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 2010:23(1):12-19

Multidrug resistant Acinetobacter baumanii: clinical update and new highlights

A. HERNÁNDEZ, E. GARCÍA, G. YAGÜE, J. GÓMEZ 

 

The role of multidrug resistant Acinetobacter baumanii and its clinical relevance have been recently appreciated as a ubiquitous opportunistic nosocomial pathogen. Risk factors associated with A. baumanii infection include severe underlying diseases, previous surgery, invasive procedures, treatment with broad-spectrum antibiotics, length of hospital stay, admission to intensive care units (ICU). Carbapenem-multidrug resistant A. baumanii infections are probably associated to greater severity and more complications; in our cohort mortality was 49.3% and related mortality (within 72 hours) was 10.39%. However, severe underlying diseases probably play an important role in the clinical outcome of patients with MDR-C A. baumanii infection and controversy exists regarding the real mortality attributable to antimicrobial resistance because a high proportion of deaths took place > 7 days after diagnosis. Nevertheless, in our experience, carbapenem resistance, inappropriate therapy and monotherapy are associated to a higher mortality. Special attention should be paid to design well-controlled prospective clinical trials to determine the optimal antimicrobial therapy in critically ill patients suspected of having MDR Acinetobacter infection.

 
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Rev Esp Quimioter 2010:23(3):126-134

Critical study of spanish adult consumer profile of antibiotics on the basis of National Surveys of Health in 1993, 1995, 1997, 2001 and 2003 

J. L. BAQUERO, J. BARBERÁN, D.MARTÍNEZ   

 

Objective: The objective of this study has been to examine antibiotic consumption in Spain through the use of the National Surveys of Health (NSH) .
Material and methods: Taking the NSH, between 1993 and 2003, certain variables regarding the consumption of antibiotics have been analyzed; putting these into groups according to their typology, habits, comorbidity and the utilization of health resources. This information has been compared with published data by other authors.
Results: The consumption of antibiotics was approximately 3%, and 9-19% of this was not prescribed. Significant statistical associations have been observed between the consumption of antibiotics and other aspects such as academic and income levels, habits such as smoking, general health, certain chronic diseases, being bed-ridden due to disease; and also the use of certain medicines and the anti-influenza vaccine.
Conclusions: Consumption of antibiotics coincides with described data by other authors, and this was always higher than prescribed. The association with other variables may be limited by the inadequate NSH design in order to know the exact consumption of antibiotics.   

 
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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.    

 
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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 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 2010:23(1):20-26

Pseudomonas aeruginosa: antimicrobial resistance in clinical isolates. Castellón 2004 -2008

F. J. PARDO, M. D. TIRADO, E. D. GARCÍA, J. GRANADOS, A. CAMPOS, R. MORENO 

 

Retrospective study of antimicrobial susceptibility of 1.943 Pseudomonas aeruginosa clinical isolates to amikacin, tobramycin, gentamicin, ceftazidime, cefepime, meropenem, piperacillin-tazobactam and ciprofloxacin during a five year period. The percentage of resistance went from 2.07% to amikacin from 15.89% to ciprofloxacin. These percentages showed differences depending on the extra or intrahospitalary origin, departments and samples. Isolates from hospital patients were significantly more resistant than the ones from ambulatory patients (p≤0.001:tobramycin, 13.74% vs 5.05%; gentamicin, 13.74% vs 8.26%; ceftazidime, 12.67% vs 4.24%; cefepime, 11.48% vs 7.07%; meropenem, 8.57% vs 2.06%),except for amikacin (1.98% vs 2.2%, p=0.74), piperacillin/tazobactam (6.07% vs 4.55%, p=0.14) and ciprofloxacin (17.17% vs 13.97%, p=0.06). Critical care department and respiratory samples showed the highest resistance percentages while surgery department and invasive samples showed the lowest. Multidrug-resistance was found in 4.8% of the isolates. When comparing our data with those from our previous study (1992-2003), we observed a significant reduction in antibiotic resistance to amikacin (7.74% vs 2.07%, p<0.001), tobramycin (13.61% vs 10.26%, p<0.001), gentamicin (30,85% vs 14.73%, p<0,001), ceftazidime (14.63% vs 9,28%, p<0.001), cefepime (12,31% vs 9.71%, p=0.005), and meropenem (7.74% vs 2.07%, p=0.001); and there were no changes in resistance to piperacillin- tazobactam (4.26% vs 5.46%, p=0,06) and ciprofloxacin (16.02% vs 15.89%, p=0.89). In the last years, the susceptibility pattern of P. aeruginosa to antimicrobial agents has changed in our health district, and it is very different from the one described in national studies so it would be very important to monitore susceptibility of clinical isolates periodically.

 
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Rev Esp Quimioter 2010:23(3):135-143

Impact factor and quality of scientific publications on Microbiology: the example of the Spanish Journal of Chemotherapy 

D. CARABANTES   

 

Introduction. The impact factor of a journal is the quantitative analysis of the number of citations obtained during a specific period of time. This currently is the standard tool to measure the quality of the publication and a way to evaluate the research trajectory of a scientist.
Methods. Search for bibliometric indicators: Journal Citation Reports, SCImago Journal Rank and Potencial Impact Factor for the Spanish Medical Journals of the Instituto de Historia de la Ciencia y Documentación López Piñero (IHCD). To identify criteria of editorial quality, of visibility and of spreading by reviewing databases such as the Online Regional Information System for Scholarly Journals from Latin America, the Caribbean, Spain and Portugal (LATINDEX), SciELO (Scientific Electronic Library Online), DIALNET and the Collective Periodical Publications Catalogue of Spanish Healthcare Science Libraries, known as C17.
Results. For the first time, the Spanish Journal of Chemotherapy appears in the 2009 edition of JCR, previously by joined the two spanish journals Clinical Microbiology and Infectious Diseases and International Microbiology, both ranked at a lower position. While calculating factors of national and international impact of the five publications included in the category of Pharmacology and Pharmacy as part of theproject initiated by the IHCD, the Spanish Journal of Chemotherapy showed the best results.
Conclusions.The Spanish Journal of Chemotherapy obtained good results in analysed bibliometric indicators, positioning it at the top of the ranking of Spanish medical journals. A good spreading helped to maintain visibility on the publication in the editorial field.   

 
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