Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.

The diffused and prolonged SARS-CoV-2 transmission lead to high levels of hospitalization. During this period, the focus of sanitary structures was to contain COVID-19 mortality and this may have reduced the application of health associated infection (HAI) and multidrug resistant microorganism (MDRO) prevention programs.

A search was performed in PubMed, Science Direct, and Google Scholar databases to identify clinical observational studies that reported the impact of COVID-19 pandemic on the prevalence or incidence on HAIs and/or MDROs from December 2019 to August 2024 in Italy. Studies were included if they reported a comparison with pre-pandemic period and had a full-text available. Eligible studies were assessed for risk of bias and quality with NHI Quality Assessment Tool by two researchers independently. Data were represented in tables and a narrative synthesis was made in the text.

Selected studies included 4 studies reporting data on HAI (1497 total patients) and 11 studies reporting data on MDRO (80388 total patients). The majority of the studies reported an increase in HAI prevalence (9-11.1 % range) and MDRO, in particular, gram negative MDRO had an increase range of 0.8 %-45.6 % and gram positive MDRO an increase range of 0.5 %-81.8 % from pre- to post-COVID-19 period in the different studies considered CONCLUSION: These findings underscore the critical need for active surveillance in hospital wards, the implementation of antibiotic stewardship and prescribing programs to mitigate the impact of such crises on healthcare-associated infections and antimicrobial resistance. Furthermore, permanent training of healthcare personnel is necessary.

In 2022, the U.S. Centers for Disease Control and Prevention reported increases in antimicrobial resistance (AMR) across U.S. hospitals during the COVID-19 pandemic. The key drivers and lasting effects of this phenomenon remain unexplored.

To determine the incidence of AMR infections in U.S. hospitals during and beyond the pandemic and identify factors contributing to AMR.

Retrospective cohort study.

243 U.S. hospitals.

Adult hospitalizations, excluding inpatient transfers.

Prepandemic (January 2018 to December 2019), peak pandemic (March 2020 to February 2022), and waning pandemic (March to December 2022).

Incidence of methicillin-resistant Staphylococcus aureus; vancomycin-resistant Enterococci; extended-spectrum cephalosporin-resistant Enterobacterales; and carbapenem-resistant Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa infections was evaluated among 120 continuously reporting hospitals. Infections detected more than 3 days after admission were classified as hospital-onset. Antibiotic exposure was estimated using a duration- and spectrum-weighted index. A competing risks analysis was done in 243 hospitals to identify risk factors for resistance.

During the peak of the COVID-19 pandemic, AMR infections increased from 182 to 193 per 10 000 hospitalizations (6.5% [95% CI, 5.1% to 8.0%]). Hospital-onset AMR infections increased from 28.9 to 38.0 per 10 000 hospitalizations (31.5% [CI, 27.3% to 35.8%]). Factors associated with hospital-onset AMR included illness severity (intensive care unit admission, mechanical ventilation, vasopressors, COVID-19 diagnosis), comorbidities (Elixhauser Comorbidity Index), and prior exposure to antibiotics, but not hospital factors. Prevalence of AMR returned to prepandemic levels as the pandemic waned (182 to 182 per 10 000 hospitalizations; 0.4% [CI, -1.4% to 2.2%]), however, hospital-onset AMR remained above baseline (28.9 to 32.3 per 10 000 hospitalizations; 11.6% [CI, 6.8% to 16.7%]).

Residual confounding; unknown appropriateness of antibiotics.

Sustained increases in hospital-onset AMR infections occurred in U.S. hospitals during the pandemic and were strongly associated with antibiotic exposure.

National Institutes of Health Clinical Center; National Heart, Lung, and Blood Institute; and National Institute of Allergy and Infectious Diseases Intramural Research Programs.

Climate change poses substantial challenges in containing antimicrobial resistance (AMR) from a One Health perspective. Using 4,502 AMR surveillance records involving 32 million tested isolates from 101 countries (1999-2022), we analyzed the impact of socioeconomic and environmental factors on AMR. We also established forecast models based on several scenarios, considering antimicrobial consumption reduction, sustainable development initiatives and different shared socioeconomic pathways under climate change. Our findings reveal growing AMR disparities between high-income countries and low- and middle-income countries under different shared socioeconomic pathway scenarios. By 2050, compared with the baseline, sustainable development efforts showed the most prominent effect by reducing AMR prevalence by 5.1% (95% confidence interval (CI): 0.0-26.6%), surpassing the effect of antimicrobial consumption reduction. Key contributors include reducing out-of-pocket health expenses (3.6% (95% CI: -0.5 to 21.4%)); comprehensive immunization coverage (1.2% (95% CI: -0.1% to 8.2%)); adequate health investments (0.2% (95% CI: 0.0-2.4%)) and universal access to water, sanitation and hygiene services (0.1% (95% CI: 0.0-0.4%)). These findings highlight the importance of sustainable development strategies as the most effective approach to help low- and middle-income countries address the dual challenges of climate change and AMR.

Lower respiratory tract infections (LRTIs) are a leading cause of mortality worldwide and can be difficult to diagnose in critically ill patients, as non-infectious causes of respiratory failure can present with similar clinical features.

We developed a LRTI diagnostic method combining the pulmonary transcriptomic biomarker FABP4 with electronic medical record (EMR) text assessment using the large language model Generative Pre-trained Transformer 4 (GPT-4). We evaluated this approach in a prospective cohort of critically ill adults with acute respiratory failure from whom tracheal aspirate FABP4 expression was measured by RNA sequencing. Patients with LRTI or non-infectious conditions were identified using retrospective, multi-physician clinical adjudication. We then confirmed our findings by applying this method to an independent validation cohort of 115 adults with acute respiratory failure.

In the derivation cohort, a combined classifier incorporating FABP4 expression and GPT-4-assisted EMR analysis achieved an AUC of 0.93 (±0.08) and an accuracy of 84%, outperforming FABP4 expression alone (AUC 0.84 ± 0.11) and GPT-4-based analysis alone (AUC 0.83 ± 0.07). By comparison, the primary medical team's admission diagnosis had an accuracy of 72%. In the validation cohort, the combined classifier yielded an AUC of 0.98 (±0.04) and an accuracy of 96%.

Integrating a host transcriptional biomarker with EMR text analysis using a large language model may offer a promising new approach to improving the diagnosis of LRTIs in critically ill adults.

To date, no studies have specifically addressed seasonal variation in the use of intravenous broad-spectrum antimicrobials. This study aimed to examine the seasonal patterns of the use of intravenous broad-spectrum antimicrobials by utilizing a nationwide Japanese infection control surveillance database.

This retrospective cohort study extracted the days of therapy (DOT) for intravenous broad-spectrum antimicrobials and the detection rates of drug-resistant bacteria from the database between 2018 and 2023. Seasonal variation was analyzed using these values through seasonal and trend decomposition using loess.

The DOT for carbapenems, tazobactam/piperacillin, fourth-generation cephalosporins, and fluoroquinolones showed seasonal variation, peaking in fall. Conversely, no significant seasonal variation was observed in the DOT for anti-methicillin-resistant Staphylococcus aureus (MRSA) agents. The detection rates of Pseudomonas aeruginosa, Klebsiella aerogenes, and Enterobacter cloacae exhibited seasonal variation and peaked in fall. The detection rates of Enterococcus faecium exhibited seasonal variation as well, though no distinct peaks were observed. There was no significant seasonal variation in the detection rates of third-generation cephalosporin-resistant Escherichia coli or MRSA.

The findings of this study indicate seasonal variation in the use of intravenous broad-spectrum antimicrobials. This seasonality was likely influenced by various factors, including the detection rates of drug-resistant bacteria. The study underscores the importance of appropriate antimicrobial stewardship and interventions against drug-resistant organisms, particularly during fall.

Baimao-Longdan-Congrong-Fang (BLCF), a traditional Chinese herbal formula described in the Taiping Shenghui Fang (998 AD), consists of medicinal plants with heat-clearing and tonifying properties. BLCF has a promise as a treatment for Staphylococcus aureus (S. aureus) pneumonia, according to its historical use and current pharmacological research.

In this study, the inhibitory effects of BLCF on S. aureus virulence factors were evaluated in vitro, and its mechanisms of action were investigated in a methicillin-resistant S. aureus (MRSA) pneumonia mouse model.

The inhibitory effect of BLCF on S. aureus virulence factors, including sortase A (SrtA) and α-hemolysin (Hla), was investigated by fluorescence resonance energy transfer (FRET) and hemolysis assays. A C57BL/6J mouse model of MRSA pneumonia was employed to evaluate its therapeutic efficacy. Accordingly, an integrated strategy of medicinal chemistry, network pharmacology analysis, GEO database analysis, bioinformatics, molecular docking, molecular dynamics simulation, GeneMANIA-based functional association (GMFA), and GSEA was used to identify and illustrate potential therapeutic targets and mechanisms. Subsequently, the mechanistic results were confirmed by Western blot analysis and RT-qPCR.

While BLCF exhibited weak inhibitory activity against S. aureus USA300, Newman, and SA37 strains, it significantly suppressed SrtA-related virulence functions without affecting bacterial growth. FRET and hemolysis assays confirmed that BLCF inhibited SrtA activity (IC50 = 1.25 mg/mL) while decreasing hemolytic activity. Furthermore, BLCF protected mice from MRSA infection, increasing their survival rates. Bioinformatics analysis identified 26 active compounds and 2 hub genes (Tnf and Mmp9) that were associated with 5 types of immune cell, including activated CD4 T cells, myeloid-derived suppressor cells, activated dendritic cells, macrophages, and mast cells. Molecular docking revealed 3 active compounds (isoacteoside, verbascoside, and echinacoside) that exhibited strong binding affinities to TNF, MMP9, and SrtA. Molecular dynamics simulations validated the stable interactions between isoacteoside and the target proteins, yielding binding energies of -136.76 ± 8.83 kJ/mol, -174.98 ± 14.89 kJ/mol, and -186.34 ± 9.06 kJ/mol, respectively. The therapeutic effect of BLCF was closely linked to the NF-κB signaling pathway, as revealed by GMFA and GSEA analyses. In vivo, BLCF reduced lung bacterial load, improved the wet/dry ratio, and decreased inflammatory cytokines, thereby enhancing lung histopathology through modulation of the TNF-α/TNFR1/NF-κB/MMP9 axis.

BLCF can effectively treat MRSA pneumonia in mice by inhibiting SrtA activity, decreasing hemolytic activity, and regulating the TNF-α/TNFR1/NF-κB/MMP9 axis. These findings suggest BLCF, a traditional herbal formula, as a promising novel therapeutic approach to treat pneumonia.

Antibiotic resistance is a global environmental and health threat. Approximately 4.95 million deaths were associated with antibiotic resistance in 2019, including 1.27 million deaths that were directly attributable to bacterial antimicrobial resistance. Hospital wastewater is one of the key sources for the spread of clinically relevant antibiotic resistance genes (ARGs) into the environment. Understanding the current situation of ARGs in hospital wastewater is of great significance. Here, we review the prevalence of ARGs and antibiotic-resistant bacteria (ARB) in hospital wastewater and wastewater from other places and the treatment methods used. We further discuss the intersection between ARGs and COVID-19 during the pandemic. This review highlights the issues associated with the dissemination of critical ARGs from hospital wastewater into the environment. It is imperative to implement more effective processes for hospital wastewater treatment to eliminate ARGs, particularly during the current long COVID-19 period.

Despite the widespread adoption of antimicrobial stewardship (AMS) programs, their effectiveness varies because of differing regional policies and socioeconomic factors. This study aimed to assess the impact of AMS at a Chinese tertiary care hospital on inpatient antimicrobial use and bacterial resistance during the COVID-19 outbreak.

An interrupted time-series regression analysis was conducted to compare inpatient antimicrobial use between pre- and post-intervention periods. The Chi-squared test and linear regression analysis were used to compare bacterial resistance and illustrate temporal trends in bacterial resistance, respectively.

Following the AMS strategy implementation, we observed a significant decrease in antimicrobial consumption at unrestricted (β2 = -6.38, P = 0.004), restricted (β2 = -17.81, P < 0.001), and special levels (β2 = -2.32, P < 0.001). Despite a reduction in the use of third-generation cephalosporins and macrolides (β2 = -6.85, P < 0.001; β2 = -2.82, P < 0.001), an increase in the trend of use was observed post-intervention (β3 = 0.15, P < 0.001; β3 = 0.04, P = 0.001). Methicillin resistance in Staphylococcus aureus significantly decreased (β = -0.23, P < 0.001) from 52.85% to 40.92%. Conversely, the prevalence of carbapenem-resistant Klebsiella pneumonia increased from 4.69% to 10.87% (P < 0.001), whereas resistance to Acinetobacter baumannii and Pseudomonas aeruginosa marginally decreased (P<0.05). We observed decreases in the antimicrobial utilization rate (β2 = -11.86, P = 0.003) and combination utilization rate (β2 = -12.36, P = 0.011) post-intervention. No significant changes in special-level antimicrobial and prophylactic agent use in category I incisional surgeries were observed.

An AMS program in a Chinese tertiary facilitated effective management of antimicrobial use and reduction of bacterial resistance during the COVID-19 pandemic, in the context of combined infection prevention and control measures. The findings provide useful insights for the implementation of antimicrobial stewardship in future public health crises.

Outpatient healthcare facilities represent potential sources of healthcare-associated infections (HAIs). The purpose of this study was to survey high-contact surfaces in an outpatient physical therapy clinic, characterize the microbiome of those surfaces, and investigate the effects of a microbiome-specific cleaning and hygiene plan. Hand sanitizer containing a fluorescent probe used by patients and staff identified surface contact. High-contact surfaces were analyzed for bacterial DNA and SARS-CoV-2. A microbiome-specific cleaning and hygiene plan was developed based on initial analysis. After the implementation of the revised cleaning regimen, microbial community diversity and predicted metagenome content (PICRUSt) were employed for differential analysis. Patients had greater surface contact than staff. Ralstonia pickettii was the dominant species pre-cleaning, comprising 49.76% of the total, and observed on 79.5% of surfaces. The cleaning and hygiene plan significantly increased Shannon diversity, and R. pickettii decreased to 4.05% of total bacteria. SARS-CoV-2 was not observed on any surfaces. This study found ecological dominance by a single species in this outpatient clinic, suggesting a potential source of HAIs. However, a microbiome-specific cleaning strategy was successful in diversifying the microbiome and reducing ecological dominance. Additional research is needed to confirm these findings.

Antibiotic resistance is a growing global health threat, and understanding local trends in bacterial isolates and their susceptibility patterns is crucial for effective infection control and antimicrobial stewardship. The coronavirus disease 2019 (COVID-19) pandemic has introduced additional complexities, potentially influencing these patterns.

To analyze trends in bacterial isolates and their antibiotic susceptibility patterns at Salmaniya Medical Complex from 2018 to 2023, with a specific focus on the impact of the COVID-19 pandemic on these trends.

A retrospective analysis of microbiological data was conducted, covering the period from 2018 to 2023. The study included key bacterial pathogens such as Escherichia coli (E. coli), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus, among others. The antibiotic susceptibility profiles of these isolates were assessed using standard laboratory methods. To contextualize the findings, the findings were compared with similar studies from other regions, including China, India, Romania, Saudi Arabia, the United Arab Emirates, Malaysia, and United States.

The study revealed fluctuating trends in the prevalence of bacterial isolates, with notable changes during the COVID-19 pandemic. For example, a significant increase in the prevalence of Staphylococcus aureus was observed during the pandemic years, while the prevalence of E. coli showed a more variable pattern. Antibiotic resistance rates varied among the different pathogens, with a concerning rise in resistance to commonly used antibiotics, particularly among Klebsiella pneumoniae and E. coli. Additionally, the study identified an alarming increase in the prevalence of multidrug-resistant (MDR) strains, especially within Klebsiella pneumoniae and E. coli isolates. The impact of the COVID-19 pandemic on these trends was evident, with shifts in the frequency, resistance patterns, and the emergence of MDR bacteria among several key pathogens.

This study highlights the dynamic nature of bacterial isolates and their antibiotic susceptibility patterns at Salmaniya Medical Complex, particularly in the context of the COVID-19 pandemic. The findings underscore the need for continuous monitoring and effective anti-microbial stewardship programs to combat the evolving threat of antibiotic resistance. Further research and policy initiatives are required to address the identified challenges and improve patient outcomes in the face of these ongoing challenges.

The impact of public health interventions against the COVID-19 pandemic on the occurrence of Enterobacteriaceae outbreaks in hospitals remains unclear.

To determine the effect of the COVID-19 national health alert on the secular trend of Enterobacteriaceae outbreaks in Chilean public hospitals while characterizing their antibiotic resistance patterns.

Nationwide retrospective ecological study using interrupted time series analysis of monthly outbreak-related cases over three periods: pre-pandemic (January 2017-February 2020), health alert (March 2020-August 2023), and post-pandemic (September-December 2023).

A total of 106 outbreaks, 1,131 associated cases, and 254 deaths were identified in 47/196 (24.0%) hospitals. Cases increased gradually (0.39 cases-month, 95% CI 0.02-0.75; p=0.040) in the pre-pandemic years. A sudden rise of 33.42 cases (95% CI 7.53-59.31 cases; p=0.012) in March 2020, followed by a gradual decrease (1.28 cases-month, 95% CI 0.38-2.17; p=0.006) during the health alert. A rebound of 18.02 cases (95% CI 2.89-33.15; p=0.020) occurred in September 2023 and preceded a gradual post-pandemic decline (6.21 cases-month, 95% CI 1.11-11.31; p=0.018). Prevalence of cases caused by carbapenemase-producing enterobacteria rose significantly (p<0.001) during (79.9%) and after the health alert (100.0%) compared to the pre-alert period (35.3%).

The COVID-19 national health alert was associated with significant shifts in the secular trend of cases associated with Enterobacteriaceae outbreaks in Chilean public hospitals, including abrupt increases at the beginning and end of the health alert and gradual decreases during and after this period. A sharp increase in carbapenemase production was observed across outbreaks after the pandemic onset.

Background: Globally, community pharmacists worldwide have prescribed more over-the-counter systemic antibiotics, posing significant issues for international organizations tackling antibiotic-resistant bacteria, a major global threat, due to the accessibility in pharmacies. Objectives: This study aimed to examine the Jordanian pharmacists' antibiotic selection and over-the-counter antibiotic prescriptions. Methods: A total of 244 community pharmacists participated in an online standardized survey, which examined five essential domains including sources and trust of pharmacy antibiotic prescription information, category and frequency of permitted antimicrobials, prescription-free antimicrobials, interactions, antimicrobial prescription issues for pharmacists, and pharmacy staff's knowledge of non-prescription antimicrobial questions and answers. Results: This study found that 1-pharmacists are confident in prescribing antibiotics and they use various tools to improve their skills. 2-Antibiotics were the most sought antimicrobials without a prescription, followed by antifungals and antivirals. 3-Throat, urinary tract, chest, and otitis media are the most common infections that require antibiotics. Pharmacists prescribe penicillin for 75% of throat infections, Fluoroquinolones for 48.2% of urinary tract infections, and cephalosporins for 35.9%. Macrolides are the most prevalent otitis media treatment (43.2%). 4-Some people obtain antimicrobial prescriptions without a valid reason or diagnosis. 5-Many pharmacists (171/244, 70%) agree or strongly believe that antibiotic prescription information is difficult to obtain. 6-Many pharmacists (183/200, 91.5%) aimed to educate patients on the risks and correct use of antimicrobials without prescriptions. Conclusions: These results show that Jordanian community pharmacists follow clinical antibiotic prescribing guidelines and conduct antimicrobial stewardship, yet they demand antimicrobials without prescriptions and lack decision support tools. Antibiotic classes address most diseases, and pharmacists emphasize antimicrobial misuse.

During COVID-19 pandemic, use of antimicrobial has been shown to be reduced coupled with various respiratory infections. We investigated whether this effect on reduction of antibiotic prescription can be sustained after resumption of normalcy and lifting of public health measures.

We compared the wholesale supply of antimicrobials using mean annual Daily Defined Dose/1000 inhabitants (DID) in different sectors in pre-COVID-19 (2014-2019), COVID-19 (2020-2022) and post-COVID-19 (2023) periods. We grouped the data according to AWaRe categorisation namely Access, Watch and Reserve defined by WHO, and analysed the trends of the top 10 antibiotics and broad-spectrum antimicrobials. The trends in statutory notifiable diseases including scarlet fever, pneumococcal infections, chickenpox, tuberculosis, and pertussis and influenza-like-illness detected by sentinel surveillance system was analysed by negative-binominal regression.

Compared to baseline level, an overall reduction of 27.2% of antimicrobial utilization was observed during the pandemic years, with a rebound recorded in 2023, up to 89.5% of the pre-pandemic level. The access group of antimicrobials accounted for 57.9% in 2014 gradually increased to 60.2% in 2023 across the pandemic years. Concurrently, reduction in incidence of scarlet fever, pneumococcal infections, chickenpox, tuberculosis, pertussis and influenza-like-illness was observed during COVID-19 pandemic with statistical decreasing trend, p<0.05 for scarlet fever, pneumococcal infections and chickenpox. Rebound in all these infections was reported in 2023, except for chickenpox which showed continued decrease in incidence.

We demonstrated a substantial reduction of antibiotic use during the COVID-19 pandemic, which rebounded in 2023, likely due to increased incidence of respiratory diseases after lifting of public health and social measures. We urged for close monitoring of the antimicrobial resistance pattern of different bacteria due to the inter-connectiveness and global impact of these two pandemics.

This study explored the potential of electroplating sludge (ESs) as a novel and effective photocatalyst for the photodegradation of ciprofloxacin in aqueous solutions. The characterization of the ESs was evaluated using sophisticated techniques, such as XRD, SEM, TEM, EDX, FTIR, and BET. ESs-derived photocatalyst materials were found to primarily consist of various metal oxides (Ni-O, Cu-O), which can absorb ultraviolet or visible light. The effectiveness of photodegradation was assessed by measuring the decomposition of Ciprofloxacin (CIP) in aqueous solutions. The results showed that after 180 min of UVA illumination, a remarkable photodegradation effectiveness of 93.87% was achieved for a CIP concentration of 10 mg L-1, pH = 9, catalyst dose of 1.0 g/L indicating ESs as an effective method for removing CIP from wastewater. The effect of other factors, such as other antibiotics, dyes, and phenol, were also carried out to illustrate high dominant capacity in the degradation of organic compounds. The radical scavenger demonstrated that h+ and O2●- are the main species for the degradation of CIP. This research presents an adaptable, scalable framework for sustainable electroplating sludge reuse. The easily implementable method promises widespread adoption, enhancing sustainability and resource efficiency by repurposing the treated waste as a photocatalyst for antibiotic degradation.Implications: This research investigates the potential of electroplating sludge (ESs) as a sustainable and effective photocatalyst for the degradation of ciprofloxacin (CIP) in wastewater. This study demonstrates that ESs, containing photoactive metal oxides, can effectively degrade CIP under ultraviolet light irradiation. This research suggests that ESs offer a cost-effective and environmentally friendly approach to wastewater treatment, promoting a circular economy. The findings contribute to the development of sustainable solutions for a cleaner and safer environment.

The evolution of antimicrobial resistance among critically ill patients before, during, and after the COVID-19 surge remains unclear.

We retrospectively analyzed critically ill mechanically ventilated adult patients admitted to 8 Brazilian hospitals from Jan 1, 2018 to Apr 30, 2023. We stratified the patients into 3 periods: pre-surge (Jan 01, 2018-Mar 01, 2020), surge (Mar 01, 2020-Oct 01, 2021), and post-surge (after October 01, 2021). Positive cultures, pathogen prevalence, and resistance rates were analyzed using rate ratios (RR) with 95% confidence intervals (CI).

Among 9,780 patients (3,718 pre-surge, 3,815 surge, 2,247 post-surge), those in surge period were younger (median: 70 vs 74 pre-surge vs 75 post surge) and had longer invasive mechanical ventilation duration (median 7 vs 5 days). Blood and respiratory cultures increased across periods (56.9 pre-surge vs 69.4 surge vs 70.4 patients/1,000 patient-days post-surge). Isolation of carbapenem-resistant gram-negatives increased during the surge (RR [95% CI]: 1.8 [1.5-2.2], decreased in post-surge (0.72 [0.6-0.9]), and remained higher than pre-surge (1.3 [1.0-1.6]). Resistance rates for Pseudomonas aeruginosa reduced in post-surge, whereas Klebsiella pneumoniae doubled during the surge, and remained elevated.

Carbapenem resistance increased during the surge period. Although it decreased post-surge, it remained higher than pre-pandemic rates.

The COVID-19 pandemic, as well as associated prevention and control measures, have impacted the entire healthcare system, including the use patterns of medicine. However, the impact of COVID-19 on the use of antibiotics has not yet been extensively evaluated in China. This study aimed to evaluate the impact of the pandemic on the consumption and expenditure of antibiotics in public healthcare institutions in Shaanxi Province, China.

We used longitudinal data from the Shaanxi provincial drug procurement database in this study. An interrupted time-series analysis was performed to evaluate the effects of COVID-19 on consumption and expenditures of antibiotics in public healthcare institutions in Shaanxi from 1 January 2017 to 31 December 2020. Antibiotic consumption was expressed as the number of defined daily doses (DDDs) per 1,000 residents per day (DIDs), based on the population of Shaanxi Province at the end of each year from the National Bureau of Statistics. The pre-pandemic period was from January 2017 to January 2020, and the post-pandemic period was from February 2020 to December 2020.

A declining trend in antibiotic consumption was observed immediately following the COVID-19 pandemic (β2 = -4.099; p < 0.001). Regarding the route of administration, a larger decrease in the consumption of oral antibiotics was observed compared to parenteral (β2 = -3.056; p < 0.001). The decrease in antibiotic consumption in the Watch category (β2 = -2.164; p < 0.001) was larger than in the Access category (β2 = -1.773; p < 0.001), and penicillins (J01C) (β2 = -1.261; p < 0.001) showed a higher decline than cephalosporins (J01D) (β2 = -1.147; p < 0.001). An increasing trend of broad-spectrum antibiotic consumption was observed after the onset of the pandemic (β3 = 0.021; p = 0.015). Expenditures on and consumption of antibiotics follow essentially the same trend.

Despite an initial decline in antibiotic consumption at the start of the COVID-19 pandemic, it had returned to prior levels by the end of 2020. Findings underscore the continued importance of antibiotic stewardship initiatives.

There is a pressing need for global surveillance of ESBL-producing Escherichia coli due to its health impacts, travel and increased antibiotic use during the COVID-19 pandemic. This systematic review and meta-analysis aimed to summarize evidence investigating the global prevalence of ESBL E. coli.

Four databases, including Embase, MEDLINE, PubMed and Web of Science, were searched for quantitative studies that reported prevalence data of faecal carriage of ESBL-producing E. coli published between 23 April 2021 and 22 April 2024. Meta-analysis was performed using the inverse variance heterogeneity model.

Of the 25 studies (13 901 unique participants) included for final analysis, the overall pooled prevalence of ESBL E. coli was 25.4% (95% CI, 19.7%-31.2%). The pooled prevalences of ESBL E. coli in healthy individuals in community settings and inpatients in healthcare settings were 23.4% (95% CI, 14.7%-32.2%) and 27.7% (95% CI, 18.8%-36.7%), respectively. Nearly one-third of the included studies (32%) were from the Western Pacific Region. There was a significant between-group difference for studies with different WHO regions and healthcare contact.

The pooled prevalence of ESBL E. coli remains high and there was a significant between-group difference for different WHO regions, with the highest being in Asian regions. Standardized surveillance of antimicrobial resistance and antibiotic stewardship especially in these regions are needed to enhance the control of this global emergency.

Antimicrobial resistance is a global threat to public health, with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREfm) being major contributors. Despite their clinical impact, comprehensive assessments of changes of the burden of bloodstream infections in terms of Disability-Adjusted Life Years (DALYs) and attributable deaths over time are lacking, particularly in Germany.

We used data from the Antimicrobial Resistance Surveillance system, which covered about 30% of German hospitals. Bloodstream infections were defined by a VREfm or MRSA-positive blood culture. We estimated incidences as a first step to further use these rates to calculate DALYs and attributable deaths using the Burden of Communicable Disease in Europe toolkit. The analysis included stratification by age, sex and region.

From 2017 to 2023, 6262 MRSA and 5442 VREfm blood culture-positive isolates were identified. The incidence of MRSA bloodstream infections decreased from 4.0 to 2.1 per 100,000 population, with estimated DALYs decreasing from 14.6 to 8.6 per 100,000 and attributable deaths from 591 to 316. Conversely, VREfm-BSI incidence doubled from 1.7 to a peak of 3.0 (2021) before declining back to 1.7 per 100,000 in 2023, with estimated DALYs increasing from 8.9 to 16.5 and then decreasing to 8.5 per 100,000 and attributable deaths increasing from 317 to 327. Men and people over 60 years had the highest burden, with noticeable regional differences.

MRSA and VREfm bloodstream infections followed different trends in the past and now present a comparable burden in Germany. Both pathogens pose a significant threat, particularly to hospitalised older aged men. Our findings highlight the need for targeted prevention and continued surveillance of MRSA and VREfm to reduce infections and their impact.

Carbapenem-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA) are among WHO's priority pathogens with antimicrobial resistance (AMR). Studies suggest potential impacts of the COVID-19-pandemic on AMR. We described changes in AMR incidence and epidemiology in Germany during the COVID-19-pandemic.

We used two independent datasets, statutory surveillance and laboratory-based Antibiotic Resistance Surveillance (ARS). We included statutory notifications of infections/colonisations of carbapenem-resistant Acinetobacter spp., Klebsiella pneumoniae, Escherichia coli (CRA/CRKP/CREC) and invasive MRSA. Using Poisson/negative binomial regression and assuming continued pre-pandemic (2015/2017-2020) trends, we projected hypothetical notifications as if the pandemic had not occurred. We quantified annual changes during the pandemic period (2020-2022) by comparing to observed notifications. Additional models considered inpatient reductions, seasonality, infections only, or resistant isolates from ARS.

CRA notified cases were reduced by -30% (95%CI -39%|-20%) in 2020, -23% (-36%|-8%) in 2021, but + 32% (+ 6%|+64%) higher in 2022 relative to hypothetical pre-pandemic projections. Changes were - 35%/-31%/+6% for CRKP, -40%/-61%/-48% for CREC and - 33%/-25%/-20% for MRSA. Statutory-models accounting for fewer inpatients, seasonality and infections only showed similar trends, as did ARS-models for resistant isolates and infections. International mobility for CRA, CRKP and CREC decreased in 2020-2021, then increased in 2022.

We observed significant reductions of AMR notifications and infections during 2020-2021, also when accounting for fewer inpatients. We conclude a genuine reduction of AMR spread occurred during the pandemic. Factors like fewer hospitalisations and reduced international mobility contributed. Rising international mobility may partly explain increases for CRA, CRKP and CREC in 2022. A solid understanding of AMR trends improves infection prevention and control.

Based on the fact that beta-lactam antibiotics demonstrate time-dependent killing, different dosing strategies have been implemented to increase the time that free (f) (unbound) antibiotic concentrations remain above the Minimal Inhibitory Concentration (MIC), including prolonged and continuous infusion. Multiple studies have been performed that compared continuous with traditional intermittent infusion to improve outcomes in patients with severe sepsis and/or septic shock. These studies have yielded inconsistent results for patients as measured by clinical response to treatment and mortality due to heterogeneity of included patients, pathogens, dosing strategies and the absence of Therapeutic Drug Monitoring (TDM). The MERCY and BLING III studies failed to show a difference in mortality between patients randomized to receive continuous and intermittent infusion of beta-lactam antibiotics.
 A deeper understanding of pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms that occur in critically ill patients should guide us in dose optimization and improvement in methodology for future clinical trials.

Healthcare-acquired infections due to multidrug-resistant organisms (MDR-HAIs) pose globally significant challenges to healthcare systems, leading to increased morbidity, mortality, and healthcare costs. According to the World Health Organization, the COVID-19 pandemic significantly impacted the burden of MDR-HAIs. The aim of this study was to investigate the dynamics and epidemiology of MDR-HAIs in inpatients at the University of Leipzig Medical Center (ULMC) before and during the COVID-19 pandemic.

We compared data from inpatients with bacterial infections from 2017 to 2019 (pre-COVID-19) and from 2021to 2023 (during COVID-19) in a cross-sectional, monocentric, retrospective survey. This study focused on selected multidrug-resistant organisms (MDROs) and four clinical specimens. We analyzed the risk factors for MDR-HAIs using logistic regression models.

Out of 342,705 inpatients, 32,206 were diagnosed with a bacterial infection. The prevalence increased significantly from 8.09% (pre-COVID-19) to 10.79% (during COVID-19) (p < 0.001), but the proportion of MDROs decreased from 10.14% to 8.07%. The proportions of MDR-HAIs were 59.86% and 56.67%, respectively. The proportion of carbapenem-resistant Klebsiella pneumoniae and Enterobacter cloacae increased significantly. The risk of MDR-HAIs during COVID-19 decreased by 18% compared to pre-COVID-19 (p = 0.047). Longer hospital stays increased the risk of MDR-HAIs in both periods. This risk significantly decreased for children and the elderly during COVID-19.

These findings show that it is also important to analyze epidemiological data at the facility level in order to evaluate the effectiveness of infection control practices even during unprecedented health crises like the COVID-19 pandemic.

Background/Objectives: Antimicrobial resistance represents a growing global health crisis, demanding innovative approaches to improve antibiotic stewardship. Artificial intelligence (AI) chatbots based on large language models have shown potential as tools to support clinicians, especially non-specialists, in optimizing antibiotic therapy. This review aims to synthesize current evidence on the capabilities, limitations, and future directions for AI chatbots in enhancing antibiotic selection and patient outcomes. Methods: A narrative review was conducted by analyzing studies published in the last five years across databases such as PubMed, SCOPUS, Web of Science, and Google Scholar. The review focused on research discussing AI-based chatbots, antibiotic stewardship, and clinical decision support systems. Studies were evaluated for methodological soundness and significance, and the findings were synthesized narratively. Results: Current evidence highlights the ability of AI chatbots to assist in guideline-based antibiotic recommendations, improve medical education, and enhance clinical decision-making. Promising results include satisfactory accuracy in preliminary diagnostic and prescriptive tasks. However, challenges such as inconsistent handling of clinical nuances, susceptibility to unsafe advice, algorithmic biases, data privacy concerns, and limited clinical validation underscore the importance of human oversight and refinement. Conclusions: AI chatbots have the potential to complement antibiotic stewardship efforts by promoting appropriate antibiotic use and improving patient outcomes. Realizing this potential will require rigorous clinical trials, interdisciplinary collaboration, regulatory clarity, and tailored algorithmic improvements to ensure their safe and effective integration into clinical practice.

Carbapenem-resistant Acinetobacter baumannii has been associated with over three hundred thousand annual deaths globally. It is resistant to most available antibiotics and associated with high morbidity and mortality. No global consensus currently exists for treatment strategies that balance safety and efficacy because of heterogeneity of treatment regimens in current clinical practice and scarcity of large-scale controlled studies arising from difficulties in establishing robust clinical outcomes. This review outlines the epidemiology and resistance mechanisms of carbapenem-resistant A. baumannii, then summarizes available clinical data on each approved agent with activity against this pathogen. Emerging treatment options such as cefiderocol and sulbactam-durlobactam show promise, but their success hinges on comprehensive clinical validation and access in regions most impacted by this pathogen. New therapeutic modalities that are in various stages of clinical development are also discussed.

Urinary tract infection (UTI) is one of the most common bacterial infections in clinical practice. Given the rapid increase in antimicrobial resistance and the scarcity of new antibiotics, along with the absence of individual antibiogram testing in some countries, there is an urgent need for robust surveillance systems.

This study aimed to provide evidence for the surveillance of resistance, a crucial component in developing national UTI treatment guidelines and guiding empirical therapy decisions.

This study utilized a retrospective, serial cross-sectional design.

Antimicrobial surveillance was conducted using data collected from January 1, 2017 to December 31, 2021. A total of 2595 patients with UTIs were recruited for this study. From these patients, 2004 bacterial isolates were identified and subjected to epidemiological and antibiotic resistance analyses.

Escherichia coli (E. coli, 42.7%), Pseudomonas aeruginosa (P. aeruginosa, 11.9%), and Klebsiella pneumoniae (K. pneumoniae, 10.9%) were identified as the predominant causes of UTIs. E. coli isolates demonstrated a high level of sensitivity (80%-90%) to carbapenems (imipenem, ertapenem, and meropenem), aminoglycosides (amikacin), piperacillin/tazobactam, cefoperazone/sulbactam, and fosfomycin. The antibiotic resistance rates of K. pneumoniae strains consistently exceeded 50%, except for amikacin, ertapenem, imipenem, meropenem, and fosfomycin. Notably, all K. pneumoniae strains isolated from patients with UTIs were resistant to ampicillin. During the coronavirus disease pandemic, the E. coli and K. pneumoniae isolates exhibited reduced antibiotic resistance compared to the pre-pandemic period. The resistance rate of P. aeruginosa isolates remained consistently high (60%-70%).

Amikacin, ertapenem, imipenem, meropenem, and fosfomycin are promising treatment options for enterobacterial UTIs. However, their efficacy against P. aeruginosa is limited. This study revealed alarmingly high rates of primary etiological pathogen resistance to commonly prescribed empirical therapies for UTIs. These findings provide crucial data for optimizing national guidelines and implementing personalized treatment strategies to enhance the effectiveness of UTI treatments.

Increased spread of antimicrobial resistance by Gram-Negative Bacilli (GNB) poses a global challenge, with exacerbated burden post-pandemic. The aim of this study was to investigate the in vitro activity of ceftolozane/tazobactam and its comparators against the frequently identified GNB isolated from patients admitted to Brazilian medical sites between the year 2018‒2019 and 2020‒2021. The impact of pandemic on antimicrobial resistance and presence of β-lactamase genes were also evaluated. Antimicrobial susceptibility testing and molecular characterization of ß-lactamase encoding genes using Polymerase Chain Reaction (PCR) and DNA sequencing were carried out from GNB isolated mostly from intra-abdominal, respiratory, and urinary tract infections and interpreted following BrCAST/EUCAST guidelines. A total of 3994 GNB isolates were evaluated which mostly included E. coli, K. pneumoniae and P. aeruginosa. Ceftolozane/tazobactam remained highly active against E. coli isolates during both 2018‒2019 (96.0 %) and 2020‒2021 (98.5 %). Among K. pneumoniae, ceftolozane/tazobactam (47.6 % and 43.0 % susceptible during 2018‒2019 and 2020‒2021, respectively) showed poor activity due to blaKPC-2. Colistin and ceftolozane/tazobactam were the most active β-lactam agents tested against P. aeruginosa in 2018‒2019 (99.3 % and 88.8 %) and 2020‒2021 (100 % and 92.8 %), including ceftazidime and meropenem resistant isolates. β-lactamase encoding gene characterization was carried out and both carbapenemases and Extended-Spectrum β-Lactamase (ESBL) producers were found in E. coli, K. pneumoniae and P. aeruginosa isolates. Ceftolozane/tazobactam documented remarkable in vitro activity against E. coli and P. aeruginosa isolates in Brazil, both pre- and post-pandemic periods and could constitute an effective therapeutic option for the treatment of urinary tract infections, intra-abdominal infections, and respiratory tract infections.

The world has gone through the COVID-19 pandemic and has now returned to normalcy. We reviewed the strategies and public health actions conducted in Hong Kong during the COVID-19 pandemic, and reflected on the lessons learned, which are potentially useful in the fight against antimicrobial resistance (AMR). We recommended extending wastewater surveillance for AMR, apart from SARS-CoV2. We suggested exploring the use of rapid tests in outpatients to aid clinical diagnosis and reduce antibiotic use for viral infections. Stringent infection control measures are crucial to prevent nosocomial transmission of resistant microorganisms, such as vancomycin-resistant enterococci and carbapenemase-producing Enterobacterales in hospitals and in elderly homes. Taking COVID-19 experiences as a reference, transparent data, the prompt dissemination of information, and strategic risk communication should be adopted to maintain sustained behavioral changes in AMR. We also encouraged the adoption of information technology, artificial intelligence, and machine learning in antimicrobial stewardship programs. We also discussed the potential merits and limitations of these strategies. The lessons learned from the COVID-19 pandemic may provide insights into the long battle against AMR.

Antibiotic-resistant bloodstream infections (ARB BSI) cause an enormous disease and economic burden. We assessed the impact of ARB BSI caused by high- and critical-priority pathogens in hospitalised Chilean patients compared to BSI caused by susceptible bacteria.

We conducted a retrospective cohort study from 2018 to 2022 in three Chilean hospitals and measured the association of ARB BSI with in-hospital mortality, length of hospitalisation (LOS), and intensive care unit (ICU) admission. We focused on BSI caused by Acinetobacter baumannii, Enterobacterales, Staphylococcus aureus, Enterococcus species, and Pseudomonas aeruginosa. We addressed confounding using propensity scores, inverse probability weighting, and multivariate regressions. We stratified by community- and hospital-acquired BSI and assessed total hospital and productivity costs.

We studied 1218 adult patients experiencing 1349 BSI episodes, with 47.3% attributed to ARB. Predominant pathogens were Staphylococcus aureus (33% Methicillin-resistant 'MRSA'), Enterobacterales (50% Carbapenem-resistant 'CRE'), and Pseudomonas aeruginosa (65% Carbapenem-resistant 'CRPA'). Approximately 80% of BSI were hospital-acquired. ARB was associated with extended LOS (incidence risk ratio IRR = 1.14, 95% CI = 1.05-1.24), increased ICU admissions (odds ratio OR = 1.25; 1.07-1.46), and higher mortality (OR = 1.42, 1.20-1.68) following index blood culture across all BSI episodes. In-hospital mortality risk, adjusted for time-varying and fixed confounders, was 1.35-fold higher (1.16-1.58) for ARB patients, with higher hazard ratios for hospital-acquired MRSA and CRE at 1.37 and 1.48, respectively. Using a societal perspective and a 5% discount rate, we estimated excess costs for ARB at $12,600 per patient, with an estimated annual excess burden of 2270 disability-adjusted life years (DALYs) and $9.6 (5.0-16.4) million.

It is urgent to develop and implement interventions to reduce the burden of ARB BSIs, particularly from MRSA and CRE.

Agencia Nacional de Investigación y Desarrollo ANID, Chile.

Antimicrobial stewardship (AMS) programmes seek to reduce the risk of antimicrobial resistance by minimizing inappropriate antimicrobial use. The SARS-CoV-2 coronavirus (COVID-19) pandemic was characterized by initial widespread use of antimicrobials in patients with COVID-19, with potential negative effects on AMS efforts.

To explore the impact of the pandemic on the AMS workforce in Scottish acute care hospitals.

Individual, semi-structured online interviews were conducted with a purposive sample of clinical staff who had an AMS focused role in Scottish Health Boards. Interviews explored staff experiences of facilitating AMS during the pandemic. Data were analysed using inductive content analysis.

Thirteen staff from seven of 15 Scotland Health Boards participated. The data revealed negative (including staff redeployment and shortages) and positive effects (including improved working relationships and use of technology) on the AMS workforce. Notably, greater appreciation of the work of the AMS team was a positive outcome.

The robust qualitative methods applied in this original study have generated greater understanding of factors that impeded AMS services in Scotland during the pandemic. These findings may resonate internationally. Adaptation to technology and investment in the workforce are recommended to improve the resilience of AMS services in future crises.

This study aims to meticulously map the bibliometric landscape of drug-drug interactions (DDIs) in clinical research. This represents the first use of bibliometric analysis to comprehensively highlight the evolutionary trends and core themes in this critical field of pharmacology. An exhaustive bibliometric search was performed within the Web of Science Core Collection, aiming to comprehensively gather literature on DDIs in clinical settings. A combination of sophisticated analytical tools including DIKW, VOSviewer, and Citespace was utilized for an in-depth exploration of bibliometric patterns and trends. Of the 3421 initially identified articles, 2622 were considered relevant. The analysis revealed a marked escalation in DDIs publications, with a peak observed in 2020. Five principal thematic clusters emerged: Safety and Adverse Reactions, Drug Metabolism and Efficacy, Disease and Drug Treatment, Research Methods and Practices, and Special Populations and Combined Medication. Key insights included the escalating significance of drug metabolism in pharmacokinetics, heightened focus on cardiovascular and antiviral therapeutics, and the advancing frontier of personalized medicine. Additionally, the analysis underscored the necessity for strategic attention to vulnerable populations and innovative methodological approaches. This study calls for the global harmonization of research methods in DDIs clinical investigations, advocating for the integration of personalized medicine paradigms and the implementation of cutting-edge computational analytics. It highlights the imperative for inclusive and collaborative research approaches to adeptly address the intricate challenges of contemporary pharmacotherapy.

While the pandemic is behind us, the world community faces a global threat of bacterial resistance outbreak. One of the key ways to combat the spread of multi-resistant bacteria is infection prevention and control tactics using modern antiseptic and disinfectant compositions. Herein, we continue the path to unravel the structure-activity relationship (SAR) of potent pyridine-derived biocide class bis-quaternary ammonium compounds (QACs). In this study, twenty dihydroxynaphthalene-derivative bis-QACs were subjected to extensive microbiological analysis on planktonic cells and biofilms of the ESKAPE microorganisms. Among them, hit compounds were superior in their bacteriostatic and bactericidal action to commercial mono-QACs and were comparable to the best bis-QAC antiseptic on the market. SAR analysis indicated that the linker conformation does not significantly affect the activity, though structure symmetry and especially lipophilicity had an influence on antibacterial performance. Furthermore, we delve deeper in investigation of the antimicrobial potential of bis-QACs and conducted a variety of assays, including time-kill kinetics, bacterial resistance formation, cell morphology, and cytotoxicity. Studies showed promising results for compounds 5d and 6d, indicating 2 to 3-fold less cytotoxicity and hemotoxicity compared to commercial QACs. Moreover, SEM imaging revealed that bis-QACs can cause severe membrane damage to S. aureus and P. aeruginosa strains, confirming great potential of novel compounds as antiseptic and disinfectant.

Antibiotic resistance poses a serious threat to the current healthcare system, negatively impacting the effectiveness of many antimicrobial treatments. The situation is exacerbated by the widespread overuse and abuse of available antibiotics, accelerating the evolution of resistance. Thus, there is an urgent need for novel approaches to therapy to overcome established resistance mechanisms. Plants produce molecules capable of inhibiting bacterial growth in various ways, offering promising paths for the development of alternative antibiotic medicine. This review emphasizes the necessity of research efforts on plant-derived chemicals in the hopes of finding and creating novel drugs that can successfully target resistant bacterial populations. Investigating these natural chemicals allows us to improve our knowledge of novel antimicrobial pathways and also expands our antibacterial repertoire with novel molecules. Simultaneously, it is still necessary to utilize present antibiotics sparingly; prudent prescribing practices must be encouraged to extend the effectiveness of current medications. The combination of innovative drug research and responsible drug usage offers an integrated strategy for managing the antibiotic resistance challenge.

Acinetobacter baumannii-a multidrug-resistant (MDR) pathogen that causes, for example, skin and soft tissue wounds; urinary tract infections; pneumonia; bacteremia; and endocarditis, particularly due to its ability to form robust biofilms-poses a significant challenge in clinical settings. This structure protects the bacteria from immune responses and antibiotic treatments, making infections difficult to eradicate. Given the rise in antibiotic resistance, alternative therapeutic approaches are urgently needed. Bacteriophage-based strategies have emerged as a promising solution for combating A. baumannii biofilms. Phages, which are viruses that specifically infect bacteria, offer a targeted and effective means of disrupting biofilm and lysing bacterial cells. This review explores the current advancements in bacteriophage therapy, focusing on its potential for treating A. baumannii biofilm-related infections. We described the mechanisms by which phages interact with biofilms, the challenges in phage therapy implementation, and the strategies being developed to enhance its efficacy (phage cocktails, engineered phages, combination therapies with antibiotics). Understanding the role of bacteriophages in both biofilm disruption and in inhibition of its forming could pave the way for innovative treatments in combating MDR A. baumannii infections as well as the prevention of their development.

Background/Objectives. Our study aimed to determine the development of antibiotic resistance during the peri-pandemic period in a regional secondary care hospital using an interrupted time series analysis. Methods. We analyzed data from seven years, accounting for 441,149 patient days. The incidence density of multidrug-resistant bacteria (MDR) burden and infection was reported per 1000 patient days. Results. During the COVID-19 period, a significant increase in the mean incidence density of the total MDR burden from 4.93 to 5.81 per 1000 patient days was observed (p = 0.007). On the other hand, the mean incidence density of MDR infections decreased from 1.61 to 1.29 per 1000 patient days (p = 0.019). Using the interrupted time series analysis, the same trends were observed, namely the overall increasing trend in MDR burden and the overall decreasing trend in MDR infections. This divergent trend is mainly due to similar trends in several Gram-negative MDR, namely ESBL-EC, ESBL-KP and CRE. Conclusions. Due to the increasing burden of MDR, it is necessary to strengthen AMR surveillance. In addition, strict infection prevention and control measures, and antimicrobial stewardship programs continue to be important components in the fight against resistant bacteria.

The escalating global threat of antibiotic resistance necessitates innovative strategies, such as the combination of antibiotics with adjuvants. Monotherapy with rifampicin is more likely to induce resistance in pathogens compared to other antibiotics. Herein, we found that the antihypertensive drug guanethidine enhanced the activity of rifampicin against certain clinically resistant Gram-negative bacteria, resulting in a reduction of up to 128-fold in the minimum inhibitory concentration. In infected animal models, this combination has achieved treatment benefits, including increased survival and decreased bacterial burden. The antimicrobial mechanism of guanethidine in synergy with rifampicin involves the disruption of the outer membrane of Gram-negative bacteria, leading to dissipation of the proton motive force. This results in an increase in reactive oxygen species and a reduction in ATP synthesis, severely disturbing energy metabolism and ultimately increasing bacterial mortality. In summary, guanethidine has the potential to become a novel adjuvant for rifampicin, offering a new option for the treatment of clinical Gram-negative bacterial infections.

Alteration in the etiology of pediatric bloodstream infections (BSIs) and antimicrobial resistance (AMR) is not well known during the Coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the impact of the COVID-19 pandemic on pediatric BSIs and alteration in antimicrobial resistance phenotypes in Gram-positive bacteria.

The frequency of BSIs among children under 18 years old was retrospectively recorded in a tertiary children's hospital in Tehran, Iran from February 2020 to December 2022. The status of COVID-19 infection using reverse transcription polymerase chain reaction, bacteremia/fungemia according to BACTEC 9120 Culture System results, characterization of bacteria using biochemical tests, and antimicrobial susceptibility patterns for Gram-positive bacterial isolates using disk diffusion method were determined. Statistical analysis was done to measure the correlation of COVID-19 infection with BSIs and AMR.

Out of 13,345 COVID-19 tests and 4,194 BACTEC blood culture requests, bacteremia/fungemia were confirmed in 10.37% (435/4,194) of the patients who requested both tests simultaneously. The COVID-19 infection was confirmed in 25.3% (110/435) of the patients with bacteremia/fungemia. The infection with characterized Gram-positive bacteria (GPB) and fungi was detected in 32.3% (140/433) and 8.31% (36/433) of the cases, respectively. Coagulase-negative Staphylococcus (CNS, 72, 16.62%), S. aureus (36, 8.3%), and Enterococcus spp. (22, 5%) were among the common isolates. Candida spp. and non-Candida yeasts were detected in 6.7% and 13.4% of the cases, respectively. A positive correlation was shown between the CNS bacteremia and COVID-19 infection (p-value = 0.019). Antibiotic susceptibility testing results showed the highest frequency of resistance to azithromycin among CNS, azithromycin and tetracycline among S. aureus and tetracycline among Enterococcus spp. Methicillin-resistance phenotype in the S. aureus (MRSA) and coagulase-negative Staphylococcus spp. (MR-CNS) was detected in 40% and 61.5% of the strains, respectively and the Enterococci were resistant to vancomycin in 33.3% of the isolates.

A decline in the trend of BSIs by GPB and an increase in AMR was shown in children during the COVID-19 pandemic. Increasing antibiotic resistance is a concern; however, chloramphenicol, linezolid, and vancomycin remain active against common causes of GPB-BSIs.

There are conflicting recommendations on whether to use or not to use fluoroquinolone prophylaxis in pediatric oncology patients. An international pediatric clinical practice guideline (CPG) recommends administering levofloxacin prophylaxis in patients with acute myeloblastic leukemia and relapsed acute lymphoblastic leukemia receiving intensive chemotherapy as this practice has been found to reduce episodes of fever and bacteremia. A separate European CPG does not recommend levofloxacin prophylaxis because of concerns for adverse effects, including potentiation of fluoroquinolone resistance and possible increased resistance to other classes of antibiotics. The nuance of the decision to give or not give prophylaxis is discussed in the context of published evidence defining the risks and benefits of levofloxacin prophylaxis for pediatric leukemia patients at high risk for bacterial infection. Knowledge gaps are also identified to guide further investigations to optimize the use of fluoroquinolone prophylaxis in pediatric patients receiving chemotherapy for cancer or undergoing a hematopoietic cell transplantation.

SUMMARYHealthcare-associated infections (HAIs) represent a burden for public health with a high prevalence and high death rates associated with them. Pathogens with a high potential for antimicrobial resistance, such as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and Clostridioides difficile, are responsible for most HAIs. Despite the implementation of infection prevention and control intervention, globally, HAIs prevalence is stable and they are mainly due to endogenous pathogens. It is undeniable that complementary to infection prevention and control measures, prophylactic approaches by active or passive immunization are needed. Specific groups at-risk (elderly people, chronic condition as immunocompromised) and also healthcare workers are key targets. Medical procedures and specific interventions are known to be at risk of HAIs, in addition to hospital environmental exposure. Vaccines or monoclonal antibodies can be seen as attractive preventive approaches for HAIs. In this review, we present an overview of the vaccines and monoclonal antibodies in clinical development for prevention of the major bacterial HAIs pathogens. Based on the current state of knowledge, we look at the challenges and future perspectives to improve prevention by these means.