Unnecessary antibiotic use significantly contributes to increasing bacterial resistance, medical costs and the risk of drug-related adverse events. The blood marker procalcitonin increases in bacterial infections and decreases when patients recover from the infection. Hence, procalcitonin may be used to support clinical decision making for the initiation and discontinuation of antibiotic therapy in patients with a clinical suspicion of infection. Randomised controlled trials have demonstrated that such a strategy works, particularly in patients with an infection of the respiratory tract. However, most of these individual studies did not include enough patients to allow for a conclusive assessment about safety (low statistical power). Thus, the risk for mortality and severe complications associated with procalcitonin-guided decision making remained unclear.
This systematic review included individual patient data from 14 randomised controlled trials with a total of 4211 participants. When looking at these combined data, we found no increased risk for all-cause mortality or treatment failure when procalcitonin was used to guide initiation and duration of antibiotic treatment in participants with acute respiratory infections compared to control participants. However, we found a consistent reduction of antibiotic use, mainly due to lower prescription rates in primary care and lower duration of antibiotic courses in emergency department and intensive care unit patients. This analysis is limited to adult patients with respiratory infections excluding patients who were immuno-compromised (i.e. HIV positive, those receiving immuno-suppressive therapies or chemotherapy). Most trials were conducted in Europe and China and similar studies in other countries including the United States are warranted.

https://pure.rug.nl/ws/files/71631497/Schuetz_et_al_2017_Cochrane_Database_of_Systematic_Reviews.pdf

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections

Fungal spores can account for large proportions of air particulate matter, and they may potentially influence the hydrological cycle and climate as nuclei for water droplets and ice crystals in clouds, fog, and precipitation. Moreover, some fungi are major pathogens and allergens. The diversity of airborne fungi is, however, not well-known. By DNA analysis we found pronounced differences in the relative abundance and seasonal cycles of various groups of fungi in coarse and fine particulate matter, with more plant pathogens in the coarse fraction and more human pathogens and allergens in the respirable fine particle fraction (<3 μm). Moreover, the ratio of Basidiomycota to Ascomycota was found to be much higher than previously assumed, which might also apply to the biosphere.

High Diversity of Fungi in Air Particulate Matter

Red cell pyruvate kinase (PK) deficiency is the most frequent enzyme abnormality of the glycolytic pathway causing hereditary non-spherocytic haemolytic anaemia. The degree of haemolysis varies widely, ranging from very mild or fully compensated forms, to life-threatening neonatal anaemia and jaundice necessitating exchange transfusions. Erythrocyte PK is synthesized under the control of the PK-LR gene located on chromosome 1. To date, more than 150 different mutations in the PK-LR gene have been associated with PK deficiency. First attempts to delineate the biochemical and clinical consequences of the molecular defect were mainly based on the observation of the few homozygous patients and on the analysis of the three-dimensional structure of the enzyme. More recently, the comparison of the recombinant mutants of human red cell PK with the wild-type enzyme has enabled the effects of amino acid replacements on the enzyme molecular properties to be determined and help to correlate genotype to clinical phenotype.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2141.2005.05527.x

Red cell pyruvate kinase deficiency: molecular and clinical aspects

Several controlled clinical studies have evaluated the potential of the infection biomarker procalcitonin (PCT) to improve the diagnostic work-up of patients with bacterial infections and its influence on decisions regarding antibiotic therapy. Most research has focused on lower respiratory tract infections and critically ill sepsis patients. A clinical utility for PCT has also been found for patients with urinary tract infections, postoperative infections, meningitis, and patients with acute heart failure with possible superinfection (i.e., pneumonia). In these indications, PCT levels measured on hospital admission were found to substantially reduce the initiation of antibiotic treatment in low-risk situations (i.e., bronchitis, chronic obstructive pulmonary disease exacerbation). For more severe infections (i.e., pneumonia, sepsis), antibiotic stewardship by monitoring of PCT kinetics resulted in shorter antibiotic treatment durations with early cessation of therapy. Importantly, these strategies appear to be safe without increasing the risk for mortality, recurrent infections, or treatment failures. PCT kinetics also proved to have prognostic value correlating with disease severity (i.e., pancreatitis, abdominal infection) and resolution of illness (i.e., sepsis). Although promising findings have been published in these different types of infections, there are a number of limitations regarding PCT, including suboptimal sensitivity and/or specificity, which makes a careful interpretation of PCT in the clinical context mandatory. This narrative review aims to update clinicians on the strengths and limitations of PCT for patient management, focusing on research conducted within the last 4 years.

/pdf/procalcitonin-guided-diagnosis-and-antibiotic-stewardship-pqltj0i1pv.pdf

Procalcitonin-guided diagnosis and antibiotic stewardship revisited

Point-of-care diagnostics for infectious diseases: From methods to devices.

Background: Automated systems have enabled the counting of particles in urine to be standardized. Their superiority over traditional sediment analysis has been well documented, but they have not gained wide acceptance. The reasons for this are that sediment analysis has been performed and interpreted for decades. Additionally, pathologic casts and other unknown particles still must be confirmed under the microscope. Furthermore, comparison between the methods has revealed outliers and thus decreased confidence in automation.

Methods: We used the standardized KOVA cell chamber system to count particles and compared the results with UF-100 flow cytometry as an alternative to traditional sediment analysis.

Results: We compared 252 randomly selected urine samples and obtained a review rate of 33%. Microscopic verification was necessary because of the presence of casts, yeast, sperm, dysmorphic erythrocytes, and some misclassified erythrocytes or leukocytes that were detected by incongruent dipstick results and abnormal scattergrams. We obtained correlation coefficients of 0.966 for erythrocytes and 0.935 for leukocytes. Criteria for an algorithm to identify samples that needed microscopic review were derived from comparisons between the number of particles from UF-100, dipstick results, cell chamber counting, and sediment analysis.

Conclusions: Automated cell counting combined with microscopic counting with a standardized cell chamber system is useful. An objective algorithm for review criteria can be developed via systematic comparison of UF-100 flow cytometry and microscopy. Only urine samples that meet these criteria need to be confirmed microscopically.

Quantitative Urine Particle Analysis: Integrative Approach for the Optimal Combination of Automation with UF-100 and Microscopic Review with KOVA Cell Chamber

Detection limit of architect hepatitis C core antigen assay in correlation with HCV RNA, and renewed confirmation algorithm for reactive anti-HCV samples.

Background: Urinary tract infections (UTIs) are common drivers of antibiotic use. The minimal effective duration of antibiotic therapy for UTIs is unknown, but any reduction is important to diminish selection pressure for antibiotic resistance, costs, and drug-related side-effects. The aim of this study was to investigate whether an algorithm based on procalcitonin (PCT) and quantitative pyuria reduces antibiotic exposure. Methods: From April 2012 to March 2014, we conducted a factorial design randomized controlled open-label trial. Immunocompetent adults with community-acquired non-catheter-related UTI were enrolled in the emergency department of a tertiary-care 600-bed hospital in northwestern Switzerland. Clinical presentation was used to guide initiation and duration of antibiotic therapy according to current guidelines (control group) or with a PCT-pyuria-based algorithm (PCT-pyuria group). The primary endpoint was overall antibiotic exposure within 90 days. Secondary endpoints included duration of the initial antibiotic therapy, persistent infection 7 days after end of therapy and 30 days after enrollment, recurrence and rehospitalizations within 90 days. Results: Overall, 394 patients were screened, 228 met predefined exclusion criteria, 30 declined to participate, and 11 were not eligible. Of these, 125 (76% women) were enrolled in the intention-to-treat (ITT) analysis and 96 patients with microbiologically confirmed UTI constituted the per protocol group; 84 of 125 (67%) patients had a febrile UTI, 28 (22%) had bacteremia, 5 (4%) died, and 3 (2%) were lost to follow-up. Overall antibiotic exposure within 90 days was shorter in the PCT-pyuria group than in the control group (median 7.0 [IQR, 5.0–14.0] vs. 10.0 [IQR, 7.0–16.0] days, P=0.011) in the ITT analysis. Mortality, rates of persistent infections, recurrences, and rehospitalizations were not different. Conclusions: A PCT-pyuria-based algorithm reduced antibiotic exposure by 30% when compared to current guidelines without apparent negative effects on clinical outcomes.

/pdf/procalcitonin-and-pyuria-based-algorithm-reduces-antibiotic-4k9x15ympp.pdf

Procalcitonin and pyuria-based algorithm reduces antibiotic use in urinary tract infections: a randomized controlled trial

Die vorliegende Arbeit soll die in der Praxis tatigen Arzte unterstutzen, die Messergebnisse um Krankheiten des hamatologischen Formenkreises besser zu interpretieren. Es werden die Referenzbereiche der haufigsten hamatologischen Labormessgrosen, gruppiert nach Indikationen oder Methoden, vorgestellt. Die aufgefuhrten Daten stutzen sich auf Referenzbereiche von schweizerischen Hamatologie-Laboratorien und auf eine grose Anzahl von Literaturangaben. Je nach Literaturquelle oder Labor weisen die verglichenen Werte teilweise betrachtliche Unterschiede auf. Die aufgefuhrten Werte sind deshalb als – gut ausgewahlte – Richtwerte zu interpretieren. Die wichtigsten Abhangigkeiten des Referenzbereiches einer Messgrose von unveranderlichen Einflussgrosen wie Alter oder Geschlecht wurden, falls gesichert vorhanden, berucksichtigt. Fur andere physiologische, jedoch kurzfristig veranderliche Einflussgrosen sind in der Regel keine spezifischen Referenzbereiche erhaltlich. Der betrachtliche Einfluss von Faktoren wie Str...

Cornelia Ottiger

Papers

Quantitative Urine Particle Analysis: Integrative Approach for the Optimal Combination of Automation with UF-100 and Microscopic Review with KOVA Cell Chamber

Detection limit of architect hepatitis C core antigen assay in correlation with HCV RNA, and renewed confirmation algorithm for reactive anti-HCV samples.

Procalcitonin and pyuria-based algorithm reduces antibiotic use in urinary tract infections: a randomized controlled trial

Metaanalysis of reference values in hematology

Time-course of quantitative urinary leukocytes and bacteria counts during antibiotic therapy in women with symptoms of urinary tract infection.