Bacterial Infections In Adults Research Articles

Physicochemical Characterization of the Oral Biotherapeutic Drug IMUNOR®.

IMUNOR is an oral biotherapeutic drug that had been developed, registered, and approved in 1997 in the Czech Republic and Slovakia. IMUNOR is a dialyzable leukocyte extract (DLE) prepared from swine leukocytes. It is characterized as a mixture of small peptides with molecular weights smaller than 12 kDa and a specific portion of nucleotides. The medical uses of IMUNOR include therapeutic applications within its registered range of indications, primarily for the treatment of immunodeficiencies, allergies, and certain acute or relapsing bacterial infections in adults and children. Despite the long-term clinical application of DLE, with strong evidence of positive therapeutic effects and no serious side effects, a detailed physicochemical specification of this mixture was lacking. We developed several methods for more in-depth physicochemical characterization of IMUNOR, including a spectrophotometric method for quantification of the total protein concentration and total DNA concentration in a mixture, several chromatographic methods for identification of individual components present in significant concentrations in IMUNOR, such as HPLC methods and the Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis method, and characterization of amino acid composition of this mixture. For the investigation of the variability among different batches of IMUNOR, five to nine representative batches from a standard manufacturing process on an industrial scale were utilized. Using the analytical methods, we verified and confirmed the batch-to-batch reproducibility of the biological product IMUNOR.

Early Diagnosis of Neonatal Sepsis Using the Leukocyte Alkaline Phosphatase Score: A Cohort Study

Introduction: The clinical features of sepsis in neonates are subtle and non specific, requiring a high index of suspicion for early diagnosis. Blood culture is the gold standard for diagnosis, but it is time consuming. Therefore, there is a need for a costeffective and reliable screening tool. The Leukocyte Alkaline Phosphatase (LAP) activity of neutrophils is known to increase during bacterial infections in adults. Aim: To determine the activity of LAP in Neonatal Sepsis (NS) and compare the results with blood culture. Materials and Methods: This is a prospective cohort study conducted from January 2018 to June 2019 at Mandya Institute of Medical Sciences, Karnataka, India. Total of 200 neonates by their haematological profile were clinically suspected of having sepsis. A peripheral smear was prepared from a drop of blood and stained to assess the LAP activity. In each smear, a total of 100 consecutive segmented neutrophils were examined and were rated from 0 to 4 according to the red granular precipitate intensity within their cytoplasm. The possible range of 0-400. The blood culture report was obtained from the case sheet. The neonates were divided into two groups: Group 1 consisted of culture-proven sepsis cases, and Group 2 consisted of neonates with clinical suspicion of sepsis but negative blood culture results. Descriptive analysis was performed using mean and standard deviation for quantitative variables, and frequency and proportion for categorical variables. Chi-square test was conducted, and a p-value <0.05 was considered statistically significant. Results: Out of the 200 cases studied, 64 neonates showed a positive blood culture. The most common causative organism observed was Klebsiella pneumoniae, which was seen in 56 neonates. The age of the neonates ranged from newborn to 28 days old, with 115 being male. Furthermore, 116 neonates were term neonates, and 146 presented with early onset sepsis. The study revealed a wide range of LAP activity in both groups. In the culture-positive sepsis group, the LAP activity ranged from 36 to 350, while in the clinical sepsis group, it ranged from 10 to 354. Due to the broad range of LAP scores observed, it is concluded that LAP activity is not useful as a screening test. Conclusion: Findings of the present study indicate that LAP activity exhibited a wide range in both the culture-proven and clinical sepsis groups. However, due to this variability, LAP activity does not appear to be a reliable screening test for NS. While LAP activity assessment may still hold diagnostic value, further research is needed to refine its utility and explore its clinical relevance.

Clinical Timing-Sequence Warning Models for Serious Bacterial Infections in Adults Based on Machine Learning: Retrospective Study.

Serious bacterial infections (SBIs) are linked to unplanned hospital admissions and a high mortality rate. The early identification of SBIs is crucial in clinical practice. This study aims to establish and validate clinically applicable models designed to identify SBIs in patients with infective fever. Clinical data from 945 patients with infective fever, encompassing demographic and laboratory indicators, were retrospectively collected from a 2200-bed teaching hospital between January 2013 and December 2020. The data were randomly divided into training and test sets at a ratio of 7:3. Various machine learning (ML) algorithms, including Boruta, Lasso (least absolute shrinkage and selection operator), and recursive feature elimination, were utilized for feature filtering. The selected features were subsequently used to construct models predicting SBIs using logistic regression (LR), random forest (RF), and extreme gradient boosting (XGBoost) with 5-fold cross-validation. Performance metrics, including the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC), accuracy, sensitivity, and other relevant parameters, were used to assess model performance. Considering both model performance and clinical needs, 2 clinical timing-sequence warning models were ultimately confirmed using LR analysis. The corresponding predictive nomograms were then plotted for clinical use. Moreover, a physician, blinded to the study, collected additional data from the same center involving 164 patients during 2021. The nomograms developed in the study were then applied in clinical practice to further validate their clinical utility. In total, 69.9% (661/945) of the patients developed SBIs. Age, hemoglobin, neutrophil-to-lymphocyte ratio, fibrinogen, and C-reactive protein levels were identified as important features by at least two ML algorithms. Considering the collection sequence of these indicators and clinical demands, 2 timing-sequence models predicting the SBI risk were constructed accordingly: the early admission model (model 1) and the model within 24 hours of admission (model 2). LR demonstrated better stability than RF and XGBoost in both models and performed the best in model 2, with an AUC, accuracy, and sensitivity of 0.780 (95% CI 0.720-841), 0.754 (95% CI 0.698-804), and 0.776 (95% CI 0.711-832), respectively. XGBoost had an advantage over LR in AUC (0.708, 95% CI 0.641-775 vs 0.686, 95% CI 0.617-754), while RF achieved better accuracy (0.729, 95% CI 0.673-780) and sensitivity (0.790, 95% CI 0.728-844) than the other 2 approaches in model 1. Two SBI-risk prediction nomograms were developed for clinical use based on LR, and they exhibited good performance with an accuracy of 0.707 and 0.750 and a sensitivity of 0.729 and 0.927 in clinical application. The clinical timing-sequence warning models demonstrated efficacy in predicting SBIs in patients suspected of having infective fever and in clinical application, suggesting good potential in clinical decision-making. Nevertheless, additional prospective and multicenter studies are necessary to further confirm their clinical utility.

Practicability of the German guidelines on skin and soft tissue infections

The guidelines on calculated parenteral initial treatment of bacterial infections in adults from 2018 were the first German language S2k guidelines for these infections. This article summarizes the experiences with respect to their practicality in the clinical routine and the resulting supplementations and comments. In view of the many different terms for soft tissue infections, the guidelines had to first establish some definitions and diagnostic criteria. Among others, the guidelines introduced the provisional term limited phlegmons (phlegmons are usuallytermedcellulitis in Angloamerican literature) for the frequent initially superficial soft tissue infections with Staphylococcus aureus, which do not always extend to the fascia, in order to differentiate them from erysipelas caused by Streptoccocus, which in contrast to phlegmons always respond to penicillin. The general symptoms present in erysipela are a practical differential criterion. Somewhat more complex are the definitions and recommendations for the severe forms of phlegmon, which involve the fascia and are accompanied by necrosis, so that here the practicality of the guidelines needs to prove its worth over time. The guidelines also give recommendations how to proceed in case of alleged or confirmed hypersensitivity to beta-lactam antibiotics. Currently, relevant guidelines recommend, and it is correspondingly here elaborated, that in acute cases a beta-lactam antibiotic with side chains other than those in the suspected drug may present an alternative without prior testing. Therefore, cefazolin, that does not share any side chains with other beta-lactam antibiotics, could be administered under appropriate precautionary measures. The term cellulitis is avoided in the guidelines. Since it is used frequently, and also for non-infectious dermatoses, the various meanings are discussed and distinguished from each other.

Pharmacokinetics and safety of a single dose of telavancin in pediatric subjects 2-17 years of age.

Antimicrobial resistance increases infection morbidity in both adults and children, necessitating the development of new therapeutic options. Telavancin, an antibiotic approved in the United States for certain bacterial infections in adults, has not been examined in pediatric patients. The objectives of this study were to evaluate the short-term safety and pharmacokinetics (PK) of a single intravenous infusion of telavancin in pediatric patients. Single-dose safety and PK of 10 mg/kg telavancin was investigated in pediatric subjects >12 months to ≤17 years of age with known or suspected bacterial infection. Plasma was collected up to 24-h post-infusion and analyzed for concentrations of telavancin and its metabolite for noncompartmental PK analysis. Safety was monitored by physical exams, vital signs, laboratory values, and adverse events following telavancin administration. Twenty-two subjects were enrolled: 14 subjects in Cohort 1 (12-17 years), 7 subjects in Cohort 2 (6-11 years), and 1 subject in Cohort 3 (2-5 years). A single dose of telavancin was well-tolerated in all pediatric age cohorts without clinically significant effects. All age groups exhibited increased clearance of telavancin and reduced exposure to telavancin compared to adults, with mean peak plasma concentrations of 58.3 µg/mL (Cohort 1), 60.1 µg/mL (Cohort 2), and 53.1 µg/mL (Cohort 3). A 10 mg/kg dose of telavancin was well tolerated in pediatric subjects. Telavancin exposure was lower in pediatric subjects compared to adult subjects. Further studies are needed to determine the dose required in phase 3 clinical trials in pediatrics.

Omadacycline for treatment of acute bacterial infections: a meta-analysis of phase II/III trials

ObjectiveThis study aims to assess the clinical efficacy and safety of omadacycline for the treatment of acute bacterial infections.MethodsA search of PubMed, Embase, Cochrane Library, and Clinical Trials was conducted up to July 1, 2022. We included only randomized controlled trials (RCTs), in which omadacycline and other antibiotics were evaluated for treating acute bacterial infections in adults. The primary outcomes were clinical response and microbiological response, whereas the secondary outcome was the risk of adverse events (AEs).ResultsA total of seven RCTs involving 2841 patients with acute bacterial infection were included. Overall, our study illustrated that the clinical cure ratio of omadacycline was similar to the comparators in the treatment of acute bacterial infections (OR = 1.18, 95%CI = 0.96, 1.46, I2 = 29%). Omadacycline had a microbiological eradication rate similar to comparators in the treatment of acute bacterial infections (OR = 1.02, 95%CI = 0.81, 1.29, I2 = 42%). No statistical differences were observed between omadacycline and the comparators in terms of infection caused by Staphylococcus aureus (OR = 1.14, 95%CI = 0.80, 1.63, I2 = 0%), methicillin-resistant S. aureus (MRSA, OR = 1.28, 95%CI = 0.73, 2.24, I2 = 0%), methicillin-susceptible S. aureus (MSSA, OR = 1.12, 95%CI = 0.69, 1.81, I2 = 0%), and Enterococcus faecalis (OR = 2.47, 95%CI = 0.36, 16.97, I2 = 7%). A significant difference was found between omadacycline and the comparators for the risk of any AEs and treatment related AEs. The risk of discontinuation of the study drug due to an AEs was lower for omadacycline than for the comparators.ConclusionOmadacycline is as good as comparators in terms of efficacy and tolerance in the treatment of acute bacterial infections in adult patients. Thus, omadacycline is an appropriate option for antibiotic therapy in adult patients with acute bacterial infections.

MxA for differentiating viral and bacterial infections in adults: a prospective, exploratory study.

Inappropriate antibiotic prescription in patients with viral infections contributes to the surge of antibiotic resistance. Viral infections induce the expression of the antiviral protein MxA in monocytes, which is a promising biomarker to differentiate between viral and bacterial diseases. In this prospective, exploratory study, we aimed to determine the diagnostic value of monocyte MxA expression in adults with viral, bacterial or co-infections. We measured monocyte MxA expression using flow cytometry in a cohort of 61 adults with various viral, bacterial and co-infections including patients receiving immunosuppressive therapy. Monocyte MxA expression in virus-infected patients was significantly higher compared to bacterial infections (83.3 [66.8, 109.4] vs. 33.8 [29.3, 47.8] mean fluorescence intensity [MFI]; p < 0.0001) but not co-infections (53.1 [33.9, 88.9] MFI). At a threshold of 62.2 MFI, the area under the ROC curve (AUC) to differentiate between viral and bacterial infections was 0.9, with a sensitivity and specificity of 92.3% and 84.6%, respectively. Immunosuppressive therapy did not affect monocyte MxA expression in virus-infected patients. Our findings corroborate the diagnostic performance of MxA in differentiating viral and bacterial infections but also point to an important caveat of MxA in viral-bacterial co-infections. This study extends previous reports and indicates that MxA is also a useful biomarker in immunocompromised patients.

PD32-05 RATE OF PROGRESSION TO SEPSIS FOLLOWING PRESENTATION FOR ACUTE CYSTITIS

You have accessJournal of UrologyCME1 May 2022PD32-05 RATE OF PROGRESSION TO SEPSIS FOLLOWING PRESENTATION FOR ACUTE CYSTITIS Daniela Kaefer, Jeffrey Chiang, and A. Lenore Ackerman Daniela KaeferDaniela Kaefer More articles by this author , Jeffrey ChiangJeffrey Chiang More articles by this author , and A. Lenore AckermanA. Lenore Ackerman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002583.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary tract infection is one of the leading causes of bacterial infections in adults, with an annual incidence of 3% for males and 12.6% for females. Annual cost of UTI care is in excess of $3 billion dollars in the US alone, and with abundant outpatient antibiotic prescriptions written for cystitis despite a lack of evidence that this improves outcomes. We aimed to evaluate the incidence of presentation for cystitis at a tertiary academic medical center, associated rate of culture confirmed urinary tract infections, and rate of progression to sepsis based on initial visit type. We hypothesized a higher positive culture rate and progression to sepsis for patients initially presenting in the hospital setting. METHODS: We queried the Discovery Data Mart administered by the UCLA Office of Health Informatics and Analytics to identify direct patient encounters for acute cystitis based on corresponding ICD code from January 1, 2013 through July 1, 2021. Encounters were characterized as outpatient (office or telemedicine), or hospital-based encounters. Corresponding urinalysis and culture data was obtained in addition to patient demographics. Encounters were screened for subsequent outpatient encounters, hospital admissions, or sepsis diagnosis within seven days of initial visit. RESULTS: We identified 511,622 encounters for acute cystitis, of which 181,568 met inclusion criteria. The majority of encounters were office visits (74.5%) compared to hospital-based (21.9%) or telemedicine (3.6%) visits. Only 32,326 (17.8%) were associated with a positive urine culture. A urinalysis was not ordered in 67,386 (37.1%) of encounters, with telemedicine having a significantly lower rate of UA orders (3% vs 78% hospital and 61% office, p<0.00001). 42,772 patients had a follow up encounter within 7 days, of which only 6,411 were hospital encounters. Only 946 patients (0.5%) progressed to sepsis within 7 days, the majority of which were hospital encounters (1% vs 0.3 office and telemedicine, p<0.00001). CONCLUSIONS: Overall rate of progression to sepsis within one week following diagnosis of acute cystitis is low. Initial encounter in a hospital setting showed higher rate of progression compared to outpatient office or telemedicine visits. Risk of empiric antibiotic therapy and antibiotic stewardship must be considered given low rate of positive cultures and overall risk of progression to sepsis. Source of Funding: none © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e548 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniela Kaefer More articles by this author Jeffrey Chiang More articles by this author A. Lenore Ackerman More articles by this author Expand All Advertisement PDF DownloadLoading ...

Calculated parenteral initial treatment of bacterial infections: Introduction and antibiotics.

This is the first chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.This guideline is a revision of the recommendations published in 2010, taking into account recent substances and studies. As with previous revisions, the current situation of pathogen resistance and the results of new clinical trials are considered. The results are the present recommendations for parenteral calculated initial therapy of bacterial infections in adults. If several treatment options are mentioned, they are not always equivalent in their spectrum of microbiological activity. Therapeutic alternatives offer the opportunity to consider pathogen epidemiology, to avoid antibiotic intolerances or to escalate or de-escalate treatment in a manner suited to the situation. This article describes the different therapy options.

Calculated parenteral initial treatment of bacterial infections: Bone and joint infections.

This is the 10th chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.This chapter deals with bacterial Infections of bones, joints and prosthetic joints. One of the most pressing points is that after an initial empirical therapy a targeted antimicrobial which penetrates well to the point of infection and is tolerated well over the usually long duration of the therapy is chosen.

Calculated parenteral initial therapy of bacterial infections: Bacterial meningitis.

This is the thirteenth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Bacterial meningitis is a life-threatening infectious disease with high mortality and disability rates requiring prompt initiation of antimicrobial treatment to lower these rates.

Calculated parenteral initial treatment of bacterial infections: Respiratory infections.

This is the fifth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.It provides recommendations for the empirical and targeted antimicrobial treatment of lower respiratory tract infections, with a special emphasis on the treatment of acute exacerbation of COPD, community-acquired pneumonia and hospital-acquired pneumonia.

Calculated initial parenteral treatment of bacterial infections: Bacterial endocarditis.

This is the twelfth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.The bacterial endocarditis is characterised by a constant incidence but a shift in the patient population due to the use of prosthetic heart valves and foreign materials like pacemakers and the increasing application of invasive medical procedures. This is linked to a change in the predominant infecting organisms towards staphylococci. This chapter gives recommendations for the interdisciplinary management of infective endocarditis from the diagnostic workup over prevention to therapy with a focus on antibiotic therapy.

Calculated parenteral initial treatment of bacterial infections: Infections in the ear, nose, throat and mouth and jaw area.

This is the sixth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.The chapter deals with the antibacterial treatment of more severe infections of the ear, the nose, the throat and the maxillofacial region, including odontogenic and salivary gland infections.

Calculated initial parenteral treatment of bacterial infections: Bacterial gastrointestinal infections.

This is the fourteenth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Bacterial gastrointestinal infections are still the leading cause of death worldwide. The chapter describes the etiology of bacterial gastrointestinal infections in Germany and their frequency. Recommendations are given for the calculated therapy of these infections and for targeted antibiotic therapy for known pathogens. Particular attention is paid to Clostridium difficile. The diagnostic and therapeutic options of antibiotic therapy of the various infection patterns in this pathogen are discussed.

Calculated parenteral initial treatment of bacterial infections: Microbiology.

This is the second chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Preliminary microbiological findings regarding the patient and their immediate environment are crucial for the calculation of treatment with antibiotics in each case, as well as the resistance situation of the ward on which the patient is being cared for. If such data is not available, regional or supra-regional data can be used as a fallback. This chapter describes the methods of susceptibility testing, informs about the resistance situation in Germany and describes the main resistance mechanisms of bacterial pathogens against antibiotics. Further, the chapter informs about collateral damage of antibiotics as well as medical measures against increasing resistance.

Calculated parenteral initial therapy of bacterial infections: Antibiotic treatment in the elderly.

This is the fifteenth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Multimorbidity, an atypical symptomatology of infections in combination with multimedication, the associated interaction risks and serious consequences of synergistic side effects characterize the conditions when deciding on the use of antibiotics in old age. Strict decision regarding the indication itself, choice of the best antibiotic even considering rare side effects which may be dangerous in the elderly, determining the correct dose, dosing interval and the shortest possible duration according to the physiological status of the patient as well as monitoring effectiveness and toxicity detect expected and unexpected side effects early. Recommendations must reflect the peculiarities of antibiotic treatment in elderly patients.

Calculated initial parenteral treatment of bacterial infections: Safety and tolerabilty.

This is the fourth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Safety and tolerability of antimicrobial agents will be discussed in this chapter. Toxic, allergic and biological effects can be differentiated on the basis of their pathogenesis. The question of differences in the tolerability of specific antibiotics is of particular importance. However, due to limitations of the available data, it cannot be answered for most agents with the desired accuracy. For an assessment of rare side effects, results from the postmarketing surveillance have to be used.

Calculated parenteral initial treatment of bacterial infections: Infections of the kidneys and the genito-urinary tract.

This is the eighth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.The chapter deals with the treatment of more severe infections of the kidney and the urogenital tract, including urosepsis. Recommendations for empiric and targeted antibacterial treatment are given.

Calculated parenteral initial treatment of bacterial infections: Intra-abdominal infections.

This is the seventh chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.The chapter deals with the empirical and targeted antimicrobial therapy of complicated intra-abdominal infections. It includes recommendations for antibacterial and antifungal treatment.