Jens Otto Jarløv

Excretion of ciprofloxacin in sweat and multiresistant Staphylococcus epidermidis

BACKGROUND Staphylococcus epidermidis develops resistance to ciprofloxacin rapidly. That this antibiotic is excreted in apocrine and eccrine sweat of healthy individuals might be the reason for the development of such resistance. We assessed whether S epidermidis isolated from the axilla and nasal flora of healthy people could develop resistance to ciprofloxacin after a 1-week course of this antibiotic. METHODS The concentration of ciprofloxacin in sweat was measured in seven volunteers after oral administration of 750 mg ciprofloxacin twice daily for 7 days, and the development of resistance in S epidermidis from axilla and nostrils was monitored during and 2 months after the treatment. Genotyping of S epidermidis was done by restriction fragment length polymorphism. FINDINGS The mean concentration of ciprofloxacin in sweat increased during the 7 days of treatment-from 2.2 micrograms/mL 2.5 h after the first tablet to 2.5 micrograms/mL after the fifth tablet, and 5.5 micrograms/mL after the 13th tablet. All persons harboured susceptible S epidermidis (minimal inhibitory concentration [MIC] 0.25 microgram/mL) in axilla and nostrils before treatment. Four resistant strains were detected, two intermediate-level (MIC 4-12 micrograms/mL) and two high-level (MIC > 32 micrograms/mL). Three of these strains were found in all the participants, and a ciprofloxacin-sensitive variant of one of the high-level resistant strains was also found before the start of the treatment. The high-level resistant strains were also resistant to methicillin, erythromycin, gentamicin, sulphonamide, and trimethoprim. A mean of 2.7 days after the start of the treatment, development of ciprofloxacin resistance was detected in S epidermidis from the axilla of all persons, compared with 11 days for the appearance of resistant S epidermidis in nostrils. The resistant strains persisted for an average of 37 and 39 days in axilla and nostrils, respectively, after the end of the treatment. INTERPRETATION The rapid development of resistance to ciprofloxacin due to excretion of this drug into the sweat might be involved in the development of multiresistant S epidermidis and possibly other skin bacteria in hospitals and in communities with high use of ciprofloxacin or related drugs.

Comparing Whole-Genome Sequencing with Sanger Sequencing for spa Typing of Methicillin-Resistant Staphylococcus aureus

ABSTRACT spa typing of methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been done by PCR amplification and Sanger sequencing of the spa repeat region. At Hvidovre Hospital, Denmark, whole-genome sequencing (WGS) of all MRSA isolates has been performed routinely since January 2013, and an in-house analysis pipeline determines the spa types. Due to national surveillance, all MRSA isolates are sent to Statens Serum Institut, where the spa type is determined by PCR and Sanger sequencing. The purpose of this study was to evaluate the reliability of the spa types obtained by 150-bp paired-end Illumina WGS. MRSA isolates from new MRSA patients in 2013 (n = 699) in the capital region of Denmark were included. We found a 97% agreement between spa types obtained by the two methods. All isolates achieved a spa type by both methods. Nineteen isolates differed in spa types by the two methods, in most cases due to the lack of 24-bp repeats in the whole-genome-sequenced isolates. These related but incorrect spa types should have no consequence in outbreak investigations, since all epidemiologically linked isolates, regardless of spa type, will be included in the single nucleotide polymorphism (SNP) analysis. This will reveal the close relatedness of the spa types. In conclusion, our data show that WGS is a reliable method to determine the spa type of MRSA.

Coagulase‐negative staphylococci in a major Danish university hospital: diversity in antibiotic susceptibility between wards

Over a one‐year period, all coagulase‐negative staphylococci (CoNS) from blood cultures, cerebrospinal fluids and peritoneal effluents from patients in a major Danish university hospital were investigated for susceptibility to penicillin G; methicillin; gentamicin; netilmicin; amikacin; erythromycin; clindamycin; fusidic acid; rifampicin; tetracycline; chloramphenicol; ciprofloxacin; teicoplanin; and vancomycin. Among the CoNS‐isolates, 56% were resistant to methicillin, 51% to gentamicin, 28% to ciprofloxacin, and 5% to teicoplanin. Blood culture CoNS‐isolates from patients with a central venous catheter (CVC) were more often resistant to various antibiotics compared to CoNS‐isolates from patients without a CVC, e.g. methicillin (72%vs 21%), gentamicin (65%vs 22%) (p<0.00000001). Great diversity in antibiotic resistance between the wards was found; methicillin resistance (in most cases multiple antibiotic resistance) was in particular associated with consumption of broad‐spectrum (β‐lactams, quinolones, and total antibiotic consumption in a ward. Thus, the antibiotic policy of a ward is an important factor for antibiotic resistance among CoNS.

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

OBJECTIVES We 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. METHODS The 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). RESULTS Direct 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)]. CONCLUSIONS The 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.

Antibiotic prophylaxis for transrectal prostate biopsy—a new strategy

BACKGROUND Fluoroquinolones 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. PATIENTS AND METHODS This 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. RESULTS One 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%). CONCLUSIONS The 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.

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 (n = 139,398) in the Capital Region of Denmark. Main outcome measures: High use of antibiotics identified by number of antibiotic prescriptions (≥ 3 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.

Autologous transfusion of shed mediastinal blood after coronary artery bypass grafting and bacterial contamination

BACKGROUND Autologous transfusion of shed mediastinal blood is often used after coronary artery bypass grafting (CABG). Shed blood has in a few studies been cultured during the first postoperative hours. However, autologous transfusion might in some cases be continued for several hours and no study has yet examined the bacterial contamination of shed blood later than 6 hours postoperatively. METHODS Seventy-five patients undergoing electively performed CABG were included. Cultures of shed blood were taken at initiation of the autologous transfusion and the following morning. Infection variables were measured preoperatively and postoperatively. Infectious complications during the first postoperative week were registered. RESULTS The frequency of patients with bacterial growth in the first culture was 0.22 (95% confidence interval: 0.12 to 0.31) compared with 0.04 (95% confidence interval: -0.044 to 0.087) in the second culture (p < 0.002). We found no significant difference in infection variables between patients with or without bacterial growth in the cultures. No patients suffered from early postoperative infectious complications. CONCLUSIONS There is no further contamination of the shed blood during the period between initiating the autologous transfusion and the following morning.

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% (n = 574). 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.