Global spread of carbapenem-resistant Enterobacteriaceae: Epidemiological features, resistance mechanisms, detection and therapy

Bacterial drug resistance has become a global public health threat, among which the infection of carbapenem-resistant Enterobacterales (CRE) is one of the top noticeable issues in the global anti-infection area due to limited therapy options. In recent years, the prevalence of CRE transmission around the world has increased, and the transmission of COVID-19 has intensified the situation to a certain extent. CRE resistance can be induced by carbapenemase, porin, efflux pump, penicillin-binding protein alteration, and biofilm production. Deletion, mutation, insertion, and post-transcriptional modification of corresponding coding genes may affect the sensitivity of Enterobacterales bacteria to carbapenems. Clinical and laboratory methods to detect CRE and explore its resistance mechanisms are being developed. Due to the limited options of antibiotics, the clinical treatment of CRE infection also faces severe challenges. The clinical therapies of CRE include single or combined use of antibiotics, and some new antibiotics and treatment methods are also being developed. Hence, this review summarizes the epidemiology, resistance mechanisms, screening and clinical treatments of CRE infection, to provide references for clinical prevention, control and treatment of CRE infection. © 2022 Elsevier GmbH

Seasonal variation and ecological risk assessment of Pharmaceuticals and Personal Care Products (PPCPs) in a typical semi-enclosed bay — The Bohai Bay in northern China

The Bohai Bay as a typical semi-enclosed bay in northern China with poor water exchange capacity and significant coastal urbanization, is greatly influenced by land-based inputs and human activities. As a class of pseudo-persistent organic pollutants, the spatial and temporal distribution of Pharmaceuticals and Personal Care Products (PPCPs) is particularly important to the ecological environment, and it will be imperfect to assess the ecological risk of PPCPs for the lack of systematic investigation of their distribution in different season. 14 typical PPCPs were selected to analyze the spatial and temporal distribution in the Bohai Bay by combining online solid-phase extraction (SPE) and HPLC-MS/MS techniques in this study, and their ecological risks to aquatic organisms were assessed by risk quotients (RQs) and concentration addition (CA) model. It was found that PPCPs widely presented in the Bohai Bay with significant differences of spatial and seasonal distribution. The concentrations of ∑PPCPs were higher in autumn than in summer. The distribution of individual pollutants also showed significant seasonal differences. The high values were mainly distributed in estuaries and near-shore outfalls. Mariculture activities in the northern part of the Bohai Bay made a greater contribution to the input of PPCPs. Caffeine, florfenicol, enrofloxacin and norfloxacin were the main pollutants in the Bohai Bay, with detection frequencies exceeding 80 %. The ecological risk of PPCPs to algae was significantly higher than that to invertebrates and fish. CA model indicated that the potential mixture risk of total PPCPs was not negligible, with 34 % and 88 % of stations having mixture risk in summer and autumn, respectively. The temporary stagnation of productive life caused by Covid-19 weakened the input of PPCPs to the Bohai Bay, reducing the cumulative effects of the pollutants. This study was the first full-coverage investigation of PPCPs in the Bohai Bay for different seasons, providing an important basis for the ecological risk assessment and pollution prevention of PPCPs in the bay. © 2022 Elsevier B.V.

Restricting access to antibiotics: The effectiveness of a ‘no repeats' government policy intervention

Background Australia has a high rate of antibiotic use. Government policy interventions are one strategy to optimise the use of antibiotics. On 1 April 2020, the Australian Government Department of Health introduced a policy intervention to increase the quality use of four antibiotics. Objectives To assess if the government policy intervention improved the appropriate supply of the four antibiotics amoxicillin, amoxicillin-clavulanic acid, cefalexin and roxithromycin. Method This study employed a retrospective cohort study design comparing a 10% sample (n = 345,018) of four antibiotics prescribed and dispensed in Australia during a three-month period (May, June, July) in 2019, and again in 2020 (after the policy intervention). The 10% sample of PBS data was obtained from the Australian Government Department of Health. Descriptive statistics, bivariate and multivariable logistic regression analysis were carried out. Results The results suggest the policy change improved the appropriate supply of original prescriptions in 2020 compared to 2019 OR = 1.75 (95% CI = 1.68–1.82, p < 0.001), and appropriate supply of repeat prescriptions OR = 1.56 (95% CI = 1.25–1.96, p < 0.001). In 2020, the proportion of appropriate supply of original prescriptions increased by an absolute difference of 1.8% (95% CI = 1.6–1.9%;P < 0.001), and appropriate supply of repeat prescriptions increased by 3.9% (95% CI = 2.2–5.5%;P < 0.001). The total number of antibiotic prescriptions prescribed and dispensed in 2019 (N = 219,960) reduced in 2020 (N = 125,058) after the policy intervention. Conclusion The study provides evidence for the impact of a government policy intervention to improve the appropriate supply of antibiotics, although some of the reduction in antibiotic use was likely due to the concomitant COVID-19 pandemic. Further research is required to assess the impact of the intervention outside a pandemic.

Airborne antibiotic resistome and human health risk in railway stations during COVID-19 pandemic

Antimicrobial resistance is recognized as one of the greatest public health concerns. It is becoming an increasingly threat during the COVID-19 pandemic due to increasing usage of antimicrobials, such as antibiotics and disinfectants, in healthcare facilities or public spaces. To explore the characteristics of airborne antibiotic resistome in public transport systems, we assessed distribution and health risks of airborne antibiotic resistome and microbiome in railway stations before and after the pandemic outbreak by culture-independent and culture-dependent metagenomic analysis. Results showed that the diversity of airborne antibiotic resistance genes (ARGs) decreased following the pandemic, while the relative abundance of core ARGs increased. A total of 159 horizontally acquired ARGs, predominantly confering resistance to macrolides and aminoglycosides, were identified in the airborne bacteria and dust samples. Meanwhile, the abundance of horizontally acquired ARGs hosted by pathogens increased during the pandemic. A bloom of clinically important antibiotic (tigecycline and meropenem) resistant bacteria was found following the pandemic outbreak. 251 high-quality metagenome-assembled genomes (MAGs) were recovered from 27 metagenomes, and 86 genera and 125 species were classified. Relative abundance of ARG-carrying MAGs, taxonomically assigned to genus of Bacillus, Pseudomonas, Acinetobacter, and Staphylococcus, was found increased during the pandemic. Bayesian source tracking estimated that human skin and anthropogenic activities were presumptive resistome sources for the public transit air. Moreover, risk assessment based on resistome and microbiome data revealed elevated airborne health risks during the pandemic. © 2023 The Authors

How Antimicrobial Resistance Is Linked to Climate Change: An Overview of Two Intertwined Global Challenges.

Globally, antimicrobial resistance (AMR) and climate change (CC) are two of the top health emergencies, and can be considered as two interlinked public health priorities. The complex commonalities between AMR and CC should be deeply investigated in a One Health perspective. Here, we provided an overview of the current knowledge about the relationship between AMR and CC. Overall, the studies included pointed out the need for applying a systemic approach to planetary health. Firstly, CC increasingly brings humans and animals into contact, leading to outbreaks of zoonotic and vector-borne diseases with pandemic potential. Although it is well-established that antimicrobial use in human, animal and environmental sectors is one of the main drivers of AMR, the COVID-19 pandemic is exacerbating the current scenario, by influencing the use of antibiotics, personal protective equipment, and biocides. This also results in higher concentrations of contaminants (e.g., microplastics) in natural water bodies, which cannot be completely removed from wastewater treatment plants, and which could sustain the AMR spread. Our overview underlined the lack of studies on the direct relationship between AMR and CC, and encouraged further research to investigate the multiple aspects involved, and its effect on human health.

Evaluation of Dalbavancin Use on Clinical Outcomes, Cost-Savings, and Adherence at a Large Safety Net Hospital.

Dalbavancin is a second-generation lipoglycopeptide antibiotic with activity against Gram-positive organisms. Dalbavancin is Food and Drug Administration (FDA)-approved for acute bacterial skin and soft tissue infections (ABSSTIs). There is a lack of substantial data on dalbavancin in more invasive infections, particularly in high-risk populations (patients with intravenous drug use and unstable living conditions). In this retrospective observational study, we reviewed all patients that received at least one dose of dalbavancin in an inpatient or outpatient setting at Parkland Hospital from February of 2019 to August of 2021. The demographics, type of infection, and rationale for dalbavancin were collected at the baseline. Clinical failure was measured by an avoidance of emergency department (ED) visits or hospital readmission at 30, 60, and 90 days. A separate analysis was conducted to estimate hospital, rehabilitation, or nursing facility days saved based on the projected length of treatment. 40 patients were included, and the majority were uninsured (85%), experiencing homelessness (60%), or had intravenous drug use (IDU) (57.5%). Indications for use included ABSSTIs (45%), bloodstream infection (67.5%), osteomyelitis (40%), infective endocarditis (10%), and septic arthritis (10%). Clinical failure was observed in 5 of the 40 patients (12.5%). Nonadherence to medical recommendations, a lack of source control, and ongoing IDU increased the risk of failure. Dalbavancin saved a total of 566 days of inpatient, rehabilitation, and nursing facility stays. Dalbavancin is a reasonable alternative to the standard of care in an at-risk population, offering decreased lengths of stays and cost savings. The uses of second-generation lipoglycopeptides are desirable alternatives to traditional outpatient parenteral antibiotic therapies for patients who otherwise would not qualify or for patients who desire less hospital contact in light of the COVID-19 pandemic. IMPORTANCE This study contributes additional experience to the literature of dalbavancin use in off-label indications, particularly for patients who do not qualify for outpatient parenteral antimicrobial therapy. The majority of the patient population were people who inject drugs and the uninsured. There is difficulty in tracking outcomes in this patient population, given their outpatient follow-up rates; however, we were able to track emergency room visits and readmissions throughout the majority of the local metroplex. The clinical use of dalbavancin at our institution also increased in the midst of the COVID-19 pandemic in an effort to preserve hospital resources and limit health care exposure. In addition, we are able to provide institution-specific cost-saving data with the use of dalbavancin.

The improvement of levofloxacin and tetracycline removal from simulated water by thermosensitive flocculant: Mechanisms and simulation

[Display omitted] • P(DAC-NIPAM) significantly improved the removal of levofloxacin and tetracycline. • P(DAC-NIPAM) had strong interaction with antibiotics for its multiple functional groups. • The hydrophobic groups on P(DAC-NIPAM) tightly bridged micelles of antibiotics and SDS. • Compact flocs were formed for shrinkage of P(DAC-NIPAM) molecule at the LCST. • Flocculation simulation further confirmed application feasibility of thermosensitive flocculants. Antibiotics were detected in worldwide natural water especially in COVID-19 period. The common flocculants rarely removed the dissolved antibiotics from natural water and wastewater. The flocculation improvement of organic polymer flocculants might solve the issue of antibiotic pollution or promote the removal efficiencies of antibiotics in water/wastewater treatment plants. Herein, a thermosensitive flocculant, P(DAC-NIPAM), was prepared via one-step method. It was investigated that the relationship between the various functional groups of P(DAC-NIPAM) and its flocculation performances in the treatment of simulated water containing levofloxacin, tetracycline, colloidal particles and natural organic matters. The removal mechanisms were discussed. The results indicated that the rich cationic, hydrophilic and hydrophobic groups of P(DAC-NIPAM) enhanced the interaction between flocculants and pollutants. The bridging of P(DAC-NIPAM) among micelles, charge neutralization, hydrogen bond between P(DAC-NIPAM) and two antibiotics, the shrinkage of P(DAC-NIPAM) molecule and enhancement of hydrophobicity when water temperature was above low critical solution temperature (LCST), co-flocculation and co-settlement of multiple pollutants all contributed to the efficient removal of levofloxacin and tetracycline from water. Flocculation simulation further confirmed that thermosensitive flocculant combined with heating plates was a potential candidate for antibiotic treatment in actual water treatment plants. [ FROM AUTHOR]

A review on the effect of micro- and nano-plastics pollution on the emergence of antimicrobial resistance

The recent upsurge in the studies on micro/nano plastics and antimicrobial resistance genes has proven their deleterious effects on the environmental and human health. Till-date, there is a scarcity of studies on the in-teractions of these two factors and their combined influence. The interaction of microplastics has led to the formation of new plastics namely plastiglomerates, pyroplastics. and anthropoquinas. It has long been ignored that the occurrence of microplastics has become a breeding ground for the emergence of antimicrobial resistance genes. Evidently microplastics are also associated with the occurrence of other pollutants such as polyaromatic hydrocarbons and pesticides. The increased use of antibiotics (after Covid breakout) has further elevated the detrimental effects on human health. Therefore, this study highlights the relation of microplastics with antibiotic resistance generation. The factors such as uncontrolled use of antibiotics and negligent plastic consumption has been evaluated. Furthermore, the future research prospective was provided that can be helpful in correctly identifying the seriousness of the environmental occurrence of these pollutants.

Research in brief

Brain aging and COVID-19 Many biological pathways that change with natural aging in the brain also changed in patients with severe COVID-19, say researchers who used RNA sequencing to assess changes in gene expression profiles in the brain of COVID-19 patients compared with uninfected individuals. The scientists observed that gene expression in the brain tissue of patients who died of COVID-19 closely resembled that of uninfected individuals aged 71 years or older. In genetially modified mice, the emergency mode of haematopoiesis ran without any detectable infection or increased interferon levels and these genetically modified animals were better able to fight off infection with the bacterium Listeria monocytogenes than normal mice.

Co-Infection in COVID-19 Pneumonia: Discussion Continues.

Sixty-six patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 and pneumonia on chest computer tomography were prospectively recruited. A combined respiratory swab for polymerase chain reaction (PCR), urine sample for pneumococcal and Legionella antigen, and sputum or endotracheal aspirate were collected. Urinary antigen and blood culture tests were negative in all cases as well as the PCR tests for other respiratory viruses and atypical bacterial pathogens. In total, 5 patients (7.5%) had co-infection. By PCR a high prevalence of colonization with bacterial pathogens was found. In conclusion, co-infection is rare in coronavirus disease 2019 patients, and additional examination to identify other pathogens should be performed only in selected cases.

Point Prevalence Survey of Antimicrobial Use during the COVID-19 Pandemic among Different Hospitals in Pakistan: Findings and Implications.

The COVID-19 pandemic has significantly influenced antimicrobial use in hospitals, raising concerns regarding increased antimicrobial resistance (AMR) through their overuse. The objective of this study was to assess patterns of antimicrobial prescribing during the current COVID-19 pandemic among hospitals in Pakistan, including the prevalence of COVID-19. A point prevalence survey (PPS) was performed among 11 different hospitals from November 2020 to January 2021. The study included all hospitalized patients receiving an antibiotic on the day of the PPS. The Global-PPS web-based application was used for data entry and analysis. Out of 1024 hospitalized patients, 662 (64.64%) received antimicrobials. The top three most common indications for antimicrobial use were pneumonia (13.3%), central nervous system infections (10.4%) and gastrointestinal indications (10.4%). Ceftriaxone (26.6%), metronidazole (9.7%) and vancomycin (7.9%) were the top three most commonly prescribed antimicrobials among surveyed patients, with the majority of antibiotics administered empirically (97.9%). Most antimicrobials for surgical prophylaxis were given for more than one day, which is a concern. Overall, a high percentage of antimicrobial use, including broad-spectrums, was seen among the different hospitals in Pakistan during the current COVID-19 pandemic. Multifaceted interventions are needed to enhance rational antimicrobial prescribing including limiting their prescribing post-operatively for surgical prophylaxis.

Increasing Consumption of Antibiotics during the COVID-19 Pandemic: Implications for Patient Health and Emerging Anti-Microbial Resistance.

The emergence of COVID-19 infection led to the indiscriminate use of antimicrobials without knowing their efficacy in treating the disease. The gratuitous use of antibiotics for COVID-19 treatment raises concerns about the emergence of antimicrobial resistance (AMR). In this systematic review, we performed a thorough systematic search using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of scientific databases (Scopus, Web of Science, and PubMed) to identify studies where antibiotics were prescribed to treat COVID-19 (December 2019 to December 2021). Of 970 identified studies, 130 were included in our analyses. Almost 78% of COVID-19 patients have been prescribed an antibiotic. Cephalosporins were the most prescribed (30.1% of patients) antibiotics, followed by azithromycin (26% of patients). Antibiotics were prescribed for COVID-19 patients regardless of reported severity; the overall rate of antibiotic use was similar when comparing patients with a severe or critical illness (77.4%) and patients with mild or moderate illness (76.8%). Secondary infections were mentioned in only 11 studies. We conclude that concerns related to COVID-19 and the lack of treatment strategy led to the overuse of antibiotics without proper clinical rationale. Based on our findings, we propose that antimicrobial stewardship should be retained as a priority while treating viral pandemics.

Impact of Antibiotic Consumption on the Acquisition of Extended-Spectrum ß-Lactamase Producing Enterobacterales Carriage during the COVID-19 Crisis in French Guiana.

(1) Background: During the COVID-19 outbreak, several studies showed an increased prevalence of extended-spectrum ß-lactamase producing Enterobacterales (ESBL-PE) carriage in intensive care units (ICUs). Our objective was to assess the impact of antibiotic prescriptions on the acquisition of ESBL-PE in ICUs during the COVID-19 crisis. (2) Methods: We conducted an observational study between 1 April 2020, and 31 December 2021, in the medical-surgical ICU of the Cayenne General Hospital. We defined two periods: Period 1 with routine, empirical antibiotic use, and Period 2 with no systematic empiric antibiotic prescription. (3) Results: ICU-acquired ESBL-PE carriage was 22.8% during Period 1 and 9.4% during Period 2 (p = 0.005). The main isolated ESBL-PE was Klebsiella pneumoniae (84.6% in Period 1 and 58.3% in Period 2). When using a generalized linear model with a Poisson family, exposure to cefotaxime was the only factor independently associated with ESBL-PE acquisition in ICU (p = 0.002, IRR 2.59 (95% IC 1.42-4.75)). The propensity scores matching estimated the increased risk for cefotaxime use to acquire ESBL-PE carriage at 0.096 (95% CI = 0.02-0.17), p = 0.01. (4) Conclusions: Exposure to cefotaxime in patients with severe COVID-19 is strongly associated with the emergence of ESBL-PE in the context of maximal infection control measures.

Conservative Management of a COVID-19-positive Patient With Emphysematous Pyelonephritis: A Case Report.

Herein, we present a case of emphysematous pyelonephritis with septic shock that was treated conservatively. A 44-year-old woman with diabetes mellitus presented to the emergency department with acute abdominal discomfort. Clinical examination revealed that the patient was conscious but vitally unstable. Therefore, the patient required inotropic support. A computed tomography scan revealed gas in the left kidney, suggestive of emphysematous pyelonephritis. Subsequently, the patient was treated conservatively and stabilized with broad-spectrum antibiotics, strict blood glucose management, and drainage.

MoSe2-modified ZIF-8 novel nanocomposite for photocatalytic remediation of textile dye and antibiotic-contaminated wastewater.

COVID-19-led antibiotic waste generated from hospitals and health centres may cause serious health issues and significantly impact the environment. In the coming decades, antibiotic resistance will be one of the most significant threats to global human health. Photocatalytic water remediation is an effective and promising environmental solution that can be utilized to address this issue, to convert antibiotic waste into non-toxic products by utilizing renewable and abundant solar energy. In the present study, a novel nanocomposite of zeolitic imidazolate frameworks (ZIF-8) and molybdenum diselenide (MoSe2) was efficiently synthesized by the solvothermal method for the complete degradation of the antibiotics and textile waste from water. The morphology, crystallinity and band gap of the samples were characterized by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD) and UV-visible spectroscopy. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) provide the binding information of the sample. The photocatalytic activity was tested for degradation of the antibiotics (tetracycline hydrochloride (TC) and metronidazole (MNZ)) used in COVID-19 treatment and textile dye (malachite green). Time-resolved photoluminescence spectroscopy confirmed the enhanced charge separation in the MoSe2@ZIF-8 nanocomposite with an average lifetime of 4.72 ns as compared to pristine samples. The nanocomposite showed ~ 100% removal efficiency with rate constants of 63 × 10-3, 49 × 10-3 and 42 × 10-3 min-1 for TC, MNZ and malachite green, respectively. The photocatalytic degradation of TC was carried out under different pH conditions (4, 7 and 9), and the degradation mechanism was explained on the basis of zeta potential measurements and active species trapping experiment. The by-products of the photocatalytic treatment of TC antibiotics were tested using liquid chromatography-mass spectroscopy (LC-MS), and they were found to be non-toxic for aquatic and human life. The regeneration property of the nanocomposite was confirmed by FESEM with regeneration efficiency of 88.7% in the 4th cycle. Thus, MoSe2@ZIF-8-based photocatalysts have potential application in water remediation, especially in making the antibiotic waste less toxic.

Antibiotics with Antiviral and Anti-Inflammatory Potential Against Covid-19: A Review

In Covid-19 cases, elderly patients in long-term care facilities, children younger than five years with moderate symptoms, and patients admitted to ICU or with comorbidities are at a high risk of coinfection due to evidence. Thus, in these patients, antibiotic therapy based on empirical evidence is necessary. Finding appropriate antimicrobial agents, especially with antiviral and anti-inflammatory properties, is a promising approach to target the virus and its complications, hyper-inflammation, and microorganisms resulting co-infection. Moreover, indiscriminate use of antibiotics can be accompanied by Clostridioides difficile colitis, the emergence of resistant microorganisms, and adverse drug reactions, particularly kidney damage and QT prolongation. Therefore, rational administration of efficient antibiotics is an important issue. The main objective of the present review is to provide a summary of antibiotics with possible antiviral activity against SARS-CoV-2 and anti-immunomodulatory effects to guide scientists for further research. Besides, the findings can help health professionals in the rational prescription of antibiotics in Covid-19 patients with a high risk of coinfection.