End Of Antibiotic Therapy Research Articles

Head-to-Head Comparison Between 18F-FDG PET and Leukocyte Scintigraphy to Monitor Treatment Responses in Necrotizing Otitis Externa.

Necrotizing otitis externa (NOE) is a rare disease associated with high morbidity and mortality, and there is currently no available accurate biomarker to assess treatment responses. The aim of the current study was to evaluate and directly compare the diagnostic performances of 18-Fluoro-deoxyglucose positron emission tomography (18F-FDG PET) and labeled leukocyte scintigraphy (LS) to monitor treatment responses in NOE. Consecutive patients with NOE who underwent 18F-FDG PET at the end of antibiotic therapy and planar as well as single photon emission computed tomography-labeled leukocyte scintigraphy after completing the initial antibiotic treatment were retrospectively included. Semiquantitative analyses were performed to determine the ratios of affected/nonaffected sides for PET and 4 hour and 24 hour LS acquisitions as well as the kinetic PET ratios (at diagnosis and post-treatment) and LS (4 and 24 hours). The final treatment responses were assessed by 2 experienced ENT physicians based on clinical, otoscopic, and biological data and subsequent 3-month follow-up. Seventeen patients (74.0 ± 10.6 years old, 5 women) were included. The best diagnostic performances were obtained with the PET maximum standardized uptake value (SUVmax)-lesion-to-background ratio and the tomographic LS lesion-to-background ratio at the 4-hour acquisition timepoint (thresholds of 4.1 and 1.19, yielding accuracies of 100% and 88%, respectively). In the multivariate analysis, the PET SUVmax-lesion-to-background ratio was the only predictive factor of recovery when associated with all clinical parameters (P < .001). 18F-FDG PET is the first-line imaging modality for evaluating NOE treatment responses, with excellent diagnostic performances. LS with only 4-hour acquisitions appeared to suffice to evaluate NOE treatment responses. Both biomarkers constitute early prognostic biomarkers for predicting antibiotic treatment response in patients with NOE. The institutional ethics committee (Comité d'Ethique du CHRU de Nancy) approved the evaluation of retrospective patient data, and the trial was registered at ClinicalTrials.gov (n°2023PI003-404).

Evaluation of serum VIP and aCGRP during pulmonary exacerbation in cystic fibrosis: A longitudinal pilot study of patients undergoing antibiotic therapy.

Objective monitoring of improvement during treatment of pulmonary exacerbation can be difficulty in children when pulmonary function testing cannot be obtained. Thus, the identification of predictive biomarkers to determine the efficacy of drug treatments is of high priority. The major aim of the current study was to investigate the serum levels of vasoactive intestinal peptide (VIP) and alpha calcitonin gene related peptide (aCGRP) of cystic fibrosis pediatric patients during pulmonary exacerbation and post-antibiotic therapy, and possible associations of their levels with different clinicopathological parameters. 21 patients with cystic fibrosis were recruited at onset of pulmonary exacerbation. Serum was collected at time of admission, three days post-antibiotic therapy, and two weeks post-antibiotic therapy (end of antibiotic therapy). Serum VIP and aCGRP levels were measured using ELISA. Overall least square means of serum aCGRP level but not VIP changed from time of exacerbation to completion of antibiotic therapy (p = 0.005). Serum VIP was significantly associated with the presence of diabetes mellitus (p = 0.026) and other comorbidities (p = 0.013), and with type of antibiotic therapy (p = 0.019). Serum aCGRP level was significantly associated with type of antibiotic therapy (p = 0.012) and positive Staphylococcus aureus microbiology test (p = 0.046). This study could only show significant changes in serum aCGRP levels following treatment of pulmonary exacerbations. Future studies with larger sample size are required to investigate the clinical importance of VIP and aCGRP in cystic fibrosis patients.

Red blood cell distribution width as a potential inflammatory marker in pediatric osteomyelitis

Background Red cell distribution width (RDW) has been used in the differential diagnosis of anemia and revealed to be a potential marker of inflammation. Method We conducted a retrospective study of acute-phase reactant changes in correlation with RDW among pediatric patients with osteomyelitis. Results We identified 82 patients whose mean RDW increased on average by 1% during antibiotic therapy (mean 13.9% on admission, 95% CI 13.4–14.3, and 14.9% at the end of antibiotic therapy, 95% CI 14.5–15.4). Overall, the RDW was weakly correlated with absolute neutrophil count (r = −0.21, P = 0.001), erythrocyte sedimentation rate (r = −0.17, P = 0.007), and C-reactive protein (r = −0.21, P = 0.001). The generalized estimating equation model showed a weak negative correlation between RDW and C-reactive protein during the therapy duration (B= −0.03, P = 0.008). Conclusions The mild increase in RDW, and its weak negative correlation with other acute-phase reactants during the study course, limits its utility as a therapy response marker in pediatric osteomyelitis.

489. Bile Acid Concentrations in Healthy Volunteers Receiving Oral Omadacycline or Vancomycin

Abstract Background Microbiome disruption associated with Clostridioides difficile infection (CDI) includes reduced metabolism of primary to secondary bile acids leading to increased likelihood of C. difficile germination and CDI recurrence. Omadacycline has potent in vitro activity against C. difficile but its effect on the microbiome is unknown. The purpose of this study was to assess changes in bile acid concentrations in healthy volunteers given omadacycline compared to vancomycin, the most common antibiotic used to treat CDI. Methods As part of an ongoing healthy volunteer study of adults between 18 and 40 years, subjects received a 10-day course of oral omadacycline or vancomycin. Stool samples were collected and bile acids were extracted and quantified via targeted liquid chromatography-mass spectrometry (LC-MS). For this analysis, samples collected at the end of antibiotic therapy (day 9-10) were analyzed for primary and secondary bile acids. Results were compared and visualized using R (ggplot2). Results Between October 2020 and December 2021, 16 healthy volunteers aged 26 ± 5 years (male: 69%; Caucasian: 31%; mean body mass index: 23.6 ± 3.8 kg/m2) were enrolled. Concentrations of primary bile acids (cholic acid and chenodeoxycholic acid) were higher in patients receiving oral vancomycin than those receiving omadacycline (Table 1). Secondary bile acids were higher in the omadacycline arm compared to vancomycin. Secondary:primary bile ratio was higher for omadacycline (0.43) than vancomycin (0.03). Conclusion Omadacycline preserved bile acid homeostasis in the gut to a higher extent that vancomycin, suggesting reduced microbiome dysbiosis. With potent in vitro C. difficile activity, availability as an oral and IV formulations, and favorable microbiome properties, further development of omadacycline for the treatment of CDI is warranted. Disclosures Kevin W. Garey, PharmD, MS, Acurx Pharmaceuticals: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Seres Therapeutics: Grant/Research Support|Summit Pharmaceuticals: Grant/Research Support.

Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study.

The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI. A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI. Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive. Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Efficacy of Prolonged Antibiotic Therapy for Renal Cyst Infections in Polycystic Kidney Disease

ObjectiveTo determine the impact of antibiotic therapy (ATBT) on outcomes of renal cyst infection (CyI) in patients with polycystic kidney disease. Patients and MethodsWe undertook a single-center retrospective study of CyI in autosomal dominant polycystic kidney disease (January 1, 2000, through December 31, 2018). Cyst infections were classified as definite (microbiologically proven), probable (radiologic signs), or possible (clinical or biologic signs only). We studied the determinants of ATBT failure (persistence of infection beyond 72 hours of microbiologically adequate initial ATBT, with requirement for ATBT change, cyst drainage, or nephrectomy) and recurrences (>14 days after the end of ATBT). ResultsAmong 90 patients, 139 CyIs (11 definite, 74 probable, 54 possible) were compiled. Cultures were positive in 106 of 139 (76%) episodes, with Escherichia coli found in 89 of 106 (84%). Treatment failures and recurrences within 1 year of follow-up were more frequent in definite/probable CyI (20/85 [34%] and 16/85 [19%]) than in possible CyI (2/54 [4%] and 4/54 [7%]; P<.01 and P=.08, respectively). Male sex (odds ratio [OR], 7.79; 95% CI, 1.72 to 46.68; P<.01), peak C-reactive protein level above 250 mg/L (OR, 7.29; 95% CI, 1.78 to 35.74; P<.01; to convert C-reactive protein values to nmol/L, multiply by 9.524), and cyst wall thickening (OR, 7.70; 95% CI, 1.77 to 43.47; P=.01) but not the modalities of initial ATBT were independently associated with higher risk of failure. In a Cox proportional hazards model, kidney transplant recipients exhibited higher risk of recurrence (hazard ratio, 3.76; 95% CI, 1.06 to 13.37; P=.04), whereas a total duration of ATBT of 28 days or longer was protective (hazard ratio, 0.02; 95% CI, 0.00 to 0.16; P<.001), with an inverse correlation between duration and recurrence (81% for treatment <21 days, 47% for 21 to 27 days, 2% for ≥28 days; P<.0001). ConclusionInitial first-line ATBT had no significant effect on renal CyI treatment failure. Treatment duration of 28 days and longer reduced recurrences.

Ultrasound-guided placement of long peripheral cannula in children with cystic fibrosis.

BackgroundThe natural history of cystic fibrosis (CF) lung disease is a chronic deterioration of lung function with intermittent episodes of pulmonary infectious exacerbations (PExs). Reliable venous access is a milestone of effective management of such exacerbations, managed both in hospital and outpatient chronic therapy. The aim of our study was to analyze the feasibility of ultrasound‐guided positioning of long peripheral catheters (LPC) as reliable midterm venous access in children affected by CF.MethodsIn this single‐center prospective study, over a 60‐month period, we included paediatric CF subjects admitted with PExs and undergoing intravenous antibiotic treatment. LPCs were inserted in all participants by paediatric anaesthesiologists with ultrasound guide technique. Prospective data were collected assessing catheter positioning procedure and complications.ResultsA total of 122 LPC insertions were performed in 55 CF children. Participants had a median age of 6.75 years (interquatile range: 3.7−13.5) at the time of catheter insertion. Implantation was successful on the first attempt in 86% of cases; 2 (1%) major insertion‐related complications were reported. Eighty‐eight percent of catheters were electively removed at the end of antibiotic therapy without any complication. Seven percent of the catheters were removed electively for occlusion and 2% for local dislodgment.ConclusionsThe results of the present study suggest that ultrasound‐guided positioning of LPCs are safe alternative means of peripheral venous access in children with chronic diseases such as CF.

The Induced Immune Response in Patients With Infectious Spondylodiscitis: A Prospective Observational Cohort Study.

IntroductionInfectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy. Immunologic profiling of patients with infectious spondylodiscitis could allow for a personalized medicine strategy. We aimed to examine the induced immune response in patients with infectious spondylodiscitis during and after antibiotic therapy. Furthermore, we explored potential differences in the induced immune response depending on the causative pathogen and the dissemination of the disease.MethodsThis was a prospective observational cohort study that enrolled patients with infectious spondylodiscitis between February 2018 and August 2020. A blood sample was collected at baseline, after four to six weeks of antibiotic therapy (during antibiotic therapy), and three to seven months after end of antibiotic therapy (post-infection). The induced immune response was assessed using the standardized functional immune assay TruCulture®. We used a panel of three immune cell stimuli (lipopolysaccharide, Resiquimod and polyinosinic:polycytodylic acid) and an unstimulated control. For each stimulus, the induced immune response was assessed by measuring the released concentration of Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, Interferon-γ (IFN-γ) and Tumor necrosis factor-α (TNF-α) in pg/mL.ResultsIn total, 49 patients with infectious spondylodiscitis were included. The induced immune responses were generally lower than references at baseline, but the cytokine release increased in patients after treatment with antibiotic therapy. Post-infection, most of the released cytokine concentrations were within the reference range. No significant differences in the induced immune responses based on stratification according to the causative pathogen or dissemination of disease were found.ConclusionWe found lower induced immune responses in patients with infectious spondylodiscitis at baseline. However, post-infection, the immune function normalized, indicating that an underlying immune deficiency is not a prominent factor for spondylodiscitis. We did not find evidence to support the use of induced immune responses as a tool for prediction of the causative pathogen or disease dissemination, and other methods should be explored to guide optimal treatment of patients with infectious spondylodiscitis.

Impact of Antibiotic Authorisation at Three Provincial Hospitals in Thailand: Results from a Quasi-Experimental Study.

Implementing antimicrobial stewardship (AMS) at non-university hospitals is challenging. A quasi-experimental study was conducted to determine the impact of customised antibiotic authorisation implementation on antimicrobial consumption and clinical outcomes at three provincial hospitals in Thailand. Customised pre-authorisation of selected restricted antibiotics and post-authorisation of selected controlled antibiotics were undertaken and implemented at each hospital by the local AMS team with guidance from the AMS team at the university hospital. From January 2019–December 2020, there were 1802 selected patients (901 patients during the pre-implementation period and 901 patients during the post-implementation period). The most commonly used targeted antimicrobial was meropenem (49.61%), followed by piperacillin/tazobactam (36.46%). Comparison of the outcomes of the patients during the pre- and post-implementation periods revealed that the mean day of therapy of the targeted antimicrobials was significantly shorter during the post-implementation period (6.24 vs. 7.64 days; p < 0.001), the favourable clinical response (the improvement in all clinical and laboratory parameters at the end of antibiotic therapy) was significantly higher during the post-implementation period (72.70% vs. 68.04%; p = 0.03) and the mean length of hospital stay was significantly shorter during the post-implementation period (15.78 vs. 18.90 days; p < 0.001). In conclusion, implementation of antibiotic authorisation at provincial hospitals under experienced AMS team’s guidance was feasible and useful. The study results could be a good model for the implementation of customised AMS strategies at other hospitals with limited resources.

Abstract P2-12-04: Characterization of gut microbiome composition in triple negative breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background: Recent evidences showed intestinal microbiota to be implicated in carcinogenesis and response to chemotherapy and immune checkpoint inhibitors in solid tumors. Furthermore, antibiotics are known to deeply influence microbiome composition in healthy people and cancer patients. The role of gut microbiome in triple negative breast cancer (TNBC) is underexplored. Methods: In this pilot prospective study, we characterized the gut microbiome of 30 TNBC patients undergoing neoadjuvant chemotherapy at two Italian Institutions. Fecal samples were collected at 2 timepoints: at the baseline (t0) and at 1 week (t1) from CT. Microbiome was analyzed by 16S rRNA sequencing. Measures of α-diversity expressed by Richness and Simpson evenness were evaluated at the species level. β-diversity was calculated using PERMANOVA test according to UniFrac measures of dissimilarity at the species level.Tumor infiltrating lymphocytes (TILs) were assessed from diagnostic core biopsy and surgical specimen. Results: From September 2017 to March 2020, 30 TNBC patients were enrolled. Median age was 53 years, 43% were premenopausal, 43% were overweight or obese (BMI&amp;gt;25); 97% had a histologic G3 carcinoma, clinical nodal involvements was present in 57%; median TILs at diagnosis was 30%. All patients received anthracycline and taxane-based chemotherapy, including carboplatin in 23 patients (77%). A pCR was achieved in 15 (50%) patients. The overall rate of stool samples collection was 93%. With regards to t0, no differences in terms of α- and β-diversity were found.At t1, α-diversity was significantly higher in pCR group (Simpson evenness index, p=0.016). Considering clinical-pathological features, a BMI &amp;lt;24.9 was associated with higher microbiome richness (p=0.012). Measurements of β-diversity did not differ between groups.As 73% of patients during the treatment phase received antibiotics, with consequent potential microbiome impairment, we repeated analyses at t1 considering fecal samples collected &amp;gt;90 days after the end of antibiotic therapy (N=17). At this analysis, β-diversity evaluated with Unifrac measure was significantly correlated with pCR (p=0.035), with Haemophilus Influentiae being significantly enriched in non-pCR group. Conclusions: Fecal microbiome collection and analysis in this population is feasible and deserves further investigation with regards its association with response to chemotherapy. Citation Format: Grazia Maria Vernaci, Davide Massa, Ilaria Patuzzi, Alice Menichetti, Tommaso Giarratano, Gaia Griguolo, Federica Miglietta, Matteo Fassan, Edoardo Savarino, PierFranco Conte, Valentina Guarneri, Maria Vittoria Dieci. Characterization of gut microbiome composition in triple negative breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-04.

Патогенетические особенности антибиотик-ассоциированного синдрома на примере биологической модели

Antibiotic therapy is an integral part of current therapeutic practice to save patients’ lives. However, as with any therapeutic intervention, the development of adverse events is possible, one of which is the antibiotic-associated syndrome (AAS). Objective. To study the pathogenetic features of AAS extraintestinal manifestations using a biological model as an example. Materials and methods. This study was conducted using the biological model (outbred male mice) between 2019 and 2020 on the basis of the Central Research Institute of Epidemiology of Rospotrebnadzor. Experimental animals were injected with amoxicillin/clavulanic acid and cefotaxime in two therapeutic doses, average and maximum. The recalculation of drug doses was carried out depending on the animal’s body weight. The comparison was performed in four study groups and one control group, which were distinguished according to the dose and type of antibacterial agent. The histological examination of internal organs (large intestine, small intestine, liver, pancreas, kidney, lung, heart, testicles, spleen, stomach, duodenum, skin, bladder) was conducted at two time points: 24 hours after antibiotic administration and 7 days after the end of antibiotic therapy. Results. The results of histological examination at the first time point (24 hours after antibiotic administration) demonstrated that the use of the studied antibacterial agents at the average therapeutic dose did not cause significant morphological changes in the organs of mice, while the administration of maximum dose led to the development of reactive changes, primarily in the vascular system. The results of histological examination in the experimental groups at the second control time point (7 days after the end of antibiotic therapy) showed a systemic reaction in the organs of mice, expressed primarily in perivascular leukocyte infiltration. Similar changes were registered in the group of experimental animals that were injected with average therapeutic doses of antibacterial agents. Conclusion. AAS is characterized by systemic and homogeneous pathomorphological changes in various tissues, which explains not only the development of antibiotic-associated diarrhea, but also its extraintestinal symptoms. Our findings allow to suggest that antibiotics, especially when used irrationally, increase the risks of pathology associated with a systemic inflammatory response, in particular atherosclerosis and obesity, at the population level. Key words: antibiotic-associated diarrhea, antibiotic-associated syndrome

Сравнительный анализ ультразвуковой биомикроскопии между фемто-ассистированным и ультразвуковым удалением катаракты при подвывихе хрусталика

Purpose of the study to carry out a comparative analysis of the state of the zonular fibers before and after surgery on UBM between femtolaser assisted and classical ultrasound cataract removal. Material and methods. 19 patients (38 eyes) with age-related cataracts. 22 eyes were with pseudo-exfoliative syndrome. All patients were examined with grade 1 lens subluxation. The first group of 19 eyes underwent cataract femto-phacoemulsification. The second group included 19 eyes without using a femtolaser. The state of the fibers was determined on the UBM on the fifth day after the operation at the end of antibiotic therapy. Results. The data showed the presence of a statistically significant difference between the group with femto-assistance and the group without it. In the first group, UBM analysis showed that the state of the zonular fibers remained in the same state in 16 of 19 eyes. In the second group, 11 of 19 eyes required ring implantation with suturing to the sclera and 3 required IOL implantation with seamless fixation to the sclera and vitrectomy. Conclusions. The appropriate path to surgery depends on the most accurate objective assessment of the condition of the lens ligaments, since the position of the IOL is one of the main factors for a good result expected by the patient after surgery. Reducing the «trauma» of the eye with lens surgery has been a key success factor and femtolaser guidance provides valuable assistance in obtaining it. Key words: lens subluxation, femtosecond laser, UBM.

General principles of uncomplicated cystitis therapy during pregnancy

Urinary tract infections during pregnancy are associated with severe complications. Earlier initiation of antibiotic treatment for acute uncomplicated cystitis, reduces the various complications.Objective. To assess the effectiveness of fosfomycin in the treatment of acute uncomplicated cystitis during II and III trimester of pregnancy.Material and methods. The study included 74 pregnant women who had acute uncomplicated cystitis in II or III trimesters. All patients received fosfomycin trometamol 3.754 g (equivalent to 3 g fosfomycin) as antimicrobial therapy for acute uncomplicated cystitis. The drug was prescribed to 24 pregnant women in the II, and 50 in the III trimester of pregnancy.Results. After treatment with fosfomycin signs of acute cystitis gone in all patients. At the same time, regression of clinical symptoms was noted during the next days after therapy in 95.9% (n = 71) of cases. Repeated microbiological test of the middle portion of urine was performed 7 days after the end of antibiotic therapy. In 94.6% (n = 70) cases, total elimination of the pathogen was achieved. In 5.4% (n = 4) cases, there was a significant decrease of colonization Follow-up for three months showed the absence of recurrence of acute cystitis in all pregnant women who were included in the study.Conclusion. Fosfomycin is a highly effective drug in the treatment of uncomplicated cystitis during pregnancy.

S183 Infusion of Bezlotoxumab at the End of an Antibiotic Treatment Course for Prevention of Recurrent Clostridioides difficile Infection

Introduction: Clostridioides difficile infection (CDI) is the leading cause of infectious diarrhea in the western world. Despite proper antibiotic treatment, recurrence is common, occurring in 25% of patients after first infection. The risk of recurrence increases with each subsequent episode. Bezlotoxumab is a monoclonal antibody given as adjuvant therapy directed against CD toxin B. The proposed mechanism is that it enters the intestinal lumen through damaged gap junctions and prevents recurrence by neutralizing toxin B produced by residual CD spores which germinate after cessation of antibiotics. In the MODIFY I/II trials, Bezlotoxumab reduced recurrent CDI (rCDI) in comparison to placebo by 10%. Moreover, sustained clinical cure at 12 weeks was achieved with Bezlotoxumab in 64% of subjects as compared to 54% of placebo-arm subjects. While timing of Bezlotoxumab administration was studied during the MODIFY I/II trial, there is a paucity of data regarding the timing of infusion in real world scenarios. Methods: We performed a retrospective study of CDI cases at an academic community hospital in a tri-county area. Inclusion criteria included at least one prior rCDI, defined as CDI within less than three months of resolution of a prior episode, and having received infusion of Bezlotoxumab within 48 hours of final dose of antibiotic for rCDI. For these patients, metrics reviewed include whether rCDI occurred following Bezlotoxumab, patient characteristics including medical co-morbidities, and overall medical risk as denoted by Charlson Comorbidity Index. Results: Six patients fit inclusion criteria. 5/6 patients did not experience rCDI following Bezlotoxumab infusion (Table 1). Patient 5 had underlying Ulcerative Colitis and developed rCDI 11 days after Bezlotoxumab but was then cured after 2 fecal microbiota transplant procedures. 4/5 patients whose CDI resolved experienced a self-limited diarrhea episode within 14 days of infusion that resolved without additional intervention. Conclusion: Infusion of Bezlotoxumab near the end of antibiotic therapy appears to be effective for prevention of rCDI in a real-world setting, and thus provides a simple regimen for treatment. We hypothesize that administration of Bezlotoxumab at the end of a treatment course maximizes its efficacy by ensuring a high antibody titer during the period of high risk for rCDI. Future studies should include higher number of patients and direct comparisons against patients receiving Bezlotoxumab earlier in CDI therapy.Table 1.: Patient Demographics and CDI Recurrence after Bezlotoxumab.

Цефалоспориніндукований біліарний сладж у дітей

Актуальність. Одним із побічних ефектів дії цефалоспоринів ІІІ покоління є формування цефалоспориніндукованого біліарного псевдолітіазу (ЦІБПЛ). Мета. Вивчити особливості формування біліарного сладжа при застосуванні цефалоспоринів ІІІ покоління в терапії гострих респіраторних інфекційних захворювань у дітей. Матеріали та методи. Обстежено 46 дітей віком від 2 до 15 років з гострими респіраторними інфекційними захворюваннями, які отримували в терапії цефалоспорини ІІІ покоління парентеральним шляхом введення у вікових дозах. У всіх дітей до початку лікування і після закінчення антибіотикотерапії оцінювали показники біохімічного дослідження крові і дані ехосонографії (ультразвукове дослідження) біліарного тракту. Результати. За даними УЗД у 10 пацієнтів (21,7 %) з гострими респіраторними інфекційними захворюваннями після проведеного курсу терапії цефалоспоринами ІІІ покоління виявлено неоднорідний вміст у просвіті жовчного міхура у вигляді гіперехогенного субстрату, що свідчило про формування ЦІБПЛ. Середній вік пацієнтів із ЦІБПЛ становив 9,05 ± 1,44 року і перебував у межах від 4 до 15 років. Встановлено, що у 60 % обстежених дітей формування ЦІБПЛ протікало субклінічно. Результати біохімічного дослідження сироватки крові показали, що у дітей із ЦІБПЛ спостерігалося підвищення активності аланінамінотрансферази, аспартатамінотрансферази і лужної фосфатази. Було встановлено, що ЦІБПЛ відзначається у 22,9 % дітей на тлі терапії цефтріаксоном, у 9 % пацієнтів — цефтазидимом. Біліарний сладж формувався у 54,5 % хворих, які отримували цефтріаксон у високих дозах (100 мг/кг/добу), і в 75 % випадків — після 10-денного застосування даного антибіотика. Висновки. Отримані результати показали, що на тлі застосування цефалоспоринів ІІІ покоління при терапії гострих респіраторних інфекційних захворювань у 21,7 % хворих дітей відбувається формування ЦІБПЛ. Особливо високий ризик розвитку ЦІБПЛ відзначається при використанні високих доз цефтріаксону і пролонгованої терапії цефалоспоринами.

Short midline catheters: High success rates for antibiotic therapy in children with cystic fibrosis.

Short midline catheter use in paediatric populations appears to be increasing, however data on success rates and efficacy are sparse. This study aims to describe the success rate when midline venous catheters are employed as a single device for intravenous antibiotic therapy in paediatric patients with cystic fibrosis. A retrospective cohort study was performed in a single institution, retrieving electronic medical record data from July 2017 through March 2020. The primary outcome was device success, defined as a catheter that remained functional until the end of antibiotic therapy. Reasons for device failure were categorized in a standard fashion. Primary outcome data were available for 116 catheter insertions, involving 49 patients and 55 proceduralists. The success rate was 84% (n = 98). Median age at insertion was 15 years (range 4-19) and median weight 52 kg (13-81). Soft, polyether block amide, Arrow® Seldinger Arterial Catheters were employed. Only 16 patients (14%) required general anaesthesia. Median time to failure was 6 days, and median time to successful completion of treatment was 13 days. Six of 18 failures occurred within 48 h and were likely insertion complications. The most common reasons for device failure were occlusion, extravasation, phlebitis and dislodgement. More than half of patients (56%) received antibiotic therapy at home. There is a high single device success rate when inserting short midlines for 13-day intravenous pulmonary antibiotic therapy in children with cystic fibrosis. These results should be confirmed with a prospective study.

Temocillin versus carbapenems for urinary tract infection due to ESBL-producing Enterobacteriaceae: a multicenter matched case-control study

ObjectivesTo compare the efficacy of temocillin with carbapenems for extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae urinary tract infections (ESBL-E UTI). MethodsA multicenter retrospective case-control study of adults with ESBL-E UTI was conducted between January 2015 and October 2019. Cases received temocillin ≥ 50% of the effective antibiotic therapy duration and controls exclusively received carbapenem; they were statistically matched (1:1 ratio) on 6-month period, sex and age. The clinical cure at the end of antibiotic therapy was analysed using conditional logistic regression. ResultsSeventy-two temocillin cases were matched to 72 carbapenem controls. Most (67%) were male, median age was 69.4 years, 81 (56%) were immunocompromised, including 44 (31%) solid organ transplant recipients. There was no difference between cases and controls for baseline characteristics and microorganisms involved: Klebsiella pneumoniae in 59 (41%), Escherichia coli in 57 (40%), and Enterobacter spp. in 24 (17%). The median time from admission to effective antibiotic therapy was 0 days [range, 0–2]. Among cases, first-line antibiotic therapy (≤ 72 hours) was temocillin in six (8%) and carbapenems in 39 (54%). Temocillin was given at the median daily dose of 4 g [range, 2–4] after 3 days [range, 2–5] of carbapenems. Patients received temocillin for 81% [range, 70–93] of the effective antibiotic course duration over 11 days [range, 8–14]. The effective antibiotic duration was similar in cases and controls (P = 0.067). Clinical cure at the end of antibiotic therapy was 94% (68/72) in cases vs. 99% (71/72) in controls (P = 0.206), with no difference among immunocompromised and solid organ transplant patients (P > 0.050). ConclusionsTemocillin effectively relayed β-lactams, including carbapenems, to treat (complicated) ESBL-E UTI. Its efficacy was consistent among kidney transplant recipients.

Presepsin (Soluble CD14 Subtype) as an Early Marker of Neonatal Sepsis and Septic Shock: A Prospective Diagnostic Trial.

In the context of suspected neonatal sepsis, early diagnosis and stratification of patients according to clinical severity is not yet effectively achieved. In this diagnostic trial, we aimed to assess the accuracy of presepsin (PSEP) for the diagnosis and early stratification of supposedly septic neonates. PSEP, C-reactive protein (CRP), and procalcitonin (PCT) were assessed at the onset of sepsis suspicion (T0), every 12–24 h for the first 48 h (T1–T4), and at the end of antibiotic therapy (T5). Enrolled neonates were stratified into three groups (infection, sepsis, septic shock) according to Wynn and Wong’s definitions. Sensitivity, specificity, and area under the ROC curve (AUC) according to the severity of clinical conditions were assessed. We enrolled 58 neonates with infection, 77 with sepsis, and 24 with septic shock. PSEP levels were higher in neonates with septic shock (median 1557.5 pg/mL) and sepsis (median 1361 pg/mL) compared to those with infection (median 977.5 pg/mL) at T0 (p < 0.01). Neither CRP nor PCT could distinguish the three groups at T0. PSEP’s AUC was 0.90 (95% CI: 0.854–0.943) for sepsis and 0.94 (95% CI: 0.885–0.988) for septic shock. Maximum Youden index was 1013 pg/mL (84.4% sensitivity, 88% specificity) for sepsis, and 971.5 pg/mL for septic shock (92% sensitivity, 86% specificity). However, differences in PSEP between neonates with positive and negative blood culture were limited. Thus, PSEP was an early biomarker of neonatal sepsis severity, but did not support the early identification of neonates with positive blood culture.

Temporal Gut Microbial Changes Predict Recurrent Clostridiodes Difficile Infection in Patients With and Without Ulcerative Colitis.

Ulcerative colitis (UC) carries an increased risk of primary and recurrent Clostridiodes difficile infection (rCDI), and CDI is associated with UC flares. We hypothesized that specific fecal microbial changes associate with UC flare and rCDI. We conducted a prospective observational cohort study of 57 patients with UC and CDI, CDI only, and UC only. Stool samples were collected at baseline, at the end of antibiotic therapy, and after reconstitution for 16S rRNA sequencing. The primary outcomes were recurrent UC flare and rCDI. Logistic regression and Lasso models were constructed for analysis. There were 21 (45.7%) patients with rCDI, whereas 11 (34.4%) developed UC flare. Patients with rCDI demonstrated significant interindividual (P = 0.008) and intraindividual differences (P = 0.004) in community structure by Jensen-Shannon distance (JSD) compared with non-rCDI. Two cross-validated Lasso regression models predicted risk of rCDI: a baseline model with female gender, hospitalization for UC in the past year, increased Ruminococcaceae and Verrucomicrobia, and decreased Eubacteriaceae, Enterobacteriaceae, Lachnospiraceae, and Veillonellaceae (AuROC, 0.94); and a model 14 days after completion of antibiotics with female gender, increased Shannon diversity, Ruminococcaceae and Enterobacteriaceae, and decreased community richness and Faecalibacterium (AuROC, 0.9). Adding JSD between baseline and post-treatment samples to the latter model improved fit (AuROC, 0.94). A baseline model including UC hospitalization in the past year and increased Bacteroidetes was associated with increased risk for UC flare (AuROC, 0.88). Fecal microbial features at baseline and after therapy predict rCDI risk in patients with and without UC. These results may help risk stratify patients to guide management.

The effect of probiotic Vetom 2 on the microbial intestinal landscape in calves after antibiotic therapyThe effect of probiotic Vetom 2 on the microbial intestinal flora in calves after antibiotic therapy

Intestinal microflora is directly and actively involved in ensuring the constancy of the internal environment of the microorganism. Disruption of the normal composition of the microflora of the gastrointestinal tract is accompanied by the development of dysbacteriosis. The most important role in restoring the normal intestinal microbiocenosis belongs to bacterial probiotic preparations. The aim of our study was to study the effect of Vetom 2 on the microbial intestinal landscape in calves after antibiotic therapy. Studies were conducted in AO Uchkhoz Prigorodnoye on calves of black pied breed. Five groups of 5 calves each were formed: healthy calves, calves with dyspepsia before antibiotic therapy, calves with dyspepsia during antibiotic therapy, calves after completing antibiotic therapy who did not receive Vetom 2, calves receiving Vetom 2 after completing antibiotic therapy. Feces of calves of all groups were bacteriologically investigated on the content of Escherichia, Streptococcus, Staphylococcus, Salmonella, Pseudomonas aeruginosa. We found that in animals of all experimental groups, the microbial landscape of the intestine is not the same. In diseased calves, before antibiotic therapy, the number of opportunistic microorganisms is much higher relative to the group of healthy animals. During treatment, these figures decrease. The number of conditionally pathogenic microorganisms in calves treated with Vetom 2 during rehabilitation after the end of antibiotic therapy was lower—unlike in the group of calves that did not receive Vetom 2 during rehabilitation—as a result of suppression of growth and development of conditionally pathogenic microorganisms in the intestines of calves after antibiotic therapy by bacterial strains included in Vetom 2.