Use of Azithromycin Attributable to Acute SARS-CoV-2 Infection.

PURPOSE: In the early stages of the COVID-19 pandemic, preliminary results that later proved to be incorrect suggested the possible efficacy of anti-infective drugs such as azithromycin for the treatment of SARS-CoV-2 infection. These preliminary data may have influenced the prescription of azithromycin. However, no individual-level data linking the use of this antibiotic to acute SARS-CoV-2 infection are available. The present analysis aims to fill this gap. METHODS: A retrospective population-based cohort design was used including patients diagnosed with SARS-CoV-2 infection in the period ranging from February 2020 to February 2022. The data source for antibiotic consumption was the drug database of outpatient prescriptions of Emilia-Romagna Region (Italy). Antibiotics were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. Consumption rates and percentages of azithromycin DDDs (defined daily doses) during the acute phase of the infection were compared with a previous control period and with the post-acute phase. Analyses were stratified by four groups according to the prevalent virus variant at time of diagnosis. RESULTS: Comparing the previous control period with the acute phase of infections, the rates of azithromycin consumption (DDD per 1000 individuals per day) increased from 1.17 to 23.11, from 0.80 to 33.03, from 0.81 to 21.01, and from 1.02 to 9.76, in the pre-Alpha, Alpha, Delta, and Omicron periods, respectively. Similarly, the percentages of individuals receiving azithromycin, and the azithromycin DDDs percentages over total systemic antibiotics DDDs increased in acute phases of infection compared with control periods. The consumption rates and percentages returned to preinfection levels in the post-acute phase. In the study period, 12.9% of the use of azithromycin in the entire adult population of Emilia-Romagna was attributable to acute SARS-CoV-2 infection. CONCLUSIONS: Considering the low likelihood of bacterial coinfections, the increased azithromycin consumption in the acute phase of SARS-CoV-2 infection suggests inappropriate prescribing of this antibiotic.

The incidence and risk factors of selected drug prescriptions and outpatient care after SARS-CoV-2 infection in low-risk subjects: a multicenter population-based cohort study.

Background: Knowledge about the dynamics of transmission of SARS-CoV-2 and the clinical aspects of COVID-19 has steadily increased over time, although evidence of the determinants of disease severity and duration is still limited and mainly focused on older adult and fragile populations. Methods: The present study was conceived and carried out in the Emilia-Romagna (E-R) and Veneto Regions, Italy, within the context of the EU's Horizon 2020 research project called ORCHESTRA (Connecting European Cohorts to increase common and effective response to SARS-CoV-2 pandemic) (www.orchestra-cohort.eu). The study has a multicenter retrospective population-based cohort design and aimed to investigate the incidence and risk factors of access to specific healthcare services (outpatient visits and diagnostics, drug prescriptions) during the post-acute phase from day-31 to day-365 after SARS-CoV-2 infection, in a healthy population at low risk of severe acute COVID-19. The study made use of previously recorded large-scale healthcare data available in the administrative databases of the two Italian Regions. The statistical analysis made use of methods for competing risks. Risk factors were assessed separately in the two Regions and results were pooled using random effects meta-analysis. Results: There were 35,128 subjects in E-R and 88,881 in Veneto who were included in the data analysis. The outcome (access to selected health services) occurred in a high percentage of subjects in the post-acute phase (25% in E-R and 21% in Veneto). Outpatient care was observed more frequently than drug prescriptions (18% vs. 12% in E-R and 15% vs. 10% in Veneto). Risk factors associated with the outcome were female sex, age greater than 40 years, baseline risk of hospitalization and death, moderate to severe acute COVID-19, and acute extrapulmonary complications. Conclusion: The outcome of interest may be considered as a proxy for long-term effects of COVID-19 needing clinical attention. Our data suggest that this outcome occurs in a substantial percentage of cases, even among a previously healthy population with low or mild severity of acute COVID-19. The study results provide useful insights into planning COVID-19-related services.

Reduction trend of mcr-1 circulation in Emilia-Romagna Region, Italy.

This study aims to describe trends of mcr-positive Enterobacterales in humans based on laboratory surveillance with a defined catchment population. The data source is the Micro-RER surveillance system, established in Emilia-Romagna region (Italy), to monitor the trend of mcr resistance. Enterobacterales isolates from human clinical samples with minimum inhibitory concentration (MIC) ≥ 2 mg/L for colistin were sent to the study reference laboratory for the detection of mcr genes. Isolates prospectively collected in the period 2018-2020 were considered for the assessment of population rates and trends; further analyses were carried out for the evaluation of clonality and horizontal mcr gene transfer. Previous isolates from local laboratory collection were also described. In the period 2018-2020, 1164 isolates were sent to the reference laboratory, and 51 (4.4%) were confirmed as mcr-positive: 50 mcr-1 (42 Escherichia coli, 6 Klebsiella pneumoniae, 2 Salmonella enterica) and 1 mcr-4 (Enterobacter cloacae). The number of mcr-positive isolates dropped from 24 in the first half of 2018 to 3 in the whole of 2020 (trend p value < 0.001). Genomic analyses showed the predominant role of the horizontal transfer of mcr genes through plasmids or dissemination of transposable elements compared to clonal dissemination of mcr-positive microorganisms. The study results demonstrate a substantial decrease in the circulation of mcr-1 plasmid genes in Emilia-Romagna Region.

Reducing antibiotic prescriptions in children is not associated with higher rate of complications.

Acute otitis media (AOM) and sore throat are common reasons for antibiotic prescription in children. Starting from 2007, evidence-based guidelines and other multifaceted improvement activities (ProBA project) were implemented in Emilia-Romagna, a northern Italian region. Antibiotic prescription rate in the region decreased with time (37% relative reduction from 2005 to 2019). Within the ProBA project, this retrospective observational study, including all hospitals of the region, aims to assess if lower rate of antibiotic prescription was associated with an increased rate of acute mastoiditis and acute rheumatic fever (ARF). Hospital admission rates for acute mastoiditis and ARF from 2005 to 2019 were calculated using ICD-9 codes. Hospital intervention rates for myringotomy, incision of mastoid, and mastoidectomy were also assessed. A comparison with antibiotic prescription rate in the pediatric population was performed. Data were gathered using administrative databases and trends were calculated using Poisson regression. During the study period, rate of mastoiditis and similar diagnosis declined from 54.1 to 33.6 per 100.000 (ß coefficient = - 0.047, p value < 0.001) and rate of surgical treatment from 134.6 to 89.6 per 100.000 (ß coefficient = - 0.036, p value < 0.001), whereas rate of ARF remained stable at around 4.4-4.8 per 100.000 (ß coefficient = - 0.009, p value = 0.472).Conclusion: ProBA project implementation-recommending 5 days of amoxicillin for AOM when needed and 6 days of amoxicillin when streptococcal pharyngitis is detected-was associated with a reduced antibiotic use without an increase of complications. What is Known: • Acute otitis media (AOM) and streptococcal pharyngitis are common pediatric infections and frequent cause of antibiotics prescription. • Fear of rare complications like mastoiditis and acute rheumatic fever can hinder health professionals' compliance with evidence-based guideline. What is New: • Guidelines recommending a short course of antibiotics for AOM and streptococcal pharyngitis are associated with reduced antibiotic prescriptions and no increase of complications. • Analysis based on administrative databases is useful for monitoring projects and supporting health professionals in complying with guidelines.

Formula feeding increases the risk of antibiotic prescriptions in children up to 2 years: results from a cohort study.

Association between the use of infant formula and risks for infants' health is seldom studied in western countries. We set up a historical cohort based on record linkage analysis, combining the data from administrative databases providing individual data. Infants receiving the second dose of pediatric immunization between 2015 and 2017 were included. The main outcome measure was antibiotic prescriptions from enrolment up to 24 months of age, by infant feeding category at enrolment. The extended Cox regression technique was used to account for recurrent events. The infants' cohort included 40,258 5-month-old infants; during the study period, 60,932 antibiotic prescriptions were filled. Compared with infants fully breastfed, children fed with both maternal milk and formula received 106 more antibiotic prescriptions per 1000 children/year, whereas infants receiving formula only had 138 excess prescriptions per 1000 children/year. The association with infant feeding was statistically significant and remained unchanged after adjustment for common confounders (adjusted hazard ratio, HR, for complementary feeding vs full breastfeeding 1.09; 95%CI 1.05 to 1.12; formula only versus full breastfeeding adj. HR 1.12; 95%CI 1.08 to 1.16).Conclusion: In our cohort, we observed a positive association between infant formula use considered a proxy of infections antibiotic prescription rate, considered a proxy of infections. The association followed a gradient.What is Known:• Formula feeding is associated with increased morbidity and mortality even in western countries, but still, it is common.• Information on formula are seldom unbiased; thus, public perception of risks is distorted.What is New:• In a large Italian cohort of infants, formula feeding at 5 months of age results to be associated with an increased rate of antibiotic prescription (considered to be a proxy of infection) up to 24 months of age: the association follows a dose-response relationship.• Record linkage analysis using administrative databases provides useful information at a limited cost.

Antimicrobial use in European long-term care facilities: results from the third point prevalence survey of healthcare-associated infections and antimicrobial use, 2016 to 2017.

Antimicrobials are commonly prescribed and contribute to the development of antimicrobial resistance in long-term care facilities (LTCFs). In 2010, the European Centre for Disease Prevention and Control initiated point prevalence surveys (PPS) of healthcare-associated infections and antimicrobial use in European LTCFs, performed by external contractors as the Healthcare-Associated infections in Long-Term care facilities (HALT) projects. Here, we investigated prevalence and characteristics of antimicrobial use and antimicrobial stewardship indicators in European LTCFs in 2016-17. Twenty-four European Union/European Economic Area (EU/EEA) countries, the former Yugoslav Republic of Macedonia and Serbia participated in the third PPS in European LTCFs. Overall, 4.9% (95% confidence interval: 4.8-5.1) of LTCF residents in the EU/EEA participating countries received at least one antimicrobial. The most commonly reported Anatomical Therapeutic Chemical (ATC) groups were beta-lactam antibacterials/penicillins (J01C), other antibacterials (J01X) (e.g. glycopeptide antibacterials, polymyxins), quinolones (J01M), sulfonamides and trimethoprim (J01E), and other beta-lactams (J01D). Urinary tract infections and respiratory tract infections were the main indications for antimicrobial prescription. This PPS provides updated and detailed information on antimicrobial use in LTCFs across the EU/EEA that can be used to identify targets for future interventions, follow-up of these interventions and promote prudent use of antimicrobials in European LTCFs.

Observational pre-post study showed that a quality improvement project reduced paediatric antibiotic prescribing rates in primary care.

AIM: This study assessed the effectiveness of a quality improvement project that aimed to promote more considered antibiotic prescribing in paediatric primary care. METHOD: This was an observational pre-post study that used patient-level prescribing data from the Emilia-Romagna region of Italy to monitor indicators from 2005 to 2016. Multilevel interventions and activities were started in 2007 and these included developing guidelines and updates, disseminating evidence, audits and feedback, public information campaigns, engaging health managers and performance incentives. The primary outcomes were total antibiotic prescription rates for children aged 0-13 years and the rates for specific drugs. RESULTS: The intervention was associated with a significant reduction in the antibiotic prescribing rate, from 1307 per 1000 children in 2005 to 881 prescriptions in 2016 (p for trend <0.001), and a significant increase in the ratio of amoxicillin to amoxicillin-clavulanic acid, from 0.6 to 1.1 (p for trend = 0.001). Prescriptions of other second-choice antibiotics also declined significantly. In contrast, antibiotic prescribing rates remained high in the rest of Italy. CONCLUSION: The intervention was effective in promoting a more considered use of antibiotic in paediatric primary care in an Italian region. Further studies are needed to confirm its effectiveness in other settings.

Multidrug-resistant infections in long-term care facilities: extended-spectrum ß-lactamase-producing Enterobacteriaceae and hypervirulent antibiotic resistant Clostridium difficile.

Infections due to multidrug-resistant (MDR) organisms in long-term care facilities (LTCFs) residents constitute a public health concern. This multicenter study investigated the frequency of ESBL-producing pathogens and MDR Clostridium difficile in clinical specimens from LTCF residents in Italy. During October 2014-March 2015, all urine and diarrheic fecal samples from LTCF residents (≥65 years) with suspected urinary tract infection or C. difficile infection, respectively, received for diagnosis by 4 hospital laboratories located in different cities were analyzed. Antibiotic susceptibility testing, characterization of resistance genes, and molecular typing of pathogens were performed. Of 806 urine cultures collected from 626 residents at 44 different LTCFs, 492 were positive for microbial infection. Of these, 158 were positive for at least an ESBL-producing Enterobacteriaceae species (32.1%), with Escherichia coli as the most frequent ESBL pathogen (23.4%) followed by Klebsiella pneumoniae (4.5%). Furthermore, 4 carbapenemase producers (0.8%) (1 E. coli with VIM-1and 3 K. pneumoniae with KPC-3) were detected. The CTX-M-15 type ESBL predominated in both E. coli (71.3%) and K. pneumoniae (77.3%). Most E. coli isolates (82.6%) belonged to the ST131/H30 clone/subclone. For K. pneumoniae, ST307 and ST15 were frequent (31.8% and 22.7%, respectively), but isolates harboring blaKPC-3 belonged to CC258. Of 136 diarrheic fecal samples collected from 111 residents at 26 different LTCFs, 21 (15.4%) were positive for toxigenic C. difficile; of these, 13 (62%) were MDR (resistant to 3 or more antimicrobial agents of different classes). The predominant C. difficile polymerase chain reaction ribotype was 356/607 (42.9%), followed by 018, 449, and 078 (14% each). Public health efforts are needed to contain the diffusion of CTX-M-producing Enterobacteriaceae and MDR C. difficile in LTCF settings.

Resistance to fluoroquinolones and treatment failure/short-term relapse of community-acquired urinary tract infections caused by Escherichia coli.

OBJECTIVES: This study aims to evaluate the impact of resistance to fluoroquinolones on the short-term outcome of community-acquired urinary tract infections (UTIs) caused by Escherichia coli. METHODS: Patients were identified and followed, during 2006, using the health care databases of the Emilia-Romagna Region. The outcome of interest was the treatment failure/short-term relapse (the re-isolation of E. coli from urine between 4 and 30 days after the first isolation). RESULTS: Resistance to fluoroquinolones increases the risk of treatment failure/short-term relapse in women with uncomplicated community-acquired UTIs caused by E. coli (Rate Ratio=1.85, 95% CI 1.32-2.60). The efficacy of fluoroquinolones for community-acquired UTIs of men was significantly modified by the resistance status of E. coli. Prescription of these agents was associated with a reduced occurrence of the outcome only in men with a ciprofloxacin sensitive first isolate (Rate Ratio=0.50, 95% CI 0.25-0.99). CONCLUSIONS: Resistance to fluoroquinolones of E. coli is a growing problem with a negative impact on the outcome of community-acquired UTIs; therefore, the prescription of these agents should be limited to infections for which they are recommended, avoiding their use in uncomplicated UTIs.