[Translated article] Vancomycin powder in the prevention of infection in primary knee and hip arthroplasty: Case-control study with 1151 arthroplasties.

BACKGROUND AND OBJECTIVE: Vancomycin powder (VP) has been positively used in spinal surgery to reduce the rate of infections. Hardly any data have been published on hip and knee joint replacement surgery, and its usefulness is questioned. Our objective was to investigate the effectiveness of VP in reducing prosthetic infection and its possible complications. METHODS: Primary hip (THA) and knee (TKA) arthroplasties were reviewed, performed by five surgeons in one hospital centre, between 2017 and 2018. One gram of VP was used on the implant prior to surgical closure based on the surgeon's preferences. With a 5-year follow-up in which the infection rate and local complications were analysed. RESULTS: One thousand one hundred and fifty-one arthroplasties were performed, 748 were TKA and 403 were THA. Nine patients were diagnosed with prosthetic infection, of which five received VP and four did not (p=0.555). Likewise, another 15 patients suffered wound complications, of which 11 received VP and 4 did not (p=0.412). There were no differences, either, in the rest of the complications depending on the use or not of VP (p=0.101). Likewise, the number of patients who needed reintervention was similar (p=0.999). No systemic complications were detected due to the use of VP. CONCLUSIONS: It has not been possible to demonstrate that the use of VP reduces the rates of prosthetic infection in the hip and knee, so we cannot recommend its use.

Sellado antibiótico de reservorios subcutáneos: estabilidad de soluciones con vancomicina / Antimicrobial lock solutions for implantable central venous devices: stability of vancomycin solutions

Los reservorios subcutáneos son un tipo de catéter venoso central (CVC). Cuando se usan catéteres venosos centrales (CVC), el personal sanitario necesita evitar dos grandes riesgos: formación de coágulos e infecciones bacterianas. Para prevenir y evitar la contaminación de los catéteres en los pacientes hospitalizados y ambulatorios, se han implementado diversas alternativas, como el llamado “sellado antibiótico de catéteres” (SAC). De este modo, se ha sugerido la utilización de soluciones con agentes antimicrobianos, a las que se suelen adicionar sustancias con efecto anticoagulante y/o con efecto antibiofilm. Empero, se requiere que la estabilidad de dichas soluciones sea comprobada mediante técnicas como la cromatografía líquida de alta resolución (HPLC), además de las pruebas de eficacia antimicrobiana, para así poder establecer la seguridad de los pacientes. En este entorno, se plantea el presente trabajo de revisión bibliográfica, con el objetivo de incluir las investigaciones de mayor representación clínica a este respecto, para evidenciar el comportamiento de las soluciones de sellado antibiótico de catéteres en distintas condiciones de almacenamiento y uso. En particular, esta revisión se centra en soluciones con vancomicina. De acuerdo con los estudios consultados, las soluciones de vancomicina con citrato de sodio (agente quelante) son las que presentan las mejores características en cuanto a estabilidad físico-química y eficacia como soluciones de sellado.(AU)

Subcutaneous reservoirs are a type of central venous catheter. When using central venous catheters, healthcare workers need to avoid two major risks: clot formation and bacterial infections. To prevent and avoid catheter contamination in both hospitalized patients and outpatients, several strategies have been carried out, such as the so-called ” antibiotic-based catheter lock solution”. Therefore, it has been suggested to implement the use of solutions with antimicrobial agents, to which anticoagulant and/or antibiofilm substances are often added.However, the stability of such solutions needs to be tested by techniques such as high performance liquid chromatography (HPLC), in addition to antimicrobial efficacy testing, in order to establish patient safety. In consequence, this literature review aims to include the most clinically representative research towards these aspects, to demonstrate the behaviour of antibiotic-based catheter lock solutions under different conditions of storage and use. In particular, this review focuses on solutions containing vancomycin. According to the studies consulted, vancomycin solutions with sodium citrate (chelating agent) present the best stability characteristics in terms of physicochemical properties and efficacy.(AU)

Vancomycin powder in the prevention of infection in primary knee and hip arthroplasty: Case-control study with 1151 arthroplasties. / Vancomicina en polvo en la prevención de la infección en artroplastia primaria de rodilla y cadera: estudio de casos y controles con 1.151 artroplastias.

BACKGROUND AND OBJECTIVE: Vancomycin powder (VP) has been positively used in spinal surgery to reduce the rate of infections. Hardly any data have been published on hip and knee joint replacement surgery, and its usefulness is questioned. Our objective was to investigate the effectiveness of VP in reducing prosthetic infection and its possible complications. METHODS: Primary hip (THA) and knee (TKA) arthroplasties were reviewed, performed by five surgeons in one hospital center, between 2017 and 2018. 1g of VP was used on the implant prior to surgical closure based on the surgeon's preferences. With a 5-year follow-up in which the infection rate and local complications were analyzed. RESULTS: One thousand one hundred and fifty one arthroplasties were performed, 748 were TKA and 403 were THA. Nine patients were diagnosed with prosthetic infection, of which five received VP and four did not (P=.555). Likewise, another 15 patients suffered wound complications, of which 11 received VP and 4 did not (P=.412). There were no differences, either, in the rest of the complications depending on the use or not of VP (P=.101). Likewise, the number of patients who needed reintervention was similar (P=.999). No systemic complications were detected due to the use of VP. CONCLUSIONS: It has not been possible to demonstrate that the use of VP reduces the rates of prosthetic infection in the hip and knee, so we cannot recommend its use.

Reporting antimicrobial susceptibilities and phenotypes of resistance to vancomycin in vancomycin-resistant Enterococcus spp. clinical isolates: A nationwide proficiency study / Informe de sensibilidad antimicrobiana y fenotipos de resistencia a vancomicina en aislados clínicos de Enterococcus spp. resistentes a vancomicina: estudio multicéntrico nacional

Introduction: The ability of Spanish microbiology laboratories to (a) determine antimicrobial susceptibility (AS), and (b) correctly detect the vancomycin resistance (VR) phenotype in vancomycin-resistant Enterococcus spp. (VRE) was evaluated. Methods: Three VRE isolates representing the VanA (E. faecium), VanB (E. faecium) and VanC (E. gallinarum) VR phenotypes were sent to 52 laboratories, which were asked for: (a) AS method used; (b) MICs of ampicillin, imipenem, vancomycin, teicoplanin, linezolid, daptomycin, ciprofloxacin, levofloxacin and quinupristin–dalfopristin, and high-level resistance to gentamicin and streptomycin; (c) VR phenotype. Results: (a) The most frequently used system was MicroScan; (b) according to the system, the highest percentage of discrepant MICs was found with gradient strips (21.3%). By antimicrobial, the highest rates of discrepant MICs ranged 16.7% (imipenem) to 0.7% (linezolid). No discrepant MICs were obtained with daptomycin or levofloxacin. Mayor errors (MEs) occurred with linezolid (1.1%/EUCAST) and ciprofloxacin (5.0%/CLSI), and very major errors (VMEs) with vancomycin (27.1%/EUCAST and 33.3%/CLSI) and teicoplanin (5.7%/EUCAST and 2.3%/CLSI). For linezolid, ciprofloxacin, and vancomycin, discrepant MICs were responsible for these errors, while for teicoplanin, errors were due to a misassignment of the clinical category. An unacceptable high percentage of VMEs was obtained using gradient strips (14.8%), especially with vancomycin, teicoplanin and daptomycin; (c) 86.4% of the centers identified VanA and VanB phenotypes correctly, and 95.0% the VanC phenotype. Conclusion: Most Spanish microbiology laboratories can reliably determine AS in VRE, but there is a significant percentage of inadequate interpretations (warning of false susceptibility) for teicoplanin in isolates with the VanB phenotype.(AU)

Introducción: Se evaluó la capacidad de los laboratorios de microbiología españoles para: (a) determinar la sensibilidad antimicrobiana (SA); y (b) detectar correctamente el fenotipo de resistencia a vancomicina (FRV) en Enterococcus spp. resistente a vancomicina (ERV). Métodos: Se enviaron 3 aislados de ERV (E. faecium/VanA, E. faecium/VanB y E. gallinarum/VanC) a 52 laboratorios, a los que se les solicitó: (a) método de SA; (b) CMI de ampicilina, imipenem, vancomicina, teicoplanina, linezolid, daptomicina, ciprofloxacino, levofloxacino y quinupristina-dalfopristina y resistencia de alto nivel a gentamicina y estreptomicina; y (c) fenotipo de resistencia a vancomicina. Resultados: (a) El sistema más utilizado fue MicroScan; y (b) el mayor porcentaje de CMI discrepantes se produjo con las tiras de gradiente (21,3%). Las tasas más elevadas de CMI discrepantes variaron entre el 16,7% (imipenem) y el 0,7% (linezolid). Se produjeron errores mayores con linezolid (1,1%/EUCAST) y ciprofloxacino (5,0%/CLSI) y errores máximos con vancomicina (27,1%/EUCAST y 33,3% CLSI) y teicoplanina (5,7%/EUCAST y 2,3%/CLSI). Para linezolid, ciprofloxacino y vancomicina las CMI discrepantes fueron las responsables de estos errores, mientras que para teicoplanina los errores se debieron a una asignación errónea de la categoría clínica. Se obtuvo un alto porcentaje de errores máximos utilizando tiras de gradiente (14,8%), especialmente con vancomicina, teicoplanina y daptomicina; y (c) el 86,4% de los centros identificaron correctamente los fenotipos VanA y VanB y el 95,0% el fenotipo VanC. Conclusión: La mayoría de los laboratorios de microbiología españoles determinan de forma fiable la SA en ERV, pero existe un porcentaje significativo de interpretaciones inadecuadas (falsa sensibilidad) para teicoplanina en aislados con fenotipo VanB.(AU)

Reporting antimicrobial susceptibilities and phenotypes of resistance to vancomycin in vancomycin-resistant Enterococcus spp. clinical isolates: A nationwide proficiency study.

INTRODUCTION: The ability of Spanish microbiology laboratories to (a) determine antimicrobial susceptibility (AS), and (b) correctly detect the vancomycin resistance (VR) phenotype in vancomycin-resistant Enterococcus spp. (VRE) was evaluated. METHODS: Three VRE isolates representing the VanA (E. faecium), VanB (E. faecium) and VanC (E. gallinarum) VR phenotypes were sent to 52 laboratories, which were asked for: (a) AS method used; (b) MICs of ampicillin, imipenem, vancomycin, teicoplanin, linezolid, daptomycin, ciprofloxacin, levofloxacin and quinupristin-dalfopristin, and high-level resistance to gentamicin and streptomycin; (c) VR phenotype. RESULTS: (a) The most frequently used system was MicroScan; (b) according to the system, the highest percentage of discrepant MICs was found with gradient strips (21.3%). By antimicrobial, the highest rates of discrepant MICs ranged 16.7% (imipenem) to 0.7% (linezolid). No discrepant MICs were obtained with daptomycin or levofloxacin. Mayor errors (MEs) occurred with linezolid (1.1%/EUCAST) and ciprofloxacin (5.0%/CLSI), and very major errors (VMEs) with vancomycin (27.1%/EUCAST and 33.3%/CLSI) and teicoplanin (5.7%/EUCAST and 2.3%/CLSI). For linezolid, ciprofloxacin, and vancomycin, discrepant MICs were responsible for these errors, while for teicoplanin, errors were due to a misassignment of the clinical category. An unacceptable high percentage of VMEs was obtained using gradient strips (14.8%), especially with vancomycin, teicoplanin and daptomycin; (c) 86.4% of the centers identified VanA and VanB phenotypes correctly, and 95.0% the VanC phenotype. CONCLUSION: Most Spanish microbiology laboratories can reliably determine AS in VRE, but there is a significant percentage of inadequate interpretations (warning of false susceptibility) for teicoplanin in isolates with the VanB phenotype.

Redução da taxa de filtração glomerular em pacientes críticos em uso de vancomicina: um estudo transversal / Decrease of the glomerular filtration rate in critically ill patients using vancomycin: a cross-sectional study

Objetivo: o presente trabalho teve como objetivo avaliar os fatores clínicos e medicamentosos relacionados com a redução da Taxa de Filtração Glomerular (TFG) em pacientes críticos em uso de vancomicina. Métodos: trata-se de um estudo transversal em que pacientes em uso de vancomicina, maiores de 18 anos, hospitalizados em terapia intensiva, foram selecionados no período de agosto a dezembro de 2019. Foram excluídos os pacientes que tiveram permanência inferior a 48h na unidade, aqueles com doença renal crônica e/ou que tiveram antimicrobiano suspenso nas primeiras 48h. Os dados clínicos e laboratoriais foram coletados do prontuário nas mesmas datas das coletas de amostras sanguíneas. As amostras de sangue foram coletadas no vale a partir do terceiro dia de tratamento. Os níveis de vancomicina foram medidos usando VANC VITROS ®. Os dados foram analisados através do software R. Resultados: 54 pacientes foram incluídos, sendo 68,5% do sexo masculino, 98,1% em ventilação mecânica, com foco respiratório (51,2%) e isolado Acinetobacter baumanni (38,0%). As concentrações de vancomicina variaram entre 5,0 e 50,0µg/mL, média 21,6 (DP: 10,6) µg/mL; 50% dos pacientes apresentaram concentração acima de 20µg/mL e 66,7% piora da TFG após o tratamento. A concentração de vancomicina foi a única variável diretamente relacionada com o desenvolvimento da alteração na função renal (p=0.0037). Não foi possível estabelecer a influência da comedicação na redução da taxa de filtração glomerular (TFG). Conclusão: as doses usuais de vancomicina ajustadas por meio da função renal não atingiram os níveis séricos terapêuticos recomendados de vancomicina, sendo relacionados à nefrotoxicidade.

Objective: we aimed to evaluate clinical and drug factors related to the Glomerular Filtration Rate (GFR) reduction in critically ill patients using vancomycin. Methods: This is a cross-sectional study where critically ill patients using vancomycin, aged over 18 years, were selected from August to December 2019. Patients were excluded when hospitalized for less than 48 hours in the unit, those with chronic kidney disease, and/or who had their antimicrobial suspended in the first 48 hours. Clinical and laboratory data were collected from the medical record on the same days as the blood sample collection. All blood samples were collected at the trough during the third day of vancomycin treatment. Vancomycin levels were measured using VANC VITROS ®. Data analysis was analyzed by R software. Results: 54 patients were included, 68.5% male, 98.1% mechanical ventilation, respiratory focus (51.2%), and isolation of Acinetobacter baumanni (38.0%). Vancomycin concentrations ranged between 5.0 and 50.0µg/mL, mean of 21.6 (SD: 10.6) µg/mL; 50% of patients with concentrations above 20µg/mL and 66.7% worsened GFR after vancomycin treatment. Vancomycin concentration was the only variable directly related to the development of renal malfunction (p=0.0037). It was not possible to establish the influence of co-medication in the reduction of the glomerular filtration rate (GFR). Conclusion: the usual doses of vancomycin adjusted by renal function did not reach the recommended therapeutic serum levels of vancomycin, being related to nephrotoxicity.

Fecal concentration of intravenous vancomycin preparation after oral administration in an experimental model: preclinical assay.

INTRODUCTION: Clostridioides difficile (C. difficile) infection is the main cause of nosocomial diarrhea. First-line treatment is oral vancomycin, but that presentation is not commercially available in Latin America. Our aim was to determine the fecal concentration of the oral administration of the conventional dose of an intravenous vancomycin preparation (VCM), in an experimental model. METHODS: A preclinical trial was conducted on 18 male mice (Balb/c strain), in three batches. The following doses of VCM were administered: 125 mg in batch A; 500 mg in batch B; and VCM-placebo in batch C. After receiving the doses, the mice were placed in metabolic cages, by batch. Feces were collected and the fecal concentration of VCM was analyzed through high pressure liquid chromatography 2, 4 and 6 h after drug administration. RESULTS: The 125 mg dose of VCM reached the minimum inhibitory concentration (MIC) for C. difficile, without reaching the minimum bactericidal concentration (MBC90), at 2, 4, and 6 h (521, 688, and 280 mg/L, respectively). Likewise, the 500 mg dose of VCM reached the MIC at 2 h, increased gradually, and reached MBC90 between 4 and 6 h, in feces (1,062 and 1,779 mg/L, respectively), ANOVA, p = 0.0005. CONCLUSION: The fecal concentration of vancomycin was dependent on the intragastric dose administered. Only the 500 mg dose of VCM reached therapeutic concentration for C. difficile (MIC and MBC90), in the mice. We suggest starting a dose of 500 mg QID for achieving therapeutic concentration against C. difficile, as soon as 4 h after the first dose.

Agranulocitosis secundaria a uso de vancomicina en pediatría. reporte de caso

La vancomicina es un antibiótico de uso común en pacientes hospitalizados. Se han descrito múltiples efectos adversos relacionados a este fármaco, de los cuales la agranulocitosis es una entidad poco frecuente pero potencial mente grave. Este caso muestra una consecuencia médica secundaria al uso prolongado de este antibiótico, generando una neutropenia profunda posterior a 24 días de tratamiento, presentándose clínicamente con un pico febril aislado. Se asume que esta situación es consecuencia de una respuesta inmunológica inadecuada del huésped, por lo que la suspensión del agente etiológico es la clave del tratamiento. Existen pocos reportes de estos casos en la población pediátrica y debe considerarse un efecto secundario que requiere vigilancia estrecha para evitar repercusiones clínicas.

Vancomycin is a commonly used antibiotic in hospitalized patients. Multiple adverse effects related to this drug have been described, of which agranulocytosis is a rare but potentially serious entity. This case shows a medical consequence secondary to the prolonged use of this antibiotic, generating profound neutropenia after 24 days of treatment, presenting clinically with an isolated feverish peak. It is assumed that this situation is the consequence of an inadequate immunological response of the host, for which reason the suspension of the etiological agent is the key to treatment. There are few reports of these effects in the pediatric population and should be considered a side effect that requires close monitoring to avoid clinical repercussions.

Dermatosis ampollar por IgA lineal inducida por Vancomicina: reporte de un caso / Vancomycin-induced linear igabollous dermatosis: a case report

RESUMEN La dermatosis ampollar por IgA lineal del adulto (DLA) es una enfermedad autoinmune adquirida infrecuente, caracterizada por el depósito lineal de anticuerpos IgA en la membrana basal. La mayoría de los casos reportados son de causa idiopática, pero esta entidad también se ha visto asociada a ciertos fármacos, siendo la vancomicina el más frecuente. Se presenta un caso de DLA asociada a vancomicina, con extensa afectación cutánea y compromiso mucoso, tratado con dapsona y corticoides sistémicos con buena respuesta.

ABSTRACT Adult linear IgA bollous dermatosis (LABD) is a rare acquired autoimmune disease characterized by linear deposition of IgA antibodies on the basement membrane. Most of the reported cases are of idiopathic cause, but this entity has also been associated with certain drugs, vancomycin being the most frequent. We present a case of LABD associated with vancomycine, with extensive skin and mucosal involvement, treated with dapsone and systemic corticosteroids with a good response.

Risk of acute kidney injury and cost-effectiveness analysis comparing vancomycin and linezolid for the treatment of pediatric patients infected with Gram-positive bacteria / Risco de lesão renal aguda e custo-efetividade comparando vancomicina e linezolida para o tratamento de pacientes pediátricos infectados por bactérias Gram-positivas

Objective: This study aimed to compare the occurrence of acute kidney injury (AKI) in pediatric patients who used vancomycin (VAN) or linezolid (LNZ) to treat Gram-positive coccus (GPC) infections and to assess which treatment (VAN or LNZ) is the most cost-effective considering a pediatric hospital perspective. Methods: A retrospective cohort was performed to evaluate the occurrence of nephrotoxicity in pediatric patients without previous AKI, with GPC infections that used LNZ, or VAN monitored by serum VAN levels. Initially, descriptive analysis and Fisher and chisquare test were performed for this comparison. Then, a cost-effectiveness analysis was conducted through a decision tree model. The outcomes of interest were the rate of AKI related to the drug and the rate of admission to the intensive care unit (ICU) and cure. Results: In patients without previous acute kidney injury (AKI), 20% developed nephrotoxicity associated with VAN versus 9.6% in the LNZ group (p = 0.241). As there was no difference in nephrotoxicity between VAN andlinezolid (LNZ), vancomycin (VAN) monitored by serum VAN levels can optimize and rationalize the treatment. The nephrotoxicity risk criterion should not guide the prescription for LNZ. Furthermore, the average global cost of treatment with VAN was approximately R$ 43,000, while for LNZ, it was R$ 71,000. Conclusion: VAN was considered dominant (lower cost and greater effectiveness) over LNZ for treating patients with GPC infection.

Objetivo: Este estudo objetivou comparar a ocorrência de lesão renal aguda (LRA) em pacientes pediátricos que usaram vancomicina (VAN) ou linezolida (LNZ) para tratar infecções por cocos Gram-positivos (CGP) e avaliar qual tratamento (VAN ou LNZ) é o mais custo-efetivo considerando a perspectiva de um hospital pediátrico. Métodos: Foi realizada uma coorte retrospectiva para avaliar a ocorrência de nefrotoxicidade em pacientes pediátricos sem LRA prévia, com infecções por CGP que utilizaram LNZ ou VAN, combinada com vancocinemia. Para essa comparação, inicialmente foram realizados análise descritiva e testes de Fisher e qui-quadrado. Em seguida, foi realizada uma análise de custo-efetividade por meio de um modelo de árvore de decisão. Os desfechos de interesse foram a taxa de LRA relacionada ao medicamento e a taxa de internação em unidade de terapia intensiva e cura. Resultados: Nos pacientes sem LRA prévia, 20% deles desenvolveram nefrotoxicidade associada à VAN versus 9,6% no grupo LNZ (p = 0,241). Como não houve diferença na nefrotoxicidade entre VAN e LNZ, a VAN combinada com a vancocinemia pode otimizar e racionalizar o tratamento, e a prescrição de LNZ não deve ser guiada pelo critério de risco de nefrotoxicidade. Além disso, o custo médio global do tratamento com VAN foi de aproximadamente R$ 43.000, enquanto para LNZ foi de R$ 71.000. Conclusão: Assim, a VAN foi considerada dominante (menor custo e maior eficácia) sobre a LNZ para o tratamento de pacientes com infecção por CGP.

Susceptibility to Vancomycin of Biofilm Producing Staphylococci Isolated from Tertiary Care Hospital of Nepal / Susceptibilidad a la vancomicina de estafilococos productores de biopelículas aislados del hospital de atención terciaria de Nepal

Background: Methicillin resistance and biofilm-producing Staphylococci are emerging as multidrug-resistant strains narrowing the efficacy of antimicrobial therapy. Although vancomycin is used as the drug of choice to treat such isolates, different studies worldwide have documented the emergence of strains that are intermediately susceptible or resistant to this antibiotic. Objective: The study aimed to determine the minimum inhibitory concentration of vancomycin to methicillin-resistant and biofilm-producing staphylococci isolated from different clinical specimens. Methods: 375 staphylococci isolated from different clinical specimens over one year were included in the study. Biofilm formation was determined by the Tissue culture plate method (TCP), and ica genes were identified by Polymerase Chain Reaction (PCR). Antibiotic susceptibility and methicillin resistance were done following Clinical and Laboratory Standards Institute (CLSI) guidelines. The minimum inhibitory concentration (MIC) of vancomycin in all isolates was determined by the agar dilution method. Results:Among 375 Staphylococci studied, 43% and 57% represented S. aureus and Coagulase-Negative Staphylococci (CNS), respectively. The rate of Methicillin-Resistant S. aureus (MRSA) and Methicillin-Resistant Coagulase Negative Staphylococci (MRCNS) were 81.4% and 66.8% respectively and determined by the disc diffusion method. The most potential antibiotics were tetracycline and chloramphenicol showing sensitivity to more than 90% isolates. The Minimum Inhibitory Concentration (MIC) value of oxacillin for staphylococci ranged from 0.125-32 µg/ml. Oxacillin agar diffusion method showed 51.6% and 79.9% isolates as MRSA and MRCNS, respectively, revealing a very high percentage of S. aureus and CNS isolates as methicillin-resistant. All isolates had susceptible vancomycin MICs that ranged from 0.125-2 µg/ml. Two S. aureus isolated from Central Venous Catheter (CVC) and catheter specimens were detected with intermediate susceptibility to vancomycin. Similarly, three CNS isolated from blood, CVC, and wound/pus (w/p) were intermediately susceptible to vancomycin. Strong biofilm formation was observed in 22.1% of clinical isolates, and the ica gene was detected among 22.9% of isolates. Only one S. aureus detected as a biofilm producer by the TCP method was found to have intermediate susceptibility to vancomycin. Conclusions: The increment in vancomycin MIC among methicillin-resistant and biofilm-producing staphylococci is alarming. Strict control measures to prevent methicillin-resistant isolates spread and routine surveillance for vancomycin-resistant isolates must be incorporated in hospitals to prevent antimicrobial treatment failure

Antecedentes: Los estafilococos resistentes a la meticilina y productores de biopelículas están surgiendo como cepas multirresistentes que reducen la eficacia del tratamiento antimicrobiano. Aunque la vancomicina se utiliza como fármaco de elección para tratar dichos aislados, diferentes estudios realizados en todo el mundo han documentado la aparición de cepas intermedias susceptibles o resistentes a este antibiótico. Objetivo: El estudio tenía como objetivo determinar la concentración mínima inhibitoria de la vancomicina para los estafilococos resistentes a la meticilina y productores de biofilm aislados de diferentes muestras clínicas. Métodos: Se incluyeron en el estudio 375 estafilococos aislados de diferentes muestras clínicas durante un año. La formación de biopelículas se determinó mediante el método de la placa de cultivo de tejidos (TCP), y los genes ica se identificaron mediante la reacción en cadena de la polimerasa (PCR). La susceptibilidad a los antibióticos y la resistencia a la meticilina se realizaron siguiendo las directrices del Clinical and Laboratory Standards Institute (CLSI). La concentración inhibitoria mínima (MIC) de vancomicina en todos los aislados se determinó por el método de dilución en agar. Resultados:Entre los 375 estafilococos estudiados, el 43% y el 57% representaban S. aureus y estafilococos coagulasa-negativos (ECN), respectivamente. La tasa de S. aureus resistente a la meticilina (SARM) y de estafilococos coagulasa negativos resistentes a la meticilina (ECNM) fue del 81,4% y el 66,8%, respectivamente, y se determinó por el método de difusión de discos. Los antibióticos más potenciales fueron la tetraciclina y el cloranfenicol, que mostraron una sensibilidad superior al 90% de los aislados. El valor de la concentración inhibitoria mínima (CIM) de la oxacilina para los estafilococos osciló entre 0,125-32 µg/ml. El método de difusión en agar de la oxacilina mostró que el 51,6% y el 79,9% de los aislados eran SARM y MRCNS, respectivamente, lo que revela que un porcentaje muy elevado de los aislados de S. aureus y CNS son resistentes a la meticilina. Todos los aislados tenían MIC de vancomicina susceptibles que oscilaban entre 0,125-2 µg/ml. Se detectaron dos S. aureus aislados de muestras de catéteres venosos centrales (CVC) y catéteres con una susceptibilidad intermedia a la vancomicina. Del mismo modo, tres S. aureus aislados de sangre, CVC y herida/pus (w/p) fueron intermedianamente susceptibles a la vancomicina. Se observó una fuerte formación de biopelículas en el 22,1% de los aislados clínicos, y se detectó el gen ica en el 22,9% de los aislados. Sólo un S. aureus detectado como productor de biopelículas por el método TCP resultó tener una susceptibilidad intermedia a la vancomicina. Conclusiones: El incremento de la MIC de vancomicina entre los estafilococos resistentes a la meticilina y productores de biofilm es alarmante. Para evitar el fracaso del tratamiento antimicrobiano, deben incorporarse en los hospitales medidas de control estrictas para prevenir la propagación de los aislados resistentes a la meticilina y una vigilancia rutinaria de los aislados resistentes a la vancomicina

Vancomicina frente a daptomicina como tratamiento de las bacteriemias asociadas a catéter y causadas por grampositivos en el paciente oncológico / Vancomycin versus daptomycin for the treatment of confirmed gram-positive catheter-related bloodstream infections in oncology patients

Objetivo: Analizar la eficacia y seguridad de la daptomicina frente ala vancomicina en el tratamiento de las infecciones del torrente sanguíneoasociadas a catéter vascular en pacientes oncológicos.Método: Se realizó un estudio retrospectivo que incluyó a los pacientesingresados en la Unidad de Oncología-Médica entre 2010-2018 coninfección del torrente sanguíneo asociada a catéter vascular causadapor grampositivos, y que fueron tratados con vancomicina o daptomicina.Como objetivos principales se determinaron la tasa de mortalidad portodas las causas a los 30 días, el reingreso hospitalario a los 30 días yla duración de la estancia hospitalaria.Resultados: El estudio incluyó 70 pacientes con infecciones del torrentesanguíneo asociadas a catéter vascular: el 61,4% (n = 43) recibió vancomicinay el 38,6% (n = 27) daptomicina. El 78,5% (n = 55) de las bacteriasaisladas presentaron una concentración mínima inhibitoria de vancomicina≤ 1 μg/ml. No se observaron diferencias entre ambos grupos depacientes en cuanto a la tasa de mortalidad a 30 días (32,6% [n = 14] frente al 29,6% [n = 8]; p = 0,797), la tasa de reingreso a 30 días (30,2%[n = 13] frente al 29,6% [n = 8]; p = 0,957) o la duración de la hospitalización(18,9 frente a 16,5 días; p = 0,562). La tasa de nefrotoxicidadfue equivalente en ambos grupos: 7% (n = 3) para vancomicina frente al7,4% (n = 2) para daptomicina (p = 0,946).Conclusiones: Nuestros resultados muestran que ambos antibióticos sonequivalentes en su seguridad y eficacia. Por ello, vancomicina deberíaseguir siendo el tratamiento de elección para la infección del torrentesanguíneo asociada a catéter vascular, especialmente en centros con unabaja prevalencia de cepas con una susceptibilidad disminuida a vancomicina.

Objective: To analyse the effectiveness and safety of daptomycin versusvancomycin on the management catheter-related bloodstream infectionsin oncology patients.Method: A retrospective study was carried out including all patientsadmitted at the Medical Oncology Unit between 2010 and 2018 withpositive blood cultures confirmed catheter-related bloodstream infectionsdue to gram-positive microorganism, who were treated with either vancomycinor daptomycin. The primary end point was all cause 30-daysmortality, 30-days hospital readmission and length of hospital stay (lengthof hospital stay).Results: A total of 70 patients with catheter-related bloodstream infectionswere included in the present study: vancomycin was administeredto 61.4% (n = 43) and daptomycin to 38.6% (n = 27) of patients.78.5% (n = 55) of isolated bacteria showed a vancomycin minimuminhibitory concentration ≤ 1 μg/ml. No differences were observed betweenthe two groups of patients regarding the 30-day mortality rate rate (32.6% [n = 14] versus 29.6% [n = 8]; p = 0.797), the 30-day re-admissionrate (30.2% [n = 13] versus 29.6% [n = 8]; p = 0.957) or the lengthof hospital stay (18.9 versus 16.5 days; p = 0.562). Nephrotoxicity ratewas equivalent in both groups: a 7% (n = 3) of vancomycin goup versus a7.4% (n = 2) of daptomycin group (p = 0.946).Conclusions: Our results show that both antibiotics are equivalent intheir safety and effectiveness. Therefore, vancomycin should continuebeing the treatment of chose for gram-positive catheter-related bloodstreaminfections, in particular at hospital centres with a low prevalence ofstrains that show diminished susceptibility to vancomycin.

Monitoramento orientado pela área sob a curva da vancomicina em pacientes pediátricos / Vancomycin area under the curve-guided monitoring in pediatric patients

RESUMO Objetivo: Avaliar a probabilidade de atingir o alvo pela razão entre a área sob a curva e a concentração inibitória mínima de vancomicina em pacientes pediátricos após o esquema de dose empírica e demonstrar a aplicabilidade desse método para o monitoramento da vancomicina. Metódos: Foi realizado um estudo de coorte retrospectivo que incluiu pacientes pediátricos com função renal normal internados entre janeiro e dezembro de 2020. O modelo de um compartimento com cinética de primeira ordem foi utilizado para estimar os parâmetros farmacocinéticos, e a área sob a curva foi calculada pela regra do trapézio. O alvo terapêutico foi definido como a razão entre a área sob a curva e a concentração inibitória mínima ≥ 400 e < 600. O teste do qui-quadrado foi aplicado para comparar a probabilidade de atingir o alvo nos grupos etários, enquanto os parâmetros farmacocinéticos foram comparados pelo teste de Kruskal-Wallis com o teste de Dunn para análises post hoc. Consideraram-se significativos os valores de p < 0,05. Resultados: Foram analisados, no total, 42 pares de níveis de vancomicina de 17 pacientes inscritos neste estudo. Após a dose diária empírica de vancomicina, o alvo terapêutico foi atingido em cinco (29%) pacientes; quatro pacientes (24%) apresentavam razão entre a área sob a curva inicial supraterapêutica e o valor de concentração inibitória mínima (> 600mg.h/L) e oito (47%) tinham valores subterapêuticos (< 400mg.h/L). Os patógenos mais identificados foram Staphylococcus spp. (n = 7). Os níveis de vale e as áreas sob a curva mostraram valores moderados de correlação (R2 = 0,73). Um (6%) paciente apresentou lesão renal aguda. Conclusão: A maioria dos pacientes não atingiu o alvo terapêutico com esquema de dose empírica de vancomicina, e a implementação de dosagem baseada na área sob a curva usando duas medições de amostra permitiu ajustes de dose em tempo real com base nos parâmetros farmacocinéticos dos indivíduos.

ABSTRACT Objective: To assess the percentage of vancomycin area under the curve/minimum inhibitory concentration target attainment in pediatric patients after the empirical dose regimen and to demonstrate the applicability of this method for vancomycin monitoring. Methods: A retrospective cohort study was performed including pediatric patients with normal renal function admitted between January 2020 and December 2020. The one-compartment model with first-order kinetics was used to estimate the pharmacokinetic parameters, and the area under the curve was calculated by the trapezoidal rule. The therapeutic target was defined as area under the curve/minimum inhibitory concentration ≥ 400 and < 600. The Chi-squared test was applied to compare the percentage of target attainment over age groups, while the pharmacokinetic parameters were compared by the Kruskal-Wallis test with Dunn's test for post hoc analyses. We considered significant p-values < 0.05. Results: In total, 42 pairs of vancomycin levels were analyzed from 17 patients enrolled in this study. After empirical vancomycin daily dosing, the therapeutic target was achieved in five (29%) patients; four patients (24%) had a supratherapeutic initial area under the curve/minimum inhibitory concentration value (> 600mg.h/L), and eight (47%) patients had subtherapeutic values (< 400mg.h/L). The most identified pathogens were Staphylococcus spp. (n = 7). Trough levels and areas under the curve showed moderate correlation values (R2 = 0.73). Acute kidney injury occurred in one (6%) patient. Conclusion: Most patients did not reach the therapeutic target with a vancomycin empirical dose regimen, and the implementation of area under the curve-based dosing using two sample measurements allowed for real-time dose adjustments based on individuals' pharmacokinetic parameters.

Inducción de remisión con gentamicina y vancomicina oral en enfermedad inflamatoria intestinal de inicio temprano / Very early onset inflammatory bowel disease remission induced with oral gentamicin and vancomycin

La enfermedad inflamatoria intestinal de inicio temprano se manifiesta en pacientes pediátricos antes de los 6 años de edad. Habitualmente se asocia a diversas causas, siendo descrita frecuentemente la disbiosis como factor desencadenante. Esta población presenta comúnmente refractariedad a los tratamientos inmunosupresores más empleados.Presentamos el caso de un paciente con colitis no clasificable y corticodependiente de un año de evolución ingresado en nuestro centro que no había respondido a terapia inmunosupresora intensificada. Se plantea terapia con antibióticos orales como inducción de la remisión del brote de actividad en combinación con su tratamiento inmunomodulador habitual. Si bien inicialmente se obtiene la remisión clínica, el paciente experimenta posteriormente al alta un nuevo brote de actividad siendo necesaria una segunda reinducción con antibióticos que no resulta eficaz, motivando su suspensión. (AU)

Very early onset inflammatory bowel disease occurs in children under 6 years age. It is frequently associated to a diverse ethiology, dysbiosis being usually described as a triggering factor. Commonly, this population is highly resilient to inmmunosuppressant therapies.We report here a medical case of a patient diagnosed with unclassified and steroid-dependent colitis, with a year of evolution, who had no responded to intensified therapy at home, and, therefore, was hospitalized at our centre. Treatment with oral antibiotics was intended as remission induction in combination with his usual inmmunomodulator treatment. Although clinical remission was observed at first stage, a new activity outbreak emerged requiring a second round of antibiotics therapy, which was unsuccessful and currently withdrawned. (AU)

Estabilidade do cloridrato de vancomicina empregado em soluções de selo antimicrobiano de cateteres intravenosos centrais / Stability of vancomycin hydrochloride employed in antimicrobial seal solutions of central intravenous catheters / Estabilidad del clorhidrato de vancomicina utilizado en soluciones de sellado antimicrobiano para catéteres intravenosos centrales

Resumo Objetivo: verificar a estabilidade do cloridrato de vancomicina em soluções de selo antimicrobiano sem e com associação de heparina sódica segundo a temperatura e tempo de associação. Método: estudo experimental delineado para análise de potencial hidrogeniônico e concentração por cromatografia líquida de alta eficiência de soluções de cloridrato de vancomicina (n=06) e cloridrato de vancomicina e heparina sódica (n=06). Submeteram-se as soluções estudadas à ausência de luz, 22°C e 37°C. Análises em triplicadas (n=192) ocorreram no momento inicial (T0), três (T3), oito (T8) e 24 horas (T24) após preparo. Os dados foram submetidos à análise de variância (p≤0,05). Resultados: a concentração do antimicrobiano a 22°C apresentou redução (T0-T8) e posterior elevação (T24); o potencial hidrogeniônico diminuiu significativamente ao longo do tempo. Em 37°C a concentração aumentou em até T3 e reduziu em T24, com redução de potencial hidrogeniônico até 24 horas. A concentração das soluções de cloridrato de vancomicina e heparina sódica apresentaram variação com redução a 22°C acompanhada de aumento de potencial hidrogeniônico. Observou-se formação de precipitado por inspeção visual da associação cloridrato de vancomicina e heparina sódica (T3). Conclusão: evidenciou-se estabilidade farmacológica do cloridrato de vancomicina (5 mg/mL) e incompatibilidade física com heparina sódica (100 UI/mL) após três horas de associação nas soluções de selo antimicrobiano estudadas.

Abstract Objective: to verify the stability of vancomycin hydrochloride in antimicrobial seal solutions with and without association of heparin sodium according to temperature and association time. Method: an experimental study designed for the analysis of hydrogenionic potential and concentration by means of high-efficiency liquid chromatography of vancomycin hydrochloride (n=06) and vancomycin hydrochloride and heparin sodium (n=06). The solutions studied were submitted to absence of light, as well as to 22°C and 37°C. Analyses in triplicate (n=192) were performed at the initial moment (T0) and three (T3), eight (T8) and 24 hours (T24) after preparation. The data were submitted to analysis of variance (p≤0.05). Results: concentration of the antimicrobial at 22°C presented a reduction (T0-T8) and a subsequent increase (T24); hydrogenionic potential decreased significantly over time. At 37°C, the concentration increased up to T3 and decreased at T24, with a reduction of hydrogenionic potential up to 24 hours. Concentration of the vancomycin hydrochloride and heparin sodium solutions varied with a reduction at 22°C, accompanied by increased hydrogenionic potential. Precipitate formation was observed by visual inspection of the vancomycin hydrochloride-heparin sodium association (T3). Conclusion: pharmacological stability of vancomycin hydrochloride (5 mg/mL) and physical incompatibility with heparin sodium (100 IU/mL) were evidenced after three hours of association in the antimicrobial seal solutions studied.

Resumen Objetivo: verificar la estabilidad del clorhidrato de vancomicina en soluciones de sellado antimicrobiano solo y combinado con heparina sódica según la temperatura y el tiempo de combinación. Método: estudio experimental diseñado para analizar el potencial de hidrógeno y la concentración por cromatografía líquida de alta resolución de soluciones de clorhidrato de vancomicina (n=06) y de clorhidrato de vancomicina y heparina sódica (n=06). Las soluciones estudiadas fueron sometidas a ausencia de luz, 22°C y 37°C. Se realizaron análisis por triplicado (n=192) en el momento inicial (T0), a las tres (T3), ocho (T8) y 24 horas (T24) después de la preparación. Los datos fueron sometidos a análisis de varianza (p≤0,05). Resultados: la concentración de antimicrobiano a 22°C mostró una reducción (T0-T8) y un posterior aumento (T24); el potencial de hidrógeno disminuyó significativamente con el tiempo. A 37°C, la concentración aumentó hasta T3 y disminuyó en T24, el potencial de hidrógeno disminuyó hasta las 24 horas. La concentración de las soluciones de clorhidrato de vancomicina y heparina sódica mostró variación con la reducción a 22°C acompañada de un aumento del potencial de hidrógeno. Mediante inspección visual se observó la formación de un precipitado al combinar clorhidrato de vancomicina y heparina sódica (T3). Conclusión: el clorhidrato de vancomicina (5 mg/ml) presentó evidencia de estabilidad farmacológica e incompatibilidad física con la heparina sódica (100 UI/ml) después de las tres horas de haberse realizado la combinación en las soluciones de sellado antimicrobiano estudiadas.

Patrones de administración de vancomicina en pacientes críticamente enfermos / Vancomycin administration patterns in critically ill patients

Resumen La vancomicina es un antimicrobiano ampliamente utilizado en unidades de cuidado intensivo para el tratamiento de infecciones por cocos Gram positivos. El principal parámetro PK/PD, predictor de la actividad de la vancomicina, es el AUC/MIC mayor a 400, logrado mediante concentraciones plasmáticas del fármaco de 15 a 20 mg/l en el contexto de un paciente con función renal normal. En los pacientes críticos, se generan cambios en los patrones farmacocinéticos que llevan a dosis sub-terapéuticas del antibiótico y monitoreo constante de las concentraciones plasmáticas. Por tanto, se realizó una búsqueda de la literatura con el objetivo de conocer cuál es el mejor régimen de administración de vancomicina en pacientes críticamente enfermos y establecer los parámetros básicos de prescripción en esta población. Se encontró que la infusión continua de vancomicina se relacionó con mejores resultados, alcanzando más tempranamente los niveles planeados de concentración plasmática. La dosis de carga estuvo en el intervalo de 15 a 30 mg/k y la dosis de mantenimiento se dio en promedio entre 30 a 40 mg/K día. La concentración plasmática meta de vancomicina usada en la mayoría de los estudios oscila entre 15 y 20 mg/l. Como conclusión, se obtiene que la forma de administración en infusión continua, muestra mejor resultado, comparada con la administración intermitente; las dosis altas tanto en carga como en mantenimiento son las más recomendadas y no incrementan el riesgo de nefrotoxicidad; las estrategias PK/PD son útiles para el ajuste de la dosis de los pacientes críticamente enfermos.

Abstract Vancomycin is an antimicrobial used in intensive care units for the treatment of Gram-positive cocci infections. The main PK/PD parameter, predictor of vancomycin activity, is the AUC/MIC greater than 400; this is reached with plasma drug concentrations of 15 to 20 mg/l in the context of a patient with normal renal function. In critically ill patients, there are changes in the pharmacokinetic patterns that lead to sub-therapeutic doses of the antibiotic and a requirement for monitoring the vancomycin levels. There was reviewed literature on this field to determine the best vancomycin administration regimen in critically ill patients, and to establish the basic prescription parameters in this population. It was found that continuous infusion of vancomycin was associated with better results since it reached the necessary plasma concentration levels earlier. The loading dose was in the range of 15 to 30 mg/kg and the maintenance dose averaged between 30 to 40 mg/kg per day. The target plasma concentration of vancomycin used in most of the studies ranged between 15 and 20 mg/l. In conclusion, the continuous administration of vancomycin shows better results compared to intermittent administration. High doses in loading and maintenance are the most recommended since these do not increase the risk of nephrotoxicity. Finally, PK/PD strategies are useful for adjusting the dose of critically ill patients.

Infecciones intrahospitalarias por estafilococo coagulasa negativo en una unidad de neonatología / Coagulase negative streptococci nosocomial infections at a neonatal intensive care unit / Infecções intra-hospitalares por estafilococo coagulasa negativa numa unidade de neonatologia

Introducción: la sepsis tardía por estafilococo coagulasa negativo (SCoN) es una causa común de morbimortalidad en la unidad neonatal. Los SCoN son los microorganismos más frecuentemente involucrados con aproximadamente el 50% de los casos. El objetivo de este estudio es analizar la incidencia y las características de los neonatos portadores de sepsis tardía por SCoN. Materiales y métodos: se realizó un estudio descriptivo, longitudinal, retrospectivo. Se utilizaron las bases de datos del laboratorio de microbiología del hospital y las historias clínicas electrónicas para obtener la información. El período de estudio analizado fueron los años 2018 y 2019 en la unidad de cuidados intensivos e intermedios de recién nacidos del Centro Hospitalario Pereira Rossell. Resultados: obtuvimos una incidencia de 2,5% de los ingresos a cuidados intensivos e intermedios (25 pacientes). La edad gestacional al nacer fue de 28 semanas (25,0-35,0) y la mediana del peso fue de 1.070 g (730,0-2.365,0). La media de edad gestacional posmenstrual al momento del diagnóstico fue de 32,92±7,921 semanas. Por sospecha de sepsis precoz, 17 pacientes habían recibido un curso de antibióticos previo. El signo clínico más frecuentemente observado fue el deterioro del estado general, en 11 pacientes, seguido de distensión abdominal en 6 y fiebre en 5. Dentro de los SCoN, el más frecuentemente aislado fue el Staphylococcus epidermidis (13 pacientes); 22 pacientes recibieron tratamiento, 18 de ellos con vancomicina-meropenem y 4 con monoterapia con vancomicina. Conclusión: estos patógenos representan una causa importante de morbimortalidad en la unidad neonatal, particularmente en pacientes que presentan mayor gravedad y mayor necesidad de soporte vital. Se necesitan pautas claras de interpretación del rol de estos microorganismos y de abordaje de pacientes con riesgo de sepsis tardía, incluyendo el tratamiento antibiótico empírico.

Introduction: Coagulase Negative Staphylococci (CoNS) late onset sepsis is a common cause of morbidity and mortality in the neonatal intensive care unit (NICU). CoNS are the most frequently isolated microorganisms and total 50% of cases. The objective of this study is to analyze the incidence and characteristics of newborns carriers of late onset CoNS. Materials and methods: we performed a descriptive, retrospective, longitudinal study. Data was obtained from the hospital's microbiology laboratory database and electronic medical records. Patients included were those admitted to NICU during the period between 2018 and 2019. Results: we obtained an incidence of 2.5% of patients admitted to the NICU (25 patients). Median gestational age at birth was 28 weeks 25.0-35.0 and median birth weight was 1.070 g 730.0-2365.0. Mean gestational age at the time of diagnosis was 32.92±7.921 weeks. 17 patients had received an antibiotics course at birth because of early onset sepsis suspicion. The most frequently observed clinical symptom was deterioration of general condition, 11 patients, followed by abdominal distention in 6 and fever in 5. Among CoNS, the most frequently isolated pathogen was Staphylococcus epidermidis (13 patients). 22 patients received treatment, 18 a combination of vancomycin and meropenem and 4 received vancomycin monotherapy. Conclusion: these pathogens are a common cause of morbidity and mortality in the newborn intensive care unit, particularly in patients with more serious conditions and in those who require more advanced life support measures. Clearer interpretation of their role is needed as well as to determine a proper approach to patients at risk of late onset sepsis, including empiric antibiotic treatment.

Sepse tardia para Staphylococcus coagulase negativa (SCoN) é uma causa comum de morbidade e mortalidade na unidade neonatal. SCoNs são os microrganismos mais frequentemente envolvidos e representam aproximadamente 50% dos casos. O objetivo deste estudo é analisar a incidência e as características de neonatos com sepse tardia por SCoN. Materiais e métodos: foi realizado um estudo descritivo, longitudinal e retrospectivo. Usamos os bancos de dados do laboratório de microbiologia e prontuários médicos eletrônicos de nosso hospital para obter as informações. O período de estudo analisado foi de 2018 e 2019 na unidade de terapia intensiva e intermediária para recém-nascidos do Centro Hospitalar Pereira Rossell. Resultados: obtivemos uma incidência de 2,5% de internações em Terapia Intensiva e Intermediária (25 pacientes). A idade gestacional ao nascer foi de 28 semanas 25,0-35,0 e o peso médio foi de 1070g 730,0-2365,0. A média da idade gestacional pós-menstrual no momento do diagnóstico foi de 32,92 ± 7,921 semanas. 17 pacientes haviam recebido um curso anterior de antibióticos por suspeita de sepse precoce. O sinal clínico mais frequentemente observado foi deterioração do estado geral em 11 pacientes, seguido por distensão abdominal em 6 e febre em 5. Dentre os SCoN, o mais isolado foi o Staphylococcus Epidermidis (13 pacientes). 22 pacientes receberam tratamento, 18 deles com Vancomicina-Meropenem e 4 com Vancomicina em monoterapia. Conclusão: esses patógenos representam uma importante causa de morbimortalidade na unidade neonatal, principalmente em pacientes com maior gravidade e maior necessidade de suporte de vida. Orientações claras são necessárias para interpretar o papel desses microrganismos e para abordar pacientes com risco de sepse tardia, incluindo tratamento com antibióticos.

Monitorización de concentraciones plasmáticas de vancomicina en pacientes críticos de un hospital público de Córdoba, Argentina / Monitoring of plasma vancomycin concentrations in critically ill patients in a public hospital of Córdoba, Argentina

Introducción: La monitorización de las concentraciones plasmáticas de antimicrobianos utilizados para tratar infecciones en pacientes críticos es una de las estrategias propuestas para mejorar los resultados clínicos. La monitorización de vancomicina reduce el riesgo de resistencia bacteriana y de nefrotoxicidad relacionada con altas concentraciones plasmáticas. El estudio fue realizado en un hospital público de la provincia de Córdoba, Argentina, que contiene 43 unidades críticas de atención al paciente. Aunque la indicación de vancomicina es frecuente, la solicitud de niveles plasmáticos de fármacos es inusualMétodo: El Servicio de Farmacia realizó un estudio piloto prospectivo durante 14 semanas, implementando el monitoreo de las concentraciones plasmáticas de vancomicina y el cálculo del índice ABC24/CIM (área bajo la curva de concentración-tiempo durante un período de 24 horas/concentración inhibitoria mínima).Objetivos: Determinar el porcentaje de pacientes con concentraciones plasmáticas valle fuera del rango terapéutico descrito en la literatura y la dosis que sería necesaria para obtener un ABC24/CIM ≥400.Resultados: Se realizaron 36 solicitudes de monitorización de vancomicina en 31 pacientes. El 78% de las concentraciones plasmáticas determinadas estaban fuera del rango terapéutico y sólo en 8 pacientes se obtuvo un ABC24/CIM ≥400.Conclusiones: Este estudio fue el primer paso para implementar la farmacocinética clínica en la institución y evidenció la importancia de la monitorización terapéutica y la individualización de la dosis. En pacientes críticos y con un aclaramiento de creatinina elevado se necesitarían dosis mayores a las utilizadas en este estudio. (AU)

Introduction: Monitoring plasma concentrations of antimicrobials used to treat infections in critically ill patients is one of the strategies proposed to improve clinical results. Vancomycin monitoring reduces the risk of bacterial resistance and nephrotoxicity related to high plasma concentrations. The study was carried out in a public hospital in the province of Córdoba, Argentina, which contains 43 critical patient care units. Although the indication for vancomycin is frequent, the request for plasma levels of drugs is unusual.Method: The Pharmacy Service carried out a prospective pilot study for 14 weeks, implementing the monitoring of plasma vancomycin concentrations and the calculation of the ABC24/MIC index (area under the concentration-time curve over a 24-hour period/inhibitory concentration minimum).Objectives: To determine the percentage of patients with trough plasma concentrations outside the therapeutic range described in the literature and the dose that would be necessary to obtain an ABC24/CIM ≥400.Results: 36 requests for vancomycin monitoring were made in 31 patients. 78% of the determined plasma concentrations were outside the therapeutic range and only in 8 patients was an ABC24/CIM ≥400 obtained.Conclusions: This study was the first step to implement clinical pharmacokinetics in the institution and showed the importance of therapeutic monitoring and dose individualization. In critically ill patients with high creatinine clearance, higher doses than those used in this study would be required. (AU)

Impacto del monitoreo terapéutico de vancomicina y amikacina en la optimización de dosis de antimicrobianos en pacientes pediátricos / Impact of the vancomycin and amikacin therapeutic monitoring in the optimization of antimicrobial dose in pediatric patients

INTRODUCCIÓN: La monitorización de antimicrobianos mediante sus concentraciones plasmáticas permite determinar la posología óptima de éstos, conducta esencial en pediatría. OBJETIVOS: Describir la monitorización de concentraciones plasmáticas de antimicrobianos y el ajuste de dosis en población pediátrica para determinar si las dosis utilizadas alcanzan rangos terapéuticos. PACIENTES Y MÉTODOS: Estudio descriptivo, retrospectivo, utilizando una base de datos con medición de concentraciones plasmáticas de amikacina y vancomicina en pacientes pediátricos del Hospital San Borja Arriarán, entre 2015-2018. Se determinó el número de pacientes que alcanzó rango terapéutico con dosis inicial, cuántos requirieron ajuste y sus características. RESULTADOS: Se monitorizó 104 concentraciones totales. Para vancomicina 65 concentraciones plasmáticas eran basales encontrándose fuera de rango terapéutico 56,5%; de los que requirieron ajuste, 25% fueron neonatos con mayor probabilidad de estar fuera de rango versus otros (p = 0,022). Para amikacina la Cpeak estuvo en rango en 60% de mediciones; 15,4% requirió ajuste incluyendo pacientes con fibrosis quística y oncológicos. No fue necesario efectuar ajustes en pacientes sin co-morbilidad. CONCLUSIÓN: La medición de concentraciones plasmáticas es necesaria para ajustar de forma individualizada la dosis, especialmente en pacientes pediátricos con fibrosis quística, oncológicos y en neonatología, donde es más probable no alcanzar rango terapéutico con las dosis iniciales.

BACKGROUND: The monitoring of antimicrobial therapy through plasma levels makes it possible to determine the optimal dosage of antimicrobials, an essential approach in pediatrics. AIM: To describe the monitoring of plasma antimicrobial levels and dose adjustment in the pediatric population to determine if the doses used reach therapeutic ranges. METHODS: Retrospective, descriptive study using a database with measurement of plasma levels of amikacin and vancomycin in pediatric patients at San Borja Arriarán Hospital between 2015-2018. The number of patients who reached the therapeutic range with the initial dose, how many required adjustment and their characteristics were determined. RESULTS: 104 total levels were monitored. For vancomycin 65 plasmatic levels were baseline, being outside the therapeutic range 56.5%; 25% of those requiring adjustment were neonates with a higher probability of being out of range versus others (p = 0.022). For amikacin, Cpeak was in range in 60% of measurements; 15.4% required adjustment, including patients with cystic fibrosis and cancer, without adjustments in patients without comorbidity. CONCLUSION: Measurement of plasma levels is necessary to individually adjust the dose, especially in pediatric patients with cystic fibrosis, oncology and in neonatology where it is more likely not to reach a therapeutic range with initial doses.

Bacteriemia por Leuconostoc spp: Descripción de un caso / A case of bacteremia caused by Leuconostoc spp

Leuconostoc spp es una bacteria tipo coco gram-positivo; recientemente se ha demostrado su potencial patógeno, sobre todo en pacientes inmunodeprimidos y con factores de riesgo como la patología oncológica. Dentro de los cuadros clínicos que pueden producir destacan: neumonía, meningitis, endocarditis o bacteriemia, siendo estas últimas las más frecuentes. Cabe destacar su resistencia intrínseca al tratamiento con vancomicina, siendo el tratamiento de elección en estos casos la penicilina y otros fármacos pertenecientes al grupo de los beta-lactámicos. (AU)

Leuconostoc spp is a gram-positive bacterium which pathogenic potential has been recently demonstrated, especially in immunocompromised patients and in those with risk factors la oncologic diseases. It can cause infections presented as pneumonia, meningitis, endocarditis or bacteremia, being the last two the most frequent ones. It can be highlighted its intrinsic resistance to vancomycin, which makes penicillin and other beta-lactam antibiotics the first treatment options. (AU)