Quantifying topical antimicrobial use before and during participation in an antimicrobial stewardship programme in Dutch companion animal clinics

The emergence of bacterial strains resistant to topical antimicrobials in both human and veterinary medicine has raised concerns over retaining the efficacy of these preparations. Yet, little information is available regarding the use of topical antimicrobials in either sector for planning targeted interventions. This study aims to quantify the use of topical antimicrobials in 44 Dutch companion animal clinics before and during their participation in an antimicrobial stewardship programme (ASP), to explore the effect of the intervention on topical antimicrobial use (AMU). Hence, prescription and clinic animal population data, collected from July 2012 until June 2018 were used. Specifically, the period from July 2012 until June 2015 was defined as pre-intervention period, whereas clinics started to participate in the ASP from March 2016 onwards. As quantification metric, the Defined Daily Dose for Animals (DDDA) was used and a mixed effect times series model with auto-regression was applied to monthly topical AMU data. The intervention effect was modelled using a step function with a change in (linear) time trend and clinic characteristics, as potential determinants of topical AMU, were assessed using a multivariable regression model. A seasonal pattern was identified, in the pre-intervention period, where topical AMU was highest in July-August and lowest in February-March. In addition, total topical AMU appeared to significantly decrease over time in the pre-intervention period and the proportion of dogs in the clinic was positively associated with topical AMU. The intervention effect was significant only for second line and for skin product AMU. This study demonstrates that during participation in an ASP, second line and skin product AMU decreased in Dutch companion animal clinics. Additionally, this study demonstrates the existence of a seasonal effect and a decrease in topical AMU over time already before introduction of a targeted intervention

Ο ρόλος του Ο.Α.Σ.Π. στους μεγάλους σεισμούς της Ελλάδας

Οι σεισμοί του 1978 στη Θεσσαλονίκη και του 1981στην Αθήνα συνετέλεσαν στην ίδρυση το 1983 του Οργανισμού Αντισεισμικού Σχεδιασμού και Προστασίας. Σε όλα τα μετέπειτα σημαντικά σεισμικά γεγονότα στην Ελλάδα ο Οργανισμός έλαβε μέρος στην διαχείριση της έκτακτης ανάγκης, ως σύνδεσμος μεταξύ Πολιτείας, πολίτη, τεχνικού δυναμικού της χώρας, ερευνητικών και ακαδημαϊκών φορέων. Το 1986 ο καταστροφικός σεισμός 6,2R στη Μεσσηνία προκάλεσε ανθρώπινα θύματα, σημαντικές ζημιές στις κατασκευές και υποδομές με κοινωνικές και οικονομικές επιπτώσεις. Το 1988 ισχυρός σεισμός 6.0 R.στην Ηλεία,προκάλεσε σημαντικές βλάβες στο λιμάνι της Κυλλήνης, Βαρθολομιό,στο φράγκικο κάστρο, ρευστοποιήσεις στις εκβολές του Πηνειού και μετάθεση ακτογραμμών. Το 1995 ισχυρός σεισμός 6.6R.έπληξε τα Γρεβενά και την Κοζάνη. Πολλά χωριά καταστράφηκαν. Υπήρξαν τραυματισμοί, καταρρεύσεις κτιρίων και διάφορες βλάβες από το σεισμό Το 1995 επίσης ισχυρός σεισμός 6.2R. στο Αίγιο, προκάλεσε πολλά ανθρώπινα θύματα και σοβαρές υλικές καταστροφές, κατάρρευση πολυκατοικίας και ξενοδοχείου, διάρρηξη εδάφους, ρευστοποιήσεις, αποκόλληση ακτών, κατολισθήσεις. Το 1999 ο σεισμός της Αθήνας, 5,9R., προκάλεσε επίσης πολλά ανθρώπινα θύματα και σημαντικές ζημιές στις κατασκευές και υποδομές. Το 2003 ισχυρός σεισμός 6,4 R.στη Λευκάδα προκάλεσε βλάβες σε κτίρια, μνημεία πολιτιστικής κληρονομιάς, λιμάνια και πτώσεις βράχων. Το 2006 ο ισχυρός σεισμός 6,9R.στη θαλάσσια περιοχή των Κυθήρων – Αντικυθήρων προκάλεσε βλάβες σε παλαιά κυρίως σπίτια, στην πλατεία, στην εκκλησία, ζημιές και πτώσεις βράχων. Τον Απρίλιο 2007 σεισμικές δονήσεις με μεγέθη 5 και 5.4 βαθμών της κλίμακας Richter στην λίμνη Τριχωνίδα στην Αιτωλοακαρνανία προκάλεσαν ρωγμές σε κτίρια και βλάβες σε χωριά. Το 2008 οισχυρός σεισμός μεγέθους 6,5R.στη Β.Δ. Πελοπόννησο, κυρίως στην Ηλεία και Αχαία προκάλεσε ανθρώπινες απώλειες, τραυματισμούς και βλάβες σε κτίρια, στο σιδηροδρομικό δίκτυο καθώς και βροχοπτώσεις, ρευστοποιήσεις κ.λ.π. Τον Αύγουστο του 2013 ισχυρός σεισμός μεγέθους5.1R. στην περιοχή Αμφίκλειας - Ρεγκινίουστη Φθιώτιδα προκάλεσε ρωγμές, διακοπή ρεύματος κ.ά. 4 Τον Ιανουάριο του 2013 στην πολύ ισχυρή σεισμική δόνηση 5,8R.στο θαλάσσιο χώρο 44km ΑΝΑ της Λήμνου δεν υπήρξαν αναφορές για ζημιές. Το 2014 πολύ ισχυρές σεισμικές δονήσεις 5,8και 5,7 R. στην Κεφαλονιά προκάλεσαν βλάβες σε κτίρια και υποδομές, (λιμάνι Ληξουρίου), βραχοπτώσεις, κατολισθήσεις και εδαφικές διαρρήξεις. Το 2015η πολύ ισχυρή σεισμική δόνηση 6,0 R., με επικεντρική περιοχή 13 χλμ. Δ της Λευκάδας προκάλεσε δύο θύματα, και βραχοπτώσεις. Το 2016 ισχυρή σεισμική δόνηση 5,3 R., με επικεντρική περιοχή 12 χλμ. ΒΔ των Ιωαννίνων και σεισμική ακολουθία περίπου δύο μηνών, προκάλεσε καταπτώσεις βραχοτεμαχίων. Το 2017 πολύ ισχυρή σεισμική δόνηση 6.1 R. στη Λέσβο, στον θαλάσσιο χώρο 34km ΝΝΔ της Μυτιλήνης προκάλεσε το θάνατο ενός ανθρώπου και εκτεταμένες βλάβες σε κτίρια. Το 2017 η πολύ ισχυρή σεισμική δόνηση 6.2R.,σε εστιακό βάθος 10km, 23km Β.Α. της Κω., προκάλεσε ανθρώπινα θύματα, τραυματίες, βλάβες σε κτίρια, μνημεία πολιτιστικής κληρονομιάς και στο κύριο λιμάνι της νήσου.The earthquakes of 1978 in Thessaloniki and of 1981 in Athens led to the establishment in 1983 of the Organization for Antiseismic Planning and Protection (O.A.P.P.). At all subsequent significant seismic events in Greece, the Organization has taken part in the administration of the emergency events, as link between the State, the citizens, the technical manpower of the country, research and academic establishments. In 1986, a catastrophic earthquake 6,2 R in Messinia caused fatalities, significant damages to buildings and the infrastructure, with social and economic repercussions. In 1988, a powerful earthquake 6,0 R in Ilia, caused significant damages to the Kyllini port, Bartholomio, the historic castle, earth liquidization at the estuaries of Pinios river and movement of shore lines. In 1995, a powerful earthquake 6,6 R hit Grevena and Kozani. Many villages were destroyed. There were injuries, building collapses and various damages due to the seismic vibration. In 1995 also, a powerful earthquake 6,2 R in Aegio, caused a lot of fatalities and serious material damages, collapse of a block of flats and a hotel, earth cracking and liquidization, share detachment and landslides. In 1999, the earthquake in Athens of 5,9 R, caused also a lot of fatalities and significant damages to buildings and infrastructure. In 2003, a powerful earthquake 6,4 R in Leukada Island, caused damages to buildings, monuments, ports and rock falls. In 2006, a powerful earthquake 6,9 R at the sea area of Kythira and Antikythira islands, caused damages to (mainly) old houses, the square, the church, and rock falls. In April 2007, seismic vibrations at the size of 5 and 5,4 R at Trichonida lake in Aitoloakarnania, caused crackings to buildings and damages to villages. In 2008, the powerful earthquake 6,5 R at N.W. Peloponnese, mainly at Ilia and Achaia, caused fatalities, injuries and damages to buildings, the railway network as well as rock falls and soil liguidization. In August 2013, a powerful earthquake 5,1 R in the area of Amphikleia – Reginio in Pthiotida, caused crackings, power interruptions, etc. In January 2013, at the strong scismic vibration 5,8 R in the sea area 44 km East of Limnos island, there were no reports for damages. 6 In 2014, strong seismic vibrations 5,8 and 5,7 R in Kefalonia island, caused damages to buildings and infrastructure (Lixouri port), rock falls, landslides and earth crackings. In 2015, the powerful seismic vibration 6,0 R with epicentric area 13 km West of Leukada island, caused two fatalities and rock falls. In 2016, a powerful seismic vibration 5,3 R, with epicentric area 12 km NW of loannina followed by a seismic sequence of about 2 months, caused rock falls. In 2017, a powerful earthquake 6,1 R at the sea area 34 km SW of Lesbos island, caused one fatality and extended damages to buildings. In 2017, a powerful earthquake 6,2 R at a focal depth of 10 Km, 23Km NE of Kos island, caused fatalities, injuries, damages to buildings, monuments and the main port of the island

Quantifying topical antimicrobial use before and during participation in an antimicrobial stewardship programme in Dutch companion animal clinics

The emergence of bacterial strains resistant to topical antimicrobials in both human and veterinary medicine has raised concerns over retaining the efficacy of these preparations. Yet, little information is available regarding the use of topical antimicrobials in either sector for planning targeted interventions. This study aims to quantify the use of topical antimicrobials in 44 Dutch companion animal clinics before and during their participation in an antimicrobial stewardship programme (ASP), to explore the effect of the intervention on topical antimicrobial use (AMU). Hence, prescription and clinic animal population data, collected from July 2012 until June 2018 were used. Specifically, the period from July 2012 until June 2015 was defined as pre-intervention period, whereas clinics started to participate in the ASP from March 2016 onwards. As quantification metric, the Defined Daily Dose for Animals (DDDA) was used and a mixed effect times series model with auto-regression was applied to monthly topical AMU data. The intervention effect was modelled using a step function with a change in (linear) time trend and clinic characteristics, as potential determinants of topical AMU, were assessed using a multivariable regression model. A seasonal pattern was identified, in the pre-intervention period, where topical AMU was highest in July-August and lowest in February-March. In addition, total topical AMU appeared to significantly decrease over time in the pre-intervention period and the proportion of dogs in the clinic was positively associated with topical AMU. The intervention effect was significant only for second line and for skin product AMU. This study demonstrates that during participation in an ASP, second line and skin product AMU decreased in Dutch companion animal clinics. Additionally, this study demonstrates the existence of a seasonal effect and a decrease in topical AMU over time already before introduction of a targeted intervention

Effect estimates for potential determinants of topical AMU.

The results are the output of a multivariable regression model for total, first line, second line topical AMU and ear and eye product AMU. The data are log-transformed.</p

Results of the statistical model regarding the pre-intervention period (July 2012-June 2015).

(a) Time trend over the months with y-axis displaying the geometric mean ratio (GMR) and x-axis the date (year and month). Time trends were modelled using natural regression splines. The GMR compares the geometric mean (GM) of topical AMU in each month to the average GM across the three-year period (GMR = 1 on January 2014 by definition). The grey lines depict the clinic-specific estimates, whereas the red line depicts the mean of the random effects distribution. Time trend is displayed for total topical AMU. (b) Seasonal pattern of total topical AMU. In the y-axis the GMR is displayed and on the x-axis the months. The seasonal effect was modelled using harmonic functions. The GMR compares the GM of topical AMU in each month to the average GM across the year (GMR = 1 on the month of May by definition). The grey lines depict the clinic-specific estimates, whereas the red line depicts the mean of the random effects distribution.</p

Intervention effect regarding 2^nd line topical AMU.

Intervention effect regarding 2nd line topical AMU.</p

Separate intervention elements as offered during the ASP.

The time point when these elements were offered as well as who were involved and the estimated time investment are displayed. “S-team”refers to a Support-Team that was assembled for the ASP and is comparable to the human Antibiotic Stewardship-Teams (A-teams). The S-team was comprised of a veterinary microbiologist, a veterinary specialist in internal medicine of companion animals, a veterinary pharmacologist, a hospital pharmacist and the project leader. (TIF)</p

Classification of veterinary AMU according to Dutch policy on veterinary AMU [25].

Classification of veterinary AMU according to Dutch policy on veterinary AMU [25].</p

Intervention effect regarding 1^st line topical AMU.

Intervention effect regarding 1st line topical AMU.</p

Intervention effect regarding skin product AMU.

The emergence of bacterial strains resistant to topical antimicrobials in both human and veterinary medicine has raised concerns over retaining the efficacy of these preparations. Yet, little information is available regarding the use of topical antimicrobials in either sector for planning targeted interventions. This study aims to quantify the use of topical antimicrobials in 44 Dutch companion animal clinics before and during their participation in an antimicrobial stewardship programme (ASP), to explore the effect of the intervention on topical antimicrobial use (AMU). Hence, prescription and clinic animal population data, collected from July 2012 until June 2018 were used. Specifically, the period from July 2012 until June 2015 was defined as pre-intervention period, whereas clinics started to participate in the ASP from March 2016 onwards. As quantification metric, the Defined Daily Dose for Animals (DDDA) was used and a mixed effect times series model with auto-regression was applied to monthly topical AMU data. The intervention effect was modelled using a step function with a change in (linear) time trend and clinic characteristics, as potential determinants of topical AMU, were assessed using a multivariable regression model. A seasonal pattern was identified, in the pre-intervention period, where topical AMU was highest in July-August and lowest in February-March. In addition, total topical AMU appeared to significantly decrease over time in the pre-intervention period and the proportion of dogs in the clinic was positively associated with topical AMU. The intervention effect was significant only for second line and for skin product AMU. This study demonstrates that during participation in an ASP, second line and skin product AMU decreased in Dutch companion animal clinics. Additionally, this study demonstrates the existence of a seasonal effect and a decrease in topical AMU over time already before introduction of a targeted intervention.</div