Compliance with antibiotic therapy guidelines in french paediatric intensive care units: a multicentre observational study.

BACKGROUND: Bacterial infections (BIs) are widespread in ICUs. The aims of this study were to assess compliance with antibiotic recommendations and factors associated with non-compliance. METHODS: We conducted an observational study in eight French Paediatric and Neonatal ICUs with an antimicrobial stewardship programme (ASP) organised once a week for the most part. All children receiving antibiotics for a suspected or proven BI were evaluated. Newborns < 72 h old, neonates < 37 weeks, age ≥ 18 years and children under surgical antimicrobial prophylaxis were excluded. RESULTS: 139 suspected (or proven) BI episodes in 134 children were prospectively included during six separate time-periods over one year. The final diagnosis was 26.6% with no BI, 40.3% presumed (i.e., not documented) BI and 35.3% documented BI. Non-compliance with antibiotic recommendations occurred in 51.1%. The main reasons for non-compliance were inappropriate choice of antimicrobials (27.3%), duration of one or more antimicrobials (26.3%) and length of antibiotic therapy (18.0%). In multivariate analyses, the main independent risk factors for non-compliance were prescribing ≥ 2 antibiotics (OR 4.06, 95%CI 1.69-9.74, p = 0.0017), duration of broad-spectrum antibiotic therapy ≥ 4 days (OR 2.59, 95%CI 1.16-5.78, p = 0.0199), neurologic compromise at ICU admission (OR 3.41, 95%CI 1.04-11.20, p = 0.0431), suspected catheter-related bacteraemia (ORs 3.70 and 5.42, 95%CIs 1.32 to 15.07, p < 0.02), a BI site classified as "other" (ORs 3.29 and 15.88, 95%CIs 1.16 to 104.76, p < 0.03), sepsis with ≥ 2 organ dysfunctions (OR 4.21, 95%CI 1.42-12.55, p = 0.0098), late-onset ventilator-associated pneumonia (OR 6.30, 95%CI 1.15-34.44, p = 0.0338) and ≥ 1 risk factor for extended-spectrum ß-lactamase-producing Enterobacteriaceae (OR 2.56, 95%CI 1.07-6.14, p = 0.0353). Main independent factors for compliance were using antibiotic therapy protocols (OR 0.42, 95%CI 0.19-0.92, p = 0.0313), respiratory failure at ICU admission (OR 0.36, 95%CI 0.14-0.90, p = 0.0281) and aspiration pneumonia (OR 0.37, 95%CI 0.14-0.99, p = 0.0486). CONCLUSIONS: Half of antibiotic prescriptions remain non-compliant with guidelines. Intensivists should reassess on a day-to-day basis the benefit of using several antimicrobials or any broad-spectrum antibiotics and stop antibiotics that are no longer indicated. Developing consensus about treating specific illnesses and using department protocols seem necessary to reduce non-compliance. A daily ASP could also improve compliance in these situations. TRIAL REGISTRATION: ClinicalTrials.gov: number NCT04642560. The date of first trial registration was 24/11/2020.

A comparative genomics study of the microbiome and freshwater resistome in Southern Pantanal.

This study explores the resistome and bacterial diversity of two small lakes in the Southern Pantanal, one in Aquidauana sub-region, close to a farm, and one in Abobral sub-region, an environmentally preserved area. Shotgun metagenomic sequencing data from water column samples collected near and far from the floating macrophyte Eichhornia crassipes were used. The Abobral small lake exhibited the highest diversity and abundance of antibiotic resistance genes (ARGs), antibiotic resistance classes (ARGCs), phylum, and genus. RPOB2 and its resistance class, multidrug resistance, were the most abundant ARG and ARGC, respectively. Pseudomonadota was the dominant phylum across all sites, and Streptomyces was the most abundant genus considering all sites.

Antimicrobial treatment of lower respiratory tract infections in children.

Lower respiratory tract infections (LRTI) encompass a wide range of clinical syndromes, prominently including bronchiolitis, bronchitis and pneumonia. LRTIs are the second leading cause of antibiotic prescriptions. The vast majority of these infections are due to (or triggered by) viruses and are self-limited diseases. Pneumonia in children is responsible for significant morbidity and mortality worldwide. For clinicians, one of the main difficulties consists in diagnosing pneumonia in febrile children with (or without) cough. The diagnosis is given on the basis of anamnesis, clinical examination and (if necessary) complementary examinations, with chest X-ray or thoracic ultrasound; biological markers are particularly important. Over recent years, since the implementation of PCV13, the bacterial epidemiology of pneumonia and empyema has evolved; involvement in these diseases of pneumococcus has been reduced, and resistance to penicillin has lessened - and remained extremely low. In 2021, according to the National Pneumococcal Reference Center, only 6% of the strains isolated from blood cultures in children are resistant to amoxicillin. The therapeutic choices proposed in this article are in full compliance with the previously published official French recommendations.

Antimicrobial treatment of urinary tract infections in children.

Urinary tract infections are the most frequently proven bacterial infections in pediatrics. The treatment options proposed in this guide are based on recommendations published by the Groupe de Pathologie Infectieuse de Pédiatrique (GPIP-SFP). Except in rare situations (newborns, neutropenia, sepsis), a positive urine dipstick for leukocytes and/or nitrites should precede a urine culture examination and any antibiotic therapy. After rising steadily between 2000 and 2012, the proportion of Escherichia coli strains resistant to extended-spectrum ß-lactamases (E-ESBL) has remained stable over the last ten years (between 7% and 10% in pediatrics). However, in many cases no oral antibiotic is active on E-ESBL leading either to prolonged parenteral treatment, or to use of a non-orthodox combination such as cefixime + clavulanate. With the aim of avoiding penem antibiotics and encouraging outpatient management, this guide favors initial treatment of febrile urinary tract infections (suspected or actual E-ESBL infection), with amikacin. Amikacin remains active against the majority of E-ESBL strains. It could be prescribed as monotherapy for patients in pediatric emergency departments or otherwise hospitalized patients.

Feasibility of a multidisciplinary approach for medical review among elderly patients in four Italian long-term nursing homes.

OBJECTIVES: To establish the feasibility and the specific tasks of a multidisciplinary team approach for medical review in four nursing homes for the elderly in Italy. METHODS: Prospective study conducted between November 2012 and September 2013. Review of therapies was performed by seven clinical pharmacists and four nurses using composite criteria for drug discrepancy evaluation with subsequent submission to 31 physicians. RESULTS: The rate of prevalence of drug discrepancies recorded for 2556 medications reviewed in 333 patients was 34.1% (871/2556). Of these, only 35.5% (309/871) were accepted by clinicians. The highest clinician acceptance rates were observed for drug substitutions (91.3%, 211/231) and dosing regimen modifications (96.4%, 53/55). A significant decrease in the mean number of medications prescribed per patient (from 7.7±2.8 to 7.3±2.7, p<0.05) was observed. CONCLUSIONS: Interventions aimed at improving interactions between pharmacists and physicians and awareness among physicians of major pharmacological interactions should be encouraged.

4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice.

The analgesic drug dipyrone is used to treat side effects (including pain and fever) of cancer chemotherapeutic agents. Dipyrone is metabolized to 4-aminoantipyrine (4-AA), a PGE2-dependent blocker and inhibitor of cyclooxygenase (COX). We evaluated the genotoxic, mutagenic, apoptotic, and immunomodulatory activities of 4-AA in vivo and the effects of its combination with the antineoplastic drugs doxorubicin, cisplatin, and cyclophosphamide. 4-AA did not cause genotoxic/mutagenic damage, splenic phagocytosis, or leukocyte alterations. However, when combined with the antineoplastic agents, 4-AA decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. These results suggest that 4-AA might interfere with DNA damage-mediated chemotherapy.

mTOR pathway and mTOR inhibitors as agents for cancer therapy.

Research into mTOR, mammalian Target Of Rapamycin as an important drug target continues to be extremely interesting, both in terms of the increased molecular knowledge being acquired at the basis of various human diseases, and also for possible applications in drug cancer therapy. The mTOR signaling system plays a key role in several transduction pathways that are necessary for cell cycle progression and cellular proliferation. Drugs known as mTOR inhibitors have been included in ongoing and in recently completed cancer trials. New insights into the mTOR signaling system are helping to clarify the functionality of key mTOR components, and especially their possible role in apoptosis, angiogenesis and tumor progression. Three other molecules, already approved for therapeutic use and being commercialized (Everolimius, Temsirolimus and Zotarolimus) are added to Rapamycin (also known as Sirolimus), the parent drug of the mTOR inhibitors. Of these, only Temsirolimus is currently approved in the treatment of renal cell carcinoma, while the others are approved for organ transplant rejection and coronary artery restenosis. There are at least 10 other molecules currently under development for clinical and preclinical studies. This review offers an updated synopsis of the mTOR signaling system, in particular as regards relevant aspects of cancer research, looks at the known mTOR inhibitors and gives a systematic vision of current trials for each individual molecule subject to clinical investigation.

Phytophthora infestans-triggered response of growth- and defense-related genes in potato cultivars with different levels of resistance under the influence of nitrogen availability.

The effects of high and low N concentrations on the Solanum tuberosum-Phytophthora infestans interaction were studied in the potato cultivars Bettina, New York 121, Indira and Arkula, which exhibited different levels of resistance. Aboveground biomass and Chl and N content were significantly higher in all cultivars grown in higher N environments, while C:N ratios were lower, confirming successful application of N. High availability of N significantly increased susceptibility of three of the four potato cultivars, and amounts of pathogen within the infected leaflets determined in a quantitative real-time reverse transcriptase-polymerase chain reaction reflected this. Differential gene expression of P. infestans-induced and -repressed genes derived from three subtracted cDNA libraries at 0, 24, 48 and 72 h post-inoculation was studied in parallel. P. infestans attack led to an induction of defense-related and at the same time repression of growth-related potato genes mainly encoding photosynthetic genes. High N supply led to higher transcript abundance of photosynthetic genes such as Chl a/b-binding protein and ribulose bisphosphate carboxylase. N-dependent suppression of defense-related compounds in absence of the pathogen was not observed. Better N nutrition appeared to allow the plants to invest more resources in defense reactions.

Hepatic adverse drug reactions: a case/non-case study in Italy.

OBJECTIVE: Adverse drug reactions (ADRs) can involve all tissues and organs. Liver injuries are considered among the most serious and are a cause for concern among physicians and patients. To assess the extent of drug-induced liver injuries in Italy we compared the number of cases of hepatic ADRs with reports of all other drug-related reactions present in the same database. METHODS: Spontaneous reports from six Italian Regions collected from January 1990 to May 2005 were analysed. Adverse reactions were classified according to WHO Adverse Reaction Terminology for causality assessment, and only those with "certain", "probable" or "possible" causality assessment were included. Association between drugs and hepatic ADRs was assessed using the case/non case method, calculating the ADR reporting odds ratio (ROR) as a measure of disproportionality. RESULTS: On May 2005, the database contained 35,767 ADR reports, of which 11,829 were excluded because they were unclassifiable or unlikely in terms of causality assessment. Therefore, the analysis was carried out on 23,938 reports, of which 1,069 concerned hepatic ADRs (cases) and 22,869 concerned non-cases. The proportion of serious ADRs was about 40% in the overall database, and about 74% among cases. The drug classes with the highest number of cases were statins (ROR = 2.9, 95% CI 2.4-3.5), antiplatelet agents (ROR = 3.5; 95% CI 2.6-4.6), NSAIDs (ROR = 2.9; 95% CI 2.1-3.9) and macrolides (ROR = 1.7; 95% CI 1.2-2.3). CONCLUSION: Hepatic adverse drug reactions remain a serious concern for several drugs widely used in clinical practice. Monitoring hepatic enzymes on a monthly basis for the first 6 months of treatment has been suggested for patients taking medications known to be hepatotoxic. A better knowledge of the epidemiology and mechanisms of hepatic ADRs may contribute to minimising their occurrence.

Fluvastatin and hepatic reactions: a signal from spontaneous reporting in Italy.

BACKGROUND: Signal detection is a crucial element in recognising new adverse drug reactions (ADRs) as soon as possible. HMG-CoA reductase inhibitors ('statins'), the most potent cholesterol-lowering drugs, are generally well tolerated but can occasionally lead to liver toxicity. Pre- and postmarketing studies on statins revealed an incidence of 0.1-3% elevation in hepatic transaminase levels. However, these elevations are asymptomatic, reversible, dose related or probably due to other causes. Postmarketing studies clearly showed the lack of evidence of hepatotoxicity from statins, apart from some isolated case reports of serious hepatic damage described in the literature. It is still unclear whether serious hepatic reactions are dose related and more frequent than the expected rate in the general population. OBJECTIVE: In this study, the hypothesis that fluvastatin could cause serious liver injuries more than the other statins is investigated, in the light of a quantitative and qualitative signal analysis, drug consumption data and evidence from the literature. METHODS: The Italian Interregional Group of Pharmacovigilance (Gruppo Interregionale di Farmacovigilanza; GIF) is an example of signal detection within the Italian spontaneous ADR reporting system. The GIF database holds reports of suspected ADRs submitted by five Italian pharmacovigilance regional centres. In the GIF database, all reports of suspected ADRs are classified according to the WHO criteria for causality assessment. The reactions are coded according to the WHO Adverse Reaction Terminology and classified as serious or non-serious events on the basis of the WHO Critical Term List. Every 6 months the GIF database is analysed to extract potential signals through a qualitative case-by-case analysis and using a quantitative methodology called proportional reporting ratio (PRR). This methodology permitted us to identify the potential signal 'fluvastatin and hepatic reactions'. RESULTS: At 31 December 2004, the GIF database contained 35 757 reports with an annual reporting rate of 170 reports per million inhabitants. We found a total of 1260 reports of ADRs related to statins, including 178 of hepatic reactions. Sixty-nine reports were attributed to fluvastatin, which showed the highest PRR in comparison with the other statins. Fluvastatin was associated with 33 serious reactions, mainly hepatitis and cholestatic hepatitis. The number of reports of severe hepatotoxicity associated with fluvastatin started to increase from 2002. About half of them did not report other suspected or concomitant drugs and in one third the hepatotoxicity occurred after <1 month of therapy. Twenty-seven out of 33 patients were female, and fluvastatin was administered at 80 mg/day in 81% of cases reporting complete data on drug dosage. CONCLUSION: In the literature, serious hepatic reactions are rarely described in patients taking statins; however, data gathered by GIF suggest that cases of hepatotoxicity are reported more often than expected. In addition, GIF data seem to reveal that fluvastatin is more likely to cause hepatic reactions than the other statins. However, this is a preliminary signal and future evaluations are certainly needed to confirm it and to quantify this possible risk.

Analysis of differentially expressed genes in a susceptible and moderately resistant potato cultivar upon Phytophthora infestans infection.

SUMMARY To gain deeper understanding of the host-pathogen interaction in the system potato-Phytophthora infestans, subtractive hybridization in combination with cDNA array hybridization was used. Leaflets of a moderately resistant and a susceptible potato cultivar were inoculated with P. infestans. The infection of the potato leaves was quantified by real-time quantitative PCR. Using infected and control tissue, two cDNA libraries highly enriched for P. infestans-induced genes were prepared. Within 531 clones randomly picked and sequenced from the libraries, 285 unigenes were found, from which 182 clones were selected for further analysis by cDNA array hybridization. Sixteen hours post inoculation genes were not induced significantly, whereas 72 h post inoculation induction of gene expression was clearly detectable. In both cultivars, 143 genes were induced moderately (>/= two-fold), and 35 of the selected genes appeared to be strongly induced (>/= seven-fold). Among these clones were mainly genes associated with stress and/or defence mechanisms. The strongest gene induction was found in 4-week-old susceptible plants. In the moderately resistant cultivar, transcripts of a number of genes accumulate with plant age; as a result, induction of gene expression upon infection was less pronounced. Down-regulation of three genes was observed in both cultivars, upon infection. Transcript levels of these three genes increased in uninfected plants within 4 weeks of growth. Other differences in defence responses of the two cultivars could be determined and their effects are discussed.

Correlación del diagnóstico clinicopsiquiátrico, psicológico y la tomografía axial computarizada de cráneos en pacientes alcohólicos / Correlation of the clinical, psychiatry and psychologic diagnosis and the cranial computarized axial tomography in alcoholic patients

Se estudiaron 44 pacientes alcohólicos a los cuales se les realizó un estudio clinicopsiquiátrico y evaluación psicológica, utilizándose un sistema de metódicas, tanto tradicionales como patopsicológicas a través de las cuales se estudiaron los procesos de memoria, atención y percepción, realizándose a estos pacientes además TAC de cráneo para conocer la posible correspondencia entre los tres métodos diagnósticos. Se encontró que un 45,46% de los pacientes presentaron alteraciones cerebrales en las TAC, una correspondencia entre estos hallazgos con el mayor tiempo de evolución, alto consumo y frecuencia, correspondencia entre estas alteraciones, la presencia de un SOEC y la existencia de dependencia, el sistema de metódicas psicológicas aplicadas pudieron establecer un diagnóstico diferencial entre los pacientes con un SOEC y los que no lo presentaban. Hubo un porcentaje alto de coincidencia entre los tres métodos diagnósticos entre sí y valorados en conjunto demostrando su utilidad en la labor asistencial.

Estudio Piloto sobre los conocimientos, percepción y conducta ante el parasitismo intestinal en una comunidad / Pilot study on knowledges, perception and behaviour in front of intestinal parasitism in a community

Las conclusiones preliminares que se brindan en este trabajo derivaron de un estudio sobre los conocimientos, percepción y conducta que tienen los miembros de una comunidad pecuaria en relación con el parasitismo intestinal. Adicionalmente se realizaron 3 exámenes de heces para conocer el grado de infestación por parásitos intestinales. Se compararon los resultados entre los parasitados y se demostró la necesidad de incrementar aún más la educación para la salud que se imparte a la población