Administration Of Antimicrobial Agents Research Articles

Gastrointestinal response to the early administration of antimicrobial agents in growing turkeys infected with Escherichia coli

This study investigated the effects of the early administration of enrofloxacin (E) or doxycycline (D) for the first 5 consecutive days of life, or the continuous administration of the coccidiostat monensin (M) throughout the rearing period on gastrointestinal function in turkeys infected with avian pathogenic Escherichia coli (APEC) in an early or later stage of rearing. Experiment 1 lasted 21 d, and turkeys in groups E, D, and M were infected with APEC on d 15. Experiment 2 lasted 56 d, and it had a factorial arrangement of treatments where birds in groups E, D, and M were infected with APEC on d 15 or d 50. In both experiments, control groups (C) consisted of infected and uninfected birds without antibiotic or coccidiostat administration. On d 21 (Experiment 1) and d 56 (Experiment 2), 8 birds from each subgroup were killed, and the ileal and cecal digesta were sampled to analyze the activity of bacterial enzymes and the concentrations of short-chain fatty acids (SCFA). The experimental treatments did not affect the final body weight or body weight gain of birds. Both experiments demonstrated that APEC contributed to an increase in ammonia levels of the cecal digesta (means from 2 experiments: 0.311 vs. 0.225 mg/g in uninfected birds) and ileal pH (6.79 vs. 6.00) and viscosity (2.43 vs. 1.83 mPa⋅s). Moreover, the E. coli challenge enhanced the extracellular activity of several cecal bacterial enzymes, especially in older turkeys infected with APEC in a later stage of life. The continuous administration of monensin throughout the rearing period resulted in a weaker gastrointestinal response in older birds, compared with the other 2 antibiotics administered for the first 5 d of life. The results of the study are inconclusive as both desirable and undesirable effects of preventive early short-term antibiotic therapy were observed in turkeys, including normalization of ileal viscosity and cecal ammonia concentration (positive effect), and disruption in cecal SCFA production (negative effect).

Techniques for conservative treatment of peri-implantitis

Relevance. Dental implants are widely used to restore the patient’s teeth. They have become aworthy alternative to removable dentures. With the accumulation of clinical experience, the indications for dental implantation expanded, and as aresult, the evaluation of long-term results became possible. In parallel with the expansion of clinical use of dental implants and the introduction of the technology into everyday practice, the experience of complications and errors accumulated, and from single publications in the 1990s, at the very beginning of development, to large-­scale studies in the 10s. And if in the early period of implantology development the success of treatment was mainly associated with implant survival, then modern research focuses on the state of tissues around the implant, and the influence of processes in them on the overall outcome of treatment. One of the main complications is inflammation of peri-implant tissues - peri-implantitis. Modern authors define peri-implantitis as an inflammatory process affecting the tissues around afunctionally integrated implant, resulting in loss of supporting bone. Continued bone loss around the implant can significantly impair implant stability and function. The authors review the scientific literature describing experimental conservative treatment protocols for peri-implantitis and attempts to achieve osseointegration. Conclusion. The reviewed literature advocated various methods of surgical regenerative treatment for peri-implantitis, including the use of bone substitutes, methods of detoxification of implant surfaces, and the administration of antimicrobial agents. There are many different protocols for the treatment of peri-implantitis; they all share the same goal of reducing disease progression and bone loss by eliminating bacterial infection. The controversy over the proper approach to treating peri-implantitis and restoring osseointegration clearly demonstrates the need for more research to answer this question.

Association of short-course antimicrobial therapy and bacterial resistance in acute cholangitis: Retrospective cohort study.

Background and study aims Although the number of resistant bacteria tends to increase with prolonged antimicrobial therapy, no studies have examined the relationship between the duration of antimicrobial therapy and increase in the number of resistant bacteria in acute cholangitis. We hypothesized that the short-term administration of antimicrobial agents in acute cholangitis would suppress bacterial resistance. Patients and methods This was a single-center, retrospective, observational study of patients with acute cholangitis admitted between January 2018 and June 2020 who met the following criteria: successful biliary drainage, positive blood or bile cultures, bacteria identified from cultures sensitive to antimicrobials, and subsequent cholangitis recurrence by January 2022. The patients were divided into two groups: those whose causative organisms at the time of recurrence became resistant to the antimicrobial agents used at the time of initial admission (resistant group) and those who remained susceptible (susceptible group). Multivariate analysis was used to examine risk factors associated with the development of resistant pathogens. Multivariate analysis investigated antibiotics used with the length of 3 days or shorter after endoscopic retrograde cholangiopancreatography (ERCP) and previously reported risk factors for the development of bacterial resistance. Results In total, 89 eligible patients were included in this study. There were no significant differences in patient background or ERCP findings between the groups. The use of antibiotics, completed within 3 days after ERCP, was associated with a lower risk of developing bacterial resistance (odds ratio, 0.17; 95% confidence interval, 0.04-0.65; P =0.01). Conclusions In acute cholangitis, the administration of antimicrobials within 3 days of ERCP may suppress the development of resistant bacteria.

Effect of rapid cefpodoxime disk screening for early detection of third-generation cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae bacteremia

BackgroundSeveral methods have been reported for detecting resistance genes or phenotypic testing on the day of positive blood culture in Escherichia coli or Klebsiella pneumoniae bacteremia. However, some facilities have not introduced these methods because of costs or other reasons. Toyota Kosei Hospital introduced cefpodoxime (CPDX) rapid screening on May 7, 2018, to enable early detection of third-generation cephalosporin resistance. In this study, we aimed to evaluate the effects of intervention with an Antimicrobial Stewardship Team using CPDX rapid screening.MethodsCefotaxime (CTX)-resistant E. coli or K. pneumoniae bacteremia cases were selected retrospectively and divided into two groups: the pre-CPDX screening (June 1, 2015, to May 6, 2018) and CPDX screening groups (July 7, 2018, to August 31, 2021). The primary outcome was the proportion of cases in which modifications were made to the administration of susceptible antimicrobial agents within 24 h of blood culture-positive reports.ResultsOverall, 63 patients in the pre-CPDX screening group and 84 patients in the CPDX screening group were eligible for analysis. The proportion of patients who modified to susceptible antimicrobial agents within 24 h of blood culture-positive reports was significantly increased in the CPDX screening group compared to that in the pre-CPDX screening group (6.3% vs. 22.6%, p = 0.010).ConclusionThe results demonstrated that in CTX-resistant E. coli or K. pneumoniae bacteremia, CPDX rapid screening increased the proportion of early initiation of appropriate antimicrobial agents.

Cerebellar Abscess A rare case

Paediatric brain abscess is a rare disease with a high risk of morbidity and mortality. Brain abscess seems to occur most commonly in the age group of 4-10 years, with the least frequent sites being the cerebellum and brainstem. A cerebellar abscess is characterized by headache, nystagmus, ipsilateral ataxia, dysmetria, and vomiting [1]. Advanced diagnostic modalities such as MRI and CT scans and early administration of antimicrobial agents have drastically reduced the mortality and morbidity associated with brain abscesses.

Alternative Antimicrobial Irrigation Strategies for the Treatment of Infections in Children: A Review of the Existing Literature.

As a synergistic treatment approach with systemic antimicrobial therapy or a systemic antibiotic-sparing strategy, the local administration of antimicrobial agents has been proposed as an alternative route for complicated infections. With the rationale of concentrating the active principle in the desired target site, avoiding potentially toxic systemic levels and bypassing anatomical and physiological barriers, local irrigation or infusion of antibiotics may effectively shorten the antimicrobial therapy course and reduce both infection-related and systemic therapy-related complications. Although evidence from the adult population supports its use in selected patients with an acceptable safety profile, data specifically focused on the pediatric population are limited. To provide a rapid and easily accessible tool for clinical practice, we synthesized the most relevant evidence on the use of local antimicrobial agents in common severe infections in children: meningitis, mediastinitis, pleural infections, recurrent urinary infections, and peritonitis. A literature search was performed using predefined combined keywords through an electronic research database (PubMed). Described molecules, dosages, routes, treated age groups, and related efficacy have been summarized for prompt application to clinical practice. It should, however, be noted that the evidence for the pediatric population remains limited, and the local administration of several molecules remains off-label. A careful multidisciplinary and patient-tailored evaluation, as well as a rational use of available guidelines, should always be the basis of clinical decision making in settings where local administration of antibiotics may be considered.

The Impact of the COVID-19 Pandemic on Antimicrobial Resistance and Management of Bloodstream Infections.

The pressure of the COVID-19 pandemic on healthcare systems led to limited roles of infectious diseases services, increased rates of irrational use of antimicrobials, and incidence of infections by multidrug-resistant microorganisms. The aim of the present study is to evaluate the incidence of antimicrobial resistance and the management of bloodstream infections before and during the COVID-19 pandemic at the University General Hospital of Alexandroupolis (Greece). This is a retrospective study conducted from January 2018 to December 2022. Data were collected from the University Microbiology Laboratory per semester regarding the isolated strains of Gram-positive and -negative bacteria in blood cultures and respiratory samples in hospitalized patients in medical and surgical wards and in the intensive care unit (ICU). Additionally, bloodstream infections with requested infectious disease consultations were reported (n = 400), determining whether these were carried out via telephone contact or at the patient's bedside. Demographic data, comorbidities, focus of infection, antimicrobial regimen, duration of treatment, length of hospitalization, and clinical outcome were analyzed. A total of 4569 strains of Gram-positive and -negative bacteria were isolated. An increasing trend was reported compared to the pre-pandemic period in the incidence of resistant Gram-negative bacteria, particularly in ICUs. Prior antimicrobial use and the rate of hospital-acquired infections were increased significantly during the pandemic. In the pre-pandemic period 2018-2019, a total of 246 infectious disease consultations were carried out, while during the period 2020-2022, the number was 154, with the percentage of telephone consultations 15% and 76%, respectively. Detection of the source of infection and timely administration of appropriate antimicrobial agents were more frequently recorded before the pandemic, and 28-day mortality was significantly reduced in cases with bedside consultations. The empowering of infectious disease surveillance programs and committees, rational use of antimicrobials agents, and bedside infectious disease consultations are vital in order to reduce the impact of infections caused by multidrug-resistant strains.

THE EMPIRIC ANTIMICROBIAL THERAPY: THE COMPARISON OF INITIAL CHOICE WITH THE RESULTS OF MICROBIOLOGICAL INVESTIGATIONS. AN OBSERVATIONAL STUDY

Introduction: Hospital infections are serious medical problem, causing deterioration in patients’ outcome, prolonged hospital stay and increase costs of hospitalization. Rapid administration of wide spectrum antimicrobial agents is a well known way to increase patient survival rate. Aim: To analyze the efficacy of initial empiric antimicrobial treatment in a large academic hospital. Methods: In this retrospective cohort study, the initial choice of empiric therapy was compared with the results of the microbiological investigation and the susceptibility/resistance of isolated pathogens. Results: Between February 1, 2018 and February 1, 2020, a total number of 267 samples were analyzed. Amongst all 267 samples 163 (61%) were positive and 104 (39%) were negative. In those 163 samples 247 pathogens were isolated. In empirical therapy the most frequently administered antibiotic was meropenem (55/267, 20.6%), vancomycin (16/267, 6%), meropenem with vancomycin (14/267, 5.2%), ceftazidime (11/267, 4.1%), and imipenem/cilastatin (5/267, 1.9%). The total number of samples where the empiric therapy corresponded with the results of microbiological tests was 166. There were forty-seven (28.3%) Gram positive bacteria, including 11 MRSA and 1 VRE, and 119 (71.7%) Gram negative pathogens, including 35 K. pneumoniae ESBL+, 12 A. baumannii, and 2 E. coli ESBL+. In 81 cases, the isolated pathogens were resistant to empirically administered drugs. The empiric antimicrobial therapy complied with the results of microbiological analyses in 67.2% (166/247) of cases. Conclusion: In our center, meropenem and vancomycin seem to be a good choice in empiric therapy.

High Occurrence of Multiple-Drug Resistance Mediated by Integron in Aeromonas Isolated from Fish-Livestock Integrated Farms

Fish-livestock integrated farming is a traditional practice in South China and Southeast Asia. The administration of antimicrobial agents in livestock may potentially facilitate the spread of antimicrobial resistance to aquaculture through the drainage of livestock manure. Aeromonas spp. are fish pathogens that are the predominant bacteria in water bodies. The aim of this study was to characterize multiple-drug-resistantAeromonas spp. isolated from integrated and nonintegrated fish-livestock farms and to investigate the occurrence of class 1 integrons. Of the 481 Aeromonas strains examined in this study, isolates from pig manure, fish, and environmental samples from pig-fish or goose-fish integrated farms were significantly more resistant to various antimicrobial agents than those from nonintegrated farms P < 0.05 . High rates of resistance to nalidixic acid and sulfamonomethoxine were observed in the isolates from the integrated farm. Fifty Aeromonas isolates (10.4%) from integrated farms contained class 1 integrons. In addition, 96.0% (48/50) of the integron-positive strains displayed multiple-drug resistance. Ten types of gene cassette arrays were determined by sequencing, including dfrA17, dfrA12-orfF-aadA2, catB8, dfrB4-catB3-aadA1, aac6(6′)-Ib-cr-arr-3, aac-II-blaOXA-21-catB3, aar2-aacA4-drfA1-orfC, aac(6′)-Ib-cr, dfrA15, and dfrB4-catB3-blaOXA-10-aadA1. Notably, among the 50 integron-positive isolates, twenty isolates showed integrons located in plasmids, which may facilitate the transmission of resistance in integrated farms. Our investigation confirmed the high prevalence of multiple antimicrobial resistances mediated by class 1 integrons in Aeromonas isolates from integrated farms. Therefore, it is necessary to establish a risk assessment method for antimicrobial resistance in aquaculture.

Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model

The treatment for osteomyelitis consists of surgical debridement, filling of the dead space, soft tissue coverage, and intravenous administration of antimicrobial (AM) agents for long periods. Biomaterials for local delivery of AM agents, while providing controllable antibiotic release rates and simultaneously acting as a bone scaffold, may be a valuable alternative; thus, avoiding systemic AM side effects. V-HEPHAPC is a heparinized nanohydroxyapatite (nHA)/collagen biocomposite loaded with vancomycin that has been previously studied and tested in vitro. It enables a vancomycin-releasing profile with an intense initial burst, followed by a sustained release with concentrations above the Minimum Inhibitory Concentration (MIC) for MRSA. In vitro results have also shown that cellular viability is not compromised, suggesting that V-HEPHAPC granules may be a promising alternative device for the treatment of osteomyelitis. In the present study, V-HEPHAPC (HEPHAPC with vancomycin) granules were used as a vancomycin carrier to treat MRSA osteomyelitis. First, in vivo Good Laboratory Practice (GLP) toxicological tests were performed in a rabbit model, assuring that HEPHAPC and V-HEPHAPC have no relevant side effects. Second, V-HEPHAPC proved to be an efficient drug carrier and bone substitute to control MRSA infection and simultaneously reconstruct the bone cavity in a sheep model.

Leiomioma de muñón uterino: Reporte de caso

Leiomyoma is a slow-growing, non-metastatic tumor that can affect any structure of the animal’s body that has a smooth muscle, being diagnosed more frequently in the genital tract of middle-aged to elderly and non-neutered female dogs. In cases of this neoplasm in the uterus, the disease is rarely related to any clinical sign, it’s often diagnosed incidentally. However, signs resulting from visceral compression, increased abdominal volume, vaginal secretion and pyometra may be present. X-ray and ultrasound exams are important to identify the location and origin of the mass, but the diagnosis is confirmed only through histopathological examination. In the present report, a spayed, mixed breed, 14-year-old female dog with abdominal enlargement and difficulty urinating was treated. When performing the ultrasound and x-ray examination, the presence of a mass caudal to the bladder of around 6 cm was observed. The animal was referred to surgery for excision of the nodule and referral of the structure to histopathology, which confirmed the leiomyoma. The postoperative period was carried out with the administration of anti-inflammatory and antimicrobial agents, the evolution of the treatment was favorable and the animal recovered well. Thus, knowing this type of tumor and its occurrences, it is clear that this case is uncommon and that its findings can contribute to knowledge for a more assertive diagnosis of this pathology in other female dogs.

Enterococcus casseliflavus Infection: A Review of Clinical Features and Treatment.

Some Enterococcus species, including Enterococcus faecalis and E. faecium, are increasingly becoming a common cause of nosocomial infections, accounting for the majority of human enterococcal infections, while other species, such as E. casseliflavus, have also been shown to be pathogenic to humans due to the increase in immunocompromised patients. These infections vary widely in their mode of transmission, symptoms, and other characteristics. Treatment is difficult in some cases because enterococci are resistant to numerous antimicrobial agents. Enterococcus faecalis and E. faecium are the best-known opportunistic pathogens, but others, including E. casseliflavus, occasionally cause opportunistic infections. This review summarizes the clinical features of E. casseliflavus infections and discusses effective therapeutic strategies. Bacteremia was the most common form of E. casseliflavus infections. Because E. casseliflavus carries the VanC gene, which confers resistance to vancomycin, less resistant drugs such as ampicillin were found more effective in treating the bacteremia. The second most common form of E. casseliflavus infection was trauma-induced endophthalmitis. This was commonly reported in active young to middle-aged patients. Vitreoretinal surgery and local or systemic administration of sensitive antimicrobial agents seem to be key to successful treatment. Other conditions such as infective endocarditis, meningitis, peritonitis, and pyothorax have also been reported as forms of E. casseliflavus infection. This review clarifies the clinical features of E. casseliflavus infection and provides important insights into its treatment.

Case of pneumococcal (PRSP) bronchitis: Gram staining as the earliest and useful indicator for evaluating the effectiveness of antimicrobial therapy in outpatient.

A 75-year-old man was seen in the general practice in our hospital because of fever of 38-39℃, cough and purulent sputa on January 8 th . Six days before visit, he had the chief complaint. The day before, he visited a clinic. The chest X-ray showed no pneumonia shadow suggesting of bronchitis with old tuberculous changes. Azithromycin was administered, but no improvement was seen. The doctor sent him to our hospital. Gram-stained sputum samples showed gram- positive diplococcus, later identified as Streptococcus pneumoniae (PRSP). He was administered two grams of ampicillin for 30 minutes. Gram-stained sputum samples showed smaller or gram-negative pneumococci at the completion of administration of the agent, and a decreased number of extracellular cocci and increased number of phagocyted small and weekly stained cocci at two hours after completion of administration. We estimated the effectiveness of ampicillin and prescribe 2g of amoxicillin hydrate (AMPC) (500mgX4) for 2days followed by 1.5g of AMPC (500mgX3) for the next 5days (till 2/15). He was seen on the 7 th day (2/14) again with no fever, a decreased amount of cough and sputa. The culture of the sputum on the first day (2/8) revealed Streptococcus (PRSP) 3+ resistant to penicillin and ampicillin. But Gram-stained sputum samples showed little number of cocci and we confirmed the effectiveness of ampicillin prescribing no additional antimicrobial agent. He was seen on the 12 th (2/19) to follow up the course, and getting better with little cough having watery sputa. The culture of the sputum on the 7 th (2/14) day revealed no Streptococcus. However, Gram-stained sputum samples showed some extracellular cocci suggesting of pneumococci, and we predicted the coming relapse of bronchitis. We prescribed new ketolide antimicrobial drug telithromycin (TEL,300mgX 2) for 3days. On the 15 th (2/22) he visited our hospital again with no respiratory symptom and Gram-stained sputum samples showed no cocci suggestive of pneumococcus. He recovered from bronchitis. We present here a case in which morphological changes and/or a decreased number of extracellular S. pneumoniae observed in Gram-stained sputum samples obtained after the first administration of antimicrobial agents presented useful information as a reliable therapeutic indicator of the effectiveness of the first administered agent, and follow up check of Gram-stained sputum could prevent the relapse of bronchitis before worsening in outpatient.

978. Effectiveness of oral cephalexin as completing treatment for bacteremic vertebral osteomyelitis caused by Methicillin-susceptible Staphylococcus aureus

Abstract Background Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (VO). Oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, but data on pyogenic VO are scarce. Methods This retrospective study included adult patients treated with oral cephalexin as the completing treatment for pyogenic VO with bacteremia due to MSSA at the National Center for Global Health and Medicine Hospital, Japan from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing the improvement in symptoms and laboratory and imaging results after intravenous (IV) administration of antimicrobial agents and after oral cephalexin treatment, using a 5-point scale (Table). A score of 4 or 5 indicated treatment success. Results This study included 15 patients (8 [53%] females), with median age 75 years (interquartile range [IQR], 67.5–80.5), median body weight 57.0 kg (IQR, 45.5–62.5), and median Charlson comorbidity index score 2 (IQR, 0–4). Ten patients (67%) had lesions in the lumbar spine. Six patients had lesions at multiple sites (cervical and thoracic, n=1; cervical and lumbar, n=2; thoracic and lumbar, n=1; and lumbar and sacral, n=2). Twelve patients (80%) had spinal abscesses and four (27%) had remote abscesses, but none had concomitant endocarditis. In 11 patients with normal renal function, 1,500–2,000 mg/day of cephalexin was administered. Surgical intervention was performed in five cases (33%). The median duration of IV antibiotics, cephalexin, and total treatment was 36 (IQR, 32–61; range, 21–86), 29 (IQR, 19–82; range, 8–251), and 86 (IQR, 59–125; range, 37–337) days, respectively. Majority patients (≥80%) received either cefazolin or ceftriaxone as IV therapy. Two patients used oral antimicrobials other than cephalexin outside of the cephalexin treatment period. Treatment success rate after cephalexin therapy was 87%. None of the patients had recurrence during a median follow-up of 119 days (IQR, 48.5-350). Conclusion In patients with bacteremic VO due to MSSA, completing treatment with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective IV antimicrobial therapy is provided. Disclosures All Authors: No reported disclosures.

The Role of Outer Membrane Proteins in UPEC Antimicrobial Resistance: A Systematic Review.

Uropathogenic Escherichia coli (UPEC) are one of the most common agents of urinary tract infection. In the last decade, several UPEC strains have acquired antibiotic resistance mechanisms and some have become resistant to all classes of antibiotics. UPEC outer membrane proteins (OMPs) seem to have a decisive role not only in the processes of invasion and colonization of the bladder mucosa, but also in mechanisms of drug resistance, by which bacteria avoid killing by antimicrobial molecules. This systematic review was performed according to the PRISMA guidelines, aiming to characterize UPEC OMPs and identify their potential role in antimicrobial resistance. The search was limited to studies in English published during the last decade. Twenty-nine studies were included for revision and, among the 76 proteins identified, seven were associated with antibiotic resistance. Indeed, OmpC was associated with β-lactams resistance and OmpF with β-lactams and fluoroquinolone resistance. In turn, TolC, OmpX, YddB, TosA and murein lipoprotein (Lpp) were associated with fluoroquinolones, enrofloxacin, novobiocin, β-lactams and globomycin resistances, respectively. The clinical implications of UPEC resistance to antimicrobial agents in both veterinary and human medicine must propel the implementation of new strategies of administration of antimicrobial agents, while also promoting the development of improved antimicrobials, protective vaccines and specific inhibitors of virulence and resistance factors.

Clinical laboratory diagnostics in dentistry: Application of microbiological methods.

Diagnosis and treatment in dentistry are based on clinical examination of the patients. Given that the major oral diseases are of microbial biofilm etiology, it can be expected that performing microbiological analysis on samples collected from the patient could deliver supportive evidence to facilitate the decision-making process by the clinician. Applicable microbiological methods range from microscopy, to culture, to molecular techniques, which can be performed easily within dedicated laboratories proximal to the clinics, such as ones in academic dental institutions. Periodontal and endodontic infections, along with odontogenic abscesses, have been identified as conditions in which applied clinical microbiology may be beneficial for the patient. Administration of antimicrobial agents, backed by microbiological analysis, can yield more predictable treatment outcomes in refractory or early-occurring forms of periodontitis. Confirming a sterile root canal using a culture-negative sample during endodontic treatment may ensure the longevity of its outcome and prevent secondary infections. Susceptibility testing of samples obtained from odontogenic abscesses may facilitate the selection of the appropriate antimicrobial treatment to prevent further spread of the infection.

Integrating structured and unstructured data for timely prediction of bloodstream infection among children.

Hospitalized children with central venous lines (CVLs) are at higher risk of hospital-acquired infections. Information in electronic health records (EHRs) can be employed in training deep learning models to predict the onset of these infections. We incorporated clinical notes in addition to structured EHR data to predict serious bloodstream infections, defined as positive blood culture followed by at least 4 days of new antimicrobial agent administration, among hospitalized children with CVLs. Structured EHR information and clinical notes were extracted for a retrospective cohort including all hospitalized patients with CVLs at a single tertiary care pediatric health system from 2013 to 2018. Deep learning models were trained to determine the added benefit of incorporating the information embedded in clinical notes in predicting serious bloodstream infection. A total of 24,351 patient encounters met inclusion criteria. The best-performing model restricted to structured EHR data had a specificity of 0.951 and positive predictive value (PPV) of 0.056 when the sensitivity was set to 0.85. The addition of contextualized word embeddings improved the specificity to 0.981 and PPV to 0.113. Integrating clinical notes with structured EHR data improved the prediction of serious bloodstream infections among pediatric patients with CVLs. Developed an advanced infection prediction model in pediatrics that integrates the structured and unstructured EHRs. Extracted information from clinical notes to do timely prediction in a clinical setting. Developed a deep learning model framework that can be employed in predicting rare events in a complex and dynamic environment.

Two plus One: Combination Therapy Tri-systems Involving Two Membrane-Disrupting Antimicrobial Macromolecules and Antibiotics.

The escalating issue of multidrug-resistant (MDR) bacteria indicates the urgent need for new and effective strategies to combat this global health challenge. Here, we describe a new combinatorial approach that can be put forward for experimental therapy application against MDR bacteria. Specifically, we have developed a tri-system that includes the coadministration of two different membrane-disrupting-type antimicrobial agents─a synthetic antimicrobial polymer P and an antimicrobial peptide (AMP) colistin methanesulfonate (Col)─in conjunction with an antibiotic [doxycycline (Dox), rifampicin (Rif), or azithromycin (Azi)]. Traditionally, the administration of membrane-disrupting antimicrobial agents causes toxicity, but, in comparison, we demonstrated synergy and biocompatibility using this combinatorial approach. Checkerboard assays showed the occurrence of synergistic interactions in Col-Dox-P, Col-Rif-P, and Col-Azi-P tri-systems against wild-type and MDR Pseudomonas aeruginosa, with the Col-Dox-P system being the most effective. The ability to synergize thus enables the use of a lower dosage in combinations compared to the standalone agents. The tri-systems not only demonstrated bacteriostatic activity but were also bactericidal. For example, the Col-Dox-P system (at 8, 4, and 8 μg mL-1, respectively) and the Col-Rif-P system (at 4, 8, and 16 μg mL-1, respectively) were able to kill >99.999% of planktonic P. aeruginosa cells within 3 h of treatment. More importantly, an improvement of the therapeutic/selectivity index was achieved via combination therapy. Taking the Col-Dox-P system as an example, its biocompatibility with murine embryonic fibroblast cells was found to be comparable to that of polymer P alone despite the synergistic enhancement in antimicrobial activity of the combination. This resulted in a significant increase in selectivity by 16-fold for the Col-Dox-P combination system compared to P alone. Furthermore, the broad applicability of this tri-system strategy was demonstrated via the successful application of the AMP melittin in place of Col or P. Overall, this study sheds new insights on the application of membrane-disrupting antimicrobial agents in combination therapy and their potential for safer clinical use. Additionally, the information gathered in this study could inform the development of future combination therapy systems involving the simultaneous employment of multiple AMPs with antibiotics.

Antibiotic Administration within Two Days after Successful Endoscopic Retrograde Cholangiopancreatography Is Sufficient for Mild and Moderate Acute Cholangitis.

To prevent the increase of resistant bacteria, it is important to minimize the use of antimicrobial agents. Studies have found that administration for ≤3 days after successful endoscopic retrograde cholangiopancreatography (ERCP) is appropriate. Therefore, the present study aimed to verify if administration of antimicrobial agents can be further shortened to ≤2 days after ERCP. We divided 390 patients with mild and moderate cholangitis who underwent technically successful ERCP from January 2018 to June 2020 and had positive blood or bile cultures into two groups: antibiotic therapy within two days of ERCP (short-course therapy, SCT; n = 59, 15.1%), and for >3 days (long-course therapy, LCT; n = 331, 84.9%). The increased severity after admission and other outcomes were compared between the two groups, and the risk factors for increased severity were verified. There were no between-group differences in patient characteristics. Total length of hospital stay was shorter in SCT than in LCT, and other outcomes in SCT were not significantly different from those in LCT. Being 80 or older was a risk factor for increased severity; however, SCT was not associated with increased severity. Antimicrobial therapy for ≤2 days after successful ERCP is adequate in patients with mild and moderate acute cholangitis.

A dominant clonal lineage of Streptococcus uberis in cattle in Germany

Bovine mastitis causes enormous economic losses in the dairy industry with Streptococcus uberis as one of the most common bacterial pathogens causing clinical and subclinical variations. In most cases mastitis can be cured by intramammary administration of antimicrobial agents. However, the severity of the clinical manifestations can vary greatly from mild to severe symtoms. In this study, a comparative genomic analysis of 24 S. uberis isolates from three dairy farms in Germany, affected by different courses of infection was conducted. While there were sporadic mild infections in farm A and B, a large number of infections were observed within a very short period of time in farm C. The comparison of virulence genes, antimicrobial resistance genes and prophage regions revealed no features that might be responsible for this severe course. However, almost all isolates from farm C showed the same, novel MLST profile (ST1373), thus a clonal outbreak cannot be excluded, whereby the actual reason for the particular virulence remains unknown. This study demonstrates the importance of extensive metagenomic studies, including the host genomes and the environment, to gain further evidence on the pathogenicity of S. uberis.