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.    

 
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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 2012:25(1):10-16

Macrolides and staphylococcal biofilms                

J. PARRA-RUIZ, C. VIDAILLAC, M. J. RYBAK                            

Medical device-associated infections represent a growing problem with limited or no therapeutic options beyond implant removal. Bacterial biofilm is the major and the final determinant of the poor prognosis of these difficult-to-treat infections. Due to the high antimicrobial resistance level of bacteria organized in biofilms, combination therapy is most often recommended, and macrolides may represent antibiotics of choice. Their anti-biofilm activity has been successfully used in-vitro and in-vivo against biofilm-associated infections caused by Pseudomonas aeruginosa and other Gram-negative bacilli. However there is only little data regarding their clinical interest against infections involving staphylococcal biofilms. Despite controversial reports, there is growing in-vitro and in-vivo evidences of anti-staphylococcal biofilm activity of macrolides that could represent a significant advance in the battle against implant-related infections. 

 
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Rev Esp Quimioter 2012:25(2):147-154

Prospective comparison of severity scores for predicting mortality in community-acquired pneumonia              

S. LUQUE, J. GEA, P. SABALLS, O. FERRÁNDEZ, N. BERENGUER, S. GRAU                                                                      

 
Introduction. Specific prognostic models for communityacquired pneumonia (CAP) to guide treatment decisions have been developed, such us the Pneumonia Severity Index (PSI) and the Confusion, Urea nitrogen, Respiratory rate, Blood pressure and age ≥ 65 years index (CURB-65). Additionally, general models are available such as the Mortality Probability Model (MPM-II). So far, which score performs better in CAP remains controversial. The objective was to compare PSI and CURB-65 and the general model, MPM-II, for predicting 30-day mortality in patients admitted with CAP.
Methods. Prospective observational study including all consecutive patients hospitalised with a confirmed diagnosis of CAP and treated according to the hospital guidelines. Comparison of the overall discriminatory power of the models was performed by calculating the area under a receiver operator characteristic curve (AUC ROC curve) and calibration through the Goodness-of-fit test.
Results. One hundred and fifty two patients were included (mean age 73.0 years; 69.1% male; 75.0% with more than one comorbid condition). Seventy-five percent of the patients were classified as high-risk subjects according to the PSI, versus 61.2% according to the CURB-65. The 30-day mortality rate was 11.8%. All three scores obtained acceptable and similar values of the AUCs of the ROC curve for predicting mortality. Despite all rules showed good calibration, this seemed to be better for CURB-65. CURB-65 also revealed the highest positive likelihood ratio.
Conclusions. CURB-65 performs similar to PSI or MPMII for predicting 30-day mortality in patients with CAP. Consequently, this simple model can be regarded as a valid alternative to the more complex rules.

 

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Rev Esp Quimioter 2012:25(4):269-273

Discrepancy in the disk diffusion susceptibility test of Pseudomonas aeruginosa strains isolated from cystic fibrosis patients after anaerobic preincubation and its potential clinical relevance                    

F. CAFINI, C. GARCÍA REY, P. BAS, M. L. GÓMEZ-LUS, I. SÁNCHEZ, S. VÁZQUEZ, J. PRIETO                                                                                   

Introduction. In cystic fibrosis, the Pseudomonas aeruginosa cells grow inside the thick mucus layer. In spite of being an obligate aerobe, P. aeruginosa is able to grow in a limited oxygen environment. Bacterial cells could be suddenly exposed to high oxygen levels due to the movements of the mucus mass. The aim of study was to determine the impact of a previous anaerobic incubation on the antimicrobial susceptibility of P. aeruginosa strains isolated from patients with cystic fibrosis.
Materials and Methods. Four P. aeruginosa strains were used in this study (ATCC 23389 and 3 clinical isolates). The disk diffusion method was used to determine the antimicrobial susceptibility.
Results. The anaerobic pre-incubation produced changes on the susceptibility in all studied strains. All susceptible strains after an aerobic incubation remained susceptible after an anaerobic incubation except one clinical strain, which became resistant to betalactams. The response was strain-dependent and the most significant increase in susceptibility was observed in two of the three clinical isolates when ciprofloxacin was used.
Conclusions. The antimicrobial susceptibility of P. aeruginosa strains varies after their exposure to anaerobic conditions. Treatments promoting mucus fluidization could contribute to increase the antimicrobial efficacy.  

 

Rev Esp Quimioter 2012:25(4):269-273 [pdf]

 

 

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Rev Esp Quimioter 2010:23(1):4-11

Nonantimicrobial effects of tetracyclines

L. GARCÍA-ÁLVAREZ, J. A. OTEO

 

Tetracyclines are a family of antibiotics very common in clinical practice that have been used in not infectious affections. One of their most studied actions is their ability to inhibit matrix metalloproteinases (MMPs), a group of proteinases that have been implicated in pathological processes as oncogenesis and inflammation. Tetracyclines have been shown to play an important role in malignant angiogenesis and cancer invasion, which is related with tumor aggressiveness and metastatic potential. They also show anti-inflammatory activity in neurological, respiratory, bone and heart diseases, and in rheumatologic and dermatologic processes. The aim of this review is to make an updating about the non antimicrobial actions of tetracyclines, specially their therapeutic applications in different diseases.

 
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Rev Esp Quimioter 2010:23(3):122-125

Antifungal activity of posaconazole against Candida spp. and non-Candida clinical yeasts isolates 

A. J. CARRILLO-MUÑOZ, C. TUR-TUR, J. M. HERNÁNDEZ-MOLINA, G. QUINDÓS, C. MARCOS-ARIAS, E. ERASO, D. CÁRDENES, O. ORTIZ-MAESTRO, P. SANTOS, D. ESTIVILL, C. GUARDIA, G. GIUSIANO 

 

The in vitro antifungal activity of posaconazole was tested against 315 yeast clinical isolates and 11 ATCC reference strains by means an agar diffusion method (Neosensitabs, Rosco,Denmark) based in CLSI M44-A2 document. Posaconazole activity was excellent against Cryptococcus and Rhodotorula species studied and showed very good activity against most species of Candida tested. A total of 13 clinical isolates (4.1%) were resistant: Candida albicans (n=5), Candida glabrata (n=5), Candida tropicalis (n=1), Geotrichum australiensis (n=1) and Geotrichum capitatum (n=1). Our results suggest posaconazole is an effective antifungal agent against the most clinically important yeasts species (92.7% of susceptibility). Agar diffusion method provides good conditions for the posaconazole susceptibility study in the routine laboratory.  

 
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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.    

 
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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 2012:25(1):17-24

Liposomal amphotericin B: a unique pharmacokinetic profile. An unfinished story                

J. R. AZANZA, J. BARBERÁN                            

La anfotericina B en su formulación liposómica continúa siendo un fármaco de referencia en el tratamiento de las infecciones fúngicas sistémicas a pesar del tiempo transcurrido desde que se desarrolló. La ausencia de resistencias de los hongos, la farmacocinética, y el mejor perfil de tolerabilidad en relación con el resto formulaciones de anfotericina B, son motivos suficientes para justificar su protagonismo, El liposoma que contiene la anfotericina B liposómica es muy estable en relación con la presencia de colesterol y los fosfolípidos no presentan termolabilidad, por ello la anfotericina B apenas está presente en forma libre (<1%) lo que explica la baja incidencia de efectos relacionados con la administración y la reducción de la incidencia de nefrotoxicidad (mitad que con la anfotericina B complejo lipidico) y que incluso en algún estudio a dosis de 1 mg/kg se ha mostrado inexistente.Este perfil justifica concentraciones plasmáticas muy elevadas y un volumen de distribución y aclaramiento reducidos, con una semivida de eliminación muy prolongada. Existen evidencias que señalan que el liposoma a través de la anfotericina B es capaz de fijarse al ergosterol presente en membrana de hongo y sólo en ese momento se produciría la liberación del antifúngico que ejercería su efecto farmacológico.

 
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