Rev Esp Quimioter 2011:24(1):32-36

Rapid detection of clarithromycin resistant Helicobacter pylori strains in Spanish patients by polymerase chain reaction-restriction fragment length polymorphism 

S. AGUDO, G. PÉREZ-PÉREZ, T. ALARCÓN, M. LÓPEZ-BREA    

 

Introduction. The aim of this study was to characterize the mutations types present in the 23S rRNA gene related to H. pylori clarithromycin-resistance strains in Spain and evaluate a novel PCR-RFLP method for detection of the most frequent point mutation in our population.
Methods. Gastric biopsies were obtained by endoscopy from patients with gastric symptoms. H. pylori was cultured according to standard microbiological procedures and clarithromycin resistance was determined by E-test. DNA extraction was performed by NucliSens platform with the NucliSens magnetic extraction reagents (bioMérieux) according to the manufacturer instructions. Analyses for point mutations in 23S rRNA gene strains were performed by sequence analysis of amplified polymerase chain reaction products. Restriction fragment length polymorphism was performed using BsaI enzyme to detect restriction sites that correspond to the mutation (A2143G).
Results. We found 42 out of 118 (35.6%) strains resistant to clarithromycin by E-test. E-test results were confirmed for the presence of point mutation in 34 (88.1%) of these strains. Mutation A2143G was found in 85.3% of the strains. Analyses with the restriction enzyme BsaI was able to confirm the presence of A2143G mutation. There were 8 H. pylori strains resistant to clarithromycin by E-test but without any point mutationin the 23 rRNA gene.
Conclusions. We conclude that PCR-RFLP is a reliable method to detect clarithromycin-resistance H. pylori strains in countries with a high prevalence of clarithromycin-resistance as Spain. It may be useful before choosing regimens of H. pylori eradication.    

 
Rev Esp Quimioter 2011:24(1):32-36 [pdf]

Rev Esp Quimioter 2011:24(3):136-142

Which is the best empirical treatment in patients with urethritis?      

M. A. ORELLANA, M. L. GÓMEZ–LUS            

 

Objective. To know the best empirical treatment of urethritis in patients at the City Center of Madrid.
Methods. 2.021 urethral exudates were analyzed in men between January 2003-December 2007. In addition to the traditional cultures, it was determined the presence of Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Trichomonas vaginalis and Herpes simplex. The susceptibility of N.gonorrhoeae and Haemophilus spp was performed by disk diffusion method and U. urealyticum by Mycoplasma IST.
Results. The percentage of positive samples was: 30.6%. The most frequently isolated microorganisms were: U. urealyticum 9.9%, N. gonorrhoeae 7.4%, C. trachomatis 5.1% and Haemophilus spp 3.8%. The resistance of N. gonorrhoeae in the first period was: penicillin 11.8%, tetracycline 5.9%, ciprofloxacin 8.8% and presence of betalactamase 11.8%. In the second period: penicillin 9.7%, amoxicillin/clavulanic acid 1.4%, tetracycline 8.3%, ciprofloxacin 23.6% and presence of betalactamase 10.5%. Resistance to ciprofloxacin in non-MSM (men having sex with men) was 20% and in MSM 56.2% (p <0.05). Resistance of Haemophilus spp in the first period was: 38.2% ampicillin, amoxicillin/clavulanic acid 8.8%, clarithromycin 35.3%, cotrimoxazole 64.7%, cefuroxime 5.9%, ciprofloxacin 8.8%, tetracycline 12.1% and presence of betalactamase 26.5%. In the second period: presence of betalactamase 41.9%, ampicillin 53.1%, amoxicillin/clavulanic acid 9.4%, cefuroxime 9.4%, clarithromycin 18.7%, tetracycline 34.4%, ciprofloxacin 15.6%, and cotrimoxazole 68.7%. Resistance of U. urealyticum was: ciprofloxacin 80.7%, ofloxacin 32.4%, erythromycin 17.5%, azithromycin 9.6%, tetracycline 3.5% and doxycycline 0.8%.
Conclusions. N. gonorrhoeae showed a level of resistance to tetracycline and ciprofloxacin higher in the second period, being significant for ciprofloxacin (p<0.05). Quinolone resistance was higher in MSM. Haemophilus spp showed a level of resistance to ampicillin, ciprofloxacin and tetracycline higher in the second period, being significant for tetracycline (p <0.05). U.urealyticum showed high level of resistance to ciprofloxacin (80.7%) and ofloxacin (32.4%) and low level of resistance to doxycycline (0.8%) and tetracycline (3.5%).

 

 
Rev Esp Quimioter 2011:24(3):136-142 [pdf]

Rev Esp Quimioter 2011:24(1):37-41

Prosthetic joint infection by Candida spp 

E. GARCÍA-OLTRA, S. GARCÍA-RAMIRO, J. C MARTÍNEZ, R. TIBAU, G. BORI, J. BOSCH, J. MENSA, A. SORIANO     

 

Introduction: Fungal periprosthetic infectionis a rare entity. The aim of this report was to review our experience in two different educational hospitals.
Material and methods: patients with documented prosthetic joint infection due to Candida spp. from February 2002 to October 2010 were retrospectively reviewed. Demographics, microbiological data, treatment and outcome of each patient was recorded.
Results: Ten patients, 8 women and 2 men, with a meanage of 77.7 (range 66-92) years were identified. Nine patients had previous bacterial infection, received antibiotic treatment for more than 15 days and required multiple surgeries. The most frequent species was C. albicans with 6 cases. All patients received fluconazole and surgical treatment consisted of debridement without removing the implant in 3 cases and 2-stage exchange with a spacer in 7. The first surgical and antifungal approach failed in all cases and a second debridement was necessary in one case, a resection arthroplasty in 8 and chronic suppressive treatment with fluconazol in one. After a mean follow-up of 31 (range 2-67) months, two patients were free of infection.
Conclusion: Prosthetic joint infection was associated with long-term antibiotic treatment and multiples previous surgeries. Treatment with fluconazol and debridement or two stage replacement with a spacer was associated with a high failure rate.    

 
Rev Esp Quimioter 2011:24(1):37-41 [pdf]

Rev Esp Quimioter 2011:24(3):143-150

Economic evaluation of interventions for infectious diseases in Spain: systematic review and comparative analysis      

F. CATALÁ-LÓPEZ, A. GARCÍA-ALTÉS, E.  ÁLVAREZ-MARTÍN, R. GÈNOVA-MALERAS, C. MORANT-GINESTAR            

 

Background: There exists the need to evaluate interventions addressed to prevent, control and reduce the burden of the infectious diseases; being economic evaluation an instrument can help to allocate healthcare resources efficiently. In this context, we assessed the evolution of economic evaluation of interventions for infectious diseases published in Spain, as well as we compared their main methodological characteristics with those of the studies directed to other diseases.
Methods: Systematic review and comparative analysis calculating odds ratios (OR). Electronic searches for literature beetwen 1983 and 2008 were conducted in PubMed/MEDLINE, SCOPUS, ISI Web of Knowledge, CRD, IME e IBECS, and manually in specialized journals and technical reports. The following variables were identified to analyze the characteristics of the reports: journal and year of publication, intervention, type of study, design, perspective, type of costs, financing source, and decision-making recommendations.
Results: One-hundred and one studies were included in the review. The main characteristics of the reports were: cost-effectiveness analysis (n=56; 55.4%), treatments evaluations (n=60;59.4%) and the use of decision analysis and mathematical simulation models (n=63; 62.4%). Economic evaluation studies of infectious diseases showed the following associations (compared to a cohort of studies of other disease conditions [n=376]): cost-benefit
analysis (OR, 3.55; 95% confidence interval [CI], 1.63 to 7.74), prevention (OR, 4.14; 95% CI, 2.49 to 6.90), and societal perspective (OR, 2.55; 95% CI, 1.43 to 4.56).
Conclusion: Although there is an increase in the number of economic evaluations of infectious diseases published during last decades, the studies showed heterogeneity in the quality of the information regarding methods of analysis and data sources.

 

 
Rev Esp Quimioter 2011:24(3):143-150 [pdf]

Rev Esp Quimioter 2011:24(1):42-47

Clinical experience with linezolid for the treatment of neurosurgical infections  

D. SOUSA, P. LLINARES, H. MEIJIDE, J.M. GUTIÉRREZ, E. MIGUEZ, E. SÁNCHEZ, L. CASTELO, A. MENA      

 

Objectives: We sought to evaluate the clinical use of linezolid for the treatment of neurosurgical infections.
Methods: Retrospective observational study of a cohort of hospitalized patients who received linezolid for a culture-positive neurosurgical infection from July 2004 to February 2009 in a tertiary hospital in Spain.
Results: Seventeen patients were included in the study. Main comorbidities among these patients included one or more of the following: subarachnoidal or intraventricular hemorrhage (n=8), solid neurological cancer (n=7), corticosteroids(n=9) and hydrocephalus (n=6). Eight patients underwent acraniotomy and fourteen patients had an external ventriculardrainage (EVD) as predisposing factors for infection. Meningitis was the most common infection (11; 64.7%), followed by ventriculitis (4; 23.5%) and brain abscesses (2;11.8%). The main causative organisms were coagulase-negative Staphylococcus spp. (13; 76.5%). Linezolid was used as theinitial therapy in 8 episodes, after therapy failure in 6 and forother reasons in 3. The oral route was used in 9 (52.9%) episodes; linezolid was initiated orally in 2 cases. The mean duration of treatment was 26.5 days (range 15-58). No adverse events were reported. Sixteen (94.1%) patients were considered cured.There was one recurrence. The mean length of hospital stay was 45.6 (range 15-112) days and the mean duration of follow-up was 7.2 (range 0.4-32) months. No related deaths occurred during active episodes.
Conclusions: Linezolid was mainly indicated in post-neurosurgical EVD-associated infections due to coagulase-negative Staphylococcus spp. It was used as initial therapy in most cases. A high rate of clinical cure was observed and no related adverse events were reported. More than half of the patients were benefited by the advantages of the oral route of administration.
    

 
Rev Esp Quimioter 2011:24(1):42-47 [pdf]

Rev Esp Quimioter 2011:24(3):151-153

Usefulness of monitoring linezolid trough serum concentration in prolonged treatments      

R. SOUSA, R. LÓPEZ, J. C. MARTÍNEZ-PASTOR, C. CERVERA, G. BORI, S. GARCÍA-RAMIRO, J. MENSA, A. SORIANO           

 

Linezolid has proven valuable in musculoskeletal infections, however, failure and resistance have been described and toxicity is worrisome when more than 28 days are necessary. We describe the first 5 cases in whom linezolid trough serum concentrations were weekly measured and its relationship with clinical outcome and toxicity.
 

 
Rev Esp Quimioter 2011:24(3):151-153 [pdf]

Rev Esp Quimioter 2011:24(2):57-66

Bacteraemia due to Escherichia coli producing extended-spectrum betalactamases (ESBL): clinical relevance and today’s insights  

A. M. GARCÍA-HERNÁNDEZ, E. GARCÍA-VÁZQUEZ, A. HERNÁNDEZ-TORRES, J. RUIZ, G. YAGÜE, J. A. HERRERO, J. GÓMEZ     

 

Antibiotic resistance is an old problem with new face as the rate of infections due to multidrug resistant bacteria is higher everyday and the number of new antibiotics to overwhelm the problem is becoming smaller. E. coli is the most frequent agent causing nosocomial or community-acquired bacteraemia being in our country 10% of them extended-spectrum betalactamases (ESBL) producing E. coli isolates. Nowadays the number of community- acquired or health-related infections caused by these ESBL producing E. coli is increasing. CTX-M has also become the most frequent ESBL compared to other enzymes. The role of these enzymes as a virulence factor increasing mortality in patients with bacteraemia due to E. coli is not well defined. The relevance of ESBL-E. coli seems to be related with the higher frequency of inadequate treatment and therefore the importance of identifying factors or features that might predict that the patient’s infection is due to one of these isolates. In terms of prevention and control of infection measures, the role of patient’s isolation is not clear but a proper prescription of antibiotics and antibiotic control policies are probably important to reduce the problem.    

 
Rev Esp Quimioter 2011:24(2):57-66 [pdf]

Rev Esp Quimioter 2011:24(3):154-163

Pharmacoeconomic assessment of daptomycin as first-line therapy for bacteraemia and complicated skin and skin structure infections caused by gram-positive pathogens in Spain      


S. GRAU, P. REBOLLO, J. CUERVO, S. GIL-PARRADO           
 

Objective: To assess the efficiency of daptomycin as firstline therapy (D) versus daptomycin as salvage therapy after vancomycin (V→D ) or linezolid (L→D) failure in gram-positive bacteraemia and complicated skin and skin-structure infections (cSSTIs).
Methods: Cost-effectiveness analysis of 161 bacteraemia and 84 cSSTIs patients comparing the above mentioned therapeutic alternatives was performed using the data from 27 Spanish hospitals involved in the EUCORE study. Direct medical costs were considered. Patients were observed from the first antibiotic dose for infection until either the end of daptomycin therapy or exitus. A multivariate Monte Carlo probabilistic sensitivity analysis was applied for costs (lognormal distribution) and effectiveness (normal distribution).
Results: In terms of effectiveness there were no statistical differences between groups but referring total costs per patient, there were significant differences. Sensitivity analysis confirmed that D dominates over L→D between 44.2%-62.1% of simulations in bacteraemia and between 48.2%-67.5% in cSSTIs. In comparison to V→D, D dominance was detected in 29.2%-33.2% of simulations in bacteraemia and between 48.2%-59.3% in cSSTIs.
Conclusions: Daptomycin as first-line therapy dominates over daptomycin as salvage therapy after linezolid failure both in bacteraemia and cSSTIs. Comparing daptomycin as first-line therapy with its use after vancomycin failure, in cSSTIs the former is dominant. In bacteremia daptomycin as first line therapy is as effective as daptomycin as salvage therapy after vancomycin failure and implies lower costs. 

 
Rev Esp Quimioter 2011:24(3):154-163 [pdf]

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.
 

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

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. 

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