Vaccine effectiveness against COVID-19 related hospital admission in the Netherlands by medical risk condition: A test-negative case-control study.

INTRODUCTION: Vaccination remains crucial in reducing COVID-19 hospitalizations and mitigating the strain on healthcare systems. We conducted a multicenter study to assess vaccine effectiveness (VE) of primary and booster vaccination against hospitalization and to identify subgroups with reduced VE. METHODS: From March to July 2021 and October 2021 to January 2022, a test-negative case-control study was conducted in nine Dutch hospitals. The study included adults eligible for COVID-19 vaccination who were hospitalized with respiratory symptoms. Cases tested positive for SARS-CoV-2 within 14 days prior to or 48 h after admission, while controls tested negative. Logistic regression was used to calculate VE, adjusting for calendar week, sex, age, nursing home residency and comorbidity. We explored COVID-19 case characteristics and whether there are subgroups with less effective protection by vaccination against COVID-19 hospitalization. RESULTS: Between October 2021 to January 2022, when the Delta variant was dominant, 335 cases and 277 controls were included. VE of primary and booster vaccination was 78 % (95 % CI: 65-86), and 89 % (95 % CI: 69-96), respectively. Using data from both study periods, including 700 cases and 511 controls, VE of primary vaccination was significantly reduced in those aged 60+ and patients with malignancy, chronic cardiac disease or an immunocompromising condition. CONCLUSION: Although VE against hospitalization was 78% and increased to 89% after boosting during the Delta-dominant study period, VE was lower in certain high risk groups, for which indirect protection or other protective measures might be of added importance.

Comparative effectiveness of ß-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study.

OBJECTIVES: Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia. METHODS: We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses. RESULTS: In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2-3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0-3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73-1.60 and HR 1.22, 95% CI 0.88-1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42-4.52 and sHR 1.93, 95% CI 0.67-5.60]. CONCLUSIONS: In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.

Vaccine effectiveness against COVID-19 related hospital admission in the Netherlands: A test-negative case-control study.

INTRODUCTION: Real-world vaccine effectiveness (VE) estimates are essential to identify potential groups at higher risk of break-through infections and to guide policy. We assessed the VE of COVID-19 vaccination against COVID-19 hospitalization, while adjusting and stratifying for patient characteristics. METHODS: We performed a test-negative case-control study in six Dutch hospitals. The study population consisted of adults eligible for COVID-19 vaccination hospitalized between May 1 and June 28, 2021 with respiratory symptoms. Cases were defined as patients who tested positive for SARS-CoV-2 by PCR during the first 48 h of admission or within 14 days prior to hospital admission. Controls were patients tested negative at admission and did not have a positive test during the 2 weeks prior to hospitalization. VE was calculated using multivariable logistic regression, adjusting for calendar week, sex, age, comorbidity and nursing home residency. Subgroup analysis was performed for age, sex and different comorbidities. Secondary endpoints were ICU-admission and mortality. RESULTS: 379 cases and 255 controls were included of whom 157 (18%) were vaccinated prior to admission. Five cases (1%) and 40 controls (16%) were fully vaccinated (VE: 93%; 95% CI: 81 - 98), and 40 cases (11%) and 70 controls (27%) were partially vaccinated (VE: 70%; 95% CI: 50-82). A strongly protective effect of vaccination was found in all comorbidity subgroups. No ICU-admission or mortality were reported among fully vaccinated cases. Of unvaccinated cases, mortality was 10% and 19% was admitted at the ICU. CONCLUSION: COVID-19 vaccination provides a strong protective effect against COVID-19 related hospital admission, in patients with and without comorbidity.

[Gastric acid suppression and antibiotic resistance; the role of a meta-analysis]. / Maagzuurremming en antibioticaresistentie.

We discuss a meta-analysis that reported on the association between gastric acid suppression and carriage with antibiotic resistant bacteria, with a special focus on the association for carriage with ESBL-producing Gram-negative bacteria in non-hospitalized subjects. Results from a recent population-based study (not included in the meta-analysis) were added to this subgroup of the meta-analysis. The data point to a positive, yet minor, association between gastric acid suppression and carriage with ESBL-producing Gram-negative bacteria in non-hospitalized subjects in the Netherlands.

O-serotype distribution of Escherichia coli bloodstream infection isolates in critically ill patients in The Netherlands.

OBJECTIVES: Invasive infections by extra-intestinal pathogenic Escherichia coli (ExPEC) strains are increasing. We determined O-serogroups of E. coli isolates from ICU patients having bloodstream infections (BSI) and the potential coverage of a 10-valent O-polysaccharide conjugate vaccine currently in development for the prevention of invasive ExPEC disease. METHODS: We studied E. coli BSI among patients admitted to a tertiary ICU in the Netherlands between April 2011 and November 2016. O-serogroups were determined in vitro by agglutination and whole genome sequencing. RESULTS: Among 714 ICU patients having BSI, 70 (10%) had an E. coli BSI. Among 68 (97%) isolates serogrouped, the most common serogroups were O25 (n = 11; 16%), O8 (n = 5; 7%), O2 (n = 4; 6%), O6 (n = 4; 6%), and O15 (n = 4; 6%). The theoretical coverage of a 10-valent ExPEC vaccine was 54% (n = 37). CONCLUSIONS: A multi-valent ExPEC O-polysaccharide conjugate vaccine in development could potentially aid in the prevention of E. coli BSI in Dutch ICU patients.

Comparative genomics of ESBL-producing Escherichia coli (ESBL-Ec) reveals a similar distribution of the 10 most prevalent ESBL-Ec clones and ESBL genes among human community faecal and extra-intestinal infection isolates in the Netherlands (2014-17).

INTRODUCTION: The human gut microbiota is an important reservoir of ESBL-producing Escherichia coli (ESBL-Ec). Community surveillance studies of ESBL-Ec to monitor circulating clones and ESBL genes are logistically challenging and costly. OBJECTIVES: To evaluate if isolates obtained in routine clinical practice can be used as an alternative to monitor the distribution of clones and ESBL genes circulating in the community. METHODS: WGS was performed on 451 Dutch ESBL-Ec isolates (2014-17), including 162 community faeces and 289 urine and blood isolates. We compared proportions of 10 most frequently identified STs, PopPUNK-based sequence clusters (SCs) and ESBL gene subtypes and the degree of similarity using Czekanowski's proportional similarity index (PSI). RESULTS: Nine out of 10 most prevalent STs and SCs and 8/10 most prevalent ESBL genes in clinical ESBL-Ec were also the most common types in community faeces. The proportions of ST131 (39% versus 23%) and SC131 (40% versus 25%) were higher in clinical isolates than in community faeces (P < 0.01). Within ST131, H30Rx (C2) subclade was more prevalent among clinical isolates (55% versus 26%, P < 0.01). The proportion of ESBL gene blaCTX-M-1 was lower in clinical isolates (5% versus 18%, P < 0.01). Czekanowski's PSI confirmed that the differences in ESBL-Ec from community faeces and clinical isolates were limited. CONCLUSIONS: Distributions of the 10 most prevalent clones and ESBL genes from ESBL-Ec community gut colonization and extra-intestinal infection overlapped in majority, indicating that isolates from routine clinical practice could be used to monitor ESBL-Ec clones and ESBL genes in the community.

Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection, a cohort study.

OBJECTIVE: Short-course aminoglycosides as adjunctive empirical therapy to ß-lactams in patients with a clinical suspicion of sepsis are used to broaden antibiotic susceptibility coverage and to enhance bacterial killing. We quantified the impact of this approach on 30-day mortality in a subset of sepsis patients with a Gram-negative bloodstream infection. METHODS: From a prospective cohort study conducted in seven hospitals in the Netherlands between June 2013 and November 2015, we selected all patients with Gram-negative bloodstream infection (GN-BSI). Short-course aminoglycoside therapy was defined as tobramycin, gentamicin or amikacin initiated within a 48-hour time window around blood-culture obtainment, and prescribed for a maximum of 2 days. The outcome of interest was 30-day all-cause mortality. Confounders were selected a priori for adjustment using a propensity score analysis with inverse probability weighting. RESULTS: A total of 626 individuals with GN-BSI who received ß-lactams were included; 156 (24.9%) also received aminoglycosides for a median of 1 day. Patients receiving aminoglycosides more often had septic shock (31/156, 19.9% versus 34/470, 7.2%) and had an eight-fold lower risk of inappropriate treatment (3/156, 1.9% versus 69/470, 14.7%). Thirty-day mortality was 17.3% (27/156) and 13.6% (64/470) for patients receiving and not receiving aminoglycosides, respectively; yielding crude and adjusted odds ratios for 30-day mortality for patients treated with aminoglycosides of 1.33 (95% CI 0.80-2.15) and 1.57 (0.84-2.93), respectively. CONCLUSIONS: Short-course adjunctive aminoglycoside treatment as part of empirical therapy with ß-lactam antibiotics in patients with GN-BSI did not result in improved outcomes, despite better antibiotic coverage of pathogens.

Universal risk assessment upon hospital admission for screening of carriage with multidrug-resistant micro-organisms in a Dutch tertiary care centre.

BACKGROUND: In Dutch hospitals a six-point questionnaire is currently mandatory for risk assessment to identify carriers of multidrug-resistant organisms (MDROs) at the time of hospitalization. Presence of one or more risk factors is followed by pre-emptive isolation and microbiological culturing. AIM: To evaluate the yield of the universal risk assessment in identifying MDRO carriers upon hospitalization. METHODS: A cross-sectional study was performed using routine healthcare data in a Dutch tertiary hospital between January 1st, 2015 and August 1st, 2019. MDRO risk assessment upon hospitalization included assessment of: known MDRO carriage, previous hospitalization in another Dutch hospital during an outbreak or a foreign hospital, living in an asylum centre, exposure to livestock farming, and household membership of a meticillin-resistant Staphylococcus aureus carrier. FINDINGS: In total, 144,051 admissions of 84,485 unique patients were included; 4480 (3.1%) admissions had a positive MDRO risk assessment. In 1516 (34%) admissions microbiological screening was performed, of which 341 (23%) yielded MDRO. Eighty-one patients were categorized as new MDRO carriers, as identified through MDRO risk assessment, reflecting 0.06% (95% confidence interval: 0.04-0.07) of all admissions and 1.8% (1.4-2.2) of those with positive risk assessment. As a result, the number of 'MDRO risk assessments needed to perform' and individual 'MDRO questions needed to ask' to detect one new MDRO carrier upon hospitalization were 1778 and 10,420, respectively. CONCLUSION: The yield of the current strategy of MDRO risk assessment upon hospitalization is limited and it needs thorough reconsideration.

The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal function.

OBJECTIVES: We evaluated the effect of renal function on clinical failure rates of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in primary care. METHODS: Data were retrospectively obtained from 78 Dutch general practitioner (GP) practices between 2013 and 2019. Eligible episodes in patients (>11 years) were those requiring 5 days of nitrofurantoin (NF5), single-dose fosfomycin-trometamol (FT1), 3 days of trimethoprim (TMP3) for uncomplicated cystitis, or 7 days of nitrofurantoin (NF7) or trimethoprim (TMP7) for complicated cystitis. Clinical failure was defined as second antibiotic prescription for cystitis or pyelonephritis within 28 days post-prescription. Mixed effects regression analysis was used, with patient and GP practice as random effects and demography, comorbidity, and cystitis history as fixed effects. RESULTS: Adjusted odds ratios (aORs) for clinical failure per 10mL/min decrease in estimated glomerular filtration rate (eGFR) were 1.05 (95% CI: 1.01-1.09) for NF5 (n = 24,591), 0.96 (95% CI: 0.92-1.01) for FT1 (n = 5359), 0.98 (95% CI: 0.89-1.08) for TMP3 (n = 1064), 1.05 (95% CI: 1.02-1.09) for NF7 (n = 10,628) and 1.02 (95% CI: 0.93-1.14) for TMP7 (n = 831). In uncomplicated cystitis and eGFR ≥60 mL/min, clinical failures occurred in 14.6% (1895/12 980) of NF5-treated, 20.7% (266/1283) of FT1-treated (aOR versus NF5 1.37, 95% CI 1.18-1.59) and 20.8% (66/318) of TMP3-treated patients (aOR 1.42, 95% CI 1.07-1.87 versus NF5). In uncomplicated cystitis and eGFR <60 mL/min, FT1 resulted in 16.0% (39/244) and NF5 in 23.3% clinical failures (110/472), aOR: 0.61, 95% CI: 0.39-0.95). CONCLUSIONS: In eGFR ≥60 mL/min treatment with fosfomycin or trimethoprim for uncomplicated cystitis was associated with more clinical failure than treatment with nitrofurantoin, while in eGFR <60 mL/min nitrofurantoin was associated with more clinical failure than fosfomycin-trometamol. Renal function, if known, should be considered in the clinical decision-making for cystitis treatment.

Seasonality in carriage of extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae in the general population: a pooled analysis of nationwide cross-sectional studies.

Infections due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) are often preceded by asymptomatic carriage. Higher incidences in enteric infectious diseases during summer have been reported. Here, we assessed whether the presence of seasonality in intestinal ESBL-Escherichia coli/Klebsiella pneumoniae (ESBL-E/K) carriage in the general Dutch population exists. From 2014 to 2017, the faecal carriage of ESBL-E/K in healthy individuals was determined in three cross-sectional studies in the Netherlands, including 5985 subjects. Results were pooled to identify seasonal trends in prevalence (by month of sampling). Multivariate logistic regression analysis was used to calculate pooled odds ratios and 95% confidence intervals. Results were adjusted for age, sex, antibiotic use and travel. Overall prevalence of ESBL-E/K carriage was 4.3% (n = 260 ESBL-E/K-positive), with differences between months ranging from 2.6% to 7.4%. Compared to January, the monthly prevalence of ESBL-E carriage was highest in August (OR 1.88, 95% CI 1.02-3.49) and September (OR 2.25, 95% CI 1.30-3.89). The observed monthly differences in ESBL-E/K carriage rates suggest that there is seasonal variation in exposure to ESBL-E/K other than due to travelling and antibiotic use. This should be taken into account in designing future ESBL-E prevalence studies in temperate regions.

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.

The effects of topical antibiotics on eradication and acquisition of third-generation cephalosporin and carbapenem-resistant Gram-negative bacteria in ICU patients; a post hoc analysis from a multicentre cluster-randomized trial.

OBJECTIVES: The aim was to quantify the effects of selective digestive tract decontamination (SDD) consisting of a mouth paste and gastro-enteral suspension, selective oropharyngeal decontamination with a mouth paste (SOD) and 1-2% chlorhexidine (CHX) mouthwash on eradication and acquisition of carriage of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and carbapenem-resistant Gram-negative bacteria (CR-GNB) in Intensive Care Unit (ICU) patients. METHODS: This was a nested cohort study within a cluster-randomized cross-over trial in six European countries and 13 ICUs with 8665 patients. Eradication and acquisition during ICU stay of 3GCR-E and CR-GNB were investigated separately in the rectum and respiratory tract for the three interventions and compared with standard care (SC) using Cox-regression competing events analyses. RESULTS: Adjusted cause specific hazard ratios (CSHR) for eradication of rectal carriage for SDD were 1.76 (95% CI 1.31-2.36) for 3GCR-E and 3.17 (95% CI 1.60-6.29) for CR-GNB compared with SC. For the respiratory tract, adjusted CSHR for eradication of 3GCR-E were 1.47 (0.98-2.20) for SDD and 1.38 (0.92-2.06) for SOD compared with SC, and for eradication of CR-GNB these were 0.77 (0.41- 1.45) for SDD and 0.81 (0.44-1.51) for SOD, compared with SC. Adjusted CSHRs for acquisition of rectal carriage during SDD (compared with SC) were 0.51 (0.40-0.64) for 3GCR-E and of 0.56 (0.40-0.78) for CR-GNB. Adjusted CSHRs for acquiring respiratory tract carriage with 3GCR-E compared with SC were 0.38 (0.28-0.50) for SDD and 0.55 (0.42-0.71) for SOD, and for CR-GNB 0.46 (0.33-0.64) during SDD and 0.60 (0.44-0.81) during SOD, respectively. SOD was not associated with eradication or acquisition of 3GCR-E and CR-GNB in the rectum. CONCLUSIONS: Among mechanically ventilated ICU patients, SDD was associated with more eradication and less acquisition of 3GCR-E and CR-GNB in the rectum than SC. SDD and SOD were associated with less acquisition of both 3GCR-E and CR-GNB than SC in the respiratory tract.

Faecal carriage, risk factors, acquisition and persistence of ESBL-producing Enterobacteriaceae in dogs and cats and co-carriage with humans belonging to the same household.

BACKGROUND: ESBL-producing Enterobacteriaceae (ESBL-E) are observed in many reservoirs. Pets might play an important role in the dissemination of ESBL-E to humans since they live closely together. OBJECTIVES: To identify prevalence, risk factors, molecular characteristics, persistence and acquisition of ESBL-E in dogs and cats, and co-carriage in human-pet pairs belonging to the same household. METHODS: In a nationwide study, one person per household was randomly invited to complete a questionnaire and to submit a faecal sample. Dog and cat owners were invited to also submit a faecal sample from their pet. Repeated sampling after 1 and 6 months was performed in a subset. ESBL-E were obtained through selective culture and characterized by WGS. Logistic regression analyses and random forest models were performed to identify risk factors. RESULTS: The prevalence of ESBL-E carriage in these cohorts was 3.8% (95% CI: 2.7%-5.4%) for human participants (n=550), 10.7% (95% CI: 8.3%-13.7%) for dogs (n=555) and 1.4% (95% CI: 0.5%-3.8%) for cats (n=285). Among animals, blaCTX-M-1 was most abundant, followed by blaCTX-M-15. In dogs, persistence of carriage was 57.1% at 1 month and 42.9% at 6 months. Eating raw meat [OR: 8.8, 95% CI: 4.7-16.4; population attributable risk (PAR): 46.5%, 95% CI: 41.3%-49.3%] and dry food (OR: 0.2, 95% CI: 0.1-0.5; PAR: 56.5%, 95% CI: 33.2%-66.6%) were predictors for ESBL-E carriage in dogs. Human-dog co-carriage was demonstrated in five households. Human-cat co-carriage was not observed. CONCLUSIONS: ESBL-E prevalence was higher in dogs than in humans and lowest in cats. The main risk factor for ESBL-E carriage was eating raw meat. Co-carriage in dogs and household members was uncommon.

Profile of the SeptiCyte™ LAB gene expression assay to diagnose infection in critically ill patients.

Sepsis is a severe and frequently occurring clinical syndrome, caused by the inflammatory response to infections. Recent studies on the human transcriptome during sepsis have yielded several gene-expression assays that might assist physicians during clinical assessment of patients suspected of sepsis. SeptiCyte™ LAB (Immunexpress, Seattle, WA) is the first gene expression assay that was cleared by the FDA in the United States to distinguish infectious from non-infectious causes of systemic inflammation in critically ill patients. The test consists of the simultaneous amplification of four RNA transcripts (CEACAM4, LAMP1, PLAC8, and PLA2G7) in whole blood using a quantitative real-time PCR reaction. This review provides an overview of the challenges in the diagnosis of sepsis, the development of gene expression signatures, and a detailed description of available clinical performance studies evaluating SeptiCyte™ LAB.

The quality of studies evaluating antimicrobial stewardship interventions: a systematic review.

BACKGROUND: Antimicrobial stewardship aims to optimize antibiotic use and minimize selection of antimicrobial resistance. The methodological quality of published studies in this field is unknown. AIMS: Our objective was to perform a comprehensive systematic review of antimicrobial stewardship research design and identify features which limit validity and translation of research findings into clinical practice. SOURCES: The following online database was searched: PubMed. STUDY ELIGIBILITY CRITERIA: Studies published between January 1950 and January 2017, evaluating any antimicrobial stewardship intervention in the community or hospital setting, without restriction on study design or outcome. CONTENT: We extracted data on pre-specified design quality features and factors that may influence design choices including (1) clinical setting, (2) age group studied, (3) when the study was conducted, (4) geographical region, and (5) financial support received. The initial search yielded 17 382 articles; 1008 were selected for full-text screening, of which 825 were included. Most studies (675/825, 82%) were non-experimental; 104 (15%) used interrupted time series analysis, 41 (6%) used external controls, and 19 (3%) used both. Studies in the community setting fulfilled a median of five out of 10 quality features (IQR 3-7) and 3 (IQR 2-4) in the hospital setting. Community setting studies (25%, 205/825) were significantly more likely to use randomization (OR 5.9; 95% CI 3.8-9.2), external controls (OR 5.6; 95% CI 3.6-8.5), and multiple centres (OR 10.5; 95% CI 7.1-15.7). From all studies, only 48% (398/825) reported clinical and 23% (190/825) reported microbiological outcomes. Quality did not improve over time. IMPLICATIONS: Overall quality of antimicrobial stewardship studies is low and has not improved over time. Most studies do not report clinical and microbiological outcome data. Studies conducted in the community setting were associated with better quality. These limitations should inform the design of future stewardship evaluations so that a robust evidence base can be built to guide clinical practice.

Relevance of healthcare-associated pneumonia for empirical antibiotic therapy in the Netherlands.

BACKGROUND: There is no consensus whether patients with healthcare-associated pneumonia (HCAP) should be considered as a patient with hospital-acquired pneumonia (HAP) and treated with broad-spectrum antibiotics, or as a patient with community-acquired pneumonia (CAP), and treated with narrow-spectrum antibiotics. HCAP research has focused mostly on the predictive value for non-susceptibility to broad-spectrum antibiotics and multi-drug resistant pathogens, in settings with moderate to high levels of antibiotic resistance. We investigated whether HCAP criteria predicts non-susceptibility to different empirical strategies, including narrow-spectrum antibiotics in the Dutch setting. METHODS: In a post hoc analysis of patients with moderate-severe CAP in seven Dutch hospitals, we compared in vitro antibiotic susceptibilities of definite and possible causative pathogens of CAP and HCAP to amoxicillin and broader antibiotic regimens. In a sensitivity analysis, pathogens with missing susceptibilities were assumed susceptible (best-case scenario) or non-susceptible (worst-case scenario). RESULTS: Among 2,283 patients with moderate-severe CAP, 23.1% (n = 527) were classified as HCAP. Non-susceptibility to amoxicillin ranged from 11.3% (95% CI 9.9-12.8%; best-case) to 14.4% (95% CI 12.8-16.1%; worst-case) in CAP patients and from 16.7% (95% CI 13.8-20.1%; best-case) to 19.7% (95% CI 16.6-23.3%; worst-case) in HCAP patients. The largest reduction in non-susceptibility was achieved by adding ciprofloxacin to amoxicillin treatment in both CAP patients (10% absolute risk reduction) and HCAP patients (11-16% reduction). CONCLUSIONS: In the Netherlands, HCAP criteria predict higher amoxicillin non-susceptibility in patients hospitalized with moderate-severe CAP. Although broadening the antibiotic spectrum of empiric treatment reduced the likelihood of non-susceptibility, absolute reductions of non-susceptibility in HCAP patients were too low to justify the universal use of broad-spectrum empirical therapy.No abstract available.

Carriage of antibiotic-resistant Gram-negative bacteria after discontinuation of selective decontamination of the digestive tract (SDD) or selective oropharyngeal decontamination (SOD).

BACKGROUND: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) reduce colonization with antibiotic-resistant Gram-negative bacteria (ARGNB), incidence of nosocomial infections and improve survival in ICU patients. The effect on bacterial gut colonization might be caused by growth suppression by antibiotics during SDD/SOD. We investigated intestinal colonization with ARGNB after discharge from ICU and discontinuation of SDD or SOD. METHODS: We performed a prospective, observational follow-up study in regular hospital wards of three teaching hospitals in the Netherlands in patients discharged from the ICU, who were participating in a cluster randomized trial comparing SDD with SOD. We determined rectal carriage with ARGNB at ICU discharge (time (T) = 0) and 3, 6 and 10 days after discharge. The primary endpoint was time to first colonization with ARGNB that was not present at T = 0. Bacteria that are intrinsically resistant to antibiotics were not included in the primary analysis, but were included in post-hoc analysis. RESULTS: Of 1370 patients screened for inclusion, 996 patients had samples at T = 0 (507 after SDD and 489 after SOD). At ICU discharge, the prevalence of intestinal carriage with any ARGNB was 22/507 (4.3%) after SDD and 87/489 (17.8%) after SOD (p < 0.0001): 426 (SDD) and 409 (SOD) patients had at least one follow-up sample for analysis. The hazard rate for acquiring carriage of ARGNB after discontinuation of SDD, compared to SOD, in the ICU was 0.61 (95% CI 0.40-0.91, p = 0.02), and cumulative risks of acquisition of at least one ARGNB until day 10 were 13% (SDD) and 18% (SOD). At day 10 after ICU discharge, the prevalence of intestinal carriage with ARGNB was 11.3% (26/230 patients) after SDD and 12.5% (28/224 patients) after SOD (p = 0.7). In post-hoc analysis of all ARGNB, including intrinsically resistant bacteria, colonization at ICU discharge was lower after SDD (4.9 vs. 22.3%, p < 0.0001), but acquisition rates after ICU discharge were similar in both groups. CONCLUSIONS: Intestinal carriage at ICU discharge and the acquisition rate of ARGNB after ICU discharge are lower after SDD than after SOD. The prevalence of intestinal carriage with ARGNB at 10 days after ICU discharge was comparable in both groups, suggesting rapid clearance of ARGNB from the gut after ICU discharge. TRIAL REGISTRATION: Netherlands Trial Registry, NTR3311 . Registered on 28 february 2012.