Consumption Of Quinolones Research Articles

Results of a 5 year Antimicrobial Stewardship program in a North Italian Hospital

Abstract Issue A National Action Plan (PNCAR) to fight antimicrobial resistance has been launched in Italy in 2017, further revised in 2022. In order to reduce inappropriate exposure to antibiotics and infections from multidrug resistant bacteria, a structured system of surveillance and monitoring according to PNCAR standards has been set up in all Italian regions. In the Hospital of Cittadella (District of Padua, Veneto region), special focus has been given to the reduction of antibiotic consumption, in particular quinolones, third generation cephalosporins, carbapenems and macrolides. Description Multidisciplinary meetings have been monthly organized by the hospital Antimicrobial Stewardship Group, with the aim of coordinating the implementation of specific stewardship actions. A quantitative estimate of antibiotic consumption (defined daily dose - DDD - consumption per 100 days of hospitalization) has been provided by the Regional data warehouse from 2019 to 2023 regarding all classes of antibiotics. Results Between 2019 and 2023 a clear decrease in the consumption of quinolones (from 8 to 5,8 DDD, -28%) and carbapenems (from 2,5 to 1,3 DDD, -48%) was observed but, at the same time, an increase in the consumption of third generation cephalosporins (from 9 to 15,7 DDD, +74%) has been reported. This can be explained as a direct consequence of the correct application of therapy guidelines, which in several cases suggest the use of ceftriaxone instead of meropenem. Finally, after an increase in the consumption of macrolides during the first COVID-19 pandemic wave, the consumption of this class of antibiotics has returned to pre-pandemic level. Lessons Constant monitoring of antimicrobial consumption and the identification of warning situations that may need to implement specific actions are the cornerstone of Antimicrobial Stewardship programs. Targets must be defined analyzing data of bacterial resistance rates and infections from multidrug resistant bacteria. Key messages • In Antimicrobial Stewardship programs it is important to adopt constant monitoring of antimicrobial consumption. • Antimicrobial stewardship programs need to be adapted according to the characteristics of each hospital.

2230. Consumption of Quinolones, Macrolides, and Beta-Lactam Antibiotics at a Tertiary Care Veterans Affairs Medical Center (VAMC) during COVID-19 Pre-pandemic and Pandemic periods: A 4-year Analysis and Implications for Antimicrobial Stewardship

Abstract Background During the coronavirus disease 2019 (COVID-19) pandemic, antimicrobial use increased tremendously. Evidence suggests that the pandemic has resulted in an increased rate of AMR due to inadvertent antibiotic use. This likely reflects difficulties in distinguishing COVID-19 from community-acquired pneumonia when patients first arrive at a hospital. Strengthening antimicrobial stewardship (AMS) efforts by formulating policies for the use of antibiotics is crucial to prevent emergence of AMR. Methods A retrospective analysis to assess changes in antibiotic use during the pandemic and pre-pandemic patterns was done. Results : In the inpatient setting, there was an overall decrease in antibiotic use (all units that follow are in DOT/1000 BDOC) from an average of 380 to 300, vancomycin from 90 to 62, cefazolin from 30 to 17, Linezolid from 5 to 2, Zosyn from 57 to 30 from pre-pandemic period (Jan 2019) to pandemic period (Dec 2022). Antimicrobials that showed an increase during the pandemic included ceftriaxone from 70 to 82, Cefepime from 5 to 8, Levofloxacin from 2 to 5, and fluconazole from 4 to 10 compared to pre-pandemic use. In the outpatient settings (units are in fills/1000 unique patients), levofloxacin use doubled from 3 to 6, cefuroxime use increased from 0.5 to 2 and Azithromycin use dropped from 80 to < 20, with concomitant increase in doxycycline use from 45 to 60. Outpatient antibiotic prescriptions were high for levofloxacin, doxycycline and cefuroxime and increases corresponded to peaks in cases of COVID-19. Conclusion Our analysis demonstrates that COVID-19 had shifted the antibiotic consumption curve towards treatment of pneumonia and invasive fungal infections (in seriously ill patients) which has key implications for AMS. Implementation of stringent AMS and mandatory Infectious disease consultation for all COVID 19 infections helped keep our antibiotic consumption well below the national average and curtail AMR. Disclosures All Authors: No reported disclosures

Geographic distribution of antibiotic resistance of Helicobacter pylori: A study in Bulgaria.

Prevalence of antibiotic resistant Helicobacter pylori was compared between 50 patients living outside the capital city and 50 matched pairs of capital city residents (CCRs). H. pylori isolates from 2018 to 2022 were included. Resistance rates in CCRs and those living elsewhere were 4.0 and 6.0% toamoxicillin, 48.0 and 42.0% to metronidazole, 30 and 30% to clarithromycin, and 4.0 and 4.0% to tetracycline, respectively. Levofloxacin resistance was higher (38.0%) in the capital city vs 20.0% (P=0.047) in the country. Odd ratio for levofloxacin resistance between pair-matched groups was 2.45 (95% CI, OR 1.0-6.02, P value = 0.05) and relative risk for fluoroquinolone resistance was 1.90 (95% CI for RR 0.98-3.67) for CCRs vs residents in other regions. Resistance rates to levofloxacin and clarithromycin were worryingly high in our study, most probably due to the high quinolone consumption (2.86 DDD/day in 2017) in Bulgaria and the increase in macrolide, lincosamide and streptogramin consumption, especially of azithromycin, by >42% with the start of COVID-19 pandemic. Briefly, antibiotic resistance of H. pylori has a dynamic change, and it can display different patterns in certain geographic regions. The results imply that antibiotic consumption should be carefully controlled and unjustified use of levofloxacin should be restricted, especially in some large cities. Antibiotic policy should be further strengthened and regular monitoring of resistance in various geographic regions is needed for treatment optimization.

Ciprofloxacin Concentrations 1/1000th the MIC Can Select for Antimicrobial Resistance in N. gonorrhoeae-Important Implications for Maximum Residue Limits in Food.

Background: Concentrations of fluoroquinolones up to 200-fold lower than the minimal inhibitory concentration (MIC) have been shown to be able to select for antimicrobial resistance in E. coli and Salmonella spp. (the minimum selection concentration—MSC). We hypothesized that the low concentrations of quinolones found in meat may play a role in the genesis of quinolone resistance in Neisseria gonorrhoeae. We aimed to (i) establish the ciprofloxacin MSC for N. gonorrhoeae and (ii) assess if, at the ecological level, the prevalence of gonococcal ciprofloxacin resistance is associated with the concentration of quinolones used in food animal production, which is an important determinant of long-term low-dose exposure to ciprofloxacin in humans. Methods: (i) To assess if subinhibitory ciprofloxacin concentrations could select for de novo generated resistant mutants, a susceptible WHO-P N. gonorrhoeae isolate was serially passaged at 1, 1:10, 1:100 and 1:1000 of the ciprofloxacin MIC of WHO-P (0.004 mg/L) on GC agar plates. (ii) Spearman’s correlation was used to assess the association between the prevalence of ciprofloxacin resistance in N. gonorrhoeae and quinolone use for animals and quinolone consumption by humans. Results: Ciprofloxacin concentrations as low as 0.004 µg/L (1/1000 of the MIC of WHO-P) were able to select for ciprofloxacin resistance. The prevalence of ciprofloxacin resistance in N. gonorrhoeae was positively associated with quinolone use for food animals (ρ = 0.47; p = 0.004; N = 34). Conclusion: Further individual level research is required to assess if low doses of ciprofloxacin from ingested foodstuffs are able to select for ciprofloxacin resistance in bacteria colonizing humans and other species.

Antibiotic Prescription in the Community-Dwelling Elderly Population in Lombardy, Italy: A Sub-Analysis of the EDU.RE.DRUG Study.

Inappropriate consumption and over-prescription of antibiotics have been extensively reported. Our aim was to specifically evaluate the antibiotic prescribing patterns and appropriateness among the elderly (≥65 years) from the Lombardy region (Italy) in primary care. Antibiotic consumption (as DID: DDD/1000 inhabitants × day) and prevalence rates in 2018 were assessed, and the prescribing quality was evaluated using ESAC-based indicators and WHO-AWaRe criteria. A multivariate logistic regression analysis was performed to evaluate the association between the probability of receiving an antibiotic prescription and patients’ and physicians’ characteristics. A total of 237,004 antibiotic users were included (mean age ± SD 75.98 ± 7.63; males 42.7%). Antibacterial consumption was equal to 17.2 DID, with values increasing with age in both males and females. The study found that the proportion of patients with at least one antibiotic prescription in 2018 was around 39.1%, with different age-related trends between males and females. Consumption (as DID) of cephalosporines (65–74 years: 1.65; 75–84 years: 2.06; ≥85 years: 2.86) and quinolones (3.88, 4.61, 4.96, respectively) increased with growing age, while consumption of penicillins (6.21, 6.08, 6.04, respectively) and macrolides, lincosamides, and streptogramins (3.25, 2.91, 2.64, respectively) decreased. In 2018, antibiotics considered to have higher toxicity concerns or resistance potential, as reported by WHO-AWaRe tool, were consumed more intensively than those to be used as first choices, independent of age and sex. The probability of receiving an antibiotic prescription was greater in females, in subjects with polypharmacy, in treatment with respiratory drugs, anti-inflammatory agents or glucocorticoids, and with previous hospitalization; but increasing age was less associated with exposition to antibiotics.

Alzheimer's Disease-Related Dysbiosis Might Be Triggered by Certain Classes of Antibiotics with Time-Lapse: New Insights into the Pathogenesis?

Several putative factors are identified in the literature as causative agents or risk factors for the development of Alzheimer's disease (AD). The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades, but recent studies raised the possible role of dysbiosis in the development of AD, which prevents memory loss. Finding possible associations between antibiotic consumption patterns and the prevalence of AD in European countries. Antibiotic consumption (European Centre for Disease Prevention and Control, ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, has been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation. A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the years 1997-2007 (r: 0.37, p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-2018, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (r: 0.406, p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (r: 0.344, p: 0.063), but none for the years 1997-2007 (r: 0.256, p: 0.241). Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.

Country-level association between antimicrobial consumption and resistance in Neisseria meningitidis: An ecological study

BackgroundIt is unclear what is responsible for the large variations in the prevalence of meningococcal resistance to cephalosporins and quinolones. MethodsWe used mixed-effects linear regression to assess if country-level prevalence of reduced susceptibility to cefotaxime and ciprofloxacin was associated with the population-level consumption of cephalosporins and quinolones in 13 European countries. ResultsPositive correlations were found between the prevalence of reduced susceptibility to ciprofloxacin and the consumption of quinolones (coef. 0.16, 95% CI 0.05–0.27; P = 0.003). The same positive association was found for cefotaxime/cephalosporins (coef. 0.1, 95% CI 0.04–0.15; P = 0.001). ConclusionsMeningococcal reduced susceptibility to cefotaxime and ciprofloxacin is linked to homologous class antimicrobial consumption. This finding provides additional motivation for strengthening antimicrobial stewardship programs.

Positive Association between the Use of Quinolones in Food Animals and the Prevalence of Fluoroquinolone Resistance in E. coli and K. pneumoniae, A. baumannii and P. aeruginosa: A Global Ecological Analysis.

(1) Background: It is unclear what underpins the large global variations in the prevalence of fluoroquinolone resistance in Gram-negative bacteria. We tested the hypothesis that different intensities in the use of quinolones for food-animals play a role. (2) Methods: We used Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in human infections with Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was correlated with the use of quinolones for food producing animals. Linear regression was used to assess the relative contributions of country-level quinolone consumption for food-animals and humans on fluoroquinolone resistance in these 4 species. (3) Results: The prevalence of fluoroquinolone resistance in each species was positively associated with quinolone use for food-producing animals (E. coli [ρ = 0.55; p < 0.001], K. pneumoniae [ρ = 0.58; p < 0.001]; A. baumanii [ρ = 0.54; p = 0.004]; P. aeruginosa [ρ = 0.48; p = 0.008]). Linear regression revealed that both quinolone consumption in humans and food animals were independently associated with fluoroquinolone resistance in E. coli and A. baumanii. (4) Conclusions: Besides the prudent use of quinolones in humans, reducing quinolone use in food-producing animals may help retard the spread of fluoroquinolone resistance in various Gram-negative bacterial species.

Decreasing incidence of Acinetobacter baumannii pneumonia and trends in antibiotic consumption: A single-center retrospective observational study.

To describe the epidemiology of Acinetobacter baumannnii (AB) pneumonia at our center, including the antibiotic exposure patterns of individual AB pneumonia cases and to investigate whether hospital-wide antibiotic consumption trends were associated with trends in AB pneumonia incidence. Single-center retrospective study with case-control and ecological components. US private tertiary-care hospital. All hospitalized patients with AB infection from 2008 to 2019 were identified through laboratory records; for those with AB pneumonia, medical records were queried for detailed characteristics and antibiotic exposures in the 30 days preceding pneumonia diagnosis. Hospital-wide antibiotic consumption data from 2015 through 2019 were obtained through pharmacy records. Incidence of both pneumonia and nonrespiratory AB infections decreased from 2008 to 2019. Among the 175 patients with AB pneumonia, the most frequent antibiotic exposure was vancomycin (101 patients). During the 2015-2019 period when hospital-wide antibiotic consumption data were available, carbapenem consumption increased, and trends negatively correlated with those of AB pneumonia (r = -0.48; P = .031) and AB infection at any site (r = -0.63; P = .003). Conversely, the decline in AB infection at any site correlated positively with concurrent declines in vancomycin (r = 0.55; P = .012) and quinolone consumption (r = 0.51; P = .022). We observed decreasing incidence of AB infection despite concurrently increasing carbapenem consumption, possibly associated with declining vancomycin and quinolone consumption. Future research should evaluate a potential role for glycopeptide and quinolone exposure in the pathogenesis of AB infection.

Consumption of quinolones in the community, European Union/European Economic Area, 1997-2017.

ObjectivesData on quinolone consumption in the community were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of main subgroups of quinolones.MethodsFor the period 1997–2017, data on consumption of quinolones, i.e. ATC group J01M, in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Quinolone consumption was analysed by subgroups based on pharmacokinetic profile, and presented as trends, seasonal variation, presence of change-points and compositional changes.ResultsIn 2017, quinolone consumption in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 8.2 between countries with the highest (Bulgaria) and the lowest (Norway) consumption. The second-generation quinolones accounted for >50% of quinolone consumption in most countries. Quinolone consumption significantly increased up to 2001, and did not change significantly afterwards. Seasonal variation increased significantly over time. Proportional consumption of third-generation quinolones significantly increased over time relative to that of second-generation quinolones, while proportional consumption of both third- and second-generation quinolones significantly increased relative to that of first-generation quinolones. Levofloxacin and moxifloxacin represented >40% of quinolone consumption in the community in southern EU/EEA countries.ConclusionsQuinolone consumption in the community is no longer increasing in the EU/EEA, but its seasonal variation continues to increase significantly as is the proportion of quinolones to treat respiratory infections.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Quinolones.

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available.

Helicobacter pylori resistance to antibiotics in Europe in 2018 and its relationship to antibiotic consumption in the community

ObjectiveOur aim was to prospectively assess the antibiotic resistance rates in Helicobacter pylori strains in Europe in 2018 and to study the link between antibiotic consumption in the community and...

Gonorrhoea treatment combined with population-level general cephalosporin and quinolone consumption may select for Neisseria gonorrhoeae antimicrobial resistance at the levels of NG-MAST genogroup: An ecological study in Europe

ObjectivesThe prevalence of Neisseria gonorrhoeae NG-MAST genogroup G1407, associated with decreased susceptibility to extended-spectrum cephalosporins and fluoroquinolone resistance, has declined in Europe and it switched from circulating predominantly in men who have sex with men (MSM) in 2009–2010 to heterosexuals in 2013. We hypothesise that changes to gonorrhoea treatment guidelines combined with differences in country-level consumption of cephalosporins and quinolones contributed to this shift. MethodsLinear regression was used to evaluate the association between changes in prevalence of G1407 between 2009–2010 and 2013 and country-level consumption of quinolones and cephalosporins in 2011/12 in 20 European countries. ResultsWhilst the prevalence of G1407 declined between 2009–2010 and 2013 in the EU/EEA, its absolute prevalence increased by 10% or more in three countries. The national prevalence of G1407 in 2013 was positively associated with population-level general cephalosporin and quinolone consumption in the preceding 2 years. The association between the prevalence of G1407 and proportion of the national sample derived from MSM was non-significant in 2009–2010 and was negative in 2013. ConclusionsOur results are broadly compatible with the hypothesis that changes in gonorrhoea therapy to the more efficacious ceftriaxone (plus azithromycin) from 2010 to 2011 onwards resulted in a reduced prevalence of the resistance-associated G1407 overall but in MSM in particular. High population-level consumption of quinolones and cephalosporins in certain countries then contributed to the selection of G1407 predominantly in heterosexuals in these countries.

Trends of Adult Antimicrobial Hospital Consumption in Catalonia (Spain) from 2008 to 2018

Background: Antimicrobial resistance is a disturbing problem in the health system. A relationship between the use of certain antimicrobials and a resistance increase has been proposed. Since this phenomenon is not usually attributed to specific uses of antimicrobials but preferably to its evolution over the years, the analysis of the antimicrobial consumption over time can justify the epidemiological situation of a given region in terms of resistance and possible increases and decreases for specific microorganisms. The objective of this study was to analyze the evolution of the use of antimicrobials in Catalonia during 2008–2018 through the VINCat program (Infection Control and Antimicrobial Stewardship Catalonian Program). Methods: The number of hospitals participating in the VINCat increased from 46 in 2008 to 63 in 2018 (ie, 68.8% and 85.7% of all adult acute-care hospital beds in Catalonia, respectively). Hospitalization days recorded at the participating hospitals increased from 2,991,053 in 2008 to 3,714,938 in 2018. The Anatomical Therapeutic Chemical Classification (ATC) defined daily dose (DDD) index was used for monitoring antimicrobial consumption. Simple linear regressions were performed, the linear relationship was checked by ANOVA tests, and the Pearson correlation (Pc) coefficients were obtained. Values of P ≤ .05 were considered statistically significant. Results: From 2008 to 2018, there was a statistically significant increase of global antibacterial consumption (65.50 vs 71.73 DDD per 100 bed days; P = .001) and antimycotic consumption (3.09 vs 3.45 DDD per 100 bed days, P = .012) due to an increase of consumption in the surgical units. At the same time, there was a decrease in the consumption of antimycotics in the medical units (4.35 vs 3.90 DDD per 100 bed days; P =.029). Cephalosporins and carbapenem consumption increased both globally (10.88 vs 13.86 DDD per 100 bed days; P &lt; .001) and in medical and surgical units (3.26 vs 5.38 DDD per 100 bed days; P &lt; .001). This increase was mainly associated with ceftriaxone (3.45 vs 5.46 DDD per 100 bed days; P &lt; .001) and meropenem (1.12 vs 3.08 DDD per 100 bed days; P &lt; .001). There was a global decrease in the consumption of penicillins (26.10 vs 24.24 DDD per 100 bed days; P = .012) and quinolones (11.63 vs 9.61 DDD per 100 bed days; P = .004). This trend was observed also in ICUs and medical units but not in surgical units, for which only quinolones showed a significant decrease. Decreases in the use of amoxicillin/clavulanate acid (17.80 vs 14.24 DDD per 100 bed days; P &lt; .001) and ciprofloxacin (5.68 vs 4.01 DDD per 100 bed days; P &lt; .001) were observed. Conclusions: The increase in the use of antimicrobials in Catalonia is concerning. This increase is attributable to the use of these drugs in surgical units. Antibiotic stewardship measures should be aimed primarily at these units. The increasing use of carbapenems should be analyzed.Funding: NoneDisclosures: Juan Pablo Horcajada reports consulting fees from MSD, Pfizer, and Menarini as well as speaker honoraria from MSD, Pfizer, and Zambon.

Quinolones (ATC-group J01M): the state of the pharmaceutical market, analysis of consumption in Ukraine and in some European countries in 2013-2018

The synthesis of the first antibiotic of the Quinolone group took place in 1958. Since then, Quinolones are widely used in clinical practice around the world due to their wide antibacterial spectrum of action.Aim. To study the pharmaceutical market of Ukraine of the Quinolone antibiotics group, as well as determine the volumes of their consumption in 2013-2018.Materials and methods. The analysis of the assortment of antibiotics of the Quinolone group was carried out according to the WHO Collaborating Center by methodologies for statistical analysis of drugs and according to the State Register of Medicines of Ukraine. The consumption was calculated using a standardized ATC/DDD methodology recommended by the WHO.Results. Eleven INNs of the Quinolone group antibiotics are presented at the pharmaceutical market of Ukraine, as well as 6 INNs of combinations with Quinolones. In 2018, 159 trade names (TNs) of Quinolones were registered in Ukraine; 40.25 % of them are of domestic production (64 TNs). The consumption of Quinolones for the study period increased from 1.77 DID in 2016 to 1.83 DID in 2018. In general, the ABD consumption in the countries of the European Union and the European Economic Area (EU/EEA) decreased during the study period from с 1.77 DID in 2013 to 1.5 DID in 2018.Conclusions. Eleven INNs of Quinolone group antibiotics are presented at the pharmaceutical market of Ukraine, as well as 6 INNs of combinations with Quinolones presented by 159 TNs in 2018. The consumption of Quinolones increased over the study period from 1.77 DID in 2016 to 1.83 DID in 2018. Within 2013-2016 the consumption of Quinolone antibiotics in Ukraine was lower than in the EU/EEA, but in 2017 the consumption in Ukraine increased to 0.15 DID, and in 2018 the difference increased to 0.33 DID.

Quinolone Consumption by Mothers Increases Their Children's Risk of Acquiring Quinolone-Resistant Bacteriuria.

Quinolone resistance has been documented in the pediatric population, although their use is limited in children. This study investigated the effect of maternal quinolone use on gram-negative bacterial resistance to quinolones in their offspring. We conducted a population-based, unmatched case-control study during 2010-2017. Cases were all children aged 0.5-17 years with community acquired, gram-negative quinolone-resistant bacteriuria. Controls were similar children with quinolone-sensitive bacteriuria. Only the first positive urine cultures for each child were included. Data on quinolones dispensed to the mother, any antibiotics dispensed to the children, age, sex, ethnicity, and prior hospitalizations were collected. Children with previous quinolone use were excluded. The study population consisted of 40 204 children. Quinolone resistance was detected in 2182 (5.3%) urine cultures. The median age was 5 years, with 93.7% females and 77.6% Jewish. A total of 26 937 (65%) of the children received any antibiotic and 1359 (3.2%) of the mothers received quinolones in the 6 months preceding bacteriuria. Independent risk factors were quinolone dispensed to the mothers (odds ratio [OR], 1.50 [95% confidence interval {CI}, 1.22-1.85]), Arab ethnicity (OR, 1.99 [95% CI, 1.81-2.19]), and antibiotic dispensed to the child (OR, 1.54 [95% CI, 1.38-1.71]). Compared with children aged 12-17 years, younger children had 1.33-1.43 increased odds for quinolone-resistant bacteriuria. Quinolone prescription to mothers was linked to increased risk of community-acquired, quinolone-resistant bacteria in their offspring, by about 50%. This is another example of the deleterious ecological effects of antibiotic use and should be considered when prescribing antibiotics.

Outpatient Antibiotic Consumption for Urinary Infections in Croatia 2005 - 2014: What can be Learned from Utilization Trends.

AimThe aim of this study was to determine quantities of antibiotics used mainly or exclusively for urinary tract infections in Croatia between 2005 and 2014, to describe utilisation trends, and general consequences of antibiotic consumption on antimicrobial resistance.MethodsAntibiotic utilisation data were obtained from annual reports of both the Croatian Drug Agency and Croatian Academy of Medical Sciences. Antibiotic consumption was expressed in DDD/1000 inhabitants/day (DDD TID). Antimicrobial resistance was analysed for E. coli, E. faecalis, E. faecium, P. aeruginosa, Klebsiella spp., P. mirabilis. Descriptive statistics were used to process data and calculate trends.ResultsOverall, utilisation of antibacterials decreased by 4.8% (from 3,35 to 3,19 DDD TID), while trends of individual agents varied substantially – from 87% decline for ceftibuten to 160% rise for levofloxacin. The consumption of quinolones increased by 32.3%. This was mostly due to increased ciprofloxacin consumption (144% raise). Sulfamethoxazole-trimethoprim declined by 57%, while nitrofurantoin increased by 86%. The use of fosfomycin was marginal. Antimicrobial resistance of E. coli increased against quinolones by 54.5%, and against nitrofurantoin by 2–3%. Quinolone resistance of other pathogens (Klebiella spp, Proteus mirabilis), increased variably – between 17.2% (Klebsiella) and 90% (Proteus), while for P. aeruginosa remained the same at 22%.ConclusionHigh rates of antimicrobial utilisation require prescribing restrictions and educational interventions. The increased use of fluoroquinolones is a potentially serious public health threat due to the rapid development of resistance among uropathogens. This threat can be avoided by greater use of nitrofurantoin and fosfomycin.

Detection of the Novel optrA Gene Among Linezolid-Resistant Enterococci in Barcelona, Spain.

The purpose of this study was to describe the presence of the novel optrA gene among clinical isolates of enterococci in a Spanish teaching hospital (May 2016-April 2017). optrA and cfr genes were screened by PCR in all isolates showing linezolid minimal inhibitory concentration (MIC) ≥4 mg/L. The genetic relatedness of the isolates, the presence of resistance and virulence genes, and the genetic environment of optrA were assessed by whole-genome sequencing (WGS). Six of 1,640 enterococci had linezolid MIC ≥4 mg/L. Among them, the optrA gene was detected in five Enterococcus faecalis isolated from unrelated patients. Although none of them had received linezolid or chloramphenicol, all had antecedents of recent quinolone consumption. WGS analysis revealed the existence of two different genotypes: ST585 and ST474. cfr was not detected in any of the isolates. No mutations were detected among the 23S ribosomal RNA and the ribosomal proteins L3, L4, and L22. Both genotypes also carried genes related to aminoglycoside, lincosamide, macrolide, phenicol, and tetracycline resistance. Detection of optrA in a setting with low linezolid consumption and among patients without antecedents of oxazolidinone therapy is of concern.

The consumption of quinolones in Portugal, 2005–2014

Background Inadequate consumption of antibiotics has social costs as well as serious health consequences including lower response to treatments, prolonged illness, increasing number of hospitalizations and higher risk of complications and mortality. Being aware of the evolution of antibiotic consumption and its pattern of use is essential to develop action plans, which may contribute to their appropriate use. The aim of our study was to assess the evolution of quinolones consumption in Portugal, Health Regions and Districts of Portugal, from 2005 to 2014. Methods Descriptive observational study using as source of information a database of antibiotics prescription in ambulatory provided by Infarmed, National Authority of Medicines and Health Products. Two methods of consumption evaluation were used: DID, expressed in DDD per 1000 inhabitants per day; and PID, expressed in number of packages per 1000 inhabitants per day. Results The quinolone consumption, using the DID method, ranged from 2.42 DID to 2.12 DID, between 2005 and 2014, corresponding to a decrease of 12.35%. At the district level, during the ten years of consumption reporting, it is worth noting the decrease in consumption of quinolones in the vast majority of districts. The district with the greatest consumption reduction was Beja, with a decrease of 28.36% (DID). Regarding the use of the PID method, consumption ranged from 0.315 PID in 2005 to 0.257 PID in 2014, corresponding to a decrease of 18.31%. At district level, all districts decreased consumption in the 10 years under study, with the exception of Portalegre, which had an increase of 5.60%. The district of Beja was the one that showed a greater decrease in the consumption of quinolones (34.44%). In relation to the different generations of quinolones, it was found that the first generation has suffered an important decrease in its consumption (ofloxacin - 73.1%), and the second generation is the most consumed (77%), mainly due to ciprofloxacin and levofloxacin. Ciprofloxacin is the quinolone most consumed, and levofloxacin was the quinolone that presented the greatest increase in consumption. Conclusion This study allowed to verify the differences of results, according to different methods. It was concluded that for a good characterization of consumption differences between health regions and districts, it is necessary to use more than one method of study. Despite the decrease in consumption of quinolones, Portugal continues to have a high consumption when compared to other European countries.

Human Campylobacter jejuni and Campylobacter coli Isolates: Demographic Pattern and Antimicrobial Susceptibility to Clinically Important Antimicrobials used in Livestock

Background: Campylobacteriosis is the leading zoonotic disease in developed countries with C. jejuni and C. coli being the two predominant causative pathogens. It has been shown that quinolone consumption in livestock is associated with increased quinolone resistance of Campylobacter isolates from food producing animals and infected patients. However, susceptibility testing of clinical isolates is not commonly performed and, consequently, resistance rates of human C. jejuni and C. coli isolates in areas of high consumption of antimicrobials in livestock may be undervalued. A strong association between C. jejuni infections and patients` age and gender has been highlighted by several authors. However, there is still little information on the demographic pattern in C. coli infections.Methods: 1135 C. jejuni and 156 C. coli human isolates were obtained within a rural region of Germany. The study area was characterised by intensive swine and poultry farming involving high consumption of clinically important antimicrobials. Isolates were analysed for susceptibility to amoxicillin, ciprofloxacin, tetracycline and erythromycin using the EUCAST disc diffusion method. Furthermore, data were stratified with respect to patients age and gender.Results: Contrary to male-biased distribution in C. jejuni isolates, C. coli was the predominant species in female patients with a maximum female surplus in young children and middle-aged adults. Resistance rates of C. coli vs. C. jejuni to amoxicillin, ciprofloxacin, tetracycline and erythromycin were 46.2% vs. 48.3%, 62.8% vs. 64.5%, 68.6% vs. 35.2% and 14.7 vs. 0.6%, respectively. Resistance rates were found to correlate with usage of these antimicrobials in livestock.Conclusion: The high prevalence of C. coli in female patients may point to sex-specific behavioural or physiological aspects. The observed high to moderate resistance rates of Campylobacter isolates warrant prudent use of antimicrobials in livestock as well as routine susceptibility testing of human isolates to ensure efficacy of antimicrobial therapy.