Use Of Anti-infective Agents Research Articles

Characterization of Coinfections in Patients with COVID-19.

Little is known about coinfections in patients with COVID-19, with antibiotics often initiated empirically. To determine the rates and characteristics of early and late coinfections in COVID-19 patients and to characterize the use of anti-infective agents, especially antibiotics. This retrospective chart review involved patients with COVID-19 who were admitted to Lions Gate Hospital (Vancouver, British Columbia) between January 1 and June 30, 2020. Data were extracted from electronic medical records, and descriptive statistics were used to analyze the data. Of the 48 patients admitted during the study period, 10 (21%) were determined to have coinfections: 3 (6%) had early coinfections and 7 (15%) had late coinfections. Early empiric use of antibiotics was observed in 32 (67%) patients; for 29 (91%) of these 32 patients, the therapy was deemed inappropriate. Patients with coinfections had longer hospital stays and more complications. Despite low rates of early coinfection, empiric antibiotics were started for a majority of the patients. Most late coinfections occurred in patients in the intensive care unit who required mechanical ventilation. Patients with coinfections had poorer outcomes than those without coinfections.

Antibiotic stewardship

The spread of antimicrobial resistance (AMR) is one of the greatest threats to global health and causes very many deaths. Also in the context of sepsis-the severest complication of certain infectious diseases-does AMR play arole. Wise use of anti-infectives and application of antibiotic stewardship (AMS) principles can reduce the spread of AMR and improve the quality of management of patients with infectious diseases. Correct use of anti-infective agents includes the correct diagnostic approach and documentation of the (suspected) diagnosis, guideline-conform diagnostic workup and treatment selection, re-evaluation and tailoring during the course of treatment, afocus on treatment de-escalation depending on clinical response and microbiology results, dose optimization, and, if possible, conversion to oral therapy, and early termination of treatment if the suspected diagnosis is not confirmed. Particularly adherence to the guideline-conform treatment duration can reduce unnecessary use of anti-infectives. Prevention of infections via adherence to vaccination recommendations also contributes to areduction in the use of anti-infectives. Interdisciplinary collaboration with infectious diseases and AMS specialists, as recommended for sepsis, also improves treatment quality and patient outcomes. Particularly for complex infections such as endocarditis cases should be discussed in multidisciplinary teams including specialists in infectious diseases. In this manner, decisive steps against the spread of AMR and towards maintenance of the efficacy of available anti-infective drugs can be taken.

P329 Stool multiplex molecular PCR assay in comparison to conventional stool tests for detecting gastrointestinal infections as cause of flares in Inflammatory Bowel Disease

Abstract Background Inflammatory bowel disease (IBD) is characterized by unpredictable flares. Other than natural history, flares can be caused by superadded gastrointestinal (GI) tract infections. Diagnosis of infection is conventionally made by microscopy and culture of stool specimens. These are limited by lengthy turnaround time, low sensitivity, inability to detect agents other than bacteria, and effect of pre-test antibiotic usage.Stool multiplex molecular PCR assay allows simultaneous detection of nucleic acids from 23 bacteria, viruses and parasites. Methods We aimed to: 1. Compare infectious organisms detected by stool multiplex PCR assay and conventional stool tests during flare in patients with IBD. 2. Determine impact of detection of infective agents in the management of flares, as measured by use of anti-infective agents. In this single centre, prospective, cohort study, every patient underwent conventional stool tests (microscopy, culture and Clostridioides Difficile toxin assay) and multiplex PCR assay by Biofire® FilmArray test. Consenting patients above 18 years with IBD flare were included. Patients with colorectal cancer, toxic megacolon, intestinal perforation, previous IBD surgery were excluded. Results Of 60 patients, 53 patients were of Ulcerative colitis (UC) and 7 were of Crohn’s disease (CD). The mean age of patients with UC was 42.32 years and that of CD was 37.5 years. Of the patients with UC, 26 were male and 27 were female. In CD, 4 were male and 3 were female. Stool Biofire® resulted in better organism detection rate (Table 1) and more frequent need for change in management (Table 2) as compared to conventional tests. The cost per stool Biofire® was INR 12000 (€142) and that of conventional stool tests INR 4300 (€51). However, the cost to achieve one positive result on stool Biofire® that led to change in management was INR 65,454 (€773) as compared to INR 86,000 (€1015) for conventional stool tests. Conclusion Stool Biofire® resulted in significantly more organism detection (33 vs 6 pts). It also led to more frequent need for change in management as compared to conventional stools tests (11 vs 3 pts). It also proved more cost-effective than conventional stool tests in terms of change in management of flare in patients with IBD.

Impact of High-Dose Anti-Infective Agents on the Osteogenic Response of Mesenchymal Stem Cells.

Treatment of infected nonunions and severe bone infections is a huge challenge in modern orthopedics. Their treatment routinely includes the use of anti-infective agents. Although frequently used, little is known about their impact on the osteogenesis of mesenchymal stem cells. In a high- and low-dose set-up, this study evaluates the effects of the antibiotics Gentamicin and Vancomycin as well as the antifungal agent Voriconazole on the ability of mesenchymal stem cells to differentiate into osteoblast-like cells and synthesize hydroxyapatite in a monolayer cell culture. The osteogenic activity was assessed by measuring calcium and phosphate concentrations as well as alkaline phosphatase activity and osteocalcin concentration in the cell culture medium supernatant. The amount of hydroxyapatite was measured directly by radioactive 99mTechnetium-HDP labeling. Regarding the osteogenic markers, it could be concluded that the osteogenesis was successful within the groups treated with osteogenic cell culture media. The results revealed that all anti-infective agents have a cytotoxic effect on mesenchymal stem cells, especially in higher concentrations, whereas the measured absolute amount of hydroxyapatite was independent of the anti-infective agent used. Normed to the number of cells it can therefore be concluded that the above-mentioned anti-infective agents actually have a positive effect on osteogenesis while high-dose Gentamycin, in particular, is apparently capable of boosting the deposition of minerals.

Impact of medical care, including use of anti-infective agents, on prognosis of COVID-19 hospitalized patients over time

IntroductionThe effect of anti-infective agents in COVID-19 is unclear. The impact of changes in practice on prognosis over time has not been evaluated. MethodsSingle center, retrospective study in adults hospitalized in a medicine ward for COVID-19 from March 5th to April 25th 2020. Patient characteristics were compared between two periods (before/after March 19th) considering French guidelines. The aim of the study was to evaluate how medical care impacted unfavorable outcome, namely admission to intensive care unit (ICU) and/or death. ResultsA total of 132 patients were admitted: mean age 59.0±16.3 years; mean C-reactive protein (CRP) level 84.0±71.1 mg/L; 46% had a lymphocyte count <1000/mm3. Prescribed anti-infective agents were lopinavir-ritonavir (n=12), azithromycin (AZI) (n=28) and AZI combined with hydroxychloroquine (HCQ) (n=52). There was a significant decrease in ICU admission, from 43% to 12%, between the two periods (P<0.0001). Delays until transfer to ICU were similar between periods (P=0.86). Pulmonary computerized tomography (CT)-scans were performed significantly more often with time (from 50% to 90%, P<0.0001), and oxygen-dependency (53% vs 80%, P=0.001) and prescription of AZI±HCQ (from 25% to 76%, P<0.0001) were also greater over time. Multivariate analyses showed a reduction of unfavorable outcome in patients receiving AZI±HCQ (hazard ratio [HR]=0.45, 95% confidence interval [CI: 0.21-0.97], P=0.04), particularly among an identified category of individuals (lymphocyte ≥1000/mm3 or CRP ≥100 mg/L). ConclusionThe present study showed a significant decrease in admission to ICU over time, which was probably related to multiple factors, including a better indication of pulmonary CT-scan, oxygen therapy, and a suitable prescription of anti-infective agents.

Predicting acute respiratory infection in Chinese healthy individuals: A effective way of patient care

Several anti-infective agents are available in the treatment of acute respiratory infection. Use of anti-infective agents has hardly been directed by laboratory finding. We hypothesis the clinical fore casters of acute respiratory can assist in making right treatment decision and avoid needless use of antibiotic. This nurse led care research designed to observe predictive factors this can assist in making right treatment decision and avoid needless use of antibiotic. In this retrospective study, medical records of adults and who were suffering from acute respiratory infection and had influenza like symptoms which includes high body temperature, body ache, muscle pain, cough, and sore throat. Based on the signs and symptoms, patients were subjected in laboratory examination and culture test. Medical records of Chinese patients with confirm diagnosis of influenza was selected. We also assessed the medical records of patients with no influenza based on laboratory investigation. Correlation of signs and symptoms with laboratory examination was performed to identify the best predictive factors of acute respiratory infection which can assist in making right treatment decision and avoid needless use of antibiotic. Medical records of 1220 adults who were suffering from influenza like symptoms at baseline were reviewed by nurse. Of total subjects, a total of 824 (67.5%) were identified to have acute respiratory infection (influenza). We observed significantly higher incidence of cough, high body tem (fever) and both was noted among the patients who had acute respiratory infection (influenza) compared to those patients with no acute respiratory infection (influenza). Mixed model analysis revealed high correlation of two symptoms (cough and fever) with acute respiratory infection (influenza). The results of this nurse led care research suggested that Chinese patients who experienced cough and fever within first 48 h of onset of acute respiratory infection are more likely to have influenza, and thus appropriate antiviral therapy is recommended in patients with acute respiratory infection (influenza). Prediction of acute respiratory infection based on early symptoms is one of the effective ways of patient care. Our study results will assist in making right treatment decision and avoid needless use of antibiotic.

Drug use in delivery hospitalization: Pelotas births cohort, 2015.

ABSTRACTOBJECTIVE:Trace the pattern of drug use during delivery hospitalization.METHOD:Cross-sectional study carried out from June to October 2015, included in the 2015 Pelotas births cohort. All women living in the urban area of the city who were hospitalized for delivery were part of the sample. We collected information regarding drug prescription and drug use by mothers during the whole period of hospitalization. Sociodemographic data were obtained in interview after delivery, and other data were obtained from medical charts. The drugs were classified according to the Anatomical Therapeutic Chemical system.RESULTS:All study participants (1,392 women) used at least one drug, with the mean amount being larger the higher the age of the mother, both prepartum/during delivery and postpartum. It was also higher in cases of spinal anesthesia or general anesthesia, cesarean deliveries, school hospitals, and longer hospitalizations. Analysis of the sample as a whole showed no significant difference in the number of drugs used according to hospitalization type, but when stratified by length of hospital stay the mean was higher in SUS hospitalizations than in private and health insurance hospitalizations. Drugs for the nervous system were the most used (30.5%), followed by drugs for the alimentary tract and metabolism (13.8%). The use of anti-infective agents and drugs that act on the cardiovascular and respiratory systems was higher in mothers who underwent cesarean delivery. This study showed high drug consumption in the delivery hospitalization period, and showed cesarean delivery and epidural anesthesia as the main factors related to high drug consumption in this period.CONCLUSIONS:We found high drug consumption in the delivery hospitalization period, and the main factors were cesarean delivery and epidural anesthesia. Drugs that act on the nervous system were the most used.

Antibiotic stewardship : Measures for optimizing prescription of anti-infective agents

Antibiotic stewardship (ABS) comprises abundle of different interventions to improve anti-infective treatment in ahospital setting. An important component of ABS interventions is the interdisciplinary approach to infection management. Besides improving infrastructural aspects on ahospital level, including surveillance of the use of anti-infective agents and nosocomial infections, collation and interpretation of statistics on resistance and formulation of local treatment guidelines, ABS teams go to the wards and advise treating physicians on antibiotic therapy. Frequent approaches for optimization are selection of substances, administration route, dosing of medication and duration of treatment. An important overall objective of ABS is the reduction of resistance induction in order to preserve the therapeutic efficiency of antibiotics. Anumber of studies have shown that this goal can be achieved in different clinical settings without negatively affecting patient outcome. The strategies of ABS can also be applied with no problems to critically ill patients on the intensive care unit.

Local antibiotic therapy

The treatment of superficial wound infections with local antibiotics is considered to be problematic as it is accompanied by an increased risk of resistance development and ineffectiveness in deeper regions. On the contrary, the local application of antibiotics is useful in arthroplasty and necessary if implants are utilized. The reason for this is the prevention of a rapid biofilm formation on foreign implants and aresulting infection may remain undiscovered until it becomes chronic. Apart from exogenous material, necrotic tissue (e. g. bone sequestra) provides suitable retreat areas for pathogens in the body. Because of the characteristics of bone and joint infections and an exceptional infection recurrence rate, acombined approach is required. Systemic antibiotic prophylaxis is able to reduce the number of pathogens acquired by perioperative contamination or hematogenic spread from another focus of infection; however, systemically applied antibiotics often fail to form an effective colonization barrier around the implant because their ability to penetrate the bone is relatively low. On the other hand, the high concentration of locally released antibiotics leads to an effective protection of the implant from bacteria in situ. Thus, for the treatment of implant-associated infections, systemic and local application of anti-infective agents is areliable adjuvant measure that improves the therapeutic success. Polymethylmethacrylate (PMMA) bone cement is the most commonly used local drug carrier. Based on clinical and microbiological results, microbiologists and infectious disease experts together with the surgeon and pharmacist determine which anti-infective agents are indicated for systemic and local, PMMA cement-related application. Because there is no evident concept for the local application, unlike the recommendation for systemic use of anti-infective agents, this review article describes which aspects should be taken into account.

Antiinfective therapy for pregnant or lactating patients in the emergency department.

Special considerations in pharmacotherapy for infectious diseases in pregnant and lactating women in the emergency department (ED) setting are reviewed. With many women turning to the ED as a source of primary care, it is essential for pharmacists involved in providing ED services to guide the selection of appropriate antiinfective agents during pregnancy and lactation; this area of practice is complicated by the very limited body of published data on the safety and efficacy of maternal antimicrobial use and potential fetal or neonatal adverse effects. Infectious diseases commonly encountered in the ED include sexually transmitted diseases, bacterial vaginosis and other vaginal infections, respiratory and urinary tract infections, and pneumonia. Recommended first-line therapies for pregnant or lactating women may differ from those recommended for other patient populations. Although some widely used antiinfective classes and agents are generally considered safe for use in pregnant women, others (e.g., clarithromycin, fluoroquinolones) have been linked to birth defects and neonatal adverse effects. In addition to guiding ED practitioners in the appropriate use of antiinfective agents in pregnant women and nursing mothers, pharmacists can reinforce the importance of appropriate follow-up care (including specialist referral or culture testing in some cases) and ongoing preventive health measures such as vaccine administration. The use of antiinfective agents in pregnant or lactating women requires consideration not only of the drugs' effectiveness but also their possible effects on the fetus or newborn and the nature of follow-up care. References are available to help clinicians make treatment decisions.

Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

BackgroundThe limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen.MethodsWe established a C. elegans – S. aureus liquid-based assay to screen for potential anti-infectives against S. aureus. The assay was utilized to screen 37 natural extracts and 29 synthetic compounds for the ability to extend the lifespan of infected nematodes. Disc diffusion and MIC microdilution tests were used to evaluate the anti-microbial properties of these natural extracts and synthetic compounds whilst in vivo bacterial CFU within the C. elegans gut were also enumerated.ResultsWe screened a total of 37 natural extracts and 29 synthetic compounds for anti-infective properties. The screen successfully revealed 14 natural extracts from six plants (Nypa fruticans, Swietenia macrophylla, Curcuma longa, Eurycoma longifolia, Orthosiphon stamineus and Silybum eburneum) and one marine sample (Faunus ater) that improved the survival of S. aureus-infected worms by at least 2.8-fold as well as 14 synthetic compounds that prolonged the survival of S. aureus-infected nematodes by 4-fold or greater. An anti-microbial screen of all positive hits demonstrated that 8/28 hits had no effect on S. aureus growth. Of these 8 candidates, 5 of them also protected the worms from MRSA infection. We also noted that worms exposed to N. fruticans root and O. stamineus leaf extracts showed reduced intestinal colonization by live S. aureus. This suggests that these extracts could possibly activate host immunity to eliminate the bacteria or interfere with factor/s that prevents pathogen accumulation.ConclusionWe have successfully demonstrated the utility of this liquid-based screen to identify anti-infective substances that prolong S. aureus-infected host survival without affecting bacterial cell viability.

Reduction in Use of Anti-Infective Agents and Incidence of Infections After the Introduction of Antimicrobial Stewardship Program and Enhanced infection Prevention Program Supported by a Newly Implemented Decision Support System

The imperative to reduce the incidence of healthcare-associated infections (HAIs) by 50% over a 12 month period was identified as a strategic challenge from a clinical and financial standpoint for an acute care community hospital with operating 297 beds. The following describes the impact of introducing a multidisciplinary antibiotic stewardship program (ASP) and enhanced infection prevention program featuring the use of a decision support system (DSS). The results of physician acceptance, antimicrobial use, and subsequent impact on incidence of HAIs will be presented.

Potential microbial origins of schizophrenia and their treatments

Schizophrenia is a severe brain disease that affects approximately 1% of the world's population. Extensive study into the indication of and causes of this disease has been ongoing for decades. Historical review of research into associated abnormalities and markers common in schizophrenic patients has demonstrated a correlation with potential microbial origins in the development of the disease. While infectious etiologies could be responsible for some cases of schizophrenia, no consistent use of anti-infective agents has been developed for its prevention or treatment. Elucidation of the mechanisms for infectious roots of schizophrenia may open new avenues for effective treatment.

Predictors of unstable anticoagulation in African Americans

We sought to identify contributors to unstable anticoagulation in African Americans. Sixty African Americans on warfarin were enrolled. Cytochrome P450 2C9 and vitamin K epoxide reductase genotypes and vitamin K intake were assessed, and clinical and dietary data during the 12 months prior to enrollment were collected. Data were compared between stable and unstable patients, classified based on the proportion of international normalized ratio (INR) values outside the therapeutic range. The median proportion of out-of-range INRs among study participants was 44%; 28 patients had a higher proportion of INRs out-of-range and were included in the unstable group, with the remaining constituting the stable group. The median (IQR) number of clinic visits/year was higher among unstable versus stable patients [18 (15-22) vs. 16 (13-19); P = 0.03]. Higher warfarin doses, lower adherence, vomiting or diarrhea, and use of antiinfective agents were more common among unstable patients. Genotype was not associated with anticoagulation stability. After regression analysis, only poor adherence and gastrointestinal illness remained predictive of unstable anticoagulation. In a control group of Caucasians of similar age and sex distribution, poor adherence, but not gastrointestinal illness, was associated with unstable anticoagulation. We conclude that poor warfarin adherence and gastrointestinal illness are major contributors to unstable anticoagulation in African Americans. Our data suggest that, similar to Caucasians, improving warfarin adherence rates may be an important mean to improve anticoagulation control in African Americans. In addition, close monitoring during acute illness may be particularly important in this population.

Therapeutic Interventions for the Treatment and Control of Influenza

Objective: To review antiviral management of influenza and discuss recent developments in antiviral resistance. Data Sources: Literature retrieval was accessed through MEDLINE/PubMed (1977–February 2007) using the terms influenza, resistance, adamantanes, and neuraminidase inhibitors, treatment, and prevention. In addition, reference citations from identified publications were reviewed. Study Selection and Data Extraction: All articles in English identified from the data sources were evaluated. Data Synthesis: Infection with influenza is associated with 36,000 deaths and more than 200,000 hospitalizations in the US each year and results in a large economic burden on society. We reviewed 7 trials describing management of influenza; the results showed that 92% of influenza cases demonstrated adamantane resistance in 2005. Selection of treatment for influenza with a neuraminidase inhibitor should be based on patient preference, past medical history, and managed care restrictions since one agent has not demonstrated superiority. Early initiation of treatment, within 12 hours of symptom onset (compared with 48 h), has resulted in illness being shortened by more than 3 days. Conclusions shown in the trials reviewed here regarding the consequences of increasing incidence of influenza A resistance include: viral surveillance cultures are important, influenza has a significant global impact, and inappropriate use of antiinfective agents results in local and global resistance. Conclusions: Therapeutic options for the management of influenza include the neuraminidase inhibitors, zanamavir and oseltamivir. Unfortunately, new classes of antiviral drugs for influenza will not be forthcoming in the near future. Adamantane resistance is now commonly demonstrated in influenza. At this time, efforts should be made to minimize patient risk for infection.

Use of anti-infective agents during lactation, Part 3: Antivirals, antifungals, and urinary antiseptics.

Because many antibiotics are excreted into the breast milk, it can be difficult for a practitioner to choose an antibiotic for a lactating patient that will have minimal risks to her nursing infant. This article is the last of a three-part series discussing the use of anti-infective agents during lactation. The authors review general information with regard to use and common side effects for several classes of antibiotics. They summarize information, including available safety data, documented milk concentrations, milk-to-plasma ratios, and other pharmacokinetic properties, to help practitioners choose antibiotics that may be considered safe to use in the lactating mother.

Use of anti-infective agents during lactation: Part 2--Aminoglycosides, macrolides, quinolones, sulfonamides, trimethoprim, tetracyclines, chloramphenicol, clindamycin, and metronidazole.

Because many antibiotics are excreted into breast milk, it can be difficult for a practitioner to choose an antibiotic for a lactating patient that will have minimal risks to her nursing infant. This article is the second of a three-part series discussing the use of anti-infective agents during lactation. The authors review general information regarding use and common side effects for several classes of antibiotics. They also summarize information, including documented milk concentrations, milk-to-plasma ratios, and other pharmacokinetic properties, in a table that can help practitioners choose antibiotics that may be considered safe to use in the lactating mother.

Use of anti-infective agents during lactation: Part 1--Beta-lactam antibiotics, vancomycin, quinupristin-dalfopristin, and linezolid.

Because many antibiotics are excreted into the breast milk, it can be difficult for a practitioner to choose an antibiotic for a lactating patient that will have minimal risks to her nursing infant. This article is the first of a three-part series discussing the use of anti-infective agents during lactation. The authors review general information regarding use and common side effects of several classes of antibiotics. They also summarize information, including documented milk concentrations, milk-to-plasma ratios, and other pharmacokinetic properties, in a table that can help practitioners choose antibiotics that may be considered safe for the lactating mother.

ANTIBIOTIC SELECTION FOR PATIENTS WITH SEPTIC SHOCK

Early recognition of the sepsis syndrome, prompt administration of broad-spectrum antibiotics, surgical intervention when indicated, and aggressive supportive care in intensive care units remain the therapeutic strategies for patients with sepsis. Antibiotic selection is based on many factors including the most probable source of infection, the most likely pathogens, and knowledge of antibiotic susceptibility patterns for community- and hospital-acquired infections. Unfortunately, with this approach, mortality remains unacceptably high. Adjuvant therapies such as antiendotoxin antibodies, cytokine antagonists, and anti-inflammatory agents aimed at blunting the host immune response to bacterial infection have provided little clinical benefit to date. As our understanding of the pathophysiology of sepsis progresses, perhaps newer modalities will improve clinical outcome. At this time, preventive strategies, including optimal vaccine use, effective infection control practices, judicious use and care of intravascular lines and indwelling urinary catheters, and appropriate use of anti-infective agents to prevent microbial resistance should be used to decrease the incidence of infection and subsequent sepsis.

A modern look at folkloric use of anti-infective agents.

Infectious diseases are of ancient origin, and mankind has a venerable history of use of higher plant extracts for the therapy of such infections. Some such agents survive in use from earlier times--quinine, emetine, and sanguinarine, for example--but the modern use of fermentation-based antibiotics has greatly overshadowed work on agents from other sources. After a brief review of the present status of the field of antibiotics, this review focuses upon the present status of antimicrobial agents from higher plants with particular reference to agents from plants with a folkloric reputation for treatment of infections. In particular, recent work on the tropical genus Erythrina is emphasized. The use of modern microbiological techniques demonstrates that higher plants frequently exhibit significant potency against human bacterial and fungal pathogens, that many genera are involved, that many folkloric uses can be rationalized on this basis, that the active constituents are readily isolated by bioassay-directed techniques, that their chemical structures are types uncommon amongst fermentation-based agents but are familiar to natural product chemists, that their antimicrobial spectra are comparatively narrow but that their potency is often reasonable, that they are comparatively easy to synthesize and the unnatural analogues so produced can possess enhanced therapeutic potential and, thus, it is concluded that such work generates a gratifying number of novel lead structures and that the possibility of finding additional agents for human or agricultural use based upon higher plant agents is realistic.