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To assess the effect of new legislation on the dispensing of antimicrobials without prescription from pharmacies in Greece.
The study included 110 pharmacies in the greater Athens Metropolitan area.
Volunteer collaborators visited 110 pharmacies in the greater Athens Metropolitan area in December 2021 and January 2022. They asked for either ciprofloxacin or amoxicillin-clavulanate acid (6:5 ratio) without providing a prescription, without simulating symptoms, and without offering justification or insisting. Fluoroquinolones have additional dispensing restrictions in Greece. Results were compared to a 2008 study. In 2020, legislation allowed the dispensing of antibiotics from pharmacies only with an electronic prescription, overriding the 1973 forbidding the dispensing of all medications without prescriptions.
All pharmacists refused to dispense ciprofloxacin without a prescription. Only 1 pharmacy dispensed amoxicillin-clavulanate without a prescription. Compared to the 2008 study, dispensing of amoxicillin-clavulanate without a prescription dropped from 100% in 2008 to 1% in 2021 and dispensing ciprofloxacin without a prescription dropped from 53% in 2008 to 0% in 2021.
A new and enforced law that requires electronic prescribing led to a dramatic reduction of antibiotic dispensing without prescription compared to 12 years ago. Similar initiatives could help solve the problem of antibiotic consumption and resistance in Greece and elsewhere.
We surveyed antimicrobials used in Greek pediatric hematology–oncology (PHO) and bone marrow transplant (BMT) units before and after an intervention involving education regarding the 2017 clinical practice guidelines (CPG) for the management of febrile neutropenia in children with cancer and hematopoietic stem-cell transplant recipients.
Antibiotic prescribing practices were prospectively recorded between June 2016 and November 2017.
In December 2017, baseline data feedback was provided, and CPG education was provided. Prescribing practices were followed for one more year. For antibiotic stewardship, days of therapy, and length of therapy were calculated.
Five of the 6 PHO units in Greece and the single pediatric BMT unit participated.
Admitted children in each unit who received the first 15 new antibiotic courses each month.
Administration of ≥4 antibiotics simultaneously and administration of antibiotics with overlapping activity for ≥2 days were significantly more common in PHO units in general hospitals compared to children’s hospitals. Use of at least 1 antifungal was recorded in ∼47% of the patients before and after the intervention. De-escalation and/or discontinuation of antibiotics on day 6 of initial treatment increased significantly from 43% to 53.5% (P = .032). Although the number of patients requiring intensive care support for sepsis did not change, a significant drop was noted in all-cause mortality (P = .008).
We recorded the antibiotic prescribing practices in Greek PHO and BMT units, we achieved improved prescribing with a simple intervention, and we identified areas in need of improvement.
To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.
The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).
Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.
A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level “harm index” for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.
We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.
To audit clinical practice and implement an intervention to promote appropriate use of perioperative antimicrobial prophylaxis (PAP).
Prospective multicenter before-and-after study.
This study was conducted in 7 surgical departments of 3 major Greek hospitals.
Active PAP surveillance in adults undergoing elective surgical procedures was performed before and after implementation of a multimodal intervention. The surveillance monitored use of appropriate antimicrobial agent according to international and local guidelines, appropriate timing and duration of PAP, overall compliance with all 3 parameters and the occurrence of surgical site infections (SSIs). The intervention included education, audit, and feedback.
Overall, 1,447 patients were included: 768 before and 679 after intervention. Overall compliance increased from 28.2% to 43.9% (P = .001). Use of antimicrobial agents compliant to international guidelines increased from 89.6% to 96.3% (P = .001). In 4 of 7 departments, compliance with appropriate timing was already >90%; an increase from 44.3% to 73% (P = .001) and from 20.4% to 60% (P = .001), respectively, was achieved in 2 other departments, whereas a decrease from 64.1% to 10.9% (P = .001) was observed in 1 department. All but one department achieved a shorter PAP duration, and most achieved duration of ~2 days. SSIs significantly decreased from 6.9% to 4% (P = .026). After the intervention, it was 2.3 times more likely for appropriate antimicrobial use, 14.7 times more likely to administer an antimicrobial for the appropriate duration and 5.3 times more likely to administer an overall appropriate PAP.
An intervention based on education, audit, and feedback can significantly contribute to improvement of appropriate PAP administration; further improvement in duration is needed.
To estimate the attributable mortality, length of stay (LOS), and healthcare cost of pediatric and neonatal healthcare-acquired bloodstream infections (HA-BSIs).
A systematic review and meta-analysis.
A systematic search (January 2000–September 2018) was conducted in PubMed, Cochrane, and CINAHL databases. Reference lists of selected articles were screened to identify additional studies. Case–control or cohort studies were eligible for inclusion when full text was available in English and data for at least 1 of the following criteria were provided: attributable or excess LOS, healthcare cost, or mortality rate due to HA-BSI. Study quality was evaluated using the Critical Appraisal Skills Programme Tool (CASP). Study selection and quality assessment were conducted by 2 independent researchers, and a third researcher was consulted to resolve any disagreements. Fixed- or random-effect models, as appropriate, were used to synthesize data. Heterogeneity and publication bias were evaluated.
In total, 21 studies were included in the systematic review and 13 studies were included in the meta-analysis. Attributable mean LOS ranged between 4 and 27.8 days; healthcare cost ranged between $1,642.16 and $160,804 (2019 USD) per patient with HA-BSI; and mortality rate ranged between 1.43% and 24%. The pooled mean attributable hospital LOS was 16.91 days (95% confidence interval [CI], 13.70–20.11) and the pooled attributable mortality rate was 8% (95% CI, 6–9). A meta-analysis was not conducted for cost due to lack of eligible studies.
Pediatric HA-BSIs have a significant impact on mortality, LOS, and healthcare cost, further highlighting the need for implementation of HA-BSI prevention strategies.
Active daily surveillance of central-line days (CLDs) in the assessment of rates of central-line–associated bloodstream infections (CLABSIs) is time-consuming and burdensome for healthcare workers. Sampling of denominator data is a method that could reduce the time necessary to conduct active surveillance.
To evaluate the accuracy of various sampling strategies in the estimation of CLABSI rates in adult and pediatric units in Greece.
Daily denominator data were collected across Greece for 6 consecutive months in 33 units: 11 adult units, 4 pediatric intensive care units (PICUs), 12 neonatal intensive care units (NICUs), and 6 pediatric oncology units. Overall, 32 samples were evaluated using the following strategies: (1) 1 fixed day per week, (2) 2 fixed days per week, and (3) 1 fixed week per month. The CLDs for each month were estimated as follows: (number of sample CLDs/number of sampled days) × 30. The estimated CLDs were used to calculate CLABSI rates. The accuracy of the estimated CLABSI rates was assessed by calculating the percentage error (PE): [(observed CLABSI rates − estimated CLABSI rates)/observed CLABSI rates].
Compared to other strategies, sampling over 2 fixed days per week provided the most accurate estimates of CLABSI rates for all types of units. Percentage of estimated CLABSI rates with PE ≤±5% using the strategy of 2 fixed days per week ranged between 74.6% and 88.7% in NICUs. This range was 79.4%–94.1% in pediatric onology units, 62.5%–91.7% in PICUs, and 80.3%–92.4% in adult units. Further evaluation with intraclass correlation coefficients and Bland-Altman plots indicated that the estimated CLABSI rates were reliable.
Sampling over 2 fixed days per week provides a valid alternative to daily collection of CLABSI denominator data. Adoption of such a monitoring method could be an important step toward better and less burdensome infection control and prevention.
To determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection.
Three-arm nonmasked randomized controlled trial.
Five academic medical centers in Southeastern Pennsylvania.
Adults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members.
Enrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders.
MAIN OUTCOME MEASURES
Owing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case.
Of 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018).
Total household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearance
Following implementation of automatic end dates for antimicrobial orders to facilitate antimicrobial stewardship at a large, academic children’s hospital, no differences were observed in patient mortality, length of stay, or readmission rates, even among patients with documented bacteremia.
The incidence of Clostridium difficile infection (CDI) has increased and has been associated with poor outcomes among hospitalized children, including increased risk of death. The purpose of this study was to identify risk factors for all-cause in-hospital mortality among children with CDI.
A multicenter cohort of children with CDI, aged 1–18 years, was established among children hospitalized at 41 freestanding children’s hospitals between January 1, 2006 and August 31, 2011. Children with CDI were identified using a validated case-finding tool (ICD-9-CM code for CDI plus C. difficile test charge). Only the first CDI-related hospitalization during the study period was used. Risk factors for all-cause in-hospital mortality within 30 days of C. difficile test were evaluated using a multivariable logistic regression model.
We identified 7,318 children with CDI during the study period. The median age of this cohort was 6 years [interquartile range (IQR): 2–13]; the mortality rate was 1.5% (n=109); and the median number of days between C. difficile testing and death was 12 (IQR, 7–20). Independent risk factors for death included older age [adjusted odds ratio (OR, 95% confidence interval), 2.29 (1.40–3.77)], underlying malignancy [3.57 (2.36–5.40)], cardiovascular disease [2.06 (1.28–3.30)], hematologic/immunologic condition [1.89 (1.05–3.39)], gastric acid suppression [2.70 (1.43–5.08)], and presence of >1 severity of illness marker [3.88 (2.44–6.19)].
Patients with select chronic conditions and more severe disease are at increased risk of death. Identifying risk factors for in-hospital mortality can help detect subpopulations of children that may benefit from targeted CDI prevention and treatment strategies.
Infect Control Hosp Epidemiol 2015;36(10):1183–1189
To identify risk factors for recurrent methicillin-resistant Staphylococcus aureus (MRSA) colonization.
Prospective cohort study conducted from January 1, 2010, through December 31, 2012.
Five adult and pediatric academic medical centers.
Subjects (ie, index cases) who presented with acute community-onset MRSA skin and soft-tissue infection.
Index cases and all household members performed self-sampling for MRSA colonization every 2 weeks for 6 months. Clearance of colonization was defined as 2 consecutive sampling periods with negative surveillance cultures. Recurrent colonization was defined as any positive MRSA surveillance culture after clearance. Index cases with recurrent MRSA colonization were compared with those without recurrence on the basis of antibiotic exposure, household demographic characteristics, and presence of MRSA colonization in household members.
The study cohort comprised 195 index cases; recurrent MRSA colonization occurred in 85 (43.6%). Median time to recurrence was 53 days (interquartile range, 36–84 days). Treatment with clindamycin was associated with lower risk of recurrence (odds ratio, 0.52; 95% CI, 0.29–0.93). Higher percentage of household members younger than 18 was associated with increased risk of recurrence (odds ratio, 1.01; 95% CI, 1.00–1.02). The association between MRSA colonization in household members and recurrent colonization in index cases did not reach statistical significance in primary analyses.
A large proportion of patients initially presenting with MRSA skin and soft-tissue infection will have recurrent colonization after clearance. The reduced rate of recurrent colonization associated with clindamycin may indicate a unique role for this antibiotic in the treatment of such infection.
Infect. Control Hosp. Epidemiol. 2015;36(7):786–793
To compare practice patterns regarding the diagnosis and management of streptococcal pharyngitis across pediatric primary care practices.
Retrospective cohort study.
All encounters to 25 pediatric primary care practices sharing an electronic health record.
Streptococcal pharyngitis was defined by an International Classification of Diseases, Ninth Revision code for acute pharyngitis, positive laboratory test, antibiotic prescription, and absence of an alternative bacterial infection. Logistic regression models standardizing for patient-level characteristics were used to compare diagnosis, testing, and broad-spectrum antibiotic treatment for children with pharyngitis across practices. Fixed-effects models and likelihood ratio tests were conducted to analyze within-practice variation.
Of 399,793 acute encounters in 1 calendar year, there were 52,658 diagnoses of acute pharyngitis, including 12,445 diagnoses of streptococcal pharyngitis. After excluding encounters by patients with chronic conditions and standardizing for age, sex, insurance type, and race, there was significant variability across and within practices in the diagnosis and testing for streptococcal pharyngitis. Excluding patients with antibiotic allergies or prior antibiotic use, off-guideline antibiotic prescribing for confirmed group A streptococcal pharyngitis ranged from 1% to 33% across practices (P < .001). At the clinician level, 13 of 25 sites demonstrated significant within-practice variability in off-guideline antibiotic prescribing (P ≤ .05). Only 18 of the 222 clinicians in the network accounted for half of all off-guideline antibiotic prescribing.
Significant variability in the diagnosis and treatment of pharyngitis exists across and within pediatric practices, which cannot be explained by relevant clinical or demographic factors. Our data support clinician-targeted interventions to improve adherence to prescribing guidelines for this common condition.
Inappropriate antibiotic prescribing commonly occurs in pediatric outpatients with acute respiratory tract infections. Antimicrobial stewardship programs are recommended for use in the hospital, but less is known about whether and how they will work in the ambulatory setting. Following a successful cluster-randomized trial to improve prescribing for common acute respiratory tract infections using education plus audit and feedback in a large, pediatric primary care network, we sought to explore the perceptions of the intervention and antibiotic overuse among participating clinicians.
We conducted a qualitative study using semistructured interviews with 24 pediatricians from 6 primary care practices who participated in an outpatient antimicrobial stewardship intervention. All interviews were transcribed and analyzed using a modified grounded theory approach.
Deep skepticism of the audit and feedback reports emerged. Respondents ignored reports or expressed distrust about them. One respondent admitted to gaming behavior. When asked about antibiotic overuse, respondents recognized it as a problem, but they believed it was driven by the behaviors of nonpediatric physicians. Parent pressure for antibiotics was identified by all respondents as a major barrier to the more judicious use of antibiotics. Respondents reported that they sometimes “caved” to parent pressure for social reasons.
To improve the effectiveness and sustainability of outpatient antimicrobial stewardship, it is critical to boost the credibility of audit data, engage primary care pediatricians in recognizing that their behavior contributes to antibiotic overuse, and address parent pressure to prescribe antibiotics.
(See the commentary by Van Schooneveld and Rupp, on pages1100–1102.)
Although prior authorization and prospective audit with feedback are both effective antimicrobial stewardship program (ASP) strategies, the relative impact of these approaches remains unclear. We compared these core ASP strategies at an academic medical center.
We compared antimicrobial use during the 24 months before and after implementation of an ASP strategy change. The ASP used prior authorization alone during the preintervention period, June 2007 through May 2009. In June 2009, many antimicrobials were unrestricted and prospective audit was implemented for cefepime, piperacillin/tazobactam, and vancomycin, marking the start of the postintervention period, July 2009 through June 2011. All adult inpatients who received more than or equal to 1 dose of an antimicrobial were included. The primary end point was antimicrobial consumption in days of therapy per 1,000 patient-days (DOT/1,000-PD). Secondary end points included length of stay (LOS).
In total, 55,336 patients were included (29,660 preintervention and 25,676 postintervention). During the preintervention period, both total systemic antimicrobial use (−9.75 DOT/1,000-PD per month) and broad-spectrum anti-gram-negative antimicrobial use (−4.00 DOT/1,000-PD) declined. After the introduction of prospective audit with feedback, however, both total antimicrobial use (+9.65 DOT/1,000-PD per month; P < .001) and broad-spectrum anti-gram-negative antimicrobial use (+4.80 DOT/1,000-PD per month; P < .001) increased significantly. Use of cefepime and piperacillin/tazobactam both significantly increased after the intervention (P = .03). Hospital LOS and LOS after first antimicrobial dose also significantly increased after the intervention (P = .016 and .004, respectively).
Significant increases in antimicrobial consumption and LOS were observed after the change in ASP strategy.
Infect Control Hosp Epidemiol 2014;35(9):1092-1099
Antimicrobial susceptibility patterns across US pediatric healthcare institutions are unknown. A national pooled pediatric antibiogram (1) identifies nationwide trends in antimicrobial resistance, (2) allows across-hospital benchmarking, and (3) provides guidance for empirical antimicrobial regimens for institutions unable to generate pediatric antibiograms.
In January 2012, a request for submission of pediatric antibiograms between 2005 and 2011 was sent to 233 US hospitals. A summary antibiogram was compiled from participating institutions to generate proportions of antimicrobial susceptibility. Temporal and regional comparisons were evaluated using χ² tests and logistic regression, respectively.
Of 200 institutions (85%) responding to our survey, 78 (39%) reported generating pediatric antibiograms, and 55 (71%) submitted antibiograms. Carbapenems had the highest activity against the majority of gram-negative organisms tested, but no antibiotic had more than 90% activity against Pseudomonas aeruginosa. Approximately 50% of all Staphylococcus aureus isolates were methicillin resistant. Western hospitals had significantly lower proportions of S. aureus that were methicillin resistant compared with all other regions tested. Overall, 21% of S. aureus isolates had resistance to clindamycin. Among Enterococcus faecium isolates, the prevalence of susceptibility to ampicillin (25%) and vancomycin (45%) was low but improved over time (P < .01), and 8% of E. faecium isolates were resistant to linezolid. Southern hospitals reported significantly higher prevalence of E. faecium with susceptibilities to ampicillin, vancomycin, and linezolid compared with the other 3 regions (P < .01).
A pooled, pediatric antibiogram can identify nationwide antimicrobial resistance patterns for common pathogens and might serve as a useful tool for benchmarking resistance and informing national prescribing guidelines for children.
Antimicrobial stewardship programs (ASPs) are recommended to optimize antimicrobial use for hospitalized patients. Although mechanisms for the implementation of ASPs have been described, data-driven approaches to prioritize specific conditions and antimicrobials for intervention have not been established. We aimed to develop a strategy for identifying high-impact targets for antimicrobial stewardship efforts.
Retrospective cross-sectional study.
Setting and Patients.
Children admitted to 32 freestanding children's hospitals in the United States in 2010.
We identified the conditions with the largest proportional contribution to the total days of antibiotic therapy prescribed to all hospitalized children. For the 4 highest-using conditions, we examined variability between hospitals in antibiotic selection patterns for use of either first- or second-line therapies depending on the condition. Antibiotic use was determined using standardized probability of exposure to selected agents and standardized days of therapy per 1,000 patient-days, adjusting for patient demographics and severity of illness.
In 2010, 524,364 children received 2,082,929 days of antibiotic therapy. Surgical patients received 43% of all antibiotics. The 4 highest-using conditions—pneumonia, appendicitis, cystic fibrosis, and skin and soft-tissue infection—represent 1% of all conditions yet accounted for more than 10% of all antibiotic use. Wide variability in antibiotic use occurred for 3 of these 4 conditions.
Antibiotic use in children's hospitals varied broadly across institutions when examining diagnoses individually and adjusting for severity of illness. Identifying conditions with both frequent and variable antimicrobial use informs the prioritization of high-impact targets for future antimicrobial stewardship interventions.
We describe the prevalence of and risk factors for colonization with extended-spectrum β-lactamase (ESBL)–producing Escherichia coli and Klebsiella species (ESBL-EK) in hospitalized patients. The prevalence of colonization with ESBL-EK was 2.6%. Colonization was associated with cirrhosis, longer duration of hospital stay prior to surveillance, and prior exposure to clindamycin or meropenem.
To determine the frequency of false-positive Clostridium difficile toxin enzyme immunoassay (EIA) results in hospitalized children and to examine potential reasons for this false positivity.
Two tertiary care pediatric hospitals.
As part of a natural history study, prospectively collected EIA-positive stools were cultured for toxigenic C. difficile, and characteristics of children with false-positive and true-positive EIA results were compared. EIA-positive/culture-negative samples were recultured after dilution and enrichment steps, were evaluated for presence of the tcdB gene by polymerase chain reaction (PCR), and were further cultured for Clostridium sordellii, a cause of false-positive EIA toxin assays.
Of 112 EIA-positive stools cultured, 72 grew toxigenic C. difficile and 40 did not, indicating a positive predictive value of 64% in this population. The estimated prevalence of C. difficile infection (CDI) in the study sites among children tested for this pathogen was 5%–7%. Children with false-positive EIA results were significantly younger than those with true-positive tests but did not differ in other characteristics. No false-positive specimens yielded C. difficile when cultured after enrichment or serial dilution, 1 specimen was positive for tcdB by PCR, and none grew C. sordellii.
Approximately one-third of EIA tests used to evaluate pediatric inpatients for CDI were falsely positive. This finding was likely due to the low prevalence of CDI in pediatric hospitals, which diminishes the test's positive predictive value. These data raise concerns about the use of EIA assays to diagnosis CDI in children.