Rev Esp Quimioter 2011:24(2):67-73

Pharmaecology  

J. GONZÁLEZ, A. ORERO, V. OLMO, D. MARTÍNEZ, J. PRIETO, J. A. BAHLSEN,  F. ZARAGOZÁ,  J. HONORATO       

 

Two of the main characteristics of western societies in the last fifty years have been the medicalization of the human life and the environmental degradation. The first one has forced human being to consider medicines use related to what would be rational, reasonable and well-reasoned. The second one brought us to a new ecologist conscience.
In relation to the “human social system”, the effects of medication can be considered very positive as a whole, particularly those related to the amazing increase of expectative and quality of life. But, along with those unquestionable beneficial effects, medicines have also caused some negative effects for other biotic and abiotic systems, such as microbian alterations and their undesirable consequences which have involved the massive use of antibiotics in medicine and veterinary, the uncontrolled elimination of millions of doses of all kind of drugs, additives and excipients, etc., as well as atmospheric contamination and degradation of forests and deep oceans which can have been caused by investigation and production of determinated drugs. In this context pharmaecology appears as a scientific discipline that studies the research (R), development (D), production (P), and utilization (U) of drugs and medical substances in relation to the environment. From a farmaecologic perspective the drugs utilization has its development in three main contexts, all of them closely related: prescription quality, farmaceutical care, and patient’s active participation in his own disease and treatment. 

 
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Rev Esp Quimioter 2011:24(4):175-183

Antimycobacterial natural products – an opportunity for the Colombian biodiversity       


J. BUENO, E. D. COY, E. STASHENKO            

It is estimated that one-third part of the world population is infected with the tubercle bacillus. While only a small percentage of infected individuals will develop clinical tuberculosis, each year there are approximately eight million new cases and two million deaths. Mycobacterium tuberculosis is thus responsible for more human mortality than any other single microbial species. The goals of tuberculosis control are focused to cure active disease, prevent relapse, reduce transmission and avert the emergence of drug-resistance. For over 50 years, natural products have served us well on combating infectious bacteria and fungi. During the 20th century, microbial and plant secondary metabolites have helped to double our life span, reduced pain and suffering, and revolutionized medicine. Colombia is a megadiverse country with enormous potential to offer leads for new antimycobacterial drugs. The principal aim of this article is to show a state of the art on antimycobacterial natural products research in Colombia compared to the rest of the world, in order to develop programs for bioprospecting with a view to determining the biological activity for pharmaceutical and industrial application of natural products in our country. 

 
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Rev Esp Quimioter 2011:24(2):74-78

Activity of vancomycin, ciprofloxacin, daptomycin, and linezolid against coagulase-negative staphylococci bacteremia   

M. FAJARDO, R. HIDALGO, S. RODRÍGUEZ, F. F. RODRÍGUEZ-VIDIGAL, A. VERA, M. ROBLES       

 

Objective. Multiresistant coagulase-negative staphylococci (CNS) infections are mainly increased in hospitalized patients. We have studied the activity of vancomycin, ciprofloxacin, daptomycin and linezolid in methicillin-resistant CNS strains, isolated from true blood cultures.
Methods. We collected 87 strains of different CNS species from positive blood cultures. Staphylococci were identified by MicroScan Walkaway (Dade Behring, Siemens) and with the Api ID 32 Staph (BioMerieux, France). The susceptibility to oxacillin, vancomycin and ciprofloxacin was performed by automatic microdilution plate as cited above. The susceptibility to daptomycin and linezolid was performed by Etest (AB BioMerieux, Solna, Sweden). Interpretative criteria were done following the CLSI guidelines.
Results. Eighty-seven CNS strains were studied: 55 (63%) were S. epidermidis, 15 (17%) S. haemolyticus, 10 (12%) S. hominis, and 7 (8%) other species. Fifty-three (61%) strains showed loss of susceptibility to vancomycin, MIC = 2 mg/L. Ciprofloxacin resistance, MIC > 2 mg/L, was observed in 56 (64%) strains. Daptomycin resistance was not observed, with a susceptibility range between 0.032-1 mg/L and modal value of 0.25 mg/L. Ten strains (11.5%) resistant to linezolid were observed. Nine patients were in ICU, where the average length of stay was 38 days (range 16-58 days) and one belonged to Hepato-Pancreatic Surgery, where he stayed for 64 days.
Conclusions. Low susceptibility to vancomycin is frecuent in the CNS strains studied in our hospital. Daptomycin shows a high efficacy against CNS, and it could be useful for the treatment of primary bacteremia or catheter associated bacteremia. The massive and continuous use of linezolid has led to the appearance of resistance. 

 
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Rev Esp Quimioter 2011:24(4):184-190

Bacteroides mobilizable and conjugative genetic elements: antibiotic resistance among clinical isolates          


C. QUESADA-GÓMEZ              

The conjugation is one of the most important mechanisms of horizontal gene transfer in prokaryotes, leading to genetic variation within a species and the acquisition of new traits, such as antibiotic resistance. Bacteroides is an obligate anaerobe of the colon and a significant opportunistic pathogen. Antibiotic resistance among Bacteroides spp. is rapidly increasing, largely due to the dissemination of DNA transfer factors (plasmids and transposons) harbored by members of this genus. Transfer factors can be divided into two classes, conjugative and mobilizable. Species of the intestinal Bacteroides have yielded different resistance plasmids, all of which have been intensely studied, the plasmids encode high-level MLS resistance conferred by a conserved erm gene. It has been reported an interesting observation associated with the transfer of several of these types of elements, all of which conferred Tcr and displayed greatly increased transfer efficiency following exposure to tetracycline. Many of the conjugative transposons (CTns) in Bacteroides are related to various genetic elements (such as CTnDOT, CTnERL, NBU and others). CTnDOT carries a tetracycline resistance gene, tetQ, and an erythromycin resistance gene, ermF. Resistance to drugs used to treat Bacteroides infections, such as clindamycin, has also been increasing. These conjugal elements have been found in Bacteroides clinical isolates. Thus, horizontal gene transfer could conceivably have played a role in the rising incidence of resistance in this bacterial group. 

 
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Rev Esp Quimioter 2011:24(2):79-83

Do general practitioners follow the therapeutical recommendations of cystitis in women?. INURA study   

G.RABANAQUE, A. LÓPEZ, J. M. COTS, C. LLOR       

 

Objective: The management of lower urinary tract infections varies from physician to physician. The aim of this study was to assess whether general practitioners follow the evidence-based guidelines for the management of cystitis in women.
Methods: Cross-sectional study carried out from March to July 2009 in which physicians consecutively registered in a template during a 8-week period the first six episodes of cystitis by means attended at the medical consultation. Age, episode of infection, associated morbidity, antibiotic prescription, and type of antibiotic course (short or long regimen) were determined.
Results: Out of 176 physicians invited to participate, 110 included 658 women with lower urinary tract infections with antibiotic treatment being administered in 634 cases. Short courses were given to 385 women (60.7%) and 249 women were given long schedules (39.3%). A total of 343 out of all noncomplicated cystitis were treated with short courses (62.9%) and 75 out of complicated cystitis were treated with long courses (66.4%). First-choice antibiotics were administered as empiric treatment in only 111 women (17.5%).
Conclusions: These results highlight a poor adherence of general practitioners to current recommendations of clinical practice guidelines in cystitis with a low utilization of first-choice antibiotics. 

 
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Rev Esp Quimioter 2011:24(4):191-197

Outpatient use of topical antimicrobials in Spain associated with other drugs (2005-2007)          


P. MORI, D. MARTÍNEZ, J. BENEIT, E. PACHECO, J. GONZÁLEZ              

Introduction: The consumption of antibiotics for systemic use has been well studied. However, data of topical use in our country are an anecdotal reference in the literature.
Objective: To evaluate the outpatient use of topical antimicrobials in Spain associated with other drugs during the period December 2005 and November 2007.
Methods: A descriptive quantitative study was conducted between December 1, 2005 to November 30, 2007. The sample amounted to a total of 112 drugs, representing 131 dosage forms. The data on consumption of drugs were sold by the company Intercontinental Marketing Services (IMS), while demographic data were obtained from the municipal census of 2006 and 2007. The study variables were grouped into three categories: those relating to consumption, those on medications and other variables such as geographic location and time period.
Results: During the study period the outpatient consumption of topical antimicrobials in Spain was 41.755.951 vials (130.637.368 euros) whose composition included associations between antimicrobials or antimicrobials with other drugs. The average monthly consumption amounted to 1.739.831 vials and 5.443.223 euros. The dermal route of administration was the most dispensed and according to the Anatomical, Therapeutic, Chemical classification system (ATC) and the D07CC subgroup was the most used. The association between tobramycin and dexamethasone ophthalmic suspension as 30% was the drug most used in Spain.
Conclusions: The consumption of topical antimicrobials in Spain during the period 2006-2007 increased by 2.36% in the number of vials and 7.28% in economic cost. These antimicrobials were more used in summer. The average cost of a topical antimicrobial was half (3.13 euros) compared to the average cost of a drug (7.89 euros).group. 

 
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Rev Esp Quimioter 2011:24(2):84-90

Resistance of Streptococcus pneumoniae isolated from Lebanese patients between 2005 and 2009    

Z. DAOUD, M. KOURANI, R. SAAB, M. A. NADER, M. HAJJAR        

 

Introduction: Streptococcus pneumoniae is an important organism in view of its prevalence and ability to cause serious infections; its resistance to antimicrobial agents is increasing worldwide. The purpose of this study was to evaluate the patterns of resistance of S. pneumoniae to penicillin, macrolides and various other antibiotics in strains isolated from Lebanese patients.
Methods: 121 strains isolated between January 2005 and January 2009 from two university hospitals in Beirut were identified and tested for MIC determination using the E-test method. The presence of erm(B) and mef(A/E) genes was investigated using PCR.
Results: The majority of the strains (73.5%) were isolated from respiratory tract infections, 50.4% were isolated in winter, 15.7% were invasive strains, 61.9% came from male patients, and 68.5% from adults. Out of 121 isolates, 58 were susceptible to penicillin, 61 were intermediate, and 2 were fully resistant to this antibiotic. Amoxicillin-clavunanic acid and cefpodoxime showed 100% activity on all tested isolates. In general, the MICs90 appear to fluctuate within the same range over the four years. The erm(B) gene was detected in 85.3% of the isolates, mef(A/E) in 19.5% whereas erm(A) was not detected in any of the macrolide resistant strains.

Discussion: The results of this study have important impact on the empirical antibiotic prescriptions; the increasing prevalence of resistance jeopardises the treatment choices posing a serious threat. Further surveillance and epidemiological serotyping are needed to monitor the local and regional resistance patterns and to track the spread route of resistance.  

 
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Rev Esp Quimioter 2011:24(4):198-203

Treatment of chronic hepatitis C virus infection. A study of best predictors for response          


N. OSPINA, J. L. RODRÍGUEZ, M. HERNÁNDEZ, C. GARCÍA, J. M. MARTÍN, E. REDONDO, L. OLIVIA, M. J. PENA              

Objective: The aim of this study was evaluate the rate of sustained viral response (SVR) and the influence of different factors on the SVR in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon alfa 2a and ribavirin.
Methods: We retrospectively analysed 272 naïve patients with chronic hepatitis C who had been treated for 24 weeks or 48 weeks and had been followed for an additional 6 months thereafter.
Results: Out of 272 patients, 243 completed the entire treatment. The overall SVR rate in intent-to-treat analysis was 66.5% and in treated patients was 74.5%. In an univariate analysis, the SVR was associated with age <40 years (84.4%), pre-treatment viral load <500.000 IU/ml (86.9%), non-1 genotype HCV (86.4%), non cirrhosis or pre-cirrhosis (76.5%), rapid virologic response (RVR) (91.4%) and early virologic response (EVR) (83.8%). In the multivariate logistic regression analysis, the presence of an infection caused by a non-1 genotype and to achieve ERV were independent predictors of SVR. The RVR and histological stage of liver disease were not included in the multivariate analysis because these data were not available in most of the patients. The PPV and NVP of RVR were 91.5% and 48.7% respectively, of EVR were 83.8% and 95.8% respectively and of complete EVR were 91.3% and 78.7%, respectively.
Conclusions: The SVR was higher than in other studies. The genotype and EVR were independent factors to predict the effect of antiviral therapy. The EVR had a high NPV and the complete EVR a high PPV. 

 
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Rev Esp Quimioter 2011:24(2):91-95

Antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus strains from outpatient individuals    

L. GARCÍA-AGUDO, M. HUERTAS, M. A. ASENCIO EGEA, R. CARRANZA, P. GARCÍA-MARTOS         

 

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged worldwide as a cause of infections among patients without risk factors. This CA-MRSA is different from nosocomial strains in terms of epidemiology, microbiology and clinical manifestations. We report the epidemiologic characteristics and resistance to antimicrobial agents of CA-MRSA strains isolated in the last three years in the Microbiology Lab of Hospital General La Mancha-Centro (Alcázar de San Juan, Ciudad Real).
Methods: We performed a retrospective analysis of microbiological cultures in patients with S. aureus diagnosed from 2007 to 2009 in La Mancha-Centro Health-Care Area, within Castilla-La Mancha Community.
Results: The distribution of CA-MRSA in the studied period was 26 out of a total of 97 S. aureus isolates in 2007 (26.8%), 40/113 in 2008 (35.4%) and 57/157 in 2009 (36.3%). The percentage from purulent skin and soft tissue infections was 63.4%. All strains were susceptible to linezolid, quinupristin/dalfopristin, and glycopeptides. The resistance was high to fluoroquinolones (94.3%), erythromycin (87.0%), tobramycin (82.9%), and clindamycin (65.3%).
Conclusions: CA-MRSA isolates percentage increased along the period of the study. The majority were obtained from skin and soft tissue specimens. The most commonly associated antimicrobial resistance was to fluoroquinolones, erythromycin, tobramycin and clindamycin. An understanding of the CAMRSA epidemiology is important to prevent these organisms from becoming endemic in the world. 

 
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Rev Esp Quimioter 2011:24(4):204-208

Predictive factors for pneumonia in adults infected with the new pandemic A (H1H1) influenza virus          


E. LERMA, L. SORLÍ, M. MONTERO, V. MAS, E. LÓPEZ, C. VILAPLANA, F. ÁLAVAREZ-LERMA, H. KNOBEL, J. P. HORCAJADA              

Background: On April 2009 a new A (H1N1) influenza virus was identified with a higher incidence of severe outcome in younger people, most of them with pneumonia.The objective of our study was to identify the predictive risk factors of pneumonia in patients with the new A (H1N1) influenza virus infection.
Methods: Prospective cohort study of adults infected with the new A (H1N1) influenza virus, admitted in a universitary hospital, from june 2009 to January 2010. Pneumonia was defined as the presence of any pulmonary infiltrate of any distribution with no other evident cause, in the chest radiography. A comparative analysis was made with patients with A (H1N1) influenza without pneumonia.
Results: 281 patients with influenza A (H1N1) were treated. Thirty of them (10.6%) had pneumonia and 11 (3.9%) required intensive care. The global mortality was 0.7%. For the comparative analysis, 42 patients with influenza A (H1N1) without pneumonia were analysed (20 hospitalized and 22 nonhospitalised).
In the multivariate analysis, obesity (BMI>30), (OR: 3.8; IC 95%: 0.99-15.0), time since symptom onset until hospital admission (OR 1.34; IC 95% 1.04-1.72), serum C reactive protein levels (OR:1.10; IC 95%: 0.98-1.24) and serum IgG2 levels (OR:1.08; IC 95%: 1.0- 1.01), were identified as independent risk factors for pneumonia.
Conclusion: Obesity, delay in medical care and higher levels of C reactive protein and IgG2 were predictive factors for pneumonia in adult patients with A (H1N1) influenza infection. 

 
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