Adjunctive daptomycin attenuates brain damage and hearing loss more efficiently than rifampin in infant rat pneumococcal meningitis

Exacerbation of cerebrospinal fluid (CSF) inflammation in response to bacteriolysis by beta-lactam antibiotics contributes to brain damage and neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic acting on Gram-positive bacteria, lessens inflammation and brain injury compared to ceftriaxone. With a view to a clinical application for pediatric bacterial meningitis, we investigated the effect of combining daptomycin or rifampin with ceftriaxone in an infant rat pneumococcal meningitis model. Eleven-day-old Wistar rats with pneumococcal meningitis were randomized to treatment starting at 18 h after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed 15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22 h after the initiation of therapy and was assessed for concentrations of defined chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h after infection and hearing loss was assessed at 3 weeks after infection. Daptomycin plus ceftriaxone versus ceftriaxone significantly (P < 0.04) lowered CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and interleukin 6 (IL-6) at 6 h and MIP-1α, IL-6, and IL-10 at 22 h after initiation of therapy, led to significantly (P < 0.01) less apoptosis, and significantly (P < 0.01) improved hearing capacity. While rifampin plus ceftriaxone versus ceftriaxone also led to lower CSF inflammation (P < 0.02 for IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity. Adjuvant daptomycin could therefore offer added benefits for the treatment of pediatric pneumococcal meningitis.

Heteroresistance to penicillin in Streptococcus pneumoniae

Heteroresistance to beta-lactam antibiotics has been mainly described for staphylococci, for which it complicates diagnostic procedures and therapeutic success. This study investigated whether heteroresistance to penicillin exists in Streptococcus pneumoniae. Population analysis profile (PAP) showed the presence of subpopulations with higher penicillin resistance in four of nine clinical pneumococcal strains obtained from a local surveillance program (representing the multiresistant clones ST179, ST276, and ST344) and in seven of 16 reference strains (representing the international clones Spain(23F)-1, Spain(9V)-3, Spain(14)-5, Hungary(19A)-6, South Africa(19A)-13, Taiwan(23F)-15, and Finland(6B)-12). Heteroresistant strains had penicillin minimal inhibitory concentrations (MICs) (for the majority of cells) in the intermediate- to high-level range (0.19-2.0 mug/ml). PAP curves suggested the presence of subpopulations also for the highly penicillin-resistant strains Taiwan(19F)-14, Poland(23F)-16, CSR(19A)-11, and CSR(14)-10. PAP of bacterial subpopulations with higher penicillin resistance showed a shift toward higher penicillin-resistance levels, which reverted upon multiple passages on antibiotic-free media. Convergence to a homotypic resistance phenotype did not occur. Comparison of two strains of clone ST179 showed a correlation between the heteroresistant phenotype and a higher-penicillin MIC and a greater number of altered penicillin-binding proteins (PBP1a, -2b, and -2x), respectively. Therefore, heteroresistance to penicillin occurs in international multiresistant clones of S. pneumoniae. Pneumococci may use heteroresistance to penicillin as a tool during their evolution to high penicillin resistance, because it gives the bacteria an opportunity to explore growth in the presence of antibiotics before acquisition of resistance genes.

New therapies for pneumococcal meningitis

The treatment of pneumococcal meningitis remains a major challenge, as reflected by the continued high morbidity and case fatality of the disease. The worldwide increase of penicillin-resistant pneumococci and more recently cephalosporin- and vancomycin-tolerant pneumococci has jeopardised the efficacy of standard treatments based on extended spectrum cephalosporins alone or in combination with vancomycin. This review provides a summary of newly developed antibiotics tested in the rabbit meningitis model. In particular, newer beta-lactam monotherapies (cefepime, meropenem, ertapenem), recently developed quinolones (garenoxacin, gemifloxacin, gatifloxacin, moxifloxacin) and a lipopeptide antibiotic (daptomycin) are discussed. A special emphasis is placed on the potential role of combination treatments with some of the new compounds, which are of interest based on the background of increasing resistance problems due to their often synergistic activity in the rabbit model of pneumococcal meningitis.

Once daily dosing of netilmicin in neonatal and pediatric intensive care

OBJECTIVE: To examine a once daily dosing regimen of netilmicin in critically ill neonates and children. DESIGN AND SETTING: Open, prospective study on 81 antibiotic courses in 77 critically ill neonates and children, hospitalized in a multidisciplinary pediatric/neonatal intensive care unit. For combined empiric therapy (aminoglycoside and beta-lactam), netilmicin was given intravenously over 5 min once every 24 h. The dose ranged from 3.5-6 mg/kg, mainly depending upon gestational and postnatal age. Peak levels were determined by immunoassay 30 min after the second dose and trough levels 1 h before the third and fifth dose or after adaptation of dosing. RESULTS: All peak levels (n = 28) were clearly above 12 mumol/l (mean 22, range 13-41 mumol/l). Eighty-nine trough levels were within desired limits (< 4 mumol/l) and 11 (11%) above 4 mumol/l, mostly in conjunction with impaired renal function. CONCLUSIONS: Optimal peak and trough levels of netilmicin can be achieved by once daily dosing, adapted to gestational/postnatal age and renal function.

Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter.

The presence of a proton-coupled electrogenic high-affinity peptide transporter in the apical membrane of tubular cells has been demonstrated by microperfusion studies and by use of brush border membrane vesicles. The transporter mediates tubular uptake of filtered di- and tripeptides and aminocephalosporin antibiotics. We have used expression cloning in Xenopus laevis oocytes for identification and characterization of the renal high-affinity peptide transporter. Injection of poly(A)+ RNA isolated from rabbit kidney cortex into oocytes resulted in expression of a pH-dependent transport activity for the aminocephalosporin antibiotic cefadroxil. After size fractionation of poly(A)+ RNA the transport activity was identified in the 3.0- to 5.0-kb fractions, which were used for construction of a cDNA library. The library was screened for expression of cefadroxil transport after injection of complementary RNA synthesized in vitro from different pools of clones. A single clone (rPepT2) was isolated that stimulated cefadroxil uptake into oocytes approximately 70-fold at a pH of 6.0. Kinetic analysis of cefadroxil uptake expressed by the transporter's complementary RNA showed a single saturable high-affinity transport system shared by dipeptides, tripeptides, and selected amino-beta-lactam antibiotics. Electrophysiological studies established that the transport activity is electrogenic and affected by membrane potential. Sequencing of the cDNA predicts a protein of 729 amino acids with 12 membrane-spanning domains. Although there is a significant amino acid sequence identity (47%) to the recently cloned peptide transporters from rabbit and human small intestine, the renal transporter shows distinct structural and functional differences.

Cefepime versus cefpirome: The importance of creatinine clearance

Standard dosage recommendations for beta-lactam antibiotics can result in very low drug levels in intensive care (IC) patients without renal dysfunction. We compared the pharmacokinetics of two fourth-generation cephalosporins, cefepime and cefpirome, and examined the relationship of drug clearance (CL) to creatinine clearance (CLCR). Two separate but similar pharmacokinetic studies (which used 2 g twice daily for each antibiotic) were conducted. Blood was sampled after an initial and a subsequent antibiotic dose. Drug plasma concentrations were measured, and pharmacokinetic analyses were conducted and compared. The pharmacokinetics of cefepime and cefpirome are similar in IC patients. Any differences in drug CL can largely be attributed to differences in CLCR. Despite normal plasma creatinine concentrations, 54% of patients' antibiotic concentrations were less than the minimum inhibitory concentration (MIC) (4 mg/L) for >20% of the dosing interval. Thirty-four percent of patients had CLCR >144 mL/min (20% higher than the expected maximum of 120 mL/min). Only CLCR was an independent predictor of antibiotic CL. Time above MIC was predicted only by CLCR. Some IC patients have a very large CLCR which results in very low levels of studied antibiotics. Either shortening the dosage interval or using continuous infusions would prevent low levels and keep troughs above the MIC for longer periods. In view of the lack of bedside measurement of cephalosporin levels, we suggest that more frequent use be made of CLCR to allow prediction of small concentrations clinically.

Vancomycin use in a brazilian teaching hospital: comparison with the Hospital Infection Controlpractices Advisory Committee Guidelines (HICPAC)

This study describes vancomycin prescribing patterns in an average complexity hospital and compare the guidelines proposed by the Hospital Infection Control Practices Advisory Committee (HICPAC). The study was conducted in a 256-bed secondary-care hospital. Data were collected of all patients given vancomycin from March 2003 to February 2004, using a standardized chart-extraction form designed. Appropriate and inappropriate use was reviewed according to the Hospital Infection Control Practices Advisory Committee (HICPAC) guidelines on prudent vancomycin use. Out of 118 prescriptions, 95 (80.5%) were considered appropriate. Out of these 95 orders, 77 (81.1%) were administered for empiric treatment of suspected Gram-positive infections, 17 (17.9%) were administered for treatment of proven Gram-positive infections (76.5% identified as Staphyloccocus aureus-like agents) and 1 (1.0%) for beta-lactam allergy. The majority of the patients (96.6%) had recently used an antimicrobial medication (3 months). The mean pre-treatment hospitalization period was 11±10 days. Out of the 118 treatments, 67 (56.8%) were for nosocomial infections. The more frequent indications for vancomycin use were pneumonia (48.3%) and primary sepsis (18.6%), accounting for more than 66% of all treatments. No restriction policy was suggested because vancomycin use was considered adequate in the majority of the treatment cases. The broad empiric use of this antimicrobial was greater than expected in the institution and its use should be revised.

The Penicillium chrysogenum aclA gene encodes a broad-substrate-specificity acyl-coenzyme A ligase involved in activation of adipic acid, a side-chain precursor for cephem antibiotics

Activation of the cephalosporin side-chain precursor to the corresponding CoA-thioester is an essential step for its incorporation into the P-lactam backbone. To identify an acyl-CoA ligase involved in activation of adipate, we searched in the genome database of Penicillium chrysogenum for putative structural genes encoding acyl-CoA ligases. Chemostat-based transcriptome analysis was used to identify the one presenting the highest expression level when cells were grown in the presence of adipate. Deletion of the gene renamed aclA, led to a 32% decreased specific rate of adipate consumption and a threefold reduction of adipoyl-6-aminopenicillanic acid levels, but did not affect penicillin V production. After overexpression in Escherichia coli, the purified protein was shown to have a broad substrate range including adipate. Finally, protein-fusion with cyan-fluorescent protein showed co-localization with microbody-borne acyl-transferase. Identification and functional characterization of aclA may aid in developing future metabolic engineering strategies for improving the production of different cephalosporins. (C) 2009 Elsevier Inc. All rights reserved.

Influence of Pluronic (R) F68 on Ceftazidime Biological Activity in Parenteral Solutions

beta-Lactam antimicrobials are known to have a low concentration/therapeutic response. However, extending the period in which beta-lactam are free in the plasma does directly influence therapeutic outcomes. The objective of this study was to evaluate the influence of Pluronic (R) F68 on the antimicrobial activity of ceftazidime when admixed with aminophylline in parenteral solutions by the evaluation of its minimal inhibitory concentration (MIC) within 24 h. Ceftazidime, aminophylline, and Pluronics (R) F68 were evaluated using the MIC method against Escherichia coli and Pseudomonas aeruginosa, with these compounds individually and associated in the same parenteral solutions. When Pluronics (R) F68 was admixtured with ceftazidime alone or with ceftazidime and aminophylline, it was possible to observe lower MIC values not only at 24 h but also at 0 h for both microorganisms. This indicates that Pluronics (R) F68 may be able to enhance ceftazidime antimicrobial activity in the presence or absence of aminophylline. This fact suggests that Pluronics (R) F68 can be applied to allow the administration of ceftazidime under continuous infusion in parenteral solutions, beneficiating hospital pharmacotherapy. It may also be possible to reduce ceftazidime doses in formulations achieving the same therapeutic results. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:715-720, 2011

Avaliação da qualidade do leite e caracterização de laticínios do estado do Espírito Santo

O leite é um alimento de grande importância na alimentação humana e amplamente consumido. Desta forma, justifica-se o estudo de suas características e a avaliação de procedimentos higiênicos durante toda a sua cadeia produtiva, desde a ordenha até o seu processamento. O objetivo do trabalho foi caracterizar laticínios localizados no estado do Espírito Santo, bem como avaliar as características de qualidade do leite cru e do leite pasteurizado de quatro estabelecimentos. O estudo foi dividido em quatro etapas: 1) seleção de dois laticínios com Selo de Inspeção Federal (SIF) e dois laticínios com Selo de Inspeção Estadual (SIE); 2) Elaboração de questionário para coleta de dados; 3) coleta de amostras de leite cru refrigerado e leite pasteurizado nos laticínios selecionados e avaliação da qualidade da matéria-prima e; 4) caracterização dos quatro laticínios e avaliação das condições higiênico-sanitárias dos estabelecimentos (aplicação questionário elaborado e da Lista de Verificação de Boas Práticas de Fabricação - check-list – presente na RDC nº 275 / 2002 da Anvisa).Os resultados obtidos com as análises de composição centesimal, acidez titulável, pH e Contagem de Células Somáticas (CCS) das amostras dos laticínios SIF 1, SIF 2, SIE 1 e SIE 2 indicaram conformidade com o padrão exigido pela Instrução Normativa nº 62/2011 do MAPA. Com relação ao teste do alizarol, todas as amostras analisadas apresentaram coloração parda avermelhada sem coagulação, indicando conformidade com a exigência da legislação. Para o teste de detecção de antibiótico da classe β-lactâmicos, todas as amostras de leite dos quatro laticínios analisadas nas três coletas tiveram ausência pelo método utilizado. Em uma das amostras coletadas da indústria SIF 1 foi verificada a presença da enzima fosfatase alcalina em leite pasteurizado, indicando que o tratamento térmico não foi adequado e que, portanto, poderia haver presença de microrganismos patogênicos na amostra, ou que a enzima se renaturou, apresentando um resultado falso positivo para o teste. Além disso, foi verificado que duas amostras de leite coletadas do laticínio SIE 1 apresentaram ausência da enzima lactoperoxidase,O leite é um alimento de grande importância na alimentação humana e amplamente consumido. Desta forma, justifica-se o estudo de suas características e a avaliação de procedimentos higiênicos durante toda a sua cadeia produtiva, desde a ordenha até o seu processamento. O objetivo do trabalho foi caracterizar laticínios localizados no estado do Espírito Santo, bem como avaliar as características de qualidade do leite cru e do leite pasteurizado de quatro estabelecimentos. O estudo foi dividido em quatro etapas: 1) seleção de dois laticínios com Selo de Inspeção Federal (SIF) e dois laticínios com Selo de Inspeção Estadual (SIE); 2) Elaboração de questionário para coleta de dados; 3) coleta de amostras de leite cru refrigerado e leite pasteurizado nos laticínios selecionados e avaliação da qualidade da matéria-prima e; 4) caracterização dos quatro laticínios e avaliação das condições higiênico-sanitárias dos estabelecimentos (aplicação questionário elaborado e da Lista de Verificação de Boas Práticas de Fabricação - check-list – presente na RDC nº 275 / 2002 da Anvisa).Os resultados obtidos com as análises de composição centesimal, acidez titulável, pH e Contagem de Células Somáticas (CCS) das amostras dos laticínios SIF 1, SIF 2, SIE 1 e SIE 2 indicaram conformidade com o padrão exigido pela Instrução Normativa nº 62/2011 do MAPA. Com relação ao teste do alizarol, todas as amostras analisadas apresentaram coloração parda avermelhada sem coagulação, indicando conformidade com a exigência da legislação. Para o teste de detecção de antibiótico da classe β-lactâmicos, todas as amostras de leite dos quatro laticínios analisadas nas três coletas tiveram ausência pelo método utilizado. Em uma das amostras coletadas da indústria SIF 1 foi verificada a presença da enzima fosfatase alcalina em leite pasteurizado, indicando que o tratamento térmico não foi adequado e que, portanto, poderia haver presença de microrganismos patogênicos na amostra, ou que a enzima se renaturou, apresentando um resultado falso positivo para o teste. Além disso, foi verificado que duas amostras de leite coletadas do laticínio SIE 1 apresentaram ausência da enzima lactoperoxidase,O leite é um alimento de grande importância na alimentação humana e amplamente consumido. Desta forma, justifica-se o estudo de suas características e a avaliação de procedimentos higiênicos durante toda a sua cadeia produtiva, desde a ordenha até o seu processamento. O objetivo do trabalho foi caracterizar laticínios localizados no estado do Espírito Santo, bem como avaliar as características de qualidade do leite cru e do leite pasteurizado de quatro estabelecimentos. O estudo foi dividido em quatro etapas: 1) seleção de dois laticínios com Selo de Inspeção Federal (SIF) e dois laticínios com Selo de Inspeção Estadual (SIE); 2) Elaboração de questionário para coleta de dados; 3) coleta de amostras de leite cru refrigerado e leite pasteurizado nos laticínios selecionados e avaliação da qualidade da matéria-prima e; 4) caracterização dos quatro laticínios e avaliação das condições higiênico-sanitárias dos estabelecimentos (aplicação questionário elaborado e da Lista de Verificação de Boas Práticas de Fabricação - check-list – presente na RDC nº 275 / 2002 da Anvisa).Os resultados obtidos com as análises de composição centesimal, acidez titulável, pH e Contagem de Células Somáticas (CCS) das amostras dos laticínios SIF 1, SIF 2, SIE 1 e SIE 2 indicaram conformidade com o padrão exigido pela Instrução Normativa nº 62/2011 do MAPA. Com relação ao teste do alizarol, todas as amostras analisadas apresentaram coloração parda avermelhada sem coagulação, indicando conformidade com a exigência da legislação. Para o teste de detecção de antibiótico da classe β-lactâmicos, todas as amostras de leite dos quatro laticínios analisadas nas três coletas tiveram ausência pelo método utilizado. Em uma das amostras coletadas da indústria SIF 1 foi verificada a presença da enzima fosfatase alcalina em leite pasteurizado, indicando que o tratamento térmico não foi adequado e que, portanto, poderia haver presença de microrganismos patogênicos na amostra, ou que a enzima se renaturou, apresentando um resultado falso positivo para o teste. Além disso, foi verificado que duas amostras de leite coletadas do laticínio SIE 1 apresentaram ausência da enzima lactoperoxidase,indicando a sua desnaturação devido à superpasteurização do leite. Para as análises microbiológicas de contagem bacteriana total e bactérias psicrotróficas, foi verificado uma contagem acima do estabelecido pela legislação. Além disso, os maiores valores médios de Contagem Bacteriana Total (CBT), contagem de microrganismos psicrotróficos e coliformes totais nas amostras de leite cru refrigerado foram verificados entre os laticínios com SIF, podendo ter como causa o uso de tanques comunitários pelos produtores, tempo de transporte para coleta de leite maior do que a média dos laticínios com SIE, a falta de adoção das Boas Práticas de Ordenha e o maior volume de leite coletado de diferentes produtores. Com relação à CBT e à contagem de coliformes totais em leite pasteurizado, os maiores valores médios foram verificados também nos laticínios SIF 1 e SIF 2. Os laticínios que apresentaram maior porcentagem de adequação aos requisitos das BPF foram os laticínios SIF 1 (87,82 %) e SIF 2 (80,66 %), os quais já possuíam os POP’s (Procedimento Operacional Padronizado), CIP (Controle Integrado de Pragas) e BPF (Boas Práticas de Fabricação) implantados ou em fase final de implantação. A análise dos resultados das análises microbiológicas, da aplicação do check-list e da aplicação do questionário permitiu a conclusão de que as empresas que possuíam SIF, apesar de apresentarem uma maior porcentagem de adequação aos requisitos de boas práticas de fabricação, possuíam uma qualidade da matéria-prima menor do que as indústrias com SIE. A partir dos resultados obtidos, pode-se concluir que o estudo de laticínios no estado do Espírito Santo possibilitou o conhecimento do setor e de seus problemas, contribuindo para o emprego de ações de melhoria e prevenção de futuros problemas.

Resistance to β-lactams in bacteria isolated from different types of Portuguese cheese

The purpose of this study was to investigate the presence of beta-lactam-resistant bacteria in six different types of Portuguese cheese. The numbers of ampicillin resistant (AMP(r)) bacteria varied from 4.7 x 10(2) to 1.5 x 10(7) CFU/g. Within 172 randomly selected beta-lactam-resistant bacteria, 44 resistant phenotypes were found and 31.4% were multidrug resistant. The majority (85%) of the isolates identified belonged to the Enterobacteriaceae family. The presence of the bla(TEM) gene was detected in 80.9% of the tested isolates. The results suggest that without thermal processing of the milk and good hygienic practices, cheese may act as a vehicle of transfer of beta-lactam-resistant bacteria to the gastrointestinal tract of consumers.

Susceptibility of clinical isolates of Bacteroides fragilis group strains to cefoxitin, cefoperazone and ticarcillin/clavulanate

A total of 40 strains of the B. fragilis group was isolated from clinical specimens in two hospital centers in Fortaleza from 1993 to 1997. The most frequently isolated species was Bacteroides fragilis (19 strains) and most isolates came from intra-abdominal and wound infections. The susceptibility profile was traced for cefoxitin, cefoperazone and ticarcillin-clavulanate by using the agar dilution reference method. All isolates were susceptible to ticarcillin-clavulanate (128/2mug/ml). Resistance rates of 15 and 70% were detected to cefoxitin (64mug/ml) and cefoperazone (64mug/ml), respectively. Such regional results permit a better orientation in choosing this group of antibiotics for prophylaxis and therapy especially in relation to cefoxitin, which is frequently used in the hospital centers studied.

Acute generalized exanthematous pustulosis (AGEP). Case report

Acute Generalized Exanthematous Pustulosis (AGEP) is a drug-induced dermatosis characterized by an acute episode of sterile pustules over erythematous-edematous skin. It is accompanied by an episode of fever, which regresses a few days after discontinuation of the drug that caused the condition or as a result of corticosteroid treatment. The main triggering drugs are antibiotics, mainly beta-lactam ones. Other medications, such as antifungal agents, non steroid anti-inflammatory drugs, analgesics, antiarrhythmic, anticonvulsant and antidepressant drugs, may also be responsible. Histologically, it is characterized by the existence of vasculitis, associated with non-follicular subcorneal pustules. A case of a Caucasian female outpatient unit of Dermatology with AGEP, who presented with generalized pustulosis lesions after the use of cephalosporin for urinary infection is related. The diagnosis was confirmed by the clinical and pathological correlations, the resolution of the dermatosis after discontinuation of the drug and use of systemic corticosteroid treatment, and the recurrence of the disorder after the introduction of a similar drug. The importance of the recognition of this drug-induced dermatosis is given by its main differential clinical and histological diagnoses: generalized pustular psoriasis and subcorneal pustulosis.

Development of novel active pharmaceutical ionic liquids and salts based on antibiotics and anti-fungal drugs

Ionic Liquids (ILs) are class of compounds, which have become popular since the mid-1990s. Despite the fact that ILs are defined by one physical property (melting point), many of the potential applications are now related to their biological properties. The use of a drug as a liquid can avoid some problems related to polymorphism which can influence a drug´s solubility and thus its dosages. Also, the arrangement of the anion or cation with a specific drug might be relevant in order to: a) change the correspondent biopharmaceutical drug classification system; b) for the drug formulation process and c) the change the Active Pharmaceutical Ingredients’ (APIs). The main goal of this Thesis is the synthesis and study of physicochemical and biological properties of ILs as APIs from beta-lactam antibiotics (ampicillin, penicillin G and amoxicillin) and from the anti-fungal Amphotericin B. All the APIs used here were neutralized in a buffer appropriate hydroxide cations. The cation hydroxide was obtained on Amberlite resin (in the OH form) in order to exchange halides. The biological studies of these new compounds were made using techniques like the micro dilution and colorimetric methods. Overall a total of 19 new ILs were synthesised (6 ILs based on ampicillin, 4 ILs, based on amoxicillin, 6 ILs based on penicillin G and 4 ILs based on amphotericin B) and characterized by spectroscopic and analytical methods in order to confirm their structure and purity. The study of the biological properties of the synthesised ILs showed that some have antimicrobial activity against bacteria and yeast cells, even in resistant bacteria. Also this work allowed to show that ILs based on ampicillin could be used as anti-tumour agents. This proves that with a careful selection of the organic cation, it is possible to provoke important physico-chemical and biological alteration in the properties of ILs-APIs with great impact, having in mind their applications.