Urine biomarkers in cancer detection: A systematic review of preanalytical parameters and applied methods.

The aim of this review was to explore the status of urine sampling as a liquid biopsy for noninvasive cancer research by reviewing used preanalytical parameters and protocols. We searched two main health sciences databases, PubMed and Web of Science. From all eligible publications (2010-2022), information was extracted regarding: (a) study population characteristics, (b) cancer type, (c) urine preanalytics, (d) analyte class, (e) isolation method, (f) detection method, (g) comparator used, (h) biomarker type, (i) conclusion and (j) sensitivity and specificity. The search query identified 7835 records, of which 924 unique publications remained after screening the title, abstract and full text. Our analysis demonstrated that many publications did not report information about the preanalytical parameters of their urine samples, even though several other studies have shown the importance of standardization of sample handling. Interestingly, it was noted that urine is used for many cancer types and not just cancers originating from the urogenital tract. Many different types of relevant analytes have been shown to be found in urine. Additionally, future considerations and recommendations are discussed: (a) the heterogeneous nature of urine, (b) the need for standardized practice protocols and (c) the road toward the clinic. Urine is an emerging liquid biopsy with broad applicability in different analytes and several cancer types. However, standard practice protocols for sample handling and processing would help to elaborate the clinical utility of urine in cancer research, detection and disease monitoring.

Impact of Collection Volume and DNA Extraction Method on the Detection of Biomarkers and HPV DNA in First-Void Urine.

The potential of first-void (FV) urine as a non-invasive liquid biopsy for detection of human papillomavirus (HPV) DNA and other biomarkers has been increasingly recognized over the past decade. In this study, we investigated whether the volume of this initial urine stream has an impact on the analytical performance of biomarkers. In parallel, we evaluated different DNA extraction protocols and introduced an internal control in the urine preservative. Twenty-five women, diagnosed with high-risk HPV, provided three home-collected FV urine samples using three FV urine collection devices (Colli-Pee) with collector tubes that differ in volume (4, 10, 20 mL). Each collector tube was prefilled with Urine Conservation Medium spiked with phocine herpesvirus 1 (PhHV-1) DNA as internal control. Five different DNA extraction protocols were compared, followed by PCR for GAPDH and PhHV-1 (qPCR), HPV DNA, and HBB (HPV-Risk Assay), and ACTB (methylation-specific qPCR). Results showed limited effects of collection volume on human and HPV DNA endpoints. In contrast, significant variations in yield for human endpoints were observed for different DNA extraction methods (p < 0.05). Additionally, the potential of PhHV-1 as internal control to monitor FV urine collection, storage, and processing was demonstrated.

Assessment of Forces in Intradermal Injection Devices: Hydrodynamic Versus Human Factors.

PURPOSE: The force that has to be exerted on the plunger for administering a given amount of fluid in a given time, has an important influence on comfort for the subject and usability for the administrator in intradermal drug delivery. The purpose of this study is to model those forces that are subject-independent, by linking needle and syringe geometry to the force required for ejecting a given fluid at a given ejection rate. MATERIAL AND METHODS: We extend the well-known Hagen-Poiseuille formula to predict pressure drop induced by a fluid passing through a cylindrical body. The model investigates the relation between the pressure drop in needles and the theoretic Hagen-Poiseuille prediction and is validated in fifteen needles from 26G up to 33G suited for intradermal drug delivery. We also provide a method to assess forces exerted by operators in real world conditions. RESULTS: The model is highly linear in each individual needle with R-square values ranging from 75% up to 99.9%. Ten out of fifteen needles exhibit R-square values above 99%. A proof-of-concept for force assessment is provided by logging forces in operators in real life conditions. CONCLUSIONS: The force assessment method and the model can be used to pinpoint needle geometry for intradermal injection devices, tuning comfort for subjects and usability for operators.

Preclinical evaluation of performance, safety and usability of VAX-ID®, a novel intradermal injection device.

The recent SARS-Cov2 pandemic and mpox health emergency have led to renewed interest in intradermal vaccination due to its dose sparing potential. Indeed, intradermal vaccination is particularly of interest for use in mass vaccination campaigns, pandemic preparedness programs, and/or for vaccines that are expensive or in short supply. Moreover, the rich immune network in the skin makes it an attractive target not only for prophylactic vaccination, but also for therapeutic vaccination, like immunotherapy and (dendritic) cell-based therapies. The aim of the current paper was to provide an overview of preclinical data generated with VAX-ID®, a novel intradermal drug delivery device, to allow assessing it performance, safety and usability. The device can overcome challenges seen with the Mantoux technique whereby the needle needs to be inserted under a shallow angle. Various parameters of VAX-ID® were evaluated, including dead-space volume, dose accuracy, penetration depth & liquid deposit in piglets, as well as usability by healthcare professionals. The device has shown to have a low dead volume and a high dose accuracy. Importantly, the device performed successful injections at a predefined depth into the dermis with a high safety profile as confirmed by visual and histological evaluation in piglets. Moreover, the device was rated as easy to use by healthcare professionals. The combined preclinical performance and usability findings indicate that VAX-ID® can provide reliable, standardized and accurate drug delivery in the dermal layer of the skin with a high ease of use. The device offers a solution for injection of various prophylactic as well as therapeutic vaccines.

UAS™-A Urine Preservative for Oncology Applications.

Liquid biopsy is a revolutionary tool that is gaining momentum in the field of cancer research. As a body fluid, urine can be used in non-invasive diagnostics for various types of cancer. We investigated the performance of UAS™ as a preservative for urinary analytes. Firstly, the need for urine preservation was investigated using urine samples from healthy volunteers. Secondly, the performance of UAS™ was assessed for cell-free DNA (cfDNA) and host cell integrity during storage at room temperature (RT) and after freeze-thaw cycling. Finally, UAS™ was used in a clinical setting on samples from breast and prostate cancer patients. In the absence of a preservative, urinary cfDNA was degraded, and bacterial overgrowth occurred at RT. In urine samples stored in UAS™, no microbial growth was seen, and cfDNA and cellular integrity were maintained for up to 14 days at RT. After freeze-thaw cycling, the preservation of host cell integrity and cfDNA showed significant improvements when using UAS™ compared to unpreserved urine samples. Additionally, UAS™ was found to be compatible with several commercially available isolation methods.

Indications for antimicrobial prescribing in European nursing homes: results from a point prevalence survey.

PURPOSE: In light of the emerging problem with multiresistant microorganisms in nursing homes (NHs), the European Surveillance of Antimicrobial Consumption NH subproject was set up to measure and describe antimicrobial use across Europe. The aim of this paper was to investigate the indications for antimicrobial use and hence identify targets for quality improvement. METHODS: Data were obtained from a point prevalence survey conducted in 323 NHs across 21 European countries. A resident questionnaire had to be completed for each resident receiving an antimicrobial, collecting data such as compound name and indication for antimicrobial prescribing. Four main indications for antimicrobial use were recorded: nasal decolonisation of methicillin-resistant Staphylococcus aureus (MRSA) carriage with mupirocin, prophylactic, empirical, and microbiologically documented treatments. The latter three treatment types were further subdivided according to the targeted infections. RESULTS: In total, 1966 residents were treated with 2046 antimicrobials. Empirical treatments were most common (54.4% of all antimicrobial therapies; prevalence: 3.39 per 100 eligible residents), followed by prophylactic (28.8%; prevalence: 1.87%) and microbiologically documented (16.1%; prevalence: 1.01%) regimes. MRSA decolonisation with nasal mupirocin (0.7%; prevalence: 0.02%) was uncommon. Antimicrobials were most frequently prescribed for the prevention or treatment of urinary (49.5%; prevalence: 3.23%) and respiratory (31.8%; prevalence: 1.81%) tract infections. A very high proportion of uroprophylaxis was reported (25.6% of all prescribed antimicrobials; prevalence: 1.67%). CONCLUSIONS: The indications for antimicrobial prescribing varied markedly between countries. We identified uroprophylaxis as a possible target for quality improvement.

European Surveillance of Antimicrobial Consumption (ESAC): quality appraisal of antibiotic use in Europe.

OBJECTIVES: To assess quality of outpatient antibiotic use in Europe in 2009 based on the 12 European Surveillance of Antimicrobial Consumption (ESAC) drug-specific quality indicators and to evaluate changes in quality between 2004 and 2009. METHODS: Quality of outpatient antibiotic use in 2009 was compared between 32 countries by calculating the indicator values for 2009 for each of the 12 ESAC drug-specific quality indicators based on outpatient antibiotic use data expressed in defined daily doses per 1000 inhabitants per day (DID). For each of the indicators we grouped the 2009 indicator values into four quartiles. To evaluate changes in quality between 2004 and 2009, based on their respective indicator values, countries were also grouped according to the quartile distribution of the 2004 indicator values. Only countries able to deliver data for both years were included in this analysis. RESULTS: In 2009 a difference in the quality of outpatient antibiotic use between Nordic and Southern European countries was observed. Quality of outpatient antibiotic use decreased between 2004 and 2009. In particular, there were increases in the quality indicators [J01F_DID], [J01M_DID], [J01CR_%] and [J01_B/N], i.e. the use of macrolides, lincosamides and streptogramins in DID, the use of quinolones in DID, the proportional use of combinations of penicillins, including ß-lactamase inhibitors and the ratio of broad- to narrow-spectrum antibiotics. CONCLUSIONS: Quality of outpatient antibiotic use in DID decreased between 2004 and 2009. A continuous effort to improve outpatient antibiotic consumption seems to be essential to reduce outpatient antibiotic use in general and the use of broad-spectrum antibiotics in particular.

Identification of targets for quality improvement in antimicrobial prescribing: the web-based ESAC Point Prevalence Survey 2009.

OBJECTIVES: Since electronic prescribing is limited to few hospitals, point prevalence surveys, such as the standardized European Surveillance of Antimicrobial Consumption point prevalence survey (ESAC PPS), are an alternative tool for monitoring prescribing and helping to identify performance indicators and prescribing trends. The main objective of this study was to identify and assess targets for quality improvement. METHODS: Each hospital had to carry out the survey within 2 weeks. Each department had to be surveyed in 1 day. Data collected, for all inpatients, included age and gender. For patients on systemic antimicrobial treatment, the antimicrobial/s, infection/prophylaxis site, reason in medical notes and guideline compliance were also collected. A central database using a web-based tool (WebPPS) developed in-house was used for data entry. RESULTS: Combination of two or more antimicrobials accounted for 30% of use. Surgical prophylaxis was prolonged (>1 day) in 53% of cases. 'Intensive care' had higher proportions of treated patients (53% versus 29%), combination therapy (49% versus 31%), hospital-acquired infections (49% versus 31%) and parenteral administration (91% versus 61%). 'Reason in notes' was documented in 76%, and 'guideline compliance' occurred in 62% of patients. CONCLUSIONS: The ESAC PPS provided useful information on the quality of prescribing, which identified a number of targets for quality improvement. These could apply to specific departments or whole hospitals. Intensive care, which has different characteristics, should not be compared with general wards with respect to combination therapy, hospital-acquired infections or parenteral proportion. The study confirmed that the ESAC PPS methodology can be used on a large number of hospitals at regional, national, continental or global level.

European Surveillance of Antimicrobial Consumption (ESAC): systemic antiviral use in Europe.

OBJECTIVES: To assess the total systemic antiviral use in Europe and to identify the antiviral substances most commonly used. METHODS: Within the European Surveillance of Antimicrobial Consumption (ESAC; www.esac.ua.ac.be), using the anatomical therapeutic chemical (ATC) classification and defined daily dose (DDD) measurement unit, data on total (out- and inpatient) systemic antiviral use (ATC J05), aggregated at the level of the active substance, were collected for 2008, and use was expressed in DDD (WHO ATC/DDD, version 2010) per 1000 inhabitants per day (DID). Antiviral substances were grouped according to their main indication. RESULTS: In Europe, 12 countries (Belgium, Croatia, Denmark, Estonia, Finland, France, Hungary, Italy, Luxembourg, Russia, Slovenia and Sweden) provided total (out- and inpatient) data and 4 countries (Austria, the Netherlands, Portugal and Norway) provided outpatient data only. Total systemic antiviral use varied by a factor of 10.95 between the country with the highest (3.53 DID in France) and the country with the lowest (0.32 DID in Croatia) use. HIV/AIDS antivirals represented more than 50% of the total antiviral use in most countries. The amount and spectrum of antivirals used varied greatly between countries. CONCLUSIONS: Our study demonstrated a wide variation of total systemic antiviral use in several European countries, as striking as that of outpatient systemic antibiotic, antimycotic and antifungal use. The variation is mainly determined by the use of HIV/AIDS antivirals. These observations should stimulate further analysis to understand the variation of specific antiviral substances. The ESAC data facilitate auditing of antiviral prescriptions and evaluation of the implementation of guidelines and public health policies.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient penicillin use in Europe (1997-2009).

BACKGROUND: Data on 13 years (1997-2009) of outpatient penicillin use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project and analysed in detail. METHODS: For the period 1997-2009, data on outpatient use of systemic penicillins aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011) and expressed in DDD per 1000 inhabitants per day (DID). For detailed analysis of trends over time, seasonal variation and composition of outpatient penicillin use in 33 European countries, we distinguished between narrow-spectrum penicillins (NSP), broad-spectrum penicillins (BSP), penicillinase-resistant penicillins (PRP) and combinations with ß-lactamase inhibitors (COP). RESULTS: Total outpatient penicillin (ATC group J01C) use in 2009 varied by a factor of 3.8 between the countries with the highest (16.08 DID in France) and lowest (4.23 DID in the Russian Federation) use. COP represented 45.8%, BSP 40.7%, NSP 10.8% and PRP 2.6% of total European outpatient penicillin use. Total outpatient penicillin use significantly increased over time by 1.53 (SD 0.71) DID between 1997 and 2009. COP (mainly co-amoxiclav) increased by 2.17 (SD 0.40) DID, which was the result of its absolute increase as well as the observed shift from NSP and BSP towards COP. This increase exceeded 10% in 20 countries, where it coincided with a similar decrease in either BSP (15 countries) or NSP (5 countries). CONCLUSIONS: Penicillins represented the most widely used antibiotic subgroup in all 33 participating countries, albeit with considerable variation in their use patterns. For Europe, a continuous increase in overall penicillin use and of COP use was observed during the period 1997-2009.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient cephalosporin use in Europe (1997-2009).

BACKGROUND: Data on 13 years of outpatient cephalosporin use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC), and analysed in detail. METHODS: For the period 1997-2009, data on outpatient use of systemic cephalosporins aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011) and expressed in DDD per 1000 inhabitants per day (DID). For detailed analysis of trends over time, seasonal variation and composition of outpatient cephalosporin use in 33 European countries, we distinguished between first-generation (J01DB), second-generation (J01DC), third-generation (J01DD) and fourth-generation (J01DE) cephalosporins. RESULTS: Total outpatient cephalosporin use in 2009 varied from 8.7 DID in Greece to 0.03 DID in Denmark. In general, use was higher in Southern and Eastern European countries than in Northern European countries. Total outpatient cephalosporin use increased over time by 0.364 (SD 0.473) DID between 1997 and 2009. Cephalosporin use increased for half of the countries. Low-consuming Northern European countries and the UK further decreased their use. Second-generation cephalosporins increased by >20% in seven countries (mainly cefuroxime), coinciding with a decrease in first-generation cephalosporins. Substantial parenteral use of third-generation substances (mainly ceftriaxone) was observed in France, Italy and the Russian Federation. CONCLUSIONS: Since 1997, the use of the older (narrow-spectrum) cephalosporins decreased in favour of the newer (i.e. broad-spectrum) cephalosporins in most countries. Extreme variations between European countries in cephalosporin use over time suggest that they are to a large extent inappropriately used.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient antibiotic use in Europe (1997-2009).

OBJECTIVES: To describe total outpatient systemic antibiotic use in Europe from 1997 to 2009 and to analyse statistically trends of total use and composition of use over time. METHODS: For the period 1997-2009, data on outpatient use of systemic antibiotics aggregated at the level of the active substance were collected and expressed in defined daily doses (WHO, version 2011) and packages per 1000 inhabitants per day (DID and PID, respectively). Outpatient antibiotic (ATC J01) use in DID in the 33 European countries able to deliver valid data was analysed using longitudinal and compositional data analyses. RESULTS: Total outpatient antibiotic use in 2009 varied by a factor of 3.8 between the countries with the highest (38.6 DID in Greece) and lowest (10.2 DID in Romania) use. For Europe, a significant increase was found in total outpatient antibiotic use, as well as a significant seasonal variation, which decreased over time from 1997 to 2009. Relative use of penicillins and quinolones significantly increased over time with respect to sulphonamides and trimethoprim, and relative use of quinolones increased with respect to macrolide/lincosamide/streptogramin as well. More detailed analyses of these major antibiotic subgroups will be described in separate papers. CONCLUSIONS: Outpatient antibiotic use in Europe measured as DID has increased since 1997, whereas seasonal variation has decreased over time. European Surveillance of Antimicrobial Consumption (ESAC) data on outpatient antibiotic use in Europe enable countries to audit their antibiotic use. Complemented by longitudinal and compositional data analyses, these data provide a tool for assessing public health strategies aimed at reducing antibiotic resistance and optimizing antibiotic prescribing.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient quinolone use in Europe (1997-2009).

BACKGROUND: Data on more than a decade of outpatient quinolone use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC). METHODS: For the period 1997-2009, data on outpatient use of systemic quinolones aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011), and expressed in DDD and packages per 1000 inhabitants per day (DID and PID, respectively). Using a classification based on pharmacokinetic and in vitro potency profiles, quinolone use was analysed with regard to trends over time, seasonal variation and composition. RESULTS: Total outpatient quinolone use in 2009 varied by a factor of 7.5 between the country with the highest (Italy, 3.61 DID) and the country with the lowest (the UK, 0.48 DID) quinolone use. The second-generation quinolones accounted for >50% of quinolone use (mainly ciprofloxacin), except for Croatia, where first-generation quinolones (mainly norfloxacin) were mostly used. A significant increase in outpatient quinolone use was found for Europe, as well as a large seasonal variation, which increased significantly over time from 1997 to 2009. Relative use of third-generation quinolones significantly increased over time with respect to the use of second-generation quinolones, while the relative use of both significantly increased with respect to the first-generation quinolones. Levofloxacin and moxifloxacin (respiratory quinolones) represented >10% of quinolone outpatient use in 17 countries, with extreme seasonal variation in all countries. CONCLUSIONS: There was a substantial increase and change in the pattern of quinolone use between 1997 and 2009, a period during which quinolones that are effective for the treatment of respiratory tract infections were introduced. These quinolones are not the first-line antibiotics for this indication and their use should generally be limited, and quinolones should ideally show no substantial seasonal variation in terms of their use.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in Europe (1997-2009).

BACKGROUND: Data on more than a decade of outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in Europe were collected from 33 countries as part of the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC). METHODS: For the period 1997-2009, data on outpatient use of systemic tetracyclines, sulphonamides and trimethoprim, and other antibacterials aggregated at the level of the active substance were collected and expressed in defined daily doses (DDD; WHO, version 2011) per 1000 inhabitants per day (DID). Using the Anatomical Therapeutic Chemical (ATC) classification, trends in the use of tetracyclines (J01A), sulphonamides and trimethoprim (J01E) and other antibacterials (J01X) over time, seasonal variation and composition of use were analysed. RESULTS: In 2009, the variations in outpatient use of systemic tetracyclines, sulphonamides and trimethoprim, and other antibacterials between countries, and also in the composition of use over time, were huge. For tetracyclines a significant and for sulphonamides and trimethoprim a non-significant decrease in use was observed between 1997 and 2009 in Europe. The seasonal variation in their use significantly decreased over time. For the other antibacterials, no significant changes in the volume of use or its seasonal variation were seen. CONCLUSIONS: As for all other major antibiotic subgroups, a striking variation in use and composition of use between countries in Europe was observed for outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials. In combination with the decreasing use, especially of recommended substances, this represents an opportunity not only to reduce antibiotic use but also to improve its quality.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient macrolide, lincosamide and streptogramin (MLS) use in Europe (1997-2009).

BACKGROUND: Data on more than a decade of outpatient macrolide, lincosamide and streptogramin (MLS) use in Europe were collected from 33 countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC), using the WHO Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) methodology. METHODS: For the period 1997-2009, data on outpatient use of systemic MLS aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2011) per 1000 inhabitants per day (DID). Using a classification based on mean plasma elimination half-life, macrolide use was analysed for trends over time, seasonal variation and composition. RESULTS: Total outpatient MLS use in 2009 varied by a factor of 18 between the countries with highest (11.5 DID in Greece) and lowest (0.6 DID in Sweden) use. MLS use showed high seasonal variation. Short-, intermediate- and long-acting macrolides were the most commonly used agents in 2, 25 and 5 countries, respectively (mainly erythromycin, clarithromycin and azithromycin, respectively). In Sweden, mainly lincosamides (clindamycin) were used. Lincosamide use was observed in all countries, while substantial use of a streptogramin was only seen in France (pristinamycin). For Europe, a significant increase in outpatient MLS use was found, as well as a significant seasonal variation, which increased over time from 1997 to 2009. Relative use of long-acting macrolides and lincosamides significantly increased over time with respect to intermediate-acting macrolides, and relative use of the latter increased with respect to short-acting macrolides. CONCLUSIONS: The observed differences between European countries in the levels of MLS use and the extreme seasonal variations in their use suggest that this subgroup of antibiotics is still prescribed inappropriately in many countries.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient systemic antimycotic and antifungal use in Europe.

OBJECTIVES: To assess the total outpatient systemic antimycotic and antifungal use in Europe, and to identify the antimycotic and antifungal substances most commonly used. METHODS: Within ESAC (www.esac.ua.ac.be), using the anatomical therapeutic chemical (ATC) and defined daily dose (DDD) classification, data on outpatient use of all 14 antimycotics (12) and antifungals (2) for systemic use (ATC J02 and D01B, respectively), aggregated at the level of the active substance, were collected for 2007. Use was expressed in DDD (WHO ATC/DDD, version 2008) per 1000 inhabitants per day (DID). Only countries for which data on both J02 and D01B use were available were included in the analysis. RESULTS: In 20 European countries (data for Cyprus and Estonia include hospital use), total outpatient systemic antimycotic and antifungal use varied by a factor of 6.7 between the country with the highest (3.03 DID in Belgium) and the country with the lowest (0.45 in Croatia) use. Terbinafine, ketoconazole, itraconazole and fluconazole represented >94% of the total outpatient antimycotic and antifungal use in all countries. Terbinafine use represented >50% of the total systemic antimycotic and antifungal use in 16 out of 20 countries (not in Croatia, Italy, Luxembourg and Bulgaria). CONCLUSIONS: We present for the first time a standardized and validated data set of outpatient systemic antimycotic and antifungal use in Europe. Our study demonstrates a variation of antimycotic and antifungal use in Europe, as striking as that of antibiotic use. The ESAC data facilitate the auditing of antimycotic and antifungal prescribing, and the evaluation of the implementation of guidelines and public health policies to promote their judicious use.

European Surveillance of Antibiotic Consumption (ESAC) point prevalence survey 2008: paediatric antimicrobial prescribing in 32 hospitals of 21 European countries.

BACKGROUND: Antimicrobials are the most common medicines prescribed to children, but very little is known about patterns of hospital paediatric antimicrobial prescribing. This study aimed at describing paediatric antimicrobial prescribing in European hospitals to identify targets for quality improvement. METHODS: The European Surveillance of Antibiotic Consumption (ESAC) project (www.esac.ua.ac.be) collected data during 2 calendar weeks between May and June 2008 in 32 hospitals of 21 European countries with paediatric departments, using a standardized method. The ESAC point prevalence survey included all inpatient beds and identified all patients who were receiving systemic antimicrobials on the day of the survey or had received antimicrobial surgical prophylaxis on the previous day. RESULTS: Of 1799 children, 583 (32%) received one or more antimicrobials (range 17%-100%). The indications were therapeutic in 71%, prophylactic in 26% and both indications in 3% of patients. The parenteral route was used in 82% of therapeutic indications and in 63% of prophylactic indications. Third-generation cephalosporins were the most prescribed antimicrobials for therapeutic indications (18%). A high proportion of treated children received antimicrobial combinations (37%). The most commonly treated diagnosis site was the respiratory tract for both therapeutic use (30%) and prophylaxis (25%). The duration of surgical prophylaxis was >1 day in 67%. CONCLUSIONS: Targets identified for quality improvement of antimicrobial use in children included excessive use of antimicrobial combinations and a high proportion of parenteral antimicrobials, both of which require further investigation. Surgical prophylaxis for >1 day should also be curbed in order to achieve quality improvement.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient parenteral antibiotic treatment in Europe.

OBJECTIVES: To assess the proportion of parenteral treatment of the total outpatient antibiotic use in Europe, and to identify the antibiotic groups and individual antibiotics most commonly administered in this way. METHODS: Within the European Surveillance of Antimicrobial Consumption (ESAC; www.esac.ua.ac.be), using the anatomic therapeutic chemical (ATC) and defined daily dose (DDD) classification, data on outpatient use of antibacterials for systemic use (ATC J01), aggregated at the level of the active substance and expressed in DDD per 1000 inhabitants per day (DID; WHO version 2007), were extracted for 2006 by route of administration and by country. Parenteral use was expressed as a percentage of the total outpatient use in DID. RESULTS: In 20 European countries, the total outpatient antibiotic use ranged from 27.91 DID in France to 9.58 DID in Russia. The proportion of outpatient parenteral antibiotic treatment ranged from 6.75% in Russia to 0.001% in Iceland. The three most commonly used antibiotic groups for parenteral treatment in Europe were the cephalosporins (J01D; 44.58%), the aminoglycosides (J01G; 25.27%) and the penicillins (J01C; 17.78%). Four antibiotics [gentamicin (J01GB03) 18.53%; ceftriaxone (J01DD04) 17.85%; cefazolin (J01DB04) 13.16%; and lincomycin (J01FF02) 5.47%] represented more than half of the use. CONCLUSIONS: In all 20 European countries studied together, 2.04% of outpatient antibiotics were used for parenteral treatment. However, as for the total outpatient antibiotic use and the use of different antibiotic groups and antibiotics, there is a striking variation in the proportions of parenteral antibiotic use in Europe. More in-depth data on outpatient antibiotic use are needed to explain this variation.

Human papillomavirus detection in urine: Effect of a first-void urine collection device and timing of collection.

Great interest has been directed towards the use of first-void (FV) urine as a liquid biopsy for high-risk HPV DNA testing. The aim of this study was to investigate the potential effect of a first generation FV urine collection device on the detection of HPV DNA and to assess if the concentration of HPV DNA varies between FV urine collected in the morning and those collected later during the day. In this prospective cohort study, 33 self-reported HPV-positive women participated. An FV urine sample was collected by these women in the morning (first urine of the day) and another sample was collected later that day for four consecutive days using two different collection methods; i.e., the Colli-Pee® and a standard urine cup. Samples were collected at home and returned at ambient temperature to the laboratory by postal mail. HPV DNA testing was conducted with the Riatol qPCR HPV genotyping assay. Based on the combined generalized linear mixed model used, there was no significant impact of the timing of collection (morning versus later during the day) on copies of HPV DNA, whereas Colli-Pee® collected samples show higher HPV concentrations than cup collected samples. However, at high concentrations of hDNA, the benefit of the Colli-Pee® disappeared.

Genotypic diversity, antimicrobial resistance, and virulence factors of human isolates and probiotic cultures constituting two intraspecific groups of Enterococcus faecium isolates.

The intraspecific relationships among a collection of Enterococcus faecium isolates comprising probiotic cultures and human clinical isolates were investigated through the combined use of two high-resolution DNA-fingerprinting techniques. In addition, the incidences of antimicrobial resistance and virulence traits were investigated. A total of 128 E. faecium isolates from human clinical or nonclinical sources or used as probiotic cultures were subjected to fluorescent amplified fragment length polymorphism (FAFLP) fingerprinting and pulsed-field gel electrophoresis (PFGE) analysis of SmaI macrorestriction patterns. Susceptibilities to 16 antimicrobial agents were tested using broth microdilution, and the presence of the corresponding resistance genes was investigated using PCR. Multiplex PCR was used to detect the presence of the enterococcal virulence genes asa1, gelE, cylA, esp, and hyl. The results of the study showed that two intraspecific genomic groups (I and II) were obtained in FAFLP analysis. PFGE analysis demonstrated high variability within these two groups but also indicated that some probiotic cultures were indistinguishable and that a number of clinical isolates may be reisolations of commercial probiotic cultures. Compared to group II, which contained the majority of the probiotic isolates and fewer human clinical isolates, higher phenotypic and genotypic resistance frequencies were observed in group I. Two probiotic isolates were phenotypically resistant to erythromycin, one of which contained an erm(B) gene that was not transferable to enterococcal recipients. None of the probiotic E. faecium isolates demonstrated the presence of the tested virulence genes. The previously reported observation that E. faecium consists of two intraspecific genomic groups was further substantiated by FAFLP fingerprinting of 128 isolates. In combination with antimicrobial resistance and virulence testing, this grouping might represent an additional criterion in assessing the safety of new potential probiotic E. faecium isolates.