Anti-infective Administration Research Articles

Clinical impact of the implementation of monocyte distribution width (MDW) measurement on time to anti-infective administration in sepsis patients in the emergency department: a before/after cohort study

BackgroundTimely recognition of sepsis in emergency department (ED) is challenging. We evaluated the impact of implementing the biomarker monocyte distribution width (MDW) at bedside, on the time to anti-infective administration.MethodsWe conducted a before-and-after cohort study in the ED of an academic hospital in Paris, to compare sepsis patients care and outcomes, before and after the implementation of point of care (POC) MDW measurement in the ED. During post-implementation period (period-2), MDW was measured with complete blood count by ED nurses with results given in 2 min: if above 21.5 units, ED physicians were asked to consider sepsis and to start an anti-infectious as soon as possible. Primary endpoint was time to anti-infectious administration (TTA) from ED arrival, and secondary endpoints were TTA from sepsis onset (TTAS), length of stay, mortality, and hospitalization rates.ResultsIn total, 255 patients (period-1) and 180 patients (period-2) with sepsis were included. The TTA was 5.4 h (3.5–7.7) period-1 and 4.9 h (IQR 2.5–7.1) in period-2 (p = 0.06). MDW implementation significantly reduced the median TTAS from to 3.7 h (IQR 1.5–5.8) in period-1, to 2.2 h (IQR 0.5–4.5) in period-2 (p < 0.001). Mortality rates remained similar between the two periods (18% vs. 16% respectively, p = 0.4), as did hospitalization rates (93% vs. 91%, p = 0.4) and ED length of stay (7.2 h (5.3–9.8) vs 7.0 (5.4–9.4), p = 0.7).ConclusionImplementing POC MDW measurement in the ED protocols enhances the timeliness of anti-infective administration from sepsis onset, meeting current sepsis management guidelines.

The Molecular Mechanisms and Therapeutic Potential of Cranberry, D-Mannose, and Flavonoids against Infectious Diseases: The Example of Urinary Tract Infections.

The treatment of infectious diseases typically includes the administration of anti-infectives; however, the increasing rates of antimicrobial resistance (AMR) have led to attempts to develop other modalities, such as antimicrobial peptides, nanotechnology, bacteriophages, and natural products. Natural products offer a viable alternative due to their potential affordability, ease of access, and diverse biological activities. Flavonoids, a class of natural polyphenols, demonstrate broad anti-infective properties against viruses, bacteria, fungi, and parasites. Their mechanisms of action include disruption of microbial membranes, inhibition of nucleic acid synthesis, and interference with bacterial enzymes. This review explores the potential of natural compounds, such as flavonoids, as an alternative therapeutic approach to combat infectious diseases. Moreover, it discusses some commonly used natural products, such as cranberry and D-mannose, to manage urinary tract infections (UTIs). Cranberry products and D-mannose both, yet differently, inhibit the adhesion of uropathogenic bacteria to the urothelium, thus reducing the likelihood of UTI occurrence. Some studies, with methodological limitations and small patient samples, provide some encouraging results suggesting the use of these substances in the prevention of recurrent UTIs. While further research is needed to determine optimal dosages, bioavailability, and potential side effects, natural compounds hold promise as a complementary or alternative therapeutic strategy in the fight against infectious diseases.

Intrathecal Antibacterial and Antifungal Therapies.

Intrathecal administration of anti-infectives is indicated in central nervous system infections by multiresistant pathogens when drugs that can reach adequate cerebrospinal fluid (CSF) concentrations by systemic therapy are not available. Antibiotics that readily pass the blood-brain and blood-CSF barriers and/or that have low toxicity allowing an increase in the daily dosage should not be used for intrathecal therapy. Intrathecal therapy is accompanied by systemic treatment. Antibacterials indispensable for intrathecal therapy include aminoglycosides, colistin, daptomycin, tigecycline, and vancomycin. Limited experience suggests the utility of the antifungals amphotericin B and caspofungin. Intraventricular administration ensures distribution throughout the CSF compartment, whereas intralumbar dosing often fails to attain adequate antibiotic concentrations in the ventricles. The individual dose is determined by the estimated size of the CSF space and by the estimated clearance from CSF. For moderately lipophilic anti-infectives with a molecular weight above approximately 1,000 g/mol, as well as for hydrophilic drugs with a molecular weight above approximately 400 g/mol, one daily dose is normally adequate. The ventricular drain should be clamped for 15 to 120 min to facilitate the distribution of the anti-infective in the CSF space. Therapeutic drug monitoring of the trough levels is necessary only in cases of therapeutic failure.

Not all organ dysfunctions are created equal – Prevalence and mortality in sepsis

PurposeWhile organ dysfunctions within sepsis have been widely studied, interaction between measures of organ dysfunction remains an understudied area. The objective of this study is to quantify the impact of organ dysfunction on in-hospital mortality in infected population. Materials and methodsDescriptive and multivariate analyses of retrospective data including patients (age ≥ 18 years) hospitalized at the study hospital from July 2013 to April 2016 who met the criteria for an infection visit (62,057 unique visits). ResultsThe multivariate logistic regression model had an area under the curve of 0.9. Highest odds ratio (OR) associated with increased mortality risk was identified as fraction of inspired oxygen (FiO2) > 21% (OR = 5.8 and 95% Confidence Interval (CI) 1.8–35.6), and elevated lactate >2.0 mmol/L (OR = 2.45 (95% CI = 2.1–2.8)). Most commonly observed measures of organ dysfunction within mortality visits included elevated lactate (> 2.0 mmol/L), mechanical ventilation, and oxygen saturation (SpO2)/FiO2 ratio (< 421) at least once within 48 h prior to or 24 h after anti-infective administration. ConclusionThere exist differences in measures of organ dysfunction occurrence and their association with mortality. These findings support increased clinical efforts to identify sepsis patients to inform diagnostic decisions.

Review of Intraocular Pharmacokinetics of Anti-Infectives Commonly Used in the Treatment of Infectious Endophthalmitis.

Although intravitreal administration of anti-infectives represents the standard treatment for infectious endophthalmitis, the knowledge about their pharmacokinetics is still limited. In this review, we aimed to summarise the factors influencing the pharmacokinetics of the anti-infective agents. We have conducted a comprehensive review of the preclinical pharmacokinetic parameters obtained in different studies of intravitreal injections of anti-infectives performed on animals, mainly rabbits. The two aspects with the biggest influence on pharmacokinetics are the distribution in the vitreous humour and the elimination through the posterior segment. The distribution can be affected by the molecular weight of the drug, the convection flow of the vitreous, the condition of the vitreous humour depending on the age of the patient, the possible interactions between the drug and the components of the vitreous, and the presence of vitrectomy. Meanwhile, the elimination includes the metabolism of the drug, the clearance via the anterior and posterior routes, and the possible inflammation of the eye resulting from the disease. Understanding the pharmacokinetics of the anti-infectives used in clinical practice is essential for a correct application. The information provided in this review could offer guidance for selecting the best therapeutic option according to the characteristics of the drugs.

Uveítis: etiopatogenia, diagnóstico y tratamiento

ConceptUveítis is a syndrome characterized by inflammatory involvement of the ocular vascular layer between the sclera and the retina in the eyeball. They are classified by different criteria that include the topography of the uveal lesion, the pathogenesis and the etiology of the process. EtiopathogenyUveítis is due to infectious etiologies or processes of pathogenesis mediated by the immune system without evidence of microbiological trigger. These uveítis that are considered autoimmune may occur with extraocular clinical manifestations of the associated disease or be absent. Diagnosis and treatmentUveítis are processes that require an adequate ophthalmological and systemic evaluation with a rational use of resources and complementary tests. Treatment is based on the etiology or pathogenesis of the disease. It requires a local ocular control strategy of the inflammatory process and as appropriate the systemic administration of anti-infectives or immunosuppressants.

Implementation of a Value-Driven Outcomes Program to Identify High Variability in Clinical Costs and Outcomes and Association With Reduced Cost and Improved Quality.

Transformation of US health care from volume to value requires meaningful quantification of costs and outcomes at the level of individual patients. To measure the association of a value-driven outcomes tool that allocates costs of care and quality measures to individual patient encounters with cost reduction and health outcome optimization. Uncontrolled, pre-post, longitudinal, observational study measuring quality and outcomes relative to cost from 2012 to 2016 at University of Utah Health Care. Clinical improvement projects included total hip and knee joint replacement, hospitalist laboratory utilization, and management of sepsis. Physicians were given access to a tool with information about outcomes, costs (not charges), and variation and partnered with process improvement experts. Total and component inpatient and outpatient direct costs across departments; cost variability for Medicare severity diagnosis related groups measured as coefficient of variation (CV); and care costs and composite quality indexes. From July 1, 2014, to June 30, 2015, there were 1.7 million total patient visits, including 34 000 inpatient discharges. Professional costs accounted for 24.3% of total costs for inpatient episodes ($114.4 million of $470.4 million) and 41.9% of total costs for outpatient visits ($231.7 million of $553.1 million). For Medicare severity diagnosis related groups with the highest total direct costs, cost variability was highest for postoperative infection (CV = 1.71) and sepsis (CV = 1.37) and among the lowest for organ transplantation (CV ≤ 0.43). For total joint replacement, a composite quality index was 54% at baseline (n = 233 encounters) and 80% 1 year into the implementation (n = 188 encounters) (absolute change, 26%; 95% CI, 18%-35%; P < .001). Compared with the baseline year, mean direct costs were 7% lower in the implementation year (95% CI, 3%-11%; P < .001) and 11% lower in the postimplementation year (95% CI, 7%-14%; P < .001). The hospitalist laboratory testing mean cost per day was $138 (median [IQR], $113 [$79-160]; n = 2034 encounters) at baseline and $123 (median [IQR], $99 [$66-147]; n = 4276 encounters) in the evaluation period (mean difference, -$15; 95% CI, -$19 to -$11; P < .001), with no significant change in mean length of stay. For a pilot sepsis intervention, the mean time to anti-infective administration following fulfillment of systemic inflammatory response syndrome criteria in patients with infection was 7.8 hours (median [IQR], 3.4 [0.8-7.8] hours; n = 29 encounters) at baseline and 3.6 hours (median [IQR], 2.2 [1.0-4.5] hours; n = 76 encounters) in the evaluation period (mean difference, -4.1 hours; 95% CI, -9.9 to -1.0 hours; P = .02). Implementation of a multifaceted value-driven outcomes tool to identify high variability in costs and outcomes in a large single health care system was associated with reduced costs and improved quality for 3 selected clinical projects. There may be benefit for individual physicians to understand actual care costs (not charges) and outcomes achieved for individual patients with defined clinical conditions.

Study of the prevalence of nosocomial infections and associated factors in the two university hospitals of Lubumbashi, Democratic Republic of Congo

IntroductionEstimer la prévalence « un jour donné » des infections nosocomiales et déterminer leurs facteurs associés, ensuite estimer la prévalence des micro-organismes responsables des infections nosocomiales de Lubumbashi, République Démocratique du Congo.MéthodesUne étude transversale descriptive a été menée dans les deux hôpitaux de Lubumbashi au sein de cinq services d’hospitalisation (Chirurgie, Gynéco-Obstétrique, Médecine interne, Pédiatrie et Réanimation). L’échantillon était constitué de 171 patients hospitalisés et qui ont été interrogés à l’aide d’un questionnaire standardisé. La fiche médicale nous a permit de connaitre le type d’antibiotique administré au patient 48 heures après d’admission. Notre étude s’est déroulée durant le mois de février 2010 dans le cadre de la première enquête locale de prévalence des infections nosocomiales.RésultatsNotre étude a permis de recenser 59 patients atteints d’une infection nosocomiale. La prévalence globale est de 34,5% (dont 17,0% pour une infection nosocomiale acquise et 17,5% pour une infection importée). L’infection nosocomiale a été définie selon l’Organisation Mondiale de la Santé comme toute infection acquise pendant un séjour à l’hôpital et qui n’était ni présente ni en incubation au moment de l’admission du patient. Les facteurs de risque suivants ont été associés aux infections nosocomiales acquises: durée d’hospitalisation (les patients admis en long séjour, séjour de plus de sept jours d’hospitalisation avaient un risque plus élevé que ceux admis en séjour court, séjour inférieur ou égal à sept jours d’hospitalisation (Ratio de prévalence: RP =3,6 [IC a 95% 1,4-8,9]). Parmi les infections nosocomiales, les infections du site opératoire étaient les plus fréquentes (27,1%), suivies des infections pulmonaires (22,0%) et des infections urinaires (17,0%). L’examen microbiologique a permis de mettre en évidence cinq germes responsables d’une infection nosocomiale chez les patients infectés : Escherichia coli (11,9%), Staphylococcus aureus (6,8%), Pseudomonas aeruginosa (5,1%), Shigella spp (5,1%) et Salmonela typhi (1,7%). L’examen microbiologique n’a été réalisé que dans 31,0 % (n=59). La cefotaxime, céphalosporine de 3ème génération était l’antibiotique le plus prescrit (37,9%), suivi de l’amoxicilline (19,6%) et l’ampicilline (16,3%) en monothérapie. La bi et la trithérapie ont été également prescrites. La voie parentérale était la plus utilisée pour administrer un anti-infectieux. La prévalence d’infections nosocomiales différait significativement entre les deux hôpitaux universitaires ; la prévalence d’une infection nosocomiale acquise est de 22,2% aux Cliniques Universitaires de Lubumbashi et 13,1% à l’hôpital Sendwe.ConclusionDans notre travail, la prévalence globale des infections nosocomiales était de 34,5%. Les infections du site opératoire étaient les plus fréquentes (27,1%). L’Escherichia coli était le germe le plus fréquent soit 11,9%.

Investigation and analysis on anti-infective administration in out-patients of our hospital

Objective To investigate the use of anti-infective drugs in outpatients of our hospital, and to pro-mote rational administration in clinic. Methods Collecting the prescriptions of out-patient during June 2007 in our pharmscy,then statistically analyze the anti-infective drugs information in combination with adverse drug reaction (ADR) reports. Results The percentage of prescriptions was 45. 8%, the average amount of the prescriptions was 62. 56 yuan,the cost of anti-infective drugs accounted for 41.8% ,prescriptions of combined use and injection were 39.5% and 37.2% ,the ratio of ADR was 80. 6% ,irrational administration accounted for 10. 8%. Conclusion The use of anti-infective drugs in our prescriptions of out-patients has some problems, but rational use is the main trend in our hospital. Key words: Anti-infective drugs; Out-patients

Mycobacterial infection models

In July 1996 (17-20), two years after the first edition held in Helsinore (Denmark), the second symposium on the role of animal models in the investigation of antimicrobial chemotherapy took place in Reykjavik, Iceland, under the auspices of the International Society for Antiinfective Pharmacology (ISAP) and European Network for the Study of Experimental Infections (ENSEI), a working group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). This symposium was chaired by Professor Sigurdur Gudmundsun. Several aspects of animal models of infections were discussed through main lectures, poster presentations and technical demonstrations: development of new models, pathophysiologic investigations leading to potentially new therapeutic targets and evaluation of new drugs or new modalities of administration of antiinfectives, in order to improve efficacy, reduce toxicity or prevent emergence of resistance. Special attention was paid to the ethical questions raised by the use of animal models: why do we need them? How could we insure that their use is scientifically sound and that the conditions of care to the animals are definitely humane? The Editorial Board of CMI has selected s i x notes coming from the reports of this symposium, as they were thought to illustrate some of the current uses of and main questions raised by the models and to be of potential general interest for the readership of the Journal. These notes will appear divided into two parts in two consecutive issues. Claude Carbon