Managing a cluster outbreak of psittacosis in Belgium linked to a pet shop visit in The Netherlands.

In July 2013, a Belgian couple were admitted to hospital because of pneumonia. Medical history revealed contact with birds. Eleven days earlier, they had purchased a lovebird in a pet shop in The Netherlands. The bird became ill, with respiratory symptoms. The couple's daughter who accompanied them to the pet shop, reported similar symptoms, but was travelling abroad. On the suspicion of psittacosis, pharyngeal swabs from the couple were taken and sent to the Belgian reference laboratory for psittacosis. Culture and nested polymerase chain reaction (PCR) tests were positive for the presence of Chlamydia psittaci, and ompA genotyping indicated genotype A in both patients. The patients were treated with doxycycline and the daughter started quinolone therapy; all three recovered promptly. Psittacosis is a notifiable disease in Belgium and therefore local healthcare authorities were informed. They contacted their Dutch colleagues, who visited the pet shop. Seven pooled faecal samples were taken and analysed using PCR by the Dutch national reference laboratory for notifiable animal diseases for the presence of Chlamydia psittaci. Four (57%) samples tested positive, genotyping revealed genotype A. Enquiring about exposure to pet birds is essential when patients present with pneumonia. Reporting to health authorities, even across borders, is warranted to prevent further spread.

Direct molecular versus culture-based assessment of Gram-positive cocci in biopsies of patients with major abscesses and diabetic foot infections.

Major abscesses and diabetic foot infections (DFIs) are predominant subtypes of complicated skin and skin structure infections (cSSSIs), and are mainly caused by Staphylococcus aureus and ß-hemolytic streptococci. This study evaluates the potential benefit of direct pathogen-specific real-time polymerase chain reaction (PCR) assays in the identification of causative organisms of cSSSIs. One-hundred and fifty major abscess and 128 DFI biopsy samples were collected and microbial DNA was extracted by using the Universal Microbe Detection kit for tissue samples. Pathogen-specific PCRs were developed for S. aureus and its virulence factor Panton-Valentine leukocidin (PVL), Streptococcus pyogenes, S. agalactiae, S. dysgalactiae, and the S. anginosus group. Identification by pathogen-specific PCRs was compared to routine culture and both methods were considered as the gold standard for determination of the sensitivity and specificity of each assay. Direct real-time PCR assays of biopsy samples resulted in a 34 % higher detection of S. aureus, 37 % higher detection of S. pyogenes, 18 % higher detection of S. agalactiae, 4 % higher detection of S. dysgalactiae subspecies equisimilis, and 7 % higher detection of the S. anginosus group, compared to routine bacterial culture. The presence of PVL was mainly confined to S. aureus isolated from major abscess but not DFI biopsy samples. In conclusion, our pathogen-specific real-time PCR assays had a higher yield than culture methods and could be an additional method for the detection of relevant causative pathogens in biopsies.

Polymorphisms in cytokine genes IL6, TNF, IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections.

Complicated skin and skin structure infections (cSSSIs) are caused by Gram-positive and Gram-negative, aerobic and anaerobic pathogens, with a polymicrobial aetiology being frequent. Recognition of invading pathogens by the immune system results in the production of pro- and anti-inflammatory cytokines, which are extremely important for intercellular communication and control of infection. This study assessed whether genetic variation in genes encoding cytokines influences the susceptibility to cSSSIs. For the association study, 318 patients with cSSSI and 328 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) in cytokine genes IL1A, IL1B, IL1RN, TNF, IL10, IL17A, IL17F and IFNG. For immunological validation, peripheral blood mononuclear cells (PBMCs) from 74 healthy individuals, genotyped for SNPs of interest, were stimulated with Staphylococcus aureus or Escherichia coli and corresponding cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). Polymorphisms IL6 rs1800797, TNF rs1800629, IL10 rs1800871, IL17A rs8193036 and IFNG rs2069705 influenced susceptibility to cSSSIs. No differences in cytokine responses, stratified for genotype, were detected after PBMC stimulation. No association with cSSSIs was observed for polymorphisms IL1A rs17561 and rs1800587, IL1B rs16944 and rs1143627, IL1RN rs4251961, TNF rs361525, IL10 rs1800896, IL17A rs2275913 and IL17F rs763780. In conclusion, polymorphisms in IL6, TNF, IL10, IL17A and IFNG are associated with susceptibility to cSSSIs.

Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study.

OBJECTIVE: The aim was to compare the efficacy and safety of two antibiotic regimens in patients with diabetic foot infections (DFIs). METHODS: Data of a subset of patients enrolled in the RELIEF trial with DFIs requiring surgery and antibiotics were evaluated retrospectively. DFI was diagnosed on the basis of the modified Wagner, University of Texas, and PEDIS classification systems. Patients were randomized to receive either intravenous/oral moxifloxacin (MXF, N = 110) 400 mg q.d. or intravenous piperacillin/tazobactam 4.0/0.5 g t.d.s. followed by oral amoxicillin/clavulanate 875/125 mg b.d. (PIP/TAZ-AMC, N = 96), for 7-21 days until the end of treatment (EOT). The primary endpoint was clinical cure rates in the per-protocol (PP) population at the test-of-cure visit (TOC, 14-28 days after EOT). RESULTS: There were no significant differences between the demographic characteristics of PP patients in either treatment group. At TOC, MXF and PIP/TAZ-AMC had similar efficacy in both the PP and intent-to-treat (ITT) populations: MXF: 76.4 % versus PIP/TAZ-AMC: 78.1 %; 95 % confidence interval (CI) -14.5 %, 9.0 % in the PP population; MXF: 69.9 % versus PIP/TAZ-AMC: 69.1 %; 95 % CI -12.4 %, 12.1 % in the ITT population. The overall bacteriological success rates were similar in both treatment groups (MXF: 71.7 % versus PIP/TAZ-AMC: 71.8 %; 95 % CI -16.9 %, 10.7 %). A similar proportion of patients (ITT population) experienced any adverse events in both treatment groups (MXF: 30.9 % versus PIP/TAZ-AMC: 31.8 %, respectively). Death occurred in three MXF-treated patients and one PIP/TAZ-AMC-treated patient; these were unrelated to the study drugs. CONCLUSION: Moxifloxacin has shown favorable safety and efficacy profiles in DFI patients and could be an alternative antibiotic therapy in the management of DFI. CLINICAL TRIAL: NCT00402727.

Q fever across the Dutch border in Limburg province, Belgium.

Data from three different data sources were compiled to estimate the presence of Coxiella burnetii in the Belgian Limburg province for both humans and livestock. First, serological data of all samples sent to the Belgian reference centre (2003­2010) for human Q fever were analysed, showing evidence for an acute Q fever infection in 1­5% of the cases. Second, a multi-centre prospective survey was conducted in Limburg in 2010 to detect undiagnosed human cases; evidence for a recent infection with Coxiella burnetii was found in three out of 100 patients from which clinicians suspected a Mycoplasma pneumoniae infection. Third, we analyzed data from the Belgian livestock screening program (2009­2010) which consisted of investigating all reported abortions, sampling tank milk, and serological screening of cattle. The results suggest an endemicity in the Limburgian livestock which seems to be especially high in cattle.

Practice testing of generic quality indicators for responsible antibiotic use in nine hospitals in the Dutch-Belgian border area.

BACKGROUND: Inpatient quality indicators (IQIs) were previously developed to assess responsible antibiotic use. AIM: Practice testing of these QIs in the hospital setting. METHOD: This study was performed within a Dutch-Belgian border network of hospitals implementing the Infection Risk Scan (IRIS) point prevalence survey (PPS) as part of the i-4-1-Health project. Twenty out of 51 DRIVE-AB IQIs, including 13 structure and seven process IQIs, were tested. Data on structure IQIs were obtained through a web-based questionnaire sent to the hospital medical microbiologists. PPS data from October to December 2018 were used to calculate performance scores for the process QIs. FINDINGS: Nine hospitals participated. Regarding structure IQIs: the lowest performance scores were observed for recommendations for microbiological investigations in the guidelines and the use of an approval system for restricted antibiotics. In addition, most hospitals reported that some antibiotics were out of stock due to shortages. Regarding process IQIs: 697 systemic antibiotic prescriptions were used to calculate performance scores. The lowest score was observed for documentation of an antibiotic plan in the medical file (58.8%). Performance scores for IQIs on guideline compliance varied between 74.1% and 82.3% for different aspects of the antibiotic regimen (duration, choice, route, timing). CONCLUSION: This multicentre practice testing of IQIs identified improvement targets for stewardship efforts for both structure and process aspects of antibiotic care (approval system for restricted antibiotics, documentation of antibiotic plan). These results can guide the design of future PPS studies and a more extensive evaluation of the clinimetric properties of the IQIs.

Heterologous effects of vaccination and trained immunity.

Vaccines are applied to large populations, but only recently has research into immunologic responses and mechanisms started to increase exponentially. Some live vaccines, such as the tuberculosis vaccine bacillus Calmette-Guérin, protect against other infections nonspecifically by eliciting complex immune responses which are not specific antibody related. These heterologous effects are explained by the concept of trained immunity. This editorial introduces five narrative reviews offering recent insights on innate and adaptive immune memory towards a variety of pathogens.

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.

Experiences with the Dutch Working Party on antibiotic policy (SWAB).

The Dutch Working Party on Antibiotic Policy (Stichting Werkgroep AntibioticaBeleid, SWAB) was founded in 1996 as an initiative of the Society for Infectious Diseases, the Dutch Society for Medical Microbiology, and the Dutch Association of Hospital Pharmacists. Its primary goal is to contribute to the containment of antimicrobial resistance and the expanding costs incurred for the use of antibiotics. SWAB is the Intersectoral Coordinating Mechanism (ICM) for the Netherlands, and it is at present the National Antimicrobial Resistance (AMR) Focal Point. It coordinates the national surveillance of antibiotic resistance, in collaboration with the National Institute for Public Health and the Environment(RIVM), coordinates the surveillance of the use of antibiotics,and runs a guideline development programme. Information about consumption of antimicrobial agents and antimicrobial resistance among medically important bacteria is presented annually in NethMap. Over the past decade, outpatient consumption of antibiotics has risen only slightly, but in the hospital setting there was an overall significant increase in antibiotic use, due mainly to the steady reduction in the average length of patient hospital stays. In 2006 we introduced our electronic national antibiotic guide 'SWAB-ID' for the antibiotic treatment and prophylaxis of common infectious diseases in hospitals.

Mycobacterial skin and soft tissue infections: TB or not TB?

Non-tuberculous mycobacteria are a known cause of skin and soft tissue infections. However, only too often it takes inordinately long to arrive at the appropriate diagnosis and start treatment. Actively searching for predilection factors, exposure risks and specific clinical clues may speed up the diagnostic process. Deep tissue biopsy cultures are indispensable to determine the species and strain of mycobacterium, with important consequences for treatment. Less well known as a causative agent of prolonged tenosynovitis is Mycobacterium tuberculosis. We present a case series and performed a literature search concerning mycobacterial tenosynovitis.

Brucellosis, an uncommon and frequently delayed diagnosis.

In the Netherlands, brucellosis is uncommon. Diagnosis is difficult and frequently delayed. We present three patients with back pain and/or arthralgia caused by brucellosis. We emphasise the importance of considering brucellosis in patients returning from a stay in a rural area of an endemic country, who present with osteoarticular symptoms and signs of chronic inflammation. Clues to the diagnosis come from a thorough medical history.

Prevalence of drug-drug interactions in the era of HIV integrase inhibitors: a retrospective clinical study.

BACKGROUND: Antiretroviral agents pose a high risk for drug-drug interactions (DDIs), mainly but not limited to being a substrate, inducer or inhibitor of P450 cytochrome enzymes. In part metabolised by other pathways, integrase inhibitors might show a more favourable profile. The aim of this study was to investigate the prevalence of DDIs in daily clinical practice for patients starting different antiretroviral treatment (ART) regimens. METHODS: All patients starting ART in our centre from January 2009 to April 2016 were included. All prescribed co-medications since the start of ART were recorded retrospectively from the medical files and screened for DDIs using the Liverpool HIV drug interaction database. Only DDIs between antiretroviral and non-antiretroviral drugs were considered. RESULTS: We included 145 patients, of which 42% were on an integrase inhibitor-based regimen, mainly dolutegravir and elvitegravir. Of the patients, 78% (n = 113) took co-medication. Potential DDIs were seen in 63% of the patients with co-medication; contraindicated prescriptions were detected in 1%. Protease inhibitor-based ART was a risk factor for DDI (odds ratio (OR) 2.57; 95% confidence interval (CI) 1.06-6.19), in contrast to non-nucleoside reverse transcriptase inhibitor-based ART (OR 0.77; 95% CI 0.32-1.84). Concerning integrase inhibitors, a significantly lower risk was seen with dolutegravir-based treatment (OR 0.35; 95% CI 0.15-0.82), though not for elvitegravir-based ART (OR 2.51; 95% CI 0.66-9.58). CONCLUSIONS: ART regimens pose a dissimilar risk for drug-drug interactions in clinical practice. Regarding the use of integrase inhibitors, a significantly lower risk was seen with dolutegravir-based treatment.

[Optimalisation of the antibiotic policy in The Netherlands. XI. The national electronic antibiotic guide'SWAB-ID' for use in hospitals]. / Optimaliseren van het antibioticabeleid in Nederland. XI. Het nationale elektronische antibioticaboekje SWAB-ID voor ziekenhuizen.

The 'Stichting Werkgroep Antibioticabeleid' (Dutch Working Party on Antibiotic Policy) has developed an electronic national antibiotic guide for the antibiotic treatment and prophylaxis of common infectious diseases in hospitals. This guide also contains information on the most important characteristics of antimicrobial drugs. Advice on antibiotic treatment is based on existing national evidence-based guidelines, where available. Where no guideline is available, the advice is based on an inventory of the antibiotic policies of the 12 Dutch centres with an infectious disease or medical microbiology training programme. The national antibiotic guide can be accessed through the SWAB website (www.swab.nl) and can also be downloaded on PDA/PocketPC, free of charge. Every hospital antibiotic formulary committee in the Netherlands will be offered the opportunity to edit The national version for local use.

[A patient with long-term, unrecognized leishmaniasis]. / Een patiënt met jarenlang niet onderkende mucocutane leishmaniasis.

A man from Surinam presented at the Department of Internal Medicine with a perforated septum and progressive collapse of the nose. This condition had existed for 22 years, though earlier analysis had not revealed the cause. Microscopic analysis showed a granulomatous inflammatory reaction, with cultures revealing of Leishmania. The diagnosis was mucocutaneous leishmaniasis and PCR indicated Leishmania braziliensis complex. The patient was treated for mucocutaneous leishmaniasis by a 28-day course of intravenous sodium-stibogluconate therapy. Initially, treatment was stopped briefly due to neurotoxicity, but was recommenced and successfully completed. After treatment the infection parameters returned to normal and the patient was referred for reconstructive nasal surgery. Due to a low parasitic load mucocutaneous leishmaniasis can be difficult to detect, especially in chronic cases. However, the use of molecular techniques has improved both the sensitivity and specificity of detection. The ability to distinguish between different species and sub-species is of prognostic and therapeutic relevance.

International guidelines for infectious diseases: a practical guide.

A growing number of organisations have become involved in the development of guidelines for infectious diseases (ID). The degree of acceptation of guidelines varies from one country to another. Some of these national differences are determining the practices of prescribing antibiotics, and infection control both in hospitals and in the community. This review provides updated information on ID guideline programmes, in particular on the topic of antimicrobial therapy. It is aimed at clinicians, both in their role as care providers and as designers of local antibiotic guidelines (antibiotic booklets). Definitions are given and the process of development is discussed. International and national ID guideline programmes in the English language are presented. Many URLs provide access to the different websites where most guidelines can be downloaded free of charge.

National guidelines for the use of antibiotics in hospitalised adult patients: the SWAB guidelines revisited.

Since 1996, the Dutch Working Party on Antibiotic Policy (Stichting Werkgroep AntibioticaBeleid, SWAB) has been developing national guidelines for the use of antibiotics in hospitalised adult patients. As a result of both an inventory of the wishes of the users of these guidelines and the recently developed criteria for evidence-based guideline development, we have revised our format for the development of SWAB guidelines. By involving the members of the relevant professional societies and giving them the opportunity to comment on the guidelines at an early stage, we are aiming for a successful implementation of the guidelines in the hospitals.

European survey on principles of prudent antibiotic prescribing teaching in undergraduate students.

We surveyed European medical schools regarding teaching of prudent antibiotic prescribing in the undergraduate curriculum. We performed a cross-sectional survey in 13 European countries (Belgium, Croatia, Denmark, France, Germany, Italy, Netherlands, Norway, Serbia, Slovenia, Spain, Switzerland, United Kingdom) in 2013. Proportional sampling was used, resulting in the selection of two to four medical schools per country. A standardized questionnaire based on literature review and validated by a panel of experts was sent to lecturers in infectious diseases, medical microbiology and clinical pharmacology. In-depth interviews were conducted with four lecturers. Thirty-five of 37 medical schools were included in the study. Prudent antibiotic use principles were taught in all but one medical school, but only four of 13 countries had a national programme. Interactive teaching formats were used less frequently than passive formats. The teaching was mandatory for 53% of the courses and started before clinical training in 71%. We observed wide variations in exposure of students to important principles of prudent antibiotic use among countries and within the same country. Some major principles were poorly covered (e.g. reassessment and duration of antibiotic therapy, communication skills). Whereas 77% of the respondents fully agreed that the teaching of these principles should be prioritized, lack of time, mainly due to rigid curriculum policies, was the main reported barrier to implementation. Given the study design, these are probably optimistic results. Teaching of prudent antibiotic prescribing principles should be improved. National and European programmes for development of specific learning outcomes or competencies are urgently needed.

The global threat of antimicrobial resistance: science for intervention.

In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.