Optimizing design of research to evaluate antibiotic stewardship interventions: consensus recommendations of a multinational working group.

BACKGROUND: Antimicrobial stewardship interventions and programmes aim to ensure effective treatment while minimizing antimicrobial-associated harms including resistance. Practice in this vital area is undermined by the poor quality of research addressing both what specific antimicrobial use interventions are effective and how antimicrobial use improvement strategies can be implemented into practice. In 2016 we established a working party to identify the key design features that limit translation of existing research into practice and then to make recommendations for how future studies in this field should be optimally designed. The first part of this work has been published as a systematic review. Here we present the working group's final recommendations. METHODS: An international working group for design of antimicrobial stewardship intervention evaluations was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). The group comprised clinical and academic specialists in antimicrobial stewardship and clinical trial design from six European countries. Group members completed a structured questionnaire to establish the scope of work and key issues to develop ahead of a first face-to-face meeting that (a) identified the need for a comprehensive systematic review of study designs in the literature and (b) prioritized key areas where research design considerations restrict translation of findings into practice. The working group's initial outputs were reviewed by independent advisors and additional expertise was sought in specific clinical areas. At a second face-to-face meeting the working group developed a theoretical framework and specific recommendations to support optimal study design. These were finalized by the working group co-ordinators and agreed by all working group members. RESULTS: We propose a theoretical framework in which consideration of the intervention rationale the intervention setting, intervention features and the intervention aims inform selection and prioritization of outcome measures, whether the research sets out to determine superiority or non-inferiority of the intervention measured by its primary outcome(s), the most appropriate study design (e.g. experimental or quasi- experimental) and the detailed design features. We make 18 specific recommendation in three domains: outcomes, objectives and study design. CONCLUSIONS: Researchers, funders and practitioners will be able to draw on our recommendations to most efficiently evaluate antimicrobial stewardship interventions.

ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers.

SCOPE: The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings. METHODS: These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations. RECOMMENDATIONS: The panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints.

Accuracy of comprehensive PCR analysis of nasopharyngeal and oropharyngeal swabs for CT-scan-confirmed pneumonia in elderly patients: a prospective cohort study.

OBJECTIVES: We aimed to assess the accuracy of PCR detection of viruses and bacteria on nasopharyngeal and oropharyngeal swabs (NPS) for the diagnosis of pneumonia in elderly individuals. METHODS: We included consecutive hospitalized elderly individuals suspected of having pneumonia. At inclusion, NPS were collected from all participants and tested by PCR for the presence of viral and bacterial respiratory pathogens (index test, defined as comprehensive molecular testing). Routine diagnostic tests (blood and sputum culture, urine antigen detection) were also performed. The reference standard was the presence of pneumonia on a low-dose CT scan as assessed by two independent expert radiologists. RESULTS: The diagnosis of pneumonia was confirmed in 127 of 199 (64%) included patients (mean age 83 years, community-acquired pneumonia in 105 (83%)). A pathogen was identified by comprehensive molecular testing in 114 patients (57%) and by routine methods in 22 (11%). Comprehensive molecular testing was positive for viruses in 62 patients (31%) and for bacteria in 73 (37%). The sensitivity and specificity were 61% (95% CI 53%-69%) and 50% (95% CI 39%-61%) for comprehensive molecular testing, and 14% (95% CI 82%-21%) and 94% (95% CI 86%-98%) for routine testing, respectively. Positive likelihood ratio was 2.55 for routine methods and 1.23 for comprehensive molecular testing. CONCLUSION: Comprehensive molecular testing of NPS increases the number of pathogens detected compared with routine methods, but results are poorly predictive of the presence of pneumonia. Hence, comprehensive molecular testing is unlikely to impact clinical decision-making (NCT02467192). CLINICAL TRIALS REGISTRATION: NCT02467192.

A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial.

OBJECTIVES: Intestinal carriage with extended spectrum ß-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. METHODS: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35-48 days after randomization (V4). ClinicalTrials.govNCT02472600. The trial was funded by the European Commission (FP7). RESULTS: Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT). CONCLUSIONS: Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.

ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers

The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings. Methods: These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporinresistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same timepoints and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations.

Views and experiences with regard to antibiotic use of hospitalized patients in five European countries: a qualitative descriptive study.

OBJECTIVES: To explore inpatients experiences and views with regard to antibiotics in five European hospitals. METHODS: Qualitative study where a patient-centred framework was used to explore inpatients' experiences concerning antibiotic treatment. A purposeful sample of inpatients treated with antibiotics in five hospitals participated in interviews (all centres) and focus groups (Switzerland only). RESULTS: A total of 31 interviews (five in Belgium, ten in Croatia, nine in France, five in the Netherlands and two in Switzerland) and three focus groups (in Switzerland, 11 participants) were performed. The median age of participants was 61 years (range 33-86 years). The following main themes emerged: (a) patients trust doctors to take the best decisions for them even though communication concerning different antibiotic-related aspects is often insufficient, (b) patients feel that doctors do not prioritize communication due to time constraints and do not seem to adapt information based on patients' preferences, (c) patients differ in their wish to be informed but overall want to be informed on the main aspects in an understandable way, (d) patients often find reassurance in sharing information about their antibiotic treatment with close family, (e) professionals should explore patients' preferences to be involved or not in shared decision making for antibiotic treatment. CONCLUSION: Inpatients often doubt their ability to understand medical information and trust their physicians to take the best decisions for them. Tailored strategies that inform hospitalized patients, acknowledging their concerns and preferences, may be useful to promote patient involvement and to improve communication regarding antibiotic use.

Patient-related determinants of antibiotic use: a systematic review.

OBJECTIVES: We aimed to assess patient-related determinants potentially influencing antibiotic use. METHODS: Studies published in MEDLINE until 30 September 2015 were searched. We included: qualitative studies describing patients' self-reported determinants of antibiotic use; and quantitative studies on either self-reported or objectively assessed determinants associated with antibiotic use. Whenever possible, reported determinants were categorized as 'barriers' or 'facilitators' of responsible antibiotic use. RESULTS: A total of 87 studies from 33 countries were included. Seventy-five (86.2%) were quantitative and described self-reported (45/75, 60.0%), objectively assessed (20/75, 26.7%) or self-reported and objectively assessed (10/75, 13.3%) patient-related determinants. Twelve (12/87, 13.8%) were qualitative studies or had a qualitative and quantitative component. Eighty-six of the studies (98.8%) concerned the outpatient setting. We identified seven broad categories of determinants having an impact on different aspects of antibiotic use (in descending order of frequency): demographic and socio-economic characteristics, patient-doctor interactions (e.g. counselling), treatment characteristics (e.g. administration frequency), attitudes (e.g. expecting antibiotics), access to treatment (e.g. patients' direct costs), characteristics of the condition for which the antibiotic was prescribed (e.g. duration of symptoms), knowledge (e.g. regarding indications for treatment). Most determinants were classified as 'barriers' to responsible antibiotic use. CONCLUSION: A large variety of patient-related determinants impact antibiotic use. The most easily 'modifiable' determinants concern patient-doctor interactions, treatment characteristics and knowledge. Data from the inpatient setting and low- and middle-income countries were underrepresented. Further studies should develop and test interventions that take these determinants into account with the ultimate aim of improving responsible use of antibiotics.

Effect of outpatient antibiotics for urinary tract infections on antimicrobial resistance among commensal Enterobacteriaceae: a multinational prospective cohort study.

OBJECTIVES: We quantified the impact of antibiotics prescribed in primary care for urinary tract infections (UTIs) on intestinal colonization by ciprofloxacin-resistant (CIP-RE) and extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE), while accounting for household clustering. METHODS: Prospective cohort study from January 2011 to August 2013 at primary care sites in Belgium, Poland and Switzerland. We recruited outpatients requiring antibiotics for suspected UTIs or asymptomatic bacteriuria (exposed patients), outpatients not requiring antibiotics (non-exposed patients), and one to three household contacts for each patient. Faecal samples were tested for CIP-RE, ESBL-PE, nitrofurantoin-resistant Enterobacteriaceae (NIT-RE) and any Enterobacteriaceae at baseline (S1), end of antibiotics (S2) and 28 days after S2 (S3). RESULTS: We included 300 households (205 exposed, 95 non-exposed) with 716 participants. Most exposed patients received nitrofurans (86; 42%) or fluoroquinolones (76; 37%). CIP-RE were identified in 16% (328/2033) of samples from 202 (28%) participants. Fluoroquinolone treatment caused transient suppression of Enterobacteriaceae (S2) and subsequent two-fold increase in CIP-RE prevalence at S3 (adjusted prevalence ratio (aPR) 2.0, 95% CI 1.2-3.4), with corresponding number-needed-to-harm of 12. Nitrofurans had no impact on CIP-RE (aPR 1.0, 95% CI 0.5-1.8) or NIT-RE. ESBL-PE were identified in 5% (107/2058) of samples from 71 (10%) participants, with colonization not associated with antibiotic exposure. Household exposure to CIP-RE or ESBL-PE was associated with increased individual risk of colonization: aPR 1.8 (95% CI 1.3-2.5) and 3.4 (95% CI 1.3-9.0), respectively. CONCLUSIONS: These findings support avoidance of fluoroquinolones for first-line UTI therapy in primary care, and suggest potential for interventions that interrupt household circulation of resistant Enterobacteriaceae.

What is antimicrobial stewardship?

BACKGROUND: The use of the term 'antimicrobial stewardship' has grown exponentially in recent years, typically referring to programmes and interventions that aim to optimize antimicrobial use. Although antimicrobial stewardship originated within human healthcare, it is increasingly applied in broader contexts including animal health and One Health. As the use of the term 'antimicrobial stewardship' becomes more common, it is important to consider what antimicrobial stewardship is, as well as what it is not. AIMS: To review the emergence and evolution of the term 'antimicrobial stewardship'. SOURCES: We searched and reviewed existing literature and official documents, which mostly focused on antibiotics. We contacted the authors of the first publications that mentioned antimicrobial stewardship. CONTENT: We describe the historical background behind how antimicrobial stewardship came into use in clinical settings. We discuss challenges emerging from the varied descriptions of antimicrobial stewardship in the literature, including an over-emphasis on individual prescriptions, an under-emphasis on the societal implications of antimicrobial use, and language translation problems. IMPLICATIONS: To help address these challenges, we suggest viewing antimicrobial stewardship as a strategy, a coherent set of actions which promote using antimicrobials responsibly. We stress the continuous need for 'responsible use' to be defined and translated into context-specific and time-specific actions. Furthermore, we present examples of actions that can be undertaken within antimicrobial stewardship across human and animal health.

Good epidemiological practice: a narrative review of appropriate scientific methods to evaluate the impact of antimicrobial stewardship interventions.

AIMS: In this narrative review, we provide a framework for assessing the quality of evidence provided by studies investigating antimicrobial stewardship (AMS) interventions, and inform the design and planning stage for future AMS evaluation studies to determine the best strategies to keep antimicrobial resistance at bay. SOURCES: Cochrane/Pubmed. CONTENT: As AMS is mostly applied in a complex, real-world setting, bias and random time effects can jeopardize the validity of causal inference. The most important risks include simultaneously implemented infection prevention strategies and regression to the mean. Inclusion of homogeneous intervention and control arms, through randomization of the intervention, can limit these risks. However, contamination can play an important role for AMS; therefore, randomization at cluster-level, instead of randomization at individual-level, is recommended. It can be challenging to identify enough representative clusters, and implementation of a cluster-RCT (cRCT) can be costly. Controlled interrupted time series (ITS) design has a high validity as well, and is relatively straightforward to implement, although time-varying confounding should be considered. Independent of the study design, it is crucial to include multiple process, clinical outcome, microbiological and financial measures, to be able to detect possible, unintended consequences. IMPLICATIONS: Future studies assessing the impact of new AMS strategies should produce compelling evidence by opting for cRCTs, or ITS including a control arm. Furthermore, a holistic view of intended and unintended consequences should be reported, and a detailed process evaluation should be provided to adequately inform implementation of successful AMS strategies to battle the rising burden of AMR.

Cefepime plasma concentrations and clinical toxicity: a retrospective cohort study.

OBJECTIVES: Cefepime remains an important antibiotic for severe bacterial infections, yet some meta-analyses have shown elevated mortality among patients randomized to it. Therapeutic drug monitoring (TDM) of ß-lactam antibiotics is increasing, but optimal plasma concentrations remain unknown. We examined clinical outcomes of patients undergoing cefepime TDM in an initial effort to define the drug's toxicity threshold. METHODS: In this single-centre retrospective cohort study, we enrolled all adult hospitalized patients receiving cefepime and undergoing TDM from January 2013 through July 2016. The primary outcome was the incidence of clinical toxicity; a secondary outcome was clinical failure. Plasma samples were analysed via high-performance liquid chromatography with ultraviolet detection. RESULTS: A total of 161 cefepime concentrations were drawn from 93 patients. Roughly half (82/161, 51%) and one-third (49/161, 30%) were trough and steady-state levels from patients receiving intermittent and continuous infusions, respectively; median concentrations were 17.6 mg/L (IQR 9.7-35.2) and 29.2 mg/L (IQR 18.9-45.9). Ten patients (11%) experienced a neurologic event considered at least possibly related to cefepime; neurotoxicity was associated with poorer renal function (median creatinine clearance 54 (IQR 39-97) vs. 75 mL/min/1.732 (IQR 44-104)) and longer cefepime durations (mean 8.3 (SD±6.7) vs. 13.3 days (± 14.2), p = 0.071). Patients with trough levels >20 mg/L had a fivefold higher risk for neurologic events (OR 5.05, 95% CI 1.3-19.8). CONCLUSIONS: Neurotoxicity potentially related to cefepime occurred at plasma concentrations >35 mg/L. For those receiving intermittent infusions, trough concentrations >20 mg/L should be avoided until further information is available from prospective studies.

Closing the evidence gap in infectious disease: point-of-care randomization and informed consent.

The informed consent document is intended to provide basic rights to patients but often fails to do so. Patients' autonomy may be diminished by virtue of their illness; evidence shows that even patients who appear to be ideal candidates for understanding and granting informed consent rarely are, particularly those with acute infections. We argue that for low-risk trials whose purpose is to evaluate nonexperimental therapies or other measures towards which the medical community is in a state of equipoise, ethics committees should play a more active role in a more standardized fashion. Patients in the clinic are continually subject to spontaneous 'pseudo-randomizations' based on local dogma and the anecdotal experience of their physicians. Stronger ethics oversight would allow point-of-care trials to structure these spontaneous randomizations, using widely available informatics tools, in combination with opt-out informed consent where deemed appropriate.

Special considerations of antibiotic prescription in the geriatric population.

Infectious diseases pose a major challenge in the elderly for two reasons: on the one hand the susceptibility to infection increases with age and when infections occur they often present atypically-on the other hand diagnostic uncertainty is much more pronounced in the geriatric population. Reconciling the opposing aspects of optimizing patient outcomes while avoiding antibiotic overuse requires significant expertise that can be provided by an infectious diseases consultant. In addition, geriatric facilities are reservoirs for multidrug-resistant organisms and other nosocomial pathogens, and infectious diseases consultants also play a vital role in assuring appropriate infection control measures. In this review we outline the challenges of diagnosis and management of infectious diseases in the elderly, and discuss the importance of appropriate antibiotic use in the elderly in order to demonstrate the value of the infectious diseases consultant in this special setting.

Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection.

OBJECTIVES: The therapeutic arsenal for MRSA infections is limited. The aim of this study was to assess the non-inferiority of a combination of trimethoprim/sulfamethoxazole plus rifampicin versus linezolid alone for the treatment of MRSA infection. METHODS: We conducted a randomized, open-label, single-centre, non-inferiority trial comparing trimethoprim/sulfamethoxazole (160 mg/800 mg three times daily) plus rifampicin (600 mg once a day) versus linezolid (600 mg twice a day) alone in adult patients with various types of MRSA infection. Patients were allocated 1:1 to either regimen. The primary outcome was clinical cure at 6 weeks after the end of treatment (non-inferiority margin 20%) assessed by both ITT and PP analyses. Secondary outcomes included the microbiologically documented persistence of MRSA in clinical cultures, mortality and adverse events. The study protocol has been registered with ClinicalTrials.gov (NCT00711854). RESULTS: Overall, 150 patients were randomized to one of the two treatment arms between January 2009 and December 2013 and were included in the ITT analysis. Of these 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole and rifampicin group experienced clinical success (risk difference 4%, 95% CI -9.7% to 17.6%). The results were confirmed by the PP analysis, with 54/66 (81.8%) cured patients in the linezolid group versus 52/59 (88.1%) in the trimethoprim/sulfamethoxazole and rifampicin group (risk difference 6.3%, 95% CI -6.8% to 19.2%). There were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure. Four adverse drug reactions attributed to the study medication occurred in the linezolid group versus nine in the trimethoprim/sulfamethoxazole and rifampicin group. CONCLUSIONS: Compared with linezolid, trimethoprim/sulfamethoxazole and rifampicin seems to be non-inferior in the treatment of MRSA infection.

[Pneumonia in the elderly: are there any specificities? ]. / Pneumonie chez Le sujet âgé: y a-t-il des spécificités?

Pneumonia is one of the leading causes of death in the elderly. Streptococcus pneumoniae is the leading etiological agent, but the identification of a pathogen remains infrequent despite advances in microbiological methods. Antibiotic resistant organisms should be considered as potential causal agents in recently hospitalized patients and patients with recent antibiotic exposure and influenza during the flu season. The clinical diagnosis is difficult due to frequent atypical presentation. Prognostic scores are not always appropriate to predict the need for hospitalization in very old patients. Studies on the role of low-dose chest CT for the diagnosis, management and prevention should help improve the management of this disease in the future.

Success stories of implementation of antimicrobial stewardship: a narrative review.

It has been increasingly recognized that antimicrobial stewardship (AMS) has to be a key component of any efforts that aim to mitigate the current global antimicrobial resistance (AMR) crisis. It has also become evident that AMR is a problem that cannot be tackled by single institutions or physicians, but needs concerted actions at regional, national and supra-national levels. However, it is easy to become discouraged, given the problems that are often encountered when implementing AMS. The aim of this review is to highlight some of the success stories of AMS strategies, and to describe the actions that have been taken, the outcomes that have been obtained, and the obstacles that have been met. Although the best approach to effective AMS remains elusive and may vary significantly among settings, these diverse examples from a range of healthcare contexts demonstrate that effective AMS is possible. Such examples will inform others and encourage them to formally evaluate and share their results with the global stewardship community.

What do Spaniards read about the prudent use of anti-microbial agents and what do they really do?

OBJECTIVES: The prudent use of antibiotics (PUA) is promoted not only by public information campaigns, but also in the printed media and on websites. This study assesses the correspondence between PUA information in the Spanish printed media and on websites and the messages put out by national campaigns. Spaniards' use of antibiotics following the campaigns was also analysed. METHODS: A two-phase descriptive study was carried out. First, antibiotics-related news in the Spanish printed media (January 2007-May 2009) and institutional and news media websites (March-May 2009) were systematically reviewed using a data collection tool. In addition, a telephone survey on antibiotics-related knowledge and behaviours was carried out with a random sample of 1526 people living in Spain who had recently received medical care. RESULTS: In total, 29 news items containing nine different messages were identified. All the messages were similar to those promoted by the campaigns. The survey showed that even after the campaigns, relevant gaps in knowledge about the PUA persist, particularly among men (p = .005), those living in rural areas (p = .02) and the elderly (p < .001). Keeping left-over antibiotics was associated with ignorance about the association between antibiotic use and resistance (OR 3.1, 95% CI 2.3-4.2). Also, patients who ask their doctor about drug interactions are less likely to self-medicate (p = .04). CONCLUSIONS: The information reaching the Spanish public via the media seems to be similar to the messages transmitted by public information campaigns. Nevertheless, there appears to be considerable room for improvement. Promoting an active role in patients might reduce self-medication.