Send Orders for Reprints to reprints@benthamscience.net 3040 Current Topics in Medicinal Chemistry, 2013, 13, 3040-3078 1568-0266/13 $58.00+.00 © 2013 Bentham Science Publishers Native Brazilian Plants Against Nosocomial Infections: A Critical Review on their Potential and the Antimicrobial Methodology Paulo Roberto H. Moreno 1,2,* , Fabiana Inácio da Costa-Issa 1 , Agnieszka K. Rajca-Ferreira 1 , Marcos A. A. Pereira 1 and Telma M. Kaneko 1 1 Programa de Pós-Graduação em Fármacos e Medicamentos, Insumos Farmacêuticos, Faculdade de Ciências Far- macêuticas, USP, C.P. 66083, 05389-970, São Paulo, SP, Brazil; 2 Instituto de Química, Universidade de São Paulo, PO Box 26077, 05513-970, São Paulo, SP, Brazil Abstract: The growing incidences of drug-resistant pathogens have increased the attention on several medicinal plants and their metabolites for antimicrobial properties. These pathogens are the main cause of nosocomial infections which led to an increasing mortality among hospitalized patients. Taking into consideration those factors, this paper reviews the state-of-the-art of the research on antibacterial agents from native Brazilian plant species related to nosocomial infections as well as the current methods used in the investigations of the antimicrobial activity and points out the differences in techniques employed by the authors. The antimicrobial assays most frequently used were broth microdilution, agar diffu- sion, agar dilution and bioautography. The broth microdilution method should be the method of choice for testing new an- timicrobial agents from plant extracts or isolated compounds due to its advantages. At the moment, only a small part of the rich Brazilian flora has been investigated for antimicrobial activity, mostly with unfractionated extracts presenting a weak or moderate antibacterial activity. The combination of crude extract with conventional antibiotics represents a largely unexploited new form of chemotherapy with novel and multiple mechanisms of action that can overcome micro- bial resistance that needs to be further investigated. The antibacterial activity of essential oil vapours might also be an in- teresting alternative treatment of hospital environment due to their ability in preventing biofilm formation. However, in both alternatives more studies should be done on their mode of action and toxicological effects in order to optimize their use. Keywords: Antimicrobial activity, antimicrobial agents, essential oils, native brazilian plants, plant extracts, nosocomial infec- tions, therapy strategies. INTRODUCTION Infectious diseases are caused by germs that kill more people worldwide than any other single death cause. Noso- comial infection, also known as hospital–acquired infection or healthcare-associated infections (HAIs), is one of the main transmissible diseases that are amongst the major causes of the increasing morbidity in hospitalized patients. The most frequent HAIs are surgical wounds, urinary tract and lower respiratory tract infections. According to the Council of the European Union, 8–12% of patients admitted to hospitals in European countries suffer from adverse events while receiving healthcare, being HAIs the most prominent of them [1]. This shows that HAIs are not only a problem for resource-poor regions but also affects economically devel- oped countries [2]. Over the past few years in Europe, nosocomial infections affected 1 out of 10 patients admitted to hospitals and ac- counted for ca. of 5000 deaths/ year with a high cost for the public systems. On average, a patient with HAIs spent 2.5- times longer in hospital, incurring additional treatment costs, *Address correspondence to this author at the Instituto de Química, Univer- sidade de São Paulo, Av. Lineu Prestes 748 B11T 05508 000 São Paulo, SP, Brazil; Tel: +55-11-3091-3875; Fax: +55-11-3815-5579; Email: prmoreno@iq.usp.br in comparison with uninfected patient. Intensive care units (ICU) have the highest prevalence of hospital-acquired infec- tions in the hospital setting. The European Prevalence of Infection in Intensive Care Study (EPIC), involving over 4500 patients, demonstrated that the nosocomial infection prevalence rate in ICU was 20.6%. ICU patients are particu- larly at risk of hospital–acquired infections as a result of me- chanical ventilation, invasive procedures and their immune deficiency [3]. According to WHO Program for the Control of Hospital Infections [4] a prevalence survey in 55 hospitals of 14 countries representing 4 WHO Regions (Europe, East- ern Mediterranean, South-Eastern Asia and Western Pacific) showed an average of 8.7% of hospital patients that con- tracted nosocomial infections. The infection prevalence was higher in Western Pacific, South-Eastern Asia, Eastern Mediterranean regions (9.0%, 10.0%, and 11.8% respec- tively) and the lowest in Europe (7.7%) [5]. Nosocomial infections are caused by bacteria, viruses, fungi and parasites which are acquired from another hospital (cross-contamination), may be caused by the patient's own flora (endogenous infection), from an inanimate object or substance newly infected, or from another human source (environmental infection). The bacteria are the most com- mon causes of nosocomial infections being the predominant pathogens Staphylococcus aureus, Pseudomonas aeruginosa,