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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Rev Esp Quimioter 2012:25(2):155-160

Pneumococcal bacteremia in adult patients at a hospital in Madrid: serotypes and susceptibility                 

M. CORREA, J. C. SANZ, C. DE LAS CUEVAS, A. GUIU, D. DOMINGO, T. ALARCÓN, M. LÓPEZ-BREA                                                                       

 
Introduction. The aim of this study is to describe the distribution of Streptococcus pneumoniae serotypes, its antimicrobial susceptibility profiles and the relation with vaccines in pneumococcal invasive strains isolated from blood cultures of adult patients.
Methods. All pneumococci isolated (67 strains) from blood cultures were serotyped by latex agglutination (Pneumotest latex) and Quellung reaction (Statens Serum Institut, Denmark). Antimicrobial susceptibility testing to penicillin (PEN), cefotaxime (CT), erythromycin (ERY) and levofloxacin (LEV) was performed by the E-test method (Biomèrieux, France).
Results. Among the 67 strains isolated, the most prevalent serotypes were 22F (11.9%) and 3 (11.9%), the second most frequent were 7F (7.5%) and 19A (7.5%). The coverage of the strains by the pneumococcal 7-valent conjugate vaccine (VNC7V), pneumococcal 13-valent conjugate vaccine (VNC13V) and pneumococcal 23-valent polysaccharide (VNP23V) were 16, 49 and 82%, respectively. Serotypes 22F and 3 were responsible for 14 of the 48 episodes of pneumonia with bacteremia (29.2%) and only 2 of the 19 episodes (10.5%) of bacteremia without pneumonia. According to the 2007 CLSI criteria, 12 strains (17.9%) were non-susceptible to penicillin. Eleven of this 12 strains (91.7%) were resistant to erythromycin, simultaneously.
Conclusions. The most common serotypes were 22F, 3, 7F y 19A. Three of them (3, 7F y 19A) are serotypes that are covered by the new VNC13V but not by VNC7V. Serotype 22F is a serotype emergent that is not covered by the VNC7V. The percentage of non-susceptibility to penicillin and resistance to erythromycin was comparable to the percentage reported in our country.

 

Rev Esp Quimioter 2012:25(2):155-160 [pdf]

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Rev Esp Quimioter 2012:25(4):274-282

Efficacy and safety of caspofungin in critically ill patients. ProCAS Study                     

C. LEÓN-GIL, A. ÚBEDA-IGLESIAS, A. LOZA-VÁZQUEZ, M. V. DE LA TORRE, J. M. RAURICH-PUIGDEVALL, B. ÁLVAREZ-SÁNCHEZ, C. ORTIZ-LEYVA, J. M. DOMÍNGUEZ-ROLDÁN, L. SOCÍAS-CRESPI, J. GARNACHO-MONTERO AND THE PROCAS STUDY GROUP                                                                                   


Introduction. Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). ProCAS is a study sponsored by the Working Group of the Infectious Diseases of the Spanish Society of Intensive Care Medicine, which analyzes the effectiveness and safety of caspofungin in routine clinical practice conditions in the critically ill.
Methods. A prospective, multicenter, observational study designed to estimate the clinical effectiveness and safety of caspofungin acetate in the treatment of IC and IA in patients refractory to or intolerant of conventional antifungal therapy. The assessment of effectiveness both clinic and the microbiological was carried out at the end of the treatment with caspofungin.
Results. We included 98 patients, 62 IC proven, 25 probable and 11 IA probable, from 24 centers during 2005 and 2006. Treatment with caspofungin monotherapy was performed in 89.8% of cases and as first line therapy in 54.1%. The favorable clinical response obtained for IC, probable IC, and probable IA was 91.9, 84, and 81.8%, respectively. The microbiological response was favorable in 74.6, 68, and 54.6% for proven cases of IC, probable IC, and probable IA, respectively. No serious adverse effects were observed.
Conclusions. In routine clinical practice conditions, caspofungin is effective and safe for the treatment of invasive fungal infections (IC/IA). The efficacy and safety profile was similar to that observed in published clinical trials.  

 

Rev Esp Quimioter 2012:25(4):274-282 [pdf]

 

 

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Rev Esp Quimioter 2012:25(1):25-30

Activity of vancomycin, teicoplanin and linezolid in methicillin resistant coagulase-negative Staphylococci isolates from paediatric blood cultures                

M. FAJARDO, R. HIDALGO, S. RODRÍGUEZ, C. GAONA, R. M. SÁNCHEZ, R. HERNÁNDEZ, E. MARTÍNEZ, J. L. CORDEROM. T. MARTÍNEZ-IZQUIERDO                             

Introduction. Coagulase-negative-Staphylococci (CNS) are the major cause of bacteraemia and sepsis in newborns. CNS methicillin resistance and its loss of sensitivity to glycopeptide antibiotics, make treatment significantly more difficult in positive cocci infections.
Objective. To study MIC vancomycin, teicoplanin and linezolid in different species of CNS methicillin resistant isolates from blood cultures from paediatric patients.
Methods. Clinically relevant CNS methicillin resistant isolates from paediatric blood cultures from different hospitalization wards were tested. The isolates were identified by biochemical tests by means in the Combo panels 31 of MicroScan (Dade Behring, Siemens). Resistance to oxacillin and susceptibility to vancomycin, teicoplanin and linezolid were tested by microdilution panels as cited above. We also tested teicoplanin and linezolid sensitivity using Etest.
Results. 50 methicillin resistant strains were isolated: 37 (74%) S. epidermidis, 7 (14%) S. hominis, 4 (8%) S. haemolyticus and 2 (4%) Staphylococcus spp. 26 strains were observed with reduced susceptibility to vancomycin MIC = 2 mg/L, (22 S. epidermidis, 2 S. haemolyticus and 2 Staphylococcus spp.) and 21 strains with loss of susceptibility to teicoplanin, MIC = 4-16 mg/L (20 S. epidermidis and 1 S. haemolyticus). No CNS linezolid resistant was found.
Conclusions. There is a linear correlation between increased vancomycin MIC and teicoplanin MIC. There is a statistically significant difference (p <0.001) in the MIC of teicoplanin in the vancomycin group = 2 mg/L with respect to the vancomycin group ≤ 1 mg/L. We also observed very low levels of linezolid MIC for all strains. 

 
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Rev Esp Quimioter 2012:25(3):172-179

Matematical modeling of antibiotic resistance. Perspectives from a meta-analysys                 

M. J. FRESNADILLO-MARTÍNEZ, E. GARCÍA-SÁNCHEZ, E. GARCÍA-MERINO, Á. MARTÍN-DEL-REY, Á. RODRÍGUEZ-ENCINAS, G. RODRÍGUEZ-SÁNCHEZ, J. E. GARCÍA-SÁNCHEZ                                                                         

 
The antibiotic resistance is one of the greatest challenges of the international health community. The study of antibiotic resistance must be a multidisciplinary task and, in this sense, the main goal of this work is to analyze the role that Mathematical Modeling can play in this scenario. A qualitative and cuantitative analysis of the works published in the scientific literature is done by means of a search in the most important databases: MEDLINE, SCOPUS and ISI Web of Science. Consequently, there are few papers related to our topic but the existing works have been published in high-quality and impact international journals. Moreover, we can state that mathematical models are a very important and useful tool to analyze and study both the treatments protocols for resistance prevention and the assesment of control strategies in hospital environtment, or the prediction of the evolution of diseases due to resistant strains.

 

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Rev Esp Quimioter 2012:25(4):283-292

Pharmacoeconomic analysis of the treatment of methicillin-resistant Staphylococcus aureus with daptomycin or vancomycin                     

C. RUBIO-TERRÉS, D. RUBIO-RODRÍGUEZ, N. MAJOS, S. GRAU                                                                                   


Introduction. The increased morbidity, mortality and high costs associated with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) is a major public health problem. Pharmacoeconomic analysis was performed to compare the efficiency of daptomycin (DAP) against vancomycin (VAN) in the treatment of this infection.
Methods. Retrospective, deterministic and probabilistic cost-effectiveness analysis. The effectiveness of the treatments was estimated from the results of a randomized clinical trial, which compared DAP (6 mg / kg IV daily) and VAN (1 g IV every 12 hours), both with or without gentamicin (1 mg / kg IV every 8 hours). Resource utilization was estimated from the clinical trial of the drug datasheets and Spanish sources, the unit costs were obtained also from Spanish sources. Monte Carlo probabilistic analysis and deterministic analysis were performed.
Results. The clinical trial cure rates were higher with DAP (44.4%, 95% CI 43.5 to 45.4%) than with VAN (31.8%, 95% CI 30.9 to 32.7%) not statistically significant (p = 0.2203) but with economic impact. With DAP would occur less costs due to treatment failure (rescue antibiotics, additional tests, prolonged hospital stay and adverse reactions) than with VAN. In the base case the average cost of disease per patient was € 12,329 to € 12,696 with DAP and VAN (difference of 367 €). DAP treatment was dominant (more effective, with lower costs than VAN) both in the deterministic and probabilistic analysis. In the Monte Carlo simulation, DAP was the most cost-effective treatment in 100% of the 10,000 simulations, for a willingness to pay € 12,000 per additional cure (approximate cost of MRSA bacteraemia episode).
Conclusions. According to this model, daptomycin is more cost-effective than vancomycin in treating MRSA bacteremia. The higher cost of acquisition of daptomycin does not imply a higher cost of treating this infection.  

 

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Rev Esp Quimioter 2012:25(1):31-36

Respiratory infections: etiology and patterns of resistance in the hospital general of Ciudad Real                

 

 

I. CLEMENTE, M. D. MAÑAS, J. MARTÍNEZ, C. MONROY, M. SIDAHI, J. YANES                             

 

 

Objectives. Understanding the impact on our work place of increasing antibiotic resistance in respiratory infections.
Material and methods. We have performed a retrospective observational study on patients with significant sputum culture admitted to Internal Medicine Service Hospital General in Ciudad Real from January to December 2008. Information has been collected on the epidemiological, microbiological features, resistance patterns and treatment.
Results. The total number of patients included in this study was 60. In 83.3% there was a predisposing factor. In 43 cases the diagnosis was made in spring and summer months. The exacerbation of COPD was the most frequent diagnosis (61.7%). The most frequently isolated organism was Pseudomonas spp. (41.7%). In our hospital the most commonly used antimicrobials in the initial treatment are levofloxacin (36.7%) and amoxicillinclavulanate (26.7%). The antibiotics with the highest percentage of antibiotic resistance were ciprofloxacin in E. coli (66.7%) and Pseudomonas spp. (60%), penicillin for S. pneumoniae (100%).
Conclusions. The results of this study demonstrate the significant presence of resistance to most commonly used antibiotics in microorganisms which cause respiratory infections. 

 

 
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Rev Esp Quimioter 2012:25(3):180-182

Investigation of antimicrobial resistance to Enterococcus faecium                 

M. M. CASAL, M. CAUSSE, F. SOLÍS, F. RODRÍGUEZ-LÓPEZ, M. CASAL                                                                         

 
We performed a antibiotic resistance study on Enterococcus faecium isolated from intrahospitalary and extrahospitalary samples between 2004 and 2010. Three different samples were studied; urine, blood and wound swabs, considering a strain per patient. We included in the study a global amount of 637 E. faecium isolares. We employed semiautomatic system WIDER I for identification and sensitivity testing. We considered susceptibility and resistance criteria recommended by MENSURA group.We found a susceptibility rate of 48.05% to betalactams, 100% to linezolid, and 99.46% to vancomycin. The resistance to aminoglycosides ranged between 41.41 and 73.55%. We obtained 6 isolates resistant to vancomycin one of them from an extrahospitalary strain and five from intrahospitalary strains. It seems that vancomycin resistance should be controlled.

 

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Rev Esp Quimioter 2012:25(4):299-304

Antifungal prophylaxis in the haematological patient: a practical approach                     

L. VÁZQUEZ, E. CARRERAS, D. SERRANO, I. JARQUE, J. MENSA, J. BARBERÁN                                                                                   


Antifungal prophylaxis in the haematological patient is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukaemias, myelodysplastic syndromes and autologous or allogenic hematopoietic stem cell transplantation. Over the years, different scientific societies have established a series of recommendations on antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each one of the agents must be personalised, adapted to the characteristics of each patient and to possible interactions with concomitant medication.  

 

Rev Esp Quimioter 2012:25(4):299-304 [pdf]

 

 

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Rev Esp Quimioter 2012:25(1):37-41

Antimicrobial resistance in clinical patterns of Pseudomonas aeruginosa                

M. M. CASAL, M. CAUSSE, F. RODRÍGUEZ-LÓPEZ, M. CASAL                              

 

Pseudomonas aeruginosa is an opportunistic microorganism that is frequently the cause of nosocomial infections. Multiple mechanisms are involved in its natural and acquired resistance to many of the antimicrobial agents commonly used in clinical practice. We performed an antibiotic resistance study on P. aeruginosa isolated from intrahospitalary and extrahospitalary samples between 2005 and 2010 years. We included in the study a global amount of 3,029 P. aeruginosa isolates from clinical samples received at University Hospital Reina Sofia. Microbiology Service in Córdoba (Spain). Semiautomatic system WIDER I for strains identification and sensibility testing was employed. We considered susceptibility and resistance criteria recommended by MENSURA group. Results of the analysis showed that P. aeruginosa maintanied similar levels of antimicrobial susceptibility during the period 2005-2010, with increased susceptibility to amikacin, gentamicin and cefalosporins. Therewere also important differences in the degree of susceptibility between intrahospital and extrahospital strains during 2010 year, except for tobramicin and fosfomycin. The intrahospital difference in susceptibility was also evaluated, emphasizing the importance of periodically surveillance of susceptibility and resistance patterns of P. aeruginosa, in each setting in order to evaluate different therapeutic guidelines, because it is not always advisable to extrapolate data from different
regions. 

 
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