Synthesis of Gentamicins C1, C2, and C2a and Antiribosomal and Antibacterial Activity of Gentamicins B1, C1, C1a, C2, C2a, C2b, and X2.

Complementing our earlier syntheses of the gentamicins B1, C1a, C2b, and X2, we describe the synthesis of gentamicins C1, C2, and C2a characterized by methyl substitution at the 6'-position, and so present an alternative access to previous chromatographic methods for accessing these sought-after compounds. We describe the antiribosomal activity of our full set of synthetic gentamicin congeners against bacterial ribosomes and hybrid ribosomes carrying the decoding A site of the human mitochondrial, A1555G mutant mitochondrial, and cytoplasmic ribosomes and establish structure-activity relationships with the substitution pattern around ring I to antiribosomal activity, antibacterial resistance due to the presence of aminoglycoside acetyl transferases acting on the 6'-position in ring I, and literature cochlear toxicity data.

Effects of Sub-Minimum Inhibitory Concentrations of Gentamicin on Alginate Produced by Clinical Isolates of Pseudomonas aeruginosa.

Background: Bacterial virulence factors may be influenced by sub-minimum inhibitory concentrations (sub-MICs) of antibiotics. The main purpose of this study was to investigate the effects of gentamicin at sub-MICs (0.5 MIC and 0.25 MIC) on alginate production of clinical isolates of Pseudomonas aeruginosa. Materials and Methods: The minimum inhibitory concentrations of gentamicin against 88 clinical isolates of P. aeruginosa were determined using the broth microdilution method. Alginate production of the isolates in the absence and presence of gentamicin at sub-MICs was assessed by the carbazole method. The presence of alginate in clinical isolates was confirmed by the detection of alginate genes (algD and algU) using the PCR method. Results: All the isolates had the ability of alginate production and were positive for algD and algU genes. sub-MICs of gentamicin significantly increased alginate production of 34 isolates (38.6%). On the other hand, in 49 isolates (55.7%), alginate production was significantly increased after treatment with sub-MICs of gentamicin. In five isolates (5.7%), the alginate production was reduced in exposure to 0.5 MIC of gentamicin while it was increased by gentamicin at 0.25 MIC. Conclusion: This study showed different effects of gentamicin at sub-MICs on the alginate production of clinical isolates of P. aeruginosa. Further research is highly recommended to understand the mechanism of different responses of P. aeruginosa isolates to the exposure of sub-MICs of gentamicin.

Phylogeny and antimicrobial resistance of extended-spectrum beta-lactamaseproducing Escherichia coli from hospitalized oncology patients in Perú / Filogenia y resistencia de cepas de Escherichia coli productoras de betalactamasas de espectro extendido a los antibióticos en pacientes con cáncer hospitalizados en Perú.

Introduction: Healthcare-associated infections are a public health problem due to the increased morbimortality of patients, especially those with risk factors such as immunosuppression due to oncological diseases. It is essential to determine the genetic diversity of the main microorganisms causing healthcare infections by combining traditional epidemiological surveillance and molecular epidemiology for better outbreak follow-up and early detection. Objective: To determine the phylogenetic group and antibiotic resistance of Escherichia coli isolated from hospitalized oncologic patients. Materials and methods: We conducted a cross-sectional study of 67 strains of ESBL-producing Escherichia coli to determine their phylogenetic group and described their antibiotic resistance profile, beta-lactam resistance genes, as well as the type of sample and the hospitalization areas from which they were recovered. Results: The most frequent phylogenetic group was B2 (36%); 57% of B2 strains were isolated from urine and 33% came from the urology department. Resistance to ciprofloxacin and gentamicin was 92% and 53%, respectively, and 79% of the strains had the blaCTX-M gene. A significant association (p<0.05) was found between the phylogenetic groups, ciprofloxacin resistance, and the age of the patients. Conclusion: The predominant E. coli phylogroup was B2. We evidenced high resistance to ciprofloxacin and gentamicin, a high proportion of ESBL strains with the blaCTX-M gene, and a significant association between the phylogenetic group and the resistance to ciprofloxacin.

Introducción. Las infecciones asociadas con la atención en salud constituyen un problema de salud pública porque aumentan la morbimortalidad de los pacientes, sobre todo de aquellos con factores de riesgo, como la inmunosupresión debida a enfermedades oncológicas. Es importante conocer la diversidad genética de los principales microorganimos causantes de infecciones hospitalarias mediante la vigilancia epidemiológica tradicional y la epidemiología molecular, para hacer un mejor seguimiento y detectar brotes tempranamente. Objetivo. Determinar el grupo filogenético y la resistencia a antibióticos de las cepas de Escherichia coli aisladas de pacientes con cáncer hospitalizados. Materiales y métodos. Se hizo un estudio de tipo transversal que incluyó 67 cepas de Escherichia coli productoras de betalactamasas de espectro extendido (BLEE). Se determinó el grupo filogenético, el perfil de resistencia a los antibióticos, los genes de resistencia a betalactámicos, el tipo de las muestras y los servicios de hospitalización de donde fueron recuperadas. Resultados. El grupo filogenético más frecuente fue el B2 (36 %). El 57 % de las cepas B2 fueron aisladas de muestras de orina y el 33 % provenía del servicio de urología. La resistencia a ciprofloxacino y gentamicina fue de 91 y 53 %, respectivamente, y el 79 % de las cepas tenía el gen blaCTX-M. Se encontró una relación significativa (p<0,05) entre los grupos filogenéticos y la resistencia a ciprofloxacina, así como a la edad del paciente. Conclusión. El filogrupo de E. coli predominante fue el B2. Se evidenció una gran resistencia a ciprofloxacina y gentamicina, una proporción elevada de cepas BLEE con el blaCTX-M, y una relación entre el grupo filogenético y la resistencia a ciprofloxacino.

Filogenia y resistencia de cepas de Escherichia coli productoras de betalactamasas de espectro extendido a los antibióticos en pacientes con cáncer hospitalizados en Perú / Phylogeny and antimicrobial resistance of extended-spectrum beta-lactamase- producing Escherichia coli from hospitalized oncology patients in Perú

Introducción. Las infecciones asociadas con la atención en salud constituyen un problema de salud pública porque aumentan la morbimortalidad de los pacientes, sobre todo de aquellos con factores de riesgo, como la inmunosupresión debida a enfermedades oncológicas. Es importante conocer la diversidad genética de los principales microorganimos causantes de infecciones hospitalarias mediante la vigilancia epidemiológica tradicional y la epidemiología molecular, para hacer un mejor seguimiento y detectar brotes tempranamente. Objetivo. Determinar el grupo filogenético y la resistencia a antibióticos de las cepas de Escherichia coli aisladas de pacientes con cáncer hospitalizados. Materiales y métodos. Se hizo un estudio de tipo transversal que incluyó 67 cepas de Escherichia coli productoras de betalactamasas de espectro extendido (BLEE). Se determinó el grupo filogenético, el perfil de resistencia a los antibióticos, los genes de resistencia a betalactámicos, el tipo de las muestras y los servicios de hospitalización de donde fueron recuperadas. Resultados. El grupo filogenético más frecuente fue el B2 (36 %). El 57 % de las cepas B2 fueron aisladas de muestras de orina y el 33 % provenía del servicio de urología. La resistencia a ciprofloxacino y gentamicina fue de 91 y 53 %, respectivamente, y el 79 % de las cepas tenía el gen blaCTX-M. Se encontró una relación significativa (p<0,05) entre los grupos filogenéticos y la resistencia a ciprofloxacina, así como a la edad del paciente. Conclusión. El filogrupo de E. coli predominante fue el B2. Se evidenció una gran resistencia a ciprofloxacina y gentamicina, una proporción elevada de cepas BLEE con el blaCTX-M, y una relación entre el grupo filogenético y la resistencia a ciprofloxacino.

Introduction: Healthcare-associated infections are a public health problem due to the increased morbimortality of patients, especially those with risk factors such as immunosuppression due to oncological diseases. It is essential to determine the genetic diversity of the main microorganisms causing healthcare infections by combining traditional epidemiological surveillance and molecular epidemiology for better outbreak follow-up and early detection. Objective: To determine the phylogenetic group and antibiotic resistance of Escherichia coliisolated from hospitalized oncologic patients. Materials and methods: We conducted a cross-sectional study of 67 strains of ESBL-producing Escherichia coli to determine their phylogenetic group and described their antibiotic resistance profile, beta-lactam resistance genes, as well as the type of sample and the hospitalization areas from which they were recovered. Results: The most frequent phylogenetic group was B2 (36%); 57% of B2 strains were isolated from urine and 33% came from the urology department. Resistance to ciprofloxacin and gentamicin was 92% and 53%, respectively, and 79% of the strains had the blaCTX-Mgene. A significant association (p<0.05) was found between the phylogenetic groups, ciprofloxacin resistance, and the age of the patients. Conclusion: The predominant E. coli phylogroup was B2. We evidenced high resistance to ciprofloxacin and gentamicin, a high proportion of ESBL strains with the blaCTX-M gene, and a significant association between the phylogenetic group and the resistance to ciprofloxacin.

Comparación de antibióticoterapia en la apendicitis complicada en pediatría / Comparison of antibiotic therapy in complicated appendicitis in pediatrics

INTRODUCCIÓN. La apendicitis aguda es una patología pediátrica quirúrgica que en su fase complicada requiere uso de antibióticos en el postoperatorio; encontrar la mejor opción como experiencia local, fue necesario. OBJETIVO. Comparar un esquema de antibioticoterapia triple vs un doble respecto a variables: demográficas, clínicas y de costos en pacientes pediátricos con apendicitis complicada. MATERIALES y MÉTODOS. Estudio analítico transversal. Población de 133 pacientes y una muestra de 93, operados por apendicitis complicada; 58 recibieron ampicilina + metronidazol + gentamicina y 35 ceftriaxona + metronidazol. Se comparó las variables: estadía hospitalaria, complicaciones y costo monetario de cada esquema. Se realizó en la Unidad de Cirugía Pediátrica del Hospital de Especialidades Carlos Andrade Marín, en el periodo enero de 2017 a octubre de 2018. Los datos fueron analizados con R-Studio 1.8.366 para Windows. RESULTADOS. No hubo diferencia estadística con respecto a: estadía hospitalaria (p=0,261); complicaciones como infección del sitio quirúrgico (p=0,196), re-intervención quirúrgica (p=0,653) y costo (p=0,059). CONCLUSIÓN. Se comparó el esquema de antibioticoterapia triple vs un doble, utilizados en apendicitis complicada en pediatría. No se encontró diferencias estadísticamente significativas en este reporte preliminar, con la diferencia de que con el esquema doble la frecuencia de administración fue menor y se evitó la exposición a los efectos colaterales de los aminoglicósidos.

INTRODUCTION. Acute appendicitis is a pediatric surgical pathology that in its complicated phase requires the use of antibiotics during the postoperative period; finding the best option as local experience was a must. OBJECTIVE. Compare a triple vs a double antibiotic therapy scheme respect demographic, clinical and cost variables in pediatric patients whit complicated apendicitis. MATERIALS AND METHODS. Cross-sectional analytical study. Population of 133 patients and sample of 93, with complicated appendicitis; 58 received ampicillin + metronidazole + gentamicin and 35 ceftriaxone + metronidazole. The following variables were compared; hospital stay, complications and monetary cost of each scheme. It was performed in the Pediatric Surgery Unit of the Hospital of Specialties Carlos Andrade Marin, during january 2017, through october 2018. The data were analyzed with R-Studio 1.8.366 for Windows. RESULTS. There was no statistical difference regarding hospital stay (p=0.261); complications such as surgical site infection (p=0.196), re-surgical intervention (p=0.653); nor cost (p=0.059). CONCLUSION. Triple vs. Double antibiotic therapy scheme used in complicated appendicitis in pediatrics was compared. No statistically significant differences were found in this preliminary report, how ever with the double scheme the frequency of administration was lower and exposure to side effects of aminoglycosides was avoided.

Infecção do sítio cirúrgico após cesariana em uma maternidade de Manaus, Brasil: a importância do uso racional da antibioticoterapia / Surgical site infection after cesarean section in a maternity hospital in Manaus, Brazil: the importance of rational antibiotic therapy

Objetivo: Descrever o perfil epidemiológico e microbiológico das puérperas com diagnóstico de infecção após cesárea, caracterizando as infecções de sítio cirúrgico e o tratamento. Métodos: Coorte prospectiva de parturientes submetidas a parto cesáreo em maternidade pública de Manaus, Amazonas, Brasil, com diagnóstico de infecção de sítio cirúrgico, entre 1º de julho de 2019 e 30 de abril de 2020. Foram coletados dados epidemiológicos. Para a investigação do perfil microbiológico, foi realizada a identificação da cultura a partir da secreção da infecção do sítio cirúrgico e do antibiograma das culturas. Resultados: Um total de 81 pacientes foi diagnosticado com infecção de sítio cirúrgico durante o período de estudo. A taxa de infecção de sítio cirúrgico na maternidade em estudo foi de 6,0%. As pacientes possuíam baixa escolaridade e baixa renda mensal, com ocupações que requerem menor qualificação, sendo a maioria solteira. Entre as pacientes, 70,4% eram obesas e 28,4% apresentaram sobrepeso; 45,6% delas tiveram parto cesáreo de emergência e 29,6% não usaram antibióticos profiláticos. Staphylococcus aureus foi a cultura identificada mais frequentemente e apresentou resistência ao antibiótico mais prescrito: a gentamicina. Conclusão: A taxa de infecção do sítio cirúrgico foi alta durante o período do estudo. Ressaltamos a necessidade de um protocolo eficaz de identificação bacteriana e acompanhamento da puérpera. O conhecimento das características epidemiológicas e microbiológicas pode auxiliar no planejamento dos cuidados realizados pelas instituições de saúde para minimizar os casos de infecção de sítio cirúrgico e suas consequências.(AU)

Objective: To describe the epidemiological and microbiological profiles of puerperal women diagnosed with the infection after cesarean sections, characterizing the surgical site infections and treatment. Methods: Prospective cohort of parturients underwent cesarean delivery at a public maternity hospital in Manaus, Amazonas, Brazil, diagnosed with surgical site infection between July 1, 2019, and April 30, 2020. Epidemiological data were collected. To investigate the microbiological profile, both culture identification from surgical site infection secretion and antibiogram for the cultures were performed. Results: A total of 81 patients were confirmed to have surgical site infection during this study period; The surgical site infection rate in the maternity hospital under study was 6.0%. The patients presented a low level of education and monthly income, with occupations that require lower qualification, and most of them are single. Seventy point four percent of the patients were obese, and 28.4% were overweight. Forty-five point six percent of patients had an emergency cesarean delivery, and 29.6% did not use prophylactic antibiotics. Staphylococcus aureus was the most frequent culture identified from surgical site infection secretion and presented resistance to the most prescribed antibiotic, Gentamicin. Conclusion: The rate of surgical site infection was high during the study period. We highlight the need for an effective bacterial identification protocol and monitoring of puerperal women. Knowledge of epidemiological and microbiological characteristics can assist in the planning of care performed by the health institutions to minimize cases of surgical site infection and its consequences.(AU)

A randomized controlled trial on irrigation of open appendectomy wound with gentamicin- saline solution versus saline solution for prevention of surgical site infection.

BACKGROUND: Surgical site infection (SSI) is one of the most common complications after abdominal surgery. The present trial examined the efficacy of saline irrigation of open appendectomy wound with or without topical antibiotics in prevention of SSI. METHODS: This was a double-blind randomized trial on patients with acute appendicitis who underwent open appendectomy. Patients were randomly allocated to one of three equal groups; group I had layer-by-layer wound irrigation with gentamicin-saline solution, group II had wound irrigation with saline solution, and group III received no irrigation (Control group). The main outcome measures were the incidence of incisional SSI, surgical site occurrence (SSO), other complications, operation time, postoperative pain, and patients' satisfaction. RESULTS: 205 patients (113 female) of a mean age of 27.9 years were included. The average hospital stay and pain scores were similar in the three groups. Groups I and II had significantly lower rates of incisional SSI (4.3% Vs 2.9%; Vs 17.4%, p = 0.005) and SSO (24.6% Vs 13.4% Vs 43.5%; p = 0.0003) as compared to group III. Groups I and II had comparable rates of SSI and SSO. The three groups had similar rates of wound seroma, hematoma, and dehiscence. Groups I and II had significantly higher satisfaction with the procedure than group III. CONCLUSIONS: Layer-by-layer irrigation of open appendectomy wound decreased the rates of incisional SSI and SSO significantly compared to the no-irrigation group. Adding gentamicin to saline solution was useless to improve the outcome and did not decrease rates of SSI or other complications.

Vinpocetine Improves Oxidative Stress and Pro-Inflammatory Mediators in Acute Kidney Injury.

BACKGROUND: Gentamicin-induced-acute kidney injury (AKI) is a multifaceted phenomenon which previously linked to the oxidative stress only. Vinpocetine prevents reactive free radical generation which contributed in reduction of damage. Therefore, objective of the present study was to investigate the renoprotective effect of vinpocetine on gentamicin-induced-AKI in rats. METHODS: Thirty Sprague Dawley Male rat were divided into three groups. Control group (n = 10): Rats treated with distilled water + intra-peritoneal injection of normal saline 2 ml/kg/day. Gentamicin group (n = 10): Rats treated with distilled water + intra-peritoneal injection of gentamicin 100 mg/kg/day. Vinpocetine group (n = 10): Rats treated with vinpocetine + intra-peritoneal injection of gentamicin 100 mg/kg/day. Blood urea and serum creatinine were estimated by auto-analyzer. Serum malondialdehyde (MDA), superoxide dismutase (SOD), Neutrophil Gelatinase Associated Lipocalin (NGAL), kidney injury molecules (KIM-1), and Cystatin-c were measured by ELISA kit methods. RESULTS: Vinpocetine led to significant renoprotective effect on gentamicin induced-AKI through amelioration of blood urea and serum creatinine compared with gentamicin group P < 0.01. Vinpocetine improved oxidative stress through reduction of MDA serum level and elevation of SOD significantly compared with gentamicin group P = 0.001 and P = 0.03, respectively. Indeed, vinpocetine reduced glomerular and renal tubular injury via reduction of inflammatory biomarkers including KIM-1, NGALand Cystatin-c sera levels significantly P < 0.01 compared to gentamicin group. CONCLUSIONS: Vinpocetine leads to significant attenuation of gentamicin-induced-AKI through modulation of oxidative stress and pro-inflammatory pathway.

Retrospective evaluation of in vitro effect of gentamicin B1 against Fusarium species.

The in vitro susceptibility of gentamicin fractions against Fusarium growth was the subject of this retrospective study. Fusariosis was earlier an exceptionally rare human disease and an unrealistic idea to treat soil saprophytes and plant pathogens with expensive antibiotics such as gentamicins or their minor components. Disseminated fusariosis is now the second most frequent lethal fungal infection after aspergillosis especially in neutropenic patients with hematologic malignancy. Results of this study obtained between May and November 1973 were interesting but not practicable and remained unpublished. Seven Fusarium and 28 other fungal strains were tested for their susceptibility to gentamicin B1. The anti-Fusarium activity of gentamicin B1 was between 0.2 and 3.1 µg/ml minimum inhibitory concentration (MIC) values. The MIC values of clotrimazol and amphotericin B against Fusarium species were significantly higher, 3.1-12.5 µg/ml and 3.1-50 µg/ml, respectively. Gentamicin B1 and its structurally related congeners including hygromycin B, paromomycin, tobramycin (nebramycin factor 5'), nebramycin (nebramycin factor 4), and sisomicin exerted strong in vitro inhibition against Fusarium species between 0.2 and 12.5 µg/ml concentrations. The antibacterial MIC concentration of gentamicin B1 tested on 20 bacterial strains ranged between 0.1 and 50 µg/ml. Gentamicin B1, a minor fraction of the gentamicin complex, inhibited effectively the growth of Gram-positive (Staphylococcus, Streptococcus, Bacillus subtilis) bacteria and Gram-negative (Escherichia coli, Salmonella, Proteus, Pseudomonas) pathogens. Gentamicins and related aminoglycoside antibiotics are used in medical practice. It is proposed that due to the increasing incidence of fusariosis and drug resistance, gentamicin components, particularly minor fraction B1 and related aminoglycoside antibiotics, could be tested for their in vivo activity against fusariosis and aspergillosis either alone or in combination with other antifungal agents.

Fabrication and biological effect investigation of the antibacterial drug delivery system with PEG-hydrogel and gentamicin-loaded-CSt on titanium surface / 中华骨科杂志

Objective To fabricate an antibacterial controlled drug delivery system with PEG-hydrogel and gentamicin-loaded-CSt on titanium surface,and to investigate its surface characteristics,swelling behavior,drug release behavior in vitro,antiinfection performance in vivo,and tissue biocompatibility.Methods Cross-linked starch (CSt) was synthesized first and then CSt was loaded with gentamicin (GEN) as a carrier (GEN@CSt),then 4-arm-polyethylene glycol (PEG) was added to it which was mixed by ultrasound.The surface of titanium (Ti) was covered with a layer of poly dopamine (PDA).The drug-loaded hydrogel was fixed to the titanium surface,subsequently capped by poly lactic-co-glycolic acid (PLGA) membranes,and then the Ti-PDA-PEG (GEN@CSt)-PLGA composite coating was fabricated finally.Surface morphology of the system was observed,while the swelling behavior was characterized;release behavior of the composite coating was detected;the bacteriostatic experiments were carried out with staphylococcus aureus (SAU),staphylococcus epidermidis (SEP) and escherichia coli (ECO) in vitro.The animal models of infected bone defect was established in 36 New Zealand white rabbits.These animals were randomly divided into three groups.Group 1 animals were implanted with drug-loaded composite coatings.Group 2 animals were implanted with drug-free composite coatings.Group 3 animals were implanted with bare titanium rods.The infection data were collected periodically to carry out antiinfection experiments in vivo.Another 12 rabbits were divided into the experimental group and the control group randomly.Biocompatibility of the materials was observed by histopathology after implantation of the corresponding materials into the femoral condyle.Results The composite coating adhered to the titanium surface firmly,presenting a smooth and translucent shape.The ratio of CSt/PEG affects swelling behavior varied,starch-free gels maintained an equilibrium swelling of 7.4,after the ratio reached 1 ∶ 1,the equilibrium swelling ratio remained at 3.0.In-vitro the release rate of the first 8 h was fast,and the cumulative release amount accounted for 83％ of the total in the first 7 days,lasting more than 13 d.In vitro antibacterial test,the average diameter of the inhibition ring was 3.6±0.13 cm (SAU),3.4±0.11 cm (SEP),3.7±0.10 cm (ECO).In-vivo anti-infection experiment,the infection situation of the group 1 was better than the control groups 2 and 3.The pathological results indicated that inflammatory reaction in the experimental group was basically the same as the control group.Conclusion The study successfully fabricated the antibacterial controlled drug delivery system with PEG-hydrogel and gentamicin-loaded-CSt on titanium surface.The system has a reasonable drug release behavior,and effectively inhibited the growth of bacteria in vivo and in vitro.It also has good biocompatibility to stand a promising strategy to improve the orthopedics anti-infection.

Diabetes Mellitus: fator de risco para toxicidade de medicamentos / Diabetes Mellitus: factor de riesgo para toxicidad de fármacos / Diabetes Mellitus: a risk factor for drug toxicity

RESUMO Objetivo Avaliar o efeito do antibiótico gentamicina em modelo experimental na presença de Diabetes Mellitus por meio da função renal e perfil oxidativo. Método Ratos Wistar, adultos, machos, foram distribuídos nos grupos: Citrato; Gentamicina (Genta), (gentamicina 100 mg/kg de peso corporal, 1 vez ao dia, intraperitoneal, i.p., 5 dias); DM (60 mg/kg de STZ, intravenosa, i.v., dose única, diluída em tampão citrato) e DM+Genta. Foram avaliados os parâmetros fisiológicos, a função renal (clearance de creatinina), a lesão oxidativa (peróxidos e substâncias reativas ao ácido tiobarbitúrico − TBARS urinários) e a hemodinâmica renal. Resultados O grupo Diabetes Mellitus apresentou hiperglicemia crônica, associada à perda de peso corporal, polifagia, polidipsia e poliúria, além de redução da função renal, com aumento na excreção de metabólitos oxidativos. A administração de gentamicina induziu a redução do fluxo sanguíneo renal e o aumento da resistência vascular renal em ratos saudáveis. A associação do Diabetes Mellitus com gentamicina resultou em redução adicional na função renal e elevação de metabólitos oxidativos, com aumento de resistência vascular renal. Conclusão A existência de Diabetes Mellitus determinou a elevação da nefrotoxicidade da gentamicina e se confirmou como fator de risco para nefrotoxicidade de medicamentos.

RESUMEN Objetivo Evaluar el efecto del antibiótico gentamicina en modelo experimental en la presencia de Diabetes Mellitus mediante la función renal y el perfil oxidativo. Método Ratas Wistar, adultas, machos, fueron distribuidas en los grupos: Citrato; Gentamicina (Genta), (gentamicina 100 mg/kg de peso corporal, 1 vez al día, intraperitoneal, i.p., 5 días); DM (60 mg/kg de STZ, intravenosa, i.v., dosis única, diluida en tampón citrato) y DM+Genta. Fueron evaluados los parámetros fisiológicos, la función renal (aclaramiento de creatinina), la lesión oxidativa (peróxidos y sustancias reactivas al ácido tiobarbitúrico - TBARS urinarios) y la hemodinámica renal. Resultados El grupo Diabetes Mellitus presentó hiperglucemia crónica, asociada con pérdida de peso corporal, polifagia, polidipsia y poliuria, además de reducción de la función renal, con aumento en la secreción de metabolitos oxidativos. La administración de gentamicina indujo a la reducción del flujo sanguíneo renal y al incremento de la resistencia vascular renal en ratas sanas. La asociación del Diabetes Mellitus con gentamicina resultó en reducción adicional en la función renal y elevación de metabolitos oxidativos, con aumento de resistencia vascular renal. Conclusión La existencia de Diabetes Mellitus determinó la elevación de la nefrotoxicidad de la gentamicina y se confirmó como factor de riesgo para nefrotoxicidad de fármacos.

ABSTRACT Objective To assess the effect of the antibiotic Gentamicin in an experimental model in the presence of Diabetes Mellitus through renal function and oxidative profile. Method Adult male Wistar rats were distributed into groups: Citrate; Gentamicin (Genta), (intraperitoneal, i.p. gentamicin, 100 mg/kg of body weight, once a day,5 days); DM (60 mg/kg of STZ (Streptozotocin), single dose, intravenously, i.v., diluted in citrate buffer); and DM+Genta. Physiological parameters, renal function (creatinine clearance), oxidative damage (peroxides and thiobarbituric acid reactive substances - urinary TBARS) and renal hemodynamics were evaluated. Results The Diabetes Mellitus group presented chronic hyperglycemia associated with loss of body weight, polyphagia, polydipsia and polyuria, in addition to reduced renal function and with an increase in oxidative metabolite excretion. Administration of gentamicin induced a reduction in renal blood flow and increased renal vascular resistance in healthy rats. The association of Diabetes Mellitus with gentamicin resulted in an additional reduction in renal function and elevation of oxidative metabolites, with increased renal vascular resistance. Conclusion The existence of Diabetes Mellitus resulted in an elevation of gentamicin nephrotoxicity, thus confirming the risk factor for drug nephrotoxicity.

Facial carbuncle - a new method of conservative surgical management plus irrigation with antibiotic-containing solution.

OBJECTIVE: This paper reports on a non-conventional method for the management of facial carbuncles, highlighting its superiority over conventional surgical treatment in terms of cosmetic outcome and shorter duration of wound healing. BACKGROUND: The mainstay of treatment for carbuncles involves the early administration of antibiotics in combination with surgical intervention. The conventional saucerisation, or incision and drainage, under normal circumstances results in moderate to large wounds, which may need secondary surgery such as skin grafting, resulting in a longer duration of wound healing and jeopardising cosmetic outcome. CASE REPORTS: The reported three cases presented with extensive carbuncles over the chin, face and lips region. In addition to early commencement of intravenous antibiotics, the pus was drained, with minimal incision and conservative wound debridement, with the aim of maximal skin conservation. This was followed by thrice-daily irrigation with antibiotic-containing solution for a minimum of 2 consecutive days. The wounds healed within two to four weeks, without major cosmetic compromise. CONCLUSION: The new method showed superior cosmetic outcomes, with a shorter duration of wound healing. Conservative surgical management can be performed under regional anaesthesia, which may reduce morbidity and mortality; patients with facial carbuncles often have higher risks with general anaesthesia.

Priming previne a insuficiência renal aguda nefrotóxica através da estimulação do mecanismo de defesa antioxidante / Priming prevent nephrotoxic acute renal failure through stimulation of antioxidant defense mechanism

RESUMO Introdução: Priming é um mecanismo de proteção induzida pela exposição anterior de uma célula ou órgão a baixas ou mesmas concentrações de uma substância tóxica. Objetivo: analisar o mecanismo de priming induzido pela exposição a gentamicina em células tubulares proximais humanas e na insuficiência renal aguda (IRA). Métodos: Células tubulares foram expostos a 2 mM de gentamicina durante 24 horas, enquanto ratos Wistar foram expostas a 40 mg/kg durante 3 dias. Depois de uma semana, as células foram expostas à mesma concentração durante 24h e os ratos durante dez dias. Os animais condicionados foram comparados com ratos controle e tratados com gentamicina durante 10 dias. Foram analisados parâmetros bioquímicos, o estresse oxidativo foi analisado por hidroperóxidos e proteínas carboniladas urinárias, enquanto a defesa antioxidante foi estudada pela atividade antioxidante do plasma e imunomarcação e atividade da catalase, superóxido dismutase, heme oxigenase-1 (HO-1) nos rins. Necrose, apoptose, proliferação e expressão da endotelina-1 (ET-1) e HO-1 foram estudadas em células. Resultados: o condicionamento dos animais inibiu o aumento da creatinina, ureia, excreção urinária de sódio e de proteína induzida por gentamicina. Bosentana, antagonista do receptor ET-1, e hemin, indutor de HO-1, potencializaram a inibição. O mecanismo de proteção foi mediado pela indução de enzimas antioxidantes HO-1, catalase e SOD atividade e redução do estresse oxidativo. O condicionamento inibiu a morte celular e induziu a proliferação via produção de ET-1. Conclusão: o mecanismo de condicionamento é persistente e multifactorial, o estímulo da defesa antioxidante poderia mimetizar o processo de condicionamento e impedir a IRA.

ABSTRACT Introduction: Priming is the mechanism of protection induced by a previous exposition of a cell or organ to low or equal concentrations of a toxic substance. Objective: To analyze the mechanism of priming induced by the previous exposition to gentamicin in human proximal tubular cells and nephrotoxic acute renal failure (ARF). Methods: Wistar rats and tubular cells were exposed to gentamicin 2mM during 24h or 40 mg/kg during 3 days and after one rest week were exposed to the same concentration during 24h in cells and additional ten days in rats. The primed animals were compared to control rats receiving vehicle and GENTA animals treated with the gentamicin during the same period. Biochemical parameters were analyzed. The oxidative stress was analyzed by urinary hydroperoxides and carbonylated protein while antioxidant defense was studied by antioxidant activity of the plasma (FRAP), catalase, superoxide dismutase, heme-oxygenase 1 (HO-1) immunostaining and enzymatic activity in kidney. Necrosis, apoptosis, proliferation, endothelin 1 (ET-1) and HO-1 expression were studied in cells. Results: Priming of the animals inhibited the increase in creatinine, urea, sodium excretion and urinary protein induced by gentamicin. Bosentan, ET-1 receptor antagonist, and hemin, HO-1 inducer, potentiate the inhibition. The mechanism of protection was mediated by induction of the antioxidant enzymes HO-1, catalase and SOD activity and oxidative stress reduction. Priming inhibited cell death and induced proliferation through ET-1 production. Conclusion: Priming is a persistent and multifactorial mechanism, the stimulation of the antioxidant defense could mimics partially the priming process and prevent the ARF.

Bioprosthetic Aortic Valve Endocarditis in Association with Enterococcus durans.

Enterococci are common organisms associated with endocarditis, but infection by Enterococcus durans is very rare. To our knowledge, only 3 cases have been reported in the medical literature, and all 3 have involved native valves. Here we publish the first reported case (to our knowledge) of E. durans endocarditis in association with a bioprosthetic aortic valve. After the organism and its antibiotic susceptibility were identified, the 74-year-old male patient was treated successfully with teicoplanin and gentamicin, over a course of 6 weeks.

[Small doses of gentamicin drum indoor injection treatment of intractableMénière disease clinical observation of the impact of the hearing].

Objective:To study the effect of low-dose gentamicin intratympanic therapy on intractable Meniere's disease on hearing.Method:One hundred and forty cases of patients with ENT intractable Meniere's disease were selected in this clinical trial study,all patients were enrolled in the drum line intraventricular injection of low-dose gentamicin treatment.After two weeks' treatment in hospital,the patients followed-up for 1 years,all patients did pure tone audiometry,speech audiometry and on hearing threshold changes before and after treatment were comparatively analyzed; continu followed-up for 1 year and the patients' Meniere's disease therapeutic effect were analyzed.Result:After treatment,the follow up within a year of 120 patients(140 cases,20 cases were lost),36 cases never attack of vertigo symptoms,the total effective rate was 91.7%; all patients before treatment speech frequency was(67.2±2.1) dB after treatment(65.5±2.0) dB,the difference was not statistically significant(P>0.05); In the group of gentamicin treatment,all patients 1-3 kHz compare hearing thresholds and changes of 8 kHz before and after injection,the difference was not statistically significant(P>0.05); tinnitus,ear fullness episodes of a significant reduction in the overall incidence rate dropped to 2% from 7% after treatment,the difference was statistically significant(P<0.05) .Conclusion:For intractable Meniere's disease,a small dose of gentamicin intratympanic have a positive clinical effect,and no significant effect on hearing Thus,it is a worthy of promotion and application for low dose gentamincin intratympanic injection in intractable Meniere's disease.

Study of variables involved in hospital-acquired urinary tract infections at a university hospital / Estudo de variáveis envolvidas em infecção do trato urinário nosocomiais em um hospital universitário

OBJECTIVE: Analyze bacteria involved in urinary tract nosocomial infections (UTIs), their sensitivity profile, and other correlated clinical variables. METHODS: This was a retrospective study, based on the analysis of positive urine culture reports (from100,000CFU/ml) for nosocomial infection covering the years 2009, 2010 and 2011, and on medical records. Statistical analysis was performed through SPSS 19.0 software, using chi-square tests with Yates correction and Pearson's correlation coefficient. p<0.05 was considered statistically significant. RESULTS: The sample consisted of 74 positive urine cultures, 64.9% of which from females, and 58.1% of which from patients above 50 years of age. Medical conditions accounted for 87.8% of cases, and nervous and gastrointestinal problems were the most prevalent. Hospital stay ranged from 56.7±35.7 days; 51.4% of the patients used indwelling urinary catheter, 54% of whom over a 30 day period. Klebsielle pneumoniae and Escherichia coli together accounted for 60.8% of cases. Amikacin, Gentamicin, Cefoxitin, Piperacillin-tazobactam, Imipem, Meropenem and Ertapenem showed ≥50% sensitivity. There were correlations between symptoms associated to UTI and antibiotic use after urine culture (p=0.02), and catheter use and duration of hospital stay (p=0.04). CONCLUSIONS: Female patients over 50 years of age with underlying clinical conditions originated in the nervous system or the gastrointestinal apparatus making use of indwelling urinary catheters for over 30 days and a hospital stay period of 56.7±35.7 days are more likely to develop nosocomial UTIs. Amikacin, Gentamycin and Cefoxitin are feasible options for empirical antibiotic therapy against the two most prevalent bacteria.

OBJETIVO: Analisar as bactérias envolvidas nas infecções do trato urinário (ITUs) nosocomiais, perfil de sensibilidade, e outras variáveis clínicas correlacionadas. MÉTODOS: Estudo retrospectivo, com base na análise dos laudos de urocultura positiva (a partir de 100 mil UFC/ml) para infecção nosocomial abrangendo os anos 2009, 2010 e 2011, em prontuários médicos. A análise estatística foi realizada no SPSS 19.0, utilizando os testes do qui-quadrado com correção de Yates e coeficiente de correlação de Pearson. Considerou-se estatisticamente significativo p<0,05. RESULTADOS: A amostra constitui-se de 74 uroculturas positivas, sendo 64,9% do sexo feminino, com 58,1% acima de 50 anos. As patologias clínicas corresponderam a 87,8% dos casos, sendo sistema nervoso e gastrointestinal os de maiores prevalências. Tempo de permanência hospitalar foi de 56,7±35,7 dias, 51,4% fizeram uso de SVD, sendo 54% destes com uso acima de 30 dias. As bactérias Klebsielle pneumoniae e Escherichia coli representaram juntas 60,8% dos casos. Os antibióticos Amicacina, Gentamicina, Cefoxitina, Piperaciclina-tazobactam, Imipem, Meropenem e Ertapenem apresentaram sensibilidade ≥50%. Houve correlação entre sintomas associados à ITU e uso de antibiótico após urocultura (p=0,02); tempo de uso de sonda e tempo de permanência hospitalar (p=0,04). CONCLUSÕES: Pacientes femininos com mais de 50 anos e doença de base clínica, de origem no sistema nervoso ou gastrointestinal, em uso de SVD por mais de 30 dias e tempo de permanência hospitalar de 56,7±35,7 dias, estão entre as mais propensas a desenvolverem ITU nosocomial. A Amicacina, Gentamicina e Cefoxitina apresentaram opções factíveis para a antibioticoterapia empírica as duas bactérias mais prevalentes.

The effect of high concentration of magnesium with ropivacaine, gentamicin, rocuronium, and their combination on neuromuscular blockade.

BACKGROUND: Magnesium, ropivacaine, gentamicin, and rocuronium block neuromuscular (NM) transmission by different mechanisms. Therefore, concurrent administration of these agents may induce prolonged muscle paralysis via synergistic interaction. This study investigated the efficacy and safety of NM block caused by the administration of high concentrations of magnesium in combination with ropivacaine, gentamicin, and rocuronium. METHODS: Eighty-three left phrenic nerve-hemidiaphragms from male SD rats (150-250 g) were hung in Krebs solution. Three consecutive single twitch tension (ST, 0.1 Hz) and one tetanic tension (TT, 50 Hz for 1.9 s) were obtained before drug application and at each new drug concentration. The concentration of MgCl2 and MgSO4 in Krebs solution was increased until an 80 to 90% reduction in ST was reached. To test the effects of combinations of NM agents, a Krebs solution was premixed with MgCl2 alone, MgCl2 and ropivacaine, or MgCl2, ropivacaine, and gentamicin. The concentration of ropivacaine, gentamicin, or rocuronium was then progressively increased until an 80 to 90% reduction in ST was reached. The effective concentrations were estimated with a probit model. RESULTS: The potency of MgCl2 was greater than that of MgSO4, and pretreatment with MgCl2 increased the potency of gentamicin and rocuronium. Unexpectedly, MgCl2 did not potentiate ropivacaine, and the potency of gentamicin and rocuronium failed to show an increase when premixed with 0.5 µM ropivacaine. CONCLUSIONS: The concomitant administration of high concentrations of magnesium and ropivacaine together with clinically relevant concentrations of gentamicin or rocuronium potentiated NM blockade but not with clinically relevant concentrations of ropivacaine.

Resposta à Triagem Auditiva em Neonatos do Projeto Canguru Usuários de Medicamentos Ototóxicos / Hearing Screening Response in Neonates of the Kangaroo Project Using Ototoxic Medicines

Avaliar a resposta à triagem auditiva em recémnascidosque participaram do projeto Mãe Canguru eutilizaram medicamentos ototóxico. Material e métodos:Estudo do tipo transversal observacional quantitativo, comamostra de 66 pacientes. Foram incluídos na pesquisa recémnascidosque utilizaram pelo menos um medicamentoototóxico (Gentamicina, Vancomicina, e Furosemida)participantes do Projeto Canguru da Maternidade CândidaVargas em João Pessoa - PB no período de Novembro de2012 a Março de 2013. As variáveis quantitativas foramexpressas em média e desvio-padrão, e as variáveisqualitativas foram expressas por frequências absolutas erelativas. O resultado do teste de EOA e de outras variáveisfoi feito utilizando-se o teste qui-quadrado e calculada pelosoftware SPSS versão 21.0. Adotou-se o nível designificância (p) de 5%. Resultados: Dos 66 pacientesincluídos na pesquisa, 45 pacientes (68,2%) utilizaramototóxicos, e 21 (31,8%) não. A Gentamicina foi usada por43 neonatos, a Furosemida por 8 e a Vancomicina por 6.Entre os pacientes que fizeram uso de medicamento ototóxico,95,2% tinham o teste da orelhinha normal e 2 apresentaramresposta ausente (4,8%) (p=0,4). Conclusão: Resultadospositivos e negativos na triagem auditiva foram encontradostanto em recém-nascidos que usaram como naqueles quenão usaram drogas ototóxicas. Não sendo significativo ouso isolado do medicamento nos neonatos que tiveramresposta ausente no teste de EOA...

To evaluate the hearing screening response innewborns who participated in Kangaroo Mother Project andused ototoxic drugs. Material and methods: This is a crosssectional,quantitative study including a sample of 66newborns who made use of at least one ototoxic drug(gentamicin, vancomycin, and furosemide) participating ofthe Kangaroo project at the Candida Vargas Hospital in JoãoPessoa, PB, Brazil, from November 2012 to March 2013.Quantitative variables were expressed as mean and standarddeviation, and qualitative variables were expressed asabsolute and relative frequencies. The correlation betweenthe results of the OAE test and other variables was performedusing the chi-square test and calculated by SPSS softwareversion 21.0, with a significance level (p) of 5%. Results: Ofthe 66 patients included in the study, 45 (68.2%) had usedototoxic drugs and 21 (31.8%) had not. Gentamicin wasused for 43 neonates, furosemide by 8 and vancomycin by6. Among the patients who made use of ototoxic medication,95.2% had normal OAE test and 2 had absent response(4.8%) (p = 0.4). Conclusion: Positive and negative resultsin the hearing screening were found both in newborns whoused or did not use ototoxic drugs. The isolated use of drugby newborns with absent response in the OAE test was notsignificant...

The effect of high concentration of magnesium with ropivacaine, gentamicin, rocuronium, and their combination on neuromuscular blockade / 대한마취과학회지

BACKGROUND: Magnesium, ropivacaine, gentamicin, and rocuronium block neuromuscular (NM) transmission by different mechanisms. Therefore, concurrent administration of these agents may induce prolonged muscle paralysis via synergistic interaction. This study investigated the efficacy and safety of NM block caused by the administration of high concentrations of magnesium in combination with ropivacaine, gentamicin, and rocuronium. METHODS: Eighty-three left phrenic nerve-hemidiaphragms from male SD rats (150-250 g) were hung in Krebs solution. Three consecutive single twitch tension (ST, 0.1 Hz) and one tetanic tension (TT, 50 Hz for 1.9 s) were obtained before drug application and at each new drug concentration. The concentration of MgCl2 and MgSO4 in Krebs solution was increased until an 80 to 90% reduction in ST was reached. To test the effects of combinations of NM agents, a Krebs solution was premixed with MgCl2 alone, MgCl2 and ropivacaine, or MgCl2, ropivacaine, and gentamicin. The concentration of ropivacaine, gentamicin, or rocuronium was then progressively increased until an 80 to 90% reduction in ST was reached. The effective concentrations were estimated with a probit model. RESULTS: The potency of MgCl2 was greater than that of MgSO4, and pretreatment with MgCl2 increased the potency of gentamicin and rocuronium. Unexpectedly, MgCl2 did not potentiate ropivacaine, and the potency of gentamicin and rocuronium failed to show an increase when premixed with 0.5 microM ropivacaine. CONCLUSIONS: The concomitant administration of high concentrations of magnesium and ropivacaine together with clinically relevant concentrations of gentamicin or rocuronium potentiated NM blockade but not with clinically relevant concentrations of ropivacaine.

Protective effect of metformin on gentamicin-induced vestibulotoxicity in rat primary cell culture.

OBJECTIVES: One of the antidiabetic drugs, metformin, have shown that it prevented oxidative stress-induced death in several cell types through a mechanism involving the opening of the permeability transition pore and cytochrome c release. Thus, it is possible that the antioxidative effect of metformin can also serve as protection against gentamicin-induced cytotoxicity related to reactive oxygen species (ROS). The aim of this study was to examine the protective effect of metformin on gentamicin-induced vestibulotoxicity in primary cell culture derived from rat utricle. METHODS: For vestibular primary cell culture, rat utricles were dissected and incubated. Gentamicin-induced cytotoxicity was measured in both the auditory and vestibular cells. To examine the effects of metformin on gentamicin-induced cytotoxicity in the primary cell culture, the cells were pretreated with metformin at a concentration of 1 mM for 24 hours, and then exposed to 2.5 mM gentamicin for 48 hours. The intracellular ROS level was measured using a fluorescent dye, and also measured using a FACScan flow cytometer. Intracellular calcium levels in the vestibular cells were measured with calcium imaging using Fura-2 AM. RESULTS: Vestibular cells were more sensitive to gentamicin-induced cytotoxicity than auditory hair cells. Metformin protects against gentamicin-induced cytotoxicity in vestibular cells. Metformin significantly reduced a gentamicin-induced increase in ROS, and also reduced an increase in intracellular calcium concentrations in gentamicin-induced cytotoxicity. CONCLUSION: Metformin significantly reduced a gentamicin-induced increase in ROS, stabilized the intracellular calcium concentration, and inhibited gentamicin-induced apoptosis. Thus, Metformin showed protective effect on gentamicin-induced cytotoxicity in vestibular primary cell culture.