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 2012:25(1):47-55


Effect of protein binding on the activity of voriconazole alone or combined with anidulafungin against Aspergillus spp. using a time-kill methodology                

F. CAFINI, D. SEVILLANO, L. ALOU, F. GÓMEZ-AGUADO, M. T. CORCUERA, N. GONZÁLEZ, J. GUINEA, J. PRIETO                                                         

 

Objectives: the aims of the study were to explore the activity of total and free (according to protein binding) maximal concentrations achieved in serum after multiple doses of voriconazole 400/200 mg and anidulafungin 200/100 mg against Aspergillus fumigatus and Aspergillus flavus and the human albumin or serum effects on antifungal activity.
Material and methods: Time-kill curves were performed with two A. fumigatus and two A. flavus strains at voriconazole and anidulafungin Cmax concentrations using different media: a) RPMI broth (Cmax-RPMI); b) RPMI with human serum (Cmax-HS), and c) RPMI with human albumin (Cmax-HAlb). In parallel, free-drug (fCmax) concentrations considering theoretical protein binding were performed in RPMI broth. Aspergillus metabolic activity was measured by the XTT reduction assay.
Results: Voriconazol or voriconazole plus anidulafungin reduced >88.4% the metabolic activity of Aspergillus sp. at Cmax-RPMI and fCmax after 48 h of exposition. Anidulafungin alone showed poor metabolic reductions (<80.1% at Cmax-RPMI and <15% at fCmax). Anidulafungin activity, but not voriconazole activity alone or combined decreased in presence of HS or HAlb (more pronounced in A. flavus strains and HAlb). However, anidulafungin Cmax-HS or Cmax-HAlb against A. fumigatus strains were significantly more active (p<0.05) than fCmax in RPMI. These species and culture medium-dependent impact of human protein binding in the activity of anidulafungin was related to macroscopic and microscopic differences among mycelial mat grown in RPMI, HS or HAlb in whose XTT retention was different.
Conclusions: Synergism could not be demonstrated due to the high activity showed by voriconazole. Protein binding has not impact on voriconazole activity and this impact is considerably less than predicted by free concentration extrapolated from theoretical binding rate on anidulafungin. The XTT colorimetric assay needs to be standardized for use with Aspergillus spp. since without DMSO extraction the activity of echinocandins in a free-human protein RPMI medium could be overestimated. 

 
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Rev Esp Quimioter 2012:25(3):194-198


Long-term outcome of acute prosthetic joint infections due to gram-negative bacilli treated with retention of prosthesis                   

N. JAÉN, J. C. MARTÍNEZ-PASTOR, E. MUÑOZ-MAHAMUD, S. GARCÍA-RAMIRO, J. BOSCH, J. MENSA, A. SORIANO                                                                          

 
Objective: To update the clinical information of the 47 patients with a prosthetic joint infection due to Gram-negative bacilli included in a previous study and to reassess the predictors of failure after a longer follow-up.
Methods: Using the electronic files of our hospital, all the information regarding readmissions to the hospital, new surgical procedures and the reason for the new surgery (infection, aseptic loosening), and the last visit in the hospital were registered. The medical chart of the 35 patients that were considered in remission in the previous publication was reviewed.
Results: In 30 patients no clinical evidence of failure was detected and no additional surgery on the previously infected prosthesis was necessary and they were considered in long-term remission. In 5 cases a late complication was identified. One case had a reinfection due to coagulase-negative staphylococci after 22 months from the open debridement and required a 2-stage revision surgery. The other 4 cases developed an aseptic loosening and it was necessary to perform a 1-stage exchange. Receiving a fluoroquinolone when all the Gram-negatives involved in the infection were susceptible to fluoroquinolones was the only factor associated with remission in the univariate analysis (p=0.002).
Conclusion: After a long-term follow-up, our results support the importance of using fluoroquinolones in acute PJI due to Gram-negative bacilli.

 

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Rev Esp Quimioter 2010:23(1):43-47

Evaluation of pharmacodynamic target attainment with vancomycin treatment of bacteremia due to Staphylococcus aureus methicillin resistant

J. A. LEPE, M. V. GIL-NAVARRO, M. D. SANTOS-RUBIO, J. BAUTISTA, J. AZNAR

 

Objective: The objective of the study is to evaluate the ability of standard vancomycin dosing strategies actually recommended to attain the pharmacodynamic target of an area under the curve of vancomycin serum concentration versus time from 0 to 24 hours (AUC24h) to minimum inhibitory concentration (MIC) ratio greater than 400:1 for patients with a suspected or documented methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia by individual analysis and Monte Carlo simulation.
Material and methods: The study included all patients admitted with suspected or proven MRSA infection during the years 2007-2008, and who were initially treated with vancomycin at a dose of 30 mg/kg/day, and underwent pharmacokinetic monitoring. The area under the curve of vancomycin serum concentration versus time from 0 to 24 hours (AUC24h) was calculated as daily dose/clearance total (D24h/CL). Additionally, we studied 45 isolates of MRSA obtained from blood cultures in the period 2007-2008. The MIC to vancomycin was determined using Epsilon-test®. The PK-PD parameter calculated was AUC24h/MIC. Microsoft
Excel was used to perform a 10.000 subject Monte Carlo simulation. An AUC24h/MIC ≥ 400 was assumed as the target attainment.
Results: In the individual study, the percentage of patients with AUC24h/MIC50/90 ≥ 400 was 50%. The probability (%) of attaining AUC24h/MIC ratio values ≥ 400 by Monte Carlo simulation was of 66%. The vancomycin MIC value from which the scenario would have to wait a suboptimal treatment (target <90%) was >1 mg/L.
Discussion: This study shows that in the population studied to achieve a vancomycin AUC24h/MIC ≥ 400 is not always attained with the standard dose. Therefore, one would expect a high probability of suboptimal vancomycin AUC24h/MIC ratios for patients infected with organisms with vancomycin MICs of >1 mg/L treated with doses of 30 mg/kg/day.

 
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Rev Esp Quimioter 2010:23(4):169-176

Antifungal agents in the treatment of systemic infections: Relevance of mechanism of action, activity profile and resistances 

M. CUENCA-ESTRELLA   

 

The availability of different therapeutic alternatives has modified the treatment of systemic fungal infections. There commendations of antifungal therapy vary according to species which causes the mycosis and its susceptibility. Consequently, the knowledge of action mechanism, activity profile and resistances to antifungal agents are essential for the clinical practice. Amphotericin B is the antifungal agent exhibiting the broadest spectrum of activity, it is a fungicidal drug and resistances have been hardly ever described. The triazoles compounds also have a broad spectrum, but their massive use for some therapeutic indications has led to emergence of strains and species of yeasts with resistance to fluconazole and of filamentous fungi itraconazole resistant.The echinocandins exhibit fungicidal effects for yeasts andafungistatic activity against moulds, and secondary resistance to these agents is uncommon.   

 
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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 2012:25(1):56-64


Clinical characteristics and outcome of patients with pandemic 2009 Influenza A(H1N1)v virus infection admitted to hospitals with different levels of health-care 
                

M. GUTIÉRREZ-CUADRA, J.L. GONZÁLEZ-FERNÁNDEZ, P. RODRÍGUEZ-CUNDIN, C. FARIÑAS-ÁLVAREZ, M. V. SAN JUAN, J. A. PARRA, M. CARRASCOSA, M. C. FARIÑAS                                                         

Background. The outcome of patients with influenza A 2009 (H1N1)v virus infection taking into account hospital type has not been elucidated.
Objectives. To compare risk factors, clinical features and outcome of patients admitted to 3 public hospitals with different levels of health-care.
Methods: Prospective study of all non-pregnant adult patients admitted to 3 hospitals with pandemic H1N1 infection, from June 1 to December 31 and followed up until 1 month after discharge.
Results. During the study period, 111 patients with a mean age of 49 years (15-89) were hospitalized: 52 in hospital 1 (900-bed tertiary-teaching-hospital), 33 in hospital 2 (315-beds secondary-hospital) and 26 in hospital 3 (150-beds primary-care-hospital).Overall 80% of patients had at least 1 comorbid condition with no differences between hospitals. Symptoms or signs on admission were similar except for cough (P=0.01) more frequent in patients in hospital 1 and dyspnea (P=0.05), myalgia, arthralgia (P=0.04) and hypoxemia (P=0.009) present in more patients in hospital 2. In-hospital mortality rates were not statistically different between hospitals. In the stepwise analysis, independent predictors of mortality were pneumonia on admission (adjusted OR=8.68, 95%CI 1.0-82.43) and cardiac complications during hospitalization (adjusted OR=13.2, 95%CI 1.67-103.98).
Conclusions. Mortality of patients with pandemic H1N1 infection was influenced by patients underlying conditions, severity of disease (pneumonia) on admission and complications during hospitalization. Hospital-characteristics do not appear to have influenced severe outcome.. 

 
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Rev Esp Quimioter 2012:25(3):199-205


Coagulase-negative Staphylococcus bacteraemia: prognosis factors and influence of antibiotic treatment                   

A. FERNÁNDEZ-RUFETE, E. GARCÍA-VÁZQUEZ, A. HERNÁNDEZ-TORRES, M. CANTERAS, J. RUIZ, J. GÓMEZ                                                                          

 
Introduction: Coagulase-negative staphylococci (CNS) are the most frequent isolated microorganism in blood cultures; mortality has been associated to severity and to adequacy of empirical treatment but the relevance of the latter is not clearly recognised. The aims of the study were to analyze clinical and microbiological factors related to mortality in patients with CNS bacteraemia and the influence of empirical treatment in prognosis.
Patients and methods: a prospective cohort study of patients with CNS bacteraemia was performed (January to June 2010) at a university-affiliated hospital; a determination of clinical significance was made and true bacteraemia was defined according to CDC criteria. We analysed epidemiological, clinical and microbiological variables related to mortality.
Results: a total of 269 cases were included (97 were considered true bacteraemia); 92% survived and mortality was 8% (1.6% CNS bacteraemia related mortality). Staphylococcus epidermidis was the most frequent isolated species; 93 patients were included in the related mortality study of patients with true bacteraemia. Factors associated to mortality in the bivariate analysis (p<0.05) were: Winton score I-III, presence of pacemakers, sepsis or infective endocarditis and persistent bacteraemia. Adequate empirical treatment was not associated to survival.
Conclusions: severity at onset, the development of septic complications and having a pacemaker are associated to mortality in patients with CNS bacteraemia; in our cohort, inadequate empirical treatment is not related to mortality.

 

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Rev Esp Quimioter 2010:23(2):63-71

Differences in the use of tigecycline between ICU patients and non-ICU patients

F. ALVÁREZ-LERMA, L. BLANCO, J.A. RODRÍGUEZ, S. GRAU, D. CONDE-ESTÉVEZ, S. LUQUE

 

Background. Tigecycline is a new broad spectrum antibiotic that is predominantly used for the treatment of severe infections both in critically ill patients admitted to the ICU and in non-ICU patients with less severe clinical conditions.
Objetive. To assess differences in the use of tigecycline between ICU patients and non-ICU patients treated with this antibiotics.
Materials and methods. Retrospective, cohort, observational study in which cases were defined as patients who received one or more doses of tigecycline over the first 18 months after approval of the drug in a general hospital. Clinical characteristics, indications, route of administration, clinical response, tolerability and outcome were recorded in the groups of ICU and non-ICU patients. Descriptive data and results of the comparison of both cohorts are presented.
Results. A total of 103 were included in the study, 34 (33%) of which received tigecycline during their stay in the ICU. ICU patients compared to non-ICU patients had a higher SAPS II score on admission (39.0 ± 11.8 vs 26.3 ± 8.0, p < 0.001) and at the time of starting tigecycline treatment (42.2 ± 12.6 vs 25.6 ± 8.2, p < 0.001), were treated with antibiotics for more days (21.4 ± 30.6 vs 13.6 ± 30.5 days, p < 0.012) and received a greater number of antibiotic agents concomitantly (85.3% vs 47.8%,p < 0.001), presented a higher selection of emerging bacterial flora (41.2% vs 15.9%, p = 0.005), particularly Pseudomonas aeruginosa (20.6% vs 2.9%, p = 0.006), higher rate of clinical failure (58.8% vs 21.7%, p < 0.001), longer hospitalization (51.2 ± 39.4 vs 28.7 ± 26.3 days, p < 0.001) and higher overall mortality rate (50% vs 14.5%, p < 0.001) and infection-attributed mortality (20.6% vs 7.2%, p = 0.047).
Conclusions. The patient that receives tigecycline in the ICU has a higher severity level and worse clinical outcome than the non-ICU patient treated with this antibiotic. It is necessary to optimize the indications of tigecycline in the ICU to improve the clinical results.

 
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