Role of biomarkers in antimicrobial stewardship: physicians' perspectives.

Biomarkers are playing an increasingly important role in antimicrobial stewardship. Their applications have included use in algorithms that evaluate suspected bacterial infections or provide guidance on when to start or stop antibiotic therapy, or when therapy should be repeated over a short period (6-12 h). Diseases in which biomarkers are used as complementary tools to determine the initiation of antibiotics include sepsis, lower respiratory tract infection (LRTI), COVID-19, acute heart failure, infectious endocarditis, acute coronary syndrome, and acute pancreatitis. In addition, cut-off values of biomarkers have been used to inform the decision to discontinue antibiotics for diseases such as sepsis, LRTI, and febrile neutropenia. The biomarkers used in antimicrobial stewardship include procalcitonin (PCT), C-reactive protein (CRP), presepsin, and interleukin (IL)-1ß/IL-8. The cut-off values vary depending on the disease and study, with a range of 0.25-1.0 ng/mL for PCT and 8-50 mg/L for CRP. Biomarkers can complement clinical diagnosis, but further studies of microbiological biomarkers are needed to ensure appropriate antibiotic selection.

Changing patterns of bacterial profile and antimicrobial resistance in high-risk patients during the COVID-19 pandemic at a tertiary oncology hospital.

The widespread evolution of phenotypic resistance in clinical isolates over the years, coupled with the COVID-19 pandemic onset, has exacerbated the global challenge of antimicrobial resistance. This study aimed to explore changes in bacterial infection patterns and antimicrobial resistance during the COVID-19 pandemic. This study involved the periods before and during COVID-19: the pre-pandemic and pandemic eras. The surveillance results of bacterial isolates causing infections in cancer patients at an Egyptian tertiary oncology hospital were retrieved. The Vitek®2 or Phoenix systems were utilized for species identification and susceptibility testing. Statistical analyses were performed comparing microbiological trends before and during the pandemic. Out of 2856 bacterial isolates, Gram-negative bacteria (GNB) predominated (69.7%), and Gram-positive bacteria (GPB) comprised 30.3% of isolates. No significant change was found in GNB prevalence during the pandemic (P = 0.159). Elevated rates of Klebsiella and Pseudomonas species were demonstrated during the pandemic, as was a decrease in E. coli and Acinetobacter species (P < 0.001, 0.018, < 0.001, and 0.046, respectively) in hematological patients. In surgical patients, Enterobacteriaceae significantly increased (P = 0.012), while non-fermenters significantly decreased (P = 0.007). GPB species from either hematological or surgical wards exhibited no notable changes during the pandemic. GNB resistance increased in hematological patients to carbapenems, amikacin, and tigecycline and decreased in surgical patients to amikacin and cefoxitin (P < 0.001, 0.010, < 0.001, < 0.001, and 0.016, respectively). The study highlights notable shifts in the microbial landscape during the COVID-19 pandemic, particularly in the prevalence and resistance patterns of GNB in hematological and surgical wards.

Nature-Inspired Micro/Nano-Structured Antibacterial Surfaces.

The problem of bacterial resistance has become more and more common with improvements in health care. Worryingly, the misuse of antibiotics leads to an increase in bacterial multidrug resistance and the development of new antibiotics has virtually stalled. These challenges have prompted the need to combat bacterial infections with the use of radically different approaches. Taking lessons from the exciting properties of micro-/nano-natural-patterned surfaces, which can destroy cellular integrity, the construction of artificial surfaces to mimic natural functions provides new opportunities for the innovation and development of biomedicine. Due to the diversity of natural surfaces, functional surfaces inspired by natural surfaces have a wide range of applications in healthcare. Nature-inspired surface structures have emerged as an effective and durable strategy to prevent bacterial infection, opening a new way to alleviate the problem of bacterial drug resistance. The present situation of bactericidal and antifouling surfaces with natural and biomimetic micro-/nano-structures is briefly reviewed. In addition, these innovative nature-inspired methods are used to manufacture a variety of artificial surfaces to achieve extraordinary antibacterial properties. In particular, the physical antibacterial effect of nature-inspired surfaces and the functional mechanisms of chemical groups, small molecules, and ions are discussed, as well as the wide current and future applications of artificial biomimetic micro-/nano-surfaces. Current challenges and future development directions are also discussed at the end. In the future, controlling the use of micro-/nano-structures and their subsequent functions will lead to biomimetic surfaces offering great potential applications in biomedicine.

Impact of inadequate empirical antibiotic treatment on outcome of non-critically ill children with bacterial infections.

BACKGROUND: The impact of inadequate empirical antibiotic treatment on patient outcomes and hospitalization duration for non-life-threatening infections in children remains poorly understood. We aimed to assess the effects of inadequate empirical antibiotic treatment on these factors in pediatric patients. METHODS: The medical records of children admitted for infectious diseases with bacteria isolated from sterile sites between 2018 and 2020 were retrospectively reviewed. Patients who received adequate empirical treatment were compared with those who received inadequate treatment in terms of demographic, clinical, and laboratory variables. RESULTS: Forty-eight patients who received inadequate empirical antimicrobial treatment were compared to 143 patients who received adequate empirical treatment. Inadequate empirical antimicrobial treatment did not significantly affect the length of hospital stay or the incidence of complications in non-critically ill children with bacterial infections. Younger age and underlying renal abnormalities were identified as risk factors for inadequate antimicrobial treatment, while associated bacteremia was more common in the adequate antimicrobial treatment group. CONCLUSIONS: inadequate antibiotic treatment did not affect the outcomes of non-critically ill children with bacterial infectious diseases. Therefore, routine empirical broad-spectrum treatment may not be necessary for these cases, as it can lead to additional costs and contribute to antibiotic resistance. Larger prospective studies are needed to confirm these findings.

Arginine and tryptophan-rich dendritic antimicrobial peptides that disrupt membranes for bacterial infection in vivo.

The potent antibacterial activity and low resistance of antimicrobial peptides (AMPs) render them potential candidates for treating multidrug-resistant bacterial infections. Herein, a minimalist design strategy was proposed employing the "golden partner" combination of arginine (R) and tryptophan (W), along with a dendritic structure to design AMPs. By extension, the α/ε-amino group and the carboxyl group of lysine (K) were utilized to link R and W, forming dendritic peptide templates αRn(εRn)KWm-NH2 and αWn(εWn)KRm-NH2, respectively. The corresponding linear peptide templates R2nKWm-NH2 and W2nKRm-NH2 were used as controls. Their physicochemical properties, activity, toxicity, and stability were compared. Among these new peptides, the dendritic peptide R2(R2)KW4 was screened as a prospective candidate owing to its preferable antibacterial properties, biocompatibility, and stability. Additionally, R2(R2)KW4 not only effectively restrained the progression of antibiotic resistance, but also demonstrated synergistic utility when combined with conventional antibiotics due to its unique membrane-disruptive mechanism. Furthermore, R2(R2)KW4 possessed low toxicity (LD50 = 109.31 mg/kg) in vivo, while efficiently clearing E. coli in pulmonary-infected mice. In conclusion, R2(R2)KW4 has the potential to become an antimicrobial regent or adjuvant, and the minimalist design strategy of dendritic peptides provides innovative and encouraging thoughts in designing AMPs.

Navigating Antibacterial Frontiers: A Panoramic Exploration of Antibacterial Landscapes, Resistance Mechanisms, and Emerging Therapeutic Strategies.

The development of effective antibacterial solutions has become paramount in maintaining global health in this era of increasing bacterial threats and rampant antibiotic resistance. Traditional antibiotics have played a significant role in combating bacterial infections throughout history. However, the emergence of novel resistant strains necessitates constant innovation in antibacterial research. We have analyzed the data on antibacterials from the CAS Content Collection, the largest human-curated collection of published scientific knowledge, which has proven valuable for quantitative analysis of global scientific knowledge. Our analysis focuses on mining the CAS Content Collection data for recent publications (since 2012). This article aims to explore the intricate landscape of antibacterial research while reviewing the advancement from traditional antibiotics to novel and emerging antibacterial strategies. By delving into the resistance mechanisms, this paper highlights the need to find alternate strategies to address the growing concern.

Epidemiology and Management of Infections in Liver Transplant Recipients.

Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug-resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population.

Nanotechnology-driven strategies to enhance the treatment of drug-resistant bacterial infections.

The misuse of antibiotics has led to increased bacterial resistance, posing a global public health crisis and seriously endangering lives. Currently, antibiotic therapy remains the most common approach for treating bacterial infections, but its effectiveness against multidrug-resistant bacteria is diminishing due to the slow development of new antibiotics and the increase of bacterial drug resistance. Consequently, developing new a\ntimicrobial strategies and improving antibiotic efficacy to combat bacterial infection has become an urgent priority. The emergence of nanotechnology has revolutionized the traditional antibiotic treatment, presenting new opportunities for refractory bacterial infection. Here we comprehensively review the research progress in nanotechnology-based antimicrobial drug delivery and highlight diverse platforms designed to target different bacterial resistance mechanisms. We also outline the use of nanotechnology in combining antibiotic therapy with other therapeutic modalities to enhance the therapeutic effectiveness of drug-resistant bacterial infections. These innovative therapeutic strategies have the potential to enhance bacterial susceptibility and overcome bacterial resistance. Finally, the challenges and prospects for the application of nanomaterial-based antimicrobial strategies in combating bacterial resistance are discussed. This article is categorized under: Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Cascade-Targeted Nanoplatforms for Synergetic Antibiotic/ROS/NO/Immunotherapy against Intracellular Bacterial Infection.

Intracellular bacteria in dormant states can escape the immune response and tolerate high-dose antibiotic treatment, leading to severe infections. To overcome this challenge, cascade-targeted nanoplatforms that can target macrophages and intracellular bacteria, exhibiting synergetic antibiotic/reactive oxygen species (ROS)/nitric oxide (NO)/immunotherapy, were developed. These nanoplatforms were fabricated by encapsulating trehalose (Tr) and vancomycin (Van) into phosphatidylserine (PS)-coated poly[(4-allylcarbamoylphenylboric acid)-ran-(arginine-methacrylamide)-ran-(N,N'-bisacryloylcystamine)] nanoparticles (PABS), denoted as PTVP. PS on PTVP simulates a signal of "eat me" to macrophages to promote cell uptake (the first-step targeting). After the uptake, the nanoplatform in the acidic phagolysosomes could release Tr, and the exposed phenylboronic acid on the nanoplatform could target bacteria (the second-step targeting). Nanoplatforms can release Van in response to infected intracellular overexpressed glutathione (GSH) and weak acid microenvironment. l-arginine (Arg) on the nanoplatforms could be catalyzed by upregulated inducible nitric oxide synthase (iNOS) in the infected macrophages to generate nitric oxide (NO). N,N'-Bisacryloylcystamine (BAC) on nanoplatforms could deplete GSH, allow the generation of ROS in macrophages, and then upregulate proinflammatory activity, leading to the reinforced antibacterial capacity. This nanoplatform possesses macrophage and bacteria-targeting antibiotic delivery, intracellular ROS, and NO generation, and pro-inflammatory activities (immunotherapy) provides a new strategy for eradicating intracellular bacterial infections.

Increasing the Use of Enteral Antibiotics in Hospitalized Children With Uncomplicated Infections.

BACKGROUND: Route of administration is an important component of antimicrobial stewardship. Early transition from intravenous to enteral antibiotics in hospitalized children is associated with fewer catheter-related adverse events, as well as decreased costs and length of stay. Our aim was to increase the percentage of enteral antibiotic doses for hospital medicine patients with uncomplicated common bacterial infections (community-acquired pneumonia, skin and soft tissue infection, urinary tract infection, neck infection) from 50% to 80% in 6 months. METHODS: We formed a multidisciplinary team to evaluate key drivers and design plan-do-study-act cycles. Interventions included provider education, structured discussion at existing team huddles, and pocket-sized printed information. Our primary measure was the percentage of antibiotic doses given enterally to patients receiving other enteral medications. Secondary measures included antibiotic cost, number of peripheral intravenous catheters, length of stay, and 7-day readmission. We used statistical process control charts to track our measures. RESULTS: Over a 6-month baseline period and 12 months of improvement work, we observed 3183 antibiotic doses (888 in the baseline period, 2295 doses during improvement work). We observed an increase in the percentage of antibiotic doses given enterally per week for eligible patients from 50% to 67%. We observed decreased antibiotic costs and fewer peripheral intravenous catheters per encounter after the interventions. There was no change in length of stay or readmissions. CONCLUSIONS: We observed increased enteral antibiotic doses for children hospitalized with common bacterial infections. Interventions targeting culture change and communication were associated with sustained improvement.

Bullet-related bacterial wound infections among injured personnel at emergency site hospitals in Bahir Dar: prevalence, antimicrobial susceptibility and associated factors.

BACKGROUND: Bullet-related bacterial wound infection can be caused by high-velocity bullets and shrapnel injuries. In Ethiopia, significant injuries were reported that may cause severe wound infections, persistent systemic infections and may lead to amputation and mortality. The magnitude, antimicrobial susceptibility profiles, and factors associated with bacterial wound infections among patients with bullet-related injuries are not yet studied particularly at health facilities in Bahir Dar, Northwest Ethiopia. Therefore, this study was aimed to determine the prevalence, bacterial profiles, antimicrobial susceptibility profiles, and factors associated with bacterial infections among patients with bullet-related injuries at referral health facilities in Bahir Dar, Northwest Ethiopia. METHODS: A Hospital-based cross-sectional study was conducted among patients with bullet-related injuries at three referral health facilities in Bahir Dar from May 25 to July 27, 2022. A total of 384 patients with bullet-related injuries were included in the study. Sociodemographic and clinical data were collected using a structured questionnaire. Wound swabs were collected aseptically and cultured on Blood and MacConkey agar following bacteriological standards. Biochemical tests were performed to differentiate bacteria for positive cultivation and antimicrobial susceptibility profiles of the isolates were done on Muller Hinton agar using the Kirby-Bauer disk diffusion technique according to the 2021 Clinical Laboratory Standard Institute (CLSI) guideline. The data were entered using Epi-Info version 7.3 and analyzed using SPSS version 25. Descriptive data were presented using frequency, percentages, figures, and charts. Logistic regression was carried out to identify factors associated with bacterial wound infections. P-value < 0.05 was considered statistically significant. RESULTS: The prevalence of bullet-related bacterial wound infection among three referral hospitals in Bahir Dar city was 54.7%. The most commonly isolated Gram-negative organism was Klebsiella spps 49 (23.3%) while among Gram-positive organism, Staphylococcus aureus 58 (27.6%) and coagulase-negative staphylococci (CONS) 18 (8.6%). Contamination, hospitalization and smoking habit were significantly associated with the presence of bullet-related bacterial wound infections. Over 97% multidrug resistant (MDR) bacterial isolates were identified and of theses, E. coli, Proteus species, Citrobactor, and Staphylococcus aureus were highly drug resistant. CONCLUSION: Increased prevalence of bullet-related bacterial wound infection was noticed in this study. S. aureus followed by Klebsiella species were most commonly isolated bacteria. High frequency of resistance to Ampicillin, Oxacillin, Cefepime, Ceftriaxone, Ceftazidime, Vancomycin, and Norfloxacin was observed. Therefore, proper handling of bullet injuries, prompt investigation of bacterial infections, monitoring of drug sensitivity patterns and antibiotic usage are critical.

Microbial extracellular vesicles contribute to antimicrobial resistance.

With the escalating global antimicrobial resistance crisis, there is an urgent need for innovative strategies against drug-resistant microbes. Accumulating evidence indicates microbial extracellular vesicles (EVs) contribute to antimicrobial resistance. Therefore, comprehensively elucidating the roles and mechanisms of microbial EVs in conferring resistance could provide new perspectives and avenues for novel antimicrobial approaches. In this review, we systematically examine current research on antimicrobial resistance involving bacterial, fungal, and parasitic EVs, delineating the mechanisms whereby microbial EVs promote resistance. Finally, we discuss the application of bacterial EVs in antimicrobial therapy.

Research Progress on the Combination of Quorum-Sensing Inhibitors and Antibiotics against Bacterial Resistance.

Bacterial virulence factors and biofilm development can be controlled by the quorum-sensing (QS) system, which is also intimately linked to antibiotic resistance in bacteria. In previous studies, many researchers found that quorum-sensing inhibitors (QSIs) can affect the development of bacterial biofilms and prevent the synthesis of many virulence factors. However, QSIs alone have a limited ability to suppress bacteria. Fortunately, when QSIs are combined with antibiotics, they have a better therapeutic effect, and it has even been demonstrated that the two together have a synergistic antibacterial effect, which not only ensures bactericidal efficiency but also avoids the resistance caused by excessive use of antibiotics. In addition, some progress has been made through in vivo studies on the combination of QSIs and antibiotics. This article mainly expounds on the specific effect of QSIs combined with antibiotics on bacteria and the combined antibacterial mechanism of some QSIs and antibiotics. These studies will provide new strategies and means for the clinical treatment of bacterial infections in the future.

Prevalence of multidrug-resistant bacterial infections in diabetic foot ulcers: A meta-analysis.

Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta-analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%-59.78%). The prevalence of MDR gram-positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%-25.91%), and the prevalence of MDR gram-negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%-39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%-15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%-5.07%)) were the main MDR-GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR-GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%-8.95%), 6.01% (95% CI: 4.03%-8.33%), 3.59% (95% CI: 0.42%-9.30%), 3.50% (95% CI: 2.31%-4.91%), and 3.27% (95% CI: 1.74%-5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non-MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non-MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR-GNB was greater than that of MDR-GPB in DFUs. MDR S. aureus was the main MDR-GPB in DFUs, and MDR E. coli was the main MDR-GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.

A Nonbactericidal Anionic Antimicrobial Peptide Provides Prophylactic and Therapeutic Efficacies against Bacterial Infections in Mice by Immunomodulatory-Antithrombotic Duality.

Although bactericidal cationic antimicrobial peptides (AMPs) have been well characterized, less information is available about the antibacterial properties and mechanisms of action of nonbactericidal AMPs, especially nonbactericidal anionic AMPs. Herein, a novel anionic antimicrobial peptide (Gy-CATH) with a net charge of -4 was identified from the skin of the frog Glyphoglossus yunnanensis. Gy-CATH lacks direct antibacterial effects but exhibits significantly preventive and therapeutic capacities in mice that are infected with Staphylococcus aureus, Enterobacteriaceae coli, methicillin-resistant Staphylococcus aureus (MRSA), or carbapenem-resistant E. coli (CREC). In vitro and in vivo investigations proved the regulation of Gy-CATH on neutrophils and macrophages involved in the host immune defense against infection. Moreover, Gy-CATH significantly reduced the extent of pulmonary fibrin deposition and prevented thrombosis in mice, which was attributed to the regulatory role of Gy-CATH in physiological anticoagulants and platelet aggregation. These findings show that Gy-CATH is a potential candidate for the treatment of bacterial infection.

Targeted Clindamycin Delivery Systems: Promising Options for Preventing and Treating Bacterial Infections Using Biomaterials.

Targeted therapy represents a real opportunity to improve the health and lives of patients. Developments in this field are confirmed by the fact that the global market for drug carriers was worth nearly $40 million in 2022. For this reason, materials engineering and the development of new drug carrier compositions for targeted therapy has become a key area of research in pharmaceutical drug delivery in recent years. Ceramics, polymers, and metals, as well as composites, are of great interest, as when they are appropriately processed or combined with each other, it is possible to obtain biomaterials for hard tissues, soft tissues, and skin applications. After appropriate modification, these materials can release the drug directly at the site requiring a therapeutic effect. This brief literature review characterizes routes of drug delivery into the body and discusses biomaterials from different groups, options for their modification with clindamycin, an antibiotic used for infections caused by aerobic and anaerobic Gram-positive bacteria, and different methods for the final processing of carriers. Examples of coating materials for skin wound healing, acne therapy, and bone tissue fillers are given. Furthermore, the reasons why the use of antibiotic therapy is crucial for a smooth and successful recovery and the risks of bacterial infections are explained. It was demonstrated that there is no single proven delivery scheme, and that the drug can be successfully released from different carriers depending on the destination.

The Prospect of Biomimetic Immune Cell Membrane-Coated Nanomedicines for Treatment of Serious Bacterial Infections and Sepsis.

Invasive bacterial infections and sepsis are persistent global health concerns, complicated further by the escalating threat of antibiotic resistance. Over the past 40 years, collaborative endeavors to improve the diagnosis and critical care of septic patients have improved outcomes, yet grappling with the intricate immune dysfunction underlying the septic condition remains a formidable challenge. Anti-inflammatory interventions that exhibited promise in murine models failed to manifest consistent survival benefits in clinical studies through recent decades. Novel therapeutic approaches that target bacterial virulence factors, for example with monoclonal antibodies, aim to thwart pathogen-driven damage and restore an advantage to the immune system. A pioneering technology addressing this challenge is biomimetic nanoparticles-a therapeutic platform featuring nanoscale particles enveloped in natural cell membranes. Borne from the quest for a durable drug delivery system, the original red blood cell-coated nanoparticles showcased a broad capacity to absorb bacterial and environmental toxins from serum. Tailoring the membrane coating to immune cell sources imparts unique characteristics to the nanoparticles suitable for broader application in infectious disease. Their capacity to bind both inflammatory signals and virulence factors assembles the most promising sepsis therapies into a singular, pathogen-agnostic therapeutic. This review explores the ongoing work on immune cell-coated nanoparticle therapeutics for infection and sepsis. SIGNIFICANCE STATEMENT: Invasive bacterial infections and sepsis are a major global health problem made worse by expanding antibiotic resistance, meaning better treatment options are urgently needed. Biomimetic cell-membrane-coated nanoparticles are an innovative therapeutic platform that deploys a multifaceted mechanism to action to neutralize microbial virulence factors, capture endotoxins, and bind excessive host proinflammatory cytokines, seeking to reduce host tissue injury, aid in microbial clearance, and improve patient outcomes.

Tackling the threat of antimicrobial resistance in neonates and children: outcomes from the first WHO-convened Paediatric Drug Optimisation exercise for antibiotics.

Children and neonates are highly vulnerable to the impact of antimicrobial resistance. Substantial barriers are faced in relation to research and development of antibacterial agents for use in neonates, children, and adolescents aged yonger than 19 years, and focusing finite resources on the most appropriate agents for development and paediatric optimisation is urgently needed. In November and December, 2022, following the successes of previous similar disease-focused exercises, WHO convened the first Paediatric Drug Optimisation (PADO) exercise for antibiotics, aiming to provide a shortlist of antibiotics to be prioritised for paediatric research and development, especially for use in regions with the highest burden of disease attributable to serious bacterial infection. A range of antibiotics with either existing license for children or in clinical development in adults but with little paediatric data were considered, and PADO priority and PADO watch lists were formulated. This Review provides the background and overview of the exercise processes and its outcomes as well as a concise review of the literature supporting decision making. Follow-up actions to implement the outcomes from the PADO for antibiotics process are also summarised. This Review highlights the major beneficial influence the collaborative PADO process can have, both for therapeutic drug class and disease-specific themes, in uniting efforts to ensure children have access to essential medicines across the world.