Approaches to multidrug-resistant organism prevention and control in long-term care facilities for older people: a systematic review and meta-analysis

Background Despite clear evidence of benefits in acute-care hospitals, controversy over the effectiveness of IPC measures for MDROs is perceptible and evidence-based practice has not been established. Objective To investigate the effects of IPC interventions on MDRO colonization and infections in LTCFs. Data sources Ovid MEDLINE, EMBASE, and CINAHL from inception to September 2020. Eligibility criteria Original and peer-reviewed articles examining the post-intervention effects on MDRO colonization and infections in LTCFs. Interventions (i) Horizontal interventions: administrative engagement, barrier precautions, education, environmental cleaning, hand hygiene, performance improvement, and source control; and (ii) vertical intervention: active surveillance plus decolonization. Study appraisal and synthesis We employed a random-effects meta-analysis to estimate the pooled risk ratios (pRRs) for methicillin-resistant Staphylococcus aureus (MRSA) colonization by intervention duration; and conducted subgroup analyses on different intervention components. Study quality was assessed using Cochrane risk of bias tools. Results Of 3877 studies identified, 19 were eligible for inclusion (eight randomized controlled trials (RCTs)). Studies reported outcomes associated with MRSA (15 studies), vancomycin-resistant Enterococci (VRE) (four studies), Clostridium difficile (two studies), and Gram-negative bacteria (GNB) (two studies). Eleven studies were included in the meta-analysis. The pRRs were close to unity regardless of intervention duration (long: RR 0.81 [95% CI 0.60–1.10]; medium: RR 0.81 [95% CI 0.25–2.68]; short: RR 0.95 [95% CI 0.53–1.69]). Vertical interventions in studies with a small sample size showed significant reductions in MRSA colonization while horizontal interventions did not. All studies involving active administrative engagement reported reductions. The risk of bias was high in all but two studies. Conclusions Our meta-analysis did not show any beneficial effects from IPC interventions on MRSA reductions in LTCFs. Our findings highlight that the effectiveness of interventions in these facilities is likely conditional on resource availability—particularly decolonization and barrier precautions, due to their potential adverse events and uncertain effectiveness. Hence, administrative engagement is crucial for all effective IPC programmes. LTCFs should consider a pragmatic approach to reinforce standard precautions as routine practice and implement barrier precautions and decolonization to outbreak responses only.

A Retrospective Characterization of Dexmedetomidine-Suspected Fever and Its Consequences in Adult Critically Ill Patients

Background: Current evidence for dexmedetomidine-suspected fever (DSF) is limited. Lack of recognition may lead to costly or potentially harmful interventions for critically ill patients. Objective: The primary objective was to characterize escalations of care related to DSF. Secondary objectives were to describe the incidence, severity, and consequences associated with DSF. Methods: A retrospective review was conducted in critically ill adults who developed fever ≥39°C within 12 h from initiation of dexmedetomidine, with resolution of fever to <39°C within 12 h after discontinuation. The primary outcome was percentage of patients who received an escalation of care due to fever. Secondary outcomes included the percentage of patients who developed a multidrug-resistant organism or Clostridium difficile infection. Results: Eighteen of 3943 patients screened in 4099 encounters met criteria for DSF (0.4%). The majority were white (83.3%), male (66.7%), and underwent cardiac surgery (61.1%). Median (interquartile range [IQR]) time to fever onset and resolution were 5.5 (3.6-7.6) and 1.3 (1.0-2.9) h. Nine patients (50%) underwent infectious workup including antimicrobial initiation (n = 1, 5.6%), broadening of antimicrobials (n = 4, 22.2%), or culture collection (n = 9, 50%). Eleven patients (61.1%) underwent attempted temperature reduction. Twelve patients (66.7%) underwent diagnostic imaging. Incidence of multidrug-resistant organism and C. difficile infection were low (11.1 and 16.7% of fever patients, respectively). Conclusion and Relevance: Incidence of DSF was low and more common in cardiac surgery patients. Unrecognized DSF led to an escalation of care in most patients. Dexmedetomidine exposure should be considered as a potential cause of fever in critically ill adults.

Combining antibiotics with silver nanoparticles: A potential treatment strategy against antimicrobial resistance

Growing resistance to currently approved antibiotics is posing serious concern worldwide. The multidrug-resistant organisms are a major cause of mortality and morbidity around the globe. The limited options to treat infections caused by resistant organism requires alternative strategies to increase the effectiveness of antibiotic for better clinical outcomes. Recent advances in nanotechnology have enabled the drugs to be used in nanoscale to increase the effectiveness of antibiotics. The use of nanoparticles to treat infectious diseases has a long history in the pharmaceutical market, and the versatility of these particles to incorporate various materials as carriers make it an attractive option to combat the current crisis of emerging antibacterial resistance. Silver, a metal with many medical applications, has inherent antimicrobial properties. Therefore, silver NPs are appearing as one of the best options to be used in combination with antibiotics to increase effectiveness against resistant bacteria. Here, we discuss the applications and mechanisms of silver NPs to treat microbial resistance in light of recent research.

Elizabethkingia miricola Causes Intracranial Infection: A Case Study

Background:Elizabethkingia miricola is a rarely encountered bacterium in clinical practice. It is a rare gram-negative rod-shaped bacterium associated with lung and urinary tract infections, but never found in cerebrospinal fluid. This paper reports a case of an adult patient infected by E. miricola via an unknown route of infection causing a severe intracranial infection. Elizabethkingia miricola was detected by culture and Metagenomic next generation sequencing in CSF. Early identification of this strain and treatment with sensitive antibiotics is necessary to reduce morbidity and mortality.Case Report: A 24-year-old male was admitted to a West China Hospital because of headache and vomiting for 2 months. Symptom features included acute onset and long duration of illness. Notably, headache and vomiting were the primary neurological symptoms. Routine cerebrospinal fluid culture failed to identify the bacterium; however, Elizabethkingia miricola bacterium was detected via second-generation sequencing techniques. Elizabethkingia miricola was found to be a multi-drug resistant organism, hence, treatment with ceftriaxone, a commonly used drug for intracranial infections was ineffective. This strain eventually caused severe intracranial infection resulting in the death of the patient.Conclusion: In summary, this study comprehensively describes a case of an adult patient infected by E. miricola and discusses its early identification as well as application of sensitive antibiotics in the emergency setting.

How the COVID-19 pandemic changed postoperative infections in urology wards: A retrospective cohort study from two urology departments

Introduction: We aimed to compare the rate of postoperative infection and drug-resistant organism (DRO) before and during the COVID-19 pandemic in urology departments. Methods: A retrospective cohort study was carried out. Data from all elective surgical procedures carried out in two urology departments between April and June 2018 and the homologous period in 2020 were collected. Main outcomes were the number of postoperative infections during the pandemic, and the number of DROs. Sample size was calculated based on a 50% relative reduction of infections during the pandemic. Variables were compared by Chi-squared test, and multivariable logistic regression was used to estimate predictors. Results: A total of 698 patients undergoing elective surgery were included. The postoperative infection rate during the pre-pandemic period was of 14.1% compared to 12.1% during the pandemic (p=0.494). DROs were lower during the pandemic (92.3% vs. 52.4%, p=0.002). The pandemic period was the main predictor for reduced multi-drug-resistant isolates, with an odds ratio of 0.10 (p=0.010, 95% confidence interval 0.016–0.57). Conclusions: Postoperative infection rates were not significantly reduced during the COVID-19 pandemic, despite the adoption of enhanced infection preventive measures. There was, however, a decrease in the rate of DROs during this period, suggesting a secondary benefit to enhanced infection prevention practices adopted during the COVID-19 era.

Case Study - Candida auris in Skilled Nursing Facility

Candida Auris (C. auris), is a multidrug-resistant organism, first described in Japan 2009, and now a serious, emerging global health threat1. C. auris pathogen can potentiate morbidity and mortality, i.e. lifelong contact precaution isolation, intravenous antifungal treatment, hospitalization and mortality rate of 30-60%1. Los Angeles County (LAC) developed 15 new cases in May 2020, and 73 cases in July 2020, amidst COVID-19 pandemic2. A 88 year old Black female had a positive skin test for C. auris by LAC Department of Public Health (DPH) during skilled nursing facility (SNF) admission for hip fracture in September 2020. Patient’s risk factors for C. auris included: age, kidney transplantation (1998) immunosuppression on tacrolimus, fungal infection on fluconazole, drug-drug interaction between tacrolimus-fluconazole including nephrotoxicity and neurotoxicity, malnutrition, bedbound, Stage 4 sacrococcyx pressure ulcer, osteomyelitis on broad-spectrum antibiotics, chronic indwelling catheter, and healthcare setting. Our multimorbid and frail patient remained asymptomatic with C. auris under an interdisciplinary team approach, including geriatricians, infectious disease, pharmacists, SNF team and local DPH. Our patient’s psychosocial isolation and family distress with local DPH guidelines for COVID-19 SNF visitation restrictions were compounded by multifaceted coordination of patient-centered care between SNF team and specialists via telehealth. Further research in the prevention, detection, and management of C. auris is warranted to protect our vulnerable SNF residents. 1. Centers for Disease Control and Prevention. (2020). Tracking Candida auris. https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html 2. Los Angeles County Health Alert Network. (2020). CDPH Health Advisory: Resurgence of Candida auris in Healthcare Facilities in the Setting of COVID-19. http://publichealth.lacounty.gov/eprp/lahan/alerts/CAHANCauris082020.pdf

Citric acid/β-alanine carbon dots as a novel tool for delivery of plasmid DNA into E. coli cells

Successful delivery of plasmid DNA into the microbial cells is fundamental in recombinant DNA technology. Natural bacterial transformation is limited to only certain species due in part to the repulsive forces between negatively charged DNA and bacterial membranes. Most common method of DNA delivery into bacteria is artificial transformation through heat shock and electroporation. These methods require sophisticated instruments and tedious steps in preparation of competent cells. Transformation by conjugation is also not applicable to all plasmids. Nanoparticles have been used successfully in therapeutics for drug delivery into animal cells. They are starting to gain popularity in plant sciences as novel DNA nano carriers. Despite their promise as tool for DNA delivery, their use in microbial cell transformation has not been reported yet. Here we report the synthesis of carbon dots (CDs) from citric acid and β-alanine and their use in DNA delivery into E. coli cells. CDs were fabricated using microwave assisted synthesis. Plasmids carrying RFP reporter and ampicillin resistance genes were transferred to bacterial cells and further confirmed using polymerase chain reaction. Our findings indicate that CDs can be used successfully for delivery of foreign DNA of up to 10 kb into E. coli. We have demonstrated the use of β-alanine/citric acid carbon dots as nanocarriers of DNA into E. coli cells and identified their limitation in terms of the size of plasmid DNA they could carry. Use of these carbon dots is a novel method in foreign DNA delivery into bacterial cells and have a potential for the transformation of resistant organism for which there is still no reliable DNA delivery systems.

1257. Re-Evaluation of Cefepime or Piperacillin-Tazobactam to Decrease Use of Carbapenems in ESBL-Producing Enterobacterales Urinary Tract Infections (REDUCE-UTI)

Background Carbapenems (CBP) are considered first-line for infections caused by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E). However, recent literature suggests that cefepime (FEP) and piperacillin-tazobactam (TZP) may produce similar outcomes vs. CBPs for the treatment of ESBL-E urinary tract infections (UTIs). The goal of this study was to determine if non-carbapenem (NCBP) therapy with FEP or TZP is as effective as CBPs for the treatment of ESBL-E UTIs. Methods This was a retrospective observational study of patients admitted to the hospital from January 1st, 2016 to June 30th, 2020 with a urine culture positive for ESBL-E. Patients were included if they received a study antibiotic (meropenem, ertapenem, TZP, or FEP). Patients were excluded if they had any of the following: absence of pyuria, prior receipt of study antibiotic, CBP-resistant organism isolated in urine culture, polymicrobial urine culture, end-stage renal disease, or concomitant gram-negative infection. The primary outcome was clinical cure defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days, and resistance within 30 days. Results A total of 133 patients were included based on definitive therapy received; 69 (52%) received CBP and 64 (48%) received NCBP therapy. Of the total patient population, 17 (13%) were admitted to the intensive care unit, 84 (63%) had a complicated UTI, and 64 (48%) had pyelonephritis. Baseline characteristics were similar between the two groups. There was no difference in clinical cure between the CBP and NCBP therapy groups (96% vs. 97%, p = 1.0). Additionally, no differences in secondary outcomes were observed. Subgroup analyses were performed in patients with specific pathogens, uncontrolled genitourinary source, complicated UTI, and pyelonephritis. These analyses did not reveal any differences in primary or secondary outcomes between the two groups. Conclusion FEP and TZP may be reasonable CBP-sparing alternatives for the treatment of ESBL-E UTIs as clinical and microbiological outcomes were similar with these NCBP agents vs. CBPs in this study population. Disclosures Venugopalan Veena, PharmD, Melinta (Other Financial or Material Support, Received a stipend for participation in a drug registry)Merck (Other Financial or Material Support, Received a stipend for participation in a drug registry)