Magnus Arpi

Impact of antibiotic restriction on resistance levels of Escherichia coli: a controlled interrupted time series study of a hospital-wide antibiotic stewardship programme

OBJECTIVESnWe evaluated the effect of an antibiotic stewardship programme (ASP) on the use of antibiotics and resistance levels of Escherichia coli using a method that allowed direct comparison between an intervention hospital and a control hospital.nnnMETHODSnThe study was conducted as a retrospective controlled interrupted time series (ITS) at two university teaching hospitals, intervention and control, with 736 and 552 beds, respectively. The study period was between January 2008 and September 2014. We used ITS analysis to determine significant changes in antibiotic use and resistance levels of E. coli. Results were directly compared with data from the control hospital utilizing a subtracted time series (STS).nnnRESULTSnDirect comparison with the control hospital showed that the ASP was associated with a significant change in the level of use of cephalosporins [-151 DDDs/1000 bed-days (95% CI -177, -126)] and fluoroquinolones [-44.5 DDDs/1000 bed-days (95% CI -58.9, -30.1)]. Resistance of E. coli showed a significant change in slope for cefuroxime [-0.13 percentage points/month (95% CI -0.21, -0.057)] and ciprofloxacin [-0.15 percentage points/month (95% CI -0.26, -0.038)].nnnCONCLUSIONSnThe ASP significantly reduced the use of cephalosporins and fluoroquinolones, with concomitant decreasing levels of E. coli resistance to cefuroxime and ciprofloxacin. The same development was not observed at the control hospital.

Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes: A Nationwide Danish Cohort Study

Background Studies link antibiotic treatment and delivery by cesarean section with increased risk of chronic diseases through changes of the gut-microbiota. We aimed to evaluate the association of broad-spectrum antibiotic treatment during the first two years of life with subsequent onset of childhood type 1 diabetes and the potential effect-modification by mode of delivery. Materials and Methods A Danish nationwide cohort study including all singletons born during 1997–2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow-spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes. Results Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years of life (HR 1.13; 95% CI 1.02 to 1.25), however, the rate was modified by mode of delivery. Broad-spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by either intrapartum cesarean section (HR 1.70; 95% CI 1.15 to 2.51) or prelabor cesarean section (HR 1.63; 95% CI 1.11 to 2.39), but not in vaginally delivered children. Number needed to harm was 433 and 562, respectively. The association with broad-spectrum antibiotics was not modified by parity, genetic predisposition or maternal redemption of antibiotics during pregnancy or lactation. Conclusions Redemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section.

Bilateral polymicrobial osteomyelitis with Candida tropicalis and Candida krusei: a case report and an updated literature review

OBJECTIVESnWe present a case of bilateral polymicrobial osteomyelitis with Candida tropicalis and Candida krusei, and review the literature on Candida osteomyelitis.nnnMETHODSnPubMed was searched for cases of Candida osteomyelitis published in the English-language literature between 1970 and 2010.nnnCASEnA 60-year-old previously healthy man was hospitalized with gallstone pancreatitis. Between 3 weeks and 6 months after hospitalization, he developed bilateral osteomyelitis of the feet with C. tropicalis and C. krusei. The patient was treated with surgery, fluconazole, and a liposomal formulation of amphotericin B. The left lower limb was amputated, and at a 2-year follow-up, the patient had almost no pain in his right foot.nnnLITERATURE REVIEWnWe identified 40 new cases in the literature since the latest review in 2004. Most cases of Candida osteomyelitis are caused by Candida albicans, but an increasing number are caused by non-albicans species. The prognosis is favorable, with full recovery in the majority of cases.nnnCONCLUSIONSnCandida osteomyelitis should be considered when a patient presents with risk factors and pain without previous trauma, because Candida, despite being part of the normal flora, is the fourth leading cause of hematogenous nosocomial infections. The recommended treatment is surgery and fluconazole as monotherapy or initially combined with a fungicidal agent, either a different amphotericin B formulation or an echinocandin.

Quality assessment of diagnosis and antibiotic treatment of infectious diseases in primary care: a systematic review of quality indicators

Abstract Objective: To identify existing quality indicators (QIs) for diagnosis and antibiotic treatment of patients with infectious diseases in primary care. Design: A systematic literature search was performed in PubMed and EMBASE. We included studies with a description of the development of QIs for diagnosis and antibiotic use in patients with infectious diseases in primary care. We extracted information about (1) type of infection; (2) target for quality assessment; (3) methodology used for developing the QIs; and (4) whether the QIs were developed for a national or international application. The QIs were organised into three categories: (1) QIs focusing on the diagnostic process; (2) QIs focusing on the decision to prescribe antibiotics; and (3) QIs concerning the choice of antibiotics. Results: Eleven studies were included in this review and a total of 130 QIs were identified. The majority (72%) of the QIs were focusing on choice of antibiotics, 22% concerned the decision to prescribe antibiotics, and few (6%) concerned the diagnostic process. Most QIs were either related to respiratory tract infections or not related to any type of infection. A consensus method (mainly the Delphi technique), based on either a literature study or national guidelines, was used for the development of QIs in all of the studies. Conclusions: The small number of existing QIs predominantly focuses on the choice of antibiotics and is often drug-specific. There is a remarkable lack of diagnostic QIs. Future development of new QIs, especially disease-specific QIs concerning the diagnostic process, is needed. KEY POINTS In order to improve the use of antibiotics in primary care, measurable instruments, such as quality indicators, are needed to assess the quality of care being provided. A total of 11 studies were found, including 130 quality indicators for diagnosis and antibiotic treatment of infectious diseases in primary care. The majority of the identified quality indicators were focusing on the choice of antibiotics and only a few concerned the diagnostic process. All quality indicators were developed by means of a consensus method and were often based on literature studies or guidelines.

Antibiotic prophylaxis for transrectal prostate biopsy—a new strategy

BACKGROUNDnFluoroquinolones are extensively used as prophylaxis for transrectal ultrasound-guided biopsy of the prostate (TRUBP). Emerging fluoroquinolone resistance and selection of multiresistant organisms warrant new prophylactic strategies. Pivmecillinam and amoxicillin/clavulanic acid have mutual synergistic activity and the combination of these agents has a broad coverage of the majority of microorganisms causing infectious complications after TRUBP and may be a valuable future prophylactic regimen.nnnPATIENTS AND METHODSnThis was a retrospective cohort study of 2624 men that underwent TRUBP at a Danish university hospital. The patients were divided into three groups. Group 1 (n = 1220) received ciprofloxacin before TRUBP, Group 2 (n = 240) received a combination of pivmecillinam and amoxicillin/clavulanic acid before TRUBP and Group 3 (n = 1161) received an extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid before and for 2 days after TRUBP.nnnRESULTSnOne hundred and ten out of 148 (74.3%) post-TRUBP infections were caused by Escherichia coli, Klebsiella pneumoniae or Enterococcus faecalis. Group 3 with the extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid had a significantly lower rate of bacteraemia (0.9%) as compared with Group 1 (1.8%) and Group 2 (3.7%). A significant fall in the proportion of ESBL-producing Enterobacteriaceae was observed from the period when ciprofloxacin was used as prophylaxis (8.1%) compared with the subsequent period when pivmecillinam and amoxicillin/clavulanic acid was used (5.9%).nnnCONCLUSIONSnThe combination of pivmecillinam and amoxicillin/clavulanic acid is an attractive prophylaxis for TRUBP from a clinical, bacteriological and ecological point of view as compared with ciprofloxacin.

Rising incidence of Enterococcus species in microbiological specimens from orthopedic patients correlates to increased use of cefuroxime: A study concentrating on tissue samples

Background and purpose Enterococci are emerging causes of severe infections, including wound and bone infections in orthopedic patients. The main purpose of this study was to determine whether there was a correlation between the incidence of enterococci in tissue samples (biopsies) from orthopedic patients and consumption of cefuroxime in the orthopedic department. Methods and results Data were obtained from the department of clinical microbiology and the hospital pharmacy. The consumption of cefuroxime successively increased from 40 defined daily doses (DDD)/103 bed days in 2002 to 212 DDD/103 bed days in 2009. The incidence of patients with enterococci in tissue samples increased steadily from 1.03/103 bed days in 2002 to 5.90/103 bed days in 2009. Regression analysis revealed a significant correlation between the consumption of cefuroxime and the incidence of enterococci. Interpretation Continuous surveillance of species distribution, resistance rates, and antibiotic consumption is of utmost importance for optimal antibiotic strategy in orthopedic patients.

Parents’ socioeconomic factors related to high antibiotic prescribing in primary health care among children aged 0–6 years in the Capital Region of Denmark

Abstract Objective: To investigate the distribution of antibiotic prescriptions in primary health care among children aged 0–6 years and its association with socioeconomic factors. Design: A cross-sectional study describing antibiotic prescriptions and socioeconomic factors, using different population-based registers from Statistics Denmark. Setting: Antibiotic prescriptions in 2012 from primary health care in the Capital Region of Denmark. Subjects: The population of children aged 0–6 years (nu2009=u2009139,398) in the Capital Region of Denmark. Main outcome measures: High use of antibiotics identified by number of antibiotic prescriptions (≥u20093 prescriptions per year) and defined daily doses (DDD). A multinomial logistic regression analysis estimating the association between high antibiotic use and parents’ education, employment status, income, child’s sex, and ethnic background. Results: Ten percent of children accounted for 25% of the total use DDD. There was a clear tendency that the risk for high antibiotic use increased as parental educational level decreased. The risk for high use was the highest among children of mothers and fathers with basic schooling ≤10 years (OR 1.60, 95% CI 1.29–1.98, and OR 1.60, 95% CI 1.34–1.91, respectively). Low income and unemployment were not associated with high antibiotic use. Conclusion: Socioeconomic factors can only partially explain differences in antibiotic use. Further research is needed to clarify the unequal distribution of antibiotic prescribing and the association between high antibiotic use and low educational level. This would provide valuable information in the planning of strategies to promote rational use of antibiotics among children. KEY POINTS The Capital Region of Denmark has the highest rate of antibiotic prescribing in Denmark. Preschool children are among the age groups with the highest use. Ten percent of the children accounted for 25% of the total antibiotic use. Low parental educational level was associated with increased antibiotic use. Parents’ income or employment status was not found to be associated with high antibiotic use.

Matrix-assisted laser desorption/ionization-time of flight mass spectrometry identification of large colony beta-hemolytic streptococci containing Lancefield groups A, C, and G

Abstract Background: The aim of this study was to investigate whether large colony beta-hemolytic streptococci containing Lancefield groups A, C, and G can be adequately identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-ToF). Previous studies show varying results, with an identification rate from below 50% to 100%. Methods: Large colony beta-hemolytic streptococci containing Lancefield groups A, C, and G isolated from blood cultures between January 1, 2007 and May 1, 2012 were included in the study. Isolates were identified to the species level using a combination of phenotypic characteristics and 16s rRNA sequencing. The isolates were subjected to MALDI-ToF analysis. We used a two-stage approach starting with the direct method. If no valid result was obtained we proceeded to an extraction protocol. Scores above 2 were considered valid identification at the species level. Results: A total of 97 Streptococcus pyogenes, 133 Streptococcus dysgalactiae, and 2 Streptococcus canis isolates were tested; 94%, 66%, and 100% of S. pyogenes, S. dysgalactiae, and S. canis, respectively, were correctly identified by MALDI-ToF. Discussion: In most instances when the isolates were not identified by MALDI-ToF this was because MALDI-ToF was unable to differentiate between S. pyogenes and S. dysgalactiae. By removing two S. pyogenes reference spectra from the MALDI-ToF database the proportion of correctly identified isolates increased to 96% overall. MALDI-ToF is a promising method for discriminating between S. dysgalactiae, S. canis, and S. equi, although more strains need to be tested to clarify this.

Evaluating antibiotic stewardship programs in patients with bacteremia using administrative data: a cohort study

When introducing new antibiotic guidelines for empirical treatment of bacteremia, it is imperative to evaluate the performance of the new guideline. We examined the utility of administrative data to evaluate the effect of new antibiotic guidelines and the prognostic impact of appropriate empirical treatment. We categorized 2,008 adult patients diagnosed with bacteremia between 2010 and 2012 according to whether they received cephalosporins or fluoroquinolones (old regimen) or not (new regimen). We used administrative data to extract individual level data on mortality, readmission, and appropriateness of treatment, and computed adjusted hazard ratios (HRs) and 95xa0% confidence intervals (CIs) for 30-day mortality and post-discharge readmission by regimen and appropriateness of treatment. In total, 945 (47.1xa0%) were treated by the old regimen and 1,063 (52.9xa0%) by the new. The median length of stay (8xa0days) did not differ by regimen and neither did the proportion of those receiving appropriate empirical treatment (84.1xa0% vs. 85.5xa0%). However, fewer patients with the new regimen were admitted to the intensive care unit (ICU; 3.8xa0% vs. 12.0xa0%) and they had lower 30-day mortality (16.4xa0% vs. 23.4xa0%). The adjusted 30-day mortality HR for appropriate versus inappropriate treatment was 0.79 (95xa0% CI 0.62–1.01) and 0.83 (95xa0% CI 0.66–1.05) for the new versus the old regimen. The HR for 30-day readmission for appropriate versus inappropriate treatment was 0.91 (95xa0% CI 0.73–1.13) and 1.05 (95xa0% CI 0.87–1.25) for the new versus the old regimen. This study demonstrates that administrative data can be useful for evaluating the effect and quality of new bacteremia treatment guidelines.

Delayed antibiotic prescription for upper respiratory tract infections in children under primary care: Physicians’ views

Abstract Background: Overprescribing antibiotics for common or inaccurately diagnosed childhood infections is a frequent problem in primary healthcare in most countries. Delayed antibiotic prescriptions have been shown to reduce the use of antibiotics in primary healthcare. Objective: The aim was to examine primary care physicians’ views on delayed antibiotic prescriptions to preschool children with symptoms of upper respiratory tract infections (URTIs). Methods: A questionnaire was sent to 1180 physicians working in general practice in the Capital Region of Denmark, between January and March 2015. The questions focused on physicians’ attitude and use of delayed antibiotic prescriptions to children with URTIs. Results: The response rate was 49% (nu2009=u2009574). Seven per cent of the physicians often used delayed prescriptions to children with symptoms of URTI, but 46% believed that delayed prescription could reduce antibiotic use. The physicians’ views on delayed antibiotic prescription were significantly associated with their number of years working in general practice. Parents’ willingness to wait-and-see, need for reassurance, and knowledge about antibiotics influenced the physicians’ views. Also, clinical symptoms and signs, parents’ willingness to shoulder the responsibility, the capability of observation without antibiotic treatment, and structural factors like out-of-hour services were relevant factors in the decision. Conclusions: Most physicians, especially those with fewer years of practice, had a positive attitude towards delayed antibiotic prescription. Several factors influence the views of the physicians—from perceptions of parents to larger structural elements and years of experience.