An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial-an update to the published protocol.

This article reports an update to the protocol of the IMASOY trial, which was prospectively registered on clinicaltrials.gov (NCT04110340) in October 2019.

Hyperosmotic sisomicin infusion: a mouse model for hearing loss.

Losing either type of cochlear sensory hair cells leads to hearing impairment. Inner hair cells act as primary mechanoelectrical transducers, while outer hair cells enhance sound-induced vibrations within the organ of Corti. Established inner ear damage models, such as systemic administration of ototoxic aminoglycosides, yield inconsistent and variable hair cell death in mice. Overcoming this limitation, we developed a method involving surgical delivery of a hyperosmotic sisomicin solution into the posterior semicircular canal of adult mice. This procedure induced rapid and synchronous apoptotic demise of outer hair cells within 14 h, leading to irreversible hearing loss. The combination of sisomicin and hyperosmotic stress caused consistent and synergistic ototoxic damage. Inner hair cells remained until three days post-treatment, after which deterioration in structure and number was observed, culminating in a complete hair cell loss by day seven. This robust animal model provides a valuable tool for otoregenerative research, facilitating single-cell and omics-based studies toward exploring preclinical therapeutic strategies.

Azacitidine and gemtuzumab ozogamicin as post-transplant maintenance therapy for high-risk hematologic malignancies.

Disease recurrence remains the principal cause of treatment failure after allogeneic hematopoietic stem cell transplantation. Post-transplant maintenance therapy with azacitidine (AZA) is promising to prevent relapse but the outcomes are unsatisfactory in patients at high risk of recurrence. Herein, we evaluated the outcome in patients who received AZA and gemtuzumab ozogamicin (GO), anti-CD33 antibody-calicheamicin conjugate, as post-transplant maintenance therapy. Twenty-eight patients with high-risk hematologic malignancies harboring CD33-positive leukemic blasts received the maintenance therapy. AZA (30 mg/m2) was administered for 7 days, followed by GO (3 mg/m2) on day 8. The maximum number of cycles was 4. At transplant, 21 patients (75.0%) had active disease. Their 2-year overall survival, disease-free survival, relapse, and non-relapse mortality rates were 53.6%, 39.3%, 50.0%, and 10.7%, respectively. Of these patients, those with minimal residual disease at the start of maintenance therapy (n = 9) had a higher recurrence rate (66.7% vs. 42.1% at 2 years, P = 0.069) and shorter disease-free survival (11.1% vs. 52.6% at 2 years, P = 0.003). Post-transplant maintenance therapy with AZA and GO was generally tolerable but more than half of the patients eventually relapsed. Further improvements are needed to prevent relapse after transplantation in patients with high-risk hematologic malignancies.

Limited efficacy of 3 + 7 plus gemtuzumab ozogamycin in newly diagnosed fit intermediate genetic risk acute myeloid leukemia patients.

BACKGROUND: Gemtuzumab-ozogamycin (GO) is approved in combination with high-dose chemotherapy for treatment-naïve low- and intermediate-risk acute myeloid leukemia (AML). AIMS: In this retrospective real-life multicenter study, we reported efficacy and safety of GO plus high-dose chemotherapy in newly diagnosed AML patients. METHODS AND RESULTS: A total of 31 fit low- and intermediate-risk AML patients treated with GO-based regimens were retrospectively included in this real-life multicenter study, and results were compared with a control cohort treated with 3 + 7 alone. Complete remission (CR) rate after induction was 77%, and most responders (45%) underwent two GO-based consolidation, and minimal residual disease (MRD) negativity was observed in 17 cases (55%) after the end of consolidation. Low genetic risk was associated with increased CR rate compared with intermediate-risk AML (88% vs. 33%; p < .001), as well as prolonged overall survival (OS; hazard ratio, 0.16; 95% confidential interval, 0.02-0.89; p < .001). GO addition resulted in a survival benefit for low-risk AML (median OS not reached vs. 25 months; p = .19) while not for intermediate-risk subjects (10 vs. 13 months; p = .92), compared with the control group. Moreover, GO-treated patients experienced fever of unknown origin or sepsis in 42% or 36% of cases, respectively, with one death during induction due to septic shock, with similar rates compared with the control group (p = .3480 and p = .5297, respectively). No cases of veno-occlusive disease after allogeneic transplantation were observed. CONCLUSIONS: Our real-life multicenter study confirmed GO-based treatment efficacy with high MRD negativity rates in fit newly diagnosed AML patients, especially in those with low genetic risk and core binding factor, while limited benefits were observed in intermediate-risk AML. However, further validation on larger prospective cohorts is required.

Gemtuzumab ozogamicin plus midostaurin in combination with standard '7 + 3' induction therapy in newly diagnosed AML: Results from the SAL-MODULE phase I study.

We conducted a phase I trial in newly diagnosed acute myeloid leukaemia (AML) to investigate the combination of two novel targeted agents, gemtuzumab ozogamicin (GO) and midostaurin, with intensive chemotherapy in FLT3-mutated AML and CBF leukaemia. Three dose levels of midostaurin and one to three sequential doses of 3 mg/m2 GO in combination with '7 + 3' induction were evaluated. Based on safety findings in 12 patients, our results show that 3 mg/m2 GO on Days 1 + 4 and 100 mg midostaurin on Days 8-21 can be safely combined with IC in newly diagnosed AML.

Prospective evaluation of single-dose aminoglycosides for treatment of complicated cystitis in the emergency department.

BACKGROUND: Antimicrobial resistance among Enterobacterales continues to be a growing problem, particularly in those with urinary infections. Previous studies have demonstrated safety and efficacy with the use of single-dose aminoglycosides in uncomplicated cystitis. However, data in complicated infections are limited. Single-dose aminoglycosides may provide a convenient alternative for those with or at risk for resistant pathogens causing complicated urinary infections, especially when oral options are unavailable due to resistance, allergy, intolerance, or interactions with other medications. This study evaluated the safety and effectiveness of single-dose aminoglycosides in treatment of complicated cystitis in the emergency department (ED). METHODS: This was a multicenter, prospective study performed between July 2022 and March 2023 of patients who met criteria for complicated cystitis and were otherwise stable for discharge at an academic ED. Primary outcomes were clinical or microbiologic failure within 14 days of treatment. Safety was assessed by review of adverse events. Descriptive statistics were used. RESULTS: Thirteen patients were included. Complicating factors were male sex (n = 4), kidney stone (n = 2), urinary catheter (n = 6), recent urologic procedure (n = 1), urinary hardware (n = 1), antibiotic allergy precluding use of alternate oral options (n = 4), immunocompromised status (n = 2), and <1-year history of multidrug-resistant organisms on urine culture (n = 8). Eleven patients (85%) had positive urine cultures in the preceding 12 months with no oral antimicrobial option. Eight patients (62%) received amikacin (median dose 15 mg/kg), four patients (31%) received gentamicin (median dose 5 mg/kg), and one patient (8%) received tobramycin (5 mg/kg) for treatment. Ten patients (77%) reported resolved urinary symptoms after treatment and 11 patients (85%) reported no new urinary symptoms since discharge. No patient required hospital admission for treatment failure, and no adverse events were noted. CONCLUSIONS: Single-dose aminoglycosides appear to be a reasonably effective and safe treatment for complicated cystitis, which avoided hospital admission in this cohort.

A comparison of aminoglycoside antibiotic serum concentrations collected by peripheral veins and peripherally inserted central catheters in adults with cystic fibrosis.

BACKGROUND: People with cystic fibrosis (PwCF) are frequently hospitalized for treatment of pulmonary exacerbation. The Cystic Fibrosis Foundation Pulmonary Guidelines support the use of intravenous aminoglycosides with therapeutic drug monitoring for the treatment of pulmonary exacerbation due to Pseudomonas aeruginosa. Serum intravenous tobramycin concentrations are commonly collected by peripheral venipuncture (PV). Discomfort associated with collection of samples by PV prompts collection via PICC, but the accuracy of intravenous tobramycin serum levels collected by PICC has not been documented in adult PwCF. The primary study objective was to evaluate the difference between intravenous tobramycin serum levels collected by PV and PICC in adult PwCF. METHODS: The authors conducted a prospective case-control study of adult PwCF admitted to University of Utah Health for a pulmonary exacerbation receiving tobramycin by a single lumen PICC. The authors compared tobramycin peak and random serum levels collected by PV and PICC using a detailed flush and waste protocol. RESULTS: The authors analyzed a total of 19 patients with peripheral and PICC samples. The mean tobramycin peak collected by PV (27.2 mcg/mL) was similar to the mean peak collected by PICC (26.9 mcg/mL) (paired samples Wilcoxon signed-rank test, p = .94). The correlation coefficient was 0.88 (95% CI = 0.85-0.91, p < .001). CONCLUSION: Tobramycin serum samples collected by PICC appear to be similar in value to PV collections. Collecting aminoglycoside levels by PICC rather than PV may reduce patient discomfort and improve quality of life. Additional multicenter studies are needed to confirm these results.

Caracterización clínico epidemiológica de los pacientes con infecciones por estafilococo dorado / Clinical-epidemiological characterization of patients with Staphylococcus aureus infections

RESUMEN Introducción: El estafilococo dorado es una causa importante de morbilidad y mortalidad en el mundo. En Cuba, es un germen a tener en cuenta como causa de infección intrahospitalaria. Objetivo: Caracterizar, clínica y epidemiológicamente, una muestra de pacientes con infecciones causadas por estafilococo dorado. Métodos: Se realizó un estudio observacional, descriptivo y transversal en el Hospital Militar "Dr. Mario Muñoz Monroy" de Matanzas, durante el período de enero a diciembre del año 2014. La población estuvo constituida por la totalidad de los pacientes hospitalizados con el diagnóstico de infección por estafilococo dorado (120 casos), identificados por el departamento de Microbiología; luego se revisaron las historias clínicas de las cuales se obtuvo la información. Resultados: Existió un predominio del sexo masculino (64,2 por ciento), los mayores de 60 años fueron los más afectados (36,7 por ciento). La diabetes mellitus fue la enfermedad asociada más frecuente (40,8 por ciento) y la mayoría de las infecciones fueron de origen comunitario (67,5 por ciento). Los aislamientos predominaron en las muestras tomadas de las lesiones en piel y los hemocultivos con un 50,8 por ciento y 19,2 por ciento, respectivamente. Se evidenció baja sensibilidad a la vancomicina (49,2 por ciento) y al cotrimoxazol (38,3 por ciento). Conclusiones: Las infecciones por estafilococo dorado fueron más frecuentes en pacientes masculinos geriátricos de su origen extrahospitalario. El germen presentó alta resistencia a los antibióticos y de estos, los aminoglucósidos mostraron la mayor sensibilidad antimicrobiana(AU)

Introduction: Staphylococcus aureus is an important cause of morbidity and mortality in the world. In Cuba, it is a germ to be taken into account as a cause of nosocomial infection. Objective: To characterize, clinically and epidemiologically, a sample of patients with infections caused by Staphylococcus aureus. Methods: An observational, descriptive and cross-sectional study was conducted at the Military Hospital "Dr. Mario Muñoz Monroy "of Matanzas, during the period from January to December of the year 2014. The population was constituted by all the patients hospitalized with the diagnosis of infection by Staphylococcus aureus (120 cases), identified by the department of Microbiology; then the medical records from which the information was obtained were reviewed. Results: There was a predominance of males (64.2 percent) those over 60 were the most affected (36.7 percent). Diabetes mellitus was the most frequent associated disease (40.8 percent) and the majority of infections were of community origin (67.5 percent). Positivity predominated in samples taken from skin lesions and blood cultures with 50.8 percent and 19.2 percent, respectively. Low sensitivity to vancomycin (49.2 percent) and cotrimoxazole (38.3 percent) was evidenced. Conclusions: Staphylococcus aureus infections were more frequent in geriatric male patients of out-of-hospital origin. The germ showed high resistance to antibiotics and of these, the aminoglycosides showed the highest antimicrobial sensitivity(AU)

Síndrome hemofagocítico secundario a endocarditis por Bartonella henselae / Haemophagocytic syndrome secondary to endocarditis due to Bartonella henselae

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Cochleotoxicity monitoring protocol / Protocolo de monitorización de cocleototoxicidad

Introduction: Cochlear damage is frequent in long-term aminoglycosides therapy or chemotherapeutic treatments with platinum-based agents. Despite its prevalence, it is currently underestimated and underdiagnosed. A monitoring protocol is vital to the early detection of cochleotoxicity and its implementation is widely encouraged in every hospital unit. Our aim was to elaborate a cochleotoxicity monitoring protocol for patients treated with platinum compounds or aminoglycosides antibiotics. Methods: PubMed® database was searched using terms relevant to drug cochleotoxicity in order to identify the most adequate protocol. Several articles and guidelines influenced our decision. Results: There is no consensus on a universal monitoring protocol. Its formulation and application rely heavily on available resources and personnel. High-frequency audiometry and otoacoustic emissions play an important role on early detection of cochleotoxicity caused by aminoglycoside antibiotics and platinum compounds. Conclusion: A cochleotoxicity monitoring protocol consisting on an initial evaluation, treatment follow-up and post-treatment evaluation is proposed (AU)

Introducción: El daño coclear es frecuente en la terapia de aminoglucósidos a largo plazo, o en tratamientos quimioterapéuticos con agentes a base de platino. A pesar de su prevalencia, actualmente está subestimado y subdiagnosticado. Un protocolo de monitorización es vital para la detección temprana de la ototoxicidad, por lo que se incita a su implementación en todas las unidades hospitalarias. Nuestro objetivo fue elaborar un protocolo de monitorización de la cocleototoxicidad para pacientes tratados con compuestos de platino o antibióticos aminoglucósidos. Métodos: Se realizaron búsquedas en la base de datos PubMed® utilizando términos relevantes para la cocleototoxicidad de los fármacos con el fin de identificar el protocolo más adecuado. Varios artículos y directrices influyeron en nuestra decisión. Resultados: No hay consenso sobre un protocolo de monitoreo universal. Su formulación y aplicación dependen en gran medida de los recursos y el personal disponibles. La audiometría de alta frecuencia y las emisiones otoacústicas desempeñan un papel importante en la detección temprana de la cocleototoxicidad causada por los antibióticos aminoglucósidos y los compuestos de platino. Conclusión: Se propone un protocolo de monitorización de la cocleototoxicidad, consistente en una evaluación inicial, seguimiento del tratamiento y evaluación postratamiento (AU)

Nueva formulación de neomicina y estreptomicina para la descontaminación digestiva de klebsiella pneumoniae productora de carbapenemasas / Formulation of neomycin and streptomycin for the digestive decontamination of carbapenemases producing klebsiella pneumoniae

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Antibióticos y trastornos de la marcha / Antibiotics and gait disorders

Resumen. La toxicidad neurológica de muchos antibióticos se ha documentado en numerosos artículos y notas clínicas. En esta revisión se clasifican los antibióticos en función del mecanismo fisiopatogénico por el que pueden provocar un trastorno de la marcha, teniendo en cuenta tanto datos clínicos como experimentales. Se ha realizado una búsqueda exhaustiva en Google Scholar y PubMed con el objetivo de encontrar revisiones, artículos y casos clínicos acerca de trastornos de la marcha secundarios a distintos antibióticos. Se han separado los diferentes antibióticos en función del mecanismo fisiopatogénico por el cual podrían producir una alteración de la marcha. Se han clasificado en antibióticos capaces de producir ataxia cerebelosa, ataxia vestibular, ataxia sensitiva o un trastorno de la marcha extrapiramidal. El principal objetivo era agrupar todos los fármacos que pueden provocar un trastorno de la marcha, para facilitar la sospecha clínica y, en consecuencia, el tratamiento de los pacientes (AU)

Summary. The neurological toxicity of many antibiotics has been reported in a number of articles and clinical notes. In this review antibiotics are classified according to the physiopathogenic mechanism that can give rise to a gait disorder, taking both clinical and experimental data into account. An exhaustive search was conducted in Google Scholar and PubMed with the aim of finding reviews, articles and clinical cases dealing with gait disorders secondary to different antibiotics. The different antibiotics were separated according to the physiopathogenic mechanism that could cause them to trigger a gait disorder. They were classified into antibiotics capable of producing cerebellar ataxia, vestibular ataxia, sensitive ataxia or an extrapyramidal gait disorder. The main aim was to group all the drugs that can give rise to a gait disorder, in order to facilitate the clinical suspicion and, consequently, the management of patients (AU)

Tratamiento de un caso de toxicidad retiniana por aminoglucósidos con megadosis de corticoides más implante de dexametasona intravítreo (Ozurdex®) / A case of aminoglycosides induced retinal toxicity treated with megadoses of steroids and an intravitreal dexamethasone implant (Ozurdex®)

CASO CLÍNICO: Paciente que tras cirugía de glaucoma presenta pérdida súbita de visión, llegándose al diagnóstico de toxicidad retiniana por tobramicina, caracterizada por blanqueamiento retiniano con mancha rojo cereza, edema macular, y vasculitis con evolución a atrofia papilar y macular con esclerosis arteriolar. Ante la gravedad del cuadro ensayamos con megadosis de corticoides e implante intravítreo de dexametasona (Ozurdex®, Allergan S.A.) precozmente, sin buena respuesta. DISCUSIÓN: La toxicidad por aminoglucósidos es una complicación infrecuente, muy grave e idiosincrásica. Destacar que no existe tratamiento efectivo

CASE REPORT: The case is described of a patient who had a sudden loss of vision in her right eye after glaucoma surgery. A diagnosis of retinal toxicity due to tobramycin (an aminoglycoside) was reached, which was characterised by retinal whitening with a red cherry stain, macular oedema, and vasculitis that progressed to papillary and macular atrophy with arteriolar sclerosis. Given the severity of symptoms an early attempt was made with megadoses of steroids and an intravitreal dexamethasone implant (Ozurdex®, Allergan S.A.), without response. DISCUSSION: Aminoglycoside toxicity is a rare, idiosyncratic, very serious complication for which there is no effective treatment

Antibiotic dose optimization in critically ill patients / Optimización de la dosis de antibióticos en pacientes críticamente enfermos

The judicious use of existing antibiotics is essential for preserving their activity against infections. In the era of multi-drug resistance, this is of particular importance in clinical areas characterized by high antibiotic use, such as the ICU. Antibiotic dose optimization in critically ill patients requires sound knowledge not only of the altered physiology in serious infections - including severe sepsis, septic shock and ventilator-associated pneumonia - but also of the pathogen–drug exposure relationship (i.e. pharmacokinetic/pharmacodynamic index). An important consideration is the fact that extreme shifts in organ function, such as those seen in hyperdynamic patients or those with multiple organ dysfunction syndrome, can have an impact upon drug exposure, and constant vigilance is required when reviewing antibiotic dosing regimens in the critically ill. The use of continuous renal replacement therapy and extracorporeal membrane oxygenation remain important interventions in these patients; however, both of these treatments can have a profound effect on antibiotic exposure. We suggest placing emphasis on the use of therapeutic drug monitoring and dose individualization when optimizing therapy in these settings

El uso sensato de los antibióticos existentes resulta fundamental para mantener su actividad contra las infecciones. En la era de la resistencia a múltiples fármacos, esto resulta especialmente importante en áreas clínicas caracterizadas por un uso elevado de antibióticos, como por ejemplo las UCI. La optimización de la dosis de antibióticos en pacientes críticamente enfermos requiere sólidos conocimientos no solo sobre las alteraciones fisiológicas asociadas a las infecciones graves (incluida la sepsis grave, el choque séptico y la neumonía asociada a la ventilación) sino también sobre la relación entre patógenos y la exposición a fármacos (esto es, el índice farmacocinético/farmacodinámico). Es importante considerar el hecho de que los cambios extremos en la función orgánica, como los observados en pacientes hiperdinámicos o en aquellos con síndrome de disfunción multiorgánica, pueden tener un efecto sobre la exposición a los fármacos, por lo que se requiere una vigilancia constante al revisar los regímenes posológicos de los antibióticos en los pacientes críticamente enfermos. La terapia de reemplazo renal continuo y la oxigenación por membrana extracorporal siguen constituyendo intervenciones importantes en este tipo de pacientes; no obstante, ambos tratamientos pueden tener un profundo impacto sobre la exposición a los antibióticos. Sugerimos poner un especial énfasis sobre el uso de la monitorización farmacoterapéutica y sobre la individualización de la dosis al optimizar el tratamiento en estos entornos terapéuticos

The Real Practice of Antibiotic Prophylaxis for Prostate Biopsy in Korea Where the Prevalence of Quinolone-Resistant Escherichia coli Is High

PURPOSE: Transrectal ultrasonography-guided prostate biopsy (TRUS-Bx) is an essential procedure for diagnosing prostate cancer. The American Urological Association (AUA) Guideline recommends fluoroquinolone alone for 1 day during TRUS-Bx. However, this recommendation may not be appropriate in regions where the prevalence of quinolone-resistant Escherichia coli is high. We investigated the real practice of antibiotic prophylaxis for TRUS-Bx in Korea. MATERIALS AND METHODS: A total of 77 hospitals performing TRUS-Bx were identified and an e-mail was sent to the Urology Department of those hospitals. The questions in the e-mail included the choice of antibiotics before and after the procedure and the duration of antibiotic therapy after TRUS-Bx. RESULTS: A total of 54 hospitals (70.0%) responded to the e-mail. Before TRUS-Bx, all hospitals administered intravenous antibiotic prophylaxis. The percentage of hospitals that used quinolone, cephalosporin, and aminoglycoside alone was 48.1%, 20.4%, and 9.3%, respectively. The percentage of hospitals that used two or more antibiotics was 22.2%. After biopsy, all 54 hospitals prescribed oral antibiotics. The percentage of hospitals that prescribed quinolone alone, cephalosporin alone, or a combination of two or more antibiotics was 77.8%, 20.4%, and 1.8%, respectively. The duration of antibiotic use was more than 3 days in most hospitals (79.6%). Only four hospitals (7.4%) followed the AUA recommendation of a 1-day regimen. CONCLUSIONS: The AUA recommendation was not followed by most hospitals in Korea. This clinical behavior might reflect the high quinolone resistance rate in Korea, and further studies on the most efficient prophylactic antibiotics after TRUS-Bx in Korea are warranted.

The Real Practice of Antibiotic Prophylaxis for Prostate Biopsy in Korea Where the Prevalence of Quinolone-Resistant Escherichia coli Is High

PURPOSE: Transrectal ultrasonography-guided prostate biopsy (TRUS-Bx) is an essential procedure for diagnosing prostate cancer. The American Urological Association (AUA) Guideline recommends fluoroquinolone alone for 1 day during TRUS-Bx. However, this recommendation may not be appropriate in regions where the prevalence of quinolone-resistant Escherichia coli is high. We investigated the real practice of antibiotic prophylaxis for TRUS-Bx in Korea. MATERIALS AND METHODS: A total of 77 hospitals performing TRUS-Bx were identified and an e-mail was sent to the Urology Department of those hospitals. The questions in the e-mail included the choice of antibiotics before and after the procedure and the duration of antibiotic therapy after TRUS-Bx. RESULTS: A total of 54 hospitals (70.0%) responded to the e-mail. Before TRUS-Bx, all hospitals administered intravenous antibiotic prophylaxis. The percentage of hospitals that used quinolone, cephalosporin, and aminoglycoside alone was 48.1%, 20.4%, and 9.3%, respectively. The percentage of hospitals that used two or more antibiotics was 22.2%. After biopsy, all 54 hospitals prescribed oral antibiotics. The percentage of hospitals that prescribed quinolone alone, cephalosporin alone, or a combination of two or more antibiotics was 77.8%, 20.4%, and 1.8%, respectively. The duration of antibiotic use was more than 3 days in most hospitals (79.6%). Only four hospitals (7.4%) followed the AUA recommendation of a 1-day regimen. CONCLUSIONS: The AUA recommendation was not followed by most hospitals in Korea. This clinical behavior might reflect the high quinolone resistance rate in Korea, and further studies on the most efficient prophylactic antibiotics after TRUS-Bx in Korea are warranted.

Caracterización de la resistencia a aminoglicósidos mediada por enzimas modificadoras y metilasas de ARN16S en aenterobacterias / Characterization of resistance to aminoglycoside mediated by modifying enzymes and methylases ARN16S in aenterobacterias

Los aminoglicósidos son antimicrobianos ampliamente usados en la práctica clínica. El objetivo del estudio fue evaluar fenotípica y genotípicamente la resistencia a aminoglicósidos en enterobacterias aisladas de centros de salud del área metropokitana de caracas. Se estudiaron 76 cepas de enterobacterias (14 Escherichia coli, 34 klebsiella pneumoniae, 6 Serratia marcescens, 1 citrobacer freundii, 3 Enterobacter aerogenes y 18 Entorabacter cloacae) aisladas de muestras clínicas de pacientes de 11 centros hospitalarios de Caracas entre noviembre 2009 y marzo 2010, incluyéndose solo cepas con resistencia a aminoglicósidos. La identificación bioquímica fue realizada por métodos convencionales y mediante el sistema automatizado VITEK-2. Se determinó su suseptibilidad antibiótica por la técnica de difusión con discos de gentamicina, amikacina, netilmecina y tobramicina según lo establecido por CLSI 2010. Los genes de resistencia se investigaron por PCR empleando iniciadores para los genes codificantes de las enzimas AAC(3')la, AAC(3') lla AAC(6')lb, ANT(2')la, AAC(6')lbcr, APH(3') Vla y las metilasa armA, rmtA, rmtB, rmtC, rmtD y npmA. Fenotípicamente se detectó que 90,8 % de las cepas fueron resistentes a amikacina y 57,9 % presentaron resistencia cruzada a amikacina, gentamicina, tobramicina y netilmicina. De las enzimas modificadoras investigadas la más prevalente fue APH(3')Vla (56,6%) y de las metilasas la RmtD (25 %). Estos resultados sugieren que la APH(3')Vla pudiera ser la responsable de generar altos niveles de resistencia a amikacina en estas cepas, mientras que la RmtD podría ser la causante de la resistencia cruzada a amikacina, gentamicina, tobramicina y netilmicina.

Aminoglycosides are antimicrobials widely used in clinical practice. The objective of this study was to assess from a phenotypic and genotypic point of view aminoglycoside resistance in enterobacteria isolated from health centers in the metropitan area of Caracas. Seventy six enterobacteriaceae isolates (14 Escherichia coli 34 Klebsiella pneumoniae, 6 serratia marcescens, 1 Citrobacter freundii, 3 Enterobacter aerogenes and 18 Enterobacter cloacae) from clinical samples of patientes from 11 hospitals in Caracas between November 2009 and march 2010 were analyzed, including anly strains with resistance to aminoglycosides. Biochemical identification was carried out by conventional methods and automated VITEK-2. Antibiotic susceptibility was determined by disk diffusion using gentamicin, amikacin, netilmicin and tobramycin discs, according with CLSI 2010. Resistnce genes were investigated by PCR using primers for the genes coding for AAC (3') la, AAC (3') AAC(6')Ib lla, ANT(2') la, AAC(6')Ibcr, Vla APH (3') enzymes and armA, rmtA, rmtB, rmtC, rmtD and npmA metilases. Phenotypically 90.8 % of isolates were resistant to amikacin, and 57.9 % presented cross-resistance to amikacin, gentamicin, tobramycin and netilmicin. The most prevalent modifying ensymes was APH(3')Vla (53.6 %9 and the most prevalent metilase was RmtD (25 %). These results suggest that the APH(3') Vla migth be responsible for generatin high levels of resistance to amikacin inthese isolates, while RmtD was the cause of cross resistance to amikacin, gene, gentamicin, tobramycin and netilmicin.