Anti-infective Prescription Research Articles

Antibiotic Stewardship (ABS) im Kontext schwerer Infektionen

HintergrundSchwere Infektionen stellen aufgrund der häufigen Komplikationen und hohen Sterblichkeit eine große klinische Herausforderung dar.Ziel der Arbeit (Fragestellung)Am Beispiel der Sepsis, gramnegativer Blutstrominfektionen und COVID-19 sollen Anwendung und Bedeutung von Antibiotic Stewardship(ABS)-Strategien im Kontext schwerer Infektionen erläutert werden.Material und MethodeEs erfolgen die Zusammenfassung der aktuellen Literatur und Empfehlungen mit Fokus auf klinische ABS-Implikationen bei schweren Infektionen wie Sepsis, gramnegativen Blutstrominfektionen und COVID-19.ErgebnisseDie aktualisierte Sepsis-Leitlinie schlägt ein differenziertes Vorgehen zum Beginn der Antibiotikatherapie bei Patient*innen mit Sepsis, aber ohne Schock vor. Bei unsicherer Diagnose und bei fehlendem Schock kann der Zeitraum bis zur Einleitung der Antibiotikatherapie auf 3 h ausgedehnt werden. In dieser Zeit gilt es, die Differenzialdiagnostik und ein adäquates mikrobiologisches Sampling zu komplettieren, um eine Antibiotikatherapie aufgrund belastbarer Befunde zu initiieren oder alternativ zu verwerfen. Bei unkomplizierten gramnegativen Blutstrominfektionen ist eine 7‑tägige antibiotische Therapie ausreichend. Eine regelhafte Kombinationstherapie bei Blutstrominfektionen mit Pseudomonas aeruginosa ist aufgrund der bisher vorliegenden Daten nicht erforderlich. Bakterielle Koinfektionen bei COVID-19 sind selten. Eine prophylaktische antibiotische Therapie ist daher nicht gerechtfertigt. Bakterielle Sekundärinfektionen (> 48 h nach Hospitalisierung) treten v. a. bei kritisch kranken COVID-19-Patient*innen auf. Bei pulmonalen Ko- oder Sekundärinfektion ist ein therapeutisches Vorgehen entsprechend den Pneumonie-Leitlinien geboten.SchlussfolgerungenTrotz der Schwere und Komplexität der genannten Infektionen gelten die grundlegenden Prinzipien des Antibiotic Stewardship (ABS) im Sinne einer rationalen Antiinfektivaverordnung hinsichtlich Substanz, Dosis und Dauer der Therapie.

Impact of medical and pharmaceutical interventions on anti-infective prescriptions: an observational study

Impact of medical and pharmaceutical interventions on anti-infective prescriptions: an observational study

Relationship between antibiotic exposure and subsequent mental health disorders in a primary care health system

ObjectiveTo evaluate the relationship between antibiotic exposure and subsequent psychiatric disorders in a Pediatric primary care setting. Study designWe conducted a retrospective cohort study using electronic clinical record data for patients ages 8–20 years seen in the outpatient setting of a large urban primary health care practice from 1/1/13 to 12/1/2018. We employed adjusted Cox regression analyses to study the relationship between prescriptions for anti-infective agents and subsequent diagnosis of anxiety or depression. ResultsPrescription of anti-infective medication was associated with a hazard rate ratio (HRR) of 1.21 (95%-CI ​= ​1.00–1.45). A first prescription for a broad-spectrum antibiotic (compared to those with no prescription, narrow-spectrum prescription, or topical prescription) was associated with an HRR of 1.27 (95%-CI ​= ​1.04–1.54). The number of anti-infectives prescribed over the course of the study period was associated with an HRR of 1.05 (95%-CI ​= ​1.00–1.10). There was no significant relationship between prescription of topical or narrow-spectrum antibiotics, antifungal, or antiviral medication and subsequent diagnosis of anxiety or depression. Stratified analysis revealed that the association between anti-infective prescription and anxiety and depression was driven by males, among whom prescription of any antibiotic was associated with an HRR of 1.45 (95%-CI ​= ​1.05–1.99). ConclusionsInfections treated with broad-spectrum antibiotics were associated with increased risks of anxiety and/or depression, especially in males. Exploration of the relationship between antibiotic exposure and subsequent mental health disorders is warranted along with continued vigilance in antibiotic prescribing practices in children.

Trends in Outpatient Prescribing Patterns for Ocular Topical Anti-Infectives in Six Major Areas of China, 2013-2019.

Topical anti-infectives are important in the management of ocular infections, but little is known about their current status and trends in their use in China. Thus, we carried out a prescription-based, cross-sectional study using the database of Hospital Prescription Analysis Projection of China, and aimed to analyze the trend in the use of ocular topical anti-infectives for outpatients of the ophthalmology department from 2013 to 2019. A total of 2,341,719 prescriptions from 61 hospitals located in six major areas written by ophthalmologists for outpatients were identified, and 1,002,254 of the prescriptions contained at least one anti-infective. The yearly anti-infective prescriptions increased continuously from 126,828 prescriptions in 2013 to 163,434 prescriptions in 2019. The cost also increased from 4,503,711 Chinese Yuan (CNY) in 2013 to CNY 5,860,945 in 2019. However, the use rate of anti-infectives decreased slightly from 46.5% in 2013 to 41.1% in 2019. Patients aged between 19 and 45 years old had the highest anti-infective use rate. Levofloxacin was the most frequently used anti-infective and kept on increasing among all age groups, occupying 67.1% of the total cost at the end of the study. Tobramycin was more frequently used in pediatric patients than in adults, but the use still decreased. Ganciclovir was the preferred anti-viral drug over acyclovir. In conclusion, the prescriptions and cost of ocular topical anti-infectives for outpatients both increased progressively. The increasingly widespread use of levofloxacin raised concerns regarding safety in pediatrics and resistance development. The observed trends can lead to the more efficient management of ocular anti-topical anti-infectives in China.

Structural stigma and sexual orientation disparities in healthcare use: Evidence from Australian Census-linked-administrative data.

This study explores the extent to which structural stigma (which encompasses sociocultural and institutional constraining factors) is associated with sexual orientation disparities in healthcare service and prescription medicine use. Using the responses to the 2017 Australian Marriage Law Postal Survey, we use the regional percentage of votes against legalising same-sex marriage as a measure of structural stigma. We then map these results to Census-linked-administrative data, including 83,519 individuals in same-sex relationships - one of the largest administrative datasets to date where individuals in same-sex relationships are identified. Controlling for regional and individual-level confounders, we find that structural stigma is associated with increased use of nervous system medications (which largely comprise antidepressants) but reduced GP visits for both females and males in same-sex relationships. More regional stigma is also associated with reduced use of pathology services and anti-infective prescriptions for males in same-sex relationships. Altogether, our results suggest that individuals in same-sex relationships living in stigmatised regions are in poorer health but are less likely to access primary healthcare.

Impact and longevity of measles-associated immune suppression: a matched cohort study using data from the THIN general practice database in the UK

ObjectiveTo test the hypothesis that measles infection increases the incidence of non-measles infectious diseases over a prolonged period of time.DesignA population-based matched cohort study.Data sourcesThis study examined children aged 1–15...

Does low risk of infections as a marker of effective immunity predict increased risk of subsequent giant cell arteritis or polymyalgia rheumatica? A Danish population-based case-control study.

ObjectiveIt has been suggested that a hyper-effective immune system (“hyper-immunity”) is central to the pathogenesis of giant cell arteritis and polymyalgia rheumatica (GCA/PMR). We examined if a low risk of infections, as a marker of hyper-immunity, can predict increased subsequent risk of GCA/PMR.Patients and methodsWe conducted a population-based case–control study including all patients aged ≥50 years with incident GCA/PMR diagnosed between 1997 and 2012 in Northern Denmark. For each case, we selected 10 population controls matched on gender, age, place of residence, and time spent in the region. Complete history of hospital-treated infections and community-based anti-infective prescriptions was assessed in population-based registries. We used conditional logistic regression to compute OR of GCA/PMR associated with infections while adjusting for comorbidities, immunosuppressive treatment, and other potential confounders.ResultsWe included 7,225 GCA/PMR cases and 72,250 controls. When excluding all infections occurring within the last year before GCA/PMR diagnosis, there was no decreased risk for GCA/PMR in people with a history of hospital-treated infection (adjusted OR=1.04, 95% CI: 0.98–1.10) or community anti-infective treatment (adjusted OR=1.07, 95% CI: 0.99–1.16). Within the last year preceding the GCA/PMR index date, patients with hospital-treated infections (adjusted OR=1.59, 95% CI: 1.44–1.75) or community anti-infective treatment (adjusted OR=1.63, 95% CI: 1.48–1.79) had a greatly increased risk of a GCA/PMR diagnosis.ConclusionThese results do not support the hypothesis of “hyper-immunity” leading to GCA/PMR. Instead, incident GCA/PMR is preceded by a slightly increased risk of infection, which may be related to protopathic bias or support theories that infections may be directly involved in the pathogenesis of GCA/PMR.

Use of an Anti-Infective Medication Review Process at Hospital Discharge to Identify Medication Errors and Optimize Therapy

Background: Medication reconciliation is a major patient safety concern, and the impact of a structured process to evaluate anti-infective agents at hospital discharge warrants further review. Objective: The aim of this study was to (1) describe a structured, multidisciplinary approach to review anti-infectives at discharge and (2) measure the impact of a stewardship-initiated antimicrobial review process in identifying and preventing anti-infective-related medication errors (MEs) at discharge. Methods: A prospective study to evaluate adult patients discharged on anti-infectives was conducted from October 2013 to May 2014. The antimicrobial stewardship program (ASP) classified interventions on anti-infective regimens into predefined ME categories. Results: Forty-five patients who were discharged on 59 anti-infective prescriptions were included in the study. The most common indications for anti-infective regimens at discharge were pneumonia (22%, n = 10), bacteremia (18%, n = 8), and skin and soft tissue infections (16%, n = 7). An ME was identified in 42% (n = 19/45) of anti-infective regimens. Seventy percentage of ASP team recommendations were accepted which resulted in an avoidance of MEs in 68% (n = 13/19) of patients with an ME prior to discharge. Conclusion: This study describes the outcomes of a stewardship-initiated review process in preventing MEs at discharge. Developing a systematic process for a multidisciplinary ASP team to review all anti-infectives can be a valuable tool in preventing MEs at hospital discharge.

PS-094 Pharmaceutical interventions in infectious diseases

BackgroundPrescriptions analysis and validation is one of the clinical pharmacist’s main tasks. In our pharmacy, one unit is dedicated solely to the validation of antibiotics and antifungal prescriptions from every...

Compliance with Renal Dosing Guidelines for Outpatient Antiinfective Prescriptions

Background: More than 80–95% of adverse drug events occurring among renally impaired patients are related to excessive dosing. Objective: To assess current prescribing practices with antiinfectives for patients with estimated creatinine clearance (CrCl) less than 51 mL/min who were in a local health care system. Methods: Outpatient antiinfective prescriptions written during a 10-day period in July 2012 were reviewed. The following information was collected for each patient: age, sex, serum creatinine, weight, height, drug dose and schedule, and discharge unit/outpatient service. Kidney function was estimated by calculating CrCl using either the Cockcroft-Gault or the Jelliffe equation. Two resources were used to identify appropriate dosing for renal function; if the 2 resources differed, the stricter of the 2 was used for assessment. Institutional review board approval was obtained for this study. Results: A total of 91 prescriptions, written for 87 different patients, met inclusion criteria and were reviewed. Average CrCl and age among the study population was 37.82 mL/min, and 75.7 years, respectively. Doses were excessive in 30% of outpatient prescriptions. The most common medications involved in excessive dosing were trimethoprim/sulfamethoxazole (TMP/SMX), cephalexin, fluconazole, and acyclovir. TMP/SMX was dosed excessively in 80% of prescriptions. Both fluconazole and acyclovir were dosed excessively in 75% of prescriptions, while cephalexin was dosed in excess in 36% of prescriptions. A comparison of discharge units/outpatient services revealed that 56% of prescriptions from urgent care centers were dosed in excess, compared with 30% from hospital discharge, 20% from emergency department discharge, and 25% from outpatient services. Conclusions: Our study indicates that there is room for improvement when dosing antiinfective medications for outpatients with renal insufficiency. Appropriate renal dosing can help protect patients from dangerous toxicities and other adverse drug events.

Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants

The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. HCP potently increases the current amplitude of KCNQ1/KCNE1 expressed by stabilizing the channel in an open state with an EC50 of 4.61±1.29 μM. Further studies in cardiomyocytes showed that HCP significantly shortens the action potential duration at 1 μM. In addition, HCP is capable of rescuing the loss of function of the LQTs mutants caused by either impaired activation gating or phosphatidylinositol-4,5-bisphosphate (PIP2) binding affinity. Our results indicate HCP is a novel KCNQ1/KCNE1 activator and may be a useful tool compound for the development of LQTs therapeutics.

L'hygiène hospitalière et le conseil en antibiothérapie : un duo opérationnel face au problème de la diffusion des bactéries multirésistantes aux antibiotiques

The authors had for aim to show that preventing the diffusion of multidrug-resistant organism (MRO) is possible thanks to the coordination of recommended preventive actions and the implementation of a sensible anti-infective prescription policy. They also wanted to highlight the role played by the nursing care staff in enforcing recommendations. We compared the results of two health care facilities having both implemented the same strategy aimed at preventing cross-transmission and prescribing anti-infective drugs. Audits reported a very variable enforcement of recommendations. The results obtained from microbiological monitoring confirmed the essential impact of protocol enactment by every team, on the control of MRO diffusion. The antibiotherapy specialist has a key role in the suggested strategy, allowing a significant decrease in the number of anti-infective prescriptions and a more rational use. The collaboration of a hygiene specialist with an antibiotherapy specialist has proved operational in the fight against MRO diffusion, as long as the competences of both specialists are acknowledged and their cross-disciplinary activities accepted. For the entire staff, enacting a corporate culture is a crucial asset.

Multicentre evaluation of prescribing concurrence with anti-infective guidelines: epidemiological assessment of indicators.

To assess indicators for anti-infective prescribing not concurrent with regional pharmacotherapeutic treatment guidelines (PTGs) on infectious diseases. A retrospective explorative cohort study based on hospital-wide anti-infective prescription data of a 2-month cross-sectional period (n = 1037). Risk rates (absolute risks: AR), risk rate ratios (relative risks: RR) and odds ratios (OR) with 95% confidence intervals (95%CI) were estimated for patient, disease, drug, and prescriber variables considered to be potential indicators. Univariable and multivariable logistic regression analyses were performed. Non-concurrence existed of non-indicated prescribing of (particular) anti-infectives (24.3%) and prescribing of non-first choice anti-infectives (55.2%). Non-concurrent durations of treatment and dosing issues accounted for 17.2% and 16.2% respectively. Non-concurrence was associated with empirical therapy, with certain diagnoses, such as skin and soft tissue, urinary, and osteoarthrological infections, and with prescriptions involving topical dosage forms, cephalosporins, macrolides and lincosamides, and quinolones. There was also an association with certain hospitals and with prescribing by geriatricians, surgeons, pulmonologists, and urologists and, in general, junior clinicians in training. Other hospitals could use our epidemiological framework to identify their own indicators for non-concurrent prescribing. Our findings suggest tailor-made enforcement of PTG adherence for certain prescribers while conversely, adaptation of the PTGs will be required for some infectious diseases.

Epidemiological evaluation of hospital prescribing concurrence with pharmacotherapeutic guidelines on infectious diseases

Rational prescribing of anti-infectives is necessary for reasons of effectiveness, safety, resistance, and costs [1]. The aim was to assess indicators for anti-infective prescribing not concurrent with regional pharmacotherapeutic treatment guidelines (PTGs) on infectious diseases. The study was carried out in departments of clinical pharmacology in four general teaching hospitals in the Friesland Province, the Netherlands. A retrospective explorative cohort study based on hospital-wide anti-infective prescription data of a 2 month cross-sectional study period (n=1037). Data were univariably and subsequently, multivariably analysed using conditional stepwise logistic regression analysis. Absolute risks (AR), relative risks (RR) and odds ratios (OR) with 95% confidence intervals (95% CI) were estimated for patient, therapy, drug, and prescriber variables considered to be potential indicators for non-concurrent prescribing (P<0.05). At least 40% of all prescriptions were not concurrent with the PTGs. Overall, non-concurrence mainly existed of non-indicated prescribing of (particular) anti-infectives (24.3%) and prescribing of non-first choice anti-infectives (55.2%). Non-concurrent durations of treatment and dosing issues accounted for 17.2% and 16.2% respectively. Non-concurrence was associated with empiric therapy (OR 3.4, 95% CI 2.3, 5.1), with certain diagnoses, such as skin and soft tissue (OR 2.9, 95% CI 1.3, 6.5), urinary (OR 2.2, 95% CI 1.2, 4.0), and osteoarthrological infections (OR 5.4, 95% CI 11.6, 18.7), and with prescriptions involving topical dosage forms (RR 2.1, 95% CI 1.6, 2.5), cephalosporins (OR 2.1, 95% CI 1.3, 3.5), macrolides and lincosamides (OR 5.9, 95% CI 2.7, 12.0), and quinolones (OR 2.2, 95% CI 1.2, 4.1). There was also an association with prescribing geriatricians (RR 2.3, 95% CI 1.5, 3.6), surgeons (OR 2.0, 95% CI 1.4, 3.2), pulmonologists (RR 1.6, 96% CI 1.3, 2.1), and urologists (RR 2.0, 95% CI 1.1, 3.07) and, in general, assistant clinicians (RR 1.8, 95% CI 1.2, 3.8). We have provided an epidemiological framework that each hospital can use to evaluate anti-infective prescribing and assess its own predictors. Our study has been able to confirm expert opinions on supposed predictors [2, 3]. The nature and frequency of our hospitals' non-concurrence was such that tailor-made enforcement of PTG adherence will be required for some drug groups whereas for other drug groups the contents of the PTGs will be adapted.