Casper D. J. den Heijer

Prevalence and resistance of commensal Staphylococcus aureus, including meticillin-resistant S aureus, in nine European countries: a cross-sectional study

BACKGROUND Information about the prevalence of Staphylococcus aureus resistance to antimicrobial drugs has mainly been obtained from invasive strains, although the commensal microbiota is thought to be an important reservoir of resistance. We aimed to compare the prevalence of nasal S aureus carriage and antibiotic resistance, including meticillin-resistant S aureus (MRSA), in healthy patients across nine European countries. METHODS In this cross-sectional study, nasal swabs were obtained from 32,206 patients recruited by family doctors participating in existing nationwide family doctor networks in Austria, Belgium, Croatia, France, Hungary, Spain, Sweden, the Netherlands, and the UK. Eligible patients were aged 4 years or older (≥ 18 years in the UK) and presented with a non-infectious disorder. Swabs were sent to national microbiological laboratories for identification and isolation of S aureus. Antibiotic resistance testing was done at one central microbiological laboratory. We established the genotypic structure of the isolated MRSA strains with the spa typing method. FINDINGS S aureus was isolated from 6956 (21 · 6%) of 32,206 patients swabbed. The adjusted S aureus prevalence for patients older than 18 years ranged from 12 · 1% (Hungary) to 29 · 4% (Sweden). Except for penicillin, the highest recorded resistance rate was to azithromycin (from 1 · 6% in Sweden to 16 · 9% in France). In total, 91 MRSA strains were isolated, and the highest MRSA prevalence was reported in Belgium (2 · 1%). 53 different spa types were detected-the most prevalent were t002 (n = 9) and t008 (n = 8). INTERPRETATION The prevalence of S aureus nasal carriage differed across the nine European countries assessed, even after correction for age, sex, and family doctor. Generally, the prevalence of resistance, including that of MRSA, was low. The MRSA strains recorded showed genotypic heterogeneity, both within and between countries. FUNDING European Commission, 7th Framework Programme(grant agreement 223083).

The appropriateness of prescribing antibiotics in the community in Europe: study design

BackgroundOver 90% of all antibiotics in Europe are prescribed in primary care. It is important that antibiotics are prescribed that are likely to be effective; however, information about antibiotic resistance in the community is incomplete. The aim of our study is to investigate the appropriateness of antibiotic prescribing in primary care in Europe by collecting and combining patterns of antibiotic resistance patterns and antibiotic prescription patterns in primary care. We will also evaluate the appropriateness of national antibiotic prescription guidelines in relation to resistance patterns.Methods/DesignAntibiotic resistance will be studied in an opportunistic sample from the community in nine European countries. Resistance data will be collected by taking a nose swab of persons (N = 4,000 per country) visiting a primary care practice for a non-infectious disease. Staphylococcus aureus and Streptococcus pneumoniae will be isolated and tested for resistance to a range of antibiotics in one central laboratory. Data on antibiotic prescriptions over the past 5 years will be extracted from the electronic medical records of General Practitioners (GPs). The results of the study will include the prevalence and resistance data of the two species and 5 years of antibiotic prescription data in nine European countries.The odds of receiving an effective antibiotic in each country will be calculated as a measure for the appropriateness of prescribing. Multilevel analysis will be used to assess the appropriateness of prescribing. Relevant treatment guidelines of the nine participating countries will be evaluated using a standardized instrument and related to the resistance patterns in that country.DiscussionThis study will provide valuable and unique data concerning resistance patterns and prescription behaviour in primary care in nine European countries. It will provide evidence-based recommendations for antibiotic treatment guidelines that take resistance patterns into account which will be useful for both clinicians and policy makers. By improving antibiotic use we can move towards controlling the resistance problem globally.

Antibiotic Exposure and Other Risk Factors for Antimicrobial Resistance in Nasal Commensal Staphylococcus aureus: An Ecological Study in 8 European Countries

Objectives Antimicrobial resistance (AMR) has become a global public health concern which threatens the effective treatment of bacterial infections. Resistant Staphylococcus aureus (including MRSA) increasingly appears in individuals with no healthcare associated risks. Our study assessed risk factors for nasal carriage of resistant S. aureus in a multinational, healthy, community-based population, including ecological exposure to antibiotics. Methods Data were collected in eight European countries (Austria, Belgium, Croatia, France, Hungary, the Netherlands, Spain and Sweden). Commensal AMR patterns were assessed by collecting 28,929 nasal swabs from healthy persons (aged 4+). Ecological exposure to antibiotics was operationalized as systemic antibiotic treatment patterns, extracted from electronic medical records of primary care practices in which the participants were listed (10–27 per country). A multilevel analysis related AMR in nasal commensal S. aureus to antibiotic exposure and other risk factors (e.g. age and profession). Results Of the 6,093 S. aureus isolates, 77% showed resistance to at least one antibiotic. 7.1% exhibited multidrug resistance (defined as resistance to 3 or more antibiotic classes), and we found 78 cases MRSA (1.3%). A large variation in antibiotic exposure was found between and within countries. Younger age and a higher proportion of penicillin prescriptions in a practice were associated with higher odds for carriage of a resistant S. aureus. Also, we found higher multidrug resistance rates in participants working in healthcare or nurseries. Conclusions This study indicates that in a population with no recent antibiotic use, the prescription behavior of the general practitioner affects the odds for carriage of a resistant S. aureus, highlighting the need for cautious prescribing in primary care. Finally, since variation in AMR could partly be explained on a national level, policy initiatives to decrease AMR should be encouraged at the national level within Europe.

The Importance of Gender-Stratified Antibiotic Resistance Surveillance of Unselected Uropathogens: A Dutch Nationwide Extramural Surveillance Study

Few studies have been performed on urinary tract infections (UTIs) in men. In the present study, general practitioners (n = 42) from the Dutch Sentinel General Practice Network collected urinary samples from 560 male patients (≥18 years) suspected of UTI and recorded prescribed antibiotic treatment. In this way, the antibiotic susceptibility of Gram-negative uropathogens, including extended-spectrum beta-lactamase (ESBL-) producing Escherichia coli could be determined. In addition, E. coli susceptibility and antibiotic prescriptions were compared with data from a similar UTI study among women and with data collected 7 years earlier. Of 367 uropathogens (66%) identified (≥103 cfu/mL), most were Gram-negative (83%) and E. coli being isolated most frequently (51%). Antibiotic susceptibility to ciprofloxacin, norfloxacin and nitrofurantoin was 94%, 92% and 88%, respectively, whereas co-amoxiclav (76%) and co-trimoxazole (80%) showed lower susceptibilities. One ESBL (0.5%) was found. A significantly higher proportion of female UTIs was caused by E. coli compared with men (72% versus 51%, P<0.05). E. coli susceptibility tended to be lower in men compared with women, although not reaching statistical significance. No changes in E. coli susceptibility were observed over time (all P>0.05). Co-amoxiclav and nitrofurantoin prescriptions increased over time (11% versus 28% and 16% versus 23% respectively, both P<0.05), whereas co-trimoxazole prescriptions decreased (24% versus 14%, P<0.05). In conclusion, given the observed gender differences in uropathogen distribution and (tendency in) E. coli antibiotic susceptibility, empirical male UTI treatment options should be based on surveillance studies including men only. When awaiting the culture result is clinically not possible, fluoroquinolones are advised as first-choice antibiotics for male UTIs in Dutch general practices based on current antibiotic susceptibility data. The prevalence of ESBL-producers was low and no differences were observed in antibiotic susceptibility over a 7-year period. In addition, antibiotic prescriptions changed in accordance with national guidelines during this time period.

Primary care treatment guidelines for skin infections in Europe: congruence with antimicrobial resistance found in commensal Staphylococcus aureus in the community

BackgroundOver 90% of antibiotics for human use in Europe are prescribed in primary care. We assessed the congruence between primary care treatment guidelines for skin infections and commensal Staphylococcus aureus (S. aureus) antimicrobial resistance levels in community-dwelling persons.MethodsThe prevalence of antimicrobial resistance in S. aureus was analysed by taking nose swabs from healthy primary care patients in nine European countries (total N = 32,032). Primary care treatment guidelines for bacterial skin infections were interpreted with respect to these antimicrobial resistance patterns. First- and second-choice recommendations were assessed and considered congruent if resistance to the antibiotic did not exceed 20%.ResultsWe included primary care treatment guidelines for impetigo, cellulitis, folliculitis and furuncle. Treatment recommendations in all countries were consistent: most of the first-choice recommendations were beta-lactams, both for children and adults. Antimicrobial resistance levels were low, except for penicillin (on average 73% resistance). Considerable variation in antimicrobial resistance levels was found between countries, with Sweden displaying the lowest levels and Spain the highest. In some countries resistance to penicillin and azithromycin was significantly higher in children (4-17 years) compared with adults.ConclusionsMost of the first- and second-choice recommendations in the treatment guidelines for skin infections were congruent with commensal S. aureus antimicrobial resistance patterns in the community, except for two recommendations for penicillin. Given the variation in antimicrobial resistance levels between countries, age groups and health care settings, national data regarding antimicrobial resistance in the community should be taken into account when updating or developing primary care treatment guidelines.

Who tests whom? A comprehensive overview of Chlamydia trachomatis test practices in a Dutch region among different STI care providers for urogenital, anorectal and oropharyngeal sites in young people: a cross-sectional study

Objectives To evaluate and compare Chlamydia trachomatis (CT) diagnostic test practices of different sexually transmitted infection (STI) care providers in 16–29 year olds from one defined geographic Dutch region (280 000 inhabitants). Both number and proportion of positive CT tests (ie, test positivity) were assessed, and factors associated with these outcomes. Methods Data on laboratory testing and diagnosis of urogenital, anorectal and oropharyngeal CT between 2006 and 2010 were retrieved from general practitioners (GPs), gynaecologists, an STI clinic and a population-based chlamydia screening programme. Multivariable regression analyses explored associations between age, sex, test year, socio-economic status (SES) and STI care provider and the outcomes being the number of tests and test positivity. Results Overall, 22 831 tests were performed (1868 positive; 8.2%). Extragenital (ie, anorectal and oropharyngeal) tests accounted for 4% of all tests (7.5% positive) and were almost exclusively (99%) performed by the STI clinic. STI clinics tested most men (37.2% of all tested men), whereas GPs tested most women (29.9% of all tested women). GPs and STI clinics accounted for 73.3% (1326/1808) of urogenital CT diagnoses. In women, the number of tests increased with age, whereas test positivity decreased for all STI care providers. Lower SES was associated with higher test positivity in GP and gynaecology patients. Conclusions STI clinics performed most CT tests in men, whereas GPs performed most CT tests in women. GPs and STI clinics accounted for the majority of positives. Extragenital CT testing is rarely performed outside the STI clinic and needs to be promoted, especially in men who have sex with men.

Determinants of Antimicrobial Resistance in Escherichia coli Strains Isolated from Faeces and Urine of Women with Recurrent Urinary Tract Infections

For women with recurrent urinary tract infections (rUTI), the contribution of antibiotic use versus patient-related factors in determining the presence of antimicrobial resistance in faecal and urinary Escherichia coli, obtained from the same patient population, has not been assessed yet. Within the context of the ‘Non-antibiotic prophylaxis for recurrent urinary tract infections’ (NAPRUTI) study, the present study assessed determinants of antimicrobial resistance in E. coli isolated from urinary and faecal samples of women with rUTIs collected at baseline. Potential determinants of resistance were retrieved from self-administered questionnaires. From 434 asymptomatic women, 433 urinary and 424 faecal samples were obtained. E. coli was isolated from 146 (34%) urinary samples and from 336 (79%) faecal samples, and subsequently tested for antimicrobial susceptibility. Multivariable analysis showed trimethoprim/sulfamethoxazole (SXT) use three months prior to inclusion to be associated with urine E. coli resistance to amoxicillin (OR 3.6, 95% confidence interval: 1.3–9.9), amoxicillin-clavulanic acid (OR 4.4, 1.5–13.3), trimethoprim (OR 3.9, 1.4–10.5) and SXT (OR 3.2, 1.2–8.5), and with faecal E. coli resistance to trimethoprim (OR 2.0, 1.0–3.7). The number of UTIs in the preceding year was correlated with urine E. coli resistance to amoxicillin-clavulanic acid (OR 1.11, 1.01–1.22), trimethoprim (OR 1.13, 1.03–1.23) and SXT (OR 1.10, 1.01–1.19). Age was predictive for faecal E. coli resistance to amoxicillin (OR 1.02, 1.00–1.03), norfloxacin and ciprofloxacin (both OR 1.03, 1.01–1.06). In conclusion, in women with rUTI different determinants were found for urinary and faecal E. coli resistance. Previous antibiotic use and UTI history were associated with urine E. coli resistance and age was a predictor of faecal E. coli resistance. These associations could best be explained by cumulative antibiotic use.

Diagnostic approach to urinary tract infections in male general practice patients: a national surveillance study.

BACKGROUND Diagnostic urinary tract infection (UTI) studies have primarily been performed among female patients. AIM To create a diagnostic algorithm for male general practice patients suspected of UTI. DESIGN AND SETTING Surveillance study in the Dutch Sentinel General Practice Network. METHOD Clinical information and dipstick results were collected from 603 patients. Algorithm-predicted care was compared with care as usual in terms of sensitivity (antibiotic recommended when UTI was confirmed) and specificity (no antibiotic recommended when no UTI was observed). RESULTS Complete information was available from 490/603 (81%) males, of whom 66% (321/490) had a UTI. A diagnostic algorithm recommending antimicrobial prescription in the case of a positive nitrite test or a positive leukocyte esterase test in males aged ≥60 years, had a positive predictive value (PPV) of 83% (95% confidence interval [CI] = 78 to 87) and a negative predictive value (NPV) of 60% (95% CI = 52 to 66), respectively (area under the ROC curve: 0.78, 95% CI = 0.74 to 0.82). When both dipstick results were positive in males aged ≥60 years, PPV increased to 90% (95% CI = 83 to 94), whereas NPV was highest in males <60 years with negative dipstick results (71%, 95% CI = 59 to 81). Sensitivity and specificity of predicted UTI care and usual care did not differ (75% versus 79%, P = 0.30, and 70% versus 63%, P = 0.17, respectively). CONCLUSION UTI care provided to Dutch male GP patients is as accurate as predicted care from a diagnostic algorithm. The studied clinical information and dipstick tests are useful for ruling in UTI in males, but have limited value in ruling out this diagnosis.

Evaluation of phenotypic and molecular methods for identification of Streptococcus pneumoniae

AIM The objective of this study is to compare various Streptococcus pneumoniae identification methods. MATERIALS & METHODS In total, 1371 putative S. pneumoniae isolates were tested with three phenotypic methods and a molecular-based method targeting a virulence factor (CpsA). We assessed the sensitivity and the specificity of each method and widely used S. pneumoniae identification algorithm. RESULTS None of the methods or the identification algorithm used separately was able to correctly identify all S. pneumoniae isolates. Furthermore, a high rate of optochin resistance was found. CONCLUSIONS We demonstrated the failure of the current S. pneumoniae identification methods and optochin susceptibility-based algorithm. In addition, the high rate of optochin resistance might justify the necessity of a close monitoring of optochin susceptibility.

Antibiotic Use before Chlamydia and Gonorrhea Genital and Extragenital Screening in the Sexually Transmitted Infection Clinical Setting

ABSTRACT Background antibiotic use (i.e., administration of antibiotics not directly related to Chlamydia trachomatis or Neisseria gonorrhoeae infections) has been associated with a lower prevalence of genital C. trachomatis infection in a clinical setting. Associations with specific antibiotic types or with N. gonorrhoeae are lacking. Here, we assessed the prevalence of antibiotic use, the different classes and agents used, and their association with a subsequent sexually transmitted infection (STI) clinic C. trachomatis and N. gonorrhoeae test result. At our STI clinic, we systematically registered whether antibiotics were used in the past month (in 29% of the cases, the specific antibiotic agent was named). Patients were screened for urogenital C. trachomatis and N. gonorrhoeae; a third of them were also screened for anorectal and oropharyngeal C. trachomatis and N. gonorrhoeae. The proportion of antibiotics used and their association with C. trachomatis and N. gonorrhoeae prevalence were assessed for heterosexual men, men who have sex with men (MSM), and women. During 14,775 clinic consultations, antibiotic use was reported by 12.2% (95% confidence interval [CI], 11.7% to 12.7%), i.e., 14.8% of women, 8.6% of heterosexual men, and 11.6% of MSM. The most reported antibiotics were penicillins, tetracyclines, and macrolides, respectively. The prevalence was 11.0% (95% CI, 10.3% to 11.3%) for C. trachomatis and 1.9% (95% CI, 1.7% to 2.1%) for N. gonorrhoeae. Only tetracycline use was associated with a lower C. trachomatis prevalence (3%). Overall antibiotic use was associated with lower anorectal C. trachomatis prevalence in MSM only (odds ratio, 0.4; 95% CI, 0.2 to 0.8). STI clinic visitors commonly report recent antibiotic use. Even in a country with low antibiotic consumption, tetracycline use impacted C. trachomatis prevalence, while there was a notable absence of association with azithromycin.