Amikacin for the treatment of carbapenem-resistant Klebsiella pneumoniae infections: clinical efficacy and toxicity.

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients' 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 µg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P < 0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P < 0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.

Malformações congênitas: principais etiologias conhecidas, impacto populacional e necessidade de monitoramento / Birth defects: main known etiologies, population impact and the need for monitoring

OBJETIVOS: Este artigo tem por objetivo revisar as causas, o impacto dos defeitos congênitos na morbimortalidade infantil e a importância da sua vigilância, bem como apresentar como nossa comunidade acadêmica está inserida neste monitoramento. MÉTODOS: Foi realizada uma revisão da literatura nas bases de dados Medline/PubMed e Scielo, incluindo publicações de janeiro de 2010 até maio de 2018, em português e inglês. As palavras-chave utilizadas foram: "birth defects", "etiology", "infant mortality", "teratogens", "congenital abnormalities", "defeitos congênitos", "ECLAMC", "genética". Foram incluídos também livros-textos e artigos relevantes na área, independente da data de publicação, assim como sites eletrônicos de relevância. Adicionalmente, descrevemos o funcionamento do programa de monitoramento de defeitos congênitos do Hospital São Lucas da PUCRS, vinculado ao Estudo Colaborativo Latino Americano de Malformações Congênitas (ECLAMC). RESULTADOS: 971 artigos foram localizados com as combinações das palavras-chave, destes 21 foram utilizados na revisão. No conteúdo da revisão incluímos as etiologias conhecidas dos defeitos congênitos, dentre elas, estão as genéticas, multifatoriais e teratógenos físicos, químicos e biológicos. Esses dados estão resumidos das tabelas 1 a 5 deste artigo. Com relação ao monitoramento de defeitos congênitos, o ECLAMC- PUCRS avaliou 3981 recém-nascidos no período de agosto de 2016 a dezembro de 2017, e a taxa observada de malformações foi de 3,77%. CONCLUSÃO: Os defeitos congênitos são uma causa importante de morbimortalidade em todos os países, inclusive no Brasil. A compreensão de suas etiologias contribui para o aconselhamento genético das famílias, para o estabelecimento do prognóstico e intervenções terapêuticas, assim como para sua prevenção.

OBJECTIVE: This article aims to review the impact of birth defects on infant morbidity and mortality and the importance of their surveillance, to review their causes, as well as to show how our academic community is included in this monitoring. METHODS: a literature review was conducted in the Medline / PubMed and Scielo databases, including publications from January 2010 to May 2018, in Portuguese and English. The keywords used were: "birth defects", "etiology", "infant mortality", "teratogens", "congenital abnormalities", "congenital defects", "ECLAMC", "genetics". Also included were textbooks and relevant articles in the area, regardless the date of publication, as well as relevant electronic sites. Additionally, we describe the operation of the congenital defect monitoring program of the São Lucas Hospital of PUCRS, linked to the Latin American Collaborative Study of Congenital Malformations (ECLAMC). RESULTS: 971 articles were found using the keywords, from those 21 were used in the review. In the content of the review we include the known etiologies of the congenital defects, among which are the genetic, multifactorial, and physical, chemical and biological teratogens. These data are summarized in Tables 1-5 of this article. With regard to the monitoring of congenital defects, ECLAMC-PUCRS evaluated 3981 newborns from August 2016 to December 2017, and the observed malformation rate was 3.77%. CONCLUSION: Congenital defects are an important cause of morbidity and mortality in all countries, including Brazil. Understanding their etiologies contributes to the genetic counseling of families, to the establishment of prognosis and therapeutic interventions, as well as to their prevention.