Multidrug-Resistant Bacteria in the Community: An Update

Multidrug-resistant bacteria are among the most important current threats to public health. Typically, they are associated with nosocomial infections. However, some have become prevalent causes of community-acquired infections, such as Neisseria gonorrhoeae, Shigella, Salmonella, and Streptococcus pneumoniae. The community spread of multidrug-resistant bacteria is also a crucial development. An important global threat on the horizon is represented by production of carbapenemases by community-acquired hypervirulent Klebsiella pneumoniae. Such strains have already been found in Asia, Europe, and North America. Prevention of further community spread of multidrug-resistant bacteria is of the utmost importance, and will require a multidisciplinary approach involving all stakeholders

Return to Sender: The need to re-address patient antibiotic allergy labels in Australia and New Zealand

BACKGROUND: Antibiotic allergies are frequently reported and have significant impacts upon appropriate prescribing and clinical outcomes. We surveyed infectious diseases physicians, allergists, clinical immunologists and hospital pharmacists to evaluate antibiotic allergy knowledge and service delivery in Australia and New Zealand. METHODS: An online multi-choice questionnaire was developed and endorsed by representatives of the Australasian Society of Clinical Immunology and Allergy (ASCIA), Australasian Society of Infectious Diseases (ASID) and Society of Hospital Pharmacists Australia (SHPA). The 37-item survey was distributed in April 2015 to members of ASCIA, ASID, SHPA and Royal Australasian College of Physicians. RESULTS: Of 277 respondents, 94% currently use or would utilise antibiotic allergy testing (AAT) and reported seeing up to 10 patients/week labelled as antibiotic-allergic. Forty-two per cent were not aware of or did not have AAT available. Most felt that AAT would aid antibiotic selection, antibiotic appropriateness and antimicrobial stewardship (79%, 69% and 61%, respectively). Patients with histories of immediate hypersensitivity were more likely to be referred than those with delayed hypersensitivities (76% vs. 41%, p=0.0001). Lack of specialist physicians (20%) and personal experience (17%) were barriers to service delivery. A multidisciplinary approach was the preferred AAT model (53%). Knowledge gaps were identified, with the majority over-estimating rates of penicillin/cephalosporin (78%), penicillin/carbapenem (57%) and penicillin/monobactam (39%) cross-reactivity. CONCLUSIONS: A high burden of antibiotic allergy labelling and demand for AAT is complicated by a relative lack availability or awareness of AAT services in Australia and New Zealand. Antibiotic allergy education and deployment of AAT, accessible to community and hospital-based clinicians, may improve clinical decisions and reduce antibiotic allergy impacts. A collaborative approach involving ID physicians, pharmacists and allergists/immunologists is required

Characteristics and outcomes of culture-negative prosthetic joint infections from the Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort study

Introduction: Culture-negative (CN) prosthetic joint infections (PJIs) account for approximately 10 % of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJIs within a large prospective cohort study, comparing their characteristics and outcomes with culture-positive (CP) cases. Methods: The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, multicentre observational cohort study that was conducted at 27 hospitals between 2014 and 2017. We compared baseline characteristics and outcomes of all patients with CN PJI from the PIANO cohort with those of CP cases. We report on PJI diagnostic criteria in the CN cohort and apply internationally recognized PJI diagnostic guidelines to determine optimal CN PJI detection methods. Results: Of the 650 patients with 24-month outcome data available, 55 (8.5 %) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female (32 (58.2 %) vs. 245 (41.2 %); p = 0.016), involve the shoulder joint (5 (9.1 %) vs. 16 (2.7 %); p = 0.026), and have a lower mean C-reactive protein (142 mg L−1 vs. 187 mg L−1; p = 0.016). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (adjusted odds ratio, aOR, of 3.78 and 95 %CI of 1.65–8.67). Suboptimal diagnostic sampling was common in both cohorts, with CN PJI case detection enhanced using the Infectious Diseases Society of America PJI diagnostic guidelines. Conclusions: Current PJI diagnostic guidelines vary substantially in their ability to detect CN PJI, with comprehensive diagnostic sampling necessary to achieve diagnostic certainty. Definitive surgical management strategies should be determined by careful assessment of infection type, rather than by culture status alone

Comorbidities, exposure to medications, and the risk of community-acquired clostridium difficile infection: A systematic review and meta-analysis

Background. Clostridium difficile infection (CDI) has been extensively escribedin healthcare settings; however, risk factor sassociated with community-acquired (CA) CDI remain uncertain. This study aimed to synthesize the current evidence for an association between commonly prescribed medications and comorbidities with CA-CDI. methods. A systematic search was conducted in 5 electronic databases for epidemiologicstudi esthatexamined the associtation between the presence of comorbidities and exposure to medications with the risk of CA-CDI. Pooled odds ratios were estimated using 3 meta-analytic methods. Subgroup analyses by location of studies and by life stages were conducted. results. Twelve publications (n=56,776 patients) met inclusion criteria. Antimicrobial (odds ratio, 6.18; 95% CI, 3.80-10.04) and corticosteroid (1.81; 1.15-2.84) exposure were associated with increased risk of CA-CDI. Among the comorbidities, inflammatory bowel disease (odds ratio, 3.72; 95% CI, 1.52-9.12), renal failure (2.64; 1.23-5.68), hematologic cancer (1.75; 1.02-5.68), and diabetes mellitus (1.15; 1.05-1.27) were associated with CA-CDI. By location, antimicrobial exposure was associated with a higher risk of CA-CDI in the United States, whereas proton-pump inhibitor exposure was associated with a higher risk in Europe. By life stages, the risk of CA-CDI associated with antimicrobial exposure greatly increased in adults older than 65 years. conclusions. Antimicrobial exposure was the strongest risk factor associated with CA-CDI. Further studies are required to investigate the risk of CA-CDI associated with medications commonly prescribed in the community. Patients with diarrhea who have inflammatory bowel disease, renal failure, hematologic cancer, or diabetes are appropriate populations for interventional studies of screening

Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance

AbstractMany different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided

Modern clinician-initiated clinical trials to determine optimal therapy for multidrug-resistant gram-negative infections

Treatment options for multidrug-resistant (MDR) gram-negative infection are growing. However, postregistration, pragmatic, and clinician-led clinical trials in this field are few, recruit small sample sizes, and experience deficiencies in design and operations. MDR gram-negative therapeutic trials are often inefficient, only evaluating a single antibiotic or strategy at a time. Novel clinical trial designs offer potential solutions by attempting to obtain clinically meaningful conclusions at the end or during a trial, for many treatment strategies, simultaneously. An integrated, consensus approach to MDR gram-negative infection trial design is crucial

A comparison of precipitation and filtration-based SARS-CoV-2 recovery methods and the influence of temperature, turbidity, and surfactant load in urban wastewater

Wastewater-based epidemiology (WBE) has become a complimentary surveillance tool during the SARS-CoV-2 pandemic. Viral concentration methods from wastewater are still being optimised and compared, whilst viral recovery under different wastewater characteristics and storage temperatures remains poorly understood. Using urban wastewater samples, we tested three viral concentration methods; polyethylene glycol precipitation (PEG), ammonium sulphate precipitation (AS), and CP select™ InnovaPrep® (IP) ultrafiltration. We found no major difference in SARS-CoV-2 and faecal indicator virus (crAssphage) recovery from wastewater samples (n = 46) using these methods, PEG slightly (albeit non-significantly), outperformed AS and IP for SARS-CoV-2 detection, as a higher genome copies per litre (gc/l) was recorded for a larger proportion of samples. Next generation sequencing of 8 paired samples revealed non-significant differences in the quality of data between AS and IP, though IP data quality was slightly better and less variable. A controlled experiment assessed the impact of wastewater suspended solids (turbidity; 0–400 NTU), surfactant load (0–200 mg/l), and storage temperature (5–20 °C) on viral recovery using the AS and IP methods. SARS-CoV-2 recoveries were >20% with AS and  0.05), whilst surfactant and storage temperature combined were significant negative correlates (p < 0.001 and p < 0.05, respectively). In conclusion, our results show that choice of methodology had small effect on viral recovery of SARS-CoV-2 and crAssphage in wastewater samples within this study. In contrast, sample turbidity, storage temperature, and surfactant load did affect viral recovery, highlighting the need for careful consideration of the viral concentration methodology used when working with wastewater samples

City-wide wastewater genomic surveillance through the successive emergence of SARS-CoV-2 Alpha and Delta variants

Genomic surveillance of SARS-CoV-2 has provided a critical evidence base for public health decisions throughout the pandemic. Sequencing data from clinical cases has helped to understand disease transmission and the spread of novel variants. Genomic wastewater surveillance can offer important, complementary information by providing frequency estimates of all variants circulating in a population without sampling biases. Here we show that genomic SARS-CoV-2 wastewater surveillance can detect fine-scale differences within urban centres, specifically within the city of Liverpool, UK, during the emergence of Alpha and Delta variants between November 2020 and June 2021. Furthermore, wastewater and clinical sequencing match well in the estimated timing of new variant rises and the first detection of a new variant in a given area may occur in either clinical or wastewater samples. The study's main limitation was sample quality when infection prevalence was low in spring 2021, resulting in a lower resolution of the rise of the Delta variant compared to the rise of the Alpha variant in the previous winter. The correspondence between wastewater and clinical variant frequencies demonstrates the reliability of wastewater surveillance. However, discrepancies in the first detection of the Alpha variant between the two approaches highlight that wastewater monitoring can also capture missing information, possibly resulting from asymptomatic cases or communities less engaged with testing programmes, as found by a simultaneous surge testing effort across the city

Livestock-associated MRSA colonization of occupational exposed workers and households in Europe: a review

The worldwide escalation in antibiotic resistant microorganisms has sustained the increasing concerns regarding antibiotics extensive use in animal food industry, which can result in a selection pressure that is driving the emergence of strains such as methicillin-resistant staphylococcus aureus (MRSA). Human MRSA infections are a well-known cause of numerous hospitalizations and deaths associated with extremely high mortality rates for invasive infections. Both animals and humans can become bacterial reservoirs of Livestock Associated MRSA (LA-MRSA) in which colonization predisposes to staphylococcal acquisition in clinical settings and to transfer the infection to others including household members. Biomonitoring of occupational exposed individuals which spend several hours per day in direct contact with MRSA-positive animals and thus are irrefutably exposed to a high risk of nasal colonization is imperative in order to develop effective preventive strategies. Here we performed an extensive review regarding the prevalence of LA- MRSA colonization in both occupational exposed individuals and their house-holds in a European context.info:eu-repo/semantics/publishedVersio

Spin, charge and orbital ordering in ferrimagnetic insulator YBaMn2_2O5_5

The oxygen-deficient (double) perovskite YBaMn$_2$O$_5$, containing corner-linked MnO$_5$ square pyramids, is found to exhibit ferrimagnetic ordering in its ground state. In the present work we report generalized-gradient-corrected, relativistic first-principles full-potential density-functional calculations performed on YBaMn$_2$O$_5$ in the nonmagnetic, ferromagnetic and ferrimagnetic states. The charge, orbital and spin orderings are explained with site-, angular momentum- and orbital-projected density of states, charge-density plots, electronic structure and total energy studies. YBaMn$_2$O$_5$ is found to stabilize in a G-type ferrimagnetic state in accordance with experimental results. The experimentally observed insulating behavior appears only when we include ferrimagnetic ordering in our calculation. We observed significant optical anisotropy in this material originating from the combined effect of ferrimagnetic ordering and crystal field splitting. In order to gain knowledge about the presence of different valence states for Mn in YBaMn$_2$O$_5$ we have calculated $K$-edge x-ray absorption near-edge spectra for the Mn and O atoms. The presence of the different valence states for Mn is clearly established from the x-ray absorption near-edge spectra, hyperfine field parameters and the magnetic properties study. Among the experimentally proposed structures, the recently reported description based on $P$4/$nmm$ is found to represent the stable structure