Selective Antibiotics Research Articles

P-1109. A phase 2, randomized, double-blind study of ibezapolstat compared with vancomycin for the treatment of Clostridioides difficile infection: clinical and microbiome evaluation

Abstract Background Ibezapolstat (IBZ) is Gram-positive selective spectrum antibiotic that inhibits the bacterial DNA polymerase IIIC currently in clinical trial development for the treatment of C. difficile infection (CDI) in adults. In the open-label, non-comparative, phase 2a study, 10 of 10 IBZ-treated CDI patients experienced clinical cure. The purpose of the phase 2b CDI study was to assess the safety, efficacy, and microbiome change of IBZ versus vancomycin (VAN). Methods Phase 2b (ClinicalTrials.gov, number NCT04247542) was a randomized, double-blind, active-comparator study. Participants with signs and symptoms of CDI and a positive enzyme immunoassay toxin test result were recruited from 12 centers in the USA and randomly assigned (1:1) to receive oral IBZ 450 mg every 12 h or oral VAN 125 mg every 6 h for 10 days. Stool was collected daily for microbiome evaluations. The primary endpoints were clinical cure at the end of therapy visit and safety. Secondary endpoints included microbiologic and microbiome evaluations. Results Thirty patients were recruited and were assessed in the per protocol analysis. (IBZ: n=16; VAN n=14). Fifteen of 16 (93.8%) patients given IBZ had a clinical cure versus 14 of 14 (100%) patients given VAN. IBZ and VAN were well tolerated with no serious drug-related events. C. difficile was eradicated from all stool samples after day 3 of treatment for IBZ-treated patients while three VAN-treated patients had C. difficile growth after day 3. IBZ demonstrated consistent preservation of key Bacillota species while significant decreases were observed in VAN-treated patients. CDI recurrence occurred in two patients given VAN and no patients given IBZ. Conclusion In the phase 2b study, IBZ had a clinically comparable cure rate and safety profile to oral vancomycin. Favorable microbiologic and microbiome findings were observed with IBZ-treated patients along with a lower rate of CDI recurrence. These results warrant further development in phase 3 trials. Disclosures Michael Silverman, MD, Acurx: Advisor/Consultant Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support

P-65. Results from A Phase 2 Clinical Trial for Treatment of Bone And Joint Infections with Afabicin, A First-in-Class Selective Anti-Staphylococcal Antibiotic

Abstract Background Staphylococci are the most common causative pathogens in bone and joint infections (BJI). Treatment for BJI is a major clinical challenge, with recurrent and persistent infections occurring in 40% of patients. Afabicin is the most advanced FabI inhibitor in clinical development and has the potential to be the first microbiome-sparing anti-staphylococcal antibiotic. Currently, a Phase 2 trial in BJI (NCT03723551) is enrolling patients to be treated for 3-6 weeks with afabicin or standard of care (SoC). Results of the first cohort in this study (2-3 weeks treatment) are presented here Methods In an ongoing multicenter, open-label, Phase 2 study, the safety, tolerability, and efficacy of afabicin was compared to those of SoC, in the treatment of patients with BJI. Patients with osteomyelitis, septic arthritis, or prosthetic joint infections were randomized (5 afabicin: 1 SoC) to receive IV and oral treatment for 14 to 21 days. Afabicin treatment (55 mg IV/ 80 mg PO BID) was compared to a pre-defined SoC treatment. Results Twenty patients were included in microbiological intent-to-treat (mITT) population and were treated for up to 21 days with afabicin or SoC (17 afabicin and 3 SoC). The mean treatment duration was 20.1 days for afabicin and 19.7 days for SoC. Overall, osteomyelitis was the most common diagnosis (85%). The most frequent baseline pathogen was Staphylococcus aureus (19 patients), and 18 patients had methicillin-sensitive S. aureus. All 20 patients were treatment responders at End of Treatment (EoT) visit. The clinical response at 4 weeks post EoT was 13 of 15 patients in the afabicin arm, consistent with patient exposure being above PK/PD targets derived from non-clinical modeling. All 3 patients in the SOC arm achieved clinical response at 4 weeks post EoT. At 12 weeks post EoT, the clinical response rate was 13 of 15 patients in the afabicin arm and 2 of 3 patients in the SoC arm. A similar safety profile was observed in the afabicin arm versus SoC arm. Conclusion The clinical response rate and safety profile of 2-3 weeks treatment of staphylococcal BJI with afabicin was comparable to SoC. These data support exploring longer durations of treatment in the study. Additionally, the impact of Afabicin on BJI patient’s gut microbiota will be explored. Disclosures Alireza Shamaei Tousi, PhD, Debiopharm International: Salary Moritz Marquardt, n/a, Debiopharm International: Salary Annick Menetrey, n/a, Debiopharm International: Salary Justyna Nowakowska, n/a, Debiopharm International: Salary Justine Dao, n/a, Debiopharm International: Salary David Cameron, PhD, Debiopharm International S.A.: Salary Charlotte Catala-Goldschmidt, n/a, Debiopharm International: Salary Ricardo Chaves, n/a, Debiopharm International S.A.: Salary

In vitro evolution of ciprofloxacin resistance in Neisseria commensals and derived mutation population dynamics in natural Neisseria populations.

Commensal Neisseria are members of a healthy human oropharyngeal microbiome; however, they also serve as a reservoir of antimicrobial resistance for their pathogenic relatives. Despite their known importance as sources of novel genetic variation for pathogens, we still do not understand the full suite of resistance mutations commensal species can harbor. Here, we use in vitro selection to assess the mutations that emerge in response to ciprofloxacin selection in commensal Neisseria by passaging 4 replicates of 4 different species in the presence of a selective antibiotic gradient for 20 days; then categorized derived mutations with whole genome sequencing. 10/16 selected cells lines across the 4 species evolved ciprofloxacin resistance (≥ 1 ug/ml); with resistance-contributing mutations primarily emerging in DNA gyrase subunit A and B (gyrA and gyrB), topoisomerase IV subunits C and E (parC and parE), and the multiple transferable efflux pump repressor (mtrR). Of note, these derived mutations appeared in the same loci responsible for ciprofloxacin reduced susceptibility in the pathogenic Neisseria, suggesting conserved mechanisms of resistance across the genus. Additionally, we tested for zoliflodacin cross-resistance in evolved strain lines and found 6 lineages with elevated zoliflodacin minimum inhibitory concentrations. Finally, to interrogate the likelihood of experimentally derived mutations emerging and contributing to resistance in natural Neisseria, we used a population-based approach and identified GyrA 91I as a substitution circulating within commensal Neisseria populations and ParC 85C in a single gonococcal isolate. A small cluster of gonococcal isolates shared commensal alleles at parE, suggesting recent cross-species recombination events.

Outer membrane lipoproteins: late to the party, but the center of attention.

An outer membrane (OM) is the hallmark feature that is often used to distinguish "Gram-negative" bacteria. Our understanding of how the OM is built rests largely on studies of Escherichia coli. In that organism-and seemingly in all species of the Proteobacterial phyla-the essential pathways that assemble the OM each rely on one or more lipoproteins that have been trafficked to the OM. Hence, the lipoprotein trafficking pathway appeared to be foundational for the ability of these bacteria to build their OM. However, such a notion now appears to be misguided. New phylogenetic analyses now show us that lipoprotein trafficking was likely the very last of the essential OM assembly systems to have evolved. The emergence of lipoprotein trafficking must have been a powerful innovation for the ancestors of Proteobacteria, given how it assumed such a central place in OM biogenesis. In this minireview, we broadly discuss the biosynthesis and trafficking of lipoproteins and ponder why the newest OM assembly system (lipoprotein trafficking) has become so key to building the Proteobacterial OM. We examine the diversity among lipoprotein trafficking systems, noting uniting commonalities and highlighting key differences. Current novel antibiotic development is targeted against a small subset of Proteobacterial species that cause severe human diseases; several inhibitors of lipoprotein biosynthesis and OM trafficking have been recently reported that may become new antibiotics. Understanding the diversity in lipoprotein trafficking may yield selective new antibiotics that preferentially kill important human pathogens while sparing species of normal healthy flora.

Succinate-producing microbiota drives tuft cell hyperplasia to protect against Clostridioides difficile.

The role of microbes and their metabolites in modulating tuft cell (TC) dynamics in the large intestine and the relevance of this pathway to infections is unknown. Here, we uncover that microbiome-driven colonic TC hyperplasia protects against Clostridioides difficile infection. Using selective antibiotics, we demonstrate increased type 2 cytokines and TC hyperplasia in the colon but not in the ileum. We demonstrate the causal role of the microbiome in modulating this phenotype using fecal matter transplantation and administration of consortia of succinate-producing bacteria. Administration of succinate production-deficient microbes shows a reduced response in a Pou2f3-dependent manner despite similar intestinal colonization. Finally, antibiotic-treated mice prophylactically administered with succinate-producing bacteria show increased protection against C. difficile-induced morbidity and mortality. This effect is nullified in Pou2f3-/- mice, confirming that the protection occurs via the TC pathway. We propose that activation of TCs by the microbiota in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by pathogens.

Investigating the feasibility and potential of combining industry AMR monitoring systems: a comparison with WHO GLASS.

Efforts to estimate the global burden of antimicrobial resistance (AMR) have highlighted gaps in existing surveillance systems. Data gathered from hospital networks globally by pharmaceutical industries to monitor antibiotic efficacy in different bacteria represent an underused source of information to complete our knowledge of AMR burden.. We analysed available industry monitoring systems to assess to which extent combining them could help fill the gaps in our current understanding of AMR levels and trends. We analysed six industry monitoring systems (ATLAS, GEARS, SIDERO-WT, KEYSTONE, DREAM, and SOAR) obtained from the Vivli platform and reviewed their respective isolates collection and analysis protocols. Using the R software, we designed a pipeline to harmonise and combine these into a single dataset. We assessed the reliability of resistance estimates from these sources by comparing the combined dataset to the publicly available subset of WHO GLASS for shared bacteria-antibiotic-country-year combinations. Combined, the industry monitoring systems cover 18 years (4 years for GLASS), 85 countries (71), 412 bacterial species (8), and 75 antibiotics (25). Although all industry systems followed a similar centralised testing approach, the patient selection protocol and associated sampling period were unclear. Over all reported years and countries, E.coli, K. pneumoniae and S. aureus resistance rates were in >65% of cases within 0.1 of the corresponding estimate in GLASS. We did not identify systemic bias towards resistance in industry systems compared to GLASS. High agreement values for available comparisons with GLASS suggest that data for other bacteria-antibiotic-country-year combinations only present in industry systems could complement GLASS; however, for this purpose patient and isolate selection criteria must first be clarified to understand the representativeness of industry systems. This additional source of information on resistance levels could help clinicians and stakeholders prioritize testing and select appropriate antibiotics in settings with limited surveillance data.

Effectiveness of selective antibiotics use in ESBL-related UTIs

BackgroundUrinary tract infections (UTIs) are the second most common infection, affecting 150 million people each year worldwide. Enterobacteriaceae species expressing extended-spectrum β-lactamases (ESBLs) are on the rise across the globe and are becoming a severe problem in the therapeutic management of clinical cases of urinary tract infection. Knowledge of the prevalence and antibiogram profile of such isolates is essential to develop an appropriate treatment methodology. This study aimed to investigate the prevalence of Enterobacteriaceae isolates exhibiting ESBL and their selective oral antibiogram profile at the district general hospital, Polonnaruwa.ResultsA total of 4386 urine specimens received to the Microbiology Laboratory during the study period. Among them, 1081 (24.6%) showed positive results for urine culture while 200/1081 specimens showed ESBL isolates. Out of the selected 200 specimen’s majority (67.5%) of samples received from the In-Patient Department. There were 200 patients and reported that 115 (57.5%) were females and 85 (42.5%) were males. The majority (51%) of the patients belong to the age group of 55–74 years. Among the ESBLs positive specimens, the majority 74.5% (n = 149) identified organisms were E. coli followed by Klebsiella spp.17.5% (n = 35), Enterobacteriaceae 7% (n = 14) and only1% (n = 2) isolate of Proteus spp. Mecillinam (87.92%) and Nitrofurantoin (83.2%) showed higher effectiveness against E. coli. Nitrofurantoin showed the highest effectiveness against Klebsiella spp. (40%), other Enterobacteriaceae spp. (100%). Proteus spp. showed 100% effectiveness and resistance respectively against Ciprofloxacin, Cotrimoxazole and Nitrofurantoin.ConclusionThe most predominant ESBLs producing uro-pathogen was the E. coli in the study setting and E. coli had higher sensitivity rate against Mecillinam. Among currently used oral antibiotics Nitrofurantoin was the best choice for UTIs caused by ESBL producers.

Impact of causative organism identification on clinical outcomes after minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis: multicenter retrospective cohort study.

This study aimed to evaluate the difference in treatment duration and unplanned additional surgeries between patients with unidentified causative organisms on empiric antibiotics and those with identified organisms on selective antibiotics in treating thoracolumbar pyogenic spondylitis with minimally invasive posterior fixation. This multicenter retrospective cohort study included patients with thoracolumbar pyogenic spondylitis refractory to conservative treatment who underwent minimally invasive posterior fixation. Patients were divided into the identified (known causative organism) and unidentified groups (unknown causative organism). We analyzed data on demographics, antibiotic use, surgical outcomes, and infection control indicators. We included 74 patients, with 52 (70%) and 22 (30%) in the identified and unidentified groups, respectively. On admission, the identified group had higher C-reactive protein (CRP) levels and more iliopsoas abscesses. The duration to postoperative CRP negative was similar in the identified and unidentified groups (7.13 vs. 6.48 weeks, p = 0.74). Only the identified group had unplanned additional surgeries due to poor infection control, affecting 6 of 52 patients (12%). Advanced age and causative organism identification increased the additional surgery odds (odds ratio [OR], 8.25; p = 0.033 and OR, 6.83; p = 0.034, respectively). The use of empiric antibiotics in minimally invasive posterior fixation was effective without identifying the causative organism and did not prolong treatment duration. In patients with identified organisms, 12% required unplanned additional surgery, indicating a more challenging infection control. Causative organism identification was associated with the need for additional surgery, suggesting a more cautious treatment strategy for these patients.

Contribution of gut microbiota to biodegradation of polystyrene in Tenebrio molitor larvae: Microbiome under antibiotic suppression of Gram-positive, Gram-negative, and fungal microbes

The discovery of plastic biodegradation by insects such as Tenebrio molitor larvae has been well known, however, understanding of the roles of larval gut microorganisms is still very limited. The contribution of the gut microbes belonging to respective Gram-positive (G+), Gram-negative (G−), and fungal (F) groups remains unclear. In this study, we tested polystyrene (PS) biodegradation by T. molitor larvae under three selective antibiotics i.e., gentamicin sulfate (GMS) against G− bacteria, ampicillin (AMP) against G+ bacteria and nystatin (NS) against fungi. The larvae consumed and biodegraded PS foams with Mn 86.381 kDa and Mw 181.176 kDa under antibiotic suppressions at reduced rates versus control (CK) with a sequence of CK>GMS>AMP>NS group. Specifically, only NS group showed a significant decreased in consumption compared to the control. The gut microbial counts decreased with GMS, AMP, or NS addition during the PS feeding. The respective gut microbial counts decreased by 103 to 104 with GMS, AMP, or NS addition PS feeding. Analyses of DSC, TGA, FTIR confirmed oxidation and biodegradation in the presence of antibiotics. The ingested PS polymers were depolymerized and mass reduction with negative influence in the order of NS<AMP<GMS. The negative impact of antibiotic suppression on PS biodegradation process was as follows: anti-fungi reagent > anti-G+ bacteria > anti- G− bacteria. Changes in chemical functional groups are probably related to certain gut microbes, such as the fungal genus of Candida, and bacterial genera of unclassified Enterobacteriaceae and Lactobacillus. Our findings provided new insights into the mechanisms of the biodegradation of plastics in insects.

In vitro evolution of ciprofloxacin resistance in Neisseria commensals and derived mutation population dynamics in natural Neisseria populations.

Commensal Neisseria are members of a healthy human oropharyngeal microbiome; however, they also serve as a reservoir of antimicrobial resistance for their pathogenic relatives. Despite their known importance as sources of novel genetic variation for pathogens, we still do not understand the full suite of resistance mutations commensal species can harbor. Here, we use in vitro selection to assess the mutations that emerge in response to ciprofloxacin selection in commensal Neisseria by passaging 4 replicates of 4 different species in the presence of a selective antibiotic gradient for 20 days; then categorized derived mutations with whole genome sequencing. 10/16 selected cells lines across the 4 species evolved ciprofloxacin resistance (≥ 1 ug/ml); with resistance-contributing mutations primarily emerging in DNA gyrase subunit A and B (gyrA and gyrB), topoisomerase IV subunits C and E (parC and parE), and the multiple transferable efflux pump repressor (mtrR). Of note, these derived mutations appeared in the same loci responsible for ciprofloxacin reduced susceptibility in the pathogenic Neisseria, suggesting conserved mechanisms of resistance across the genus. Additionally, we tested for zoliflodacin cross-resistance in evolved strain lines and found 6 lineages with elevated zoliflodacin minimum inhibitory concentrations. Finally, to interrogate the likelihood of experimentally derived mutations emerging and contributing to resistance in natural Neisseria, we used a population-based approach and identified GyrA 91I as a substitution circulating within commensal Neisseria populations and ParC 85C in a single gonococcal isolate. Small clusters of gonococcal isolates had commensal-like alleles at parC and parE, indicating recent cross-species recombination events.

Review on anti-microbial resistance patterns of staphylococcus aureus isolated from mastitic cow’s milk: Ethiopian context

Aim of this paper is to review antimicrobial resistance profile of Staphylococcus aureus (S. aureus) isolated from mastitic cow milk in Ethiopia between 2013- 2023. S. aureus causes chronic intramammary infections, causing financial losses and challenging antimicrobial therapy globally. In Ethiopia meta-analysis of the pooled prevalence of bovine mastitis was 47.6% showing S. aureus as the major isolates accounting for 13.4% and 16.5% of clinical and subclinical mastitis. In Ethiopia, there are indication of the misuse of antibiotics coupled with the rapid spread of resistant bacterial nature and inadequate surveillance, which contributed to the problem. According to this review resistance profile of S. aureus studied in Ethiopia, the bulk of tested isolates showed alarmingly high levels of resistance to widely used antimicrobial drugs for the treatment of mastitis, particularly penicillin G and tetracycline. Variuos studies warned low susceptibility of S. aureus to commonly used antimicrobials such as penicillin G and tetracycline as a great concern because this antibiotic represents the main antibiotic group recommended for staphylococcal mastitis infection in Ethiopia. If essential steps to stop the indiscriminate use of antibiotics are not implemented, the prevalence of antibiotic-resistant S. aureus could rise posing major risks to both animal and human health. Therefore, conducting regular antimicrobial sensitivity testing before treatment helps select effective antibiotics which reduce the development of resistance to commonly used antibiotics. Further studies should be conducted to detect antimicrobial resistant strains, continiuos surveillance and monitoring of S. aureus to prevent the spread of milk-borne drug-resistant strains throughout communities.

Coordination Number Regulation of Iron Single‐Atom Nanozyme for Enhancing H2O2 Activation and Selectively Eliminating Cephalosporin Antibiotics

AbstractNanozymes present promising alternatives to natural enzymes, but controlling nanozymes' performance and employing them for selectively removing antibiotics are extremely challenging. Employing theoretical calculations to design the coordination environments of mental and coordination atoms for directing single‐atom nanozymes synthesis emerges as a promising strategy to enhance their efficiency and selectivity in antibiotic elimination. In this study, the peroxidase‐like specificity of iron single‐atom nanozymes (FeSA‐Nx, x = 2,3, and 4) with specific Fe–N coordination numbers is demonstrated based on theoretical calculations. These calculations guide the synthesis of corresponding ultra‐thin FeSA‐Nx, achieving a high degree of consistency between theoretical predictions and experimental results. FeSA‐N3 with a Fe─N3 coordination number proves to be the most effective. The efficient electron transfer from Fe─N3 site to H2O2 reduces the free energy required for •OH generation. Quantitative structure‐activity relationship (QSAR) analysis reveals a strong positive correlation between degradation efficiency of cephalosporins and their electron‐donating capabilities (R2 = 0.820–0.929), realizing selectively eliminating cephalosporins. Integration FeSA‐N3 into ceramic membrane (FeSA‐N3/CM) improves hydrophilicity, achieving continuous and stable removal of cephalosporin. This study provides valuable insights into coordination number regulating nanozyme properties for selective antibiotics removal and offers novel perspectives for FeSA‐N3 application in integrated systems.

Pharmacist review of discharge antibiotics for urinary tract infections in the emergency department

AbstractEmergency medicine (EM) pharmacists provide high‐quality patient care in a fast‐paced environment by optimizing pharmacotherapy regimens and reducing medication errors. Current literature demonstrates higher rates of medication errors with antibiotics compared with other medication classes. The aim of this quality improvement (QI) project was to reduce medication errors by 25% from baseline for antibiotic discharge prescriptions for urinary tract infections (UTIs). This QI initiative utilized the Institute for Healthcare Improvement Model for Improvement to implement a UTI stewardship intervention and prospective pharmacist review of discharge prescriptions. Patients discharged from the adult ED with an electronic prescription for UTI treatment with select antibiotics were included. The primary outcome metric was the percent of medication errors, defined as a composite of appropriate antibiotic agent, dose, frequency, and treatment duration based on our local treatment algorithm. The balancing metric was time spent per order reviewed. Data over time were assessed using statistical process control charts. A total of 534 antibiotic prescriptions were reviewed from January 9, 2022 to May 31, 2023. The most common indication was cystitis (70%), followed by pyelonephritis (17.4%) and asymptomatic bacteriuria (12.5%). Composite error rate decreased from 64.2% to 5%. Duration of therapy was the most common baseline error and was reduced from 45.3% to 11.6%. Errors in agent, dose and frequency decreased from 19.7% to 3.5%, 10.3% to 0.8% and from 5.7% to 0%, respectively. The aim of this QI initiative was achieved through a series of interventions, including prospective review of discharge antibiotics for UTIs by EM pharmacists, which reduced medication errors. This project demonstrates EM pharmacists have a positive impact in optimization of antimicrobial therapy for the treatment of UTIs.

Prophylactic Intracameral Antibiotics and Endophthalmitis After Cataract Surgery

Although the effectiveness of intracameral antibiotics to prevent postoperative endophthalmitis is described, selective use of antibiotics combined with 1% povidone iodine disinfection might be equally effective and could lead to cost reduction and avoidance of unnecessary use of antibiotics. To compare the incidence of postoperative endophthalmitis when 1% povidone iodine disinfection is applied in combination with selective intracameral antibiotics with the incidence after routine use of intracameral antibiotics in combination with 5% povidone iodine. This was a retrospective cohort study using incidence data from the ongoing endophthalmitis register of the Rotterdam Eye Hospital, a specialized hospital providing both secondary and tertiary ophthalmological care, when intracameral antibiotics were used only during cataract procedures with occurrence of a posterior capsular tear in comparison with results from cohorts described in the literature where routine antibiotics were used. All patients who had cataract (phacoemulsification) surgery at the Rotterdam Eye Hospital between 1993 and 2022 were included. No cataract surgical procedures combined with other intraocular procedures were included. Povidone iodine disinfection and intracameral antibiotics during cataract surgery either routinely or only in case of posterior capsular tears. Postoperative endophthalmitis incidence. Postoperative endophthalmitis incidence after 56 598 cataract (phacoemulsification) surgical procedures in the Rotterdam Eye Hospital between 2016 and 2022 was 0.000 (95% CI, 0.000-0.000). A PubMed literature search until September 2023 with respect to the incidence of postoperative endophthalmitis after routine antibiotic prophylaxis yielded 37 publications with an overall postoperative endophthalmitis incidence of 0.000 (95% CI, 0.000-0.000). No difference was observed between the postoperative endophthalmitis incidence during the last 7 years in the Rotterdam Eye Hospital and the overall postoperative endophthalmitis incidence after routine intracameral antibiotics prophylaxis as described in the literature. Disinfection with 1% povidone iodine in combination with selective antibiotic prophylaxis may be equally effective as routine antibiotic use and 5% povidone iodine.

Antibiotic treatment to prevent pediatric acute otitis media infectious complications: A meta-analysis.

Most US children with acute otitis media [AOM] receive prompt antibiotic treatment, though guidelines encourage watchful waiting. Previous systematic reviews of antibiotics versus watchful waiting have focused on symptom resolution and RCTs, limiting the assessment of serious, rare complications. We sought to evaluate these complications by including observational studies. RCTs and observational studies that compared antibiotics to placebo or watchful waiting for pediatric clinician diagnosed AOM were identified [PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, Central Register of Controlled Trials, and Web of Science] and reviewed for meta-analysis. Two reviewers independently extracted study characteristics, patient characteristics, and outcomes. We assessed publication bias, study bias with ROBINS-1 and RoB-2 and used random-effects models to assess treatment effects. 24 studies were included. Antibiotics decreased the risk of acute mastoiditis [incidence 0.02%, RR 0.48, 95% CI 0.40-0.59; NNT 5,368]. This protective effect may be underestimated because of misclassification of non-suppurative conditions as AOM. Intracranial complications remained too rare to assess. Antibiotics markedly increased the risk of adverse effects [incidence 10.5%, RR 1.49, 1.27-1.73; NNH 23]. Studies used non-specific criteria for acute mastoiditis, potentially underestimating treatment effects. Prompt antibiotic therapy reduces the risk for some AOM complications. The NNT to prevent serious, rare complications is high, while the NNH is relatively low. Large-scale population-based observational studies using real-world datasets with validated measures of severe complications are needed to improve understanding of risk factors for serious AOM complications, facilitate more selective antibiotic therapy, and optimize individual outcomes and public health.

First report of isolation of Fusobacterium varium from liver abscesses and ruminal and colonic epithelial tissues of feedlot cattle*

ObjectiveOur objective was to isolate and determine prevalence of Fusobacterium varium in liver abscesses and the corresponding ruminal and colonic epithelial tissues and ruminal and colonic contents of feedlot cattle. Materials and MethodsA total of 96 intact liver abscess samples and matched ruminal and colonic tissues and contents from cattle, originating from feedlots that did not receive in-feed tylosin, were collected at slaughter. Liver abscesses and ruminal and colonic tissue were ho- mogenized and then plated, before and after enrichment in lactate or lysine medium with selective antibiotics, onto blood agar and selective lactate or lysine agar for isolation of Fusobacterium and to determine prevalence and concentration. Putative colonies were tested by a quantitative PCR assay targeting the hgdA gene for species confirma- tion. Results and DiscussionNone of the liver abscess samples yielded F. varium by direct plating; however, F. varium was isolated from 3 of 96 (3.1%) following enrich- ment of the homogenate in lactate or lysine medium. In contrast to liver abscesses, F. varium was isolated by direct plating from 27.1% (26/96) of ruminal epithelial and 3.1% (3/96) of colonic epithelial tissue homogenates. Overall, 10.1%, 77.1%, 44.8%, 86.5%, and 70.1% of liver abscess, ruminal, and colonic epithelial tissues and ruminal and colonic contents were positive for F. varium, respectively. Implications and ApplicationsThe increased fre- quency of isolation and high prevalence of F. varium in ruminal tissue and, to a lesser extent, in the colonic tissue confirms its ability to invade tissues and possibly cause bacterial ruminitis. However, the relatively low frequency of F. varium isolation and low prevalence in liver abscesses suggest that it is unlikely to be an etiologic agent. Inter- estingly, there is some evidence that ruminal strains of F. varium were resistant to tylosin; therefore, it would be of interest to determine the prevalence in cattle receiving in-feed tylosin.

Comparative Retrospective Assessment of the Effectiveness and Risk Factors of Fluoroquinolones, Cephalosporines, and Selective Antibiotic Prophylaxis for Transrectal Prostate Biopsy

Introduction: Despite increasing resistance of enterobacteria against fluoroquinolones (FLU), they are still widely used during transrectal prostate biopsy (TRPB). This study was designed to analyse infectious complications and risk factors between FLU, cephalosporines (CEPH) and selective other antibiotics (O-AB) used during TRPB. Methods: 664 patients were included retrospectively (152 FLU, 452 CEPH and 60 O-AB). Infectious complications were defined as fever >38.0°C, the in-house definition of complicated urinary tract infection (cUTI) (if all applied: fever >38.0°C, leucocytosis >11.000/µL and positive urine dipstick) or postinterventional bacteriuria. Hospitalisation rate, duration and comorbidities were also assessed. χ2 and Fisher’s exact test were used for group comparison. Multivariate regression analysis assessed the association of comorbidities with infectious complications. Results: FLU and CEPH were indifferent regarding infectious complications, however in the O-AB group significantly more common compared to FLU and CEPH (11.6, 13.3, 25%, p < 0.05). Duration of hospital stay in CEPH was significantly shorter compared to FLU and O-AB (4.1 vs. 6.3 vs. 8.2 days, p < 0.05). Arterial hypertension showed increased association with fever (OR 6.002 (1.178; 30.597) p = 0.031) and cUTI (OR 6.006 (1.207; 29.891) p = 0.029). Conclusion: Infectious complications were low and indifferent between FLU and CEPH but significantly more frequent in O-AB. Arterial hypertension was significantly associated with postinterventional fever and cUTI.

Investigating the feasibility and potential of combining industry AMR monitoring systems: a comparison with WHO GLASS

Background Efforts to estimate the global burden of antimicrobial resistance (AMR) have highlighted gaps in existing surveillance systems. Data gathered from hospital networks globally by pharmaceutical industries to monitor antibiotic efficacy in different bacteria represent an additional source to track the temporal evolution of AMR. Here, we analysed available industry monitoring systems to assess to which extent combining them could help fill the gaps in our current understanding of AMR levels and trends. Methods We analysed six industry monitoring systems (ATLAS, GEARS, SIDERO-WT, KEYSTONE, DREAM, and SOAR) obtained from the Vivli platform and reviewed their respective isolates collection and analysis protocols. Using the R software, we designed a pipeline to harmonise and combine these into a single dataset. We assessed the reliability of resistance estimates from these sources by comparing the combined dataset to the publicly available subset of WHO GLASS for shared bacteria-antibiotic-country-year combinations. Results Combined, the industry monitoring systems cover 18 years (4 years for GLASS), 85 countries (71), 412 bacterial species (8), and 75 antibiotics (25). Although all industry systems followed a similar centralised testing approach, the criteria for isolate collection were unclear (patients selection, associated sampling periods…). For E.coli, K. pneumoniae and S. aureus, at least 65% of comparable resistance proportions were within 0.1 of the corresponding estimate in GLASS. We did not identify systemic bias towards resistance in industry systems compared to GLASS. Conclusions Combining industry monitoring systems can substantially strengthen our knowledge of global AMR burden across bacterial species and countries. High agreement values for available comparisons with GLASS suggest that data for other bacteria-antibiotic-country-year combinations only present in industry systems could complement GLASS, particularly for Priority Pathogens currently not covered. This valuable information on resistance levels could help clinicians and stakeholders prioritize testing and select appropriate antibiotics in settings with limited surveillance data.

Characteristics and Evolution of Microbial Drug Resistance in Burned Patients.

Wound infection is a serious complication in burn injury, which is a common form of trauma and an important public health issue. We investigated samples from burn and nonburn wounds for microbial characteristics and temporal trends of antibiotic resistance. Wound samples were collected from 369 burned patients and 927 non-burned individuals admitted from 2007 to 2017. Higher frequency of Acinetobacter baumannii, Klebsiella pneumonia, and Pseudomonas aeruginosa was observed in samples from burned individuals when compared to those from non-burned. The prevalence of different groups of bacteria varied when the samples were stratified according to age and sex. The antimicrobial resistance profiles showed a significant difference between burned and non-burned patients. The different temporal trends of antimicrobial resistance rates were also found, which may be critical for the proper selection of antibiotics in burn treatment. The present study suggested that frequent pathogens and antibacterial resistance evolution could differ between burn wounds and other wounds. Therefore, periodic surveillance of antibiotic resistance patterns in the burn unit might help physicians properly select antibiotics for treatment.

Functional domains of Acinetobacter bacteriophage tail fibers.

A rapid increase in antimicrobial resistant bacterial infections around the world is causing a global health crisis. The Gram-negative bacterium Acinetobacter baumannii is categorized as a Priority 1 pathogen for research and development of new antimicrobials by the World Health Organization due to its numerous intrinsic antibiotic resistance mechanisms and ability to quickly acquire new resistance determinants. Specialized phage enzymes, called depolymerases, degrade the bacterial capsule polysaccharide layer and show therapeutic potential by sensitizing the bacterium to phages, select antibiotics, and serum killing. The functional domains responsible for the capsule degradation activity are often found in the tail fibers of select A. baumannii phages. To further explore the functional domains associated with depolymerase activity, tail-associated proteins of 71 sequenced and fully characterized phages were identified from published literature and analyzed for functional domains using InterProScan. Multisequence alignments and phylogenetic analyses were conducted on the domain groups and assessed in the context of noted halo formation or depolymerase characterization. Proteins derived from phages noted to have halo formation or a functional depolymerase, but no functional domain hits, were modeled with AlphaFold2 Multimer, and compared to other protein models using the DALI server. The domains associated with depolymerase function were pectin lyase-like (SSF51126), tailspike binding (cd20481), (Trans)glycosidases (SSF51445), and potentially SGNH hydrolases. These findings expand our knowledge on phage depolymerases, enabling researchers to better exploit these enzymes for therapeutic use in combating the antimicrobial resistance crisis.