Positive effects of audit and feedback on antimicrobial use in hospitalized patients limited to audited patients.

Objective: Audit and feedback is an antimicrobial stewardship (AMS) strategy, with the potential to also optimize antimicrobial use in non-audited patients. This study aimed to determine whether audit and feedback reduce antimicrobial use in both audited and non-audited patients. Design: Before-after trial with a 1-year intervention period and 2.5-year historical cohort. Setting: 750-bed community hospital in the Netherlands. Patients: All patients admitted to the urology wards during the 3.5-year study period were observed. Patients were classified as using antimicrobials if any antimicrobial was used for therapeutic reasons. Patients using antimicrobials prophylactically were excluded from measurements. Intervention: The AMS team provided audit and feedback on antimicrobial use for patients using antimicrobials for 2 days. Retrospectively, antimicrobial use and length of stay (LOS) were compared with the historical cohort. Results: Audits modified antimicrobial treatment in 52.8% of the cases. De-escalating, stopping, and switching from intravenous to oral treatment accounted for 72% of these modifications. Compared to patients from the cohort, who also used antimicrobials for 2 days, antimicrobial use decreased from 14.21 DDD/patient (95% CI, 13.08-15.34) to 11.45 DDD/patient (95% CI, 8.26-14.64; P = .047) for audited patients. Furthermore, mean LOS decreased from 7.42 days (95% CI, 6.79-8.06) to 6.13 days (95% CI, 5.38-6.89; P = .031). However, looking at all patients admitted to the urology wards, the percentage of patients using antimicrobials and total antimicrobial use remained unchanged. Conclusions: Audit and feedback reduce antimicrobial use and LOS, but only for audited patients. Positive effects are not automatically transferred to patients for whom no audits have been performed.

Low-Threshold Testing for SARS-CoV-2 (COVID-19) in Long-Term Care Facilities Early in the First Pandemic Wave, the Twente Region, the Netherlands: A Possible Factor in Reducing Morbidity and Mortality.

During the first wave of the COVID-19 pandemic, there was a shortage of SARS-CoV-2 diagnostic tests, and testing patients with mild symptoms (low-threshold testing) was not recommended in the Netherlands. Despite these guidelines, to protect those who were most at risk, low-threshold testing was advocated and offered to the majority of long-term care institutions in the Twente region. In this manner, 144 healthcare workers and 96 residents tested SARS-CoV-2-positive and were isolated before the same service was provided nationwide by public health services. Strikingly, excess mortality rate in the Twente region 1 month after the introduction of this strategy was found to be 62%-89% lower than that in neighboring regions, which may be explained by this divergent testing strategy. In an emerging pandemic, early implementation of a liberal testing policy may be more effective than restricted testing in settings with a high death rate.

Improving the Development and Implementation of Audit and Feedback Systems to Support Health Care Workers in Limiting Antimicrobial Resistance in the Hospital: Scoping Review.

BACKGROUND: For eHealth technologies in general and audit and feedback (AF) systems specifically, integrating interdisciplinary theoretical underpinnings is essential, as it increases the likelihood of achieving desired outcomes by ensuring a fit among eHealth technology, stakeholders, and their context. In addition, reporting on the development and implementation process of AF systems, including substantiations of choices, enables the identification of best practices and accumulation of knowledge across studies but is often not elaborated on in publications. OBJECTIVE: This scoping review aims to provide insights into the development and implementation strategies for AF systems for a real-world problem that threatens modern health care-antimicrobial resistance-and provide an interdisciplinary conceptual framework that can serve as a checklist and guidance for making informed choices in the development and implementation of future AF systems. METHODS: A scoping review was conducted by querying PubMed, Scopus, Web of Science, IEEE Xplore Digital Library, and Embase (≥2010) for studies describing either the development or implementation process, or both, of an AF system for antimicrobial resistance or infections in hospitals. Studies reporting only on effectiveness or impact were excluded. A total of 3 independent reviewers performed the study selection, and 2 reviewers constructed the conceptual framework through the axial and selective coding of often-used theories, models, and frameworks (TMFs) from the literature on AF and eHealth development and implementation. Subsequently, the conceptual framework was used for the systematic extraction and interpretation of the studies' descriptions of AF systems and their development and implementation. RESULTS: The search resulted in 2125 studies that were screened for eligibility, of which 12 (0.56%); 2012-2020) were included. These studies described the development and implementation processes heterogeneously in terms of study aims, study targets, target groups, methods, and theoretical underpinnings. Few studies have explicitly explained how choices for the development and implementation of AF systems were substantiated by the TMFs. The conceptual framework provided insights into what is reported on the development and implementation process and revealed underreported AF system constructs (eg, AF system design; engagement with the AF system; and comparison, goal setting, and action planning) and development and implementation (eg, champions) constructs. CONCLUSIONS: This scoping review showed the current heterogeneous reporting of AF systems and their development and implementation processes and exemplified how interdisciplinary TMFs can (and should) be balanced in a conceptual framework to capture relevant AF systems and development and implementation constructs. Thereby, it provides a concrete checklist and overall guidance that supports the professionalization and harmonization of AF system development and implementation. For the development and implementation of future AF systems and other eHealth technologies, researchers and health care workers should be supported in selecting and integrating TMFs into their development and implementation process and encouraged to explicitly report on theoretical underpinnings and the substantiation of choices.

Contact precautions in single-bed or multiple-bed rooms for patients with extended-spectrum ß-lactamase-producing Enterobacteriaceae in Dutch hospitals: a cluster-randomised, crossover, non-inferiority study.

BACKGROUND: Use of single-bed rooms for control of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae is under debate; the added value when applying contact precautions has not been shown. We aimed to assess whether an isolation strategy of contact precautions in a multiple-bed room was non-inferior to a strategy of contact precautions in a single-bed room for preventing transmission of ESBL-producing Enterobacteriaceae. METHODS: We did a cluster-randomised, crossover, non-inferiority study on medical and surgical wards of 16 Dutch hospitals. During two consecutive study periods, either contact precautions in a single-bed room or contact precautions in a multiple-bed room were applied as the preferred isolation strategy for patients with ESBL-producing Enterobacteriaceae cultured from a routine clinical sample (index patients). Eligible index patients were aged 18 years or older, had no strict indication for barrier precautions in a single-bed room, had a culture result reported within 7 days of culture and before discharge, and had no wardmate known to be colonised or infected with an ESBL-producing Enterobacteriaceae isolate of the same bacterial species with a similar antibiogram. Hospitals were randomly assigned in a 1:1 ratio by computer to one of two sequences of isolation strategies, stratified by university or non-university hospital. Allocation was masked for laboratory technicians who assessed the outcomes but not for patients, treating doctors, and infection-control practitioners enrolling index patients. The primary outcome was transmission of ESBL-producing Enterobacteriaceae to wardmates, which was defined as rectal carriage of an ESBL-producing Enterobacteriaceae isolate that was clonally related to the index patient's isolate in at least one wardmate. The primary analysis was done in the per-protocol population, which included patients who were adherent to the assigned room type. A 10% non-inferiority margin for the risk difference was used to assess non-inferiority. This study is registered with Nederlands Trialregister, NTR2799. FINDINGS: 16 hospitals were randomised, eight to each sequence of isolation strategies. All hospitals randomised to the sequence single-bed room then multiple-bed room and five of eight hospitals randomised to the sequence multiple-bed room then single-bed room completed both study periods and were analysed. From April 24, 2011, to Feb 27, 2014, 1652 index patients and 12 875 wardmates were assessed for eligibility. Of those, 693 index patients and 9527 wardmates were enrolled and 463 index patients and 7093 wardmates were included in the per-protocol population. Transmission of ESBL-producing Enterobacteriaceae to at least one wardmate was identified for 11 (4%) of 275 index patients during the single-bed room strategy period and for 14 (7%) of 188 index patients during the multiple-bed room strategy period (crude risk difference 3·4%, 90% CI -0·3 to 7·1). INTERPRETATION: For patients with ESBL-producing Enterobacteriaceae cultured from a routine clinical sample, an isolation strategy of contact precautions in a multiple-bed room was non-inferior to a strategy of contact precautions in a single-bed room for preventing transmission of ESBL-producing Enterobacteriaceae. Non-inferiority of the multiple-bed room strategy might change the current single-bed room preference for isolation of patients with ESBL-producing Enterobacteriaceae and, thus, broaden infection-control options for ESBL-producing Enterobacteriaceae in daily clinical practice. FUNDING: Netherlands Organisation for Health Research and Development.

Prevalence of plasmid-mediated AmpC in Enterobacteriaceae isolated from humans and from retail meat in Zagazig, Egypt.

Background: The objective of this study was to determine the prevalence of plasmid-mediated AmpC (pAmpC) among Enterobacteriaceae isolated from humans and from retail meat in Egypt. Methods: Enterobacteriaceae were isolated from patients with suspected bloodstream infection, human fecal samples, retail chicken meat samples and retail sheep meat samples. All group I Enterobacteriaceae were analyzed for presence of pAmpC genes by PCR. Antibiotic susceptibility testing was performed in all pAmpC positive isolates, followed by phenotypic and genotypic ESBL and carbapenemase testing on indication. Results: The prevalence of pAmpC among group I Enterobacteriaceae isolated from 225 patients with bloodstream infection was 5.6% [95%CI 2.2-13.4]. Among 100 patients with community-onset gastroenteritis the prevalence in fecal samples was 4.8% [95%CI 2.1-10.7]. The prevalence among 112 chicken carcasses and 100 sheep meat samples was 2.4% [95%CI 0.7-8.4] and 1.1% [95%CI 0.2-5.7], respectively. In half of the AmpC positive isolates we detected an ESBL gene and 2 isolates harbored a carbapenemase gene. In five isolates there was resistance to at least three important alternative antibiotic drugs. Conclusions: We consider the prevalence of pAmpC in Egypt, as found in our study, moderately low. To follow future trends in prevalence of pAmpC worldwide, a standardized screening algorithm for the detection of pAmpC is needed.

Impact of single room design on the spread of multi-drug resistant bacteria in an intensive care unit.

BACKGROUND: Cross-transmission of nosocomial pathogens occurs frequently in intensive care units (ICU). The aim of this study was to investigate whether the introduction of a single room policy resulted in a decrease in transmission of multidrug-resistant (MDR) bacteria in an ICU. METHODS: We performed a retrospective study covering two periods: between January 2002 and April 2009 (old-ICU) and between May 2009 and March 2013 (new-ICU, single-room). These periods were compared with respect to the occurrence of representative MDR Gram-negative bacteria. Routine microbiological screening, was performed on all patients on admission to the ICU and then twice a week. Multi-drug resistance was defined according to a national guideline. The first isolates per patient that met the MDR-criteria, detected during the ICU admission were included in the analysis. To investigate the clonality, isolates were genotyped by DiversiLab (bioMérieux, France) or Amplified Fragment Length Polymorphism (AFLP). To guarantee the comparability of the two periods, the 'before' and 'after' periods were chosen such that they were approximately identical with respect to the following factors: number of admissions, number of beds, bed occupancy rate, per year and month. RESULTS: Despite infection prevention efforts, high prevalence of MRD bacteria continue to occur in the original facility. A marked and sustained decrease in the prevalence of MDR-GN bacteria was observed after the migration to the new ICU, while there appear to be no significant changes in the other variables including bed occupancy and numbers of patient admissions. CONCLUSION: Single room ICU design contributes significantly to the reduction of cross transmission of MRD-bacteria.

Genomic Characterization of Colistin Heteroresistance in Klebsiella pneumoniae during a Nosocomial Outbreak.

Klebsiella pneumoniae is emerging as an important nosocomial pathogen due to its rapidly increasing multidrug resistance, which has led to a renewed interest in polymyxin antibiotics, such as colistin, as antibiotics of last resort. However, heteroresistance (i.e., the presence of a subpopulation of resistant bacteria in an otherwise susceptible culture) may hamper the effectiveness of colistin treatment in patients. In a previous study, we showed that colistin resistance among extended-spectrum-beta-lactamase (ESBL)-producing K. pneumoniae isolates emerged after the introduction of selective digestive tract decontamination (SDD) in an intensive care unit (ICU). In this study, we investigated heteroresistance to colistin among ESBL-producing K. pneumoniae isolates by using population analysis profiles (PAPs). We used whole-genome sequencing (WGS) to identify the mutations that were associated with the emergence of colistin resistance in these K. pneumoniae isolates. We found five heteroresistant subpopulations, with colistin MICs ranging from 8 to 64 mg/liter, which were derived from five clonally related, colistin-susceptible clinical isolates. WGS revealed the presence of mutations in the lpxM, mgrB, phoQ, and yciM genes in colistin-resistant K. pneumoniae isolates. In two strains, mgrB was inactivated by an IS3-like or ISKpn14 insertion sequence element. Complementation in trans with the wild-type mgrB gene resulted in these strains reverting to colistin susceptibility. The MICs for colistin-susceptible strains increased 2- to 4-fold in the presence of the mutated phoQ, lpxM, and yciM alleles. In conclusion, the present study indicates that heteroresistant K. pneumoniae subpopulations may be selected for upon exposure to colistin. Mutations in mgrB and phoQ have previously been associated with colistin resistance, but we provide experimental evidence for roles of mutations in the yciM and lpxM genes in the emergence of colistin resistance in K. pneumoniae.

Plasmid-mediated AmpC: prevalence in community-acquired isolates in Amsterdam, the Netherlands, and risk factors for carriage.

OBJECTIVES: The objective of this study was to determine the prevalence of pAmpC beta-lactamases in community-acquired Gram negative bacteria in the Netherlands, and to identify possible risk factors for carriage of these strains. METHODS: Fecal samples were obtained from community-dwelling volunteers. Participants also returned a questionnaire for analysis of risk factors. Screening for pAmpC was performed with selective enrichment broth and a selective screening agar. Confirmation of AmpC-production was performed with two double disc combination tests: cefotaxime and ceftazidime with either boronic acid or cloxacillin as inhibitor. Multiplex PCR was used as gold standard for detection of pAmpC. 16S rRNA PCR and AFLP were performed as required, plasmids were identified by PCR-based replicon typing. Questionnaire results were analyzed with SPSS, version 20.0. RESULTS: Fecal samples were obtained from 550 volunteers; mean age 51 years (range: 18-91), 61% were females. pAmpC was present in seven E. coli isolates (7/550, 1.3%, 0.6-2.7 95% CI): six CMY-2-like pAmpC and one DHA. ESBL-encoding genes were found in 52/550 (9.5%, 7.3-12.2 95% CI) isolates; these were predominantly blaCTX-M genes. Two isolates had both ESBL and pAmpC. Admission to a hospital in the previous year was the only risk factor we identified. CONCLUSIONS: Our data indicate that the prevalence of pAmpC in the community seems still low. However, since pAmpC-producing isolates were not identified as ESBL producers by routine algorithms, there is consistent risk that further increase of their prevalence might go undetected.

Genomic dissection of travel-associated extended-spectrum-beta-lactamase-producing Salmonella enterica serovar typhi isolates originating from the Philippines: a one-off occurrence or a threat to effective treatment of typhoid fever?

One unreported case of extended-spectrum-beta-lactamase (ESBL)-producing Salmonella enterica serovar Typhi was identified, whole-genome sequence typed, among other analyses, and compared to other available genomes of S. Typhi. The reported strain was similar to a previously published strain harboring blaSHV-12 from the Philippines and likely part of an undetected outbreak, the first of ESBL-producing S. Typhi.

Detection and occurrence of plasmid-mediated AmpC in highly resistant gram-negative rods.

OBJECTIVES: The aim of this study was to compare the current screening methods and to evaluate confirmation tests for phenotypic plasmidal AmpC (pAmpC) detection. METHODS: For this evaluation we used 503 Enterobacteriaceae from 18 Dutch hospitals and 21 isolates previously confirmed to be pAmpC positive. All isolates were divided into three groups: isolates with 1) reduced susceptibility to ceftazidime and/or cefotaxime; 2) reduced susceptibility to cefoxitin; 3) reduced susceptibility to ceftazidime and/or cefotaxime combined with reduced susceptibility to cefoxitin. Two disk-based tests, with cloxacillin or boronic acid as inhibitor, and Etest with cefotetan-cefotetan/cloxacillin were used for phenotypic AmpC confirmation. Finally, presence of pAmpC genes was tested by multiplex and singleplex PCR. RESULTS: We identified 13 pAmpC producing Enterobacteriaceae isolates among the 503 isolates (2.6%): 9 CMY-2, 3 DHA-1 and 1 ACC-1 type in E. coli isolates. The sensitivity and specificity of reduced susceptibility to ceftazidime and/or cefotaxime in combination with cefoxitin was 97% (33/34) and 90% (289/322) respectively. The disk-based test with cloxacillin showed the best performance as phenotypic confirmation method for AmpC production. CONCLUSIONS: For routine phenotypic detection of pAmpC the screening for reduced susceptibility to third generation cephalosporins combined with reduced susceptibility to cefoxitin is recommended. Confirmation via a combination disk diffusion test using cloxacillin is the best phenotypic option. The prevalence found is worrisome, since, due to their plasmidal location, pAmpC genes may spread further and increase in prevalence.

Emergence of colistin resistance in Enterobacteriaceae after the introduction of selective digestive tract decontamination in an intensive care unit.

Selective decontamination of the digestive tract (SDD) selectively eradicates aerobic Gram-negative bacteria (AGNB) by the enteral administration of oral nonabsorbable antimicrobial agents, i.e., colistin and tobramycin. We retrospectively investigated the impact of SDD, applied for 5 years as part of an infection control program for the control of an outbreak with extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae in an intensive care unit (ICU), on resistance among AGNB. Colistin MICs were determined on stored ESBL-producing K. pneumoniae isolates using the Etest. The occurrence of both tobramycin resistance among pathogens intrinsically resistant to colistin (CIR) and bacteremia caused by ESBL-producing K. pneumoniae and CIR were investigated. Of the 134 retested ESBL-producing K. pneumoniae isolates, 28 were isolated before SDD was started, and all had MICs of <1.5 mg/liter. For the remaining 106 isolated after starting SDD, MICs ranged between 0.5 and 24 mg/liter. Tobramycin-resistant CIR isolates were found sporadically before the introduction of SDD, but their prevalence increased immediately afterward. Segmented regression analysis showed a highly significant relationship between SDD and resistance to tobramycin. Five patients were identified with bacteremia caused by ESBL-producing K. pneumoniae before SDD and 9 patients thereafter. No bacteremia caused by CIR was found before SDD, but its occurrence increased to 26 after the introduction of SDD. In conclusion, colistin resistance among ESBL-producing K. pneumoniae isolates emerged rapidly after SDD. In addition, both the occurrence and the proportion of tobramycin resistance among CIR increased under the use of SDD. SDD should not be applied in outbreak settings when resistant bacteria are prevalent.

New diagnostic microarray (Check-KPC ESBL) for detection and identification of extended-spectrum beta-lactamases in highly resistant Enterobacteriaceae.

The performance of a microarray for the detection of extended-spectrum beta-lactamases was determined on a collection of 638 highly resistant members of the family Enterobacteriaceae collected from patients in 18 hospitals in The Netherlands. The microarray had a significantly higher specificity than the phenotypic assays. It also detects carbapenemases and characterizes the resistance genes, providing epidemiological insight.

Method for phenotypic detection of extended-spectrum beta-lactamases in enterobacter species in the routine clinical setting.

In 271 Enterobacter blood culture isolates from 12 hospitals, extended-spectrum beta-lactamase (ESBL) prevalence varied between 0% and 30% per hospital. High prevalence was associated with dissemination, indicating the potential relevance of infection control measures. Screening with cefepime or Vitek 2, followed by a cefepime/cefepime-clavulanate Etest, was an accurate strategy for ESBL detection in Enterobacter isolates (positive predictive value, 100%; negative predictive value, 99%).

Detection of an Ambler class D OXA-48-type ß-lactamase in a Klebsiella pneumoniae strain in The Netherlands.

Traditionally, bacteria in The Netherlands have low levels of resistance to antibiotics. This report describes what is believed to be the first carbapenem-resistant Klebsiella pneumoniae producing an OXA-48 type ß-lactamase in The Netherlands. The isolate co-produced a CTX-M-15 type ß-lactamase and was recovered from a patient who was transferred from a hospital in India to an intensive care unit in The Netherlands. His recovery in The Netherlands was complicated by pneumonia due to the carbapenem-resistant K. pneumoniae to which he eventually succumbed. Pre-emptive screening for carbapenem-resistant Enterobacteriaceae in selected patients could be imperative to maintain the low prevalence of these highly resistant bacteria in Dutch hospitals.

Characterization of DIM-1, an integron-encoded metallo-beta-lactamase from a Pseudomonas stutzeri clinical isolate in the Netherlands.

A carbapenem-resistant Pseudomonas stutzeri strain isolated from a Dutch patient was analyzed in detail. This isolate produced a metallo-beta-lactamase (MBL) whose gene, with 43.5% GC content, was cloned and expressed in Escherichia coli. beta-Lactamase DIM-1 (for Dutch imipenemase) was weakly related to other Ambler class B beta-lactamases, sharing <52% amino acid identity with the most closely related MBL, GIM-1, and 45% identity with IMP-type MBLs. The beta-Lactamase DIM-1 significantly hydrolyzed broad-spectrum cephalosporins and carbapenems and spared aztreonam. This MBL gene was embedded in a class 1 integron containing two other gene cassettes, encoding resistance to aminoglycosides and disinfectants, that was located on a 70-kb plasmid.