Parental views of antibiotic use in children with upper respiratory tract infections in Jordan

Purpose: To assess the knowledge, attitudes and practices of parents towards antibiotics use for upper respiratory tract infections (URTIs) in Jordan. Methods: A cross-sectional study was carried out at 10 private outpatients’ pediatric clinics across Amman-Jordan from September to December 2013. During the study period, 1329 parents of young children who fulfilled the inclusion criteria and agreed to participate were interviewed, and completed a validated structured questionnaire. Results: A large proportion of parents (903, 68 %) believed that weather change was the main cause of acute URTIs in their children. Although 1098 (82.8 %) of parents were aware that the recurrent use of antibiotics leads to a decrease in effectiveness due to bacterial resistance, 859 (64.6 %) of the respondents reported that they would give antibiotics without prescription. Fathers (135, 40.2 %), were significantly more aware that URTIs follow its natural course without antibiotic administration compared to mothers (N = 327, 32.9 %), respectively (p = 0.005). Conclusion: There is a lack of adequate parental knowledge concerning the use and misuse of antibiotics in children in Jordan. National publicity campaign should be mounted to improve awareness. Furthermore, existing laws should be enforced to prevent parents from purchasing antibiotics over-thecounter (OTC).

Generation and screening of natural product-like compounds for antibiotic discovery

Avec l’apparition de plus en plus de souches de bactérie résistante aux antibiotiques, le développement de nouveaux antibiotiques est devenu une important problématique pour les agences de santé. C’est pour cela que la création de nouvelles plateformes pour accélérer la découverte de médicaments est devenu un besoin urgent. Dans les dernières décennies, la recherche était principalement orientée sur la modification de molécules préexistantes, la méta-analyse d’organismes produisant des molécules activent et l’analyse de librairies moléculaires pour trouver des molécules synthétiques activent, ce qui s’est avéré relativement inefficace. Notre but était donc de développer de nouvelles molécules avec des effets thérapeutiques de façon plus efficace à une fraction du prix et du temps comparé à ce qui se fait actuellement. Comme structure de base, nous avons utilisé des métabolites secondaires qui pouvaient altérer le fonctionnement des protéines ou l’interaction entre deux protéines. Pour générer ces molécules, j’ai concentré mes efforts sur les terpènes, une classe de métabolites secondaires qui possède un large éventail d’activités biologiques incluant des activités antibactériennes. Nous avons développé un système de chromosome artificiel de levure (YAC) qui permet à la fois l’assemblage directionnel et combinatoire de gènes qui permet la création de voies de biosynthèse artificielles. Comme preuve de concept, j’ai développé des YACs qui contiennent les gènes pour l’expression des enzymes impliquées dans la biosynthèse de la -carotène et de l’albaflavenone et produit ces molécules avec un haut rendement. Finalement, Des YACs produits à partir de librairies de gènes ont permis de créer une grande diversité de molécules.

Small-plasmid-mediated antibiotic resistance is enhanced by increases in plasmid copy number and bacterial fitness

Plasmids play a key role in the horizontal spread of antibiotic resistance determinants among bacterial pathogens. When an antibiotic resistance plasmid arrives in a new bacterial host, it produces a fitness cost, causing a competitive disadvantage for the plasmid-bearing bacterium in the absence of antibiotics. On the other hand, in the presence of antibiotics, the plasmid promotes the survival of the clone. The adaptations experienced by plasmid and bacterium in the presence of antibiotics during the first generations of coexistence will be crucial for the progress of the infection and the maintenance of plasmid-mediated resistance once the treatment is over. Here we developed a model system using the human pathogen Haemophilus influenzae carrying the small plasmid pB1000 conferring resistance to β-lactam antibiotics to investigate host and plasmid adaptations in the course of a simulated ampicillin therapy. Our results proved that plasmid-bearing clones compensated for the fitness disadvantage during the first 100 generations of plasmid-host adaptation. In addition, ampicillin treatment was associated with an increase in pB1000 copy number. The augmentation in both bacterial fitness and plasmid copy number gave rise to H. influenzae populations with higher ampicillin resistance levels. In conclusion, we show here that the modulations in bacterial fitness and plasmid copy number help a plasmid-bearing bacterium to adapt during antibiotic therapy, promoting both the survival of the host and the spread of the plasmid.

Antibiotic-resistant Klebsiella pneumoniae and Escherichia coli high-risk clones and an IncFII(k) mosaic plasmid hosting Tn1 (blaTEM-4) in isolates from 1990 to 2004

We describe the genetic background of bla(TEM-4) and the complete sequence of pRYC11::bla(TEM-4), a mosaic plasmid that is highly similar to pKpQIL-like variants, predominant among TEM-4 producers in a Spanish hospital (1990 to 2004), which belong to Klebsiella pneumoniae and Escherichia coli high-risk clones responsible for the current spread of different antibiotic resistance genes. Predominant populations of plasmids and host adapted clonal lineages seem to have greatly contributed to the spread of resistance to extended-spectrum cephalosporins.

Generation and screening of natural product-like compounds for antibiotic discovery

Avec l’apparition de plus en plus de souches de bactérie résistante aux antibiotiques, le développement de nouveaux antibiotiques est devenu une important problématique pour les agences de santé. C’est pour cela que la création de nouvelles plateformes pour accélérer la découverte de médicaments est devenu un besoin urgent. Dans les dernières décennies, la recherche était principalement orientée sur la modification de molécules préexistantes, la méta-analyse d’organismes produisant des molécules activent et l’analyse de librairies moléculaires pour trouver des molécules synthétiques activent, ce qui s’est avéré relativement inefficace. Notre but était donc de développer de nouvelles molécules avec des effets thérapeutiques de façon plus efficace à une fraction du prix et du temps comparé à ce qui se fait actuellement. Comme structure de base, nous avons utilisé des métabolites secondaires qui pouvaient altérer le fonctionnement des protéines ou l’interaction entre deux protéines. Pour générer ces molécules, j’ai concentré mes efforts sur les terpènes, une classe de métabolites secondaires qui possède un large éventail d’activités biologiques incluant des activités antibactériennes. Nous avons développé un système de chromosome artificiel de levure (YAC) qui permet à la fois l’assemblage directionnel et combinatoire de gènes qui permet la création de voies de biosynthèse artificielles. Comme preuve de concept, j’ai développé des YACs qui contiennent les gènes pour l’expression des enzymes impliquées dans la biosynthèse de la -carotène et de l’albaflavenone et produit ces molécules avec un haut rendement. Finalement, Des YACs produits à partir de librairies de gènes ont permis de créer une grande diversité de molécules.

Antibiotic resistance in the gut microbiota

Antibiotic resistance is an increasing threat to our ability to treat infectious diseases. Thus, understanding the effects of antibiotics on the gut microbiota, as well as the potential for such populations to act as a reservoir for resistance genes, is imperative. This thesis set out to investigate the gut microbiota of antibiotic treated infants compared to untreated controls using high-throughput DNA sequencing. The results demonstrated the significant effects of antibiotic treatment, resulting in increased proportions of Proteobacteria and decreased proportions of Bifidobacterium. The species diversity of bifidobacteria was also reduced. This thesis also highlights the ability of the human gut microbiota to act as an antibiotic resistance reservoir. Using metagenomic DNA extracted from faecal samples from adult males, PCR was employed to demonstrate the prevalence and diversity of aminoglycoside and β-lactam resistance genes in the adult gut microbiota and highlighted the merits of the approach adopted. Using infant faecal samples, we constructed and screened a second fosmid metagenomic bank for the same families of resistance genes and demonstrated that the infant gut microbiota is also a reservoir for resistance genes. Using in silico analysis we highlighted the existence of putative aminoglycoside and β-lactam resistance determinants within the genomes of Bifidobacterium species. In the case of the β- lactamases, these appear to be mis-annotated. However, through homologous recombination-mediated insertional inactivation, we have demonstrated that the putative aminoglycoside resistance proteins do contribute to resistance. In additional studies, we investigated the effects of short bowel syndrome on infant gut microbiota, the immune system and bile acid metabolism. We also sequenced the microbiota of the human vermiform appendix, highlighting its complexity. Finally, this thesis demonstrated the strain specific nature of 2 different probiotic CLA-producing Bifidobacterium breve on the murine gut microbiota.

Endocarditis By Kocuria Rosea In An Immunocompetent Child.

Kocuria rosea belongs to genus Kocuria (Micrococcaceae family, suborder Micrococcineae, order Actinomycetales) that includes about 11 species of bacteria. Usually, Kocuria sp are commensal organisms that colonize oropharynx, skin and mucous membrane; Kocuria sp infections have been described in the last decade commonly affecting immunocompromised patients, using intravenous catheter or peritoneal dialysis. These patients had mainly bacteremia/recurrent sepsis. We hereby describe the case of a 10-year-old girl, immunocompetent, who had endocarditis/sepsis by K. rosea which was identified in five different blood cultures by Vitek 2 ID-GPC card (BioMérieux, France). Negative HIV serology, blood count within normal range of leukocytes/neutrophils and lymphocytes, normal fractions of the complement, normal level of immunoglobulins for the age; lymphocyte immunophenotyping was also within the expected values. Thymus image was normal at chest MRI. No catheters were required. Identification of K. rosea was essential to this case, allowing the differentiation of coagulase-negative staphylococci and use of an effective antibiotic treatment. Careful laboratory analysis of Gram-positive blood-born infections may reveal more cases of Kocuria sp infections in immunocompetent patients, which may collaborate for a better understanding, prevention and early treatment of these infections in pediatrics.

Candidíase sistêmica com localização encefálica: estudo anátomo-clínico de cinco casos

Central nervous system involvement in Candida septicaemia is rare and not more than four cases have been published in Brazil. Five new cases of systemic candidiasis with cerebral lesions are reported. All patients (four adults and a child) had serious underlying diseases and were submitted to heavy long-term antibiotic therapy with multiple drugs. Seizures in one case and neck stiffness in another were the only neurologic signs that could be attributed to candidiasis. In no case were the lesions severe enough to be considered an immediate cause of death. In three patients, no macroscopic changes were evident in the brain, but microabscesses and granulomata were observed on microscopical examination; another patient had two gross areas with necrotic and haemorrhagic appearance in the cerebral hemispheres; the child had only two microscopic granulomata. The aetiological agent was demonstrated by Grocott's methenamine silver technique in all cases. Involvement of organs other than the central nervous system could be demonstrated in three autopsies. Discussion is confined mainly to such aspects as the contributory factors in the pathogenesis of systemic candidiasis as well as the marked rise in the incidence of this condition in the past few decades. It is suggested that the frequence of monilial septicaemia in Brazil may be far more serious than apparent from the scarcity of reported cases.

Necrose cerebelar extensa na anemia falciforme: relato de um caso

A 6 month-old mulatto boy was admitted on account of acute gastroenteritis, malnutrition and dehydration. In the hospital, the child developed septicemia, and temperature reached up to 38.6°C. Despite intensive antibiotic treatment, the patient died 12 days after admission. Necropsy disclosed bilateral bronchopneumonia, bilateral fronto-parietal subarachnoid hemorrhage, and extensive necrosis of the inferior half of both cerebellar hemispheres. On histopathological examination of the necrotic cerebellar cortex, numerous sickled erythrocytes were observed in petechial hemorrhages and, in lesser quantities, inside capillaries. Lesions of the central nervous system in sickle cell anemia most often involve the cerebral cortex, and a single extensive cerebellar infarction as present in this case seems extremely rare. The pathogenetic mechanism of the necrosis is unclear, since thrombosis was not observed either in large blood vessels or in capillaries. Possible contributory factors were the infectious condition (septicemia), fever, and anoxia caused by the extensive bronchopneumonia.

Cromomicose cerebral: registro de um caso

A case of brain abscess and meningitis due to pigmented fungi is reported. The patient was a 59-year-old white male, who had enjoyed excellent health until October 1977, when he developed headache, later accompanied by paresthesias and weakness in the left-sided extremities. These symptoms worsened progressively and in November of that year he had to quit his job. From February 1978 on he became inactive and anorexic. Intense continuous headache was associated with frequent episodes of vomiting. He gradually became tor-porous, and according to his relatives, suffered from visual and possibly auditory deficiency. On examination, he was malnourished and dehydrated, with decubitus ulcers. Temperature was 38,5°C. A left-sided spastic hemiplegia and prominent meningorradicular signs were noted. The CSF was examined six times between May 17th and June 1st and showed variable hypercytosis (143 to 4,437 leucocytes/ cu mm) with predominance of neutrophils (up tp 95%), low glucose and high protein concentrations. No microorganisms were identified. Electroencephalographic study disclosed a low background activity especially in left temporal areas. Despite supportive care and antibiotic therapy he lapsed into coma. Carotid angiography was normal on June 1st. He remained in deep coma until his death on June 6th, 1978. Necropsy was limited to the brain, which weighed 1,550 g after fixation and showed diffuse intense edema and hyperemia. On coronal sectioning an encapsulated abscess was found in the right basal ganglia, which also involved the internal capsule, and measured 1.5 cm in diameter. Microscopical examination disclosed large numbers of brownish fungi, appearing both as oval yeasts and as septate hyphae in the thick fibrous capsule and in the necrotic content of the abscess. The same organisms were demonstrated in moderate numbers in the leptomeninges of the medulla oblongata and , less frequently, of the hippo-campal region and cerebellum.

Orbital abscess after facial trauma

This paper reports a rare case of acute severe orbital abscess manifested 2 days after a facial trauma without bone fracture in a 20-year-old Afro-American female. The symptoms worsened within the 24 h prior to hospital admission resulting in visual disturbances such as diplopia and photophobia. The clinical findings at the first consultation included fever, periorbital swelling and redness, ptosis, proptosis and limitation of ocular movements upwards, downwards, to the right and to the left. Computed tomography scan showed proptosis with considerable soft tissue swelling on the left side and no fracture was evidenced in the facial skeleton, including the zygomatic-orbital complex. After hospital admission and antibiotic therapy intravenously the patient was conducted to the operation room and submitted to incision and drainage under general anesthesia. The orbit was approached thorough both eyelids and the maxillary sinus was reached only through the Caldwell-Luc approach. The postoperative period was uneventful and the rapid improvement of symptoms was remarkable. Visual acuity and ocular motility returned to the normal ranges within 2 days after the surgical intervention. After 12 postoperative days, the patient presented with significative improvement in the ptosis and proptosis, and acceptable scars.

Carbapenem stewardship: positive impact on hospital ecology

INTRODUCTION: Excessive group 2 carbapenem use may result in decreased bacterial susceptibility. OBJECTIVE: We evaluated the impact of a carbapenem stewardship program, restricting imipenem and meropenem use. METHODS: Ertapenem was mandated for ESBL-producing Enterobacteriaceae infections in the absence of non-fermenting Gram-negative bacilli (GNB) from April 2006 to March 2008. Group 2 carbapenems were restricted for use against GNB infections susceptible only to carbapenems and suspected GNB infections in unstable patients. Cumulative susceptibility tests were done for nosocomial pathogens before and after restriction using Clinical and Laboratory Standards Institute (CLSI) guide-lines.Vitek System or conventional identification methods were performed and susceptibility testing done by disk diffusion according to CLSI.Antibiotic consumption (t-test) and susceptibilities (McNemar's test) were determined. RESULTS: The defined daily doses (DDD) of group 2 carbapenems declined from 61.1 to 48.7 DDD/1,000 patient-days two years after ertapenem introduction (p = 0.027). Mean ertapenem consumption after restriction was 31.5 DDD/1,000 patient-days. Following ertapenem introduction no significant susceptibility changes were noticed among Gram-positive cocci. The most prevalent GNB were P. aeruginosa, Klebsiella pneumoniae, and Acinetobacter spp. There was no change in P. aeruginosa susceptibility to carbapenems. Significantly improved P. aeruginosa and K. pneumoniae ciprofloxacin susceptibilities were observed, perhaps due to decreased group 2 carbapenem use. K. pneumoniae susceptibility to trimethoprim-sulfamethoxazole improved. CONCLUSION: Preferential use of ertapenem resulted in reduced group 2 carbapenem use, with a positive impact on P. aeruginosa and K. pneumoniae susceptibility.

Efeitos do ágar no crescimento de explantes e na formação de calos em morfos pigmentares de Gracilaria domingensis (Kützing) Sonder ex Dickie (Gracilariales, Rhodophyta)

Os efeitos da concentração de ágar no crescimento de explantes e na formação de calos foram avaliados em culturas axênicas de gametófitos femininos de morfos de coloração verde e vermelha de Gracilaria domingensis (Kützing) Sonder ex Dickie. Culturas unialgáceas foram mantidas em água do mar esterilizada (30-32 ups) enriquecida com 25% da solução de von Stosch (VSES 25%), 22 ± 2 °C, fotoperíodo de 14 h, irradiância de 50-80 µmol de fótons m-2 s-1. Para a obtenção de explantes axênicos, segmentos apicais e intercalares dos dois morfos foram cultivados por 48 h em meio VSES 25% com adição de uma solução antibiótica e antifúngica, e submetidos a uma lavagem com uma solução de água do mar esterilizada com 0,5% de hipoclorito de sódio e 200 µL L-1 de detergente por 20 segundos. Para avaliar os efeitos da concentração de ágar, os segmentos axênicos foram inoculados em meio ASP 12-NTA com concentrações distintas de ágar que variaram de zero a 1%. A adição de ágar no meio inibiu o crescimento dos segmentos apicais de ambos os morfos, bem como o crescimento de segmentos intercalares do morfo verde. Observou-se uma tendência geral no crescimento dos explantes, onde a taxa de crescimento foi inversamente proporcional à concentração de ágar. A adição de ágar no meio induziu a formação de três tipos de calo, denominados conforme a região do explante onde se originaram: calo apical, calo basal e calo intermediário. As concentrações de 0,5% e 0,7% de ágar foram as concentrações ótimas para indução de calos basais e calos intermediários no morfo verde, respectivamente. A presença de ágar foi essencial para a formação de calos intermediários e apicais. Os resultados indicam que o ágar apresenta um papel na regulação dos processos morfogenéticos em morfos pigmentares de G. domingensis.

Antibacterial modified diketopiperazines from two ascidians of the genus Didemnum

The chemical investigation of the crude extract of an ascidian of the genus Didemnumled to the isolation of the modified diketopiperazine rodriguesines A (1) and (2) as a mixture of homologues, which could be identified by analysis of spectroscopic data including MS/MS experiments. The investigation of a second Didemnumsp. led to the isolation of N-acetyl-rodriguesine A (3) and N-acetyl-rodriguesine B (4). The absolute configuration of compounds 1and 2could be established by hydrolysis and Marfey's analysis and comparison with literature data reported for compound 3, previously obtained as a synthetic product. The mixture of 1and 2displayed moderate antibiotic activity against a clinical isolate of Streptococcus mutansand against S. mutansUA159 and Staphylococcus aureusATCC6538.

Degradação eletroquímica do cloranfenicol em reator de fluxo

This paper reports a study of electrochemical degradation of the chloramphenicol antibiotic in aqueous medium using a flow-by reactor with DSA® anode. The process efficiency was monitored by chloramphenicol concentration analysis with liquid chromatography (HPLC) during the experiments. Analysis of Total Organic Carbon (TOC) was performed to estimate the degradation degree and Ion Chromatography (IC) was performed to determinate inorganic ions formed during the eletrochemical degradation process. In electrochemical flow-by reactor, 52% of chloramphenicol was degraded, with 12% TOC reduction. IC analysis showed the production of chloride ions (25 mg L-1), nitrate ions (6 mg L-1) and nitrite ions (4.5 mg L-1).