[Extracorporeal removal of pathogens using a biomimetic adsorber-A new treatment strategy for the intensive care unit : Seraph® 100 Microbind® Affinity Blood Filter and its fields of application]. / Extrakorporale Erregerelimination mit biomimetischem Adsorber ­ eine neue Therapiestrategie für die Intensivmedizin : Seraph® 100 Microbind® Affinity Blood Filter und seine Anwendungsgebiete.

BACKGROUND: In 2019 the World Health Organization (WHO) listed antimicrobial resistance among the top 10 threats to global health. The Seraph® 100 Microbind® Affinity blood filter (Seraph® 100) has been in use since 2019 to eliminate pathogens from the bloodstream in addition to anti-infective pharmacotherapy. It is the first device used to rapidly and efficiently reduce the number of circulating bacteria and viruses. OBJECTIVE: After a background on the concept of extracorporeal pathogen removal in general, this review summarizes the preclinical and clinical data on the Seraph® 100 Affinity Blood Filter. The clinical effect of this treatment and potential therapeutic options are described. METHODS: Structured PubMed review including references published up to February 2024. RESULTS: Case reports, uncontrolled observational studies and data from registries show widespread clinical use of the Seraph® 100 ranging from difficult to treat bacterial (super) infections to viral infections. The treatment can be done as stand-alone hemoperfusion or in combination with all forms of kidney replacement therapy as well as in extracorporeal membrane oxygenation. CONCLUSION: The use of the Seraph® 100 varies in terms of duration, concomitant therapy and clinical settings. Due to the absence of prospective controlled trials the clinical effect cannot be properly evaluated.

Multiplexing Imaging of Closely Located Single-Nucleotide Mutations in Single Cells via Encoded in situ PCR.

Mutation accumulation in RNAs results in closely located single-nucleotide mutations (SNMs), which is highly associated with the drug resistance of pathogens. Imaging of SNMs in single cells has significance for understanding the heterogeneity of RNAs that are related to drug resistance, but the direct "see" closely located SNMs remains challenging. Herein, we designed an encoded ligation-mediated in situ polymerase chain reaction method (termed enPCR), which enabled the visualization of multiple closely located SNMs in bacterial RNAs. Unlike conventional ligation-based probes that can only discriminate a single SNM, this method can simultaneously image different SNMs at closely located sites with single-cell resolution using modular anchoring probes and encoded PCR primers. We tested the capacity of the method to detect closely located SNMs related to quinolone resistance in the gyrA gene of Salmonella enterica (S. enterica), and found that the simultaneous detection of the closely located SNMs can more precisely indicate the resistance of the S. enterica to quinolone compared to the detection of one SNM. The multiplexing imaging assay for SNMs can serve to reveal the relationship between complex cellular genotypes and phenotypes.

Acetabular Screws With Cement Augment for Tibial Plateau Defects in Dynamic Spacer Implantation: A Case of Recalcitrant Native Knee Septic Arthritis.

Treating tibial bone defects in the setting of recalcitrant native knee arthritis presents a challenging biomechanical problem for orthopaedic surgeons. A dynamic antibiotic spacer offers an effective solution to preserve patient function and manage infection. However, severe bone loss may compromise the fixation of the dynamic spacer. We describe the application of acetabular screws as rebar in a case of an Anderson Orthopaedic Research Institute type 3 defect of the medial tibial plateau. Additionally, we outline a facile method for fabricating the tibial stem component to ensure optimal fit within the intramedullary canal. Short-term follow-up (8 months) indicates successful fixation of the tibial component, absence of knee pain, and a knee range of motion up to 100 degrees.

Exploring the impact of rotavirus vaccination on antibiotic prescription and resistance: A comprehensive systematic review.

BACKGROUND: Rotavirus is a highly contagious virus responsible for a significant burden of acute gastroenteritis, particularly among infants and young children worldwide, however, vaccination against this viral agent is available. Several studies have hypothesized that rotavirus vaccination has been linked to lower rates of antibiotic resistance. AIM: To assess the relationship between rotavirus vaccination and antibiotic resistance. METHODS: The present systematic review was tailored based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Several electronic databases (PubMed/MEDLINE, Scopus and Web of Science) were searched independently by two investigators in order to retrieve relevant publications published until April 2023 that investigated the aforementioned research question. RESULTS: The comprehensive database search identified a total of 91 records. After the duplicates were removed (n = 75), we screened the titles and abstracts of 16 potentially eligible publications. After the irrelevant records were excluded (n = 5), we screened the full texts of 11 manuscripts. Finally, 5 studies were entered into the qualitative and quantitative analysis. CONCLUSION: In conclusion, all the studies support the idea that vaccinations can reduce the need for antibiotic prescriptions which could potentially contribute to mitigating antibiotic resistance. However, to fully comprehend the mechanisms of antibiotic resistance, enhance treatment guidelines, and consider diverse demographic situations, further research is necessary to use evidence-based strategies to fight antibiotic misuse and resistance.

Neutropenia Induced by Ceftriaxone and Meropenem.

Neutropenia by non-chemotherapy drugs is an extremely rare idiosyncratic life-threatening drug reaction. Ceftriaxone and meropenem are widely used broad-spectrum antibiotics and are generally safe and well tolerated. The authors present a case of neutropenia induced by ceftriaxone and meropenem in an adult patient. The resolution of neutropenia occurred within 48 hours of ceftriaxone and meropenem being discontinued. Although antibiotic-induced neutropenia is uncommon, clinicians should be mindful of this adverse drug effect because of its potential development of severe neutropenia, septicaemia, septic shock, deep-seated infections and even death. Therefore, neutropenic sepsis treatment should be initiated without delay, particularly if the patient becomes septic and febrile. Granulocyte-colony stimulation factor (G-CSF) may be administered to facilitate the recovery process with daily monitoring of neutrophil count. Mortalities from antibiotic-induced neutropenia remain rare, with a range of 2.5-5%. LEARNING POINTS: Beta-lactam antibiotics and cabapenem are widely prescribed antibiotics for the treatment of various infections, but they can uncommonly cause neutropenia as adverse effects.Severe neutropenia may lead to severe life-threatening sepsis, shock and even death.Drug-induced neutropenia typically improves with the cessation of offending agents, supportive treatment and granulocyte-colony stimulating factor (G-CSF) which may shorten the recovery time.

Molecular Characterization of Antimicrobial Resistance and Virulence Genotyping among Helicobacter pylori-Positive Dyspeptic Patients in North Iran.

BACKGROUND: Iran has a relatively high prevalence of H. pylori, which correlates with high-risk areas for gastric cancer worldwide. METHODS: Our study aimed to investigate the underlying genetic mechanisms associated with resistance to metronidazole (frxA, rdxA), clarithromycin (23S rRNA), tetracycline (16S rRNA), and fluoroquinolone (gyrA) in H. pylori-positive dyspeptic patients using PCR and sequencing. We further examined the potential correlation between resistance profiles and various virulence genotypes. RESULTS: The rates of genetic mutations associated with resistance to metronidazole, fluoroquinolone, clarithromycin, and tetracycline were found to be 68%, 32.1%, 28.4%, and 11.1%, respectively. Well-documented multiple antibiotic resistance mutations were detected, such as rdxA and frxA (with missense and frameshift alterations), gyrA (Asp91, Asn87), 23S rRNA (A2142G, A2143G), and 16S rRNA (triple-base-pair substitutions AGA926-928→TTC). The cagA+ and vacA s1/m1 types were the predominant genotypes in our study. With the exception of metronidazole and tetracycline, no significant correlation was observed between the cagA+ and cagL+ genotypes and resistance-associated mutations. CONCLUSION: The prevalence of antibiotic resistance-associated mutations in H. pylori was remarkably high in this region, particularly to metronidazole, ciprofloxacin, and clarithromycin. By conducting a simultaneous screening of virulence and resistance genotypes, clinicians can make informed decisions regarding the appropriate therapeutic regimen to prevent the escalation of antibiotic resistance against H. pylori infection in this specific geographical location.

Machine learning-based classification reveals distinct clusters of non-coding genomic allelic variations associated with Erm-mediated antibiotic resistance.

The erythromycin resistance RNA methyltransferase (erm) confers cross-resistance to all therapeutically important macrolides, lincosamides, and streptogramins (MLS phenotype). The expression of erm is often induced by the macrolide-mediated ribosome stalling in the upstream co-transcribed leader sequence, thereby triggering a conformational switch of the intergenic RNA hairpins to allow the translational initiation of erm. We investigated the evolutionary emergence of the upstream erm regulatory elements and the impact of allelic variation on erm expression and the MLS phenotype. Through systematic profiling of the upstream regulatory sequences across all known erm operons, we observed that specific erm subfamilies, such as ermB and ermC, have independently evolved distinct configurations of small upstream ORFs and palindromic repeats. A population-wide genomic analysis of the upstream ermB regions revealed substantial non-random allelic variation at numerous positions. Utilizing machine learning-based classification coupled with RNA structure modeling, we found that many alleles cooperatively influence the stability of alternative RNA hairpin structures formed by the palindromic repeats, which, in turn, affects the inducibility of ermB expression and MLS phenotypes. Subsequent experimental validation of 11 randomly selected variants demonstrated an impressive 91% accuracy in predicting MLS phenotypes. Furthermore, we uncovered a mixed distribution of MLS-sensitive and MLS-resistant ermB loci within the evolutionary tree, indicating repeated and independent evolution of MLS resistance. Taken together, this study not only elucidates the evolutionary processes driving the emergence and development of MLS resistance but also highlights the potential of using non-coding genomic allele data to predict antibiotic resistance phenotypes. IMPORTANCE: Antibiotic resistance (AR) poses a global health threat as the efficacy of available antibiotics has rapidly eroded due to the widespread transmission of AR genes. Using Erm-dependent MLS resistance as a model, this study highlights the significance of non-coding genomic allelic variations. Through a comprehensive analysis of upstream regulatory elements within the erm family, we elucidated the evolutionary emergence and development of AR mechanisms. Leveraging population-wide machine learning (ML)-based genomic analysis, we transformed substantial non-random allelic variations into discernible clusters of elements, enabling precise prediction of MLS phenotypes from non-coding regions. These findings offer deeper insight into AR evolution and demonstrate the potential of harnessing non-coding genomic allele data for accurately predicting AR phenotypes.

Correlation analysis of whole genome sequencing of a pathogenic Escherichia coli strain of Inner Mongolian origin.

Anal swabs of 1-month-old Holstein calves with diarrhea were collected from an intensive cattle farm, and a highly pathogenic Escherichia coli strain was obtained by isolation and purification. To study the virulence and resistance genes of pathogenic E. coli that cause diarrhea in calves, a strain of E. coli E12 isolated from calf diarrhea samples was used as experimental material in this experiment, and the virulence of the E12 strain were identified by the mouse infection test, and the whole genome map of the E12 strain were obtained by whole-genome sequencing and analyzed for genome characterization. The results showed that the lethality of strain E12 was 100%, the total length of E12-encoded genes was 4,294,530 bp, Cluster of Orthologous Groups of proteins (COG) annotated to 4,194 functional genes, and the virulence genes of sequenced strain E12 were compared with the virulence genes of sequenced strain E12 from the Virulence Factors of Pathogenic Bacteria (VFDB), which contained a total of 366 virulence genes in sequenced strain E12. The analysis of virulence genes of E12 revealed a total of 52 virulence genes in the iron transferrin system, 56 virulence genes in the secretory system, 41 virulence genes in bacterial toxins, and a total of 217 virulence genes in the Adhesin and Invasins group. The antibiotic resistance genes of sequenced strain E12 were identified through the Antibiotic Resistance Genes Database (ARDB) and Comprehensive Antibiotic Research Database, and it was found that its chromosome and plasmid included a total of 127 antibiotic resistance genes in four classes, and that E12 carried 71 genes related to the antibiotic efflux pumps, 36 genes related to antibiotic inactivation, and 14 antibiotic target alteration and reduced penetration into antibiotics, and 6 antibiotic resistance genes, and the resistance phenotypes were consistent with the genotypes. The pathogenic E. coli that causes diarrhea in calves on this ranch contains a large number of virulence and resistance genes. The results provide a theoretical basis for the prevention and treatment of diarrhea and other diseases caused by E. coli disease.

Metagenomic analysis reveals the mechanisms of biochar supported nano zero-valent iron in two-phase anaerobic digestion of food waste: microbial community, CAZmey, functional genes and antibiotic resistance genes.

The mechanisms of biochar supported nano zero-valent iron (BC/nZVI) on two-phase anaerobic digestion of food waste were investigated. Results indicated that the performance of both acidogenic phase and methanogenic phase was effectively facilitated. BC/nZVI with the amount of 120 mg/L increased methane production by 32.21%. In addition, BC/nZVI facilitated direct interspecies electron transfer (DIET) between Geobacter and methanogens. Further analysis showed that BC/nZVI increased the abundance of most CAZymes in acidogenic phase. The study also found that BC/nZVI had positive effects on metabolic pathways and related functional genes. The abundances of acdA and ackA in acidogenic phase were increased by 151.75% and 36.26%, respectively, and the abundances of pilA and TorZ associated with DIET were also increased. Furthermore, BC/nZVI mainly removed IMP-12, CAU-1, cmeB, ErmR, MexW, ErmG, Bla2, vgaD, MuxA, and cpxA from this system, and reduced the antibiotic resistance genes for antibiotic inactivation resistance mechanisms.

Isolation and Characterization of Bacteriophages against E.coli Urinary Tract Infection and Evaluating their Anti-biofilm Activity and Antibiotic Synergy.

Urinary tract infections (UTIs) by Uropathogenic Escherichia coli (UPEC) are a significant health concern, especially due to the increasing prevalence of antibiotic resistance. This study focuses on isolating and characterizing bacteriophages specific to UPEC strains isolated from UTI samples. The isolated phages were assessed for their ability to target and lyse UPEC in vitro, focusing on their efficacy in disrupting biofilms, a key virulence factor contributing to UTI recurrence and antibiotic resistance. The morphological structure observed by TEM belongs to Myoviridae, the phage exhibited icosahedral symmetry with a long non-constricting tail, the approximate measurement of the phage head was 39nm in diameter, and the phage tail was 105.317nm in length. One-step growth experiments showed that the latent period was approximately 20 min, followed by a rise period of 40 min, and a growth plateau was reached within 20 min and the burst size observed was 26 phages/ infected bacterial cells. These phages were capable of killing cells within the biofilms, leading to a reduction in living cell counts after a single treatment. This study highlights the potential of phages to play a significant role in disrupting, inactivating, and destroying Uropathogenic Escherichia coli (UPEC) biofilms. Such findings could be instrumental in developing treatment strategies that complement antibiotics and disinfectants. The phage-antibiotic synergistic activity was compared to have the possibility to facilitate the advancement of focused and enduring alternatives to traditional antibiotic therapies for UTIs.

Current state and novel outlook on prevention and treatment of rising antibiotic resistance in urinary tract infections.

Antibiotic-resistant bacteria are currently an important public health concern posing a serious threat due to their resistance to the current arsenal of antibiotics. Uropathogens Escherichia coli (UPEC), Proteus mirabilis, Klebsiella pneumoniae and Enterococcus faecalis, antibiotic-resistant gram-negative bacteria, cause serious cases of prolonged UTIs, increasing healthcare costs and potentially even leading to the death of an affected patient. This review discusses current knowledge about the increasing resistance to currently recommended antibiotics for UTI therapy, as well as novel therapeutic options. Traditional antibiotics are still a part of the therapy guidelines for UTIs, although they are often not effective and have serious side effects. Hence, novel drugs are being developed, such as combinations of ß-lactam antibiotics with cephalosporins and carbapenems. Siderophoric cephalosporins, such as cefiderocol, have shown potential in the treatment of individuals with significant gram-negative bacterial infections, as well as aminoglycosides, fluoroquinolones and tetracyclines that are also undergoing clinical trials. The use of cranberry and probiotics is another potential curative and preventive method that has shown antimicrobial and anti-inflammatory effects. However, further studies are needed to assess the efficacy and safety of probiotics containing cranberry extract for UTI prevention and treatment. An emerging novel approach for UTI treatment is the use of immuno-prophylactic vaccines, as well as different nanotechnology solutions such as nanoparticles (Nanoparticles). Nanoparticles have the potential to be used as delivery systems for drugs to specific targets. Furthermore, nanotechnology could enable the development of nano antibiotics with improved features by the application of different Nanoparticles in their structure, such as gold and copper Nanoparticles. However, further high-quality research is required for the synthesis and testing of these novel molecules, such as safety evaluation and pharmacovigilance.

Feasibility of Narrow-Spectrum Antimicrobial Agents for Post-Operative Intra-Abdominal Infections After Gastrectomy.

Introduction: Recently, antimicrobial resistance has received considerable attention. Broad-spectrum antimicrobial agents are recommended as the initial therapy for post-operative intra-abdominal infections. However, at our institution, we have adopted a tactic of initially treating post-operative intra-abdominal complications with relatively narrow-spectrum antimicrobial agents, such as second-generation cephalosporins. In the present study, we aimed to retrospectively analyze the use of antimicrobial agents and the resulting treatment outcomes in patients with intra-abdominal complications after gastrectomy at our facility. Methods: We conducted a retrospective observational study of patients treated with antibiotic agents for intra-abdominal infectious complications after gastrectomy between 2011 and 2021. We determined the proportion of "initial treatment failures" associated with the initial administration of antibiotic agents for post-operative intra-abdominal complications. Results: Post-operative intra-abdominal infections were observed in 29 patients. Broad-spectrum antimicrobial agents were not administered. We successfully treated 19 patients. Initial treatment failure was observed in 10 patients, of whom five experienced failure due to bacterial resistance to the initial antimicrobial agent. All 10 patients who experienced initial treatment failure were discharged after drainage procedures or other treatments. There were no deaths due to post-operative complications. Cefmetazole was used as the initial antimicrobial agent in 27 of the 29 patients. Conclusions: Considering that all patients with post-gastrectomy intra-abdominal infections were successfully treated using relatively narrow-spectrum antimicrobial agents, and initial treatment failure due to antimicrobial-resistant pathogens was 17.2%, the use of narrow-range antimicrobial agents for intra-abdominal infections after gastrectomy can be deemed appropriate.

A survey of patient practices regarding leftover antibiotics reveals a potential source of antibiotic overuse.

Taking leftover prescribed antibiotics without consulting a healthcare professional is problematic for the efficacy, safety, and antibiotic stewardship. We conducted a cross-sectional survey of adult patients in English and Spanish between January 2020 and June 2021 in six safety-net primary care clinics and two private emergency departments. We assessed the reasons for stopping prescribed antibiotics early and what was done with the leftover antibiotics. Additionally, we determined 1) prior leftover antibiotic use, 2) intention for future use of leftover antibiotics, and 3) sociodemographic factors. Of 564 survey respondents (median age of 51), 45% (251/564) reported a history of stopping antibiotics early, with 171/409 (42%) from safety net and 80/155 (52%) from the private clinics. The most common reason for stopping prescribed antibiotics early was "because you felt better" (194/251, 77%). Among survey participants, prior use of leftover antibiotics was reported by 149/564 (26%) and intention for future use of leftover antibiotics was reported by 284/564 (51%). In addition, higher education was associated with a higher likelihood of prior leftover use. Intention for future use of leftover antibiotics was more likely for those with transportation or language barriers to medical care and less likely for respondents with private insurance. Stopping prescribed antibiotics early was mostly ascribed to feeling better, and saving remaining antibiotics for future use was commonly reported. To curb nonprescription antibiotic use, all facets of the leftover antibiotic use continuum, from overprescribing to hoarding, need to be addressed.

A QSPR analysis and curvilinear regression models for various degree-based topological indices: Quinolone antibiotics.

Topological indices play an essential role in defining a chemical compound numerically and are widely used in QSPR/QSAR analysis. Using this analysis, physicochemical properties of the compounds and the topological indices are studied. Quinolones are synthetic antibiotics employed for treating the diseases caused by bacteria. Across the years, Quinolones have shifted its position from minor drug to a very significant drug to treat the infections caused by bacteria and in the urinary tract. A study is carried out on various Quinolone antibiotic drugs by computing topological indices through QSPR analysis. Curvilinear regression models such as linear, quadratic and cubic regression models are determined for all topological indices. These regression models are depicted graphically by extending for fourth degree and fifth degree models for significant topological indices with its corresponding physical property showing the variation between each model. Various studies have been carried out using linear regression models while this work is extended for curvilinear regression models using a novel concept of finding minimal R M S E . R M S E is a significant measure to find potential predictive index that fits QSAR/QSPR analysis. The goal of R M S E lies in predicting a certain property of a chemical compound based on the molecular structure.

A Difficult Differential Diagnosis in New Neck Masses: Retropharyngeal Abscess or Malignancy?

Retropharyngeal abscesses (RPAs) are rare in the adult population and rarer without an inciting event or comorbidity such as recent oral surgery, neck infection, or pharyngeal trauma. The definitive treatment is incision and drainage of the abscess. Clinical researchers have recently questioned whether invasive surgical intervention is necessary and posed the question of what role antibiotics play in management. Sequelae of RPAs are severe and include rupture of the abscess, erosion of the carotid artery, thrombophlebitis, and most seriously, airway compromise. We present a case where an atypical presentation of an RPA caused a disagreement among specialists, and the debate of whether the described case represented an abscess or malignancy caused a delay in diagnosis and treatment for the patient. Only after invasive and emergent surgical intervention was a final diagnosis able to be made. This case demonstrates the need for more research and official guidance on the management of new neck masses to hasten diagnosis and prevent devastating outcomes.

Incidence of Infection Following Local Anesthetic Transperineal Prostate Biopsy: A Single-Centre Experience.

Background Local anesthetic transperineal prostate biopsy (LATP) is a widely used diagnostic procedure for prostate cancer. As a diagnostic procedure, it should carry minimal risk. However, morbidity resulting from prostate biopsy is frequent. Prostate biopsy, like any other intervention, carries a significant risk of various infections, ranging from urinary tract infections (UTIs) to potentially life-threatening conditions like sepsis. Aim This study examined the rate of infections following a prostate biopsy at a single center and sought to identify risk factors that could increase the likelihood of developing an infection. Methods A retrospective review was conducted on all 168 patients who underwent LATP biopsy between 01/04/2022 and 01/04/2023. Data were collected from the Clinical Record and Reporting System (CRRS). Patient characteristics, including age, prostate-specific antigen (PSA) levels, prostate volume, the main indication for the biopsy, number of cores taken, antibiotic prophylaxis, and comorbidities were analyzed. The inclusion criteria encompassed all patients receiving this procedure within the specified timeframe, without restrictions on age, underlying health conditions, or medical history. No exclusion criteria were applied, aiming to comprehensively analyze and capture the full spectrum of patient outcomes and characteristics associated with these biopsies during the study period. Results In terms of socio-demographics, all patients were male with an average age (mean) of 65.5 years, a mean PSA level of 13.9 ng/dL, and an average prostate volume of 66.1 mL. On average, 23.2 biopsy cores were taken. All patients received antibiotic prophylaxis, mainly ciprofloxacin. Despite this, 1.78% of patients (n=3) developed post-biopsy infections. Two of these patients had diabetes mellitus, and two had a large prostate volume of 95 mL.

A computational workflow to determine drug candidates alternative to aminoglycosides targeting the decoding center of E. coli ribosome.

The global antibiotic resistance problem necessitates fast and effective approaches to finding novel inhibitors to treat bacterial infections. In this study, we propose a computational workflow to identify plausible high-affinity compounds from FDA-approved, investigational, and experimental libraries for the decoding center on the small subunit 30S of the E. coli ribosome. The workflow basically consists of two molecular docking calculations on the intact 30S, followed by molecular dynamics (MD) simulations coupled with MM-GBSA calculations on a truncated ribosome structure. The parameters used in the molecular docking suits, Glide and AutoDock Vina, as well as in the MD simulations with Desmond were carefully adjusted to obtain expected interactions for the ligand-rRNA complexes. A filtering procedure was followed, considering a fingerprint based on aminoglycoside's binding site on the 30S to obtain seven hit compounds either with different clinical usages or aminoglycoside derivatives under investigation, suggested for in vitro studies. The detailed workflow developed in this study promises an effective and fast approach for the estimation of binding free energies of large protein-RNA and ligand complexes.

Antibiotic usage patterns in COVID-19 patients in five tertiary hospitals from Bangladesh: A countrywide picture.

Objectives: Irrational and injudicious use of antibiotics in COVID-19 patients could be detrimental in a tropical country with a weak antibiotic stewardship policy such as Bangladesh. This study aimed to focus on the antibiotic usage patterns in COVID-19 patients in Bangladesh. Methods: This prospective observational study was performed from July 2020 to June 2021 in five tertiary hospitals in Bangladesh. Data on demographic profile, disease severity, and antibiotic usage were collected directly from the patients' hospital documents. Results: A total of 3486 (94.4%) patients were treated with at least one antibiotic; 3261 (93.6%) patients received a single antibiotic, and 225 (6.5%) received multiple antibiotics. The most used antibiotics were ceftriaxone (37.3%), co-amoxiclav (26.3%), azithromycin (10.6%), and meropenem (10.3%). According to the World Health Organization AWaRe categorization, most (2260; 69.6%) of the antibiotics prescribed in this study belonged to the "Watch" group. Culture and sensitivity reports were available in 111 cases from one center. Only 18.9% of the patients were found to be co-infected with multi-drug-resistant bacteria (52.4% yield from sputum, 28.6% from urine, and 14.3% from blood). Conclusions: Strict antibiotic prescribing policy and antibiotic stewardship should be implemented immediately to limit the future threat of antimicrobial resistance in countries such as Bangladesh.

Assay Interference Causing Persistently Elevated Vancomycin Levels Leading to Treatment Failure and Fatal Outcome.

In patients receiving vancomycin therapy, serum drug levels are routinely monitored to ensure therapeutic dosing and minimize toxicity. In rare cases, vancomycin levels may be falsely or persistently elevated without any apparent cause. In this case report, we explore a rare case of persistently elevated vancomycin levels despite discontinuation of the drug for days.  This is a case of a 69-year-old female admitted for altered mental status secondary to sepsis from leg cellulitis. Antibiotic therapy included vancomycin. To ensure proper dosing, vancomycin trough levels were collected before the fourth dose, and the result showed a high value of 39 ug/ml. Vancomycin doses were adjusted as per the Bayesian dosing software, and the same remained to be in supratherapeutic levels. The patient eventually deteriorated, and due to persistently high vancomycin levels, the antibiotic regimen was switched to a different antibiotic. Despite normal renal functions, the vancomycin levels remained high, between 27 ug/ml and 32 ug/ml, even in the absence of any further doses. Subsequently, vancomycin serum concentration was determined by another method using high-performance liquid chromatography (HPLC). Blood cultures grew both coagulase-negative Staphylococcus aureus and Achromobacter xylosoxidans. Vancomycin levels remained high a week after discontinuation of the drug. Vancomycin by HPLC assay eventually showed that vancomycin was undetectable in the blood, but, unfortunately, the results came at a time when the patient had already expired. In conclusion, clinicians should maintain a high level of suspicion if persistently higher vancomycin levels cannot be accounted for by renal function or other causes. In patients with persistently high vancomycin levels who continue to clinically deteriorate, it is crucial to consider that assay interference can result in inaccurately elevated vancomycin levels.