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(3):131-135

Rapid identification and susceptibility testing of Gram-positive cocci in BacT/ALERT blood cultures by direct inoculation into the Vitek 2 system       

A. BARREALES, M. LARA, I. HERNÁNDEZ, Ó. DÍEZ           

 

Introduction: To provide the clinician with early information about blood culture results allows a better prognosis and a reduced mortality rate of the patient with sepsis. In order to contribute to this aim, we performed a study for the identification and susceptibility profiling of positive blood cultures by direct inoculation into the automated Vitek 2 system.
Materials and Methods: Blood cultures of 57 patients with monomicrobial bacteriaemia due to gram-positive cocci
were evaluated. Addition of saponin to the fluid from blood culture bottles was performed prior to the inoculation of Vitek 2 system cards. The same samples were also examined with the standard method starting from agar plate grown subcultures.
Results: Comparison between the results obtained with the standard method and the direct method revealed that 82% of the samples were correctly identified and that 97% of the isolates showed a concordant antimicrobial susceptibility profile for all drugs tested. Compared to the standard method, the very major error rate of the direct method was just 0.5%, the major error rate was 0.5%, and the minor error rate was 2%.
Conclusion: These data suggest that addition of saponin to the fluid from blood culture bottles of the BacT/ALERT® 3D before inoculation of the appropriate Vitek 2 cards leads to the rapid and reliable identification and susceptibility profiling of gram-positive cocci in blood samples. Compared to the standard method, the direct method would reduce turnaround time by at least 24 hours.

 
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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%).

 

 
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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.

 

 
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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.
 

 
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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. 

 
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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(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(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(3):127-130

In vitro activity of retapamulin against linezolid and methicillin–resistant Staphylococcus aureus isolates       

F. J. CANDEL, G. MORALES, J. J. PICAZO           

 

 

Objectives: To determine the in vitro activity of retapamulin and other topical antibiotics (mupirocin, bacitracin, and fusidic acid) usually employed for nasal decolonization, against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and linezolid and methicillin–resistant S. aureus.
Methods: The minimum inhibitory concentrations (MICs) were determined on Mueller-Hinton agar according to the guidelines of the Clinical and Laboratory Standards Institute and of the European Committee for Antimicrobial Susceptibility Testing. Presence of the cfr gene in linezolid and methicillin–resistant S. aureus isolates was detected using polymerase chain reaction.
Results: Retapamulin inhibited all the isolates of MSSA and MRSA at 0.125 mg/L, but the 18 linezolid-resistant-MRSA strains proved resistant, with MICs over 32 mg/L. Most MSSA isolates (9/10) were susceptible to mupirocin with MICs under 0.19 mg/L, although this value decreased to half against MRSA, and almost all linezolid-resistant MRSA (17/18) strains were resistant to mupirocin with an MIC range of between 8 mg/L and 28 mg/L. The MIC of fusidic acid increased substantially against linezolid-resistant MRSA, whereas that of bacitracin showed no differences.
Conclusions: Retapamulin demonstrated excellent in vitro activity against MSSA and MRSA strains, but not against MRSA isolates harbouring the cfr gene. The results of this in vitro study support cut-off values for retapamulin of ≤ 0.5, 1, and ≥ 2 mg/L for susceptible, intermediate, and resistant strains, respectively.

 
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