calcitonin was discovered in the early 1960s [1], at which time it was assumed to be a single hormone with a yet-to-be-determined role in human physiology. Since then it has been found to be only one entity among a large array of related circulating peptides, at least one of which has a pivotal role in the host response to microbial infections [2, 3]. The aim of this review is to describe this metamorphosis of an endocrine hormone to a new class of hormokine mediators in infectious diseases.

http://grupoeclab.com.mx/Doctos/articulos/procalcitonin_review.pdf

Procalcitonin: how a hormone became a marker and mediator of sepsis.

High serum concentrations of procalcitonin, a stable 116-amino acid precursor molecule to the proteohormone calcitonin, have been reported in patients with severe systemic bacterial or fungal, but not viral, infections (1)(2). Serum procalcitonin concentrations correlated with the severity of bacterial infection and with the clinical course of the patients (3). In healthy volunteers, serum procalcitonin is barely detectable; however, it increases consistently after endotoxin injection (4). Therefore, serum procalcitonin is regarded by many authors as a useful marker of the presence, course, and prognosis of bacterial infection.

To date we are aware of three reports describing the value of procalcitonin for diagnosis of neonatal infection (1)(5)(6). The reports agree that patients with bacterial invasion have high concentrations of serum procalcitonin. However, there are some discrepancies regarding the procalcitonin concentrations in sera of newborn infants without bacterial infection.

In our study, procalcitonin concentrations were examined in 122 serum samples of …

Increased Serum Procalcitonin in Newborn Infants without Infection

Severe thermal injury causes an immune dysfunction which includes a decrease of monocyte human leukocyte antigen DR (HLA-DR) expression. Interleukin-10 exerts a negative influence on this parameter in vitro. In this study we determined the prognostic value of reduced monocyte HLA-DR expression with regard to infectious complications, and the in vivo association between monocyte HLA-DR and plasma interleukin-10 concentration. Both quantities were measured serially in 19 patients with severe burns. HLA-DR expression was determined by direct immunofluorescence on a flow cytometer, and interleukin-10 was measured by ELISA. After burn trauma the percentage of HLA-DR expressing monocytes fell markedly (median: 53% at day 2, 36% at day 4, 31% at day 7, 28% at day 9, 35% at day 12, and 42% at day 14; compared to 93% for healthy volunteers). Moreover, patients who became septic showed lower monocyte HLA-DR expression than non-septic patients; the differences were significant at day 2 (p < 0.01) and day 7 (p < 0.05). Plasma concentrations of interleukin-10 increased after thermal injury (median: 40 ng/l at day 2, 43 ng/l at day 4, 77 ng/l at day 7, 120 ng/l at day 9, 63 ng/l at day 12, and 82 ng/l at day 14). Individual HLA-DR expression and interleukin-10 concentration were negatively correlated, the association reaching statistical significance at day 4 (p=0.006) and day 7 (p=0.031). Thus, after severe burn injury monocyte HLA-DR expression has prognostic value and is negatively associated with interleukin-10 plasma concentration.

Association between reduced human leukocyte antigen (HLA)-DR expression on blood monocytes and increased plasma level of interleukin-10 in patients with severe burns.

We appreciate the comments of Dr. Martin-Denavit and co-workers on our report and the information they presented, which throws additional light on the use of serum procalcitonin (PCT) for the diagnosis of neonatal infection. They regard markedly increased serum PCT as a marker of materno-fetal infection, although …

/pdf/the-authors-of-the-report-cited-above-respond-1hmte1l3j6.pdf

The authors of the report cited above respond

Neutrophil intracellular pH and phagocytosis after thermal trauma

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Increased Serum Procalcitonin in Newborn Infants without Infection

Association between reduced human leukocyte antigen (HLA)-DR expression on blood monocytes and increased plasma level of interleukin-10 in patients with severe burns.

The authors of the report cited above respond

Neutrophil intracellular pH and phagocytosis after thermal trauma