Pseudomonas aeruginosa in the ICU: prevalence, resistance profile, and antimicrobial consumption

Abstract INTRODUCTION: Pseudomonas aeruginosa is one of the main pathogens causing infection in intensive care units (ICUs) and usually presents antimicrobial resistance. METHODS: Data were obtained from ICUs between 2010 and 2013. RESULTS: P. aeruginosa had a prevalence of 14.5% of which 48.7% were multidrug resistant. We observed increasing resistance to carbapenems and polymyxin B and growing consumption of aminoglycosides, meropenem, ceftazidime, and polymyxin B. The regression impact between resistance and consumption was significant with respect to amikacin, imipenem, meropenem, and polymyxin B. CONCLUSIONS: Monitoring antimicrobial consumption and resistant microorganisms should be reinforced to combat antimicrobial- and multi-drug resistance.

Pseudomonas aeruginosa in the ICU: prevalence, resistance profile, and antimicrobial consumption.

INTRODUCTION: Pseudomonas aeruginosa is one of the main pathogens causing infection in intensive care units (ICUs) and usually presents antimicrobial resistance. METHODS: Data were obtained from ICUs between 2010 and 2013. RESULTS: P. aeruginosa had a prevalence of 14.5% of which 48.7% were multidrug resistant. We observed increasing resistance to carbapenems and polymyxin B and growing consumption of aminoglycosides, meropenem, ceftazidime, and polymyxin B. The regression impact between resistance and consumption was significant with respect to amikacin, imipenem, meropenem, and polymyxin B. CONCLUSIONS: Monitoring antimicrobial consumption and resistant microorganisms should be reinforced to combat antimicrobial- and multi-drug resistance.

Pharmacokinetics of hydroxymethylnitrofurazone, a promising new prodrug for Chagas' disease treatment.

Hydroxymethylnitrofurazone (NFOH) is a trypanocidal prodrug of nitrofurazone (NF), devoid of mutagenic toxicity. The purpose of this work was to study the chemical conversion of NFOH into NF in sodium acetate buffer (pH 1.2 and 7.4) and in human plasma and to determine preclinical pharmacokinetic parameters in rats. At pH 1.2, the NFOH was totally transformed into NF, the parent drug, after 48 h, while at pH 7.4, after the same period, the hydrolysis rate was 20%. In human plasma, 50% of NFOH was hydrolyzed after 24 h. In the investigation of kinetic disposition, the concentration of drug in serum versus time curve was used to calculate the pharmacokinetic parameters after a single-dose regimen. NFOH showed a time to maximum concentration of drug in serum (Tmax) as 1 h, suggesting faster absorption than NF (4 h). The most important results observed were the volume of distribution (V) of NFOH through the tissues, which showed a rate that is 20-fold higher (337.5 liters/kg of body weight) than that of NF (17.64 liters/kg), and the concentration of NF obtained by in vivo metabolism of NFOH, which was about four times lower (maximum concentration of drug in serum [Cmax] = 0.83 µg/ml; area under the concentration-time curve from 0 to 12 h [AUC0-12] = 5.683 µg/ml · h) than observed for administered NF (Cmax = 2.78 µg/ml; AUC0-12 = 54.49 µg/ml · h). These findings can explain the superior activity and lower toxicity of the prodrug NFOH in relation to its parent drug and confirm NFOH as a promising anti-Chagas' disease drug candidate.

Prescrição de antibióticos a crianças atendidas no inverno em Unidade de Saúde de município paulista / Prescription of antibiotics to children in winter at a basic health unit in the state of São Paulo, Brazil

Estudos de utilização de medicamentos podem contribuir para a antibioticoterapia racional, por revelarem perfis de utilização, possíveis distorções e necessidades de intervenção. O objetivo deste trabalho foi avaliar as características das prescrições médicas de antibióticos na terapêutica de crianças de 0 a 5 anos de idade de Unidade de Saúde de Santa Bárbara d’Oeste-SP, no inverno. O estudo de delineamento transversal foi conduzido entre julho e agosto de 2008. Das 262 prescrições emitidas no período, 173 (66%) apresentaram pelo menos um antibiótico. Entre estas, identificou-se a média de 2,9 medicamentos prescritos por receita, 93% sob denominação genérica e 96% constantes na Relação Municipal de Medicamentos Essenciais. A amidalite foi a causa mais frequente de indicação de antibióticos, seguida de otite e bronquite. O fármaco mais prescrito foi a amoxicilina, exceto para doenças de pele, feridas auriculares e gastroenterocolite. Em 25% das prescrições houve associação de antibióticos, sendo 81% amoxicilina associada à penicilina benzatina potássica. A amoxicilina foi prescrita em doses diárias acima do recomendado pelos Guideliness em 63,5% das prescrições e frequentemente em conjunto com o ambroxol. A alta prevalência do emprego conjunto de fármacos de mesma classe terapêutica e o elevado número de vezes em que houve sobredose nas prescrições pode ser prejudicial à saúde das crianças.

Studies on medication use can contribute to rational antibiotic therapy, revealing use patterns, possible distortions and the need for interventions. The aim of the present study was to evaluate the use of antibiotic therapy for children aged 0 to five years at a basic health unit in the city of Santa Barbara d’Oeste (state of São Paulo, Brazil) based on prescriptions made in winter. A cross-sectional study was conducted between July and August 2008. From a total of 262 prescriptions issued in the period, 173 (66%) had at least one prescription of antibiotics. The mean number of drugs prescribed per prescription was 2.9. A total of 93% of the drugs were prescribed under the generic denomination and 96% were included on the Municipal Essential Drugs List. Tonsillitis was the most frequent indication for antibiotics, followed by otitis and bronchitis. The most prescribed drug was amoxicillin, except for skin diseases, ear injuries and gastroenterocolitis. Antibiotics were prescribed in association in 25% of the prescriptions and amoxicillin was associated with potassium benzathine penicillin in 81% of such cases. Amoxicillin was prescribed in excessive doses in 63.5% of prescriptions and often together with the ambroxol. The high frequency of joint drug prescriptions from the same therapeutic class and the large number of times in which an excessive dose was prescribed constitute a risk to child health.

Advances in prodrug design.

The background of prodrug design is presented herein as the basis for introducing new and advanced latent systems, taking into account mainly the versatility of polymers and other macromolecules as carriers. PDEPT (Polymer-Directed Enzyme Prodrug Therapy); PELT (Polymer-Enzyme Liposome Therapy); CDS (Chemical Delivery System); ADEPT(Antibody-Directed Enzyme Prodrug Therapy); GDEPT/VDEPT (Gene-Directed Enzyme Prodrug Therapy/Virus-Directed Enzyme Prodrug Therapy); ODDS (Osteotropic Drug Delivery System) and LEAPT (Lectin-directed enzyme-activated prodrug therapy) are briefly described and some examples are given.