Thesis--Auburn University, 2009. / Abstract. Includes bibl

Amikacin (AK) and enrofloxacin (EF) concentrations consistent with intra-articular and regional limb perfusion were evaluated for their effects on equine chondrocytes. We evaluated the production of prostaglandin E2 (PGE2) by equine chondrocytes in response to AK and EF administration,and if the combination of avocado soybean unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS) could reduce the production of PGE2. Monolayer cell cultures of equine chondrocytes were treated with clinically relevant concentrations of AK and EF plus combinations of ASU, GLU, and CS.AK and EF generated a dose dependent cytotoxicity. The induction of PGE2 following EF administration was significantly greater than PGE2 levels induced by positive controls. Induction of PGE2 by EF was significantly reduced in chondrocytes pretreated with ASU, GLU, and CS. We have demonstrated for the first time that EF can induce production of PGE2 in equine chondrocytes and that this effect can be attenuated with the combination of ASU, GLU, and CS.

Thesis(M.S.)--Auburn University, 2006. / Abstract. Includes bibliographic references.

Class of 2013 Abstract / Specific Aims: The objective of this study was to compare the use of amikacin 1 year before the national drug shortage and 1 year during drug shortage in order to evaluate the impact of the drug shortage on prescribing amikacin at an academic medical center. Methods: All patients admitted to an academic medical center between January 1, 2008 to December 31, 2008 before the shortage and January 1, 2011 to December 1, 2011 during the shortage who were prescribed amikacin were evaluated. Data collected included demographic information, type of infection, aminoglycoside therapy prescribed, laboratory data, culture and susceptibility data, therapy outcomes, and potential complications of aminoglycoside therapy. Appropriateness of amikacin therapy was based on each subject’s clinical condition, culture and susceptibility results, and availability of an alternative antibiotic agent. The use of amikacin was considered inappropriate in subjects with Gram-negative organisms that had either tobramycin or gentamicin minimum inhibitory concentrations of less than or equal to 2 mcg/mL. Main Results: A total of 11 subjects in 2008 and 17 subjects in 2011 who were prescribed amikacin were evaluated. The median and range duration of amikacin therapy was 2.2 days and 0-17 days in 2008. In 2011, the median and range duration of amikacin therapy was 4.6 days and 0-38 days. In 2008 and 2011, 27% and 47% were subjects with cystic fibrosis and/or a history of solid organ transplant, respectively. In 2008 73% of amikacin orders were classified as appropriate while 59% of amikacin orders were classified as appropriate in 2011. Ototoxicity was reported in one subject who received amikacin in both 2008 and 2011. Conclusion: Despite restrictions for ordering amikacin implemented during a nationwide shortage, the percentage of appropriate orders for amikacin was lower during the shortage compared to before the shortage at an academic medical center.

Philosophiae Doctor - PhD / Background: Extended-spectrum beta-lactamase-producing (ESBL) and carbapenemaseproducing Gram-negative bacilli showing resistance to cephalosporins and carbapenems respectively, have been reported from several countries globally and recently among Libyan combatants who have been transferred to European countries for advanced medical care. However, there is a lack of data about their presence in Misrata and in Libya in general. This is the first documented study aimed at investigating the prevalence and resistance mechanisms of ESBL and carbapenemase-producing K. pneumoniae isolates from Misrata. Materials and Methods: Two hundred Gram-negative bacillus isolates were collected and identified from hospitals and pathology laboratories in Misrata. Following antimicrobial susceptibility screening, those showing resistance to cephalosporin and carbapenem were tested for ESBL activity using the Modified double disc synergy test, Sensititer ESBL confirmatory MIC plates and MAST AmpC detection sets D52C and D68C. Carbapenemase activity was detected using RAPIDEC CARBA NP test, Modified Hodge test (MHT), carbapenem inactivation methods (CIM), carbapenem combined test (CCT), and by MAST carba puls set. ESBL and carbapenemases genes were detected using multiplex PCR. Results: K. pneumoniae was the predominant species (85/200) of the 14 species identified, with 56 (65.8%) showing carbapenem resistance, 16 (18.8%) were cephalosporin-resistant carbapenem-susceptible and 13 (15.2%) were susceptible to all antibiotics except ampicillin. OXA-48 was the only carbapenemase detected, with SHV, TEM and CTX-M group 1 found in almost all carbapenem and cephalosporin resistant K. pneumoniae. Rep-PCR analysis revealed multiple clones and some K. pneumoniae strains were genetically related or indistinguishable despite differences in ESBL genes or carbapenemase activity. Conclusion: The findings of this study show that carbapenemase- and ESBL-producing K. pneumoniae are prevalent in Misrata and emphasize the urgent need for optimized infection control and antibiotic stewardship programmes in the Libyan hospitals to prevent further spread of these organisms.

Tikslas: Įvertinti aminoglikozidų koncentracijos tyrimo svarbą racionaliai farmakoterapijai. Nustatyti ir įvertinti amikacino ir gentamicino koncentracijų tyrimų tendencijas Limoges universitetinėje ligonineje (CHU) ir Kauno medicinos universiteto klinikose (KMUK). Metodai: Duomenys buvo gauti iš CHU farmakologijos – toksikologijos ir statistikos skyrių bei KMUK klinikinės chemijos - hematologijos laboratorijos ir statistikos skyriaus. Apskaičiuota kiek koncentracijos tyrimo tenka vienam lovadieniui per 2007 metus, įvertintos gentamicino ir amikacino ištirtų koncentracijų duomenys bei paskirtos dozės. Duomenų statistinė analizė buvo atlikta naudojant MS Office programų paketo MS Excel skaičiuoklės ir duomenų apdorojimo programos. Rezultatai: Gentamicinui buvo atlikta 400 koncentracijos tyrimų (184 atvejų Cmax koncentracijai tirti, 216 – Cmin koncentracijai tirti) . Tirti 131 ligoniai (46 moterys ir 85 vyrai), kuriems gentamicino dozė individualiai adaptuota 221 kartą. Amikacinui buvo atlikta 169 koncentracijos tyrimai (82 atvejai Cmax koncentracijai tirti , 87 – Cmin koncentracijai tirti). Tirti 62 ligoniai (24 moterys ir 38 vyrai), kuriems amikacino dozė individualiai adaptuota 92 kartus. CHU tenka 6,85×10-4 (1:1460) gentamicino koncentracijos tyrimo vienam lovadieniui ir 2,89×10-4 (1:3456) amikacino koncentracijos tyrimo vienam lovadieniui.KMUK tenka 2,77×10-5 ( 1:36089) gentamicino koncentracijos tyrimo vienam lovadieniui. Taigi, CHU 24,72 kartais lenkia KMUK gentamicino... [toliau žr. visą tekstą] / Objectives: To evaluate the importance of researh on aminoglicozids for rational pharmacotherapy. To determine and evaluate the tendencies of studies of amikacin and gentamicin concentration in Limoges University Hospital (CHU) and Kaunas University of medicine Hospital (KMUM). Methods: The data has been received from the department of pharmacology and toxicology and the department of statistics of CHU and from the laboratory of chemistry and hematology and the department of statistics of KMUK. It has been calculated how much concentration study belongs to one bed-day in the year 2007, the data of the studied concentrations of gentamicin and amikacin have been evaluated and the doses have been administered. Statistical analysis of the data has been carried out by the use of MS Excel and data processing programs of MS Office. Results: 400 concentration studies have been carried out for gentamicin (184 cases for the study of Cmax concentration, 216 cases for the study of Cmin concentration). 131 patients (46 women and 85 men), who have been individually adapted the dose of gentamicin for 221 time, have been studied. 169 concentration studies have been carried out for amikacin (82 cases for the study of Cmax concentration, 87 cases for the study of Cmin concentration). 62 patients (24 women and 38 men), who have been individually adapted the dose of amikacin for 92 times. In CHU, there is 6.85×10-4 (1:1460) of gentamicin concentration study for one bed-day and 2.89×10-4 (1:345... [to full text]

Orientador: Daniela Ponce / Resumo: Introdução: Peritonite é complicação grave nos pacientes em diálise peritoneal (DP) e a principal causa de transição para hemodiálise. O uso intraperitoneal (IP) de aminoglicosídeo e vancomicina é opção para o tratamento empírico. No entanto, a absorção sistêmica dessas drogas é controversa e pouco estudada. Objetivo: Descrever os níveis plasmáticos e do dialisato de amicacina e vancomicina administrados IP em pacientes com peritonite em DP nos momentos de 30 e 120 min após administração, após 24h da administração da amicacina e 48h da vancomicina e associá-los com o desfecho da peritonite. Metodologia: Estudo observacional realizado de novembro/2017 a abril/2019, que incluiu 32 episódios de peritonites. Análise de amostras foi realizada no 1º, 3º e 5º dias. No momento de pico, foram consideradas concentrações terapêuticas de amicacina valores entre 25 e 35 mg/L e no vale (antes da infusão do dialisato) concentrações de 4-8 mg/L ; e de vancomicina no vale de 15–20 mg/L. Resultados: A idade foi de 60 ± 11,3 anos, a principal causa da doença renal foi diabetes (42,4%) e 63,3% eram homens. Entre as culturas 39,4% foram gram negativos, 36,3% gram positivos e 21,2% negativas. Houve cura em 84,8% dos episódios. Vancomicina foi administrada IP a cada 72h e amicacina diariamente. Avaliando-se os períodos antes e depois da peritonite, não houve mudanças no tipo de transporte peritoneal (p=0,76), mas houve diferenças na função renal residual (p=0,05) e redução do débito urinário (p=0,0... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Peritonitis is a serious complication in patients on peritoneal dialysis and the main cause of transition to hemodialysis. The intraperitoneal use of aminoglycoside and vancomycin is an option for empiric treatment. However, the systemic absorption of these drugs is controversial and little studied. Objectives: Describe intraperitoneal amikacin and vancomycin dialysate levels in patients with peritonitis on peritoneal dialysis at 30 and 120 minutes after administration, 48 hours after vancomycin and 24 hours after amikacin and associating them with the peritonitis outcome. Methodology: Observational study conducted from August 2017 to April 2019, which included 32 episodes of peritonitis. Samples were analyzed on the 1st, 3rd and 5th days. At peak moment, therapeutic concentrations of amikacin were considered to be between 25 and 35 mg/L and at baseline concentrations of 4-8 mg/L; and vancomycin at the valley moment of 15-20 mg/L. Results: Age was 60 ± 11.3 years, the main cause of kidney disease was diabetes (42.4%) and 63.3% were men. Among the cultures 39.4% were gram negative, 36.3% gram positive and 21.2% negative. There was cure in 84.8% of the episodes. Vancomycin was administered intraperitoneal every 72 hours and amikacin daily. There were no changes in the peritoneal transport type (p = 0.76), but there were differences in residual renal function (p = 0.05) and reduction in urinary output (p = 0.02). Regarding the outcomes of cure and non-cure, there w... (Complete abstract click electronic access below) / Mestre

We tested 42 strains of amikacin-resistant gram-negative bacilli with amikacin in combination with six beta-lactam antibiotics using the checkerboard and time kill curve techniques. Synergism was demonstrated with time-killing curve in 43-68% of the strains tested. Ceftazidime plus amikacin was the most active combination by the checkerboard technique, while amikacin-cefoperazone was the most active combination by the time-killing curve technique against Pseudomonas aeruginosa. Discrepancies were found between the results of the two methods used.

In der vorliegenden Untersuchung wurde der Postantibiotische Effekt (PAE) von Amikacin und Ceftazidim alleinig und in Kombination beider Antibiotika nach einmaliger und mehrfacher Exposition bei Pseudomonas aeruginosa bestimmt. Es wurden verschiedene Stämme mit unterschiedlicher Resistenz gegen Amikacin und Ceftazidim untersucht. Die MHK-Werte bewegten sich für Ceftazidim zwischen < 0,25 µg/ml bis 4 µg/ml und für Amikacin zwischen < 2 µg/ml bis 32 µg/ml. Der PAE lag nach der einmaligen Inkubation von Amikacin bei 0 bis 2,65 Stunden, von Ceftazidim bei 0 bis 2,78 Stunden und in der Kombination beider bei 2,4 bis 5,37 Stunden. Außerdem ergab die mehrmalige Exposition bei Amikacin nach der 1. Inkubation einen PAE von 0,75 bis 2,25 Stunden und stieg auf 2,3 bis 3,5 Stunden nach der 3. Inkubation an; bei Ceftazidim von 1,1 bis 2,18 Stunden Anstieg auf 1,18 bis 2,5 Stunden und bei der Kombination von Amikacin und Ceftazidim von 2,3 bis 3,75 Stunden war ein geringer Abfall auf 1,25 bis 3,25 Stunden zu verzeichnen. Es wurde ein Zusammenhang zwischen dem PAE und der MHK beobachtet: je höher die Resistenz, desto kürzer der PAE. Die Dosierungsintervalle wurden so gewählt, daß sie der klinisch üblichen dreifach Applikation pro Tag entsprachen. Aus unseren Untersuchungen läßt sich theoretisch eine einmalige Applikation pro Tag für Aminoglykoside und eine Kombinationstherapie Aminoglykosid plus Beta-Lactamantibiotika ableiten; vor allem auch, daß bei Mehrfachapplikation der PAE nicht kürzer wird. Für Ceftazidim erscheint eine Dauerinfusion bei fehlendem PAE sinnvoll. / In the current study we examinated the postantibiotic effect (PAE) of the antimicrobial agents amikacin and ceftazidime in vitro. We analyzed the PAE using both agents alone and in combination and after once and several expositions of different isolates of Pseudomonas. Different resistant stains of Pseudomonas were explored versus amikacin and ceftazidime. The observed minimum inhibitory concentration values (MIC) for ceftazidime ranged from < 0.25µg/ml to 4.0µg/ml and for amikacin from < 2.0µg/ml to 32µg/ml. After unique incubation the PAE of amikacin ranged from 0 to 2.65 hours while ceftazidime ranged from 0 to 2.78 hours. In combination of both we observed PAEs between 2.4 to 5.37 hours. A several exposition of amikacin showed after the first incubation PAEs between 0.75 to 2.25 hours increasing after third incubation from 2.3 to 3.5 hours whereas ceftazidime ranged from 1.1 to 2.18 hours and 1.18 to 2.5 hours. Both antimicrobial agents in combination had PAEs between 2.3 and 3.75 hours after first incubation and decreased low after third incubation between 1.25 and 3.25 hours. There is significant correlation to be seen between PAE and MIC-values: the higher resistance is, the shorter PAE will become.

Base teórica: Devido à diminuição do desenvolvimento de novos antimicrobianos nas últimas décadas, terapias combinadas têm sido empregadas contra bactérias multirresistentes como opção à monoterapia no tratamento de infecções graves. Para tratar infecções causadas por Peusdomonas aeruginosa resistente a carbapenêmicos, amicacina e polimixina B têm sido utilizadas em associações com imipenem, pois possuem diferentes mecanismos de ação, o que, teoricamente, indicaria a possibilidade de efeito sinérgico. Objetivo: O objetivo deste trabalho foi verificar a interação, in vitro, de amicacina e polimixina B em associação com imipenem frente a diferentes isolados de P. aeruginosa resistentes a carbapenêmico. Métodos: Foram selecionados isolados de P. aeruginosa resistentes a carbapenêmico oriundos do Hospital de Clínicas de Porto Alegre, coletados no período de janeiro a março de 2015. Foi realizada eletroforese em gel de campo pulsado e detecção do gene blaSPM-1 para selecionar diferentes clones. Seis isolados (três SPM-1 positivos e três negativos para a carbapenemase) foram selecionados para realização da técnica de time-kill, a fim de avaliar a atividade antimicrobiana das combinações de imipenem com amicacina e imipenem com polimixina B. Resultados: Sinergismo ocorreu para combinações de imipenem com amicacina em 3 isolados, dos quais um era SPM-1 positivo e dois eram SPM-1 negativos e todos apresentaram CIMs relativamente baixas a intermediárias. Quanto às combinações de imipenem com polimixina B, houve sinergismo somente para dois isolados, um SPM-1 positivo e um SPM-1 negativo, contudo houve antagonismo em 5 isolados, dois SPM-1 positivos e três SPM-1 negativos. Para 4 isolados, as combinações de imipenem com amicacina tiveram atividade bactericida, enquanto, para todos os isolados, as combinações de imipenem com polimixina B, bem como polimixina B isoladamente, 1x e 2x a CIM apresentaram atividade bactericida. Conclusão: Sinergismo pode ocorrer, para combinações de imipenem mais amicacina, quando os isolados apresentam CIMs relativamente baixas ou intermediárias para imipenem (≤16 μg/mL a 128 μg/mL) e amicacina (≤32 μg/mL). Entretanto, antagonismo aconteceu independentemente de valores altos ou baixos de concentrações inibitórias mínimas para imipenem e polimixina B. Além disso, a presença ou ausência do gene blaSPM-1 não pareceu influenciar nos resultados. / Background: Due to a decrease on new antibiotic development over the last decades, combined therapies have been employed against multigrug-resistant bacteria as an option to monotherapy in severe infection treatment. In order to treat infections caused by carbapenem resistant Pseudomonas aeruginosa, amikacin and polymyxin B have been used in associations with imipenem, because they possess different mechanisms of action, which could, theoretically, indicate the possibility of synergistic effect. Objective: The aim of this study was to verify the interaction, in vitro, of amikacin and polymyxin B in association with imipenem against various carbapenem resistant P. aeruginosa isolates. Methods: Carbapenem resistant P. aeruginosa isolates have been selected from Hospital de Clínicas de Porto Alegre, collected from January to March 2015. Pulsed field gel electrophoresis and detection of blaSPM-1 gene has been performed to select different clones. Six isolates (three SPM-1 positive and three negative for the carbapenemase) were selected for time-kill assay, in order to assess antimicrobial activity of imipenem plus amikacin and imipenem plus polymyxin B combinations. Results: Synergism occurred for combinations of imipenem plus amikacin in three isolates, from which one was SPM-1 positive and two were SPM-1 negative, and all presented relatively low to intermediate minimum inhibitory concentrations. About imipenem plus polymyxin B combinations, synergism occurred in only two isolates, one SPM-1 positive and one SPM-1 negative, however antagonism occurred in five isolates, two SPM-1 positive and three SPM-1 negative. For 4 isolates, imipenem plus amikacin combinations had bactericidal effect, while, for all isolates, combinations of imipenem plus 1x and 2x the MIC of polymyxin B presented bactericidal activity. Conclusions: Synergism can occur, for imipenem plus amikacin combinations, when isolates present relatively low or intermediate MIC of imipenem (≤16 μg/mL to 128 μg/mL) and amikacin (≤32 μg/mL). However, antagonism happened regardless high or low minimum inhibitory concentrations for imipenem and polymyxin B. Also, the presence or absence of blaSPM-1 gene did not seem to influence the results.