Regional Variation in the Interpretation of Contact Precautions for Multidrug-resistant Gram-negative bacteria: a cross-sectional survey.

BACKGROUND: Contact precautions (CP) are recommended when caring for patients with carbapenemase-producing Enterobacterales (CPE), carbapenemase-producing Pseudomonas aeruginosa (CPPA), and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E). AIM: Our aim was to determine the interpretation of CP and associated infection prevention and control (IPC) measures in the non-ICU hospital setting for patients with CPE, CPPA or ESBL-E in 11 hospitals in the Southwest of the Netherlands. METHODS: A cross-sectional survey was developed to collect information on all implemented IPC measures, including use of personal protective equipment, IPC measures for visitors, cleaning and disinfection, precautions during outpatient care and follow-up strategies. All eleven hospitals were invited to participate between November 2020 and April 2021. FINDINGS: The survey was filled together with each hospital. All hospitals installed isolation precautions for patients with CPE and CPPA during inpatient care and day admissions, whereas ten hospitals (90.9%) applied isolation precautions for patients with ESBL-E. Gloves and gowns were always used during physical contact with the patient in isolation. Large variations were identified in IPC measures for visitors, cleaning and disinfection products used, and precautions during outpatient care. Four hospitals (36.4%) actively followed up on CPE or CPPA patients with the aim to declare them CPE- or CPPA-negative as timely as possible, and two hospitals (20.0%) actively followed up on ESBL-E patients. CONCLUSION: CP are interpreted differently between hospitals, leading to regional differences in IPC measures applied in clinical settings. Harmonizing infection-control policies between the hospitals could facilitate patient transfers and benefit collective efforts of preventing transmission of MDR-GNB.

Contact investigations for antibiotic-resistant bacteria: a mixed-methods study of patients' comprehension of and compliance with self-sampling requests post-discharge.

BACKGROUND: Contact investigation is an important tool to identify unrecognized patients who are colonized with antibiotic-resistant bacteria. Many Dutch hospitals include already discharged contact patients by sending them a self-sampling request at home, incl. an information letter and sampling materials. Each hospital composes these information letters on their own initiative, however, whether discharged patients comprehend and comply with these requests remains unclear. Therefore, the aim was to provide insight into patients' comprehension of and self-reported compliance with self-sampling requests post-discharge. METHODS: This mixed-methods study was performed in eight Dutch hospitals. First, the Common European Framework of Reference (CEFR) language level of self-sampling request letters was established. Second, a questionnaire about patients' comprehension of the letter, self-reported compliance, and reasons for compliance or non-compliance were sent to patients that received such a request in 2018/2019. Finally, a random selection of questionnaire respondents was interviewed between January and March 2020 to gain additional insights. RESULTS: CEFR levels of 15 letters were established. Four letters were assigned level B1, four letters B1-B2, and seven letters B2. The majority of patients reported good comprehension of the letter they had received. Conversely, some respondents indicated that information about the bacterium (18.4%), the way in which results would be communicated (18.1%), and the self-sampling instructions (9.7%) were (partially) unclear. Furthermore, self-reported compliance was high (88.8%). Reasons to comply were personal health (84.3%), the health of others (71.9%), and general patient safety (96.1%). Compliant patients appeared to have a need for confirmation, wanted to protect family and/or friends, and felt they were providing the hospital the ability to control the transmission of antibiotic-resistant bacteria. Although a limited number of non-compliant patients responded to the questionnaire, it seemed that more patients did not comply with self-sampling requests when they received a letter in a higher CEFR-level (B2) compared to a lower CEFR-level (< B2) (9.8% vs. 2.5%, P = 0.049). CONCLUSIONS: This study showed an overall good comprehension of and high self-reported compliance with self-sampling requests post-discharge. Providing balanced information in self-sampling request letters has the potential to reduce patient's ambiguity and concerns, and can cause increased compliance with self-sampling requests.

Fatal Hemophagocytic Lymphohistiocytosis in a Patient with Miliary Tuberculosis: a Case Report.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome induced by cytotoxic T-cells. Mostly, HLH is secondary to infections, malignancies, or autoimmune disorders. HLH triggered by miliary tuberculosis is rare and mortality rates are high. We report a case of a 58-year-old, Caucasian patient admitted to the ICU with respiratory failure. After extensive tests, the diagnosis of HLH was made. Despite aggressive treatment with antibiotics, etoposide, anakinra, and tocilizumab, our patient succumbed to the illness after 18 days in the ICU. Postmortem, a diagnosis of miliary tuberculosis was made, despite negative PCR and culture of mycobacteria during clinical course. Our case demonstrates the challenges of early diagnosis of HLH and the importance of considering miliary tuberculosis as a possible underlying trigger. Supplementary Information: The online version contains supplementary material available at 10.1007/s42399-022-01232-y.

Rapid screening method for the detection of SARS-CoV-2 variants of concern.

BACKGROUND: Comprehensive and up-to-date monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) is crucial as these are characterized by their increased transmissibility, immune evasion and virulence. OBJECTIVES: To describe the wide-scale implementation of a reverse transcriptase polymerase chain reaction (RT-PCR) multiple variants assay with melting curve analysis as a routine procedure. STUDY DESIGN: We prospectively performed multiple variants RT-PCR on consecutive SARS-CoV-2 RT-PCR positive samples from patients, healthcare workers and nursing home residents from our hospital catchment area. This technique was implemented in our automated Roche FLOW system with a turn-around time of 6 h. RESULTS: Between February 1 and May 2, 2021, 989 samples were tested by the variant RT-PCR. Our method was validated by comparison of variant RT-PCR to whole genome sequencing testing. We observed an increase over time in the proportion of UK variant that became the dominant variant, and the concurrent emergence of the South-African and Brazilian variants. Prompt public health responses for infection control were possible because of this rapid screening method, resulting in early detection and reduction of unnoticed spread of VOC as early as possible. CONCLUSION: A variant RT-PCR with additional melting curve analyses is a feasible, rapid and efficient screening strategy that can be implemented in routine microbiological laboratories.

Increased expression levels of chromosomal AmpC ß-lactamase in clinical Escherichia coli isolates and their effect on susceptibility to extended-spectrum cephalosporins.

Forty-nine clinical Escherichia coli isolates, both extended-spectrum ß-lactamase (ESBL) negative and ESBL positive, were studied to investigate whether increased AmpC expression is a mechanism involved in cefoxitin resistance and if this influences the third-generation cephalosporin activity. Nine of 33 (27.2%) cefoxitin-resistant (minimum inhibitory concentration [MIC] >8 mg/L) isolates showed hyperproduction of chromosomal AmpC (c-AmpC) based on (1) at least two positive tests using AmpC inhibitors, (2) mutations in the promoter/attenuator regions, and (3) a 6.1- to 163-fold increase in c-ampC expression by quantitative reverse transcription-polymerase chain reaction. In ESBL-negative isolates, MICs of ceftazidime and cefotaxime were mostly above the wild-type (WT) level, but below the S/I breakpoint (EUCAST guideline), except for one isolate with MICs of 4 mg/L. No plasmid-mediated AmpCs were found. Periplasmic extracts of nine c-AmpC hyperproducers were preincubated with or without cefuroxime or ceftazidime and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cefuroxime and ceftazidime were stable to hydrolysis but acted as inhibitors of the enzyme. None of these isolates showed loss of porins. Thus, cefoxitin resistance has low specificity for detecting upregulated c-AmpC production. c-AmpC hyperproducing E. coli is mostly still susceptible to third-generation cephalosporins but less than WT E. coli. Surveillance of cefoxitin-resistant E. coli to monitor developments in the activity of third-generation cephalosporins against c-AmpC hyperproducers is warranted.

Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Escherichia coli.

Resistance to ciprofloxacin in Escherichia coli is increasing parallel to increased use of fluoroquinolones both in The Netherlands and in other European countries. The objective was to investigate the contribution of active efflux and expression of outer membrane proteins (OMPs) in a collection of clinical E. coli isolates collected at a clinical microbiology department in a Dutch hospital. Forty-seven E. coli isolates a wide range of ciprofloxacin minimum inhibitory concentrations and known mutations in the quinolone resistance determining region were included. A fluorometric determination of bisbenzimide efflux was used two different efflux pump inhibitors and compared to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for the expression levels of acrA, acrB, tolC, yhiV, and mdfA efflux pump genes and the OMPs ompF and ompX. Six isolates (12.7%) showed increased efflux. Although in 35 isolates (76%), overexpression of ≥1 efflux pump genes using qRT-PCR was present. Only the combined overexpression of acrAB-TolC and mdfA correlated with the phenotypic efflux assay using glucose/carbonyl cyanide m-chlorophenylhydrazone with glucose. Thus, efflux was involved in ciprofloxacin resistance in a limited number of E. coli isolates collected at a clinical microbiology department in a Dutch hospital complementing other resistance mechanisms.

Extended-spectrum ß-lactamase-producing enterobacteriaceae among travelers from the Netherlands.

A prospective cohort study was performed among travelers from the Netherlands to investigate the acquisition of carbapenemase-producing Enterobacteriaceae (CP-E) and extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) and associated risk factors. Questionnaires were administered and rectal swab samples were collected and tested before and after traveler return. Of 370 travelers, 32 (8.6%) were colonized with ESBL-E before trave,; 113 (30.5%) acquired an ESBL-E during travel, and 26 were still colonized 6 months after return. No CP-E were found. Independent risk factors for ESBL-E acquisition were travel to South and East Asia. Multilocus sequence typing showed extensive genetic diversity among Escherichia coli. Predominant ESBLs were CTX-M enzymes. The acquisition rate, 30.5%, of ESBL-E in travelers from the Netherlands to all destinations studied was high. Active surveillance for ESBL-E and CP-E and contact isolation precautions may be recommended at admission to medical facilities for patients who traveled to Asia during the previous 6 months.

Risk factors for fluoroquinolone-resistant Escherichia coli in adults with community-onset febrile urinary tract infection.

OBJECTIVES: To assess risk factors for fluoroquinolone resistance in community-onset febrile Escherichia coli urinary tract infection (UTI). METHODS: A nested case-control study within a cohort of consecutive adults with febrile UTI presenting at primary healthcare centres or emergency departments during January 2004 through December 2009. Resistance was defined using EUCAST criteria (ciprofloxacin MIC >1.0 mg/L). Cases were subjects with fluoroquinolone-resistant E. coli, and controls those with fluoroquinolone-susceptible isolates. Multivariable logistic regression analysis was used to identify potential risk factors for fluoroquinolone resistance. RESULTS: Of 787 consecutive patients, 420 had E. coli-positive urine cultures. Of these, 51 (12%) were fluoroquinolone resistant. Independent risk factors for fluoroquinolone resistance were urinary catheter [odds ratio (OR) 3.1; 95% confidence interval (CI) 0.9-11.6], recent hospitalization (OR 2.0; 95% CI 1.0-4.3) and fluoroquinolone use in the past 6 months (OR 17.5; 95% CI 6.0-50.7). Environmental factors (e.g. contact with animals or hospitalized household members) were not associated with fluoroquinolone resistance. Of fluoroquinolone-resistant strains, 33% were resistant to amoxicillin/clavulanate and 65% to trimethoprim/sulfamethoxazole; 14% were extended-spectrum ß-lactamase (ESBL) positive compared with <1% of fluoroquinolone-susceptible isolates. CONCLUSIONS: Recent hospitalization, urinary catheter and fluoroquinolone use in the past 6 months were independent risk factors for fluoroquinolone resistance in community-onset febrile E. coli UTI. Contact with animals or hospitalized household members was not associated with fluoroquinolone resistance. Fluoroquinolone resistance may be a marker of broader resistance, including ESBL positivity.

[Fatal pneumonia caused by carbapenem resistant Klebsiella pneumoniae]. / Fatale pneumonie door carbapenemresistente Klebsiella pneumoniae.

A 63-year-old Dutch man became colonized with a carbapenem resistant Klebsiella pneumoniae during a period of hospitalization in India. His recovery in the Netherlands was complicated by pneumonia due to this difficult-to-control multiresistant bacteria to which he eventually succumbed. Carbapenem resistance in Enterobacteriaceae, such as K. pneumoniae, is usually caused by carbapenemase (a betalactamase) production. Carbapenemase producing Enterobacteriaceae (CPE) are spreading throughout the world and cause difficult-to-treat infections that are associated with high mortality. This case report illustrates the clinical challenges associated with infection with these multiresistant Enterobacteriaceae. In the Netherlands, there are no guidelines for detection of CPE and carbapenemase production can frequently go undetected in clinical microbiology laboratories. As a consequence, adequate treatment of CPE infections and infection control measures to prevent the spread of CPE can be delayed. Expeditious development and implementation of existing Dutch draft guidelines for detection methods of CPE is therefore warranted.

A comparative study of two methods for attaining constant alcohol levels.

AIMS: Alcohol effects or drug-alcohol interactions are preferably studied at constant blood levels. To achieve pseudo-steady state levels, various methods are used, which usually produce adequate averages but variable individual concentration profiles. The aim was to compare two modes of alcohol administration: a 'two-step prekinetic procedure' and a 'clamping method'. METHODS: The two-step prekinetic procedure started with determination of individual pharmacokinetic (PK) parameters, during a prestudy occasion. Individual infusion regimens were calculated afterwards, based on a pseudo-steady state breath alcohol concentration (BrAC) of 0.65 g l(-1) and applied on a separate occasion. For the clamping procedure, a spreadsheet-based paradigm was developed using BrAC-guided adjustments of infusion rates, to maintain stable BrAC levels of 0.6 g l(-1). RESULTS: The mean BrAC during clamping [0.61 g l(-1), 95% confidence interval (CI) 0.58, 0.63] did not differ from its intended level of 0.6 g l(-1) (1.0% on average). In contrast, the mean BrAC during the prekinetic procedure was significantly lower than the 0.65 g l(-1) set-point (0.59 g l(-1), 95% CI 0.54, 0.63) and deviated from this target by 9.7% on average. The clamping method also showed less variation between subjects [coefficient of variation (CV) 6.2%] compared with the prekinetic procedure (CV 14.6%). CONCLUSIONS: Although the two methods differ considerably in their approach, clamping of BrAC resulted in more accurate alcohol levels than infusion based on PK modelling and does not require an extra prestudy occasion. The novel alcohol clamping paradigm can be of value in future studies of alcohol interactions or the pharmacodynamics of acute alcohol administration.