Broad-spectrum Antimicrobials Research Articles

Empiric gram-negative antibiotics usage among critically ill patients across 13 ICUs of Nepal: A retrospective cohort study

Background This study aims to investigate the associations between patient characteristics and the receipt of empiric broad-spectrum gram-negative antimicrobials among adult patients admitted to ICUs in Nepal. Methods A retrospective cohort study was conducted in 13 ICUs in Nepal between January 1st, 2020, and December 31st, 2022. Empiric antibiotic use was defined as receiving gram-negative antibiotics within the first two days of ICU admission without evidence of infection from culture. Patient characteristics between patients receiving narrow-spectrum antibiotics and broad-spectrum gram-negative antibiotics were compared. Continuous variables were compared using mean and standard deviation, with mean differences and 95% confidence intervals calculated. Categorical variables were compared using the chi-square test. A multi-level multivariable regression model assessed the relationship between selected variables and broad-spectrum antibiotic usage, treating admitting ICU as a random factor. Results Among 12,349 eligible patients, 8720 (70.6%) received Empiric gram-negative antibiotics. Of those, 3240 (37.15%) received empiric narrow-spectrum gram-negative antibiotics, and 5480 (62.8%) received Empiric broad-spectrum gram-negative antibiotics. Patients receiving broad-spectrum gram-negative antibiotics were older (57.4 vs 53.8 yrs); had higher mean heart rates (97.3 vs 89.5 bpm), respiratory rates (24 vs 21.9), a fraction of inspired oxygen ( 50% vs 40%), blood sugar levels (163.4 vs 153.9 mg/dl), total leucocyte counts (12,685 vs 10,647 cells/cu mm) and serum creatinine (2.06 vs 1.03 umol/l) compared to narrow spectrum antibiotics. Similarly, patients receiving broad-spectrum gram-negative antibiotics had lower systolic blood pressure (122.6 vs 126.5 mm Hg), partial pressure of oxygen (96.7 vs 105.3), and pH ( 7.33 vs 7.36) compared to narrow-spectrum antibiotics. On multivariable regression; patients with readmission, cardiac support, and mechanical ventilation were more likely to receive broad-spectrum antibiotics. Conclusion The rate of empiric broad-spectrum gram-negative antibiotics usage in intensive care units is significantly high and associated with features of increased severity of illness.

Discovery of Arylpiperazines with Broad-Spectrum Antimicrobial Activity and Favorable Pharmacokinetic Profiles.

Microorganisms can induce diseases with significant clinical implications for human health. Multidrug-resistant microorganisms have been on the rise worldwide over the past few decades, and no new antibiotics have been introduced to the market in a considerable amount of time. Such situation highlights the urgency of discovering new antimicrobial drugs to address this pressing issue. Therefore, the objective of this study was to identify bioactive compounds against 15 species of bacteria and 5 species of fungi of clinical relevance through in vitro screening of 58 synthetic compounds from four chemical classes of our internal library of synthetic compounds. Our findings highlight arylpiperazines 18, 20, 26, 27, and 29, and the aminothiazole 50, as potent broad-spectrum antimicrobials (MICs = 12.5 - 15.6 mg.mL-1) against clinically relevant bacteria and fungi. Additionally, these compounds displayed low cytotoxicity against various host cells and a favorable in vitro pharmacokinetic profile for oral administration. Indeed, all six showed adequate lipophilicity, high gastrointestinal permeability, metabolic stability in human and mouse liver microsomes, and satisfactory aqueous solubility. Thus, they emerge as promising starting points for hit-to-lead studies towards new antibacterial and antifungal agents, especially against Staphylococcus epidermidis, Staphylococcus aureus, Lactobacillus paracasei and Candida orthopsilosis.

Colonisation by multidrug-resistant organisms in health workers in primary care: narrow spectrum oral antimicrobials are a risk factor.

Limited information exists on carriage of multidrug-resistant organisms (MDRO) by health workers (HWs) in primary care settings. This study aims to determine the prevalence of MDRO carriage among HWs in primary care and to identify associated risk factors. A cross-sectional study was conducted across all 12 primary care units in São Caetano do Sul-SP, Brazil, from October to December 2023. Self-collected samples (nasal, oropharyngeal, and inguinal) were obtained. Environment cultures (potable water, sewage and stream water) were evaluated. Stenotrophomonas maltophilia isolates (human and environmental) were typed. The study included 265/288 (92%) of HWs in primary care teams, mostly women with a median age of 47years (IQR 38-57); 78% had no comorbidities. MDRO colonisation was found in 8.7% (23 HWs). The following bacteria were found: S. maltophilia (n = 9; 3.4%) in inguinal swabs; methicillin-resistant Staphylococcus aureus (n = 8; 3%) from all sites; extended-spectrum ß-lactamase-producing bacteria (n = 5; 2%) in inguinal swabs; and vancomycin-resistant enterococci in an inguinal swab (n = 1; 0.4%). Previous antibiotic use was significantly associated with MDRO colonisation (OR 2.91, 95% CI 1.19-7.09, p = 0.018), mainly narrow spectrum oral beta-lactams and macrolides. S. malthophilia was polyclonal and human and environmental isolates differed. Colonisation by MRSA, VRE, and ESBL-producing bacteria was low; however, 4% were surprisingly colonized by polyclonal S. maltophilia. This pathogen may also suggest using narrow-spectrum rather than the expected broad-spectrum antimicrobials. Antibiotic use was the only risk factor found, mainly with oral narrow-spectrum drugs.

Role of doxycycline post exposure prophylaxis in the prevention of sexually transmitted infections: a narrative review

Sexually transmitted infections (STIs) spread through sexual intercourse. They are caused by pathogens like Neisseria gonorrhoeae, Treponema pallidum, Chlamydia trachomatis, and Mycoplasma genitalium, and can be transmitted through direct contact or contact with genital secretions. Doxycycline is a second-generation tetracycline antibiotic with a broad antimicrobial spectrum, acting on intracellular and extracellular organisms. This review aims to explore the efficacy of doxycycline post-exposure prophylaxis (PEP) in the prevention and treatment of STIs. Some of the areas of uncertainty with the use of doxycycline PEP for STIs include the concern for developing antimicrobial resistance (AMR), the effect on the normal microbiome of the body, public acceptability, drug formulation and dosage and compliance issues. Recent clinical and observational studies have looked at using doxycycline PEP to reduce the transmission of STIs. This review aims to explore these studies to provide a comprehensive account of the current state of doxycycline PEP and its future prospects. We also look at the limitations and areas of improvement in using doxycycline PEP, opening avenues for future research. High-quality studies have shown that using doxycycline PEP can effectively reduce the transmission of STIs in a number of clinical trials as well as systematic reviews., making it a potential standard treatment for high-risk groups such as immunocompromised patients, individuals living with HIV, sex workers, and men who have sex with men (MSM).

Antifungal effect of cinnamon essential oil against Penicillium oxalicum on rice noodles.

Plant essential oils have been extensively investigated for their application in food industry due to their broad antimicrobial spectrum and safety. However, rare studies investigated their application in decontaminating rice noodles from fungal contamination. In this study, the cinnamon essential oil was screened out among 12 species of plant essential oils, and its antifungal activity against Penicillium oxalicum isolated from rice noodles was investigated. Our study revealed that cinnamon essential oil inhibited the spore germination in a concentration-dependent manner, and a dosage of 0.025% (v/v) could entirely disable the spore germination. The disruption of the fungal plasma membrane was evidenced by the change of plasma membrane permeability and the leakage of cellular components. The cinnamon essential oil in vapor phase (0.00625% [v/v]) could totally inhibit the growth of fungi inoculated on rice noodles. In addition to the potential application in inactivating fungi germination on rice noodles, this study also demonstrated the feasibility of cinnamon essential as an environmental disinfectant. This study is the first report that cinnamon essential oil has been studied for decontaminating rice noodles from fungal contamination with P. oxalicum, which not only broadens the application field of plant essential oil but also provides an alternative approach for rice noodle preservation.

Antimicrobial spectrum against wound pathogens and cytotoxicity of star-arranged poly-l-lysine-based antimicrobial peptide polymers.

Introduction. As growing numbers of patients are at higher risk of infection, novel topical broad-spectrum antimicrobials are urgently required for wound infection management. Robust pre-clinical studies should support the development of such novel antimicrobials.Gap statement. To date, evidence of robust investigation of the cytotoxicity and antimicrobial spectrum of activity of antimicrobial peptides (AMP)s is lacking in published literature. Using a more clinical lens, we address this gap in experimental approach, building on our experience with poly-l-lysine (PLL)-based AMP polymers.Aim. To evaluate the in vitro bactericidal activity and cytotoxicity of a PLL-based 16-armed star AMP polymer, designated 16-PLL10, as a novel candidate antimicrobial.Methods. Antimicrobial susceptibilities of clinical isolates and reference strains of ESKAPE (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) pathogens, to 16-PLL10 were investigated. Human erythrocyte haemolysis and keratinocyte viability assays were used to assess toxicity. Modifications were made to 16-PLL10 and re-evaluated for improvement.Results. Minimum bactericidal concentration of 16-PLL10 ranged from 1.25 µM to ≥25 µM. At 2.5 µM, 16-PLL10 was broadly bactericidal against ESKAPE strains/wound isolates. Log-reduction in colony forming units (c.f.u.) per millilitre after 1 h, ranged from 0.3 (E. cloacae) to 5.6 (K. pneumoniae). At bactericidal concentrations, 16-PLL10 was toxic to human keratinocyte and erythrocytes. Conjugates of 16-PLL10, Trifluoroacetylated (TFA)-16-PLL10, and Poly-ethylene glycol (PEG)ylated 16-PLL10, synthesised to address toxicity, only moderately reduced cytotoxicity and haemolysis.Conclusions. Due to poor selectivity indices, further development of 16-PLL10 is unlikely warranted. However, considering the unmet need for novel topical antimicrobials, the ease of AMP polymer synthesises/modification is attractive. To support more rational development, prioritising clinically relevant pathogens and human cells, to establish selective toxicity profiles in vitro, is critical. Further characterisation and discovery utilising artificial intelligence and computational screening approaches can accelerate future AMP nanomaterial development.

Exploiting human immune repertoire transgenic mice for protective monoclonal antibodies against antimicrobial resistant Acinetobacter baumannii

The use of monoclonal antibodies for the control of drug resistant nosocomial bacteria may alleviate a reliance on broad spectrum antimicrobials for treatment of infection. We identify monoclonal antibodies that may prevent infection caused by carbapenem resistant Acinetobacter baumannii. We use human immune repertoire mice (Kymouse platform mice) as a surrogate for human B cell interrogation to establish an unbiased strategy to probe the antibody-accessible target landscape of clinically relevant A. baumannii. After immunisation of the Kymouse platform mice with A. baumannii derived outer membrane vesicles (OMV) we identify 297 antibodies and analyse 26 of these for functional potential. These antibodies target lipooligosaccharide (OCL1), the Oxa-23 protein, and the KL49 capsular polysaccharide. We identify a single monoclonal antibody (mAb1416) recognising KL49 capsular polysaccharide to demonstrate prophylactic in vivo protection against a carbapenem resistant A. baumannii lineage associated with neonatal sepsis mortality in Asia. Our end-to-end approach identifies functional monoclonal antibodies with prophylactic potential against major lineages of drug resistant bacteria accounting for phylogenetic diversity and clinical relevance without existing knowledge of a specific target antigen. Such an approach might be scaled for a additional clinically important bacterial pathogens in the post-antimicrobial era.

The Road Ahead: Advancing Antifungal Vaccines and Addressing Fungal Infections in the Post-COVID World.

In impoverished nations, the COVID-19 pandemic has led to a widespread occurrence of deadly fungal diseases like mucormycosis. The limited availability of effective antifungal treatments and the emergence of drug-resistant fungal strains further exacerbate the situation. Factors such as systemic steroid use, intravenous drug misuse, and overutilization of broad-spectrum antimicrobials contribute to the prevalence of hospital-acquired infections caused by drug-resistant fungi. Fungal infections exploit compromised immune status and employ intricate mechanisms to evade immune surveillance. The immune response involves the innate and adaptive immune systems, leading to phagocytic and complement-mediated elimination of fungi. However, resistance to antifungals poses a challenge, highlighting the importance of antifungal prophylaxis and therapeutic vaccination. Understanding the host-fungal immunological interactions and developing vaccines are vital in combating fungal infections. Further research is needed to address the high mortality and morbidity associated with multidrug-resistant fungal pathogens and to develop innovative treatment drugs and vaccines. This review focuses on the global epidemiological burden of fungal infections, host-fungal immunological interactions, recent advancements in vaccine development and the road ahead.

The enduring effects of antimicrobials and lipopolysaccharide on the cellular mechanisms and behaviours associated with neurodegeneration in pubertal male and female CD1 mice

Puberty is a sensitive developmental period during which stressors can cause lasting brain and behavioural deficits. While the acute effects of pubertal lipopolysaccharide (LPS) and antimicrobial (AMNS) treatments are known, their enduring impacts on neurodegeneration-related mechanisms and behaviours remain unclear. This study examined these effects in male and female mice. At five weeks old, mice received 200ul of either broad-spectrum antimicrobials or water through oral gavage twice daily for seven days. At six weeks of age, they received an intraperitoneal injection of either saline or LPS. Four weeks later, adult mice underwent neurodegeneration-related behavioural tests, including the rotarod, forepaw stride length, reversed grid hang, open field, and buried pellet tests. Two days after the final test, brain and ileal samples were collected. Results showed that female mice treated with both AMNS and LPS exhibited deficits in neuromuscular strength, while males treated with LPS alone showed increased anxiety-like behaviours. Males treated with AMNS alone had decreased sigma-1 receptor (S1R) expression in the cornu ammonis 1 (CA1) and dentate gyrus (DG), while females treated with both AMNS and LPS had decreased S1R expression. Additionally, males treated with either LPS or AMNS had lower glial-derived neurotrophic factor receptor alpha-1 (GFRA1) expression in the primary motor cortex (M1) than females. Mice treated with LPS alone had decreased GFRA1 expression in the DG and decreased S1R expression in the secondary motor cortex (M2). These findings suggest that pubertal AMNS and LPS treatments may lead to enduring changes in biomarkers and behaviours related to neurodegeneration.

Discrimination of Common E. coli Strains in Urine by Liquid Chromatography-Ion Mobility-Tandem Mass Spectrometry and Machine Learning.

Accurate identification of bacterial strains in clinical samples is essential to provide an appropriate antibiotherapy to the patient and reduce the prescription of broad-spectrum antimicrobials, leading to antibiotic resistance. In this study, we utilized the combination of a multidimensional analytical technique, liquid chromatography-ion mobility-tandem mass spectrometry (LC-IM-MS/MS), and machine learning to accurately identify and distinguish 11 Escherichia coli (E. coli) strains in artificially contaminated urine samples. Machine learning was utilized on the LC-IM-MS/MS data of the inoculated urine samples to reveal lipid, metabolite, and peptide isomeric biomarkers for the identification of the bacteria strains. Tandem MS and LC separation proved effective in discriminating diagnostic isomers in the negative ion mode, while IM separation was more effective in resolving conformational biomarkers in the positive ion mode. Using hierarchical clustering, the strains are clustered accurately according to their group highlighting the uniqueness of the discriminating biomarkers to the class of each E. coli strain. These results show the great potential of using LC-IM-MS/MS and machine learning for targeted omics applications to diagnose infectious diseases in various environmental and clinical samples accurately.

An In Vitro and In Silico Study of Luteolin-Loaded Zinc Oxide Nanoparticles: Enhancing Bioactivity and Efficacy for Advanced Therapeutic Applications Against Cariogenic Microorganisms.

Introduction Recent studies have explored alternative methods to enhance caries prevention and treatment.Luteolin compound has been noted for its antimicrobial properties, while zinc nanoparticles (Zn NPs) are recognized for their potent antibacterial effects. This study investigates the synthesis, characterization, and antimicrobial efficacy of luteolin-loaded Zn oxide NPs (Luteo-ZnONPs) against cariogenic bacteria. By combining the biofilm-targeting capabilities of luteolin with the antimicrobial properties of Zn NPs, we aim to explore a novel approach for dental caries management. Methods Luteo-ZnONPswere synthesized and characterized using ultraviolet-visible (UV-vis) and Fourier transform infrared (FTIR) spectroscopy, confirming their successful formation and stability. Antimicrobial efficacy was assessed through minimum inhibitory concentration (MIC), demonstrating effectiveness against cariogenic bacteria such asEscherichia coli,Enterococcus faecalis, Pseudomonas aeruginosa, and Streptococcus mutans in different concentrations.The agar well plate method was employed to analyze the growth inhibitory effect of Luteo-ZnONPs (50 and 100µg/ml, respectively). Streptomycin (100µg/ml) was used as apositive control. The results (zone of inhibition (ZOI) in millimeter, mm) were represented as mean± standard deviation.One-way analysis of variance (ANOVA) was employed to detect the significance (p < 0.05) between the groups. Cytotoxicity was analyzed using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assayagainst MG63 cells, and doxorubicin was used as a positive control.Wilcoxon rank test was used for the statistical method. Gyrase Bwas downloaded from Protein Data Bank (PDB id: 6F86) and docked against luteolin using Autodock software (version 4.2).The binding score was presented as kcal/mol in table format. Results Characterization results showed that UV-vis spectroscopy revealed characteristic peaks, indicating the successful synthesis and stability of Luteo-ZnONPs. FTIRspectroscopy confirmed the presence of functional groups from luteolin compound interacting with the Zn NPs. It showed effective inhibition againstE. coli on 50µg/ml as 12.45 mm as ZOI and increased with concentration (100 µg/ml as 17.13 mm).It showed minimal ZOI onE. faecalis(8.12, 12.21 on 50 and 100µg/ml, respectively). The cytotoxicity of Luteo-ZnONPs was lesser than doxorubicin on MG63 cells with statistical high significance (p < 0.0014). These results showed thatLuteo-ZnONPs had effective antimicrobial nature againstEnterococcusfamily. Thus, gyrase BfromE. coliwas selected for the molecular docking analysis. The catalytic tunnel in gyrase B (E. coli, PDB: 6F86), influenced by Luteo-ZnONPs, indicated potential for novel, broad-spectrum antimicrobials via selective inhibition at conserved active sites. Conclusion The agar well plate and MIC confirmed that Luteo-ZnONPs exhibited potent antibacterial activity, especiallyat higher concentrations compared to streptomycin.One- way ANOVA demonstrated significant differences in antibacterial efficacy between treatments, validating its superior performance.Its strong interaction onin silicolevel showed the targeted mechanism of action. Luteo-ZnONPs showed lesser toxicity than doxorubicin on MG63 cells. These findings underscore the potential of its broad spectrum antimicrobial nature paving the way for its development into innovative, nontoxic therapeutic solutions.

Challenges and trends in Gram-negative bacterial infections in critically neonates: A seven-and-a-half-year observational study

Analyze the incidence, risk factors, and fatality rates of bloodstream infections by Gram-negative bacteria (GNB-BSIs) in a Neonatal Intensive Care Unit. This study employs a retrospective cohort design utilizing records of neonates admitted to the Neonatal Intensive Care Unit between January 2015 and June 2022. Among 1,495 neonates, 5.2% developed GNB-BSIs. The average incidence of infection per1,000 patient-days was 2.9. Primary risk factors for infection thatincluded preceeding carbapenem use were significant risk factors (odds ratio=514.4; P<.01) and fourth-generation cephalosporins (odds ratio=66; P<.01). Among the 85 GNB, 75.3% were fermenters, and 24.7% were non-fermenters. Of the isolates, 14.1% produced extended-spectrum beta-lactamase, and 2.3% carbapenem-resistant. Infection correlated with prolonged hospital stays (10-39days) and increased mortality (10%-29.9%). The high incidence of GNB-BSIs was exacerbated by the preceeding use of broad-spectrum antimicrobials, increasing the presence of multidrug-resistant isolates and fatality rates. These findings emphasize the importance of active surveillance.

Efficient removal of sulfamethazine and sulphanilamide using modified amberlite with metal organic framework based copper and cobalt

The presence of antimicrobial sulfa chemicals in water is becoming a more serious problem and action must be taken to create an effective decontamination process for wastewater treatment. In this way, current thinking has focused on removing sulfa drugs as broad-spectrum antimicrobials from water by metal organic framework ((Cu&Co)-benzenetricarboxylate, M−BTC) bound within the amberlite polymer. Here, M(Cu&Co)-BTC is synthesized and incorporated within amberlite polymer in a single step. Moreover, the adsorptive capacities of the various sulfa drugs (sulfamethazine and sulphanilamide) were investigated using M−BTC@amberlite compounds for the first time. The adsorption efficiency of the sulfa drugs was monitored (higher performance for sulfamethazine rather than sulfanilamide), and the adsorption uptake was reached 99 % within about 60 min. The adsorption isotherms were best fitted using the Langmuir and pseudo-second-order model, individually. The greatest potencies for Cu-BTC@amberlite and Co-BTC@amberlite were 205 and 306 mg/g for sulfamethazine and 326 and 488 mg/g for sulfanilamide, separately. By incorporating Co-BTC within amberlite, the absorption capacity of sulfamethazine and sulfanilamide was extended by 1.72 and 1.83 times, respectively, while incorporation of Cu-BTC within amberlite, the adsorption capacity of sulfamethazine and sulfanilamide was extended by 2.56 and 2.73 times, respectively. The attached MOFs with polymer showed very high reusability and their efficacy in uptake of sulfamethazine and sulfanilamide diminished by 14.8–15.9 % and 11.3–12.7 %, separately, after five sequential adsorption cycles. Hence, in agreement with the adsorption result, a conceivable tool is proposed. The sulfa drug adsorption performed on a range of BTC-MOFs with diverse physicochemical properties and point-by-point characterization confirmed that the highest adsorption capacity of MOFs is achieved through bi-bi interaction; H-bonding between NH sites of sulfa drug particles and O sites of carboxyl units within MOFs. In scale-up, M−BTC@amberlite has demonstrated remarkable reusability, which is enticing for potential applications in the adsorption of sulfa drugs from wastewater.

The combination of taurine and cepharanthine as a composite antibacterial agent

The indiscriminate application of diverse broad-spectrum antimicrobials has escalated nosocomial infections into a critical global public health quandary. Currently, traditional antibiotics' efficacy against these infections becomes limited, necessitating a concerted pursuit of more efficacious antimicrobial agents. It is noteworthy that taurine (tau) and cepharanthine (cep) are both biologically active compounds, with taurine constituting a vital nutrient to human health and cepharanthine exhibiting certain antibacterial attributes. However, while cepharanthine displays intrinsic antibacterial features, its monomeric utility is constrained. This study thus investigated the formulation process of merging taurine with cepharanthine, and rigorously assessed the antimicrobial potential of the taurine-cepharanthine complex (denoted as [cep][tau]). The outcomes indicated that this complex, [cep][tau], exhibited antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae, which was on par with the efficacy of cepharanthine on its own. This observation implies that taurine did not antagonize the antibacterial potency of cepharanthine, offering novel avenues for the development of innovative pharmaceuticals targeting hospital-acquired infections.

Low rates of complications and β-lactam resistance in viridans group streptococci bloodstream infection among cancer patients receiving chemotherapy.

Viridans group streptococci (VGS) bloodstream infection (BSI) frequently occurs in cancer patients receiving chemotherapy, and is associated with infective endocarditis (IE) in up to 20% of cases in the general population. In cancer patients receiving chemotherapy with VGS BSI, we aimed to: (i) determine the incidence of infective complications including IE, (ii) assess the utility of echocardiography in this patient population, (iii) determine the duration and type of antimicrobial therapy received for monomicrobial infections, and (iv) determine the evolution of antimicrobial resistance. VGS BSIs (excluding Streptococcus pneumoniae and Streptococcus pseudopneumoniae) in cancer patients receiving chemotherapy were identified from a statewide public pathology database between 2013 and 2022 at our tertiary centre. Medical records were accessed for clinical, microbiological and radiological data. Of 581 patient episodes screened, 183 episodes involving 171 patients met inclusion criteria. Of these, 51% were bone marrow transplantation (BMT) patients, 40% were non-BMT haematology patients, and 8% were solid organ malignancy patients. The median age was 55 years, and 96% were neutropenic at the time of blood culture collection. A transthoracic echocardiogram was performed for 71% of episodes, and one patient met modified Duke's criteria for definite IE, although this diagnosis was not suspected on clinical grounds. Other complications were uncommon. Benzylpenicillin resistance was rare (2.9%) and did not change over time. Most episodes (75%) were treated with piperacillin/tazobactam. For monomicrobial BSIs, the median antibiotic duration was 5 days (IQR 2-7) post-neutropenia resolution. Infective complications and antimicrobial resistance are rare in cancer patients with VGS BSI. This may provide a safe opportunity to limit both investigations (e.g. echocardiogram) and prolonged exposure to broad-spectrum antimicrobials.

Is It Safe To Use Levofloxacin For Treating Resistant Gram-Negatıve Bacterial Infections In The Pediatric Intensive Care Unit?

Objective: Hospital-associated multidrug-resistant infections are currently on the rise. Widespread resistance to antibiotics and limited therapeutic options make it a challenge to eradicate these infections. Therefore, the use of different antibiotics was increased in pediatric intensive care (PICU). Fluoroquinolones belong to a class of broad-spectrum antimicrobials, and their use in children has not been associated with any known clinical complications. In this single-centre retrospective study, we aimed to evaluate the effects, results, and safety of levofloxacin treatment. Materials and Methods: A retrospective, single-center study was conducted at a local tertiary hospital involving 22 patients who were treated with levofloxacin in the PICU from July to December 2021. Levofloxacin was initiated at a dose of 10mg/kg twice daily intravenously for 14-21 days. The study examined and evaluated various factors related to the patients, including their demographic characteristics, medical history, comorbidities, length of stay, need for mechanical ventilation support, laboratory results, type of infection/microorganism, duration of treatment, treatment response and adverse effects, morbidity and mortality. Results: Stenotrophomonas maltophilia13(59.1%) and Pseudomonas aeruginosa9(40.9%) were detected in included patients who had levofloxacin treatment 20(90.9%) of their infections were eradicated. The mortality rate was found to be 13.6%, and 19 patients (86.4%) were successfully treated. No complications related to levofloxacin were detected during the treatment period. The duration of levofloxacin treatment in patients with eradication of gram negative bacteria was 21 days (range: 14-27 days), compared to 12 days (range: 10-14 days) in patients without eradication. This difference was found to be statistically significant (p=0.007). Conclusions: Due to the challenge of eradicating infections and the rising antibiotic resistance, it may be necessary to use antibiotics that are not typically prescribed to children or to develop new drug categories. Therefore, there is a need for more multicenter, randomized controlled, and long-term observational studies to evaluate the efficacy of different and new groups of antibiotics, including levofloxacin, in treating gram-negative bacterias.

Trends in Hospital Antibacterial Consumption in Belgium (2017-2021): Evaluating the Impact of the COVID-19 Pandemic

This study aimed to evaluate the impact of the COVID-19 pandemic on antimicrobial consumption (AMC) in Belgian hospitals from 2017 to 2021, using data from the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) and the Belgian Hospitals Surveillance of Antimicrobial Consumption (BeH-SAC). Antimicrobial volume was quantified in Defined Daily Doses (DDDs), and AMC was expressed in DDDs/1000 inhabitants/day (DIDs), DDDs/1000 patient days and DDDs/1000 admissions. Linear regressions were employed to analyze 5-year trends for the ATC J01 group, at the ATC-3 level and for broad-spectrum antimicrobials. Broad-spectrum antibiotics included combinations of penicillins, incl. beta-lactamase inhibitors (J01CR), second-generation cephalosporins (J01DC), third-generation cephalosporins (J01DD), macrolides, lincosamides and streptogramins (J01F, excluding erythromycin J01FA01), and fluoroquinolones (J01MA). The compound annual growth rate (CAGR) calculated for the years preceding the pandemic was used to forecast 2020 and 2021 AMC, enabling a comparison with the actual use. Hospital AMC measured as DIDs decreased by 12% from 2019 to 2020. In contrast, when expressed as DDDs/1000 patient days and DDDs/1000 admissions, a 5% and 7% increase was observed, respectively. Antibacterials for systemic use (J01) showed a significant decrease over the 5 years only when expressed in DIDs. Notable trends included a negative trend for quinolone antibacterials (J01M) when expressed in the three incidence units, as for amphenicols (J01B) when using hospital denominators only. Positive trends were observed for sulfonamides and trimethoprim (J01E) using hospital denominators and for other beta-lactam antibacterials (J01D) with the ‘patient days’ denominator. While the consumption of all J01 antimicrobial subclasses deviated negatively from predicted use both in 2020 and 2021 when expressed in DIDs, positive deviations were recorded using hospital denominators, except for macrolides (J01F). The use of broad-spectrum antimicrobials showed a notable decrease between 2017 and 2021 when expressed in DIDs. However, when using hospital denominators, the observed use of broad-spectrum antimicrobials exceeded the forecasted values in 2020, to regress below the forecasted levels in 2021 (Figure 1). Contrary to results obtained using the widely applied country’s population as the denominator, a notable surge in AMC, particularly for broad-spectrum antimicrobials, was observed in 2020 when using hospital-specific denominators. This increase coincided with the onset of the COVID-19 crisis. These findings emphasize the need for a national hospital surveillance system that uses denominators that accurately represent the specific population being monitored. Implementing robust hospital-specific surveillance mechanisms would improve the precision of evaluations and facilitate targeted interventions aimed at optimizing antimicrobial utilization.

Understanding the Impact of Narrow Spectrum Beta-Lactam Use on Overall and Broad-Spectrum Antimicrobial Utilization in South Carolina

Background: The standardized antimicrobial administration ratio (SAAR) is a metric utilized to measure antimicrobial use within and between hospitals by comparing observed to predicted antimicrobial days of therapy. However, it remains unknown whether narrow-spectrum beta-lactam (NSBL) use adds to overall antimicrobial utilization or substitutes broad-spectrum agents. This muti-hospital cohort study examined the impact of NSBL use on overall antimicrobial utilization and the correlation between the use of NSBL and various broad-spectrum antimicrobial categories in South Carolina (SC) hospitals. Methods: SAARs were collected from all hospitals in SC that reported antimicrobial use (AU) data to the National Healthcare Safety Network (NHSN) between 2017 and 2021. SAARs collected included: overall SAAR, broad-spectrum agents predominantly used for hospital-onset infections (BSHO), broad-spectrum agents predominantly used for community-acquired infections (BSCA), NSBL, and antibacterial agents posing the highest risk for Clostridioides difficile infection (CDI). Category SAARs were combined to include data in both the adult intensive care unit (ICU) and adult wards using the formula: [(total observed antimicrobial days ICU + total observed antimicrobial days ward) / (total predicted antimicrobial days ICU + total predicted antimicrobial days wards)]. Pearson correlation coefficient (r) was used to examine the correlation between various SAARs categories. Results: A total of 38 hospitals in South Carolina reported AU to NHSN at least during one calendar year during the study period. The use of NSBL agents was negatively correlated with the use of BSHO (r = -0.596, p &lt; 0.001), BSCA (r = -0.543, p &lt; 0.001), and high-risk CDI antibiotics (r = -0.601, p &lt; 0.001). Moreover, the use of NSBL agents did not correlate with the overall SAAR (r = 0.008, p = 0.93), whereas the use of BSHO (r = 0.587, p &lt; 0.001), BSCA (r = 0.494, p &lt; 0.001), and high-risk CDI agents (r = 0.464; p &lt; 0.001) positively correlated with the overall SAAR. Conclusion: In South Carolina hospitals, the use of NSBLs does not contribute to additional antibiotic use overall as it seems to replace broad-spectrum antimicrobials in various categories. By de-escalating from broad-spectrum agents to NSBL agents, one can improve antimicrobial use without negatively impacting the overall SAAR. This observation encourages implementation of antimicrobial stewardship interventions that increase utilization of NSBLs, when appropriate, such as de-escalation of antimicrobial therapy among others without concerns for increasing the SAAR for overall antibiotic use.

Risk Factors and Outcomes of Candida auris in Southeast Michigan

Background: Candida auris is an emerging multidrug resistant fungus that presents a serious global health threat and causes severe infections with a high mortality rate in hospitalized patients with significant underlying comorbidities. We describe the risk factors and clinical outcomes associated with C. auris in Southeast Michigan. Methods: This is a retrospective case series of culture-positive C. auris patients who had contact with our healthcare facility in Detroit from 2021 to 2023. We evaluated demographics, comorbidities, risk factors, and outcomes. A comparative analysis of colonized and infected patients was performed. Results: Forty-eight (81%) colonized and 11 (19%) infected patients were included (Table); 70% were male with median age of 66 years. All variables were comparable between the two groups except chronic kidney disease, which was significantly more prevalent among colonized patients (40% vs 0, p=0.011). All patients had prior exposure to acute care hospital (ACH), 37% to long-term acute care hospital, and 42% to skilled nursing facility within 1 year of diagnosis. Chronic wounds, prior broad-spectrum antibiotic use, and indwelling devices were prevalent in both groups; more than half required mechanical ventilation in the last month, and one third had tracheostomy at the time of C. auris detection. Almost 60% had a prior history of drug-resistant organisms, including multi-drug resistant gram negative (37%) and carbapenem-resistant (20%) organisms. Blood (82%) and wound (18%) were sources of invasive candidiasis. More than half (61%) of the testing was performed at ACH. Nine patients (82%) with invasive disease were treated with echinocandins (88%); among the colonized, two (4%) were treated with echinocandins but had persistent colonization. Thirty-day mortality was not significantly different among the two groups and was nearly 20%. Conclusions: In this large cohort study, a history of healthcare exposure, drug-resistant organisms, use of broad-spectrum antibiotics, indwelling devices, and chronic wounds were common risk factors among C. auris patients. Limiting the use of broad-spectrum antimicrobials and invasive devices, adherence to infection prevention and control practices, and interfacility transfer communication are important mitigating strategies to reduce the incidence and spread of C. auris.

Skull Base Osteomyelitis: A 5-Year Review and Prognostic Outcome in a Single Tertiary Institution.

The primary objective of this study is to review the clinical parameters associated with skull base osteomyelitis (SBO), with a secondary aim of studying their association with patient outcomes 1 and 6 months after treatment initiation. This is a single-center restrospective observational study. The study was conducted from January 2018 to December 2022 at the University Malaya Medical Center in Kuala Lumpur. Patients aged over 15 years with a diagnosis of SBO were included in the study. Clinical parameters, investigations, and follow-up records were recorded. The disease outcomes were analyzed at 1 and 6 months after treatment initiation using multivariable analyses. The study identified 31 patients with SBO, the majority of whom were elderly males with comorbidities such as diabetes and hypertension. Otalgia and otorrhea were the most common symptoms, and computed tomographyscans were used for diagnosis. Pseudomonas aeruginosa was the most commonly identified pathogen, and intravenous broad-spectrum antimicrobials were used to treat all patients. Surgical intervention was required for 25% of patients, and underlying ischemic heart disease, anemia, and single nerve palsy were significantly associated with an unfavorable prognosis. Patients with higher body mass indexand elevated C-reactive protein showed poorer outcomes after 1 and 6 months of treatment, respectively. Early recognition, prompt treatment, better control of comorbidities, nutrition, and monitoring can improve SBO outcomes and reduce complications. Therefore, as the prevalence of SBO increases, diagnostic criteria or management guidelines should be established to guide the best clinical practice.